A Speech Neuroprosthesis in the Frontal Lobe and Hippocampus: Decoding High-Frequency Activity into Phonemes.

BACKGROUND AND OBJECTIVES: Loss of speech due to injury or disease is devastating. Here, we report a novel speech neuroprosthesis that artificially articulates building blocks of speech based on high-frequency activity in brain areas never harnessed for a neuroprosthesis before: anterior cingulate and orbitofrontal cortices, and hippocampus. METHODS: A 37-year-old male neurosurgical epilepsy patient with intact speech, implanted with depth electrodes for clinical reasons only, silently controlled the neuroprosthesis almost immediately and in a natural way to voluntarily produce 2 vowel sounds. RESULTS: During the first set of trials, the participant made the neuroprosthesis produce the different vowel sounds artificially with 85% accuracy. In the following trials, performance improved consistently, which may be attributed to neuroplasticity. We show that a neuroprosthesis trained on overt speech data may be controlled silently. CONCLUSION: This may open the way for a novel strategy of neuroprosthesis implantation at earlier disease stages (eg, amyotrophic lateral sclerosis), while speech is intact, for improved training that still allows silent control at later stages. The results demonstrate clinical feasibility of direct decoding of high-frequency activity that includes spiking activity in the aforementioned areas for silent production of phonemes that may serve as a part of a neuroprosthesis for replacing lost speech control pathways.

Cannabidiol-enriched oil for adult patients with drug-resistant epilepsy: Prospective clinical and electrophysiological study.

OBJECTIVE: Cannabidiol-enriched oil (CBDO) is being used increasingly to improve seizure control in adult patients with drug-resistant epilepsy (DRE), despite the lack of large-scale studies supporting its efficacy in this patient population. We aimed to assess the effects of add-on CBDO on seizure frequency as well as on gait, cognitive, affective, and sleep-quality metrics, and to explore the electrophysiological changes in responder and non-responder DRE patients treated with add-on CBDO. METHODS: We prospectively recruited adult DRE patients who were treated with add-on CBDO. Patients were evaluated prior to treatment and following 4 weeks of a maintenance daily dose of ≈260 mg CBD and ≈12 mg Δ9-tetrahydrocannabinol (THC). The outcome measures included seizure response to CBDO (defined as ≥50% decrease in seizures compared to pre-CBDO baseline), gait testing, Montreal Cognitive Assessment (MoCA), Hospital Anxiety and Depression Scale (HADS), and sleep-quality questionnaire assessments. Patients underwent electroencephalography (EEG) recording during rest as well as event-related potentials (ERPs) during visual Go/NoGo task while sitting and while walking. RESULTS: Nineteen patients were recruited, of which 16 finished pre- and post-CBDO assessments. Seven patients (43.75%) were responders demonstrating an average reduction of 82.4% in seizures, and nine patients (56.25%) were non-responders with an average seizure increase of 30.1%. No differences in demographics and clinical parameters were found between responders and non-responders at baseline. However, responders demonstrated better performance in the dual-task walking post-treatment (p = .015), and correlation between increase in MoCA and seizure reduction (r = .810, p = .027). Post-CBDO P300 amplitude was lower during No/Go-sitting in non-responders (p = .028) and during No/Go-walking in responders (p = .068). SIGNIFICANCE: CBDO treatment can reduce seizures in a subset of patients with DRE, but could aggravate seizure control in a minority of patients; yet we found no specific baseline clinical or electrophysiological characteristics that are associated with response to CBDO. However, changes in ERPs in response to treatment could be a promising direction to better identify patients who could benefit from CBDO treatment.

Therapeutic drug monitoring in pregnancy: Levetiracetam.

