Epilepsy research and treatment

Network analysis reveals converging molecular mechanisms in genetic epilepsies

The paper identifies converging molecular pathways in genetic epilepsies through network analysis of epilepsy-associated genes and highlights potential therapeutic targets.

Multi-region recordings reveal collapse of hippocampal CA3-amygdala gamma communication at seizure onset in mice

The paper uses multi-region recordings in mice to show that gamma communication between hippocampal CA3 and amygdala collapses abruptly at seizure onset.

Longitudinal Imaging in a Mouse Model of Focal Cortical Dysplasia Reveals Lesion Expansion and Loss of Pre-Discharge Neuronal Recruitment

This study uses longitudinal imaging in a mouse model of FCD II to show lesion expansion, hypoactive dysmorphic neurons, and loss of pre-discharge neuronal recruitment over time.

Histological morphometric correlates of MRI-defined cortical thinning in temporal lobe epilepsy

This study investigates the histological correlates of MRI-defined cortical thinning in temporal lobe epilepsy, finding that thinning is associated with altered neuronal packing and cell-size distributions rather than neuronal loss.

SCN1A haploinsufficiency disrupts neural progenitor networks and accelerates neurogenesis in human Dravet syndrome forebrain assembloids

This study shows that SCN1A haploinsufficiency disrupts neural progenitor networks and accelerates neurogenesis in human Dravet syndrome forebrain assembloids, leading to altered corticogenesis and circuit hyperexcitability.

A Reproducible Cortical Model of Focal Epileptiform Activity with a Multi-Biomarker Analysis Pipeline

This paper develops an acute cortical model of focal epileptiform activity in mice and introduces a multi-biomarker analysis pipeline to characterize the induced activity.

RAPTOR-targeted Antisense Oligonucleotides Restrict Pathological mTORC1 Activity in GATOR1-dependent Disease

This study develops RAPTOR-targeted ASOs to treat GATOR1-deficient diseases by reducing mTORC1 activity, improving neuronal function, and extending lifespan in models.

Biphasic Modulation of Absence Seizures by Lisuride in GAERS: Dissecting the Role of 5-HT2A Receptors

This study investigates lisuride's biphasic effects on absence seizures in GAERS, showing dose-dependent modulation and distinct roles for 5-HT2A receptors in different phases.

Connexin 40 deficiency alters the temporal profile of postictal oxygen dynamics following focal seizures.

This study shows that Cx40 deficiency changes the timing of oxygen recovery after seizures without affecting seizure duration.

Tofacitinib overrides first-line drug resistance in a pre-clinical model of epilepsy

This study shows that tofacitinib, a JAK inhibitor, reduces seizures and improves cognition in a mouse model of drug-resistant epilepsy when used as an add-on therapy to carbamazepine.

Seizures in a Dravet Syndrome mouse model inhibit the locus coeruleus but locally evoke supraphysiologic norepinephrine release

The paper investigates NE release during seizures in a Dravet Syndrome mouse model, finding inhibited LC-NE neuron activity but increased NE release in downstream regions.

Robust Induction of Spontaneous Recurrent Seizures and Hippocampal Sclerosis with Synthetic Kainic Acid in the Intrahippocampal Kainate Model

This study evaluates synthetic kainic acid injection parameters in the IHK model to reliably induce seizures while minimizing mortality.

Lack of tau expression modifies epileptogenesis associated neuroplasticity in the ventral dentate gyrus in a mouse model of temporal lobe epilepsy

The paper investigates how tau deletion affects neuroplasticity and seizure expression in a mouse model of temporal lobe epilepsy, finding increased inhibitory synaptic input in ventral dentate granule cells.

Presynaptic GABABSignaling Enhances Synaptic Inhibition Without Mitigating Persistent Dentate Gyrus Hyperexcitability After Status Epilepticus

This study examines how presynaptic GABAB receptor signaling affects DG network dynamics and inhibition after status epilepticus, finding persistent hyperexcitability and a homeostatic role for GABAB receptors in early recovery.

P2X7 receptor antagonism potentiates seizure-suppressive effects of anti-seizure medications in human resected epileptic brain tissue

This study shows that P2X7R antagonists enhance the effectiveness of anti-seizure medications in human epileptic brain tissue by reducing inflammation and improving drug response.

