references.bib

@article{ademuwagunVoltageGatedSodium2021,
  title = {Voltage {{Gated Sodium Channel Genes}} in {{Epilepsy}}: {{Mutations}}, {{Functional Studies}}, and {{Treatment Dimensions}}},
  shorttitle = {Voltage {{Gated Sodium Channel Genes}} in {{Epilepsy}}},
  author = {Ademuwagun, Ibitayo Abigail and Rotimi, Solomon Oladapo and Syrbe, Steffen and Ajamma, Yvonne Ukamaka and Adebiyi, Ezekiel},
  date = {2021-03-24},
  journaltitle = {Frontiers in Neurology},
  shortjournal = {Front. Neurol.},
  volume = {12},
  publisher = {Frontiers},
  issn = {1664-2295},
  doi = {10.3389/fneur.2021.600050},
  url = {https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.600050/full},
  urldate = {2024-04-08},
  abstract = {{$<$}p{$>$}Genetic epilepsy occurs as a result of mutations in either a single gene or an interplay of different genes. These mutations have been detected in ion channel and non-ion channel genes. A noteworthy class of ion channel genes are the voltage gated sodium channels (VGSCs) that play key roles in the depolarization phase of action potentials in neurons. Of huge significance are {$<$}italic{$>$}SCN1A, SCN1B, SCN2A, SCN3A{$<$}/italic{$>$}, and {$<$}italic{$>$}SCN8A{$<$}/italic{$>$} genes that are highly expressed in the brain. Genomic studies have revealed inherited and {$<$}italic{$>$}de novo{$<$}/italic{$>$} mutations in sodium channels that are linked to different forms of epilepsies. Due to the high frequency of sodium channel mutations in epilepsy, this review discusses the pathogenic mutations in the sodium channel genes that lead to epilepsy. In addition, it explores the functional studies on some known mutations and the clinical significance of VGSC mutations in the medical management of epilepsy. The understanding of these channel mutations may serve as a strong guide in making effective treatment decisions in patient management.{$<$}/p{$>$}},
  langid = {english},
  keywords = {depolarisation,gain-of-functions,loss-of-functions,Seizures,VGSC},
  file = {C:\Users\marc_\Zotero\storage\JMYGFY4M\Ademuwagun e.a. - 2021 - Voltage Gated Sodium Channel Genes in Epilepsy Mu.pdf}
}

@article{adiga*TherapeuticsEpilepsyReview2023,
  title = {Therapeutics of {{Epilepsy}}: {{A Review}}},
  shorttitle = {Therapeutics of {{Epilepsy}}},
  author = {Adiga *, Usha and Pb, Nandit},
  date = {2023-10-17},
  journaltitle = {International Neurourology Journal},
  volume = {27},
  number = {4},
  pages = {152--159},
  url = {http://einj.net/index.php/INJ/article/view/156},
  urldate = {2024-04-19},
  abstract = {Antiepileptic drugs (AEDs) play a crucial role in the management of epilepsy, a neurological disorder characterized by recurrent and unprovoked seizures. The rationale for using AEDs lies in their ability to modulate the excessive and synchronous electrical activity in the brain that underlies seizures. These medications aim to prevent the spread of abnormal electrical discharges, thus reducing the frequency and severity of seizures and enhancing the individual's quality of life. AEDs can be classified into several distinct classes based on their mechanisms of action. The first-generation AEDs, including phenobarbital and phenytoin, primarily target voltage-gated ion channels, particularly sodium channels, to dampen neuronal excitability. While effective, these drugs are associated with significant side effects and limited efficacy in certain seizure types. Second-generation AEDs, such as lamotrigine and levetiracetam, offer a broader range of mechanisms, including modulation of calcium channels, enhancement of inhibitory neurotransmission, and reduction of glutamate release. These drugs tend to have a more favorable side effect profile and are often preferred for their versatility. The third-generation AEDs continue to expand the therapeutic options by targeting novel mechanisms, like the sodium channel blocker lacosamide and the potassium channel opener ezogabine. Additionally, some AEDs exhibit multiple mechanisms of action, exemplified by valproate, which influences GABA levels and ion channels. The diversity of AED mechanisms enables clinicians to tailor treatments to individual patients, optimizing seizure control while minimizing adverse effects. In recent years, personalized medicine has gained prominence, allowing for a more precise selection of AEDs based on a patient's specific seizure type, underlying etiology, and potential drug interactions. The rational use of AEDs involves considering efficacy, safety, tolerability, and patient-specific factors to devise a comprehensive treatment plan. While these medications can significantly improve seizure management, it's important for healthcare providers to continuously monitor their patients, adjust doses if necessary, and explore new therapies as they emerge, ensuring the best possible outcomes for individuals with epilepsy..},
  issue = {4},
  langid = {english},
  keywords = {antiepileptics,epilepsy,mechanism of action,personalized medicine},
  file = {C:\Users\marc_\Zotero\storage\49Z4ZKFC\Adiga  en Pb - 2023 - Therapeutics of Epilepsy A Review.pdf}
}

@article{ajibolaHypothalamicGlutamateGABA2021,
  title = {Hypothalamic {{Glutamate}}/{{GABA Cotransmission Modulates Hippocampal Circuits}} and {{Supports Long-Term Potentiation}}},
  author = {Ajibola, Musa Iyiola and Wu, Jei-Wei and Abdulmajeed, Wahab Imam and Lien, Cheng-Chang},
  date = {2021-09-29},
  journaltitle = {Journal of Neuroscience},
  shortjournal = {J. Neurosci.},
  volume = {41},
  number = {39},
  eprint = {34380766},
  eprinttype = {pmid},
  pages = {8181--8196},
  publisher = {Society for Neuroscience},
  issn = {0270-6474, 1529-2401},
  doi = {10.1523/JNEUROSCI.0410-21.2021},
  url = {https://www.jneurosci.org/content/41/39/8181},
  urldate = {2024-04-17},
  abstract = {Subcortical input engages in cortico-hippocampal information processing. Neurons of the hypothalamic supramammillary nucleus (SuM) innervate the dentate gyrus (DG) by coreleasing two contrasting fast neurotransmitters, glutamate and GABA, and thereby support spatial navigation and contextual memory. However, the synaptic mechanisms by which SuM neurons regulate the DG activity and synaptic plasticity are not well understood. The DG comprises excitatory granule cells (GCs) as well as inhibitory interneurons (INs). Combining optogenetic, electrophysiological, and pharmacological approaches, we demonstrate that the SuM input differentially regulates the activities of different DG neurons in mice of either sex via distinct synaptic mechanisms. Although SuM activation results in synaptic excitation and inhibition in all postsynaptic cells, the ratio of these two components is variable and cell type-dependent. Specifically, dendrite-targeting INs receive predominantly synaptic excitation, whereas soma-targeting INs and GCs receive primarily synaptic inhibition. Although SuM excitation alone is insufficient to excite GCs, it enhances the GC spiking precision and reduces the latencies in response to excitatory drives. Furthermore, SuM excitation enhances the GC spiking in response to the cortical input, thereby promoting induction of long-term potentiation at cortical-GC synapses. Collectively, these findings provide physiological significance of the cotransmission of glutamate/GABA by SuM neurons in the DG network. SIGNIFICANCE STATEMENT The cortical-hippocampal pathways transfer mnemonic information during memory acquisition and retrieval, whereas subcortical input engages in modulation of communication between the cortex and hippocampus. The supramammillary nucleus (SuM) neurons of the hypothalamus innervate the dentate gyrus (DG) by coreleasing glutamate and GABA onto granule cells (GCs) and interneurons and support memories. However, how the SuM input regulates the activity of various DG cell types and thereby contributes to synaptic plasticity remains unexplored. Combining optogenetic and electrophysiological approaches, we demonstrate that the SuM input differentially regulates DG cell dynamics and consequently enhances GC excitability as well as synaptic plasticity at cortical input-GC synapses. Our findings highlight a significant role of glutamate/GABA cotransmission in regulating the input-output dynamics of DG circuits.},
  langid = {english},
  keywords = {cotransmission,GABA,glutamate,hypothalamus,long-term potentiation,supramammillary nucleus},
  file = {C:\Users\marc_\Zotero\storage\HFAAIJHP\Ajibola e.a. - 2021 - Hypothalamic GlutamateGABA Cotransmission Modulat.pdf}
}

@article{aldenkampEffectsEpileptiformEEG2004,
  title = {Effects of Epileptiform {{EEG}} Discharges on Cognitive Function: {{Is}} the Concept of “Transient Cognitive Impairment” Still Valid?},
  shorttitle = {Effects of Epileptiform {{EEG}} Discharges on Cognitive Function},
  author = {Aldenkamp, Albert P. and Arends, Johan},
  date = {2004-02},
  journaltitle = {Epilepsy \& Behavior},
  shortjournal = {Epilepsy \& Behavior},
  volume = {5},
  pages = {25--34},
  issn = {15255050},
  doi = {10.1016/j.yebeh.2003.11.005},
  url = {https://linkinghub.elsevier.com/retrieve/pii/S1525505003003172},
  urldate = {2024-04-11},
  abstract = {In this article we review the existing evidence on the cognitive impact of interictal epileptiform EEG discharges. Such cognitive impairment occurs exclusively in direct relation to episodes of epileptiform EEG discharges and must be distinguished from (post) ictal seizure effects and from the nonperiodic long-term ‘‘stable’’ interictal effects caused by the clinical syndrome or the underlying etiology. Especially in patients with short nonconvulsive seizures, characterized often by difficult-to-detect symptoms, the ictal or postictal effects may be overlooked and the resulting cognitive effects may be erroneously related to the epileptiform EEG discharges. The existing epidemiological data show that the prevalence of cognitive impairment during epileptiform EEG discharges is low. In one study 2.2\% of the patients referred to a specialized epilepsy center for EEG recording showed a definite relationship between epileptiform EEG discharges and cognitive impairments (‘‘transient cognitive impairment’’). Several studies have sought to analyze to what extent cognitive impairment can be attributed to epileptiform EEG discharges among the other epilepsy factors (such as the effect of the clinical syndrome). These studies show that epileptiform EEG discharges have an additional and independent effect, but this effect is mild and limited to transient mechanistic cognitive processes (alertness, mental speed). This finding concurs with clinical studies that also reported only mild effects. In only exceptional cases are epileptiform EEG discharges the dominant factor explaining cognitive impairment. In addition, some studies have indicated that such mild effects may accumulate over time (when frequent epileptiform EEG discharges persist over years) and consequently result in effects on stable aspects of cognitive function such as educational achievement and intelligence. Hence, the clinical relevance is that early detection of cognitive effects of epileptiform EEG discharges and subsequent treatment may prevent a definite impact on cognitive and educational development. The disruptive effects of epileptiform EEG discharges on long-term potentiation, as established in animal experiments, may be one of the neurophysiological mechanisms underlying this accumulation. In conclusion the concept of ‘‘transient cognitive impairment’’ is still valid, but refinement of methodology has shown that a large proportion of presumed transient cognitive impairment can be attributed to subtle seizures, while interictal epileptic activity accounts for a much smaller part of the cognitive effects than previously thought. In particular cryptogenic partial epilepsies are associated with the risk of cognitive impairment. We hope that increased clinical awareness of this need for early detection will stimulate longitudinal and prospective research that eventually also will provide an answer to the questions of when and how epileptiform discharges that are not part of a seizure need to be treated.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\2CDACHY6\Aldenkamp en Arends - 2004 - Effects of epileptiform EEG discharges on cognitiv.pdf}
}

@article{amaralDentateGyrusFundamental2007,
  title = {The Dentate Gyrus: Fundamental Neuroanatomical Organization (Dentate Gyrus for Dummies)},
  shorttitle = {The Dentate Gyrus},
  author = {Amaral, David G. and Scharfman, Helen E. and Lavenex, Pierre},
  date = {2007},
  journaltitle = {Progress in brain research},
  shortjournal = {Prog Brain Res},
  volume = {163},
  eprint = {17765709},
  eprinttype = {pmid},
  pages = {3--22},
  issn = {0079-6123},
  doi = {10.1016/S0079-6123(07)63001-5},
  url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2492885/},
  urldate = {2023-11-07},
  abstract = {The dentate gyrus is a simple cortical region that is an integral portion of the larger functional brain system called the hippocampal formation. In this review, the fundamental neuroanatomical organization of the dentate gyrus is described, including principal cell types and their connectivity, and a summary of the major extrinsic inputs of the dentate gyrus is provided. Together, this information provides essential information that can serve as an introduction to the dentate gyrus — a “dentate gyrus for dummies.”},
  pmcid = {PMC2492885},
  file = {C:\Users\marc_\Zotero\storage\BZGQAIE9\Amaral et al. - 2007 - The dentate gyrus fundamental neuroanatomical org.pdf}
}

@article{aronicaGeneExpressionProfile2007,
  title = {Gene {{Expression Profile}} in {{Temporal Lobe Epilepsy}}},
  author = {Aronica, Eleonora and Gorter, Jan A.},
  date = {2007-04-01},
  journaltitle = {The Neuroscientist},
  shortjournal = {Neuroscientist},
  volume = {13},
  number = {2},
  pages = {100--108},
  publisher = {SAGE Publications Inc STM},
  issn = {1073-8584},
  doi = {10.1177/1073858406295832},
  url = {https://doi.org/10.1177/1073858406295832},
  urldate = {2024-04-30},
  abstract = {Epilepsy is one of the most common neurological disorders. Temporal lobe epilepsy (TLE) represents the most frequent epilepsy syndrome in adult patients with resistance to pharmacological treatment. In TLE, the origin of seizure activity typically involves the hippocampal formation, which displays major neuropathological features, described with the term hippocampal sclerosis (HS). The expansion of neurosurgical epilepsy programs has offered the possibility of disposing of clinically well-characterized hippocampal tissue, so that the analysis of molecular mechanisms underlying the structural and functional reorganization occurring in the hippocampus and neighboring areas in TLE patients can be done on a large scale. The recent development of molecular biological technologies permits the analysis of changes in the expression of a large number of genes. This has opened new perspectives for epilepsy research. However, the hippocampal specimens obtained from patients with TLE most often represent an advanced stage of the pathology. For this reason, animal models that reproduce the clinical and histopathological features of TLE are helpful in detecting the early development of the pathological cascade leading to TLE with HS. An overview of recent data of gene expression profiles in human and experimental TLE is presented along with a discussion of the relevance of functional genomics, to develop new hypotheses and to detect likely candidate genes involved in epileptogenesis, as well as possible target molecules for new therapeutic approaches. NEUROSCIENTIST 13(2):100—108, 2007.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\UU88IQMT\Aronica en Gorter - 2007 - Gene Expression Profile in Temporal Lobe Epilepsy.pdf}
}

@article{arskiOscillatoryBasisWorking2021,
  title = {The {{Oscillatory Basis}} of {{Working Memory Function}} and {{Dysfunction}} in {{Epilepsy}}},
  author = {Arski, Olivia N. and Young, Julia M. and Smith, Mary-Lou and Ibrahim, George M.},
  date = {2021-01-12},
  journaltitle = {Frontiers in Human Neuroscience},
  shortjournal = {Front. Hum. Neurosci.},
  volume = {14},
  publisher = {Frontiers},
  issn = {1662-5161},
  doi = {10.3389/fnhum.2020.612024},
  url = {https://www.frontiersin.org/articles/10.3389/fnhum.2020.612024},
  urldate = {2024-04-08},
  abstract = {Working memory (WM) deficit is a pervasive co-morbidity of epilepsy. Although the pathophysiological mechanisms underpinning these impairments remain elusive, it is thought that WM depends on oscillatory interactions within and between nodes of large-scale functional networks. These include the hippocampus and default mode network as well as the prefrontal cortex and frontoparietal central executive network. Here, we review the functional roles of neural oscillations in subserving WM and the putative mechanisms by which epilepsy disrupts normative activity, leading to aberrant oscillatory signatures. We highlight the particular role of interictal epileptic activity, including interictal epileptiform discharges and high frequency oscillations (HFOs) in WM deficits. We also discuss the translational opportunities presented by greater understanding of the oscillatory basis of WM function and dysfunction in epilepsy, including the potential targets for neuromodulation.},
  langid = {english},
  keywords = {Epilepsy,High frequency oscillations,Hippocampus,neural networks,working memory},
  file = {C:\Users\marc_\Zotero\storage\BKM64P82\Arski e.a. - 2021 - The Oscillatory Basis of Working Memory Function a.pdf}
}

@article{beghiEpidemiologyEpilepsy2019,
  title = {The {{Epidemiology}} of {{Epilepsy}}},
  author = {Beghi, Ettore},
  date = {2019-12-18},
  journaltitle = {Neuroepidemiology},
  shortjournal = {Neuroepidemiology},
  volume = {54},
  number = {2},
  pages = {185--191},
  issn = {0251-5350},
  doi = {10.1159/000503831},
  url = {https://doi.org/10.1159/000503831},
  urldate = {2024-03-30},
  abstract = {Epilepsy is a chronic disease of the brain characterized by an enduring (i.e., persisting) predisposition to generate seizures, unprovoked by any immediate central nervous system insult, and by the neurobiologic, cognitive, psychological, and social consequences of seizure recurrences. Epilepsy affects both sexes and all ages with worldwide distribution. The prevalence and the incidence of epilepsy are slightly higher in men compared to women and tend to peak in the elderly, reflecting the higher frequency of stroke, neurodegenerative diseases, and tumors in this age-group. Focal seizures are more common than generalized seizures both in children and in adults. The etiology of epilepsy varies according to the sociodemographic characteristics of the affected populations and the extent of the diagnostic workup, but a documented cause is still lacking in about 50\% of cases from high-income countries (HIC). The overall prognosis of epilepsy is favorable in the majority of patients when measured by seizure freedom. Reports from low/middle-income countries (LMIC; where patients with epilepsy are largely untreated) give prevalence and remission rates that overlap those of HICs. As the incidence of epilepsy appears higher in most LMICs, the overlapping prevalence can be explained by misdiagnosis, acute symptomatic seizures and premature mortality. Studies have consistently shown that about one-half of cases tend to achieve prolonged seizure remission. However, more recent reports on the long-term prognosis of epilepsy have identified differing prognostic patterns, including early and late remission, a relapsing-remitting course, and even a worsening course (characterized by remission followed by relapse and unremitting seizures). Epilepsy per se carries a low mortality risk, but significant differences in mortality rates are expected when comparing incidence and prevalence studies, children and adults, and persons with idiopathic and symptomatic seizures. Sudden unexplained death is most frequent in people with generalized tonic-clonic seizures, nocturnal seizures, and drug refractory epilepsy.},
  file = {C\:\\Users\\marc_\\Zotero\\storage\\W3EHD2V2\\Beghi - 2019 - The Epidemiology of Epilepsy.pdf;C\:\\Users\\marc_\\Zotero\\storage\\LS4WRM7Q\\The-Epidemiology-of-Epilepsy.html}
}

@article{bernardAcquiredDendriticChannelopathy2004,
  title = {Acquired {{Dendritic Channelopathy}} in {{Temporal Lobe Epilepsy}}},
  author = {Bernard, Christophe and Anderson, Anne and Becker, Albert and Poolos, Nicholas P. and Beck, Heinz and Johnston, Daniel},
  date = {2004-07-23},
  journaltitle = {Science},
  volume = {305},
  number = {5683},
  pages = {532--535},
  publisher = {American Association for the Advancement of Science},
  doi = {10.1126/science.1097065},
  url = {https://www.science.org/doi/10.1126/science.1097065},
  urldate = {2024-03-30},
  abstract = {Inherited channelopathies are at the origin of many neurological disorders. Here we report a form of channelopathy that is acquired in experimental temporal lobe epilepsy (TLE), the most common form of epilepsy in adults. The excitability of CA1 pyramidal neuron dendrites was increased in TLE because of decreased availability of A-type potassium ion channels due to transcriptional (loss of channels) and posttranslational (increased channel phosphorylation by extracellular signal-regulated kinase) mechanisms. Kinase inhibition partly reversed dendritic excitability to control levels. Such acquired channelopathy is likely to amplify neuronal activity and may contribute to the initiation and/or propagation of seizures in TLE.},
  file = {C:\Users\marc_\Zotero\storage\6UEMGN3N\Bernard e.a. - 2004 - Acquired Dendritic Channelopathy in Temporal Lobe .pdf}
}

@article{bonanscoPlasticityHippocampalExcitatoryInhibitory2016,
  title = {Plasticity of {{Hippocampal Excitatory-Inhibitory Balance}}: {{Missing}} the {{Synaptic Control}} in the {{Epileptic Brain}}},
  shorttitle = {Plasticity of {{Hippocampal Excitatory-Inhibitory Balance}}},
  author = {Bonansco, Christian and Fuenzalida, Marco},
  date = {2016-02-24},
  journaltitle = {Neural Plasticity},
  volume = {2016},
  pages = {e8607038},
  publisher = {Hindawi},
  issn = {2090-5904},
  doi = {10.1155/2016/8607038},
  url = {https://www.hindawi.com/journals/np/2016/8607038/},
  urldate = {2024-05-02},
  abstract = {Synaptic plasticity is the capacity generated by experience to modify the neural function and, thereby, adapt our behaviour. Long-term plasticity of glutamatergic and GABAergic transmission occurs in a concerted manner, finely adjusting the excitatory-inhibitory (E/I) balance. Imbalances of E/I function are related to several neurological diseases including epilepsy. Several evidences have demonstrated that astrocytes are able to control the synaptic plasticity, with astrocytes being active partners in synaptic physiology and E/I balance. Here, we revise molecular evidences showing the epileptic stage as an abnormal form of long-term brain plasticity and propose the possible participation of astrocytes to the abnormal increase of glutamatergic and decrease of GABAergic neurotransmission in epileptic networks.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\7YQFQB74\Bonansco en Fuenzalida - 2016 - Plasticity of Hippocampal Excitatory-Inhibitory Ba.pdf}
}

@article{bookerMorphologicalDiversityConnectivity2018,
  title = {Morphological Diversity and Connectivity of Hippocampal Interneurons},
  author = {Booker, Sam A. and Vida, Imre},
  date = {2018-09-01},
  journaltitle = {Cell and Tissue Research},
  shortjournal = {Cell Tissue Res},
  volume = {373},
  number = {3},
  pages = {619--641},
  issn = {1432-0878},
  doi = {10.1007/s00441-018-2882-2},
  url = {https://doi.org/10.1007/s00441-018-2882-2},
  urldate = {2023-11-08},
  abstract = {The mammalian forebrain is constructed from ensembles of neurons that form local microcircuits giving rise to the exquisite cognitive tasks the mammalian brain can perform. Hippocampal neuronal circuits comprise populations of relatively homogenous excitatory neurons, principal cells and exceedingly heterogeneous inhibitory neurons, the interneurons. Interneurons release GABA from their axon terminals and are capable of controlling excitability in every cellular compartment of principal cells and interneurons alike; thus, they provide a brake on excess activity, control the timing of neuronal discharge and provide modulation of synaptic transmission. The dendritic and axonal morphology of interneurons, as well as their afferent and efferent connections within hippocampal circuits, is central to their ability to differentially control excitability, in a cell-type- and compartment-specific manner. This review aims to provide an up-to-date compendium of described hippocampal interneuron subtypes, with respect to their morphology, connectivity, neurochemistry and physiology, a full understanding of which will in time help to explain the rich diversity of neuronal function.},
  langid = {english},
  keywords = {Connectivity,GABA,Hippocampus,Interneuron,Morphology},
  file = {C:\Users\marc_\Zotero\storage\Y926S3ZC\Booker and Vida - 2018 - Morphological diversity and connectivity of hippoc.pdf}
}

@article{brunklausSodiumChannelEpilepsies2020,
  title = {Sodium Channel Epilepsies and Neurodevelopmental Disorders: From Disease Mechanisms to Clinical Application},
  shorttitle = {Sodium Channel Epilepsies and Neurodevelopmental Disorders},
  author = {Brunklaus, Andreas and Lal, Dennis},
  date = {2020},
  journaltitle = {Developmental Medicine \& Child Neurology},
  volume = {62},
  number = {7},
  pages = {784--792},
  issn = {1469-8749},
  doi = {10.1111/dmcn.14519},
  url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/dmcn.14519},
  urldate = {2024-04-08},
  abstract = {Genetic variants in brain-expressed voltage-gated sodium channels (SCNs) have emerged as one of the most frequent causes of Mendelian forms of epilepsy and neurodevelopmental disorders (NDDs). This review explores the biological concepts that underlie sodium channel NDDs, explains their phenotypic heterogeneity, and appraises how this knowledge may inform clinical practice. We observe that excitatory/inhibitory neuronal expression ratios of sodium channels are important regulatory mechanisms underlying brain development, homeostasis, and neurological diseases. We hypothesize that a detailed understanding of gene expression, variant tolerance, location, and function, as well as timing of seizure onset can aid the understanding of how variants in SCN1A, SCN2A, SCN3A, and SCN8A contribute to seizure aetiology and inform treatment choice. We propose a model in which variant type, development-specific gene expression, and functions of SCNs explain the heterogeneity of sodium channel associated NDDs. Understanding of basic disease mechanisms and detailed knowledge of variant characteristics have increasing influence on clinical decision making, enabling us to stratify treatment and move closer towards precision medicine in sodium channel epilepsy and NDDs. What this paper adds Sodium-channel disorder heterogeneity is explained by variant-specific gene expression timing and function. Gene tolerance and location analyses aid sodium channel variant interpretation. Sodium-channel variant characteristics can contribute to clinical decision making.},
  langid = {english},
  file = {C\:\\Users\\marc_\\Zotero\\storage\\979AU789\\Brunklaus en Lal - 2020 - Sodium channel epilepsies and neurodevelopmental d.pdf;C\:\\Users\\marc_\\Zotero\\storage\\Z5PAFE9L\\dmcn.html}
}

@article{coleStructureBasedIdentificationCharacterization2020,
  title = {Structure-{{Based Identification}} and {{Characterization}} of {{Inhibitors}} of the {{Epilepsy-Associated KNa1}}.1 ({{KCNT1}}) {{Potassium Channel}}},
  author = {Cole, Bethan A. and Johnson, Rachel M. and Dejakaisaya, Hattapark and Pilati, Nadia and Fishwick, Colin W.G. and Muench, Stephen P. and Lippiat, Jonathan D.},
  date = {2020-05},
  journaltitle = {iScience},
  shortjournal = {iScience},
  volume = {23},
  number = {5},
  pages = {101100},
  issn = {25890042},
  doi = {10.1016/j.isci.2020.101100},
  url = {https://linkinghub.elsevier.com/retrieve/pii/S2589004220302856},
  urldate = {2024-04-08},
  abstract = {Drug-resistant epileptic encephalopathies of infancy have been associated with KCNT1 gain-of-function mutations, which increase the activity of KNa1.1 sodium-activated potassium channels. Pharmacological inhibition of hyperactive KNa1.1 channels by quinidine has been proposed as a stratified treatment, but mostly this has not been successful, being linked to the low potency and lack of specificity of the drug. Here we describe the use of a previously determined cryo-electron microscopy-derived KNa1.1 structure and mutational analysis to identify how quinidine binds to the channel pore and, using computational methods, screened for compounds predicated to bind to this site. We describe six compounds that inhibited KNa1.1 channels with low- and sub-micromolar potencies, likely also through binding in the intracellular pore vestibule. In hERG inhibition and cytotoxicity assays, two compounds were ineffective. These may provide starting points for the development of new pharmacophores and could become tool compounds to study this channel further.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\9DS6TJ79\Cole e.a. - 2020 - Structure-Based Identification and Characterizatio.pdf}
}

@article{cookePlasticityHumanCentral2006,
  title = {Plasticity in the Human Central Nervous System},
  author = {Cooke, S. F. and Bliss, T. V. P.},
  date = {2006-07-01},
  journaltitle = {Brain},
  shortjournal = {Brain},
  volume = {129},
  number = {7},
  pages = {1659--1673},
  issn = {0006-8950},
  doi = {10.1093/brain/awl082},
  url = {https://doi.org/10.1093/brain/awl082},
  urldate = {2024-04-19},
  abstract = {Long-term potentiation (LTP) is a well-characterized form of synaptic plasticity that fulfils many of the criteria for a neural correlate of memory. LTP has been studied in a variety of animal models and, in rodents in particular, there is now a strong body of evidence demonstrating common underlying molecular mechanisms in LTP and memory. Results are beginning to emerge from studies of neural plasticity in humans. This review will summarize findings demonstrating that synaptic LTP can be induced in human CNS tissue and that rodent and human LTP probably share similar molecular mechanisms. We will also discuss the application of non-invasive stimulation techniques to awake human subjects to induce LTP-like long-lasting changes in localized neural activity. These techniques have potential therapeutic application in manipulating neural plasticity to treat a variety of conditions, including depression, Parkinson's disease, epilepsy and neuropathic pain.},
  file = {C\:\\Users\\marc_\\Zotero\\storage\\ITWZ498Y\\Cooke en Bliss - 2006 - Plasticity in the human central nervous system.pdf;C\:\\Users\\marc_\\Zotero\\storage\\TMGBWICH\\300527.html}
}