OBJECTIVE: Levetiracetam (LEV) is an antiseizure medication that is mainly excreted by the kidneys. Due to its low teratogenic risk, LEV is frequently prescribed for women with epilepsy (WWE). Physiological changes during gestation affect the pharmacokinetic characteristics of LEV. The goal of our study was to characterize the changes in LEV clearance during pregnancy and the postpartum period, to better plan an LEV dosing paradigm for pregnant women. METHODS: This retrospective observational study incorporated a cohort of women who were followed up at the epilepsy in pregnancy clinic at Tel Aviv Sourasky Medical Center during the years 2020-2023. Individualized target concentrations of LEV and an empirical postpartum taper were used for seizure control and to reduce toxicity likelihood. Patient visits took place every 1-2 months and included a review of medication dosage, trough LEV blood levels, week of gestation and LEV dose at the time of level measurement, and seizure diaries. Total LEV concentration/dose was calculated based on LEV levels and dose as an estimation of LEV clearance. RESULTS: A total of 263 samples were collected from 38 pregnant patients. We observed a decrease in LEV concentration/dose (C/D) as the pregnancy progressed, followed by an abrupt postpartum increase. Compared to the 3rd trimester, the most significant C/D decrease was observed at the 1st trimester (slope = .85), with no significant change in the 2nd trimester (slope = .11). A significant increase in C/D occurred postpartum (slope = 5.23). LEV dose was gradually increased by 75% during pregnancy compared to preconception. Average serum levels (µg/mL) decreased during pregnancy. During the postpartum period, serum levels increased, whereas the LEV dose was decreased by 24%, compared to the 3rd trimester. SIGNIFICANCE: LEV serum level monitoring is essential for WWE prior to and during pregnancy as well as postpartum. Our data contribute to determining a rational treatment and dosing paradigm for LEV use during both pregnancy and the postpartum period.

Grading system for assessing the confidence in the epileptogenic zone reported in published studies: A Delphi consensus study.

OBJECTIVE: This study was undertaken to develop a standardized grading system based on expert consensus for evaluating the level of confidence in the localization of the epileptogenic zone (EZ) as reported in published studies, to harmonize and facilitate systematic reviews in the field of epilepsy surgery. METHODS: We conducted a Delphi study involving 22 experts from 18 countries, who were asked to rate their level of confidence in the localization of the EZ for various theoretical clinical scenarios, using different scales. Information provided in these scenarios included one or several of the following data: magnetic resonance imaging (MRI) findings, invasive electroencephalography summary, and postoperative seizure outcome. RESULTS: The first explorative phase showed an overall interrater agreement of .347, pointing to large heterogeneity among experts' assessments, with only 17% of the 42 proposed scenarios associated with a substantial level of agreement. A majority showed preferences for the simpler scale and single-item scenarios. The successive Delphi voting phases resulted in a majority consensus across experts, with more than two thirds of respondents agreeing on the rating of each of the tested single-item scenarios. High or very high levels of confidence were ascribed to patients with either an Engel class I or class IA postoperative seizure outcome, a well-delineated EZ according to all available invasive EEG (iEEG) data, or a well-delineated focal epileptogenic lesion on MRI. MRI signs of hippocampal sclerosis or atrophy were associated with a moderate level of confidence, whereas a low level was ascribed to other MRI findings, a poorly delineated EZ according to iEEG data, or an Engel class II-IV postoperative seizure outcome. SIGNIFICANCE: The proposed grading system, based on an expert consensus, provides a simple framework to rate the level of confidence in the EZ reported in published studies in a structured and harmonized way, offering an opportunity to facilitate and increase the quality of systematic reviews and guidelines in the field of epilepsy surgery.

The COVID-19 pfizer BioNTech mRNA vaccine and the frequency of seizures.

OBJECTIVE: A nationwide vaccination operation against Coronavirus disease 2019 (COVID-19) using the BNT162b2 mRNA vaccine commenced in Israel in December 2020. People older than 60 were prioritized, and most were vaccinated shortly after. Seizures are not infrequently attributed to the vaccine despite a lack of supporting evidence. People with epilepsy (PWE) are often reluctant to get the vaccine due to concerns of seizure aggravation. We aim to examine the effect of the vaccine effort on the frequency of both new-onset seizures and recurrent seizures in PWE. METHODS: All adults who presented to the emergency department (ED) of Tel Aviv Sourasky Medical Center between January 1st and May 31st, 2017-2021, and were diagnosed with seizures were included. Demographic, clinical, and vaccination status parameters were collected using MDClone, a data acquisition tool. Vaccination rates in the general population were obtained from official governmental publications. Statistics included a sub-analysis of patients with the highest vaccination rate, people older than 60. RESULTS: 1675 cases were included. The numbers of ED visits and hospital admissions due to seizures in 2021 were comparable to preceding years after adjusting for the total number of ED visits at the same time. Out of 339 cases in 2021, 134 patients older than 60 years old presented to the ED (39.5%) compared to 124-151 in 2017-2019 (37-44%) and 103 in 2020 (33%). The vaccination rate among patients hospitalized due to seizures was similar to the general population of the same age group during the same period in Israel. There was no temporal relation between vaccination and hospitalization due to a seizure. SIGNIFICANCE: Despite very high vaccination rates in the general population in Israel and especially among people older than 60 years, no increase was observed in ED presentations due to seizures. No temporal relation was observed between vaccination and hospitalization due to a seizure. We conclude that the mass vaccination with the Pfizer BioNTech mRNA vaccine is not associated with increased seizure propensity.

