gamma epilepsy

Risk taking behavior is a symptom of multiple neuropsychiatric disorders and often lacks effective treatments. Reward circuitry regions including the amygdala, orbitofrontal cortex, insula, and anterior cingulate have been implicated in risk-taking by neuroimaging studies. Electrophysiological activity associated with risk taking in these regions is not well understood in humans. Further characterizing the neural signalling that underlies risk-taking may provide therapeutic insight into disorders associated with risk-taking...

BACKGROUND: The gamma-aminobutyric acid (GABA) variant causes developmental and epileptic encephalopathy 45 (DEE45), an autosomal dominant disorder that results in oculocortical visual impairment, reduced muscle tone, psychomotor retardation, and epilepsy. Analysis of the clinical features and genetics of DEE45 may be helpful in complementing genotype-phenotype studies. CASE PRESENTATION: We collected peripheral blood samples from the affected children and parents and extracted genomic DNA...

We investigated the differences in functional connectivity based on the source-level electroencephalography (EEG) analysis between stroke patients with and without post-stroke epilepsy (PSE). Thirty stroke patients with PSE and 35 stroke patients without PSE were enrolled. EEG was conducted during a resting state period. We used a Brainstorm program for source estimation and the connectivity matrix. Data were processed according to EEG frequency bands. We used a BRAPH program to apply a graph theoretical analysis...

Brain disturbances during development can have a lasting impact on neural function and behavior. Seizures during this critical period are linked to significant long-term consequences such as neurodevelopmental disorders, cognitive impairments, and psychiatric symptoms, resulting in a complex spectrum of multimorbidity. The hippocampus-prefrontal cortex (HPC-PFC) circuit emerges as a potential common link between such disorders. However, the mechanisms underlying these outcomes and how they relate to specific behavioral alterations are unclear...

Lafora disease is a fatal teenage-onset progressive myoclonus epilepsy and neurodegenerative disease associated with polyglucosan bodies. Polyglucosans are long-branched and as a result precipitation- and aggregation-prone glycogen. In mouse models, downregulation of glycogen synthase, the enzyme that elongates glycogen branches, prevents polyglucosan formation and rescues Lafora disease. Mouse work, however, has not yet revealed the mechanisms of polyglucosan generation, and few in vivo human studies have been performed...

The Stroop Task is a well-known neuropsychological task developed to investigate conflict processing in the human brain. Our group has utilized direct intracranial neural recordings in various brain regions during performance of a modified color-word Stroop Task to gain a mechanistic understanding of non-emotional human conflict processing. The purpose of this review article is to: 1) synthesize our own studies into a model of human conflict processing, 2) review the current literature on the Stroop Task and other conflict tasks to put our research in context, and 3) describe how these studies define a network in conflict processing...

PURPOSE: In developmental and epileptic encephalopathy with spike-and-wave activation in sleep (DEE-SWAS), the thalamocortical network is suggested to play an important role in the pathophysiology of the progression from focal epilepsy to DEE-SWAS. Ethosuximide (ESM) exerts effects by blocking T-type calcium channels in thalamic neurons. With the thalamocortical network in mind, we studied the prediction of ESM effectiveness in DEE-SWAS treatment using phase-amplitude coupling (PAC) analysis...

INTRODUCTION: Epileptiform activity is the most striking result of hyperexcitation of a group of neurons that can occur in different brain regions and then spread to other sites. Later it was shown that these rhythms have a cellular correlate in vitro called paroxysmal depolarization shift (PDS). In 13-15 DIV neuron-glial cell culture, inhibition of the GABA(A) receptors induces bursts of action potential in the form of clasters PDS and oscillations of intracellular Ca2+ concentration ([Ca2+ ]i )...

Mitochondria are critical modulators of antiviral tolerance through the release of mitochondrial RNA and DNA (mtDNA and mtRNA) fragments into the cytoplasm after infection, activating virus sensors and type-I interferon (IFN-I) response1-4 . The relevance of these mechanisms for mitochondrial diseases remains understudied. Here we investigated mitochondrial recessive ataxia syndrome (MIRAS), which is caused by a common European founder mutation in DNA polymerase gamma (POLG1)5 . Patients homozygous for the MIRAS variant p...

Gamma-aminobutyric acid (GABA) plays a crucial role in the central nervous system as an inhibitory neurotransmitter. Imbalances of this neurotransmitter are associated with neurological diseases, such as Alzheimer's and Parkinson's disease, and psychological disorders, including anxiety, depression, and stress. Since GABA has long been believed to not cross the blood-brain barrier, the effects of circulating GABA on the brain are neglected. However, emerging evidence has demonstrated that changes in both circulating and brain levels of GABA are associated with changes in gut microbiota composition and that changes in GABA levels and microbiota composition play a role in modulating mental health...