@incollection{cotterillBurstDetectionMethods2019,
  title = {Burst {{Detection Methods}}},
  booktitle = {Advances in {{Neurobiology}}},
  author = {Cotterill, Ellese and Eglen, Stephen},
  date = {2019-05-01},
  pages = {185--206},
  doi = {10.1007/978-3-030-11135-9_8},
  abstract = {‘Bursting’, defined as periods of high-frequency firing of a neuron separated by periods of quiescence, has been observed in various neuronal systems, both in vitro and in vivo. It has been associated with a range of neuronal processes, including efficient information transfer and the formation of functional networks during development, and has been shown to be sensitive to genetic and pharmacological manipulations. Accurate detection of periods of bursting activity is thus an important aspect of characterising both spontaneous and evoked neuronal network activity. A wide variety of computational methods have been developed to detect periods of bursting in spike trains recorded from neuronal networks. In this chapter, we review several of the most popular and successful of these methods.},
  isbn = {978-3-030-11134-2},
  file = {C:\Users\marc_\Zotero\storage\DKMKA6DG\Cotterill and Eglen - 2019 - Burst Detection Methods.pdf}
}

@article{cotterillComparisonComputationalMethods2016,
  title = {A Comparison of Computational Methods for Detecting Bursts in Neuronal Spike Trains and Their Application to Human Stem Cell-Derived Neuronal Networks},
  author = {Cotterill, Ellese and Charlesworth, Paul and Thomas, Christopher W. and Paulsen, Ole and Eglen, Stephen J.},
  date = {2016-08-01},
  journaltitle = {Journal of Neurophysiology},
  shortjournal = {J Neurophysiol},
  volume = {116},
  number = {2},
  eprint = {27098024},
  eprinttype = {pmid},
  pages = {306--321},
  issn = {0022-3077},
  doi = {10.1152/jn.00093.2016},
  url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4969396/},
  urldate = {2024-02-26},
  abstract = {We provide an unbiased quantitative assessment of eight existing methods for identifying bursts in neuronal spike trains. We reveal limitations in a number of commonly used burst detection techniques and provide recommendations for the best practice for accurate identification of bursts using existing techniques. An analysis of the ontogeny of bursting activity in a novel data set of recordings from human induced pluripotent stem cell-derived neuronal networks, using the highest-performing burst detectors from our study, is also presented., Accurate identification of bursting activity is an essential element in the characterization of neuronal network activity. Despite this, no one technique for identifying bursts in spike trains has been widely adopted. Instead, many methods have been developed for the analysis of bursting activity, often on an ad hoc basis. Here we provide an unbiased assessment of the effectiveness of eight of these methods at detecting bursts in a range of spike trains. We suggest a list of features that an ideal burst detection technique should possess and use synthetic data to assess each method in regard to these properties. We further employ each of the methods to reanalyze microelectrode array (MEA) recordings from mouse retinal ganglion cells and examine their coherence with bursts detected by a human observer. We show that several common burst detection techniques perform poorly at analyzing spike trains with a variety of properties. We identify four promising burst detection techniques, which are then applied to MEA recordings of networks of human induced pluripotent stem cell-derived neurons and used to describe the ontogeny of bursting activity in these networks over several months of development. We conclude that no current method can provide “perfect” burst detection results across a range of spike trains; however, two burst detection techniques, the MaxInterval and logISI methods, outperform compared with others. We provide recommendations for the robust analysis of bursting activity in experimental recordings using current techniques.},
  pmcid = {PMC4969396},
  file = {C:\Users\marc_\Zotero\storage\L9LZKRBF\Cotterill et al. - 2016 - A comparison of computational methods for detectin.pdf}
}

@article{cressmanInfluenceSodiumPotassium2009,
  title = {The Influence of Sodium and Potassium Dynamics on Excitability, Seizures, and the Stability of Persistent States: {{I}}. {{Single}} Neuron Dynamics},
  shorttitle = {The Influence of Sodium and Potassium Dynamics on Excitability, Seizures, and the Stability of Persistent States},
  author = {Cressman, John R. and Ullah, Ghanim and Ziburkus, Jokubas and Schiff, Steven J. and Barreto, Ernest},
  date = {2009-04},
  journaltitle = {Journal of computational neuroscience},
  shortjournal = {J Comput Neurosci},
  volume = {26},
  number = {2},
  eprint = {19169801},
  eprinttype = {pmid},
  pages = {159--170},
  issn = {0929-5313},
  doi = {10.1007/s10827-008-0132-4},
  url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704057/},
  urldate = {2023-11-03},
  abstract = {In these companion papers, we study how the interrelated dynamics of sodium and potassium affect the excitability of neurons, the occurrence of seizures, and the stability of persistent states of activity. In this first paper, we construct a mathematical model consisting of a single conductance-based neuron together with intra- and extracellular ion concentration dynamics. We formulate a reduction of this model that permits a detailed bifurcation analysis, and show that the reduced model is a reasonable approximation of the full model. We find that competition between intrinsic neuronal currents, sodium-potassium pumps, glia, and diffusion can produce very slow and large-amplitude oscillations in ion concentrations similar to what is seen physiologically in seizures. Using the reduced model, we identify the dynamical mechanisms that give rise to these phenomena. These models reveal several experimentally testable predictions. Our work emphasizes the critical role of ion concentration homeostasis in the proper functioning of neurons, and points to important fundamental processes that may underlie pathological states such as epilepsy.},
  pmcid = {PMC2704057},
  file = {C:\Users\marc_\Zotero\storage\V77BV2PC\Cressman e.a. - 2009 - The influence of sodium and potassium dynamics on .pdf}
}

@book{cutsuridisHippocampalMicrocircuitsComputational2018,
  title = {Hippocampal {{Microcircuits}}: {{A Computational Modeler}}'s {{Resource Book}}},
  shorttitle = {Hippocampal {{Microcircuits}}},
  editor = {Cutsuridis, Vassilis and Graham, Bruce P. and Cobb, Stuart and Vida, Imre},
  date = {2018},
  series = {Springer {{Series}} in {{Computational Neuroscience}}},
  publisher = {Springer International Publishing},
  location = {Cham},
  doi = {10.1007/978-3-319-99103-0},
  url = {http://link.springer.com/10.1007/978-3-319-99103-0},
  urldate = {2023-11-08},
  isbn = {978-3-319-99102-3 978-3-319-99103-0},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\FJQSRH7H\Cutsuridis et al. - 2018 - Hippocampal Microcircuits A Computational Modeler.pdf}
}

@article{dzhalaExcitatoryActionsEndogenously2003,
  title = {Excitatory {{Actions}} of {{Endogenously Released GABA Contribute}} to {{Initiation}} of {{Ictal Epileptiform Activity}} in the {{Developing Hippocampus}}},
  author = {Dzhala, Volodymyr I. and Staley, Kevin J.},
  date = {2003-03-01},
  journaltitle = {Journal of Neuroscience},
  shortjournal = {J. Neurosci.},
  volume = {23},
  number = {5},
  eprint = {12629188},
  eprinttype = {pmid},
  pages = {1840--1846},
  publisher = {Society for Neuroscience},
  issn = {0270-6474, 1529-2401},
  doi = {10.1523/JNEUROSCI.23-05-01840.2003},
  url = {https://www.jneurosci.org/content/23/5/1840},
  urldate = {2024-04-19},
  abstract = {In the developing rat hippocampus, ictal epileptiform activity can be elicited easily in vitro during the first three postnatal weeks. Changes in neuronal ion transport during this time cause the effects of GABAA receptor (GABAA-R) activation to shift gradually from strongly depolarizing to hyperpolarizing. It is not known whether the depolarizing effects of GABA and the propensity for ictal activity are causally linked. A key question is whether the GABA-mediated depolarization is excitatory, which we defined operationally as being sufficient to trigger action potentials. We assessed the effect of endogenous GABA on ictal activity and neuronal firing rate in hippocampal slices from postnatal day 1 (P1) to P30. In extracellular recordings, there was a strong correlation between the postnatal age at which GABAA-R antagonists decreased action potential frequency (P23) and the age at which ictal activity could be induced by elevated potassium (P23). In addition, there was a strong correlation between the fraction of slices in which ictal activity was induced by elevated potassium concentrations and the fractional decrease in action potential firing when GABAA-Rs were blocked in the presence of ionotropic glutamate receptor antagonists. Finally, ictal activity induced by elevated potassium was blocked by the GABAA-R antagonists bicuculline and SR-95531 (gabazine) and increased in frequency and duration by GABAA-R agonists isoguvacine and muscimol. Thus, the propensity of the developing hippocampus for ictal activity is highly correlated with the effect of GABA on action potential probability and reversed by GABAA antagonists, indicating that GABA-mediated excitation is causally linked to ictal activity in this developmental window.},
  langid = {english},
  keywords = {action potential,CA3,development,epileptiform activity,GABA,hippocampus},
  file = {C:\Users\marc_\Zotero\storage\GWFFYD6D\Dzhala en Staley - 2003 - Excitatory Actions of Endogenously Released GABA C.pdf}
}

@article{dzhalaMechanismsFastRipples2004,
  title = {Mechanisms of {{Fast Ripples}} in the {{Hippocampus}}},
  author = {Dzhala, Volodymyr I. and Staley, Kevin J.},
  date = {2004-10-06},
  journaltitle = {The Journal of Neuroscience},
  shortjournal = {J. Neurosci.},
  volume = {24},
  number = {40},
  pages = {8896--8906},
  issn = {0270-6474, 1529-2401},
  doi = {10.1523/JNEUROSCI.3112-04.2004},
  url = {https://www.jneurosci.org/lookup/doi/10.1523/JNEUROSCI.3112-04.2004},
  urldate = {2024-04-19},
  abstract = {Hippocampal fast ripples (FRs) have been associated with seizure onset in both human and experimental epilepsy. To characterize the mechanisms underlying FR oscillations (200-600 Hz), we studied activity of single neurons and neuronal networks in rat hippocampal slices               in vitro               . The correlation between the action potentials of bursting pyramidal cells and local field potential oscillations suggests that synchronous onset of action potential bursts and similar intrinsic firing patterns among local neurons are both necessary conditions for FR oscillations. Increasing the fidelity of individual pyramidal cell spike train timing by blocking accommodation dramatically increased FR amplitude, whereas blockade of potassium conductances decreased the fidelity of action potential timing in individual pyramidal cell action potential bursts and decreased FR amplitude. Blockade of ionotropic glutamate receptors desynchronized onset of action potential bursts in individual pyramidal cells and abolished fast ripples. Thus, synchronous burst onset mediated by recurrent excitatory synaptic transmission and similar intrinsic spike timing mechanisms in neighboring pyramidal cells are necessary conditions for FR oscillations within the hippocampal network.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\2GDNB23U\Dzhala en Staley - 2004 - Mechanisms of Fast Ripples in the Hippocampus.pdf}
}

@article{dzhalaTransitionInterictalIctal2003,
  title = {Transition from {{Interictal}} to {{Ictal Activity}} in {{Limbic Networks In Vitro}}},
  author = {Dzhala, Volodymyr I. and Staley, Kevin J.},
  date = {2003-08-27},
  journaltitle = {Journal of Neuroscience},
  shortjournal = {J. Neurosci.},
  volume = {23},
  number = {21},
  eprint = {12944517},
  eprinttype = {pmid},
  pages = {7873--7880},
  publisher = {Society for Neuroscience},
  issn = {0270-6474, 1529-2401},
  doi = {10.1523/JNEUROSCI.23-21-07873.2003},
  url = {https://www.jneurosci.org/content/23/21/7873},
  urldate = {2024-04-19},
  abstract = {The transition from brief bursts of synchronous population activity characteristic of interictal epileptiform discharges (IEDs) to more prolonged epochs of population activity characteristic of seizures (ictal-like activity) was recorded in juvenile rat hippocampal-entorhinal cortex slices and hippocampal slices using multiple-site extracellular electrodes. Epileptiform activity was elicited by either increased extracellular potassium or 4-AP. IEDs originated in the CA3 a-b region and spread bidirectionally into CA1 and CA3c dentate gyrus. The transition from IEDs to ictal-like sustained epileptiform activity was reliably preceded by (1) increase in IED propagation velocity, (2) increase in IED secondary afterdischarges and their reverberation between CA3a and CA3c, and (3) shift in the IED initiation area from CA3 a-b to CA3c. Ictal-like sustained network oscillations (10-20 Hz) originated in CA3c and spread to CA1. The pattern of hippocampal ictal-like activity was unaffected by removal of the entorhinal cortex. These findings indicate that interictal and ictal activity can originate in the same neural network, and that the transition from interictal to ictal-like-sustained activity is preceded by predictable alterations in the origin and spread of IEDs. These findings elucidate new targets for investigating the proximate causes, prediction, and treatment of seizures.},
  langid = {english},
  keywords = {CA1,CA3,dentate gyrus,entorhinal cortex,epileptiform activity,hippocampus},
  file = {C:\Users\marc_\Zotero\storage\27BTQ2EV\Dzhala en Staley - 2003 - Transition from Interictal to Ictal Activity in Li.pdf}
}

@article{eunsonClinicalGeneticExpression2000,
  title = {Clinical, Genetic, and Expression Studies of Mutations in the Potassium Channel Gene {{KCNA1}} Reveal New Phenotypic Variability},
  author = {Eunson, L. H. and Rea, R. and Zuberi, S. M. and Youroukos, S. and Panayiotopoulos, C. P. and Liguori, R. and Avoni, P. and McWilliam, R. C. and Stephenson, J. B. P. and Hanna, M. G. and Kullmann, D. M. and Spauschus, A.},
  date = {2000},
  journaltitle = {Annals of Neurology},
  volume = {48},
  number = {4},
  pages = {647--656},
  issn = {1531-8249},
  doi = {10.1002/1531-8249(200010)48:4<647::AID-ANA12>3.0.CO;2-Q},
  url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/1531-8249%28200010%2948%3A4%3C647%3A%3AAID-ANA12%3E3.0.CO%3B2-Q},
  urldate = {2024-04-30},
  abstract = {Episodic ataxia type 1 (EA1) is an autosomal dominant central nervous system potassium channelopathy characterized by brief attacks of cerebellar ataxia and continuous interictal myokymia. Point mutations in the voltage-gated potassium channel gene KCNA1 on chromosome 12p associate with EA1. We have studied 4 families and identified three new and one previously reported heterozygous point mutations in this gene. Affected members in Family A (KCNA1 G724C) exhibit partial epilepsy and myokymia but no ataxic episodes, supporting the suggestion that there is an association between mutations of KCNA1 and epilepsy. Affected members in Family B (KCNA1 C731A) exhibit myokymia alone, suggesting a new phenotype of isolated myokymia. Family C harbors the first truncation to be reported in KCNA1 (C1249T) and exhibits remarkably drug-resistant EA1. Affected members in Family D (KCNA1 G1210A) exhibit attacks typical of EA1. This mutation has recently been reported in an apparently unrelated family, although no functional studies were attempted. Heterologous expression of the proteins encoded by the mutant KCNA1 genes suggest that the four point mutations impair delayed-rectifier type potassium currents by different mechanisms. Increased neuronal excitability is likely to be the common pathophysiological basis for the disease in these families. The degree and nature of the potassium channel dysfunction may be relevant to the new phenotypic observations reported in this study. Ann Neurol 2000;48:647–656},
  langid = {english},
  file = {C\:\\Users\\marc_\\Zotero\\storage\\G2289P57\\Eunson e.a. - 2000 - Clinical, genetic, and expression studies of mutat.pdf;C\:\\Users\\marc_\\Zotero\\storage\\A6Z4A36Y\\1531-8249(200010)484647AID-ANA123.0.html}
}

@article{ewellStuffMemoriesSharp2018,
  title = {The {{Stuff}} of {{Memories}}: {{Sharp Wave Ripple Memory Consolidation}} in {{Epilepsy}}},
  shorttitle = {The {{Stuff}} of {{Memories}}},
  author = {Ewell, Laura A.},
  date = {2018},
  journaltitle = {Epilepsy Currents},
  shortjournal = {Epilepsy Curr},
  volume = {18},
  number = {4},
  eprint = {30254524},
  eprinttype = {pmid},
  pages = {253--254},
  issn = {1535-7597},
  doi = {10.5698/1535-7597.18.4.253},
  url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145387/},
  urldate = {2023-11-07},
  pmcid = {PMC6145387},
  file = {C:\Users\marc_\Zotero\storage\FWWGHJHA\Ewell - 2018 - The Stuff of Memories Sharp Wave Ripple Memory Co.pdf}
}

@article{fengGeneticVariationsGABA2022,
  title = {Genetic Variations in {{GABA}} Metabolism and Epilepsy},
  author = {Feng, Yan and Wei, Zi-Han and Liu, Chao and Li, Guo-Yan and Qiao, Xiao-Zhi and Gan, Ya-Jing and Zhang, Chu-Chu and Deng, Yan-Chun},
  date = {2022-10},
  journaltitle = {Seizure: European Journal of Epilepsy},
  shortjournal = {Seizure: European Journal of Epilepsy},
  volume = {101},
  pages = {22--29},
  issn = {10591311},
  doi = {10.1016/j.seizure.2022.07.007},
  url = {https://linkinghub.elsevier.com/retrieve/pii/S1059131122001601},
  urldate = {2024-04-01},
  abstract = {Epilepsy is a paroxysmal brain disorder that results from an imbalance between neuronal excitation and inhi­ bition. Gamma-aminobutyric acid (GABA) is the most important inhibitory neurotransmitter in the brain and plays an important role in the occurrence and development of epilepsy. Abnormalities in all aspects of GABA metabolism, including GABA synthesis, transport, genes encoding GABA receptors, and GABA inactivation, may lead to epilepsy. GABRA1, GABRA2, GABRA5, GABRB1, GABRB2, GABRB3, GABRG2 and GABBR2 are genes that encode GABA receptors and are commonly associated with epilepsy. Mutations of these genes lead to a variety of epilepsy syndromes with different clinical phenotypes, primarily by down regulating receptor expression and reducing the amplitude of GABA-evoked potentials. GABA is metabolized by GABA transaminase and succinate semi aldehyde dehydrogenase, which are encoded by the ABAT and ALDH5A1 genes, respectively. Mutations of these genes result in symptoms related to deficiency of GABA transaminase and succinate semi aldehyde de­ hydrogenase, such as epilepsy and cognitive impairment. Most of the variation in genes associated with GABA metabolism are accompanied by developmental disorders. This review focuses on advances in understanding the relationship between genetic variation in GABA metabolism and epilepsy to establish a basis for the accurate diagnosis and treatment of epilepsy.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\TKS4UI2A\Feng e.a. - 2022 - Genetic variations in GABA metabolism and epilepsy.pdf}
}

@article{fiestPrevalenceIncidenceEpilepsy2017,
  title = {Prevalence and Incidence of Epilepsy},
  author = {Fiest, Kirsten M. and Sauro, Khara M. and Wiebe, Samuel and Patten, Scott B. and Kwon, Churl-Su and Dykeman, Jonathan and Pringsheim, Tamara and Lorenzetti, Diane L. and Jetté, Nathalie},
  date = {2017-01-17},
  journaltitle = {Neurology},
  shortjournal = {Neurology},
  volume = {88},
  number = {3},
  eprint = {27986877},
  eprinttype = {pmid},
  pages = {296--303},
  issn = {0028-3878},
  doi = {10.1212/WNL.0000000000003509},
  url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5272794/},
  urldate = {2024-04-24},
  abstract = {Objective: To review population-based studies of the prevalence and incidence of epilepsy worldwide and use meta-analytic techniques to explore factors that may explain heterogeneity between estimates. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards were followed. We searched MEDLINE and EMBASE for articles published on the prevalence or incidence of epilepsy since 1985. Abstract, full-text review, and data abstraction were conducted in duplicate. Meta-analyses and meta-regressions were used to explore the association between prevalence or incidence, age group, sex, country level income, and study quality. Results: A total of 222 studies were included (197 on prevalence, 48 on incidence). The point prevalence of active epilepsy was 6.38 per 1,000 persons (95\% confidence interval [95\% CI] 5.57–7.30), while the lifetime prevalence was 7.60 per 1,000 persons (95\% CI 6.17–9.38). The annual cumulative incidence of epilepsy was 67.77 per 100,000 persons (95\% CI 56.69–81.03) while the incidence rate was 61.44 per 100,000 person-years (95\% CI 50.75–74.38). The prevalence of epilepsy did not differ by age group, sex, or study quality. The active annual period prevalence, lifetime prevalence, and incidence rate of epilepsy were higher in low to middle income countries. Epilepsies of unknown etiology and those with generalized seizures had the highest prevalence. Conclusions: This study provides a comprehensive synthesis of the prevalence and incidence of epilepsy from published international studies and offers insight into factors that contribute to heterogeneity between estimates. Significant gaps (e.g., lack of incidence studies, stratification by age groups) were identified. Standardized reporting of future epidemiologic studies of epilepsy is needed.},
  pmcid = {PMC5272794},
  file = {C:\Users\marc_\Zotero\storage\FBJU4BLL\Fiest e.a. - 2017 - Prevalence and incidence of epilepsy.pdf}
}

@article{fisherILAEOfficialReport2014,
  title = {{{ILAE Official Report}}: {{A}} Practical Clinical Definition of Epilepsy},
  shorttitle = {{{ILAE Official Report}}},
  author = {Fisher, Robert S. and Acevedo, Carlos and Arzimanoglou, Alexis and Bogacz, Alicia and Cross, J. Helen and Elger, Christian E. and Engel Jr, Jerome and Forsgren, Lars and French, Jacqueline A. and Glynn, Mike and Hesdorffer, Dale C. and Lee, B.i. and Mathern, Gary W. and Moshé, Solomon L. and Perucca, Emilio and Scheffer, Ingrid E. and Tomson, Torbjörn and Watanabe, Masako and Wiebe, Samuel},
  date = {2014},
  journaltitle = {Epilepsia},
  volume = {55},
  number = {4},
  pages = {475--482},
  issn = {1528-1167},
  doi = {10.1111/epi.12550},
  url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.12550},
  urldate = {2024-04-01},
  abstract = {Epilepsy was defined conceptually in 2005 as a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. This definition is usually practically applied as having two unprovoked seizures {$>$}24 h apart. The International League Against Epilepsy (ILAE) accepted recommendations of a task force altering the practical definition for special circumstances that do not meet the two unprovoked seizures criteria. The task force proposed that epilepsy be considered to be a disease of the brain defined by any of the following conditions: (1) At least two unprovoked (or reflex) seizures occurring {$>$}24 h apart; (2) one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60\%) after two unprovoked seizures, occurring over the next 10 years; (3) diagnosis of an epilepsy syndrome. Epilepsy is considered to be resolved for individuals who either had an age-dependent epilepsy syndrome but are now past the applicable age or who have remained seizure-free for the last 10 years and off antiseizure medicines for at least the last 5 years. “Resolved” is not necessarily identical to the conventional view of “remission or “cure.” Different practical definitions may be formed and used for various specific purposes. This revised definition of epilepsy brings the term in concordance with common use. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.},
  langid = {english},
  keywords = {Definition,Epilepsy,Recurrence,Seizure,Unprovoked},
  file = {C\:\\Users\\marc_\\Zotero\\storage\\2RHWH3NV\\Fisher e.a. - 2014 - ILAE Official Report A practical clinical definit.pdf;C\:\\Users\\marc_\\Zotero\\storage\\A9XBV88P\\epi.html}
}

@article{foitFunctionalNetworksEpilepsy2020,
  title = {Functional {{Networks}} in {{Epilepsy Presurgical Evaluation}}},
  author = {Foit, Niels Alexander and Bernasconi, Andrea and Bernasconi, Neda},
  date = {2020-07},
  journaltitle = {Neurosurgery Clinics of North America},
  shortjournal = {Neurosurgery Clinics of North America},
  volume = {31},
  number = {3},
  pages = {395--405},
  issn = {10423680},
  doi = {10.1016/j.nec.2020.03.004},
  url = {https://linkinghub.elsevier.com/retrieve/pii/S1042368020300188},
  urldate = {2024-04-01},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\CP35AG65\Foit e.a. - 2020 - Functional Networks in Epilepsy Presurgical Evalua.pdf}
}

@article{foldvaryLocalizingValueIctal2001,
  title = {The Localizing Value of Ictal {{EEG}} in Focal Epilepsy},
  author = {Foldvary, N. and Klem, G. and Hammel, J. and Bingaman, W. and Najm, I. and Lüders, H.},
  date = {2001-12-11},
  journaltitle = {Neurology},
  volume = {57},
  number = {11},
  pages = {2022--2028},
  publisher = {Wolters Kluwer},
  doi = {10.1212/WNL.57.11.2022},
  url = {https://www.neurology.org/doi/full/10.1212/WNL.57.11.2022},
  urldate = {2024-05-03},
  abstract = {Objective: To investigate the lateralization and localization of ictal EEG in focal epilepsy. Methods: A total of 486 ictal EEG of 72 patients with focal epilepsy arising from the mesial temporal, neocortical temporal, mesial frontal, dorsolateral frontal, parietal, and occipital regions were analyzed. Results: Surface ictal EEG was adequately localized in 72\% of cases, more often in temporal than extratemporal epilepsy. Localized ictal onsets were seen in 57\% of seizures and were most common in mesial temporal lobe epilepsy (MTLE), lateral frontal lobe epilepsy (LFLE), and parietal lobe epilepsy, whereas lateralized onsets predominated in neocortical temporal lobe epilepsy and generalized onsets in mesial frontal lobe epilepsy (MFLE) and occipital lobe epilepsy. Approximately two-thirds of seizures were localized, 22\% generalized, 4\% lateralized, and 6\% mislocalized/lateralized. False localization/lateralization occurred in 28\% of occipital and 16\% of parietal seizures. Rhythmic temporal theta at ictal onset was seen exclusively in temporal lobe seizures, whereas localized repetitive epileptiform activity was highly predictive of LFLE. Seizures arising from the lateral convexity and mesial regions were differentiated by a high incidence of repetitive epileptiform activity at ictal onset in the former and rhythmic theta activity in the latter. Conclusions: With the exception of mesial frontal lobe epilepsy, ictal recordings are very useful in the localization/lateralization of focal seizures. Some patterns are highly accurate in localizing the epileptogenic lobe. One limitation of ictal EEG is the potential for false localization/lateralization in occipital and parietal lobe epilepsies.}
}

@article{fritschyEpilepsyBalanceGABAA2008,
  title = {Epilepsy, {{E}}/{{I}} Balance and {{GABAA}} Receptor Plasticity},
  author = {Fritschy, Jean-Marc},
  date = {2008-03-28},
  journaltitle = {Frontiers in Molecular Neuroscience},
  shortjournal = {Front. Mol. Neurosci.},
  volume = {1},
  publisher = {Frontiers},
  issn = {1662-5099},
  doi = {10.3389/neuro.02.005.2008},
  url = {https://www.frontiersin.org/articles/10.3389/neuro.02.005.2008},
  urldate = {2024-05-02},
  abstract = {GABAA receptors mediate most of the fast inhibitory transmission in the CNS. They form heteromeric complexes assembled from a large family of subunit genes. The existence of multiple GABAA receptor subtypes differing in subunit composition, localization and functional properties underlies their role for fi ne-tuning of neuronal circuits and genesis of network oscillations. The differential regulation of GABAA receptor subtypes represents a major facet of homeostatic synaptic plasticity and contributes to the excitation/inhibition (E/I) balance under physiological conditions and upon pathological challenges. The purpose of this review is to discuss recent fi ndings highlighting the signifi cance of GABAA receptor heterogeneity for the concept of E/I balance and its relevance for epilepsy. Specifi cally, we address the following issues: (1) role for tonic inhibition, mediated by extrasynaptic GABAA receptors, for controlling neuronal excitability; (2) signifi cance of chloride ion transport for maintenance of the E/I balance in adult brain; and (3) molecular mechanisms underlying GABAA receptor regulation (traffi cking, posttranslational modifi cation, gene transcription) that are important for homoeostatic plasticity. Finally, the relevance of these fi ndings is discussed in light of the involvement of GABAA receptors in epileptic disorders, based on recent experimental studies of temporal lobe epilepsy (TLE) and absence seizures and on the identifi cation of mutations in GABAA receptor subunit genes underlying familial forms of epilepsy.},
  langid = {english},
  keywords = {absence epilepsy,homeostatic plasticity,synaptic plasticity,Temporal Lobe Epilepsy,tonic inhibition},
  file = {C:\Users\marc_\Zotero\storage\QCFQ8RHX\Fritschy - 2008 - Epilepsy, EI balance and GABAA receptor plasticit.pdf}
}