Automated Interpretation of Clinical Electroencephalograms Using Artificial Intelligence.

Importance: Electroencephalograms (EEGs) are a fundamental evaluation in neurology but require special expertise unavailable in many regions of the world. Artificial intelligence (AI) has a potential for addressing these unmet needs. Previous AI models address only limited aspects of EEG interpretation such as distinguishing abnormal from normal or identifying epileptiform activity. A comprehensive, fully automated interpretation of routine EEG based on AI suitable for clinical practice is needed. Objective: To develop and validate an AI model (Standardized Computer-based Organized Reporting of EEG-Artificial Intelligence [SCORE-AI]) with the ability to distinguish abnormal from normal EEG recordings and to classify abnormal EEG recordings into categories relevant for clinical decision-making: epileptiform-focal, epileptiform-generalized, nonepileptiform-focal, and nonepileptiform-diffuse. Design, Setting, and Participants: In this multicenter diagnostic accuracy study, a convolutional neural network model, SCORE-AI, was developed and validated using EEGs recorded between 2014 and 2020. Data were analyzed from January 17, 2022, until November 14, 2022. A total of 30 493 recordings of patients referred for EEG were included into the development data set annotated by 17 experts. Patients aged more than 3 months and not critically ill were eligible. The SCORE-AI was validated using 3 independent test data sets: a multicenter data set of 100 representative EEGs evaluated by 11 experts, a single-center data set of 9785 EEGs evaluated by 14 experts, and for benchmarking with previously published AI models, a data set of 60 EEGs with external reference standard. No patients who met eligibility criteria were excluded. Main Outcomes and Measures: Diagnostic accuracy, sensitivity, and specificity compared with the experts and the external reference standard of patients' habitual clinical episodes obtained during video-EEG recording. Results: The characteristics of the EEG data sets include development data set (N = 30 493; 14 980 men; median age, 25.3 years [95% CI, 1.3-76.2 years]), multicenter test data set (N = 100; 61 men, median age, 25.8 years [95% CI, 4.1-85.5 years]), single-center test data set (N = 9785; 5168 men; median age, 35.4 years [95% CI, 0.6-87.4 years]), and test data set with external reference standard (N = 60; 27 men; median age, 36 years [95% CI, 3-75 years]). The SCORE-AI achieved high accuracy, with an area under the receiver operating characteristic curve between 0.89 and 0.96 for the different categories of EEG abnormalities, and performance similar to human experts. Benchmarking against 3 previously published AI models was limited to comparing detection of epileptiform abnormalities. The accuracy of SCORE-AI (88.3%; 95% CI, 79.2%-94.9%) was significantly higher than the 3 previously published models (P < .001) and similar to human experts. Conclusions and Relevance: In this study, SCORE-AI achieved human expert level performance in fully automated interpretation of routine EEGs. Application of SCORE-AI may improve diagnosis and patient care in underserved areas and improve efficiency and consistency in specialized epilepsy centers.

Decreased aperiodic neural activity in Parkinson's disease and dementia with Lewy bodies.

Neural oscillations and signal complexity have been widely studied in neurodegenerative diseases, whereas aperiodic activity has not been explored yet in those disorders. Here, we assessed whether the study of aperiodic activity brings new insights relating to disease as compared to the conventional spectral and complexity analyses. Eyes-closed resting-state electroencephalography (EEG) was recorded in 21 patients with dementia with Lewy bodies (DLB), 28 patients with Parkinson's disease (PD), 27 patients with mild cognitive impairment (MCI) and 22 age-matched healthy controls. Spectral power was differentiated into its oscillatory and aperiodic components using the Irregularly Resampled Auto-Spectral Analysis. Signal complexity was explored using the Lempel-Ziv algorithm (LZC). We found that DLB patients showed steeper slopes of the aperiodic power component with large effect sizes compared to the controls and MCI and with a moderate effect size compared to PD. PD patients showed steeper slopes with a moderate effect size compared to controls and MCI. Oscillatory power and LZC differentiated only between DLB and other study groups and were not sensitive enough to detect differences between PD, MCI, and controls. In conclusion, both DLB and PD are characterized by alterations in aperiodic dynamics, which are more sensitive in detecting disease-related neural changes than the traditional spectral and complexity analyses. Our findings suggest that steeper aperiodic slopes may serve as a marker of network dysfunction in DLB and PD features.