INTRODUCTION: Deep brain stimulation (DBS) has shown remarkable success treating neurological and psychiatric disorders including Parkinson's disease, essential tremor, dystonia, epilepsy, and obsessive-compulsive disorder. DBS is now being explored to improve cognitive and functional outcomes in other psychiatric conditions, such as those characterized by reduced N-methyl-D-aspartate (NMDA) function (i.e., schizophrenia). While DBS for movement disorders generally involves high-frequency (>100 Hz) stimulation, there is evidence that low-frequency stimulation may have beneficial and persisting effects when applied to cognitive brain networks...

OBJECTIVE: In tasks involving new visuospatial information, we rely on working memory, supported by a distributed brain network. We investigated the dynamic interplay between brain regions, including cortical and white matter structures, to understand how neural interactions change with different memory loads and trials, and their subsequent impact on working memory performance. METHODS: Patients undertook a task of immediate spatial recall during intracranial EEG monitoring...

BACKGROUND AND OBJECTIVES: Epstein-Barr virus (EBV) has been strongly implicated in the pathogenesis of multiple sclerosis (MS). Despite this, there are no routinely used tests to measure cellular response to EBV. In this study, we analyzed the cellular response to EBV nuclear antigen-1 (EBNA-1) in people with MS (pwMS) using a whole blood assay. METHODS: This cross-sectional study took place in a dedicated MS clinic in a university hospital. We recruited healthy controls, people with epilepsy (PWE), and pwMS taking a range of disease-modifying treatments (DMTs) including natalizumab, anti-CD20 monoclonal antibodies (mAbs), dimethyl fumarate (DMF), and also treatment naïve...

BACKGROUND: Positive correlations between low- and high-frequency spectra from stereotactic electroencephalogram (SEEG) recordings have been implicated in pathological brain activity interictally and have been used for ictal detection in both focal and network models. OBJECTIVE: We evaluated SEEG signals in patients who ultimately underwent temporal lobectomy to evaluate their utility in seizure localization and prediction of seizure freedom post-resection. METHODS: We retrospectively analyzed cross-frequency correlations between beta and high gamma (HG) interictal SEEG signals from 22 patients...

There are considerable gaps in our understanding of the relationship between human brain activity measured at different temporal and spatial scales. Here, electrocorticography (ECoG) measures were used to predict functional MRI changes in the sensorimotor cortex in two brain states: at rest and during motor performance. The specificity of this relationship to spatial co-localisation of the two signals was also investigated. We acquired simultaneous ECoG-fMRI in the sensorimotor cortex of three patients with epilepsy...

PCDH19 clustering epilepsy (PCDH19-CE) is an X-linked epilepsy disorder associated with intellectual disability (ID) and behavioral disturbances, which is caused by PCDH19 gene variants. PCDH19 pathogenic variant leads to epilepsy in heterozygous females, not in hemizygous males and the inheritance pattern is unusual. The hypothesis of cellular interference was described as a key pathogenic mechanism. According to that, males do not develop the disease because of the uniform expression of PCDH19 (variant or wild type) unless they have a somatic variation...

OBJECTIVE: In the era of stereoelectroencephalography (SEEG), many studies have been devoted to understanding the role of interictal high-frequency oscillations. High-frequency activity (HFA) at seizure onset has been identified as a marker of epileptogenic zone. We address the physiological significance of ictal HFAs and their relation to clinical semiology. METHODS: We retrospectively identified patients with pure focal primary motor epilepsy. We selected only patients in whom SEEG electrodes were optimally placed in the motor cortex as confirmed by electrical stimulation...

Developmental and epileptic encephalopathies (DEEs) are early-onset conditions that cause intractable seizures and developmental delays. Missense variants in Gamma-aminobutyric acid type A receptor (GABAAR) subunits commonly cause DEEs. Ahring et al. (2022) showed a variant in the gene that encodes the delta subunit (GABRD) is strongly associated with the gain-of-function of extrasynaptic GABAAR. Here, we report the generation of two patient-specific human induced pluripotent stem cells (hiPSC) lines with (i) a de novo variant and (ii) a maternal variant, both for the pathogenic GABRD c...

Stiripentol (Diacomit® ) (STP) is an orally active antiseizure medication (ASM) indicated as adjunctive therapy, for the treatment of seizures associated with Dravet syndrome (DS), a severe form of childhood epilepsy, in conjunction with clobazam and, in some regions valproic acid. Since the discovery of STP, several mechanisms of action (MoA) have been described that may explain its specific effect on seizures associated with DS. STP is mainly considered as a potentiator of gamma-aminobutyric acid (GABA) neurotransmission: (i) via uptake blockade, (ii) inhibition of degradation, but also (iii) as a positive allosteric modulator of GABAA receptors, especially those containing α3 and δ subunits...

It has been suggested that cross-frequency coupling in cortico-hippocampal networks enables the maintenance of multiple visuo-spatial items in working memory. However, whether this mechanism acts as a global neural code for memory retention across sensory modalities remains to be demonstrated. Intracranial EEG data were recorded while drug-resistant patients with epilepsy performed a delayed matched-to-sample task with tone sequences. We manipulated task difficulty by varying the memory load and the duration of the silent retention period between the to-be-compared sequences...