@article{gaoPotassiumChannelsEpilepsy2022,
  title = {Potassium Channels and Epilepsy},
  author = {Gao, Kai and Lin, Zehong and Wen, Sijia and Jiang, Yuwu},
  date = {2022},
  journaltitle = {Acta Neurologica Scandinavica},
  volume = {146},
  number = {6},
  pages = {699--707},
  issn = {1600-0404},
  doi = {10.1111/ane.13695},
  url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/ane.13695},
  urldate = {2024-04-08},
  abstract = {With the development and application of next-generation sequencing technology, the aetiological diagnosis of genetic epilepsy is rapidly becoming easier and less expensive. Additionally, there is a growing body of research into precision therapy based on genetic diagnosis. The numerous genes in the potassium ion channel family constitute the largest family of ion channels: this family is divided into different subtypes. Potassium ion channels play a crucial role in the electrical activity of neurons and are directly involved in the mechanism of epileptic seizures. In China, scientific research on genetic diagnosis and studies of precision therapy for genetic epilepsy are progressing rapidly. Many cases of epilepsy caused by mutation of potassium channel genes have been identified, and several potassium channel gene targets and drug candidates have been discovered. The purpose of this review is to briefly summarize the progress of research on the precise diagnosis and treatment of potassium ion channel-related genetic epilepsy, especially the research conducted in China. Here in, we review several large cohort studies on the genetic diagnosis of epilepsy in China in recent years, summarized the proportion of potassium channel genes. We focus on the progress of precison therapy on some hot epilepsy related potassium channel genes: KCNA1, KCNA2, KCNB1, KCNC1, KCND2, KCNQ2, KCNQ3, KCNMA1, and KCNT1.},
  langid = {english},
  keywords = {epilepsy,genetic diagnosis,potassium ion channel,precision therapy},
  file = {C\:\\Users\\marc_\\Zotero\\storage\\IN6XU8P8\\Gao e.a. - 2022 - Potassium channels and epilepsy.pdf;C\:\\Users\\marc_\\Zotero\\storage\\T55H2APW\\ane.html}
}

@article{gaspariniInitiationPropagationDendritic2004,
  title = {On the {{Initiation}} and {{Propagation}} of {{Dendritic Spikes}} in {{CA1 Pyramidal Neurons}}},
  author = {Gasparini, Sonia and Migliore, Michele and Magee, Jeffrey C.},
  date = {2004-12-08},
  journaltitle = {Journal of Neuroscience},
  shortjournal = {J. Neurosci.},
  volume = {24},
  number = {49},
  eprint = {15590921},
  eprinttype = {pmid},
  pages = {11046--11056},
  publisher = {Society for Neuroscience},
  issn = {0270-6474, 1529-2401},
  doi = {10.1523/JNEUROSCI.2520-04.2004},
  url = {https://www.jneurosci.org/content/24/49/11046},
  urldate = {2023-11-13},
  abstract = {Under certain conditions, regenerative voltage spikes can be initiated locally in the dendrites of CA1 pyramidal neurons. These are interesting events that could potentially provide neurons with additional computational abilities. Using whole-cell dendritic recordings from the distal apical trunk and proximal tuft regions and realistic computer modeling, we have determined that highly synchronized and moderately clustered inputs are required for dendritic spike initiation: ∼50 synaptic inputs spread over 100 μm of the apical trunk/tuft need to be activated within 3 msec. Dendritic spikes are characterized by a more depolarized voltage threshold than at the soma [-48 ± 1 mV (n = 30) vs -56 ± 1 mV (n = 7), respectively] and are mainly generated and shaped by dendritic Na+ and K+ currents. The relative contribution of AMPA and NMDA currents is also important in determining the actual spatiotemporal requirements for dendritic spike initiation. Once initiated, dendritic spikes can easily reach the soma, but their propagation is only moderately strong, so that it can be modulated by physiologically relevant factors such as changes in the Vm and the ionic composition of the extracellular solution. With effective spike propagation, an extremely short-latency neuronal output is produced for greatly reduced input levels. Therefore, dendritic spikes function as efficient detectors of specific input patterns, ensuring that the neuronal response to high levels of input synchrony is a precisely timed action potential output.},
  langid = {english},
  keywords = {AMPA conductance,dendrite,hippocampus,integration,NMDA conductance,spike,synaptic},
  file = {C:\Users\marc_\Zotero\storage\LP7M42TC\Gasparini et al. - 2004 - On the Initiation and Propagation of Dendritic Spi.pdf}
}

@article{ghoriUncertaintyQuantificationSensitivity2023,
  title = {Uncertainty Quantification and Sensitivity Analysis of a Hippocampal {{CA3}} Pyramidal Neuron Model under Electromagnetic Induction},
  author = {Ghori, Muhammad Bilal and Kang, Yanmei},
  date = {2023-07-01},
  journaltitle = {Nonlinear Dynamics},
  shortjournal = {Nonlinear Dyn},
  volume = {111},
  number = {14},
  pages = {13457--13479},
  issn = {1573-269X},
  doi = {10.1007/s11071-023-08514-7},
  url = {https://doi.org/10.1007/s11071-023-08514-7},
  urldate = {2024-04-18},
  abstract = {Due to the huge storage capacity and complex nonlinearity associated with the memristor or memory resistor, various modified single-compartment neuron models with a flux controlled memristor for exploring the influence of electromagnetic induction on dynamical response, including spiking patterns, have been presented. This paper generalizes the relevant investigation of the electrophysiology of a hippocampal CA3 pyramidal neuron by an electromagnetic induction-based variant of the two-compartment Pinsky–Rinzel neuron model. Our emphasis was on the uncertainty quantification and sensitivity analysis of ionic channel conductivities under the electromagnetic induction effect when the two-compartment model is near the Hopf bifurcation point. It was found that the quantities of interest (QoI), such as average interspike interval and spike frequency, mainly depend on the conductivities of calcium and calcium-activated potassium channels and their mutual interactions within a periodic bursting electrical mode. In the case of the aperiodic bursting electrical mode, these QoIs are most sensitive to the conductivities of potassium delayed rectifier, calcium, calcium-activated potassium channels, and their mutual interactions. Our computational results demonstrate that the electrical activities of the hippocampal CA3 pyramidal neuron model under the influence of magnetic flux are sensitive to the transition between complex periodic and aperiodic bursting electrical modes.},
  langid = {english},
  keywords = {Electromagnetic induction,Hippocampal pyramidal neurons,Sensitivity analysis,Uncertainty quantification},
  file = {C:\Users\marc_\Zotero\storage\JCHM6YCC\Ghori en Kang - 2023 - Uncertainty quantification and sensitivity analysi.pdf}
}

@article{goldbergMechanismsEpileptogenesisConvergence2013,
  title = {Mechanisms of Epileptogenesis: A Convergence on Neural Circuit Dysfunction},
  shorttitle = {Mechanisms of Epileptogenesis},
  author = {Goldberg, Ethan M. and Coulter, Douglas A.},
  date = {2013-05},
  journaltitle = {Nature Reviews Neuroscience},
  shortjournal = {Nat Rev Neurosci},
  volume = {14},
  number = {5},
  pages = {337--349},
  publisher = {Nature Publishing Group},
  issn = {1471-0048},
  doi = {10.1038/nrn3482},
  url = {https://www.nature.com/articles/nrn3482},
  urldate = {2024-02-22},
  abstract = {Epileptogenesis is the process whereby a previously normal brain is functionally altered and biased towards the generation of the abnormal paroxysmal electrical activity that defines chronic seizures.The underlying mechanisms that drive epileptogenesis are controversial. It is unlikely that there is a singular mechanism that applies to all epilepsy syndromes.This concept classically refers to the acquired epilepsies but can be viewed as applicable to at least some genetically determined epilepsies as well.Specific themes have emerged in recent years that may represent points of convergence in the field of epileptogenesis, including abnormal signalling by large-scale molecular cascades such as mammalian target of rapamycin and repressor element 1-silencing transcription factor (REST), the dysfunction of particular neuronal cell types with seeming importance in basic mechanisms of epilepsy and dysfunction of discrete neuronal circuit elements.Seizures are by definition circuit-level phenomena that require the re-entrant activation of embedded loop structures within cortical circuits. The above-mentioned considerations further highlight circuit-level considerations and analysis in our future understanding of epileptogenesis and mechanisms of epilepsy.},
  issue = {5},
  langid = {english},
  keywords = {Neurological disorders},
  file = {C:\Users\marc_\Zotero\storage\II5D7F4X\Goldberg and Coulter - 2013 - Mechanisms of epileptogenesis a convergence on ne.pdf}
}

@article{gravesIonChannelsEpilepsy2006,
  title = {Ion Channels and Epilepsy},
  author = {Graves, T.D.},
  date = {2006-04-01},
  journaltitle = {QJM: An International Journal of Medicine},
  shortjournal = {QJM: An International Journal of Medicine},
  volume = {99},
  number = {4},
  pages = {201--217},
  issn = {1460-2725},
  doi = {10.1093/qjmed/hcl021},
  url = {https://doi.org/10.1093/qjmed/hcl021},
  urldate = {2024-04-10},
  file = {C\:\\Users\\marc_\\Zotero\\storage\\EPV5EAZ6\\Graves - 2006 - Ion channels and epilepsy.pdf;C\:\\Users\\marc_\\Zotero\\storage\\L2G5UXYQ\\2261046.html}
}

@article{hainmuellerDentateGyrusCircuits2020,
  title = {Dentate Gyrus Circuits for Encoding, Retrieval and Discrimination of Episodic Memories},
  author = {Hainmueller, Thomas and Bartos, Marlene},
  date = {2020-03},
  journaltitle = {Nature Reviews Neuroscience},
  shortjournal = {Nat Rev Neurosci},
  volume = {21},
  number = {3},
  pages = {153--168},
  publisher = {Nature Publishing Group},
  issn = {1471-0048},
  doi = {10.1038/s41583-019-0260-z},
  url = {https://www.nature.com/articles/s41583-019-0260-z},
  urldate = {2023-11-07},
  abstract = {The dentate gyrus (DG) has a key role in hippocampal memory formation. Intriguingly, DG lesions impair many, but not all, hippocampus-dependent mnemonic functions, indicating that the rest of the hippocampus (CA1–CA3) can operate autonomously under certain conditions. An extensive body of theoretical work has proposed how the architectural elements and various cell types of the DG may underlie its function in cognition. Recent studies recorded and manipulated the activity of different neuron types in the DG during memory tasks and have provided exciting new insights into the mechanisms of DG computational processes, particularly for the encoding, retrieval and discrimination of similar memories. Here, we review these DG-dependent mnemonic functions in light of the new findings and explore mechanistic links between the cellular and network properties of, and the computations performed by, the DG.},
  issue = {3},
  langid = {english},
  keywords = {Hippocampus,Learning and memory,Neural circuits},
  file = {C:\Users\marc_\Zotero\storage\DBMH8M3E\Hainmueller and Bartos - 2020 - Dentate gyrus circuits for encoding, retrieval and.pdf}
}

@article{hakamiEfficacyTolerabilityAntiseizure2021,
  title = {Efficacy and Tolerability of Antiseizure Drugs},
  author = {Hakami, Tahir},
  date = {2021-01-01},
  journaltitle = {Therapeutic Advances in Neurological Disorders},
  shortjournal = {Ther Adv Neurol Disord},
  volume = {14},
  pages = {17562864211037430},
  publisher = {SAGE Publications Ltd STM},
  issn = {1756-2864},
  doi = {10.1177/17562864211037430},
  url = {https://doi.org/10.1177/17562864211037430},
  urldate = {2024-04-30},
  abstract = {Drug-resistant epilepsy occurs in 25–30\% of patients. Furthermore, treatment with a first-generation antiseizure drug (ASD) fails in 30–40\% of individuals because of their intolerable adverse effects. Over the past three decades, 20 newer- (second- and third-)generation ASDs with unique mechanisms of action and pharmacokinetic profiles have been introduced into clinical practice. This advent has expanded the therapeutic armamentarium of epilepsy and broadens the choices of ASDs to match the individual patient’s characteristics. In recent years, research has been focused on defining the ASD of choice for different seizure types. In 2017, the International League Against Epilepsy published a new classification for seizure types and epilepsy syndrome. This classification has been of paramount importance to accurately classify the patient’s seizure type(s) and prescribe the ASD that is appropriate. A year later, the American Academy of Neurology published a new guideline for ASD selection in adult and pediatric patients with new-onset and treatment-resistant epilepsy. The guideline primarily relied on studies that compare the first-generation and second-generation ASDs, with limited data for the efficacy of third-generation drugs. While researchers have been called for investigating those drugs in future research, epilepsy specialists may wish to share their personal experiences to support the treatment guidelines. Given the rapid advances in the development of ASDs in recent years and the continuous updates in definitions, classifications, and treatment guidelines for seizure types and epilepsy syndromes, this review aims to present a complete overview of the current state of the literature about the efficacy and tolerability of ASDs and provide guidance to clinicians about selecting appropriate ASDs for initial treatment of epilepsy according to different seizure types and epilepsy syndromes based on the current literature and recent US and UK practical guidelines.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\HL3P3H3Y\Hakami - 2021 - Efficacy and tolerability of antiseizure drugs.pdf}
}

@article{hodgkinMeasurementCurrentvoltageRelations1952,
  title = {Measurement of Current-Voltage Relations in the Membrane of the Giant Axon of {{Loligo}}},
  author = {Hodgkin, A. L. and Huxley, A. F. and Katz, B.},
  date = {1952-04-28},
  journaltitle = {The Journal of Physiology},
  shortjournal = {J Physiol},
  volume = {116},
  number = {4},
  eprint = {14946712},
  eprinttype = {pmid},
  pages = {424--448},
  issn = {0022-3751},
  url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1392219/},
  urldate = {2024-04-11},
  abstract = {Images null},
  pmcid = {PMC1392219},
  file = {C:\Users\marc_\Zotero\storage\9JIJXC4F\Hodgkin e.a. - 1952 - Measurement of current-voltage relations in the me.pdf}
}

@article{hwangGeneticsTemporalLobe2012a,
  title = {Genetics of Temporal Lobe Epilepsy},
  author = {Hwang, Su-Kyeong and Hirose, Shinichi},
  date = {2012-09},
  journaltitle = {Brain and Development},
  shortjournal = {Brain and Development},
  volume = {34},
  number = {8},
  pages = {609--616},
  issn = {03877604},
  doi = {10.1016/j.braindev.2011.10.008},
  url = {https://linkinghub.elsevier.com/retrieve/pii/S0387760411003007},
  urldate = {2024-04-30},
  abstract = {The most common partial epilepsy, temporal lobe epilepsy (TLE) consists of a heterogeneous group of seizure disorders originating in the temporal lobe. TLE had been thought to develop as a result of acquired structural problems in the temporal lobe. During the past two decades, there has been growing evidence of the important influence of genetic factors, and familial and non-lesional TLE have been increasingly described. Here, we focus on the genetics of TLE and review related genes which have been studied recently. Although its molecular mechanisms are still poorly understood, TLE genetics is a fertile field, awaiting more research.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\CFU9LVRX\Hwang en Hirose - 2012 - Genetics of temporal lobe epilepsy.pdf}
}

@article{ilyasProIctalStateHuman2023,
  title = {Pro-{{Ictal State}} in {{Human Temporal Lobe Epilepsy}}},
  author = {Ilyas, Adeel and Alamoudi, Omar A. and Riley, Kristen O. and Pati, Sandipan},
  date = {2023-02-28},
  journaltitle = {NEJM Evidence},
  volume = {2},
  number = {3},
  pages = {EVIDoa2200187},
  publisher = {Massachusetts Medical Society},
  doi = {10.1056/EVIDoa2200187},
  url = {https://evidence.nejm.org/doi/full/10.1056/EVIDoa2200187},
  urldate = {2024-04-11},
  file = {C:\Users\marc_\Zotero\storage\P9EE56UQ\Ilyas e.a. - 2023 - Pro-Ictal State in Human Temporal Lobe Epilepsy.pdf}
}

@article{isomotoInwardlyRectifyingPotassium1997,
  title = {Inwardly {{Rectifying Potassium Channels}}: {{Their Molecular Heterogeneity}} and {{Function}}},
  shorttitle = {Inwardly {{Rectifying Potassium Channels}}},
  author = {Isomoto, Shojiro and Kondo, Chikako and Kurachi, Yoshihisa},
  date = {1997},
  journaltitle = {The Japanese Journal of Physiology},
  volume = {47},
  number = {1},
  pages = {11--39},
  doi = {10.2170/jjphysiol.47.11},
  keywords = {ATP-sensitive potassium channel,G protein-gated potassium channel,inwardly rectifying potassium channel,molecular cloning},
  file = {C\:\\Users\\marc_\\Zotero\\storage\\IU29YXX3\\Isomoto e.a. - 1997 - Inwardly Rectifying Potassium Channels Their Mole.pdf;C\:\\Users\\marc_\\Zotero\\storage\\JP9DCUZU\\ja.html}
}

@article{kailaGABAActionsIonic2014a,
  title = {{{GABA}} Actions and Ionic Plasticity in Epilepsy},
  author = {Kaila, Kai and Ruusuvuori, Eva and Seja, Patricia and Voipio, Juha and Puskarjov, Martin},
  date = {2014-06},
  journaltitle = {Current Opinion in Neurobiology},
  shortjournal = {Current Opinion in Neurobiology},
  volume = {26},
  pages = {34--41},
  issn = {09594388},
  doi = {10.1016/j.conb.2013.11.004},
  url = {https://linkinghub.elsevier.com/retrieve/pii/S0959438813002146},
  urldate = {2024-05-02},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\D8TLA2WK\Kaila e.a. - 2014 - GABA actions and ionic plasticity in epilepsy.pdf}
}

@article{kalitzinEpilepsyManifestationMultistate2019a,
  title = {Epilepsy as a Manifestation of a Multistate Network of Oscillatory Systems},
  author = {Kalitzin, Stiliyan and Petkov, George and Suffczynski, Piotr and Grigorovsky, Vasily and Bardakjian, Berj L. and Lopes Da Silva, Fernando and Carlen, Peter L.},
  date = {2019-10},
  journaltitle = {Neurobiology of Disease},
  shortjournal = {Neurobiology of Disease},
  volume = {130},
  pages = {104488},
  issn = {09699961},
  doi = {10.1016/j.nbd.2019.104488},
  url = {https://linkinghub.elsevier.com/retrieve/pii/S0969996119300415},
  urldate = {2024-04-11},
  abstract = {The human brain, largely accepted as the most complex biological system known, is still far from being understood in its parts or as a whole. More specifically, biological mechanisms of epileptic states and state transitions are not well understood. Here, we explore the concept of the epilepsy as a manifestation of a multistate network composed of coupled oscillatory units. We also propose that functional coupling between neuroglial elements is a dynamic process, characterized by temporal changes both at short and long time scales. We review various experimental and modelling data suggesting that epilepsy is a pathological manifestation of such a multistate network – both when viewed as a coupled oscillatory network, and as a system of multistate stable state attractors. Based on a coupled oscillators model, we propose a significant role for glial cells in modulating hyperexcitability of the neuroglial networks of the brain. Also, using these concepts, we explain a number of observable phenomena such as propagation patterns of bursts within a seizure in the isolated intact hippocampus in vitro, postictal generalized suppression in human encephalographic seizure data, and changes in seizure susceptibility in epileptic patients. Based on our conceptual model we propose potential clinical applications to estimate brain closeness to ictal transition by means of active perturbations and passive measures during ongoing activity.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\FU52FM27\Kalitzin e.a. - 2019 - Epilepsy as a manifestation of a multistate networ.pdf}
}

@article{karlocaiPhysiologicalSharpWaveripples2014,
  title = {Physiological Sharp Wave-Ripples and Interictal Events in Vitro: What’s the Difference?},
  shorttitle = {Physiological Sharp Wave-Ripples and Interictal Events in Vitro},
  author = {Karlócai, Mária R. and Kohus, Zsolt and Káli, Szabolcs and Ulbert, István and Szabó, Gábor and Máté, Zoltán and Freund, Tamás F. and Gulyás, Attila I.},
  date = {2014-02-01},
  journaltitle = {Brain},
  shortjournal = {Brain},
  volume = {137},
  number = {2},
  pages = {463--485},
  issn = {0006-8950},
  doi = {10.1093/brain/awt348},
  url = {https://doi.org/10.1093/brain/awt348},
  urldate = {2024-04-17},
  abstract = {Sharp wave-ripples and interictal events are physiological and pathological forms of transient high activity in the hippocampus with similar features. Sharp wave-ripples have been shown to be essential in memory consolidation, whereas epileptiform (interictal) events are thought to be damaging. It is essential to grasp the difference between physiological sharp wave-ripples and pathological interictal events to understand the failure of control mechanisms in the latter case. We investigated the dynamics of activity generated intrinsically in the Cornu Ammonis region 3 of the mouse hippocampus in vitro, using four different types of intervention to induce epileptiform activity. As a result, sharp wave-ripples spontaneously occurring in Cornu Ammonis region 3 disappeared, and following an asynchronous transitory phase, activity reorganized into a new form of pathological synchrony. During epileptiform events, all neurons increased their firing rate compared to sharp wave-ripples. Different cell types showed complementary firing: parvalbumin-positive basket cells and some axo-axonic cells stopped firing as a result of a depolarization block at the climax of the events in high potassium, 4-aminopyridine and zero magnesium models, but not in the gabazine model. In contrast, pyramidal cells began firing maximally at this stage. To understand the underlying mechanism we measured changes of intrinsic neuronal and transmission parameters in the high potassium model. We found that the cellular excitability increased and excitatory transmission was enhanced, whereas inhibitory transmission was compromised. We observed a strong short-term depression in parvalbumin-positive basket cell to pyramidal cell transmission. Thus, the collapse of pyramidal cell perisomatic inhibition appears to be a crucial factor in the emergence of epileptiform events.},
  file = {C\:\\Users\\marc_\\Zotero\\storage\\D93SNWHE\\Karlócai e.a. - 2014 - Physiological sharp wave-ripples and interictal ev.pdf;C\:\\Users\\marc_\\Zotero\\storage\\6DQBCVZ9\\284051.html}
}

@article{khazipovSynchronizationGABAergicInterneuronal1997,
  title = {Synchronization of {{GABAergic}} Interneuronal Network in {{CA3}} Subfield of Neonatal Rat Hippocampal Slices.},
  author = {Khazipov, R and Leinekugel, X and Khalilov, I and Gaiarsa, J L and Ben-Ari, Y},
  date = {1997},
  journaltitle = {The Journal of Physiology},
  volume = {498},
  number = {3},
  pages = {763--772},
  issn = {1469-7793},
  doi = {10.1113/jphysiol.1997.sp021900},
  url = {https://onlinelibrary.wiley.com/doi/abs/10.1113/jphysiol.1997.sp021900},
  urldate = {2024-04-17},
  abstract = {1. Cell-attached and whole-cell recordings from interneurons localized in the stratum radiatum of the CA3 subfield (SR-CA3) of neonatal (postnatal days 2-5) rat hippocampal slices were performed to study their activity during the generation of GABAergic giant depolarizing potentials (GDPs) in CA3 pyramidal cells. 2. Dual recordings revealed that during the generation of GDPs in CA3 pyramidal cells, the interneurons fire bursts of spikes, on average 4.5 +/- 1.4 spikes per burst (cell-attached mode). There bursts were induced by periodical large inward currents (interneuronal GDPs) recorded in whole-cell mode. 3. Interneuronal GDPs revealed typical features of polysynaptic neuronal network-driven events: they were blocked by TTX and by high divalent cation medium and they could be evoked in an all-or-none manner by electrical stimulation in different regions of the hippocampus. The network elements required for the generation of GDPs are present in local CA3 circuits since spontaneous GDPs were present in the isolated CA3 subfield of the hippocampal slice. 4. Interneuronal GDPs were mediated by GABAA and glutamate receptors, since: (i) their reversal potential strongly depended on [Cl-]i; (ii) at the reversal potential of GABAA postsynaptic currents an inward component of GDPs was composed of events with the same kinetics as alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor-mediated EPSCs; and (iii) once GABAA receptors were blocked intracellularly by dialysis with F(-)-MgATP-free solution, the remaining component of interneuronal GDPs reversed near 0 mV and rectified at membrane potentials more negative than -20 mV, suggesting an important contribution of NMDA receptors in addition to AMPA receptors. 5. In cell-attached recordings from interneurons, electrical stimulation in the stratum radiatum evoked a burst of spikes that corresponded to evoked GDPs. Pharmacological study of this response revealed that excitation of SR-CA3 interneurons during GDPs is determined by the co-operative depolarizing actions mediated by GABAA and glutamate (AMPA and NMDA) receptors. Interestingly, after blockade of AMPA receptors, GABAA receptor-mediated depolarization enabled the activation of NMDA receptors presumably via attenuation of their voltage-dependent magnesium block. 6. It is concluded that synchronous activation of SR-CA3 interneurons during generation of GDPs is mediated synaptically and is determined by the co-operation of (i) excitatory GABAergic connections between interneurons and (ii) glutamatergic connections to interneurons originating presumably from the pyramidal cells.},
  langid = {english},
  file = {C\:\\Users\\marc_\\Zotero\\storage\\5CRSIASW\\Khazipov e.a. - 1997 - Synchronization of GABAergic interneuronal network.pdf;C\:\\Users\\marc_\\Zotero\\storage\\NP6YDS5L\\jphysiol.1997.html}
}

@article{kitchiginaAlterationsCoherentTheta2018,
  title = {Alterations of {{Coherent Theta}} and {{Gamma Network Oscillations}} as an {{Early Biomarker}} of {{Temporal Lobe Epilepsy}} and {{Alzheimer}}’s {{Disease}}},
  author = {Kitchigina, Valentina F.},
  date = {2018-08-27},
  journaltitle = {Frontiers in Integrative Neuroscience},
  shortjournal = {Front Integr Neurosci},
  volume = {12},
  eprint = {30210311},
  eprinttype = {pmid},
  pages = {36},
  issn = {1662-5145},
  doi = {10.3389/fnint.2018.00036},
  url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6119809/},
  urldate = {2024-01-16},
  abstract = {Alzheimer’s disease (AD) and temporal lobe epilepsy (TLE) are the most common forms of neurodegenerative disorders characterized by the loss of cells and progressive irreversible alteration of cognitive functions, such as attention and memory. AD may be an important cause of epilepsy in the elderly. Early diagnosis of diseases is very important for their successful treatment. Many efforts have been done for defining new biomarkers of these diseases. Significant advances have been made in the searching of some AD and TLE reliable biomarkers, including cerebrospinal fluid and plasma measurements and glucose positron emission tomography. However, there is a great need for the biomarkers that would reflect changes of brain activity within few milliseconds to obtain information about cognitive disturbances. Successful early detection of AD and TLE requires specific biomarkers capable of distinguishing individuals with the progressing disease from ones with other pathologies that affect cognition. In this article, we review recent evidence suggesting that magnetoencephalographic recordings and coherent analysis coupled with behavioral evaluation can be a promising approach to an early detection of AD and TLE., Highlights –Data reviewed include the results of clinical and experimental studies.–Theta and gamma rhythms are disturbed in epilepsy and AD.–Common and different behavioral and oscillatory features of pathologies are compared.–Coherent analysis can be useful for an early diagnostics of diseases.},
  pmcid = {PMC6119809},
  file = {C:\Users\marc_\Zotero\storage\PWCZUJPS\Kitchigina - 2018 - Alterations of Coherent Theta and Gamma Network Os.pdf}
}