Intracerebroventricular administration for delivery of antiseizure therapeutics: Challenges and opportunities.

Intracerebroventricular (ICV) administration is increasingly being explored as a means for delivering antiseizure and antiepileptic therapies to epileptic brain tissue. This route bypasses the blood-brain barrier, thus enabling the delivery of therapeutics that are restricted from the brain, while reducing the risk of systemic adverse reactions. Nevertheless, projections from studies in patients with other diseases suggest that efficacy of some ICV-delivered therapeutics may be limited when the epileptogenic tissue or network circuits are localized more than a few millimeters away from the ventricles. In this article, we present the characteristics of the cerebrospinal fluid as a drug administration site, the brain barriers, and their relevance to treating focal and generalized epilepsies. We refer to ICV delivery of advanced therapies for treating neurodevelopmental disorders with epilepsy. We describe properties of therapeutic compounds, from small molecules to RNA-based therapeutics, proteins, and viral vectors, which can make them either fitting or poor candidates for ICV administration in epilepsy. We additionally provide an overview of preclinical studies and clinical trials involving the ICV route of delivery. Finally, we compare ICV delivery with other routes of administration that bypass the cerebral circulation. This review aims to provide information that will hopefully help investigators select candidate patients and therapeutics for ICV therapies, and to highlight advantages and challenges inherent to this approach.

New Insights on DR and DQ Human Leukocyte Antigens in Anti-LGI1 Encephalitis.

BACKGROUND AND OBJECTIVES: To explore the clinical characteristics and HLA associations of patients with anti-leucine-rich glioma-inactivated 1 encephalitis (LGI1E) from a large single center in Israel. Anti-LGI1E is the most commonly diagnosed antibody-associated encephalitic syndrome in adults. Recent studies of various populations reveal significant associations with specific HLA genes. We examined the clinical characteristics and HLA associations of a cohort of Israeli patients. METHODS: Seventeen consecutive patients with anti-LGI1E diagnosed at Tel Aviv Medical Center between the years 2011 and 2018 were included. HLA typing was performed using next-generation sequencing at the tissue typing laboratory of Sheba Medical Center and compared with data from the Ezer Mizion Bone Marrow Donor Registry, containing over 1,000,000 samples. RESULTS: Our cohort displayed a male predominance and median age at onset in the 7th decade, as previously reported. The most common presenting symptom was seizures. Notably, paroxysmal dizziness spells were significantly more common than previously reported (35%), whereas faciobrachial dystonic seizures were found only in 23%. HLA analysis revealed overrepresentation of DRB1*07:01 (OR: 3.18, CI: 20.9 p < 1.e-5) and DRB1*04:02 (OR: 3.8, CI: 20.1 p < 1.e-5), as well as of the DQ allele DQB1*02:02 (OR: 2.8, CI: 14.2 p < 0.0001) as previously reported. A novel overrepresentation observed among our patients was of the DQB1*03:02 allele (OR: 2.3, CI: 6.9 p < 0.008). In addition, we found DR-DQ associations, among patients with anti-LGI1E, that showed complete or near-complete linkage disequilibrium (LD). By applying LD analysis to an unprecedentedly large control cohort, we were able to show that although in the general population, DQB*03:02 is not fully associated with DRB1*04:02, in the patient population, both alleles are always coupled, suggesting the DRB1*04:02 association to be primary to disease predisposition. In silico predictions performed for the overrepresented DQ alleles reveal them to be strong binders of LGI1-derived peptides, similarly to overrepresented DR alleles. These predictions suggest a possible correlation between peptide binding sites of paired DR-DQ alleles. DISCUSSION: Our cohort presents distinct immune characteristics with substantially higher overrepresentation of DRB1*04:02 and slightly lower overrepresentation of DQB1*07:01 compared with previous reports implying differences between different populations. DQ-DR interactions found in our cohort may shed additional light on the complex role of immunogenetics in the pathogenesis of anti-LGI1E, implying a possible relevance of certain DQ alleles and DR-DQ interactions.