Block of Thalamic 5-HT2A Receptors modulates Tonic GABA-A Inhibition but not Absence Seizures

The paper investigates the role of 5-HT2A receptor signaling in modulating tonic GABA-A inhibition and absence seizures in GAERS rats, finding that while it affects tonic currents, it does not alter seizure occurrence.

Molecular context of pathogenic variants is associated with phenotype and treatment response in SCN8A-related disorders

The paper maps molecular features of SCN8A variants to clinical outcomes and treatment response in SCN8A-related disorders, identifying regions and features associated with phenotypic variability.

Sleep spindle deficits in childhood absence epilepsy improve with antiseizure treatment and disease resolution

This study examines sleep spindle activity in children with childhood absence epilepsy (CAE) and finds that spindle rates decrease with active disease but improve with treatment and disease resolution.

Spike-wave discharges reflect widespread, but non-uniform, cortical hypersynchrony during immobility

This study investigates spike-wave discharges (SWDs) in mice, showing they cause widespread cortical hypersynchrony, with varying effects across brain regions and potential behavioral influences.

Presynaptic mechanism of epileptiform activities in forward-programmed human excitatory neuronal networks

The paper investigates the presynaptic mechanisms underlying epileptiform activities in human excitatory neuronal networks, finding that deceleration of rhythmic discharges is linked to vesicle translocation between pools.

Parvalbumin interneurons and dentate gyrus homeostatic dysregulation shape epileptogenesis in Angelman syndrome model mice

This study identifies parvalbumin interneurons and dentate gyrus remodeling as key factors in epileptogenesis in Angelman syndrome model mice.

Sleep fragmentation drives local, network-specific epileptic activity in human epilepsy

This study shows that sleep fragmentation increases local epileptic activity in specific brain regions without affecting broader network propagation.

Midline Thalamic Neurons Show Early Hypersynchrony During Absence Seizures in Mouse Models

The paper identifies early hypersynchrony in midline thalamic neurons during absence seizures in mouse models and shows that disrupting this activity stops seizures.

WNK-SPAK/OSR1 signaling pathway facilitates ictal activity via reduced neuronal chloride extrusion rate

This study shows that inhibiting the WNK-SPAK/OSR1 pathway reduces neuronal chloride intracellular levels and suppresses ictal-like discharges by enhancing chloride extrusion through NKCC1 and KCC2.

A De Novo, Intragenic Modifier in Cis Rescues Scn8a-N1768D Epilepsy and Defines a Therapeutic Window Bounded by Gain- and Loss-of-Function

The paper identifies a de novo frameshift variant that rescues a Gain-of-function SCN8A epilepsy phenotype by reducing NaV1.6 expression within a therapeutic window.

HIPPOCAMPAL TAU RELATED SIGNAL INDEXES HYPEREXCITABILITY AND NREM SLEEP MEMORY DYSFUNCTION IN TEMPORAL LOBE EPILEPSY

This study links higher hippocampal 18F-MK6240 uptake in TLE to increased seizure burden, altered NREM sleep microstructure, and impaired memory.

Mistrafficking of KCC2 promotes hyperexcitability in hippocampal circuitry in a murine model of Christianson Syndrome

The paper identifies endosomal dysfunction in a murine model of Christianson Syndrome as a cause of inhibitory circuit hyperexcitability through KCC2 mistrafficking.

Polygenic Risk and Genetic Predisposition in Post-Traumatic Epilepsy: A Framework for Risk Estimation

The paper identifies polygenic risk variants for post-traumatic epilepsy using whole-exome sequencing and develops a risk estimation framework.

Fast-ripples are emergent properties of neuronal networks

Most fast-ripples (250-500 Hz) in rat and human recordings are consistent with chance clustering of action potentials; in awake patients, distinct events make up an estimated 37.5% of detections.

Cis-Attenuation of Pathogenic Scn8a Variant Causing Childhood Epilepsy Reveals Opposing Transcriptional Programs Driving NaV1.6 Gain and Loss of Function Phenotypes

The paper identifies opposing transcriptional programs in SCN8A-related epilepsy, showing distinct cellular responses to gain- and loss-of-function mutations and suggesting therapeutic strategies.