@article{koyamaDentateCircuitryModel2016,
  title = {Dentate {{Circuitry}} as a {{Model}} to {{Study Epileptogenesis}}},
  author = {Koyama, Ryuta},
  date = {2016},
  journaltitle = {Biological \& Pharmaceutical Bulletin},
  shortjournal = {Biological \& Pharmaceutical Bulletin},
  volume = {39},
  number = {6},
  pages = {891--896},
  issn = {0918-6158, 1347-5215},
  doi = {10.1248/bpb.b16-00125},
  url = {https://www.jstage.jst.go.jp/article/bpb/39/6/39_b16-00125/_article},
  urldate = {2023-11-07},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\ZARJIHLP\Koyama - 2016 - Dentate Circuitry as a Model to Study Epileptogene.pdf}
}

@article{leaoOLMInterneuronsDifferentially2012,
  title = {{{OLM}} Interneurons Differentially Modulate {{CA3}} and Entorhinal Inputs to Hippocampal {{CA1}} Neurons},
  author = {Leão, Richardson N. and Mikulovic, Sanja and Leão, Katarina E. and Munguba, Hermany and Gezelius, Henrik and Enjin, Anders and Patra, Kalicharan and Eriksson, Anders and Loew, Leslie M. and Tort, Adriano B. L. and Kullander, Klas},
  date = {2012-11},
  journaltitle = {Nature Neuroscience},
  shortjournal = {Nat Neurosci},
  volume = {15},
  number = {11},
  pages = {1524--1530},
  publisher = {Nature Publishing Group},
  issn = {1546-1726},
  doi = {10.1038/nn.3235},
  url = {https://www.nature.com/articles/nn.3235},
  urldate = {2024-04-17},
  abstract = {The authors selectively target a population of hippocampal interneurons called oriens lacunosum-moleculare (OLM) cells with the Chrna2 promoter to demonstrate that these cells differentially modulate CA3 and entorhinal inputs to CA1 pyramidal cells. They also find that OLM cells receive fast cholinergic inputs, providing a plausible explanation for how nicotine affects hippocampal plasticity.},
  langid = {english},
  keywords = {Cellular neuroscience,Hippocampus,Neurotransmitters},
  file = {C:\Users\marc_\Zotero\storage\GUYDZK3B\Leão e.a. - 2012 - OLM interneurons differentially modulate CA3 and e.pdf}
}

@article{leitePlasticitySynapticStrength2005,
  title = {Plasticity, {{Synaptic Strength}}, and {{Epilepsy}}: {{What Can We Learn}} from {{Ultrastructural Data}}?},
  shorttitle = {Plasticity, {{Synaptic Strength}}, and {{Epilepsy}}},
  author = {Leite, João Pereira and Neder, Luciano and Arisi, Gabriel Maisonnave and Carlotti Jr., Carlos Gilberto and Assirati, João Alberto and Moreira, Jorge Eduardo},
  date = {2005},
  journaltitle = {Epilepsia},
  volume = {46},
  number = {s5},
  pages = {134--141},
  issn = {1528-1167},
  doi = {10.1111/j.1528-1167.2005.01021.x},
  url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1528-1167.2005.01021.x},
  urldate = {2024-04-19},
  abstract = {Summary: Central nervous system synapses have an intrinsic plastic capacity to adapt to new conditions with rapid changes in their structure. Such activity-dependent refinement occurs during development and learning, and shares features with diseases such as epilepsy. Quantitative ultrastructural studies based on serial sectioning and reconstructions have shown various structural changes associated with synaptic strength involving both dendritic spines and postsynaptic densities (PSDs) during long-term potentiation (LTP). In this review, we focus on experimental studies that have analyzed at the ultrastructural level the consequences of LTP in rodents, and plastic changes in the hippocampus of experimental models of epilepsy and human tissue obtained during surgeries for intractable temporal lobe epilepsy (TLE). Modifications in spine morphology, increases in the proportion of synapses with perforated PSDs, and formation of multiple spine boutons arising from the same dendrite are the possible sequence of events that accompany hippocampal LTP. Structural remodeling of mossy fiber synapses and formation of aberrant synaptic contacts in the dentate gyrus are common features in experimental models of epilepsy and in human TLE. Combined electrophysiological and ultrastructural studies in kindled rats and chronic epileptic animals have indicated the occurrence of seizure- and neuron loss-induced changes in the hippocampal network. In these experiments, the synaptic contacts on granule cells are similar to those described for LTP. Such changes could be associated with enhancement of synaptic efficiency and may be important in epileptogenesis.},
  langid = {english},
  keywords = {Dendritic spines,Experimental models of epilepsy,LTP,Perforated synapses,Postsynaptic density,Temporal lobe epilepsy},
  file = {C\:\\Users\\marc_\\Zotero\\storage\\YCJD4AI8\\Leite e.a. - 2005 - Plasticity, Synaptic Strength, and Epilepsy What .pdf;C\:\\Users\\marc_\\Zotero\\storage\\3QAPQPAA\\j.1528-1167.2005.01021.html}
}

@article{lemaireModelingNaV1SCN1A2021,
  title = {Modeling {{NaV1}}.1/{{SCN1A}} Sodium Channel Mutations in a Microcircuit with Realistic Ion Concentration Dynamics Suggests Differential {{GABAergic}} Mechanisms Leading to Hyperexcitability in Epilepsy and Hemiplegic Migraine},
  author = {Lemaire, Louisiane and Desroches, Mathieu and Krupa, Martin and Pizzamiglio, Lara and Scalmani, Paolo and Mantegazza, Massimo},
  date = {2021-07-27},
  journaltitle = {PLOS Computational Biology},
  shortjournal = {PLOS Computational Biology},
  volume = {17},
  number = {7},
  pages = {e1009239},
  publisher = {Public Library of Science},
  issn = {1553-7358},
  doi = {10.1371/journal.pcbi.1009239},
  url = {https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1009239},
  urldate = {2024-04-08},
  abstract = {Loss of function mutations of SCN1A, the gene coding for the voltage-gated sodium channel NaV1.1, cause different types of epilepsy, whereas gain of function mutations cause sporadic and familial hemiplegic migraine type 3 (FHM-3). However, it is not clear yet how these opposite effects can induce paroxysmal pathological activities involving neuronal networks’ hyperexcitability that are specific of epilepsy (seizures) or migraine (cortical spreading depolarization, CSD). To better understand differential mechanisms leading to the initiation of these pathological activities, we used a two-neuron conductance-based model of interconnected GABAergic and pyramidal glutamatergic neurons, in which we incorporated ionic concentration dynamics in both neurons. We modeled FHM-3 mutations by increasing the persistent sodium current in the interneuron and epileptogenic mutations by decreasing the sodium conductance in the interneuron. Therefore, we studied both FHM-3 and epileptogenic mutations within the same framework, modifying only two parameters. In our model, the key effect of gain of function FHM-3 mutations is ion fluxes modification at each action potential (in particular the larger activation of voltage-gated potassium channels induced by the NaV1.1 gain of function), and the resulting CSD-triggering extracellular potassium accumulation, which is not caused only by modifications of firing frequency. Loss of function epileptogenic mutations, on the other hand, increase GABAergic neurons’ susceptibility to depolarization block, without major modifications of firing frequency before it. Our modeling results connect qualitatively to experimental data: potassium accumulation in the case of FHM-3 mutations and facilitated depolarization block of the GABAergic neuron in the case of epileptogenic mutations. Both these effects can lead to pyramidal neuron hyperexcitability, inducing in the migraine condition depolarization block of both the GABAergic and the pyramidal neuron. Overall, our findings suggest different mechanisms of network hyperexcitability for migraine and epileptogenic NaV1.1 mutations, implying that the modifications of firing frequency may not be the only relevant pathological mechanism.},
  langid = {english},
  keywords = {Action potentials,Depolarization,Epilepsy,Intracellular membranes,Membrane potential,Migraine,Mouse models,Neurons},
  file = {C:\Users\marc_\Zotero\storage\YKQEJDSL\Lemaire e.a. - 2021 - Modeling NaV1.1SCN1A sodium channel mutations in .pdf}
}

@article{lercheIonChannelsGenetic2013,
  title = {Ion Channels in Genetic and Acquired Forms of Epilepsy},
  author = {Lerche, Holger and Shah, Mala and Beck, Heinz and Noebels, Jeff and Johnston, Dan and Vincent, Angela},
  date = {2013},
  journaltitle = {The Journal of Physiology},
  volume = {591},
  number = {4},
  pages = {753--764},
  issn = {1469-7793},
  doi = {10.1113/jphysiol.2012.240606},
  url = {https://onlinelibrary.wiley.com/doi/abs/10.1113/jphysiol.2012.240606},
  urldate = {2024-04-10},
  abstract = {Genetic mutations causing dysfunction of both voltage- and ligand-gated ion channels make a major contribution to the cause of many different types of familial epilepsy. Key mechanisms comprise defective Na+ channels of inhibitory neurons, or GABAA receptors affecting pre- or postsynaptic GABAergic inhibition, or a dysfunction of different types of channels at axon initial segments. Many of these ion channel mutations have been modelled in mice, which has largely contributed to the understanding of where and how the ion channel defects lead to neuronal hyperexcitability. Animal models of febrile seizures or mesial temporal epilepsy have shown that dendritic K+ channels, hyperpolarization-activated cation channels and T-type Ca2+ channels play important roles in the generation of seizures. For the latter, it has been shown that suppression of their function by pharmacological mechanisms or in knock-out mice can antagonize epileptogenesis. Defects of ion channel function are also associated with forms of acquired epilepsy. Autoantibodies directed against ion channels or associated proteins, such as K+ channels, LGI1 or NMDA receptors, have been identified in epileptic disorders that can largely be included under the term limbic encephalitis which includes limbic seizures, status epilepticus and psychiatric symptoms. We conclude that ion channels and associated proteins are important players in different types of genetic and acquired epilepsies. Nevertheless, the molecular bases for most common forms of epilepsy are not yet clear, and evidence to be discussed indicates just how much more we need to understand about the complex mechanisms that underlie epileptogenesis.},
  langid = {english},
  file = {C\:\\Users\\marc_\\Zotero\\storage\\JVFCKCUU\\Lerche e.a. - 2013 - Ion channels in genetic and acquired forms of epil.pdf;C\:\\Users\\marc_\\Zotero\\storage\\5LIZ2KT7\\jphysiol.2012.html}
}

@article{leungPhasicModulationHippocampal2020a,
  title = {Phasic Modulation of Hippocampal Synaptic Plasticity by Theta Rhythm.},
  author = {Leung, L. Stan and Law, Clayton S. H.},
  date = {2020-12},
  journaltitle = {Behavioral Neuroscience},
  shortjournal = {Behavioral Neuroscience},
  volume = {134},
  number = {6},
  pages = {595--612},
  issn = {1939-0084, 0735-7044},
  doi = {10.1037/bne0000354},
  url = {https://doi.apa.org/doi/10.1037/bne0000354},
  urldate = {2024-04-18},
  abstract = {Theta rhythm and long-term potentiation (LTP) are 2 remarkable discoveries. The theta rhythm is an oscillatory neural activity of 3–10 Hz in the hippocampus. LTP is implicated as a cellular basis of memory, but the function of theta oscillation in memory is not clear. This review suggests that theta rhythm bestows optimal conditions for hippocampal LTP and memory encoding. Theta rhythm in hippocampal CA1 is generated mainly by 2 oscillating dipoles—somatic-inhibition and phase-shifted, distal dendritic excitation, with a smaller contribution by rhythmic proximal (CA3) excitation and distal inhibition. Our recent study showed that LTP of the excitatory synapses on the basal or apical dendrites of CA1 pyramidal cells peaked twice in a theta cycle, at the rising (R) and the midcycle (M) phase of the theta rhythm recorded at the distal apical dendrites. In contrast, evoked population spike excitability peaked at a single phase near the midcycle. We infer that R and M peaks of LTP correspond to maximal dendritic depolarization and maximal somatic depolarization of CA1 pyramidal cells, respectively. A ϳ50° phase shift between LTP-versus-theta-phase functions suggests independent LTP at the basal and apical dendrites. It is argued that theta phase– dependent LTP occurs under physiological conditions, by pairing presynaptic activity with oscillating postsynaptic depolarization. Place cells, showing intrinsic membrane potential oscillations, are ideal LTP participants. It is suggested that theta phase– dependent LTP contributes to memory encoding, and disruption of either theta oscillation or LTP may disrupt memory in various neurological disorders, including epilepsy and Alzheimer’s disease.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\556YWZ7F\Leung en Law - 2020 - Phasic modulation of hippocampal synaptic plastici.pdf}
}

@article{liFeatureExtractionRecognition2013,
  title = {Feature Extraction and Recognition of Ictal {{EEG}} Using {{EMD}} and {{SVM}}},
  author = {Li, Shufang and Zhou, Weidong and Yuan, Qi and Geng, Shujuan and Cai, Dongmei},
  date = {2013-08},
  journaltitle = {Computers in Biology and Medicine},
  shortjournal = {Computers in Biology and Medicine},
  volume = {43},
  number = {7},
  pages = {807--816},
  issn = {00104825},
  doi = {10.1016/j.compbiomed.2013.04.002},
  url = {https://linkinghub.elsevier.com/retrieve/pii/S0010482513000905},
  urldate = {2024-05-03},
  abstract = {Automatic seizure detection is significant for long-term monitoring of epilepsy, as well as for diagnostics and rehabilitation, and can decrease the duration of work required when inspecting the EEG signals. In this study we propose a novel method for feature extraction and pattern recognition of ictal EEG, based upon empirical mode decomposition (EMD) and support vector machine (SVM). First the EEG signal is decomposed into Intrinsic Mode Functions (IMFs) using EMD, and then the coefficient of variation and fluctuation index of IMFs are extracted as features. SVM is then used as the classifier for recognition of ictal EEG. The experimental results show that this algorithm can achieve the sensitivity of 97.00\% and specificity of 96.25\% for interictal and ictal EEGs, and the sensitivity of 98.00\% and specificity of 99.40\% for normal and ictal EEGs on Bonn data sets. Besides, the experiment with interictal and ictal EEGs from Qilu Hospital dataset also yields a satisfactory sensitivity of 98.05\% and specificity of 100\%.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\FNU8RQ94\Li e.a. - 2013 - Feature extraction and recognition of ictal EEG us.pdf}
}

@article{liStudyBrainNetwork2023,
  title = {Study of Brain Network Alternations in Non-Lesional Epilepsy Patients by {{BOLD-fMRI}}},
  author = {Li, Zhisen and Hou, Xiaoxia and Lu, Yanli and Zhao, Huimin and Wang, Meixia and Xu, Bo and Shi, Qianru and Gui, Qian and Wu, Guanhui and Shen, Mingqiang and Zhu, Wei and Xu, Qinrong and Dong, Xiaofeng and Cheng, Qingzhang and Zhang, Jibin and Feng, Hongxuan},
  date = {2023-01-18},
  journaltitle = {Frontiers in Neuroscience},
  shortjournal = {Front. Neurosci.},
  volume = {16},
  publisher = {Frontiers},
  issn = {1662-453X},
  doi = {10.3389/fnins.2022.1031163},
  url = {https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2022.1031163/full},
  urldate = {2024-04-01},
  abstract = {{$<$}sec{$><$}title{$>$}Objective{$<$}/title{$><$}p{$>$}To investigate the changes of brain network in epilepsy patients without intracranial lesions under resting conditions.{$<$}/p{$><$}/sec{$><$}sec{$><$}title{$>$}Methods{$<$}/title{$><$}p{$>$}Twenty-six non-lesional epileptic patients and 42 normal controls were enrolled for BOLD-fMRI examination. The differences in brain network topological characteristics and functional network connectivity between the epilepsy group and the healthy controls were compared using graph theory analysis and independent component analysis.{$<$}/p{$><$}/sec{$><$}sec{$><$}title{$>$}Results{$<$}/title{$><$}p{$>$}The area under the curve for local efficiency was significantly lower in the epilepsy patients compared with healthy controls, while there were no differences in global indicators. Patients with epilepsy had higher functional connectivity in 4 connected components than healthy controls (orbital superior frontal gyrus and medial superior frontal gyrus, medial superior frontal gyrus and angular gyrus, superior parietal gyrus and paracentral lobule, lingual gyrus, and thalamus). In addition, functional connectivity was enhanced in the default mode network, frontoparietal network, dorsal attention network, sensorimotor network, and auditory network in the epilepsy group.{$<$}/p{$><$}/sec{$><$}sec{$><$}title{$>$}Conclusion{$<$}/title{$><$}p{$>$}The topological characteristics and functional connectivity of brain networks are changed in in non-lesional epilepsy patients. Abnormal functional connectivity may suggest reduced brain efficiency in epilepsy patients and also may be a compensatory response to brain function early at earlier stages of the disease.{$<$}/p{$><$}/sec{$>$}},
  langid = {english},
  keywords = {BOLD-fMRI,brain network,Epilepsy,graph theory analysis,Independent Component Analysis},
  file = {C:\Users\marc_\Zotero\storage\VPK4YCWC\Li e.a. - 2023 - Study of brain network alternations in non-lesiona.pdf}
}

@article{liuEpileptogenicZoneLocation2021,
  title = {Epileptogenic {{Zone Location}} of {{Temporal Lobe Epilepsy}} by {{Cross-Frequency Coupling Analysis}}},
  author = {Liu, Xiaotong and Han, Fang and Fu, Rui and Wang, Qingyun and Luan, Guoming},
  date = {2021-11-16},
  journaltitle = {Frontiers in Neurology},
  shortjournal = {Front. Neurol.},
  volume = {12},
  publisher = {Frontiers},
  issn = {1664-2295},
  doi = {10.3389/fneur.2021.764821},
  url = {https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.764821/full},
  urldate = {2024-05-03},
  abstract = {{$<$}p{$>$}Epilepsy is a chronic brain disease with dysfunctional brain networks, and electroencephalography (EEG) is an important tool for epileptogenic zone (EZ) identification, with rich information about frequencies. Different frequency oscillations have different contributions to brain function, and cross-frequency coupling (CFC) has been found to exist within brain regions. Cross-channel and inter-channel analysis should be both focused because they help to analyze how epilepsy networks change and also localize the EZ. In this paper, we analyzed long-term stereo-electroencephalography (SEEG) data from 17 patients with temporal lobe epilepsy. Single-channel and cross-channel CFC features were combined to establish functional brain networks, and the network characteristics under different periods and the localization of EZ were analyzed. It was observed that theta–gamma phase amplitude coupling (PAC) within the electrodes in the seizure region increased during the ictal ({$<$}italic{$>$}p{$<$}/italic{$>$} \&lt; 0.05). Theta–gamma and delta–gamma PAC of cross-channel were enhanced in the early and mid-late ictal, respectively. It was also found that there was a strong cross-frequency coupling state between channels of EZ in the functional network during the ictal, along with a more regular network than interictal. The accuracy rate of EZ localization was 82.4\%. Overall, the combination of single-channel and multi-channel cross-band coupling analysis can help identify seizures and localize EZ for temporal lobe epilepsy. Rhythmic coupling reveals a relationship between the functional network and the seizure status of epilepsy.{$<$}/p{$>$}},
  langid = {english},
  keywords = {Cross-frequency coupling,epileptogenic zone,functional network,SEEG,Temporal Lobe Epilepsy},
  file = {C:\Users\marc_\Zotero\storage\L5HIZY2N\Liu e.a. - 2021 - Epileptogenic Zone Location of Temporal Lobe Epile.pdf}
}

@article{liuRescuingKv10Protein2020,
  title = {Rescuing {{Kv10}}.2 Protein Changes Cognitive and Emotional Function in Kainic Acid-Induced Status Epilepticus Rats},
  author = {Liu, Yamei and Duan, Yanhong and Du, Dongshu and Chen, Fuxue},
  date = {2020-05-01},
  journaltitle = {Epilepsy \& Behavior},
  shortjournal = {Epilepsy \& Behavior},
  volume = {106},
  pages = {106894},
  issn = {1525-5050},
  doi = {10.1016/j.yebeh.2019.106894},
  url = {https://www.sciencedirect.com/science/article/pii/S1525505019312107},
  urldate = {2024-04-30},
  abstract = {Voltage-gated potassium (Kv) channels are widely expressed in the central and peripheral nervous system and are crucial mediators of neuronal excitability. Importantly, these channels also actively participate in cellular and molecular signaling pathways that regulate the life and death processes of neurons. The current study used a kainic acid (KA)-induced temporal lobe epilepsy model to examine the role of the Kv10.2 gene in status epilepticus (SE). Lentiviral plasmids containing the coding sequence region of the KCNH5 gene (LV-KCNH5) were injected into the CA3 subarea of the right dorsal hippocampus within 24\,h in post-SE rats to rescue Kv10.2 protein expression. Open-field and elevated plus maze test results indicated that anxiety-like behavior was ameliorated in the KA\,+\,LV-KCNH5 group rats compared with the SE group rats, and working memory was improved in the Y-maze test. However, the spatial reference memory of the LV-KCNH5 group rats did not improve in the Morris water maze test, and no difference was found in the light–dark transition box test. The results of this study indicate that Kv10.2 protein may play an important role in epilepsy, providing new potential therapeutic directions and drug targets for epilepsy treatment.},
  keywords = {Behavioral experiment,Epilepsy,Hippocampus,Kv10.2},
  file = {C:\Users\marc_\Zotero\storage\MN6QRIZ2\S1525505019312107.html}
}

@article{ludersEpileptogenicZoneGeneral2006,
  title = {The Epileptogenic Zone: General Principles},
  shorttitle = {The Epileptogenic Zone},
  author = {Lüders, Hans O. and Najm, Imad and Nair, Dileep and Widdess-Walsh, Peter and Bingman, William},
  date = {2006-08},
  journaltitle = {Epileptic Disorders: International Epilepsy Journal with Videotape},
  shortjournal = {Epileptic Disord},
  volume = {8 Suppl 2},
  eprint = {17012067},
  eprinttype = {pmid},
  pages = {S1-9},
  issn = {1294-9361},
  langid = {english},
  keywords = {Cerebral Cortex,Electroencephalography,History 19th Century,History 20th Century,Humans,Magnetic Resonance Imaging,Models Theoretical,Neurology,Seizures},
  file = {C:\Users\marc_\Zotero\storage\6BJT2HEU\Lüders e.a. - 2006 - The epileptogenic zone general principles.pdf}
}

@article{lyttonComputerModellingEpilepsy2008,
  title = {Computer Modelling of Epilepsy},
  author = {Lytton, William W.},
  date = {2008-08},
  journaltitle = {Nature Reviews Neuroscience},
  shortjournal = {Nat Rev Neurosci},
  volume = {9},
  number = {8},
  pages = {626--637},
  publisher = {Nature Publishing Group},
  issn = {1471-0048},
  doi = {10.1038/nrn2416},
  url = {https://www.nature.com/articles/nrn2416},
  urldate = {2024-04-01},
  abstract = {Computer modelling of epilepsy is a branch of systems biology, a science that aims to combine the discoveries made by reductionist approaches into systems in order to understand how primary pathologies and secondary reactions interact to produce disease. Epilepsy, a dynamical disease of the brain, is well suited to study from the perspective of dynamical systems.Epilepsy is a complex set of syndromes with the commonality of recurrent seizures. Not only do the many individual epilepsy syndromes have different causes, but most epilepsies develop owing to the interaction of many causes at molecular, cellular, network and developmental levels, defying efforts to define simple cause-and-effect relations and suggesting the need for computer modelling.Knowledge discovery and data mining provides the substrate and support for dynamical modelling and allows the findings to be applied back to the research and clinical settings. The various dynamical modelling techniques that are used include stochastic models, low-dimensional (lumped) deterministic models and detailed neuronal network models.Computer models are applied across the range of epilepsy phenomenology, from the molecular to the clinical. At the patient level, Markov models have been used to assess patterns of remission and relapse in pediatric epilepsy. At the molecular level, deterministic models can predict alterations in cellular activity with ion-channel mutations.Many seizure models simulate activity at the network level. Some of these are lumped models, which use mean-field approximations to reduce the activity of many neurons to simple oscillators that are then coupled to produce complex activity patterns. Other models incorporate the details of neural activity and synaptic interactions, in order to reach down to the molecular level at which drug effects take place.Uncommonly among areas of neuroscience research, computer modelling is immediately accessible through downloads of established models. An intrinsically collaborative activity, the future of the endeavour lies in the cooperative efforts of clinicians, experimentalists and modellers.},
  langid = {english},
  keywords = {Animal Genetics and Genomics,Behavioral Sciences,Biological Techniques,Biomedicine,general,Neurobiology,Neurosciences},
  file = {C:\Users\marc_\Zotero\storage\D4ZTVXBE\Lytton - 2008 - Computer modelling of epilepsy.pdf}
}

@article{lyttonComputerSimulationEpilepsy2005,
  title = {Computer Simulation of Epilepsy: {{Implications}} for Seizure Spread and Behavioral Dysfunction},
  shorttitle = {Computer Simulation of Epilepsy},
  author = {Lytton, William W. and Orman, Rena and Stewart, Mark},
  date = {2005-11},
  journaltitle = {Epilepsy \& Behavior},
  shortjournal = {Epilepsy \& Behavior},
  volume = {7},
  number = {3},
  pages = {336--344},
  issn = {15255050},
  doi = {10.1016/j.yebeh.2005.06.011},
  url = {https://linkinghub.elsevier.com/retrieve/pii/S1525505005002271},
  urldate = {2024-04-01},
  abstract = {Hippocampal area CA3 has been one of the most intensively studied brain regions for computer models of epileptiform activity. As physiological studies begin to extend outward to other hippocampal and parahippocampal areas, we must extend these models to understand more complex circuitry containing diverse elements. Study of subiculum is of particular interest in this context, as it is a structure of intermediate complexity, with an inchoate columnar and laminar organization. In addition to helping us understand seizures, modeling of these structures will also help us understand the genesis of physiological activity patterns that are below threshold for seizure generation. Such modeling can also serve as a basis for speculation regarding the nonictal behavioral consequences of epilepsy.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\HRVV5L7Z\Lytton e.a. - 2005 - Computer simulation of epilepsy Implications for .pdf}
}

@article{lyttonSimulationsCorticalPyramidal1991,
  title = {Simulations of Cortical Pyramidal Neurons Synchronized by Inhibitory Interneurons},
  author = {Lytton, W. W. and Sejnowski, T. J.},
  date = {1991-09},
  journaltitle = {Journal of Neurophysiology},
  volume = {66},
  number = {3},
  pages = {1059--1079},
  publisher = {American Physiological Society},
  issn = {0022-3077},
  doi = {10.1152/jn.1991.66.3.1059},
  url = {https://journals.physiology.org/doi/abs/10.1152/jn.1991.66.3.1059},
  urldate = {2024-04-17},
  abstract = {1. The interaction between inhibitory interneurons and cortical pyramidal neurons was studied by use of computer simulations to test whether inhibitory interneurons could assist in phase-locking postsynaptic cells. Two models were used: a simplified model, which included only 3 membrane channels, and a detailed 11-channel model. 2. The 11-channel model included most of the ion channels known to be present in neocortical pyramidal neurons as well as calcium diffusion and other membrane mechanisms. The kinetics for the channels were obtained from voltage-clamp studies in a variety of preparations. The parameters were then adjusted to produce repetitive bursting similar to that seen in some cortical pyramidal cells entrained during visual stimulation. 3. Phase-locking to a train of inhibitory postsynaptic potentials (IPSPs) located on or near the soma was observed in the 3-channel model cell subjected to random synaptic bombardment. In the 11-channel model, phase-locking due to multiple IPSPs was compared with phase-locking due to multiple excitatory postsynaptic potentials (EPSPs). Phase-locking began to occur when 20\% of the IPSPs (20/100) or 40\% of the EPSPs (4,000/10,000) were synchronized. The exact percentages differed with different 11-channel models, but either EPSPs or IPSPs would generally produce entrainment with approximately 40\% synchronization. Thus 40 inhibitory boutons had an effect equivalent to 4,000 excitatory boutons in producing phase-locking. 4. Phase-locking with IPSPs in these models was possible because the IPSPs could cause either an increase or a decrease in firing rate over a limited range. The IPSPs served a modulatory role, increasing the rate of firing in some cases and decreasing it in others, depending on the state of the cell. 5. We examined frequency entrainment by IPSPs. In the 3-channel model, frequency entrainment of a postsynaptic cell was observed with a rapid train of strong (20-100 nS), brief, compound IPSPs. A 40-Hz compound IPSP train of 60 nS entrained cells having initial firing rates between 32 and 47 Hz. Below this range, cells could be partially entrained. Above the range, entrainment would fail. Frequency entrainment in the 3-channel model generally occurred on the first cycle after onset of the IPSPs. 6. Phase-locking and frequency entrainment were less robust in the 11-channel model. This was partly because bursts rather than individual spikes were being entrained. A 40-Hz, 90-nS compound IPSP train entrained a model cell upward from 34 Hz. Downward frequency entrainment also occurred.(ABSTRACT TRUNCATED AT 400 WORDS)}
}