Paroxysmal Slow-Wave Events Are Uncommon in Parkinson's Disease.

Background: Parkinson's disease (PD) is currently considered to be a multisystem neurodegenerative disease that involves cognitive alterations. EEG slowing has been associated with cognitive decline in various neurological diseases, such as PD, Alzheimer's disease (AD), and epilepsy, indicating cortical involvement. A novel method revealed that this EEG slowing is composed of paroxysmal slow-wave events (PSWE) in AD and epilepsy, but in PD it has not been tested yet. Therefore, this study aimed to examine the presence of PSWE in PD as a biomarker for cortical involvement. Methods: 31 PD patients, 28 healthy controls, and 18 juvenile myoclonic epilepsy (JME) patients (served as positive control), underwent four minutes of resting-state EEG. Spectral analyses were performed to identify PSWEs in nine brain regions. Mixed-model analysis was used to compare between groups and brain regions. The correlation between PSWEs and PD duration was examined using Spearman's test. Results: No significant differences in the number of PSWEs were observed between PD patients and controls (p > 0.478) in all brain regions. In contrast, JME patients showed a higher number of PSWEs than healthy controls in specific brain regions (p < 0.023). Specifically in the PD group, we found that a higher number of PSWEs correlated with longer disease duration. Conclusions: This study is the first to examine the temporal characteristics of EEG slowing in PD by measuring the occurrence of PSWEs. Our findings indicate that PD patients who are cognitively intact do not have electrographic manifestations of cortical involvement. However, the correlation between PSWEs and disease duration may support future studies of repeated EEG recordings along the disease course to detect early signs of cortical involvement in PD.

Abnormal gait and motor cortical processing in drug-resistant juvenile myoclonic epilepsy.

BACKGROUND: Juvenile myoclonic epilepsy (JME) is characterized by generalized seizures. Nearly 30% of JME patients are drug-resistant (DR-JME), indicating a widespread cortical dysfunction. Walking is an important function that necessitates orchestrated coordination of frontocentral cortical regions. However, gait alterations in JME have been scarcely investigated. Our aim was to assess changes in gait and motor-evoked responses in DR-JME patients. METHODS: Twenty-nine subjects (11 JME drug-responder, 8 DR-JME, and 10 healthy controls) underwent a gait analyses during usual walking and dual-task walking. Later, subjects underwent 64-channel EEG recordings while performing a simple motor task. We calculated the motor-evoked current source densities (CSD) at a priori chosen cortical regions. Gait and CSD measures were compared between groups and tasks using mixed model analysis. RESULTS: DR-JME patients demonstrated an altered gait pattern that included slower gait speed (p = .018), reduced cadence (p = .003), and smaller arm-swing amplitude (p = .011). The DR-JME group showed higher motor-evoked CSD in the postcentral gyri compared to responders (p = .049) and both JME groups showed higher CSD in the superior frontal gyri compared to healthy controls (p < .011). Moreover, higher CSD in the superior frontal gyri correlated with worse performance in dual-task walking (r > |-0.494|, p < .008). CONCLUSIONS: These alterations in gait and motor-evoked responses in DRE-JME patients reflect a more severe dysfunction of motor-cognitive neural processing in frontocentral regions, leading to poorer gait performance. Further studies are needed to investigate the predictive value of altered gait and cortical motor processing as biomarkers for poor response to treatment in JME and other epilepsy syndromes.

Electrodiagnostic artifacts due to neurostimulation devices for drug resistant epilepsy.

Background: Neurostimulation devices including vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS) are approved therapeutic options for drug resistant epilepsy (DRE). As these devices are increasingly used in clinical practice, it is of importance to recognize their artifacts in electrodiagnostic studies. Methods: This is a retrospective study of all adult DRE patients treated with neuromodulation devices for epilepsy at our center between 2012 and 2021. Available EEGs were reviewed for neurostimulator-related artifacts. Results: Fifty-two patients were included. 37% of patients had neurostimulation related electrophysiological artifacts (20% of VNS, 75% of DBS, all patients with dual VNS-DBS treatment, and in the single patient with RNS). Artifacts were intermittent, appearing most commonly simultaenously in the EEG and ECG. VNS artifacts were monomorphic appearing mostly in the lower temporal EEG electrodes, whereas DBS artifacts were with variable morphology, amplitude, and scalp distribution. At times, the artifacts resembled electrographic seizures in the EEG and mimicked extrasystole or asystole in the ECG. Conclusions: With the increasing use of neurostimulation treatments for DRE, and the need for frequent electrodiagnostic studies in this patient population, it is important clinicians recognize these electrophysiological findings as artifacts, to avoid misdiagnosis and facilitate accurate interpretation.