@article{malezieuxThetaOscillationsCoincide2020,
  title = {Theta {{Oscillations Coincide}} with {{Sustained Hyperpolarization}} in {{CA3 Pyramidal Cells}}, {{Underlying Decreased Firing}}},
  author = {Malezieux, Meryl and Kees, Ashley L. and Mulle, Christophe},
  date = {2020-07},
  journaltitle = {Cell Reports},
  shortjournal = {Cell Reports},
  volume = {32},
  number = {1},
  pages = {107868},
  issn = {22111247},
  doi = {10.1016/j.celrep.2020.107868},
  url = {https://linkinghub.elsevier.com/retrieve/pii/S2211124720308494},
  urldate = {2024-04-18},
  abstract = {Brain states modulate the membrane potential dynamics of neurons, influencing the functional repertoire of the network. Pyramidal cells (PCs) in the hippocampal CA3 are necessary for rapid memory encoding, which preferentially occurs during exploratory behavior in the high-arousal theta state. However, the relationship between the membrane potential dynamics of CA3 PCs and theta has not been explored. Here we characterize the changes in the membrane potential of PCs in relation to theta using electrophysiological recordings in awake mice. During theta, most PCs behave in a stereotypical manner, consistently hyperpolarizing timelocked to the duration of theta. Additionally, PCs display lower membrane potential variance and a reduced firing rate. In contrast, during large irregular activity, PCs show heterogeneous changes in membrane potential. This suggests coordinated hyperpolarization of PCs during theta, possibly caused by increased inhibition. This could lead to a higher signal-to-noise ratio in the small population of PCs active during theta, as observed in ensemble recordings.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\N46MRN76\Malezieux e.a. - 2020 - Theta Oscillations Coincide with Sustained Hyperpo.pdf}
}

@article{manganottiInfluenceSomatosensoryInput1998,
  title = {Influence of Somatosensory Input on Paroxysmal Activity in Benign Rolandic Epilepsy with 'Extreme Somatosensory Evoked Potentials'.},
  author = {Manganotti, P and Miniussi, C and Santorum, E and Tinazzi, M and Bonato, C and Marzi, C A and Fiaschi, A and Dalla Bernardina, B and Zanette, G},
  date = {1998-04-01},
  journaltitle = {Brain},
  shortjournal = {Brain},
  volume = {121},
  number = {4},
  pages = {647--658},
  issn = {0006-8950},
  doi = {10.1093/brain/121.4.647},
  url = {https://doi.org/10.1093/brain/121.4.647},
  urldate = {2024-05-03},
  abstract = {We studied six patients suffering from benign rolandic epilepsy of childhood with central temporal spikes who presented so-called 'extreme somatosensory evoked potentials (SEPs)' following peripheral somatosensory stimulation. Stimuli were delivered to the fingers of one hand using both a triggered tendon hammer and low-intensity electrical stimulation. The electrical stimulation was delivered in sequences in different conditions (i.e. random order, 1, 3 and 10 Hz). Both tapping and electrical stimulation produced scalp evoked potentials in all subjects, characterized by a spike followed by a slow wave, similar in morphology and scalp distribution to the spontaneously occurring spikes. This paroxysmal activity was sensitive to stimulus rate; the number of evoked spikes was inversely related to the frequency of stimulation, being maximal at 1 Hz and disappearing at high frequencies (10 Hz). Spontaneous spikes disappeared during high-frequency stimulation but were present during low-frequency stimulation. Averaged SEPs at 3-Hz stimulation showed a late high-amplitude component, identical in morphology and distribution to the single evoked spike. We therefore conclude that, in these subjects, the so-called 'extreme SEPs' are evoked spikes and that evoked and spontaneous spikes share common cortical sensorimotor generators. The evidence that these generators can be influenced by afferent input provides important information regarding the functional mechanisms involved in modulating cortical excitability in benign rolandic epilepsy. Moreover, we suggest that peripheral electrical stimulation can be used as an additional activation test in this kind of epilepsy.},
  file = {C\:\\Users\\marc_\\Zotero\\storage\\UHAEUYXG\\Manganotti e.a. - 1998 - Influence of somatosensory input on paroxysmal act.pdf;C\:\\Users\\marc_\\Zotero\\storage\\5N4TGM7K\\260855.html}
}

@article{marcelinChanneldependentDeficitTheta2009a,
  title = {H Channel-Dependent Deficit of Theta Oscillation Resonance and Phase Shift in Temporal Lobe Epilepsy},
  author = {Marcelin, Béatrice and Chauvière, Laëtitia and Becker, Albert and Migliore, Michele and Esclapez, Monique and Bernard, Christophe},
  date = {2009-03},
  journaltitle = {Neurobiology of Disease},
  shortjournal = {Neurobiology of Disease},
  volume = {33},
  number = {3},
  pages = {436--447},
  issn = {09699961},
  doi = {10.1016/j.nbd.2008.11.019},
  url = {https://linkinghub.elsevier.com/retrieve/pii/S096999610800301X},
  urldate = {2024-03-30},
  abstract = {Ih tunes hippocampal CA1 pyramidal cell dendrites to optimally respond to theta inputs (4–12 Hz), and provides a negative time delay to theta inputs. Decreased Ih activity, as seen in experimental temporal lobe epilepsy (TLE), could significantly alter the response of dendrites to theta inputs. Here we report a progressive erosion of theta resonance and phase lead in pyramidal cell dendrites during epileptogenesis in a rat model of TLE. These alterations were due to decreased Ih availability, via a decline in HCN1/HCN2 subunit expression resulting in decreased h currents, and altered kinetics of the residual channels. This acquired HCN channelopathy thus compromises temporal coding and tuning to theta inputs in pyramidal cell dendrites. Decreased theta resonance in vitro also correlated with a reduction in theta frequency and power in vivo. We suggest that the neuronal/circuitry changes associated with TLE, including altered Ih-dependent inductive mechanisms, can disrupt hippocampal theta function.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\RW93R8E6\Marcelin e.a. - 2009 - h channel-dependent deficit of theta oscillation r.pdf}
}

@article{mbizvoEpilepsyrelatedOtherCauses2019,
  title = {Epilepsy-Related and Other Causes of Mortality in People with Epilepsy: {{A}} Systematic Review of Systematic Reviews},
  shorttitle = {Epilepsy-Related and Other Causes of Mortality in People with Epilepsy},
  author = {Mbizvo, Gashirai K. and Bennett, Kyle and Simpson, Colin R. and Duncan, Susan E. and Chin, Richard F. M.},
  date = {2019-11-01},
  journaltitle = {Epilepsy Research},
  shortjournal = {Epilepsy Research},
  volume = {157},
  pages = {106192},
  issn = {0920-1211},
  doi = {10.1016/j.eplepsyres.2019.106192},
  url = {https://www.sciencedirect.com/science/article/pii/S0920121119302803},
  urldate = {2024-03-30},
  abstract = {Background This systematic review of epilepsy mortality systematic reviews evaluates comparative risks, causes, and risk factors for all-cause mortality in people with epilepsy (PWE) to specifically establish the burden of epilepsy-related deaths. Methods MEDLINE and Embase were searched from conception to 26/12/2018 for systematic reviews evaluating all-cause mortality in PWE of any age. Independent study selection, data extraction and quality assessment were performed. Deaths were separated into epilepsy-related and unrelated using a recently published classification system. Outcomes included standardized mortality ratio (SMR) and mortality rate (MR) in a primary analysis of comparative risks, causes, and risk factors for all-cause and epilepsy-related mortality. A narrative synthesis of review findings was used to present results, including from a secondary analysis of individual epilepsy-related death risk factors. Results Six moderate or high-quality systematic reviews were included in the primary analysis, evaluating 103 observational studies. All-cause mortality remained similarly high between 1950 and present (median SMR range 2.2–3.4). Africa had the highest SMR (median 5.4, range 2.6–7.2). SMRs were also higher for children {$<$}18 years (median 7.5, range 3.1–22.4) than adults (median 2.6, range 1.3–8.7), and for epilepsy-related (median 3.8, range 0.0–82.4,) than unrelated causes (median 1.7, range 0.7–17.6). Structural brain disease conferred the greatest risk for all-cause mortality (SMR range 24.0–41.5). Common epilepsy-related causes included alcohol, drowning, pneumonia, and suicide. In secondary analysis of nine additional systematic reviews, epilepsy-related death risk factors were reported for sudden unexpected death in epilepsy (SUDEP), drowning and suicide. Conclusions Premature all-cause mortality remains a major problem in PWE globally, particularly in children and young adults, with most being epilepsy-related and potentially preventable. SUDEP is only one of several other common and important epilepsy-related causes of death.},
  keywords = {Case-control study,Cohort study,Death,Overview of reviews,Seizures,SUDEP},
  file = {C\:\\Users\\marc_\\Zotero\\storage\\547JMPAH\\Mbizvo e.a. - 2019 - Epilepsy-related and other causes of mortality in .pdf;C\:\\Users\\marc_\\Zotero\\storage\\LGITPG5F\\S0920121119302803.html}
}

@article{mccormickHodgkinHuxleyModel2007,
  title = {Hodgkin and {{Huxley}} Model — Still Standing?},
  author = {McCormick, David A. and Shu, Yousheng and Yu, Yuguo},
  date = {2007-01},
  journaltitle = {Nature},
  volume = {445},
  number = {7123},
  pages = {E1-E2},
  publisher = {Nature Publishing Group},
  issn = {1476-4687},
  doi = {10.1038/nature05523},
  url = {https://www.nature.com/articles/nature05523},
  urldate = {2024-04-16},
  abstract = {Arising from: B. Naundorf, F. Wolf \& M. Volgushev Nature 440, 1060–1063 (2006); Naundorf et al. reply},
  langid = {english},
  keywords = {Humanities and Social Sciences,multidisciplinary,Science},
  file = {C:\Users\marc_\Zotero\storage\EPI6WBKT\McCormick e.a. - 2007 - Hodgkin and Huxley model — still standing.pdf}
}

@article{meadowsFunctionalBiochemicalAnalysis2002,
  title = {Functional and {{Biochemical Analysis}} of a {{Sodium Channel}} Β1 {{Subunit Mutation Responsible}} for {{Generalized Epilepsy}} with {{Febrile Seizures Plus Type}} 1},
  author = {Meadows, Laurence S. and Malhotra, Jyoti and Loukas, Andrew and Thyagarajan, Veena and Kazen-Gillespie, Kristin A. and Koopman, Matthew C. and Kriegler, Steven and Isom, Lori L. and Ragsdale, David S.},
  date = {2002-12-15},
  journaltitle = {Journal of Neuroscience},
  shortjournal = {J. Neurosci.},
  volume = {22},
  number = {24},
  eprint = {12486163},
  eprinttype = {pmid},
  pages = {10699--10709},
  publisher = {Society for Neuroscience},
  issn = {0270-6474, 1529-2401},
  doi = {10.1523/JNEUROSCI.22-24-10699.2002},
  url = {https://www.jneurosci.org/content/22/24/10699},
  urldate = {2024-04-30},
  abstract = {Generalized epilepsy with febrile seizures plus type 1 is an inherited human epileptic syndrome, associated with a cysteine-to-tryptophan (C121W) mutation in the extracellular immunoglobin domain of the auxiliary β1 subunit of the voltage-gated sodium channel. The mutation disrupts β1 function, but how this leads to epilepsy is not understood. In this study, we make several observations that may be relevant for understanding why this β1 mutation results in seizures. First, using electrophysiological recordings from mammalian cell lines, coexpressing sodium channel α subunits and either wild-type β1 or C121Wβ1, we show that loss of β1 functional modulation, caused by the C121W mutation, leads to increased sodium channel availability at hyperpolarized membrane potentials and reduced sodium channel rundown during high-frequency channel activity, compared with channels coexpressed with wild-type β1. In contrast, neither wild-type β1 nor C121Wβ1 significantly affected sodium current time course or the voltage dependence of channel activation. We also show, using a Drosophila S2 cell adhesion assay, that the C121W mutation disrupts β1–β1 homophilic cell adhesion, suggesting that the mutation may alter the ability of β1 to mediate protein–protein interactions critical for sodium channel localization. Finally, we demonstrate that neither functional modulation nor cell adhesion mediated by wild-type β1 is occluded by coexpression of C121Wβ1, arguing against the idea that the mutant β1 acts as a dominant-negative subunit. Together, these data suggest that C121Wβ1 causes subtle effects on channel function and subcellular distribution that bias neurons toward hyperexcitabity and epileptogenesis.},
  langid = {english},
  keywords = {cell adhesion,channelopathy,Drosophila S2 cells,epilepsy,patch clamp,voltage-gated sodium channel,β1 subunit},
  file = {C:\Users\marc_\Zotero\storage\QJWSED8D\Meadows e.a. - 2002 - Functional and Biochemical Analysis of a Sodium Ch.pdf}
}

@article{menendezdelapridaThresholdBehaviorInitiation2006,
  title = {Threshold {{Behavior}} in the {{Initiation}} of {{Hippocampal Population Bursts}}},
  author = {Menendez De La Prida, Liset and Huberfeld, Gilles and Cohen, Ivan and Miles, Richard},
  date = {2006-01},
  journaltitle = {Neuron},
  shortjournal = {Neuron},
  volume = {49},
  number = {1},
  pages = {131--142},
  issn = {08966273},
  doi = {10.1016/j.neuron.2005.10.034},
  url = {https://linkinghub.elsevier.com/retrieve/pii/S0896627305009578},
  urldate = {2024-04-19},
  abstract = {Hippocampal population discharges such as sharp waves, epileptiform firing, and GDPs recur at long and variable intervals. The mechanisms for their precise timing are not well understood. Here, we show that population bursts in the disinhibited CA3 region are initiated at a threshold level of population firing after recovery from a previous event. Each population discharge follows an active buildup period when synaptic traffic and cell firing increase to threshold levels. Single-cell firing can advance burst onset by increasing population firing to suprathreshold values. Population synchrony is suppressed when threshold frequencies cannot be reached due to reduced cellular excitability or synaptic efficacy. Reducing synaptic strength reveals partially synchronous population bursts that are curtailed by GABAB-mediated conductances. Excitatory glutamatergic transmission and delayed GABABmediated signals have opposing feedback effects on CA3 cell firing and so determine threshold behavior for population synchrony.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\UWM8YC3J\Menendez De La Prida e.a. - 2006 - Threshold Behavior in the Initiation of Hippocampa.pdf}
}

@article{micheliMechanisticModelNMDA2021,
  title = {A {{Mechanistic Model}} of {{NMDA}} and {{AMPA Receptor-Mediated Synaptic Transmission}} in {{Individual Hippocampal CA3-CA1 Synapses}}: {{A Computational Multiscale Approach}}},
  shorttitle = {A {{Mechanistic Model}} of {{NMDA}} and {{AMPA Receptor-Mediated Synaptic Transmission}} in {{Individual Hippocampal CA3-CA1 Synapses}}},
  author = {Micheli, Pietro and Ribeiro, Rui and Giorgetti, Alejandro},
  date = {2021-01},
  journaltitle = {International Journal of Molecular Sciences},
  volume = {22},
  number = {4},
  pages = {1536},
  publisher = {Multidisciplinary Digital Publishing Institute},
  issn = {1422-0067},
  doi = {10.3390/ijms22041536},
  url = {https://www.mdpi.com/1422-0067/22/4/1536},
  urldate = {2024-04-17},
  abstract = {Inside hippocampal circuits, neuroplasticity events that individual cells may undergo during synaptic transmissions occur in the form of Long-Term Potentiation (LTP) and Long-Term Depression (LTD). The high density of NMDA receptors expressed on the surface of the dendritic CA1 spines confers to hippocampal CA3-CA1 synapses the ability to easily undergo NMDA-mediated LTP and LTD, which is essential for some forms of explicit learning in mammals. Providing a comprehensive kinetic model that can be used for running computer simulations of the synaptic transmission process is currently a major challenge. Here, we propose a compartmentalized kinetic model for CA3-CA1 synaptic transmission. Our major goal was to tune our model in order to predict the functional impact caused by disease associated variants of NMDA receptors related to severe cognitive impairment. Indeed, for variants Glu413Gly and Cys461Phe, our model predicts negative shifts in the glutamate affinity and changes in the kinetic behavior, consistent with experimental data. These results point to the predictive power of this multiscale viewpoint, which aims to integrate the quantitative kinetic description of large interaction networks typical of system biology approaches with a focus on the quality of a few, key, molecular interactions typical of structural biology ones.},
  issue = {4},
  langid = {english},
  keywords = {AMPA,CA3-CA1 synapses,multiscale modeling,NMDA,Schaffer collateral-CA1 synapses,systems biology},
  file = {C:\Users\marc_\Zotero\storage\5WZME4MN\Micheli e.a. - 2021 - A Mechanistic Model of NMDA and AMPA Receptor-Medi.pdf}
}

@article{miglioreDendriticIhSelectivelyBlocks2004,
  title = {Dendritic {{IhSelectively Blocks Temporal Summation}} of {{Unsynchronized Distal Inputs}} in {{CA1 Pyramidal Neurons}}},
  author = {Migliore, M. and Messineo, L. and Ferrante, M.},
  date = {2004-01-01},
  journaltitle = {Journal of Computational Neuroscience},
  shortjournal = {J Comput Neurosci},
  volume = {16},
  number = {1},
  pages = {5--13},
  issn = {1573-6873},
  doi = {10.1023/B:JCNS.0000004837.81595.b0},
  url = {https://doi.org/10.1023/B:JCNS.0000004837.81595.b0},
  urldate = {2023-11-13},
  abstract = {The active dendritic conductances shape the input-output properties of many principal neurons in different brain regions, and the various ways in which they regulate neuronal excitability need to be investigated to better understand their functional consequences. Using a realistic model of a hippocampal CA1 pyramidal neuron, we show a major role for the hyperpolarization-activated current, Ih, in regulating the spike probability of a neuron when independent synaptic inputs are activated with different degrees of synchronization and at different distances from the soma. The results allowed us to make the experimentally testable prediction that the Ihin these neurons is needed to reduce neuronal excitability selectively for distal unsynchronized, but not for synchronized, inputs.},
  langid = {english},
  keywords = {CA1,dendritic integration,I h,modeling},
  file = {C:\Users\marc_\Zotero\storage\5BSI3CSI\Migliore et al. - 2004 - Dendritic IhSelectively Blocks Temporal Summation .pdf}
}

@article{miglioreParallelNetworkSimulations2006,
  title = {Parallel Network Simulations with {{NEURON}}},
  author = {Migliore, M. and Cannia, C. and Lytton, W. W. and Markram, Henry and Hines, M. L.},
  date = {2006-10-01},
  journaltitle = {Journal of Computational Neuroscience},
  shortjournal = {J Comput Neurosci},
  volume = {21},
  number = {2},
  pages = {119--129},
  issn = {1573-6873},
  doi = {10.1007/s10827-006-7949-5},
  url = {https://doi.org/10.1007/s10827-006-7949-5},
  urldate = {2024-04-01},
  abstract = {The NEURON simulation environment has been extended to support parallel network simulations. Each processor integrates the equations for its subnet over an interval equal to the minimum (interprocessor) presynaptic spike generation to postsynaptic spike delivery connection delay. The performance of three published network models with very different spike patterns exhibits superlinear speedup on Beowulf clusters and demonstrates that spike communication overhead is often less than the benefit of an increased fraction of the entire problem fitting into high speed cache. On the EPFL IBM Blue Gene, almost linear speedup was obtained up to 100 processors. Increasing one model from 500 to 40,000 realistic cells exhibited almost linear speedup on 2000 processors, with an integration time of 9.8 seconds and communication time of 1.3~seconds. The potential for speed-ups of several orders of magnitude makes practical the running of large network simulations that could otherwise not be explored.},
  langid = {english},
  keywords = {Computer simulation,Parallel computation,Realistic modeling,Spiking networks},
  file = {C:\Users\marc_\Zotero\storage\6RSGZTAU\Migliore e.a. - 2006 - Parallel network simulations with NEURON.pdf}
}

@article{mosheEpilepsyNewAdvances2015a,
  title = {Epilepsy: New Advances},
  shorttitle = {Epilepsy},
  author = {Moshé, Solomon L and Perucca, Emilio and Ryvlin, Philippe and Tomson, Torbjörn},
  date = {2015-03},
  journaltitle = {The Lancet},
  shortjournal = {The Lancet},
  volume = {385},
  number = {9971},
  pages = {884--898},
  issn = {01406736},
  doi = {10.1016/S0140-6736(14)60456-6},
  url = {https://linkinghub.elsevier.com/retrieve/pii/S0140673614604566},
  urldate = {2024-03-30},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\YBAQN65X\Moshé e.a. - 2015 - Epilepsy new advances.pdf}
}

@article{mysinMechanismsFunctionsRole2022,
  title = {From Mechanisms to Functions: {{The}} Role of Theta and Gamma Coherence in the Intrahippocampal Circuits},
  shorttitle = {From Mechanisms to Functions},
  author = {Mysin, Ivan and Shubina, Liubov},
  date = {2022},
  journaltitle = {Hippocampus},
  volume = {32},
  number = {5},
  pages = {342--358},
  issn = {1098-1063},
  doi = {10.1002/hipo.23410},
  url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/hipo.23410},
  urldate = {2024-04-18},
  abstract = {Brain rhythms are essential for information processing in neuronal networks. Oscillations recorded in different brain regions can be synchronized and have a constant phase difference, that is, they can be coherent. Coherence between local field potential (LFP) signals from different brain regions may be correlated with the performance of cognitive tasks, indicating that these regions of the brain are jointly involved in the information processing. Why does coherence occur and how is it related to the information transfer between different regions of the hippocampal formation? In this article, we discuss possible mechanisms of theta and gamma coherence and its role in the hippocampus-dependent attention and memory processes, since theta and gamma rhythms are most pronounced in these processes. We review in vivo studies of interactions between different regions of the hippocampal formation in theta and gamma frequency bands. The key propositions of the review are as follows: (1) coherence emerges from synchronous postsynaptic currents in principal neurons as a result of synchronization of neuronal spike activity; (2) the synchronization of neuronal spike patterns in two regions of the hippocampal formation can be realized through induction or resonance; (3) coherence at a specific time point reflects the transfer of information between the regions of the hippocampal formation; (4) the physiological roles of theta and gamma coherence are different due to their different functions and mechanisms of generation. All hippocampal neurons are involved in theta activity, and theta coherence arranges the firing order of principal neurons throughout the hippocampal formation. In contrast, gamma coherence reflects the coupling of active neuronal ensembles. Overall, the coherence of LFPs between different areas of the brain is an important physiological process based on the synchronized neuronal firing, and it is essential for cooperative information processing.},
  langid = {english},
  keywords = {cell assemblies,local field potentials (LFP),memory,navigation,novelty,oscillations},
  file = {C\:\\Users\\marc_\\Zotero\\storage\\BB37FJ74\\Mysin en Shubina - 2022 - From mechanisms to functions The role of theta an.pdf;C\:\\Users\\marc_\\Zotero\\storage\\RKCFZX2G\\hipo.html}
}

@article{nasrallahSeizureinducedStrengtheningRecurrent2022,
  title = {Seizure-Induced Strengthening of a Recurrent Excitatory Circuit in the Dentate Gyrus Is Proconvulsant},
  author = {Nasrallah, Kaoutsar and Frechou, M. Agustina and Yoon, Young J. and Persaud, Subrina and Gonçalves, J. Tiago and Castillo, Pablo E.},
  date = {2022-08-09},
  journaltitle = {Proceedings of the National Academy of Sciences},
  volume = {119},
  number = {32},
  pages = {e2201151119},
  publisher = {Proceedings of the National Academy of Sciences},
  doi = {10.1073/pnas.2201151119},
  url = {https://www.pnas.org/doi/full/10.1073/pnas.2201151119},
  urldate = {2023-11-07},
  abstract = {Epilepsy is a devastating brain disorder for which effective treatments are very limited. There is growing interest in early intervention, which requires a better mechanistic understanding of the early stages of this disorder. While diverse brain insults can lead to epileptic activity, a common cellular mechanism relies on uncontrolled recurrent excitatory activity. In the dentate gyrus, excitatory mossy cells (MCs) project extensively onto granule cells (GCs) throughout the hippocampus, thus establishing a recurrent MC-GC-MC excitatory loop. MCs are implicated in temporal lobe epilepsy, a common form of epilepsy, but their role during initial seizures (i.e., before the characteristic MC loss that occurs in late stages) is unclear. Here, we show that initial seizures acutely induced with an intraperitoneal kainic acid (KA) injection in adult mice, a well-established model that leads to experimental epilepsy, not only increased MC and GC activity in~vivo but also triggered a brain-derived neurotrophic factor (BDNF)–dependent long-term potentiation (LTP) at MC-GC excitatory synapses. Moreover, in~vivo induction of MC-GC LTP using MC-selective optogenetic stimulation worsened KA-induced seizures. Conversely, Bdnf genetic removal from GCs, which abolishes LTP, and selective MC silencing were both anticonvulsant. Thus, initial seizures are associated with MC-GC synaptic strengthening, which may promote later epileptic activity. Our findings reveal a potential mechanism of epileptogenesis that may help in developing therapeutic strategies for early intervention.},
  file = {C:\Users\marc_\Zotero\storage\9UR4ISMW\Nasrallah et al. - 2022 - Seizure-induced strengthening of a recurrent excit.pdf}
}

@article{neymotinKetamineDisruptsTheta2011,
  title = {Ketamine {{Disrupts Theta Modulation}} of {{Gamma}} in a {{Computer Model}} of {{Hippocampus}}},
  author = {Neymotin, Samuel A. and Lazarewicz, Maciej T. and Sherif, Mohamed and Contreras, Diego and Finkel, Leif H. and Lytton, William W.},
  date = {2011-08-10},
  journaltitle = {Journal of Neuroscience},
  shortjournal = {J. Neurosci.},
  volume = {31},
  number = {32},
  eprint = {21832203},
  eprinttype = {pmid},
  pages = {11733--11743},
  publisher = {Society for Neuroscience},
  issn = {0270-6474, 1529-2401},
  doi = {10.1523/JNEUROSCI.0501-11.2011},
  url = {https://www.jneurosci.org/content/31/32/11733},
  urldate = {2023-11-13},
  abstract = {Abnormalities in oscillations have been suggested to play a role in schizophrenia. We studied theta-modulated gamma oscillations in a computer model of hippocampal CA3 in vivo with and without simulated application of ketamine, an NMDA receptor antagonist and psychotomimetic. Networks of 1200 multicompartment neurons [pyramidal, basket, and oriens-lacunosum moleculare (OLM) cells] generated theta and gamma oscillations from intrinsic network dynamics: basket cells primarily generated gamma and amplified theta, while OLM cells strongly contributed to theta. Extrinsic medial septal inputs paced theta and amplified both theta and gamma oscillations. Exploration of NMDA receptor reduction across all location combinations demonstrated that the experimentally observed ketamine effect occurred only with isolated reduction of NMDA receptors on OLMs. In the ketamine simulations, lower OLM activity reduced theta power and disinhibited pyramidal cells, resulting in increased basket cell activation and gamma power. Our simulations predict the following: (1) ketamine increases firing rates; (2) oscillations can be generated by intrinsic hippocampal circuits; (3) medial-septum inputs pace and augment oscillations; (4) pyramidal cells lead basket cells at the gamma peak but lag at trough; (5) basket cells amplify theta rhythms; (6) ketamine alters oscillations due to primary blockade at OLM NMDA receptors; (7) ketamine alters phase relationships of cell firing; (8) ketamine reduces network responsivity to the environment; (9) ketamine effect could be reversed by providing a continuous inward current to OLM cells. We suggest that this last prediction has implications for a possible novel treatment for cognitive deficits of schizophrenia by targeting OLM cells.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\9PGHRVRB\Neymotin et al. - 2011 - Ketamine Disrupts Theta Modulation of Gamma in a C.pdf}
}

@article{nikitinPotassiumChannelsProminent2021,
  title = {Potassium Channels as Prominent Targets and Tools for the Treatment of Epilepsy},
  author = {family=Nikitin, given=ES, given-i=ES and family=Vinogradova, given=LV, given-i=LV},
  date = {2021-03-04},
  journaltitle = {Expert Opinion on Therapeutic Targets},
  volume = {25},
  number = {3},
  eprint = {33754930},
  eprinttype = {pmid},
  pages = {223--235},
  publisher = {Taylor \& Francis},
  issn = {1472-8222},
  doi = {10.1080/14728222.2021.1908263},
  url = {https://doi.org/10.1080/14728222.2021.1908263},
  urldate = {2024-04-08},
  abstract = {K+ channels are of great interest to epilepsy research as mutations in their genes are found in humans with inherited epilepsy. At the level of cellular physiology, K+~channels control neuronal intrinsic excitability and are the main contributors to membrane repolarization of active neurons. Recently, a genetically modified voltage-dependent K+ channel has been patented as a remedy for epileptic seizures. We review the role of potassium channels in excitability, clinical and experimental evidence for the association of potassium channelopathies with epilepsy, the targeting of K+~channels by drugs, and perspectives of gene therapy in epilepsy with the expression of extra K+~channels in the brain. Control over K+~conductance is of great potential benefit for the treatment of epilepsy. Nowadays, gene therapy affecting K+~channels is one of the most promising approaches to treat pharmacoresistant focal epilepsy.},
  keywords = {channelopathies,Epilepsy,gene therapy,pharmacology,potassium channels},
  file = {C:\Users\marc_\Zotero\storage\KG3PRVDA\Nikitin en Vinogradova - 2021 - Potassium channels as prominent targets and tools .pdf}
}

@article{noachtarRoleEEGEpilepsy2009,
  title = {The Role of {{EEG}} in Epilepsy: {{A}} Critical Review},
  shorttitle = {The Role of {{EEG}} in Epilepsy},
  author = {Noachtar, Soheyl and Rémi, Jan},
  date = {2009-05},
  journaltitle = {Epilepsy \& Behavior},
  shortjournal = {Epilepsy \& Behavior},
  volume = {15},
  number = {1},
  pages = {22--33},
  issn = {15255050},
  doi = {10.1016/j.yebeh.2009.02.035},
  url = {https://linkinghub.elsevier.com/retrieve/pii/S1525505009000924},
  urldate = {2024-05-03},
  abstract = {Electroencephalography (EEG) is the most specific method to define epileptogenic cortex. Its sensitivity and specificity depend on several factors such as age and recording procedures, for example, sleep recordings and activation procedures (hyperventilation, photic stimulation). EEG reveals characteristic findings in several epilepsy syndromes. Rarely, epileptiform discharges are recorded in healthy, particularly young individuals. Ictal video/EEG recording is considered to be critical in localizing the epileptogenic zone. A careful analysis of the first clinical signs and symptoms of a seizure and of the evolution of the seizure symptomatology can provide important localizing clues. Although surface EEG recordings are less sensitive than invasive studies, they provide the best overview and, therefore, the most efficient way to define the approximate localization of the epileptogenic zone. Invasive recordings are used in patients in whom the epileptogenic zone either cannot be located with noninvasive diagnostic methods or is adjacent to eloquent cortex. The most commonly used invasive electrodes are stereotactically implanted depth electrodes and subdural strip or grid electrodes. Foramen ovale and epidural electrodes are of intermediate invasiveness, but less sensitive. Invasive electrodes are subject to sampling errors if misplaced and should be used only after exhaustive noninvasive evaluations have (1) failed to localize the epileptogenic zone and (2) led to a testable hypothesis regarding this localization. Invasive EEG studies are associated with additional risks that are justifiable only if there is a good chance of obtaining essential localizing information and on a potentially resectable area.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\MIYN6267\Noachtar en Rémi - 2009 - The role of EEG in epilepsy A critical review.pdf}
}

@article{nyhusFunctionalRoleGamma2010,
  title = {Functional Role of Gamma and Theta Oscillations in Episodic Memory},
  author = {Nyhus, Erika and Curran, Tim},
  date = {2010-06},
  journaltitle = {Neuroscience \& Biobehavioral Reviews},
  shortjournal = {Neuroscience \& Biobehavioral Reviews},
  volume = {34},
  number = {7},
  pages = {1023--1035},
  issn = {01497634},
  doi = {10.1016/j.neubiorev.2009.12.014},
  url = {https://linkinghub.elsevier.com/retrieve/pii/S0149763409002115},
  urldate = {2024-04-08},
  abstract = {The primary aim of this review is to examine evidence for a functional role of gamma and theta oscillations in human episodic memory. It is proposed here that gamma and theta oscillations allow for the transient interaction between cortical structures and the hippocampus for the encoding and retrieval of episodic memories as described by the hippocampal memory indexing theory (Teyler and DiScenna, 1986). Gamma rhythms can act in the cortex to bind perceptual features and in the hippocampus to bind the rich perceptual and contextual information from diverse brain regions into episodic representations. Theta oscillations act to temporally order these individual episodic memory representations. Through feedback projections from the hippocampus to the cortex these gamma and theta patterns could cause the reinstatement of the entire episodic memory representation in the cortex. In addition, theta oscillations could allow for top-down control from the frontal cortex to the hippocampus modulating the encoding and retrieval of episodic memories.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\RKRI6MGY\Nyhus en Curran - 2010 - Functional role of gamma and theta oscillations in.pdf}
}

@article{otarulaNetworksTemporalLobe2020,
  title = {Networks in {{Temporal Lobe Epilepsy}}},
  author = {Otárula, Karina A. González and Schuele, Stephan},
  date = {2020-07-01},
  journaltitle = {Neurosurgery Clinics},
  shortjournal = {Neurosurgery Clinics},
  volume = {31},
  number = {3},
  eprint = {32475481},
  eprinttype = {pmid},
  pages = {309--317},
  publisher = {Elsevier},
  issn = {1042-3680, 1558-1349},
  doi = {10.1016/j.nec.2020.02.001},
  url = {https://www.neurosurgery.theclinics.com/article/S1042-3680(20)30014-0/fulltext},
  urldate = {2024-04-08},
  langid = {english},
  keywords = {Connectivity,Epilepsy,Networks,Temporal lobe},
  file = {C:\Users\marc_\Zotero\storage\PDBNWXZ2\Otárula en Schuele - 2020 - Networks in Temporal Lobe Epilepsy.pdf}
}

@article{oyrerIonChannelsGenetic2018,
  title = {Ion {{Channels}} in {{Genetic Epilepsy}}: {{From Genes}} and {{Mechanisms}} to {{Disease-Targeted Therapies}}},
  shorttitle = {Ion {{Channels}} in {{Genetic Epilepsy}}},
  author = {Oyrer, Julia and Maljevic, Snezana and Scheffer, Ingrid E. and Berkovic, Samuel F. and Petrou, Steven and Reid, Christopher A.},
  editor = {Sexton, Patrick M.},
  date = {2018-01-01},
  journaltitle = {Pharmacological Reviews},
  shortjournal = {Pharmacol Rev},
  volume = {70},
  number = {1},
  eprint = {29263209},
  eprinttype = {pmid},
  pages = {142--173},
  publisher = {{American Society for Pharmacology and Experimental Therapeutics}},
  issn = {0031-6997, 1521-0081},
  doi = {10.1124/pr.117.014456},
  url = {https://pharmrev.aspetjournals.org/content/70/1/142},
  urldate = {2024-04-09},
  abstract = {Epilepsy is a common and serious neurologic disease with a strong genetic component. Genetic studies have identified an increasing collection of disease-causing genes. The impact of these genetic discoveries is wide reaching—from precise diagnosis and classification of syndromes to the discovery and validation of new drug targets and the development of disease-targeted therapeutic strategies. About 25\% of genes identified in epilepsy encode ion channels. Much of our understanding of disease mechanisms comes from work focused on this class of protein. In this study, we review the genetic, molecular, and physiologic evidence supporting the pathogenic role of a number of different voltage- and ligand-activated ion channels in genetic epilepsy. We also review proposed disease mechanisms for each ion channel and highlight targeted therapeutic strategies.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\XF959IL5\Oyrer e.a. - 2018 - Ion Channels in Genetic Epilepsy From Genes and M.pdf}
}

@article{pazMicrocircuitsTheirInteractions2015,
  title = {Microcircuits and Their Interactions in Epilepsy: Is the Focus out of Focus?},
  shorttitle = {Microcircuits and Their Interactions in Epilepsy},
  author = {Paz, Jeanne T and Huguenard, John R},
  date = {2015-03},
  journaltitle = {Nature Neuroscience},
  shortjournal = {Nat Neurosci},
  volume = {18},
  number = {3},
  pages = {351--359},
  issn = {1097-6256, 1546-1726},
  doi = {10.1038/nn.3950},
  url = {https://www.nature.com/articles/nn.3950},
  urldate = {2023-10-31},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\GS5TIAHY\Paz and Huguenard - 2015 - Microcircuits and their interactions in epilepsy .pdf}
}

@article{piperNetworkguidedNeuromodulationEpilepsy2022,
  title = {Towards Network-Guided Neuromodulation for Epilepsy},
  author = {Piper, Rory J and Richardson, R Mark and Worrell, Gregory and Carmichael, David W and Baldeweg, Torsten and Litt, Brian and Denison, Timothy and Tisdall, Martin M},
  date = {2022-10-21},
  journaltitle = {Brain},
  volume = {145},
  number = {10},
  pages = {3347--3362},
  issn = {0006-8950, 1460-2156},
  doi = {10.1093/brain/awac234},
  url = {https://academic.oup.com/brain/article/145/10/3347/6623456},
  urldate = {2024-04-01},
  abstract = {Abstract             Epilepsy is well-recognized as a disorder of brain networks. There is a growing body of research to identify critical nodes within dynamic epileptic networks with the aim to target therapies that halt the onset and propagation of seizures. In parallel, intracranial neuromodulation, including deep brain stimulation and responsive neurostimulation, are well-established and expanding as therapies to reduce seizures in adults with focal-onset epilepsy; and there is emerging evidence for their efficacy in children and generalized-onset seizure disorders. The convergence of these advancing fields is driving an era of ‘network-guided neuromodulation’ for epilepsy. In this review, we distil the current literature on network mechanisms underlying neurostimulation for epilepsy. We discuss the modulation of key ‘propagation points’ in the epileptogenic network, focusing primarily on thalamic nuclei targeted in current clinical practice. These include (i) the anterior nucleus of thalamus, now a clinically approved and targeted site for open loop stimulation, and increasingly targeted for responsive neurostimulation; and (ii) the centromedian nucleus of the thalamus, a target for both deep brain stimulation and responsive neurostimulation in generalized-onset epilepsies. We discuss briefly the networks associated with other emerging neuromodulation targets, such as the pulvinar of the thalamus, piriform cortex, septal area, subthalamic nucleus, cerebellum and others. We report synergistic findings garnered from multiple modalities of investigation that have revealed structural and functional networks associated with these propagation points — including scalp and invasive EEG, and diffusion and functional MRI. We also report on intracranial recordings from implanted devices which provide us data on the dynamic networks we are aiming to modulate. Finally, we review the continuing evolution of network-guided neuromodulation for epilepsy to accelerate progress towards two translational goals: (i) to use pre-surgical network analyses to determine patient candidacy for neurostimulation for epilepsy by providing network biomarkers that predict efficacy; and (ii) to deliver precise, personalized and effective antiepileptic stimulation to prevent and arrest seizure propagation through mapping and modulation of each patients’ individual epileptogenic networks.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\K2P2T997\Piper e.a. - 2022 - Towards network-guided neuromodulation for epileps.pdf}
}

@article{renFunctionalBrainNetwork2020,
  title = {Functional Brain Network Mechanism of Executive Control Dysfunction in Temporal Lobe Epilepsy},
  author = {Ren, Yanping and Pan, Liping and Du, Xueyun and Hou, Yuying and Li, Xun and Song, Yijun},
  date = {2020-04-15},
  journaltitle = {BMC Neurology},
  shortjournal = {BMC Neurol},
  volume = {20},
  number = {1},
  pages = {137},
  issn = {1471-2377},
  doi = {10.1186/s12883-020-01711-6},
  url = {https://doi.org/10.1186/s12883-020-01711-6},
  urldate = {2024-04-08},
  abstract = {Executive control dysfunction is observed in a sizable number of patients with temporal lobe epilepsy (TLE). Neural oscillations in the theta band are increasingly recognized as having a crucial role in executive control network. The purpose of this study was to investigate the alterations in the theta band in executive control network and explore the functional brain network mechanisms of executive control dysfunction in TLE patients.},
  langid = {english},
  keywords = {Executive control,Functional connectivity,Scalp electroencephalogram,Temporal lobe epilepsy,Theta},
  file = {C:\Users\marc_\Zotero\storage\Z42GCDK4\Ren e.a. - 2020 - Functional brain network mechanism of executive co.pdf}
}

@article{royerEpilepsyBrainNetwork2022,
  title = {Epilepsy and Brain Network Hubs},
  author = {Royer, Jessica and Bernhardt, Boris C. and Larivière, Sara and Gleichgerrcht, Ezequiel and Vorderwülbecke, Bernd J. and Vulliémoz, Serge and Bonilha, Leonardo},
  date = {2022},
  journaltitle = {Epilepsia},
  volume = {63},
  number = {3},
  pages = {537--550},
  issn = {1528-1167},
  doi = {10.1111/epi.17171},
  url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.17171},
  urldate = {2024-03-30},
  abstract = {Epilepsy is a disorder of brain networks. A better understanding of structural and dynamic network properties may improve epilepsy diagnosis, treatment, and prognostics. Hubs are brain regions with high connectivity to other parts of the brain and are typically situated along the brain's most efficient communication pathways, supporting large-scale brain wiring and many higher order neural functions. The visualization and analysis of hubs offers a perspective on regional and global network organization and can provide novel insights into brain disorders and epilepsy. By notably supporting the interaction between various brain networks, hubs may be implicated in seizure spread and in epilepsy-related phenotypes. In this review, we will discuss the growing literature on atypical hub organization in common epilepsy syndromes, both related to neuroimaging of brain structure and function, and related to neurophysiological data from magneto- and electroencephalographic measures of neural dynamics. With studies increasingly exploring the clinical utility of network neuroscience approaches, we highlight the potential of hub mapping as a candidate biomarker of cognitive dysfunction and postsurgical seizure outcome. We will conclude the review with a discussion of current limitations and outlook for future research.},
  langid = {english},
  keywords = {biomarker,connectome,EEG,epilepsy,hubs,MRI,network,neuroimaging},
  file = {C\:\\Users\\marc_\\Zotero\\storage\\TBXMFAG8\\Royer e.a. - 2022 - Epilepsy and brain network hubs.pdf;C\:\\Users\\marc_\\Zotero\\storage\\55SJYJX6\\epi.html}
}

@article{sanjayImpairedDendriticInhibition2015,
  title = {Impaired Dendritic Inhibition Leads to Epileptic Activity in a Computer Model of {{CA3}}},
  author = {Sanjay, M. and Neymotin, Samuel A. and Krothapalli, Srinivasa B.},
  date = {2015},
  journaltitle = {Hippocampus},
  volume = {25},
  number = {11},
  pages = {1336--1350},
  issn = {1098-1063},
  doi = {10.1002/hipo.22440},
  url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/hipo.22440},
  urldate = {2023-11-10},
  abstract = {Temporal lobe epilepsy (TLE) is a common type of epilepsy with hippocampus as the usual site of origin. The CA3 subfield of hippocampus is reported to have a low epileptic threshold and hence initiates the disorder in patients with TLE. This study computationally investigates how impaired dendritic inhibition of pyramidal cells in the vulnerable CA3 subfield leads to generation of epileptic activity. A model of CA3 subfield consisting of 800 pyramidal cells, 200 basket cells (BC) and 200 Oriens—Lacunosum Moleculare (O-LM) interneurons was used. The dendritic inhibition provided by O-LM interneurons is reported to be selectively impaired in some TLEs. A step-wise approach is taken to investigate how alterations in network connectivity lead to generation of epileptic patterns. Initially, dendritic inhibition alone was reduced, followed by an increase in the external inputs received at the distal dendrites of pyramidal cells, and finally additional changes were made at the synapses between all neurons in the network. In the first case, when the dendritic inhibition of pyramidal cells alone was reduced, the local field potential activity changed from a theta-modulated gamma pattern to a prominently gamma frequency pattern. In the second case, in addition to this reduction of dendritic inhibition, with a simultaneous large increase in the external excitatory inputs received by pyramidal cells, the basket cells entered a state of depolarization block, causing the network to generate a typical ictal activity pattern. In the third case, when the dendritic inhibition onto the pyramidal cells was reduced and changes were simultaneously made in synaptic connectivity between all neurons in the network, the basket cells were again observed to enter depolarization block. In the third case, impairment of dendritic inhibition required to generate an ictal activity pattern was lesser than the two previous cases. Moreover, the ictal like activity began earlier in the third case. Hence, our study suggests that greater synaptic plasticity occurring in the whole network due to increase in reception of external excitatory inputs (due to impaired dendritic inhibition) makes the network more susceptible to generation of epileptic activity. © 2015 Wiley Periodicals, Inc.},
  langid = {english},
  keywords = {basket cells,depolarization block,hippocampus,ictal activity,oscillations,temporal lobe epilepsy},
  file = {C\:\\Users\\marc_\\Zotero\\storage\\ZWDXT5EI\\Sanjay et al. - 2015 - Impaired dendritic inhibition leads to epileptic a.pdf;C\:\\Users\\marc_\\Zotero\\storage\\TLIVJ9S7\\hipo.html}
}

@article{saragaActiveDendritesSpike2003,
  title = {Active Dendrites and Spike Propagation in Multicompartment Models of Oriens-Lacunosum/Moleculare Hippocampal Interneurons},
  author = {Saraga, F. and Wu, C. P. and Zhang, L. and Skinner, F. K.},
  date = {2003},
  journaltitle = {The Journal of Physiology},
  volume = {552},
  number = {3},
  pages = {673--689},
  issn = {1469-7793},
  doi = {10.1113/jphysiol.2003.046177},
  url = {https://onlinelibrary.wiley.com/doi/abs/10.1113/jphysiol.2003.046177},
  urldate = {2023-11-13},
  abstract = {It is well known that interneurons are heterogeneous in their morphologies, biophysical properties, pharmacological sensitivities and electrophysiological responses, but it is unknown how best to understand this diversity. Given their critical roles in shaping brain output, it is important to try to understand the functionality of their computational characteristics. To do this, we focus on specific interneuron subtypes. In particular, it has recently been shown that long-term potentiation is induced specifically on oriens-lacunosum/moleculare (O-LM) interneurons in hippocampus CA1 and that the same cells contain the highest density of dendritic sodium and potassium conductances measured to date. We have created multi-compartment models of an O-LM hippocampal interneuron using passive properties, channel kinetics, densities and distributions specific to this cell type, and explored its signalling characteristics. We found that spike initiation depends on both location and amount of input, as well as the intrinsic properties of the interneuron. Distal synaptic input always produces strong back-propagating spikes whereas proximal input could produce both forward- and back-propagating spikes depending on the input strength. We speculate that the highly active dendrites of these interneurons endow them with a specialized function within the hippocampal circuitry by allowing them to regulate direct and indirect signalling pathways within the hippocampus.},
  langid = {english},
  file = {C\:\\Users\\marc_\\Zotero\\storage\\TZRZAB98\\Saraga et al. - 2003 - Active dendrites and spike propagation in multicom.pdf;C\:\\Users\\marc_\\Zotero\\storage\\D3I4Y2K7\\jphysiol.2003.html}
}

@article{schefferTemporalLobeEpilepsy2006,
  title = {Temporal Lobe Epilepsy and {{GEFS}}+ Phenotypes Associated with {{SCN1B}} Mutations},
  author = {Scheffer, I. E. and Harkin, L. A. and Grinton, B. E. and Dibbens, L. M. and Turner, S. J. and Zielinski, M. A. and Xu, R. and Jackson, G. and Adams, J. and Connellan, M. and Petrou, S. and Wellard, R. M. and Briellmann, R. S. and Wallace, R. H. and Mulley, J. C. and Berkovic, S. F.},
  date = {2006-11-21},
  journaltitle = {Brain},
  shortjournal = {Brain},
  volume = {130},
  number = {1},
  pages = {100--109},
  issn = {0006-8950, 1460-2156},
  doi = {10.1093/brain/awl272},
  url = {https://academic.oup.com/brain/article-lookup/doi/10.1093/brain/awl272},
  urldate = {2024-04-30},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\RQLGK78U\Scheffer e.a. - 2006 - Temporal lobe epilepsy and GEFS+ phenotypes associ.pdf}
}

@article{schummPlasticityImpairmentExposes2022,
  title = {Plasticity Impairment Exposes {{CA3}} Vulnerability in a Hippocampal Network Model of Mild Traumatic Brain Injury},
  author = {Schumm, Samantha N. and Gabrieli, David and Meaney, David F.},
  date = {2022},
  journaltitle = {Hippocampus},
  volume = {32},
  number = {3},
  pages = {231--250},
  issn = {1098-1063},
  doi = {10.1002/hipo.23402},
  url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/hipo.23402},
  urldate = {2024-04-18},
  abstract = {Proper function of the hippocampus is critical for executing cognitive tasks such as learning and memory. Traumatic brain injury (TBI) and other neurological disorders are commonly associated with cognitive deficits and hippocampal dysfunction. Although there are many existing models of individual subregions of the hippocampus, few models attempt to integrate the primary areas into one system. In this work, we developed a computational model of the hippocampus, including the dentate gyrus, CA3, and CA1. The subregions are represented as an interconnected neuronal network, incorporating well-characterized ex vivo slice electrophysiology into the functional neuron models and well-documented anatomical connections into the network structure. In addition, since plasticity is foundational to the role of the hippocampus in learning and memory as well as necessary for studying adaptation to injury, we implemented spike-timing-dependent plasticity among the synaptic connections. Our model mimics key features of hippocampal activity, including signal frequencies in the theta and gamma bands and phase-amplitude coupling in area CA1. We also studied the effects of spike-timing-dependent plasticity impairment, a potential consequence of TBI, in our model and found that impairment decreases broadband power in CA3 and CA1 and reduces phase coherence between these two subregions, yet phase-amplitude coupling in CA1 remains intact. Altogether, our work demonstrates characteristic hippocampal activity with a scaled network model of spiking neurons and reveals the sensitive balance of plasticity mechanisms in the circuit through one manifestation of mild traumatic injury.},
  langid = {english},
  keywords = {hippocampus,mild traumatic brain injury,network,phase coherence,plasticity impairment},
  file = {C:\Users\marc_\Zotero\storage\Z5IBQJGJ\Schumm e.a. - 2022 - Plasticity impairment exposes CA3 vulnerability in.pdf}
}

@article{sparksHippocampalAdultbornGranule2020a,
  title = {Hippocampal Adult-Born Granule Cells Drive Network Activity in a Mouse Model of Chronic Temporal Lobe Epilepsy},
  author = {Sparks, F. T. and Liao, Z. and Li, W. and Grosmark, A. and Soltesz, I. and Losonczy, A.},
  date = {2020-12-01},
  journaltitle = {Nature Communications},
  shortjournal = {Nat Commun},
  volume = {11},
  number = {1},
  pages = {6138},
  publisher = {Nature Publishing Group},
  issn = {2041-1723},
  doi = {10.1038/s41467-020-19969-2},
  url = {https://www.nature.com/articles/s41467-020-19969-2},
  urldate = {2023-11-07},
  abstract = {Temporal lobe epilepsy (TLE) is characterized by recurrent seizures driven by synchronous neuronal activity. The reorganization of the dentate gyrus (DG) in TLE may create pathological conduction pathways for synchronous discharges in the temporal lobe, though critical microcircuit-level detail is missing from this pathophysiological intuition. In particular, the relative contribution of adult-born (abGC) and mature (mGC) granule cells to epileptiform network events remains unknown. We assess dynamics of abGCs and mGCs during interictal epileptiform discharges (IEDs) in mice with TLE as well as sharp-wave ripples (SPW-Rs) in healthy mice, and find that abGCs and mGCs are desynchronized and differentially recruited by IEDs compared to SPW-Rs. We introduce a neural topic model to explain these observations, and find that epileptic DG networks organize into disjoint, cell-type specific pathological ensembles in which abGCs play an outsized role. Our results characterize identified GC subpopulation dynamics in TLE, and reveal a specific contribution of abGCs to IEDs.},
  issue = {1},
  langid = {english},
  keywords = {Adult neurogenesis,Epilepsy,Hippocampus},
  file = {C:\Users\marc_\Zotero\storage\RZGBKNBM\Sparks et al. - 2020 - Hippocampal adult-born granule cells drive network.pdf}
}

@article{staceySynapticNoisePhysiological2009,
  title = {Synaptic {{Noise}} and {{Physiological Coupling Generate High-Frequency Oscillations}} in a {{Hippocampal Computational Model}}},
  author = {Stacey, William C. and Lazarewicz, Maciej T. and Litt, Brian},
  date = {2009-10},
  journaltitle = {Journal of Neurophysiology},
  volume = {102},
  number = {4},
  pages = {2342--2357},
  publisher = {American Physiological Society},
  issn = {0022-3077},
  doi = {10.1152/jn.00397.2009},
  url = {https://journals.physiology.org/doi/full/10.1152/jn.00397.2009},
  urldate = {2023-11-13},
  abstract = {There is great interest in the role of coherent oscillations in the brain. In some cases, high-frequency oscillations (HFOs) are integral to normal brain function, whereas at other times they are implicated as markers of epileptic tissue. Mechanisms underlying HFO generation, especially in abnormal tissue, are not well understood. Using a physiological computer model of hippocampus, we investigate random synaptic activity (noise) as a potential initiator of HFOs. We explore parameters necessary to produce these oscillations and quantify the response using the tools of stochastic resonance (SR) and coherence resonance (CR). As predicted by SR, when noise was added to the network the model was able to detect a subthreshold periodic signal. Addition of basket cell interneurons produced two novel SR effects: 1) improved signal detection at low noise levels and 2) formation of coherent oscillations at high noise that were entrained to harmonics of the signal frequency. The periodic signal was then removed to study oscillations generated only by noise. The combined effects of network coupling and synaptic noise produced coherent, periodic oscillations within the network, an example of CR. Our results show that, under normal coupling conditions, synaptic noise was able to produce gamma (30–100 Hz) frequency oscillations. Synaptic noise generated HFOs in the ripple range (100–200 Hz) when the network had parameters similar to pathological findings in epilepsy: increased gap junctions or recurrent synaptic connections, loss of inhibitory interneurons such as basket cells, and increased synaptic noise. The model parameters that generated these effects are comparable with published experimental data. We propose that increased synaptic noise and physiological coupling mechanisms are sufficient to generate gamma oscillations and that pathologic changes in noise and coupling similar to those in epilepsy can produce abnormal ripples.},
  file = {C:\Users\marc_\Zotero\storage\DUHNYCVI\Stacey et al. - 2009 - Synaptic Noise and Physiological Coupling Generate.pdf}
}