Anterior thalamic deep brain stimulation in epilepsy patients refractory to vagus nerve stimulation: A single center observational study.

Anterior thalamic deep brain stimulation (DBS) is a palliative treatment that may be considered in patients with drug resistant epilepsy (DRE) that fail treatment with vagus nerve stimulation (VNS). Combining VNS and DBS treatment is a therapeutic approach rarely reported. This single center observational study aims to describe response to DBS treatment in 11 epilepsy patients resistant to medications and VNS. Patients either had inactivated VNS (DBS only) or were treated with simultaneous DBS and VNS (DBS-VNS). Focal impaired awareness (FIA) and most disabling seizure rates were examined pre-DBS implantation, 3 months following implantation, and last follow up. Overall, a decrease in FIA (47.0 ± 30.7 %, p = 0.02) and most disabling seizure rate (54.8 ± 34.2 %, p = 0.03) was seen at last follow-up (average follow-up 28.5 ± 13.5 months). Eight of 11 patients were DBS responders (most disabling seizure rate reduction above 50%). No difference in seizure control was found between seven DBS only and four DBS-VNS patients. Our results argue that patients who have failed antiseizure medication and VNS therapies, could benefit from better seizure control if treated with adjunctive DBS. Larger prospective studies are needed to assess the efficacy and safety of combined neurostimulation treatments in DRE.

Rapid titration of VNS therapy reduces time-to-response in epilepsy.

BACKGROUND: Common titration strategies for vagus nerve stimulation (VNS) prioritize monitoring of tolerability during small increases in stimulation intensity over several months. Prioritization of tolerability is partially based on how quickly side effects can be perceived and reported by patients, and the delayed onset of clinical benefits from VNS. However, many practices assess the clinical benefit of VNS at one year after implantation, and excessive caution during the titration phase can significantly delay target dosing or prevent a patient from reaching a therapeutic dose entirely. OBJECTIVE: This study aimed to characterize the relationship between titration speed and the onset of clinical response to VNS. METHODS: To assess differences between more aggressive titration strategies and more conservative ones, we analyzed the relationship between time-to-dose and time-to-response using a weighted Cox regression. The target dose was empirically defined as 1.625 mA output current delivered at 250 microsecond pulse widths at 20 Hz. Patient-level outcomes and dosing data were segregated into fast (<3 months), medium (3-6 months), and slow (>6 months) cohorts based on their titration speed. RESULTS: The statistical model revealed a significant relationship between titration speed and onset of clinical response, defined as a 50% reduction from baseline in seizure frequency. Frequency of adverse events reported between each cohort trended toward higher rates of adverse events in adults who were titrated quickly; however, the pediatric population appeared to be more tolerant of titration at any speed. CONCLUSIONS: This analysis indicates that faster titration yields faster onset of clinical benefit and is especially practical in the pediatric population, though attempts to accelerate adult titration may still be warranted.

Reduced neural feedback signaling despite robust neuron and gamma auditory responses during human sleep.

During sleep, sensory stimuli rarely trigger a behavioral response or conscious perception. However, it remains unclear whether sleep inhibits specific aspects of sensory processing, such as feedforward or feedback signaling. Here, we presented auditory stimuli (for example, click-trains, words, music) during wakefulness and sleep in patients with epilepsy, while recording neuronal spiking, microwire local field potentials, intracranial electroencephalogram and polysomnography. Auditory stimuli induced robust and selective spiking and high-gamma (80-200 Hz) power responses across the lateral temporal lobe during both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Sleep only moderately attenuated response magnitudes, mainly affecting late responses beyond early auditory cortex and entrainment to rapid click-trains in NREM sleep. By contrast, auditory-induced alpha-beta (10-30 Hz) desynchronization (that is, decreased power), prevalent in wakefulness, was strongly reduced in sleep. Thus, extensive auditory responses persist during sleep whereas alpha-beta power decrease, likely reflecting neural feedback processes, is deficient. More broadly, our findings suggest that feedback signaling is key to conscious sensory processing.

VNS parameters for clinical response in Epilepsy.

BACKGROUND: While vagus nerve stimulation (VNS) has been in use for over two decades, little professional guidance exists to describe dosing and titration of therapy which is the consequence of a limited amount of evidence developed during the pre-market phase of therapy development. Post-market surveillance of dosing practice has revealed significant deviations from dosing and titration guidance offered by professional societies as well as the manufacturer. OBJECTIVE: This analysis aims to identify a target dose for VNS Therapy in Epilepsy. METHODS: Herein, VNS clinical outcomes are linked to the patient-specific dosing parameters for each study visit (n = 1178 patients). A generalized linear mixed model was built to ascertain the relationship between key stimulation parameters (i.e., Output Current, Pulse Width, Signal Frequency, and Duty Cycle) and clinical response, defined as a 50% or greater reduction in seizure frequency from baseline. Other demographic parameters of interest, such as duration of epilepsy and age at implant, were also explored. RESULTS: A population level target output current and duty cycle for VNS therapy for epilepsy was identified as 1.61 mA and 17.1% duty cycle. Patients with shorter duration of epilepsy were identified to have a higher likelihood to respond to VNS therapy (p < 0.001). While patients who were on the therapy longer were more likely to respond to the therapy, the effect did not interact with the dosing settings - suggesting that patients who have been chronically underdosed may still benefit from achieving the target dose. CONCLUSION: An opportunity exists to improve upon VNS outcomes by aligning clinical practice around this evidence-based target dose.

Seizure semiology: ILAE glossary of terms and their significance.

This educational topical review and Task Force report aims to address learning objectives of the International League Against Epilepsy (ILAE) curriculum. We sought to extract detailed features involving semiology from video recordings and interpret semiological signs and symptoms that reflect the likely localization for focal seizures in patients with epilepsy. This glossary was developed by a working group of the ILAE Commission on Diagnostic Methods incorporating the EEG Task Force. This paper identifies commonly used terms to describe seizure semiology, provides definitions, signs and symptoms, and summarizes their clinical value in localizing and lateralizing focal seizures based on consensus in the published literature. Video-EEG examples are included to illustrate important features of semiology in patients with epilepsy.

Limited Ability to Adjust N2 Amplitude During Dual Task Walking in People With Drug-Resistant Juvenile Myoclonic Epilepsy.

Juvenile myoclonic epilepsy (JME) is one of the most common epileptic syndromes; it is estimated to affect 1 in 1,000 people worldwide. Most people with JME respond well to medication, but up to 30% of them are drug-resistant. To date, there are no biomarkers for drug resistance in JME, and the poor response to medications is identified in retrospect. People with JME have frontal dysfunction manifested as impaired attention and difficulties in inhibiting habitual responses and these dysfunctions are more pronounced in drug-resistant individuals. Frontal networks play an important role in walking and therefore, gait can be used to overload the neural system and expose subtle changes between people with drug-responsive and drug-resistant JME. Electroencephalogram (EEG) is a promising tool to explore neural changes during real-time functions that combine a cognitive task while walking (dual tasking, DT). This exploratory study aimed to examine the alteration in electrical brain activity during DT in people with drug-responsive and drug-resistant JME. A total of 32 subjects (14 males and 18 females) participated: 11 drug-responsive (ages: 31.50 ± 1.50) and 8 drug-resistant (27.27 ± 2.30) people with JME, and 13 healthy controls (29.46 ± 0.69). The participants underwent EEG examination during the performance of the visual Go/NoGo (vGNG) task while sitting and while walking on a treadmill. We measured latencies and amplitudes of N2 and P3 event-related potentials, and the cognitive performance was assessed by accuracy rate and response time of Go/NoGo events. The results demonstrated that healthy controls had earlier N2 and P3 latencies than both JME groups (N2: p = 0.034 and P3: p = 0.011), however, a limited ability to adjust the N2 amplitude during walking was noticeable in the drug-resistant compared to drug-responsive. The two JME groups had lower success rates (drug-responsive p < 0.001, drug-resistant p = 0.004) than healthy controls, but the drug-resistant showed longer reaction times compared to both healthy controls (p = 0.033) and drug-responsive (p = 0.013). This study provides the first evidence that people with drug-resistant JME have changes in brain activity during highly demanding tasks that combine cognitive and motor functions compared to people with drug-responsive JME. Further research is needed to determine whether these alterations can be used as biomarkers to drug response in JME.