@article{steriadeEpilepsyKeyExperimental2020,
  title = {Epilepsy: Key Experimental Therapeutics in Early Clinical Development},
  shorttitle = {Epilepsy},
  author = {Steriade, Claude and French, Jacqueline and Devinsky, Orrin},
  date = {2020-04-02},
  journaltitle = {Expert Opinion on Investigational Drugs},
  volume = {29},
  number = {4},
  eprint = {32172604},
  eprinttype = {pmid},
  pages = {373--383},
  publisher = {Taylor \& Francis},
  issn = {1354-3784},
  doi = {10.1080/13543784.2020.1743678},
  url = {https://doi.org/10.1080/13543784.2020.1743678},
  urldate = {2024-05-02},
  abstract = {Introduction: Antiseizure medications are the mainstay of epilepsy treatment. Currently therapies are not specific to epilepsy etiology, and control seizures in two-thirds of cases. Drugs in clinical development aim to bridge that gap by targeting novel receptors and epileptogenesis. While currently approved antiseizure medications target focal or generalized epilepsies regardless of etiology, newly approved and investigational epilepsy drugs also target rare or orphan epilepsy syndrome indications, such as Lennox-Gastaut or Dravet syndrome. We identified investigational drugs through the Epilepsy Foundation pipeline tracker and conference proceedings of recent novel epilepsy drug conferences (XV AEDD, XIV EILAT). Areas covered: We review antiseizure medications in clinical development and their targets (GABA, T-type calcium channels, 5-HT, potassium channels). We also discuss drugs with unknown or multiple mechanisms of action (cannabinoids, carisbamate, cenobamate). Therapies with potential disease-modifying effects in preclinical and clinical development are then outlined, ranging from gene-targeted treatments (antisense oligonucleotide, gene therapy, antisense transcript regulators) targeting specific genetic epilepsies, mTOR inhibitors, to inflammation-targeted treatments. Expert opinion: Drugs to treat novel targets to control seizures as well as prevent epileptogenesis offer great promise. To assess disease modifying agents, we may need new clinical trial designs. Precision medicine therapies for genetic epilepsies may control seizures and restore brain health.},
  keywords = {Antiseizure medications,cenobamate,cholesterol 24-hydroxylase inhibition,epilepsy,epileptogenesis,fenfluramine,genetics,neuroinflammation},
  file = {C:\Users\marc_\Zotero\storage\MF8M86HA\Steriade e.a. - 2020 - Epilepsy key experimental therapeutics in early c.pdf}
}

@article{stokesComplementaryRolesHuman2015,
  title = {Complementary {{Roles}} of {{Human Hippocampal Subfields}} in {{Differentiation}} and {{Integration}} of {{Spatial Context}}},
  author = {Stokes, Jared and Kyle, Colin and Ekstrom, Arne D.},
  date = {2015-03-01},
  journaltitle = {Journal of Cognitive Neuroscience},
  shortjournal = {Journal of Cognitive Neuroscience},
  volume = {27},
  number = {3},
  pages = {546--559},
  issn = {0898-929X},
  doi = {10.1162/jocn_a_00736},
  url = {https://doi.org/10.1162/jocn_a_00736},
  urldate = {2024-04-30},
  abstract = {The unique circuitry of the hippocampus is thought to support the encoding and retrieval of context-rich episodic memories. Given the neuroanatomical differences between the hippocampal subfields, determining their functional roles during representation of contextual features in humans is an important yet unaddressed research goal. Prior studies suggest that, during the acquisition of information from the environment, the dentate gyrus (DG) and CA3 subfields rapidly differentiate competing contextual representations, whereas CA1, situated downstream from CA3/DG, is believed to process input from both CA3 and neocortical areas via the temporoammonic pathway. To further explore the functionality of these roles, we used high-resolution fMRI to investigate multivariate response patterns within CA3/DG and CA1 during the processing of spatial context. While undergoing functional imaging, participants viewed videos of virtual environments and were asked to discriminate between similar yet geometrically distinct cities. We manipulated a single contextual feature by systematically morphing the city configurations from one common geometric shape to another, resulting in four cities—two distinctively shaped cities and two intermediate “morphed” cities. Pattern similarity within CA3/DG scaled with geometric changes to the environment. In contrast, CA1 pattern similarity, as well as interregional pattern similarity between CA1 and parahippocampal cortex, increased for the regularly shaped configurations compared with the morphs. These results highlight different roles for subfields CA3/DG and CA1 in memory and advance our understanding of how subcomponents of the human hippocampal circuit represent contextual features of memories.},
  file = {C\:\\Users\\marc_\\Zotero\\storage\\M7JGMDPY\\Stokes e.a. - 2015 - Complementary Roles of Human Hippocampal Subfields.pdf;C\:\\Users\\marc_\\Zotero\\storage\\UVKX9TY9\\Complementary-Roles-of-Human-Hippocampal-Subfields.html}
}

@article{strianoGeneticTestingPrecision2020,
  title = {From {{Genetic Testing}} to {{Precision Medicine}} in {{Epilepsy}}},
  author = {Striano, Pasquale and Minassian, Berge A.},
  date = {2020-04},
  journaltitle = {Neurotherapeutics},
  shortjournal = {Neurotherapeutics},
  volume = {17},
  number = {2},
  pages = {609--615},
  issn = {18787479},
  doi = {10.1007/s13311-020-00835-4},
  url = {https://linkinghub.elsevier.com/retrieve/pii/S1878747923013600},
  urldate = {2024-04-09},
  abstract = {Epilepsy includes a number of medical conditions with recurrent seizures as common denominator. The large number of different syndromes and seizure types as well as the highly variable inter-individual response to the therapies makes management of this condition often challenging. In the last two decades, a genetic etiology has been revealed in more than half of all epilepsies and single gene defects in ion channels or neurotransmitter receptors have been associated with most inherited forms of epilepsy, including some focal and lesional forms as well as specific epileptic developmental encephalopathies. Several genetic tests are now available, including targeted assays up to revolutionary tools that have made sequencing of all coding (whole exome) and noncoding (whole genome) regions of the human genome possible. These recent technological advances have also driven genetic discovery in epilepsy and increased our understanding of the molecular mechanisms of many epileptic disorders, eventually providing targets for precision medicine in some syndromes, such as Dravet syndrome, pyroxidine-dependent epilepsy, and glucose transporter 1 deficiency. However, these examples represent a relatively small subset of all types of epilepsy, and to date, precision medicine in epilepsy has primarily focused on seizure control, and other clinical aspects, such as neurodevelopmental and neuropsychiatric comorbidities, have yet been possible to address. We herein summarize the most recent advances in genetic testing and provide up-to-date approaches for the choice of the correct test for some epileptic disorders and tailored treatments that are already applicable in some monogenic epilepsies. In the next years, the most probably scenario is that epilepsy treatment will be very different from the currently almost empirical approach, eventually with a “precision medicine” approach applicable on a large scale.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\3R8MFBQG\Striano en Minassian - 2020 - From Genetic Testing to Precision Medicine in Epil.pdf}
}

@article{suffczynskiDynamicsEpilepticPhenomena2006,
  title = {Dynamics of Epileptic Phenomena Determined from Statistics of Ictal Transitions},
  author = {Suffczynski, P. and family=Silva, given=F.H.L., prefix=da, useprefix=true and Parra, J. and Velis, D.N. and Bouwman, B.M. and family=Rijn, given=C.M., prefix=van, useprefix=true and family=Hese, given=P., prefix=van, useprefix=true and Boon, P. and Khosravani, H. and Derchansky, M. and Carlen, P. and Kalitzin, S.},
  date = {2006-03},
  journaltitle = {IEEE Transactions on Biomedical Engineering},
  volume = {53},
  number = {3},
  pages = {524--532},
  issn = {1558-2531},
  doi = {10.1109/TBME.2005.869800},
  url = {https://ieeexplore.ieee.org/abstract/document/1597503},
  urldate = {2024-04-11},
  abstract = {In this paper, we investigate the dynamical scenarios of transitions between normal and paroxysmal state in epilepsy. We assume that some epileptic neural network are bistable i.e., they feature two operational states, ictal and interictal that co-exist. The transitions between these two states may occur according to a Poisson process, a random walk process or as a result of deterministic time-dependent mechanisms. We analyze data from animal models of absence epilepsy, human epilepsies and in vitro models. The distributions of durations of ictal and interictal epochs are fitted with a gamma distribution. On the basis of qualitative features of the fits, we identify the dynamical processes that may have generated the underlying data. The analysis showed that the following hold. 1) The dynamics of ictal epochs differ from those of interictal states. 2) Seizure initiation can be accounted for by a random walk process while seizure termination is often mediated by deterministic mechanisms. 3) In certain cases, the transitions between ictal and interictal states can be modeled by a Poisson process operating in a bistable network. These results imply that exact prediction of seizure occurrence is not possible but termination of an ictal state by appropriate counter stimulation might be feasible.},
  eventtitle = {{{IEEE Transactions}} on {{Biomedical Engineering}}},
  keywords = {Animals,Bistability,Data analysis,duration distribution,epilepsy,Epilepsy,Hospitals,Humans,Nervous system,Neural networks,Physics,Physiology,Statistics},
  file = {C\:\\Users\\marc_\\Zotero\\storage\\69JGL334\\Suffczynski e.a. - 2006 - Dynamics of epileptic phenomena determined from st.pdf;C\:\\Users\\marc_\\Zotero\\storage\\TFJIDCIS\\1597503.html}
}

@article{symondsAdvancesEpilepsyGene2017,
  title = {Advances in Epilepsy Gene Discovery and Implications for Epilepsy Diagnosis and Treatment},
  author = {Symonds, Joseph D. and Zuberi, Sameer M. and Johnson, Michael R.},
  date = {2017-04},
  journaltitle = {Current Opinion in Neurology},
  volume = {30},
  number = {2},
  pages = {193--199},
  issn = {1350-7540, 1473-6551},
  doi = {10.1097/WCO.0000000000000433},
  url = {https://journals.lww.com/00019052-201704000-00013},
  urldate = {2024-04-01},
  abstract = {We are living in an unparalleled era of epilepsy gene discovery. Advances in clinical care from this progress are already materializing through improved clinical diagnosis and stratified medicine. The application of targeted drug repurposing based on single gene defects has shown promise for epilepsy arising from gain-of-function mutations in ion-channel subunit genes, but important barriers remain to translating these approaches to non-ion channel epilepsy genes and loss-of-function mutations. Gene network analysis offers opportunities to discover new pathways for epilepsy, to decipher epilepsy’s relationship to other neurodevelopmental traits and to frame a new approach to epilepsy drug discovery.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\Q7I9AL4W\Symonds e.a. - 2017 - Advances in epilepsy gene discovery and implicatio.pdf}
}

@article{thijsEpilepsyAdults2019a,
  title = {Epilepsy in Adults},
  author = {Thijs, Roland D and Surges, Rainer and O'Brien, Terence J and Sander, Josemir W},
  date = {2019-02},
  journaltitle = {The Lancet},
  shortjournal = {The Lancet},
  volume = {393},
  number = {10172},
  pages = {689--701},
  issn = {01406736},
  doi = {10.1016/S0140-6736(18)32596-0},
  url = {https://linkinghub.elsevier.com/retrieve/pii/S0140673618325960},
  urldate = {2024-03-30},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\KLYEYFEW\Thijs e.a. - 2019 - Epilepsy in adults.pdf}
}

@article{tortFormationGammacoherentCell2007,
  title = {On the Formation of Gamma-Coherent Cell Assemblies by Oriens Lacunosum-Moleculare Interneurons in the Hippocampus},
  author = {Tort, Adriano B. L. and Rotstein, Horacio G. and Dugladze, Tamar and Gloveli, Tengis and Kopell, Nancy J.},
  date = {2007-08-14},
  journaltitle = {Proceedings of the National Academy of Sciences},
  volume = {104},
  number = {33},
  pages = {13490--13495},
  publisher = {Proceedings of the National Academy of Sciences},
  doi = {10.1073/pnas.0705708104},
  url = {https://www.pnas.org/doi/full/10.1073/pnas.0705708104},
  urldate = {2023-11-13},
  abstract = {Gamma frequency (30–80 Hz) network oscillations have been observed in the hippocampus during several behavioral paradigms in which they are often modulated by a theta frequency (4–12 Hz) oscillation. Interneurons of the hippocampus have been shown to be crucially involved in rhythms generation, and several subtypes with distinct anatomy and physiology have been described. In particular, the oriens lacunosum-moleculare (O-LM) interneurons were shown to synapse on distal apical dendrites of pyramidal cells and to spike preferentially at theta frequency, even in the presence of gamma-field oscillations. O-LM cells have also recently been shown to present higher axonal ramification in the longitudinal axis of the hippocampus. By using a hippocampal network model composed of pyramidal cells and two types of interneurons (O-LM and basket cells), we show here that the O-LM interneurons lead to gamma coherence between anatomically distinct cell modules. We thus propose that this could be a mechanism for coupling longitudinally distant cells excited by entorhinal cortex inputs into gamma-coherent assemblies.},
  file = {C:\Users\marc_\Zotero\storage\K7JLPYYQ\Tort et al. - 2007 - On the formation of gamma-coherent cell assemblies.pdf}
}

@article{tortFormationGammacoherentCell2007a,
  title = {On the Formation of Gamma-Coherent Cell Assemblies by Oriens Lacunosum-Moleculare Interneurons in the Hippocampus},
  author = {Tort, Adriano B. L. and Rotstein, Horacio G. and Dugladze, Tamar and Gloveli, Tengis and Kopell, Nancy J.},
  date = {2007-08-14},
  journaltitle = {Proceedings of the National Academy of Sciences},
  volume = {104},
  number = {33},
  pages = {13490--13495},
  publisher = {Proceedings of the National Academy of Sciences},
  doi = {10.1073/pnas.0705708104},
  url = {https://www.pnas.org/doi/abs/10.1073/pnas.0705708104},
  urldate = {2024-04-16},
  abstract = {Gamma frequency (30–80 Hz) network oscillations have been observed in the hippocampus during several behavioral paradigms in which they are often modulated by a theta frequency (4–12 Hz) oscillation. Interneurons of the hippocampus have been shown to be crucially involved in rhythms generation, and several subtypes with distinct anatomy and physiology have been described. In particular, the oriens lacunosum-moleculare (O-LM) interneurons were shown to synapse on distal apical dendrites of pyramidal cells and to spike preferentially at theta frequency, even in the presence of gamma-field oscillations. O-LM cells have also recently been shown to present higher axonal ramification in the longitudinal axis of the hippocampus. By using a hippocampal network model composed of pyramidal cells and two types of interneurons (O-LM and basket cells), we show here that the O-LM interneurons lead to gamma coherence between anatomically distinct cell modules. We thus propose that this could be a mechanism for coupling longitudinally distant cells excited by entorhinal cortex inputs into gamma-coherent assemblies.},
  file = {C:\Users\marc_\Zotero\storage\ZZ6BHYZE\Tort e.a. - 2007 - On the formation of gamma-coherent cell assemblies.pdf}
}

@article{tukkerDistinctDendriticArborization2013,
  title = {Distinct {{Dendritic Arborization}} and {{In Vivo Firing Patterns}} of {{Parvalbumin-Expressing Basket Cells}} in the {{Hippocampal Area CA3}}},
  author = {Tukker, John J. and Lasztóczi, Bálint and Katona, Linda and Roberts, J. David B. and Pissadaki, Eleftheria K. and Dalezios, Yannis and Márton, László and Zhang, Limei and Klausberger, Thomas and Somogyi, Peter},
  date = {2013-04-17},
  journaltitle = {Journal of Neuroscience},
  shortjournal = {J. Neurosci.},
  volume = {33},
  number = {16},
  eprint = {23595740},
  eprinttype = {pmid},
  pages = {6809--6825},
  publisher = {Society for Neuroscience},
  issn = {0270-6474, 1529-2401},
  doi = {10.1523/JNEUROSCI.5052-12.2013},
  url = {https://www.jneurosci.org/content/33/16/6809},
  urldate = {2024-04-16},
  abstract = {Hippocampal CA3 area generates temporally structured network activity such as sharp waves and gamma and theta oscillations. Parvalbumin-expressing basket cells, making GABAergic synapses onto cell bodies and proximal dendrites of pyramidal cells, control pyramidal cell activity and participate in network oscillations in slice preparations, but their roles in vivo remain to be tested. We have recorded the spike timing of parvalbumin-expressing basket cells in areas CA2/3 of anesthetized rats in relation to CA3 putative pyramidal cell firing and activity locally and in area CA1. During theta oscillations, CA2/3 basket cells fired on the same phase as putative pyramidal cells, but, surprisingly, significantly later than downstream CA1 basket cells. This indicates a distinct modulation of CA3 and CA1 pyramidal cells by basket cells, which receive different inputs. We observed unexpectedly large dendritic arborization of CA2/3 basket cells in stratum lacunosum moleculare (33\% of length, 29\% surface, and 24\% synaptic input from a total of ∼35,000), different from the dendritic arborizations of CA1 basket cells. Area CA2/3 basket cells fired phase locked to both CA2/3 and CA1 gamma oscillations, and increased firing during CA1 sharp waves, thus supporting the role of CA3 networks in the generation of gamma oscillations and sharp waves. However, during ripples associated with sharp waves, firing of CA2/3 basket cells was phase locked only to local but not CA1 ripples, suggesting the independent generation of fast oscillations by basket cells in CA1 and CA2/3. The distinct spike timing of basket cells during oscillations in CA1 and CA2/3 suggests differences in synaptic inputs paralleled by differences in dendritic arborizations.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\M2GADERU\Tukker e.a. - 2013 - Distinct Dendritic Arborization and In Vivo Firing.pdf}
}

@article{unalSpatiotemporalSpecializationGABAergic2018,
  title = {Spatio-Temporal Specialization of {{GABAergic}} Septo-Hippocampal Neurons for Rhythmic Network Activity},
  author = {Unal, Gunes and Crump, Michael G. and Viney, Tim J. and Éltes, Tímea and Katona, Linda and Klausberger, Thomas and Somogyi, Peter},
  date = {2018-06-01},
  journaltitle = {Brain Structure and Function},
  shortjournal = {Brain Struct Funct},
  volume = {223},
  number = {5},
  pages = {2409--2432},
  issn = {1863-2661},
  doi = {10.1007/s00429-018-1626-0},
  url = {https://doi.org/10.1007/s00429-018-1626-0},
  urldate = {2024-04-18},
  abstract = {Medial septal GABAergic neurons of the basal forebrain innervate the hippocampus and related cortical areas, contributing to the coordination of network activity, such as theta oscillations and sharp wave-ripple events, via a preferential innervation of GABAergic interneurons. Individual medial septal neurons display diverse activity patterns, which may be related to their termination in different cortical areas and/or to the different types of innervated interneurons. To test these hypotheses, we extracellularly recorded and juxtacellularly labeled single medial septal neurons in anesthetized rats in vivo during hippocampal theta and ripple oscillations, traced their axons to distant cortical target areas, and analyzed their postsynaptic interneurons. Medial septal GABAergic neurons exhibiting different hippocampal theta phase preferences and/or sharp wave-ripple related activity terminated in restricted hippocampal regions, and selectively targeted a limited number of interneuron types, as established on the basis of molecular markers. We demonstrate the preferential innervation of bistratified cells in CA1 and of basket cells in CA3 by individual axons. One group of septal neurons was suppressed during sharp wave-ripples, maintained their firing rate across theta and non-theta network states and mainly fired along the descending phase of CA1 theta oscillations. In contrast, neurons that were active during sharp wave-ripples increased their firing significantly during “theta” compared to “non-theta” states, with most firing during the ascending phase of theta oscillations. These results demonstrate that specialized septal GABAergic neurons contribute to the coordination of network activity through parallel, target area- and cell type-selective projections to the hippocampus.},
  langid = {english},
  keywords = {Basal forebrain,GABAergic,Hippocampus,Septo-hippocampal,Sharp wave-ripple,Theta},
  file = {C:\Users\marc_\Zotero\storage\DHULRVHT\Unal e.a. - 2018 - Spatio-temporal specialization of GABAergic septo-.pdf}
}

@article{vanvreeswijkWhenInhibitionNot1994,
  title = {When Inhibition Not Excitation Synchronizes Neural Firing},
  author = {Van Vreeswijk, Carl and Abbott, L. F. and Bard Ermentrout, G.},
  date = {1994-12},
  journaltitle = {Journal of Computational Neuroscience},
  shortjournal = {J Comput Neurosci},
  volume = {1},
  number = {4},
  pages = {313--321},
  issn = {0929-5313, 1573-6873},
  doi = {10.1007/BF00961879},
  url = {http://link.springer.com/10.1007/BF00961879},
  urldate = {2024-04-17},
  abstract = {Excitatory and inhibitory synaptic coupling can have counter-intuitive effects on the synchronization of neuronal firing. While it might appear that excitatory coupling would lead to synchronization, we show that frequently inhibition rather than excitation synchronizes firing. We study two identical neurons described by integrate-and-fire models, general phase-coupled models or the Hodgkin-Huxley model with mutual, noninstantaneous excitatory or inhibitory synapses between them. We find that if the rise time of the synapse is longer than the duration of an action potential, inhibition not excitation leads to synchronized firing.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\IVEQRPFW\Van Vreeswijk e.a. - 1994 - When inhibition not excitation synchronizes neural.pdf}
}

@article{vintiTemporalLobeEpilepsy2021,
  title = {Temporal {{Lobe Epilepsy}} and {{Psychiatric Comorbidity}}},
  author = {Vinti, Valerio and Dell'Isola, Giovanni Battista and Tascini, Giorgia and Mencaroni, Elisabetta and Cara, Giuseppe Di and Striano, Pasquale and Verrotti, Alberto},
  date = {2021-11-30},
  journaltitle = {Frontiers in Neurology},
  shortjournal = {Front. Neurol.},
  volume = {12},
  publisher = {Frontiers},
  issn = {1664-2295},
  doi = {10.3389/fneur.2021.775781},
  url = {https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.775781/full},
  urldate = {2024-04-08},
  abstract = {{$<$}p{$>$}Most focal seizures originate in the temporal lobe and are commonly divided into mesial and lateral temporal epilepsy, depending upon the neuronal circuitry involved. The hallmark features of the mesial temporal epilepsy are aura, unconsciousness, and automatisms. Symptoms often overlap with the lateral temporal epilepsy. However, the latter present a less evident psychomotor arrest, frequent clones and dystonic postures, and common focal to bilateral tonic–clonic seizures. Sclerosis of the hippocampus is the most frequent cause of temporal lobe epilepsy (TLE). TLE is among all epilepsies the most frequently associated with psychiatric comorbidity. Anxiety, depression, and interictal dysphoria are recurrent psychiatric disorders in pediatric patients with TLE. In addition, these alterations are often combined with cognitive, learning, and behavioral impairment. These comorbidities occur more frequently in TLE with hippocampal sclerosis and with pharmacoresistance. According to the bidirectional hypothesis, the close relationship between TLE and psychiatric features should lead to considering common pathophysiology underlying these disorders. Psychiatric comorbidities considerably reduce the quality of life of these children and their families. Thus, early detection and appropriate management and therapeutic strategies could improve the prognosis of these patients. The aim of this review is to analyze TLE correlation with psychiatric disorders and its underlying conditions.{$<$}/p{$>$}},
  langid = {english},
  keywords = {antiseizure medications (ASMs),bi-directional hypothesis,Hippocampal Sclerosis,Psychiatric comorbidity,Temporal Lobe Epilepsy},
  file = {C:\Users\marc_\Zotero\storage\DKYE96YX\Vinti e.a. - 2021 - Temporal Lobe Epilepsy and Psychiatric Comorbidity.pdf}
}

@article{wallaceFebrileSeizuresGeneralized1998,
  title = {Febrile Seizures and Generalized Epilepsy Associated with a Mutation in the {{Na}}+-Channel SS1 Subunit Gene{{SCN1B}}},
  author = {Wallace, Robyn H. and Wang, Dao W. and Singh, Rita and Scheffer, Ingrid E. and George, Alfred L. and Phillips, Hilary A. and Saar, Kathrin and Reis, Andre and Johnson, Eric W. and Sutherland, Grant R. and Berkovic, Samuel F. and Mulley, John C.},
  date = {1998-08},
  journaltitle = {Nature Genetics},
  shortjournal = {Nat Genet},
  volume = {19},
  number = {4},
  pages = {366--370},
  publisher = {Nature Publishing Group},
  issn = {1546-1718},
  doi = {10.1038/1252},
  url = {https://www.nature.com/articles/ng0898_366},
  urldate = {2024-04-30},
  abstract = {Febrile seizures affect approximately 3\% of all children under six years of age and are by far the most common seizure disorder1. A small proportion of children with febrile seizures later develop ongoing epilepsy with afebrile seizures2. Segregation analysis suggests the majority of cases have complex inheritance3 but rare families show apparent autosomal dominant inheritance. Two putative loci have been mapped (FEB1 and FEB2), but specific genes have not yet been identified4,5. We recently described a clinical subset, termed generalized epilepsy with febrile seizures plus (GEFS+), in which many family members have seizures with fever that may persist beyond six years of age or be associated with afebrile generalized seizures6. We now report linkage, in another large GEFS+ family, to chromosome region 19q13.1 and identification of a mutation in the voltage-gated sodium (Na+)-channel ß1 subunit gene (SCN1B). The mutation changes a conserved cysteine residue disrupting a putative disulfide bridge which normally maintains an extracellular immunoglobulin-like fold. Co-expression of the mutant ß1 subunit with a brain Na+-channel ß subunit in Xenopus laevis oocytes demonstrates that the mutation interferes with the ability of the subunit to modulate channel-gating kinetics consistent with a loss-of-function allele. This observation develops the theme that idiopathic epilepsies are a family of channelopathies and raises the possibility of involvement of other Na+-channel subunit genes in febrile seizures and generalized epilepsies with complex inheritance patterns.},
  langid = {english},
  keywords = {Agriculture,Animal Genetics and Genomics,Biomedicine,Cancer Research,Gene Function,general,Human Genetics},
  file = {C:\Users\marc_\Zotero\storage\YZMSKTJM\Wallace e.a. - 1998 - Febrile seizures and generalized epilepsy associat.pdf}
}

@article{wangDoubleedgedGABAergicSynaptic2018a,
  title = {Double-Edged {{GABAergic}} Synaptic Transmission in Seizures: {{The}} Importance of Chloride Plasticity},
  shorttitle = {Double-Edged {{GABAergic}} Synaptic Transmission in Seizures},
  author = {Wang, Ying and Wang, Yi and Chen, Zhong},
  date = {2018-12},
  journaltitle = {Brain Research},
  shortjournal = {Brain Research},
  volume = {1701},
  pages = {126--136},
  issn = {00068993},
  doi = {10.1016/j.brainres.2018.09.008},
  url = {https://linkinghub.elsevier.com/retrieve/pii/S0006899318304657},
  urldate = {2024-05-02},
  abstract = {GABAergic synaptic inhibition, which is a critical regulator of neuronal excitability, is closely involved in epilepsy. Interestingly, fast GABAergic transmission mediated by Cl− permeable GABAA receptors can bi-directionally exert both seizure-suppressing and seizure-promoting actions. Accumulating evidence suggests that chloride plasticity, the driving force of GABAA receptor-mediated synaptic transmission, contributes to the double-edged role of GABAergic synapses in seizures. Large amounts of Cl− influx can overwhelm Cl− extrusion during seizures not only in healthy tissue in a short-term “activity-dependent” manner, but also in chronic epilepsy in a long-term, irreversible “pathology-dependent” manner related to the dysfunction of two chloride transporters: the chloride importer NKCC1 and the chloride exporter KCC2. In this review, we address the importance of chloride plasticity for the “activity-dependent” and “pathology-dependent” mechanisms underlying epileptic events and provide possible directions for further research, which may be clinically important for the design of GABAergic synapse-targeted precise therapeutic interventions for epilepsy.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\MFB5SA49\Wang e.a. - 2018 - Double-edged GABAergic synaptic transmission in se.pdf}
}

@article{wangFunctionalBrainNetwork2016a,
  title = {Functional Brain Network Alterations in Epilepsy: {{A}} Magnetoencephalography Study},
  shorttitle = {Functional Brain Network Alterations in Epilepsy},
  author = {Wang, Beilei and Meng, Lu},
  date = {2016-10},
  journaltitle = {Epilepsy Research},
  shortjournal = {Epilepsy Research},
  volume = {126},
  pages = {62--69},
  issn = {09201211},
  doi = {10.1016/j.eplepsyres.2016.06.014},
  url = {https://linkinghub.elsevier.com/retrieve/pii/S0920121116301000},
  urldate = {2024-04-01},
  abstract = {Objective: To test the hypotheses that brain networks of patients with epilepsy differ from that of healthy controls and functional interactions in the brain are correlated to the duration of epilepsy. Method: The present study recorded Magnetoencephalography (MEG) data from twenty patients with epilepsy and twenty healthy controls, constructed the whole functional brain network based on phase lag index (PLI), compared the differences in functional connectivity and network measures between patients with epilepsy and healthy controls, and analyzed the correlation between network measures and the duration of epilepsy. Results: The patients with epilepsy showed significant increase in mean functional connectivity in the alpha band, gamma band and ripple band, significant increase in mean clustering coefficient in the theta band, beta band and ripple band, significant increase in average shortest path length in the theta band and alpha band. Only in the alpha band, a significant negative correlation between mean clustering coefficient and the duration of epilepsy was detected. Conclusions: Our results indicated that the alterations of functional brain network are related to a functional imbalance that resulted from epileptic activity and the brain network of patients with epilepsy become more pathological over time.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\3HH6DDMX\Wang en Meng - 2016 - Functional brain network alterations in epilepsy .pdf}
}

@article{wangGammaOscillationSynaptic1996,
  title = {Gamma {{Oscillation}} by {{Synaptic Inhibition}} in a {{Hippocampal Interneuronal Network Model}}},
  author = {Wang, Xiao-Jing and Buzsáki, György},
  date = {1996-10-15},
  journaltitle = {The Journal of Neuroscience},
  shortjournal = {J Neurosci},
  volume = {16},
  number = {20},
  eprint = {8815919},
  eprinttype = {pmid},
  pages = {6402--6413},
  issn = {0270-6474},
  doi = {10.1523/JNEUROSCI.16-20-06402.1996},
  url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6578902/},
  urldate = {2023-11-03},
  abstract = {Fast neuronal oscillations (gamma, 20–80 Hz) have been observed in the neocortex and hippocampus during behavioral arousal. Using computer simulations, we investigated the hypothesis that such rhythmic activity can emerge in a random network of interconnected GABAergic fast-spiking interneurons. Specific conditions for the population synchronization, on properties of single cells and the circuit, were identified. These include the following: (1) that the amplitude of spike afterhyperpolarization be above the GABAA synaptic reversal potential; (2) that the ratio between the synaptic decay time constant and the oscillation period be sufficiently large; (3) that the effects of heterogeneities be modest because of a steep frequency–current relationship of fast-spiking neurons. Furthermore, using a population coherence measure, based on coincident firings of neural pairs, it is demonstrated that large-scale network synchronization requires a critical (minimal) average number of synaptic contacts per cell, which is not sensitive to the network size., By changing the GABAA synaptic maximal conductance, synaptic decay time constant, or the mean external excitatory drive to the network, the neuronal firing frequencies were gradually and monotonically varied. By contrast, the network synchronization was found to be high only within a frequency band coinciding with the gamma (20–80 Hz) range. We conclude that the GABAA synaptic transmission provides a suitable mechanism for synchronized gamma oscillations in a sparsely connected network of fast-spiking interneurons. In turn, the interneuronal network can presumably maintain subthreshold oscillations in principal cell populations and serve to synchronize discharges of spatially distributed neurons.},
  pmcid = {PMC6578902},
  file = {C:\Users\marc_\Zotero\storage\KBBNYX9Q\Wang en Buzsáki - 1996 - Gamma Oscillation by Synaptic Inhibition in a Hipp.pdf}
}

@article{wangGammaOscillationSynaptic1996a,
  title = {Gamma {{Oscillation}} by {{Synaptic Inhibition}} in a {{Hippocampal Interneuronal Network Model}}},
  author = {Wang, Xiao-Jing and Buzsáki, György},
  date = {1996-10-15},
  journaltitle = {Journal of Neuroscience},
  shortjournal = {J. Neurosci.},
  volume = {16},
  number = {20},
  eprint = {8815919},
  eprinttype = {pmid},
  pages = {6402--6413},
  publisher = {Society for Neuroscience},
  issn = {0270-6474, 1529-2401},
  doi = {10.1523/JNEUROSCI.16-20-06402.1996},
  url = {https://www.jneurosci.org/content/16/20/6402},
  urldate = {2023-11-13},
  abstract = {Fast neuronal oscillations (gamma, 20–80 Hz) have been observed in the neocortex and hippocampus during behavioral arousal. Using computer simulations, we investigated the hypothesis that such rhythmic activity can emerge in a random network of interconnected GABAergic fast-spiking interneurons. Specific conditions for the population synchronization, on properties of single cells and the circuit, were identified. These include the following: (1) that the amplitude of spike afterhyperpolarization be above the GABAA synaptic reversal potential; (2) that the ratio between the synaptic decay time constant and the oscillation period be sufficiently large; (3) that the effects of heterogeneities be modest because of a steep frequency–current relationship of fast-spiking neurons. Furthermore, using a population coherence measure, based on coincident firings of neural pairs, it is demonstrated that large-scale network synchronization requires a critical (minimal) average number of synaptic contacts per cell, which is not sensitive to the network size. By changing the GABAA synaptic maximal conductance, synaptic decay time constant, or the mean external excitatory drive to the network, the neuronal firing frequencies were gradually and monotonically varied. By contrast, the network synchronization was found to be high only within a frequency band coinciding with the gamma (20–80 Hz) range. We conclude that the GABAA synaptic transmission provides a suitable mechanism for synchronized gamma oscillations in a sparsely connected network of fast-spiking interneurons. In turn, the interneuronal network can presumably maintain subthreshold oscillations in principal cell populations and serve to synchronize discharges of spatially distributed neurons.},
  langid = {english},
  keywords = {computer model,GABAA,gamma rhythm,hippocampus,interneurons,synchronization},
  file = {C:\Users\marc_\Zotero\storage\ZRK2BEAC\Wang and Buzsáki - 1996 - Gamma Oscillation by Synaptic Inhibition in a Hipp.pdf}
}

@article{weiUnificationNeuronalSpikes2014,
  title = {Unification of {{Neuronal Spikes}}, {{Seizures}}, and {{Spreading Depression}}},
  author = {Wei, Yina and Ullah, Ghanim and Schiff, Steven J.},
  date = {2014-08-27},
  journaltitle = {The Journal of Neuroscience},
  shortjournal = {J Neurosci},
  volume = {34},
  number = {35},
  eprint = {25164668},
  eprinttype = {pmid},
  pages = {11733--11743},
  issn = {0270-6474},
  doi = {10.1523/JNEUROSCI.0516-14.2014},
  url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145176/},
  urldate = {2023-11-03},
  abstract = {The pathological phenomena of seizures and spreading depression have long been considered separate physiological events in the brain. By incorporating conservation of particles and charge, and accounting for the energy required to restore ionic gradients, we extend the classic Hodgkin–Huxley formalism to uncover a unification of neuronal membrane dynamics. By examining the dynamics as a function of potassium and oxygen, we now account for a wide range of neuronal activities, from spikes to seizures, spreading depression (whether high potassium or hypoxia induced), mixed seizure and spreading depression states, and the terminal anoxic “wave of death.” Such a unified framework demonstrates that all of these dynamics lie along a continuum of the repertoire of the neuron membrane. Our results demonstrate that unified frameworks for neuronal dynamics are feasible, can be achieved using existing biological structures and universal physical conservation principles, and may be of substantial importance in enabling our understanding of brain activity and in the control of pathological states.},
  pmcid = {PMC4145176},
  file = {C:\Users\marc_\Zotero\storage\VPBKJV2E\Wei e.a. - 2014 - Unification of Neuronal Spikes, Seizures, and Spre.pdf}
}

@article{wengertRolePersistentSodium2021,
  title = {The {{Role}} of the {{Persistent Sodium Current}} in {{Epilepsy}}},
  author = {Wengert, Eric R. and Patel, Manoj K.},
  date = {2021-01-01},
  journaltitle = {Epilepsy Currents},
  shortjournal = {Epilepsy Curr},
  volume = {21},
  number = {1},
  pages = {40--47},
  publisher = {SAGE Publications Inc},
  issn = {1535-7597},
  doi = {10.1177/1535759720973978},
  url = {https://doi.org/10.1177/1535759720973978},
  urldate = {2024-04-08},
  abstract = {Voltage-gated sodium channels (VGSCs) are foundational to excitable cell function: Their coordinated passage of sodium ions into the cell is critical for the generation and propagation of action potentials throughout the nervous system. The classical paradigm of action potential physiology states that sodium passes through the membrane only transiently (1-2 milliseconds), before the channels inactivate and cease to conduct sodium ions. However, in reality, a small fraction of the total sodium current (1\%-2\%) remains at steady state despite prolonged depolarization. While this persistent sodium current~(INaP) contributes to normal physiological functioning of neurons, accumulating evidence indicates a particularly pathogenic role for an elevated INaP in epilepsy (reviewed previously1). Due to significant advances over the past decade of epilepsy research concerning the importance of INaP in sodium channelopathies, this review seeks to summarize recent evidence and highlight promising novel anti-seizure medication strategies through preferentially targeting INaP.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\BCGTRKC8\Wengert en Patel - 2021 - The Role of the Persistent Sodium Current in Epile.pdf}
}

@article{whiteNetworksInterneuronsFast2000,
  title = {Networks of Interneurons with Fast and Slow γ-Aminobutyric Acid Type {{A}} ({{GABAA}}) Kinetics Provide Substrate for Mixed Gamma-Theta Rhythm},
  author = {White, John A. and Banks, Matthew I. and Pearce, Robert A. and Kopell, Nancy J.},
  date = {2000-07-05},
  journaltitle = {Proceedings of the National Academy of Sciences},
  volume = {97},
  number = {14},
  pages = {8128--8133},
  publisher = {Proceedings of the National Academy of Sciences},
  doi = {10.1073/pnas.100124097},
  url = {https://www.pnas.org/doi/full/10.1073/pnas.100124097},
  urldate = {2023-11-13},
  abstract = {During active exploration, hippocampal neurons exhibit nested rhythmic activity at theta (≈8 Hz) and gamma (≈40 Hz) frequencies. Gamma rhythms may be generated locally by interactions within a class of interneurons mediating fast GABAA (GABAA,fast) inhibitory postsynaptic currents (IPSCs), whereas theta rhythms traditionally are thought to be imposed extrinsically. However, the hippocampus contains slow biophysical mechanisms that may contribute to the theta rhythm, either as a resonance activated by extrinsic input or as a purely local phenomenon. For example, region CA1 of the hippocampus contains a slower class of GABAA (GABAA,slow) synapses, believed to be generated by a distinct group of interneurons. Recent evidence indicates that these GABAA,slow interneurons project to the GABAA,fast interneurons that contribute to hippocampal gamma rhythms. Here, we use biophysically based simulations to explore the possible ramifications of interneuronal circuits containing separate classes of GABAA,fast and GABAA,slow interneurons. Simulated interneuronal networks with fast and slow synaptic kinetics can generate mixed theta-gamma rhythmicity under restricted conditions, including strong connections among each population, weaker connections between the two populations, and homogeneity of cellular properties and drive. Under a broader range of conditions, including heterogeneity, the networks can amplify and resynchronize phasic responses to weak phase-dispersed external drive at theta frequencies to either GABAA,slow or GABAA,fast cells. GABAA,slow synapses are necessary for this process of amplification and resynchronization.},
  file = {C:\Users\marc_\Zotero\storage\LEDZVMSX\White et al. - 2000 - Networks of interneurons with fast and slow γ-amin.pdf}
}

@article{willsPeopleMesialTemporal2021,
  title = {People with Mesial Temporal Lobe Epilepsy Have Altered Thalamo-Occipital Brain Networks},
  author = {Wills, Kristin E. and González, Hernán F.J. and Johnson, Graham W. and Haas, Kevin F. and Morgan, Victoria L. and Narasimhan, Saramati and Englot, Dario J.},
  date = {2021-02},
  journaltitle = {Epilepsy \& Behavior},
  shortjournal = {Epilepsy \& Behavior},
  volume = {115},
  pages = {107645},
  issn = {15255050},
  doi = {10.1016/j.yebeh.2020.107645},
  url = {https://linkinghub.elsevier.com/retrieve/pii/S1525505020308258},
  urldate = {2024-04-08},
  abstract = {While temporal lobe epilepsy (TLE) is a focal epilepsy, previous work demonstrates that TLE causes widespread brain-network disruptions. Impaired visuospatial attention and learning in TLE may be related to thalamic arousal nuclei connectivity. Our prior preliminary work in a smaller patient cohort suggests that patients with TLE demonstrate abnormal functional connectivity between central lateral (CL) thalamic nucleus and medial occipital lobe. Others have shown pulvinar connectivity disturbances in TLE, but it is incompletely understood how TLE affects pulvinar subnuclei. Also, the effects of epilepsy surgery on thalamic functional connectivity remains poorly understood. In this study, we examine the effects of TLE on functional connectivity of two key thalamic arousal-nuclei: lateral pulvinar (PuL) and CL. We evaluate resting-state functional connectivity of the PuL and CL in 40 patients with TLE and 40 controls using fMRI. In 25 patients, postoperative images ({$>$}1 year) were also compared with preoperative images. Compared to controls, patients with TLE exhibit loss of normal positive connectivity between PuL and lateral occipital lobe (p {$<$} 0.05), and a loss of normal negative connectivity between CL and medial occipital lobe (p {$<$} 0.01, paired t-tests). FMRI amplitude of low-frequency fluctuation (ALFF) in TLE trended higher in ipsilateral PuL (p = 0.06), but was lower in the lateral occipital (p {$<$} 0.01) and medial occipital lobe in patients versus controls (p {$<$} 0.05, paired t-tests). More abnormal ALFF in the ipsilateral lateral occipital lobe is associated with worse preoperative performance on Rey Complex Figure Test Immediate (p {$<$} 0.05, r = 0.381) and Delayed scores (p {$<$} 0.05, r = 0.413, Pearson’s Correlations). After surgery, connectivity between PuL and lateral occipital lobe remains abnormal in patients (p {$<$} 0.01), but connectivity between CL and medial occipital lobe improves and is no longer different from control values (p {$>$} 0.05, ANOVA, post hoc Fischer’s LSD). In conclusion, thalamic arousal nuclei exhibit abnormal connectivity with occipital lobe in TLE, and some connections may improve after surgery. Studying thalamic arousal centers may help explain distal network disturbances in TLE.},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\BPC9XW9J\Wills e.a. - 2021 - People with mesial temporal lobe epilepsy have alt.pdf}
}

@article{witterIntrinsicExtrinsicWiring2007,
  title = {Intrinsic and Extrinsic Wiring of {{CA3}}: {{Indications}} for Connectional Heterogeneity},
  shorttitle = {Intrinsic and Extrinsic Wiring of {{CA3}}},
  author = {Witter, M. P.},
  date = {2007-11-14},
  journaltitle = {Learning \& Memory},
  shortjournal = {Learning \& Memory},
  volume = {14},
  number = {11},
  pages = {705--713},
  issn = {1072-0502},
  doi = {10.1101/lm.725207},
  url = {http://www.learnmem.org/cgi/doi/10.1101/lm.725207},
  urldate = {2024-04-01},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\EKNWNKCN\Witter - 2007 - Intrinsic and extrinsic wiring of CA3 Indications.pdf}
}

@article{wolfartHomeostasisChannelopathyAcquired2015,
  title = {Homeostasis or Channelopathy? {{Acquired}} Cell Type-Specific Ion Channel Changes in Temporal Lobe Epilepsy and Their Antiepileptic Potential},
  shorttitle = {Homeostasis or Channelopathy?},
  author = {Wolfart, Jakob and Laker, Debora},
  date = {2015-06-15},
  journaltitle = {Frontiers in Physiology},
  shortjournal = {Front. Physiol.},
  volume = {6},
  publisher = {Frontiers},
  issn = {1664-042X},
  doi = {10.3389/fphys.2015.00168},
  url = {https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2015.00168/full},
  urldate = {2024-04-10},
  abstract = {{$<$}p{$>$}Neurons continuously adapt the expression and functionality of their ion channels. For example, exposed to chronic excitotoxicity, neurons homeostatically downscale their intrinsic excitability. In contrast, the “acquired channelopathy” hypothesis suggests that proepileptic channel characteristics develop during epilepsy. We review cell type-specific channel alterations under different epileptic conditions and discuss the potential of channels that undergo homeostatic adaptations, as targets for antiepileptic drugs (AEDs). Most of the relevant studies have been performed on temporal lobe epilepsy (TLE), a widespread AED-refractory, focal epilepsy. The TLE patients, who undergo epilepsy surgery, frequently display hippocampal sclerosis (HS), which is associated with degeneration of {$<$}italic{$>$}cornu ammonis{$<$}/italic{$>$} subfield 1 pyramidal cells (CA1 PCs). Although the resected human tissue offers insights, controlled data largely stem from animal models simulating different aspects of TLE and other epilepsies. Most of the cell type-specific information is available for CA1 PCs and dentate gyrus granule cells (DG GCs). Between these two cell types, a dichotomy can be observed: while DG GCs acquire properties decreasing the intrinsic excitability (in TLE models and patients with HS), CA1 PCs develop channel characteristics increasing intrinsic excitability (in TLE models without HS only). However, thorough examination of data on these and other cell types reveals the coexistence of protective and permissive intrinsic plasticity within neurons. These mechanisms appear differentially regulated, depending on the cell type and seizure condition. Interestingly, the same channel molecules that are upregulated in DG GCs during HS-related TLE, appear as promising targets for future AEDs and gene therapies. Hence, GCs provide an example of homeostatic ion channel adaptation which can serve as a primer when designing novel anti-epileptic strategies.{$<$}/p{$>$}},
  langid = {english},
  keywords = {channelacoids,Hippocampus,Homeostasis,Kainic Acid,Pilocarpine},
  file = {C:\Users\marc_\Zotero\storage\YQBVLCRX\Wolfart en Laker - 2015 - Homeostasis or channelopathy Acquired cell type-s.pdf}
}

@article{wuIdentificationCommonBrain2023,
  title = {Identification of a Common Brain Network Associated with Lesional Epilepsy},
  author = {Wu, Di and Liu, Jinghui and Ren, Liankun},
  date = {2023-11-01},
  journaltitle = {Acta Epileptologica},
  shortjournal = {Acta Epileptologica},
  volume = {5},
  number = {1},
  pages = {26},
  issn = {2524-4434},
  doi = {10.1186/s42494-023-00138-z},
  url = {https://doi.org/10.1186/s42494-023-00138-z},
  urldate = {2024-04-01},
  abstract = {Stroke is the leading cause of neurological diseases globally. Remarkably, epilepsy is a common complication of stroke, which greatly impairs the quality of life of patients and poses a significant clinical challenge. Therefore, a better understanding of the risk factors for poststroke epilepsy is crucial. A recent study published in JAMA Neurology studied the brain network associated with poststroke epilepsy in a group of 76 patients compared to a cohort of 625 control patients using lesion mapping techniques. The results showed that negative functional connectivity between lesion locations and regions in the basal ganglia and cerebellum confers a higher risk of developing epilepsy after stroke. The lesion network nodes associated with epilepsy were identical across different lesion types including hematomas, traumas, tumors, and tubers. Furthermore, the poststroke epilepsy brain network has potential therapeutic relevance to deep brain stimulation (DBS). In a cohort of 30 patients, the functional connectivity between anterior thalamic DBS sites and the lesion network nodes was found to correlate with seizure control after DBS. In summary, the finding provides a novel method for predicting the risk of poststroke epilepsy in patients and may guide brain stimulation treatments for epilepsy.},
  keywords = {Brain network,Lesion network mapping,Neuromodulation,Poststroke epilepsy},
  file = {C:\Users\marc_\Zotero\storage\YALDNIGX\Wu e.a. - 2023 - Identification of a common brain network associate.pdf}
}

@article{yayikEpilepticStateDetection2015,
  title = {Epileptic {{State Detection}}: {{Pre-ictal}}, {{Inter-ictal}}, {{Ictal}}},
  shorttitle = {Epileptic {{State Detection}}},
  author = {Yayik, Apdullah and Yildirim, Esen and Kutlu, Yakup and Yildirim, Serdar},
  date = {2015-01-13},
  journaltitle = {International Journal of Intelligent Systems and Applications in Engineering},
  volume = {3},
  number = {1},
  pages = {14--18},
  publisher = {İsmail SARITAŞ},
  issn = {2147-6799},
  doi = {10.18201/ijisae.14531},
  url = {https://dergipark.org.tr/tr/pub/ijisae/issue/8518/105835},
  urldate = {2024-04-11},
  abstract = {Epileptic seizure detection and prediction from electroencephalography (EEG) is a vital area of research. In this study, Second-Order Difference Plot (SODP) is used to extract features based on consecutive difference of time domain values from three states of EEG (pre-ictal, ictal and inter-ictal), and Multi-Layer Neural Network classifier is used to classify these three classes. The proposed technique is tested on a publicly available EEG database and classified with Naive Bayes and k -nearest neighbor classifiers. As a result, it is shown that overall accuracy of 98.70\% can be achieved by using the proposed system with Neural Network classifier.},
  issue = {1},
  langid = {english},
  file = {C:\Users\marc_\Zotero\storage\K47WX5AP\Yayik e.a. - 2015 - Epileptic State Detection Pre-ictal, Inter-ictal,.pdf}
}

@article{yuReducedSodiumCurrent2006,
  title = {Reduced Sodium Current in {{GABAergic}} Interneurons in a Mouse Model of Severe Myoclonic Epilepsy in Infancy},
  author = {Yu, Frank H. and Mantegazza, Massimo and Westenbroek, Ruth E. and Robbins, Carol A. and Kalume, Franck and Burton, Kimberly A. and Spain, William J. and McKnight, G. Stanley and Scheuer, Todd and Catterall, William A.},
  date = {2006-09},
  journaltitle = {Nature Neuroscience},
  shortjournal = {Nat Neurosci},
  volume = {9},
  number = {9},
  pages = {1142--1149},
  publisher = {Nature Publishing Group},
  issn = {1546-1726},
  doi = {10.1038/nn1754},
  url = {https://www.nature.com/articles/nn1754},
  urldate = {2024-04-12},
  abstract = {Voltage-gated sodium channels (NaV) are critical for initiation of action potentials. Heterozygous loss-of-function mutations in NaV1.1 channels cause severe myoclonic epilepsy in infancy (SMEI). Homozygous null Scn1a−/− mice developed ataxia and died on postnatal day (P) 15 but could be sustained to P17.5 with manual feeding. Heterozygous Scn1a+/− mice had spontaneous seizures and sporadic deaths beginning after P21, with a notable dependence on genetic background. Loss of NaV1.1 did not change voltage-dependent activation or inactivation of sodium channels in hippocampal neurons. The sodium current density was, however, substantially reduced in inhibitory interneurons of Scn1a+/− and Scn1a−/− mice but not in their excitatory pyramidal neurons. An immunocytochemical survey also showed a specific upregulation of NaV1.3 channels in a subset of hippocampal interneurons. Our results indicate that reduced sodium currents in GABAergic inhibitory interneurons in Scn1a+/− heterozygotes may cause the hyperexcitability that leads to epilepsy in patients with SMEI.},
  langid = {english},
  keywords = {Animal Genetics and Genomics,Behavioral Sciences,Biological Techniques,Biomedicine,general,Neurobiology,Neurosciences}
}

@article{zhangIdentificationKeyPotassium2023,
  title = {Identification of Key Potassium Channel Genes of Temporal Lobe Epilepsy by Bioinformatics Analyses and Experimental Verification},
  author = {Zhang, Lin-ming and Chen, Ling and Zhao, Yi-fei and Duan, Wei-mei and Zhong, Lian-mei and Liu, Ming-wei},
  date = {2023-07-07},
  journaltitle = {Frontiers in Neurology},
  shortjournal = {Front. Neurol.},
  volume = {14},
  publisher = {Frontiers},
  issn = {1664-2295},
  doi = {10.3389/fneur.2023.1175007},
  url = {https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1175007/full},
  urldate = {2024-04-30},
  abstract = {{$<$}p{$>$}One of the most prevalent types of epilepsy is temporal lobe epilepsy (TLE), which has unknown etiological factors and drug resistance. The detailed mechanisms underlying potassium channels in human TLE have not yet been elucidated. Hence, this study aimed to mine potassium channel genes linked to TLE using a bioinformatic approach. The results found that Four key TLE-related potassium channel genes (TERKPCGs) were identified: potassium voltage-gated channel subfamily E member ({$<$}italic{$>$}KCNA{$<$}/italic{$>$}) 1, {$<$}italic{$>$}KCNA2{$<$}/italic{$>$}, potassium inwardly rectifying channel, subfamily J, member 11 ({$<$}italic{$>$}KCNJ11{$<$}/italic{$>$}), and {$<$}italic{$>$}KCNS1{$<$}/italic{$>$}. A protein–protein interaction (PPI) network was constructed to analyze the relationship between TERKPCGs and other key module genes. The results of gene set enrichment analysis (GSEA) for a single gene indicated that the four TERKPCGs were highly linked to the cation channel, potassium channel, respiratory chain, and oxidative phosphorylation. The mRNA-TF network was established using four mRNAs and 113 predicted transcription factors. A ceRNA network containing seven miRNAs, two mRNAs, and 244 lncRNAs was constructed based on the TERKPCGs. Three common small-molecule drugs (enflurane, promethazine, and miconazole) target {$<$}italic{$>$}KCNA1, KCNA2{$<$}/italic{$>$}, and {$<$}italic{$>$}KCNS1{$<$}/italic{$>$}. Ten small-molecule drugs (glimepiride, diazoxide, levosimendan, and thiamylal et al.) were retrieved for {$<$}italic{$>$}KCNJ11{$<$}/italic{$>$}. Compared to normal mice, the expression of {$<$}italic{$>$}KCNA1{$<$}/italic{$>$}, {$<$}italic{$>$}KCNA2{$<$}/italic{$>$}, {$<$}italic{$>$}KCNJ11{$<$}/italic{$>$}, and {$<$}italic{$>$}KCNS1{$<$}/italic{$>$} was downregulated in the brain tissue of the epilepsy mouse model at both the transcriptional and translational levels, which was consistent with the trend of human data from the public database. The results indicated that key potassium channel genes linked to TLE were identified based on bioinformatics analysis to investigate the potential significance of potassium channel genes in the development and treatment of TLE.{$<$}/p{$>$}},
  langid = {english},
  keywords = {Bioinformatics analyses,potassium channel genes,Target drugs,Temporal Lobe Epilepsy,WGCNA},
  file = {C:\Users\marc_\Zotero\storage\SRTCZ4XL\Zhang e.a. - 2023 - Identification of key potassium channel genes of t.pdf}
}

@article{zhaoPotassiumChannelrelatedEpilepsy,
  title = {Potassium Channel-Related Epilepsy: {{Pathogenesis}} and Clinical Features},
  shorttitle = {Potassium Channel-Related Epilepsy},
  author = {Zhao, Tong and Wang, Le and Chen, Fang},
  journaltitle = {Epilepsia Open},
  volume = {n/a},
  number = {n/a},
  issn = {2470-9239},
  doi = {10.1002/epi4.12934},
  url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/epi4.12934},
  urldate = {2024-04-08},
  abstract = {Variants in potassium channel-related genes are one of the most important mechanisms underlying abnormal neuronal excitation and disturbances in the cellular resting membrane potential. These variants can cause different forms of epilepsy, which can seriously affect the physical and mental health of patients, especially those with refractory epilepsy or status epilepticus, which are common among pediatric patients and are potentially life-threatening. Variants in potassium ion channel-related genes have been reported in few studies; however, to our knowledge, no systematic review has been published. This study aimed to summarize the epilepsy phenotypes, functional studies, and pharmacological advances associated with different potassium channel gene variants to assist clinical practitioners and drug development teams to develop evidence-based medicine and guide research strategies. PubMed and Google Scholar were searched for relevant literature on potassium channel-related epilepsy reported in the past 5–10 years. Various common potassium ion channel gene variants can lead to heterogeneous epilepsy phenotypes, and functional effects can result from gene deletions and compound effects. Administration of select anti-seizure medications is the primary treatment for this type of epilepsy. Most patients are refractory to anti-seizure medications, and some novel anti-seizure medications have been found to improve seizures. Use of targeted drugs to correct aberrant channel function based on the type of potassium channel gene variant can be used as an evidence-based pathway to achieve precise and individualized treatment for children with epilepsy. Plain Language Summary In this article, the pathogenesis and clinical characteristics of epilepsy caused by different types of potassium channel gene variants are reviewed in the light of the latest research literature at home and abroad, with the expectation of providing a certain theoretical basis for the diagnosis and treatment of children with this type of disease.},
  langid = {english},
  keywords = {epilepsy,functional studies,genes,potassium channels,therapy},
  file = {C\:\\Users\\marc_\\Zotero\\storage\\5QVHBMYM\\Zhao e.a. - Potassium channel-related epilepsy Pathogenesis a.pdf;C\:\\Users\\marc_\\Zotero\\storage\\CVNE9X64\\epi4.html}
}