Thalamocortical network dynamics in focal epilepsy: SEEG investigation

bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-09

Thalamic neuromodulation is clinically effective in drug-resistant epilepsy, suggesting critical contributions of the thalamus to the epileptogenic process. However, the underlying electrophysiologic mechanisms remain poorly characterized. Converging evidence implicates the thalamus in shaping large-scale functional interactions across the cortex. We hypothesized that ictal changes in thalamic activity track cortical network dynamics associated with seizure propagation. We analyzed stereo-electroencephalography recordings from 16 patients with focal epilepsy (255 seizures) with simultaneous sampling of the thalamus (anterior nucleus, N=14; pulvinar, N=11) and cortex. Cortical regions of interest included the seizure onset zone (SOZ), surrounding cortices (near-SOZ), and control regions from the contralateral hemisphere. We characterized seizure dynamics across spatial scales, from local activity within each region to network-level, inter-regional interactions. Local activity was decomposed into its periodic (oscillatory) and aperiodic components. Network interactions were characterized by directed functional connectivity computed with a multivariate method. Seizures were associated with increased broadband power (a proxy for neuronal population firing rates) and low-frequency rhythmic activity across the thalamocortical network relative to interictal baseline levels. In contrast, consistent changes in aperiodic slope (a putative marker of excitation-inhibition balance) were specific to the thalamus, which showed an early and sustained steepening (i.e., more negative slope). While local rhythms were heterogeneous across the canonical frequency bands, inter-regional interactions predominantly involved the beta band (13-30 Hz). Shortly after onset, both forward outflow from SOZ to near-SOZ and feedback inflow in the reverse direction were increased. These bidirectional effects were expressed via both a direct cortico-cortical pathway and an indirect transthalamic route, operating in parallel. These dynamics were further stratified based on seizure subtypes, leveraging the fact that there was minimal propagation of ictal activity to the near-SOZ in subclinical seizures. The ictal drop in thalamic aperiodic slope was primarily observed in clinical seizures. At the network level, whereas SOZ→near-SOZ outflow was present across seizure types, reverse feedback was particularly enhanced in clinical seizures. Multivariable regression showed that the degree of thalamic slope steepening uniquely tracked seizure-to-seizure fluctuations in the strength of near-SOZ→SOZ feedback, and further predicted seizure durations. Together these findings highlight thalamic aperiodic slope as an index of cortical network dynamics linked to seizure propagation, with potential clinical utility for further development of physiology-informed precision neuromodulation.

Hardware Technology for Point-of-Care EEG: A Comprehensive Review

Journal of Clinical Neurophysiology · 2026-03-01

SUMMARY: Rapid or point-of-care (POC) EEG devices, bolstered by advancements in portability, ease of use, wireless technology, and artificial intelligence, are transforming the EEG field. Increasing demand for immediate neurophysiologic diagnosis, previously limited by the operational complexities and specialized personnel required for traditional EEG, has driven these critical shifts. These innovations extend EEG's reach beyond traditional neurophysiology labs to diverse clinical settings, including emergency departments, intensive care units, remote locations, and homes. POC EEG is particularly valuable for diagnosing acute neurologic emergencies such as nonconvulsive status epilepticus and nonconvulsive seizures, traumatic brain injury, and stroke, enabling faster seizure detection, improved triage, and timely treatment. POC EEG systems facilitate rapid acquisition of clinically acceptable EEG by nonexperts, including physicians and other health care providers, emergency personnel, nurses, and in some cases, remote caregivers and patients. Bedside interpretation is augmented by real-time artificial intelligence algorithms. POC EEG hardware, including its sensors, headsets, amplifiers, connectivity, form factor, and power, diverges significantly from conventional EEG systems. These modifications are explicitly engineered to optimize rapid deployment, patient comfort, and operational simplicity in resource-constrained or time-sensitive scenarios. The adaptations, however, may necessitate trade-offs in signal quality, flexibility, channel count, reliability, and cost compared with laboratory-grade systems. Understanding these inherent differences and how hardware designs address them is critical for selecting the optimal POC EEG technology for a specific use.

Treatment Response to Antiseizure Medications in People With Newly Diagnosed Focal Epilepsy

JAMA Neurology · 2025-08-25 · 10 citations

Importance: Epilepsy affects approximately 65 million people worldwide, and 60% have focal seizures. Predicting seizure response and drug resistance to antiseizure medications (ASMs) in people with focal epilepsy remains difficult. Objective: To describe the expected short- and long-term response to treatment with ASMs in people with focal epilepsy using recognized definitions by the International League Against Epilepsy. Design, Setting, and Participants: The Human Epilepsy Project is an international, prospective, observational cohort study that followed up people with newly diagnosed focal epilepsy for up to 6 years between 2012 and 2020. Data were analyzed from 2023 to 2024. The Human Epilepsy Project was conducted at 34 tertiary epilepsy centers across the US, Australia, and Europe. Participants with confirmed diagnosis of focal epilepsy aged 12 to 60 years were enrolled within 4 months of treatment initiation with ASM(s). Data were analyzed from February 2024 to July 2024. Exposure: ASM (variable). Main Outcomes and Measures: The primary outcome was seizure freedom, defined as a period without seizures for 12 months or 3 times the longest pretreatment seizure-free interval, whichever was longer. Treatment response was categorized as sensitive, meaning seizure free receiving 2 or fewer adequate ASM trials; resistant, meaning having 2 or more adequate ASM trials fail; or indeterminate (neither treatment sensitive nor resistant). Results: Among 448 enrolled participants, 267 (59.6%) were female, and median (IQR) participant age was 32 (21-44) years at treatment initiation. Median (IQR) follow-up duration was 3.13 (2.33-3.55) years. Most achieved seizure freedom (267 participants of 448 [59.6%]), largely without relapse (223 [83.5%]). There were 245 treatment-sensitive participants (54.7%), 102 treatment-resistant participants (22.8%), and 101 indeterminate participants (22.5%). Among treatment-sensitive participants, most (217 [89.3%]) responded to monotherapy and half (121 [49.4%], or 27% of total cohort) became seizure free while receiving their first ASM. In the first year of treatment, 251 participants (63%) had ongoing or worsening seizures. Median time to first seizure freedom was 12.1 months (95% CI, 9.7-16.1). This occurred earlier in those who never relapsed (median, 2.2 months; 95% CI, 0.8-3.2) than those who did (median, 7.4 months; 95% CI, 4.0-10.7). Those with infrequent pretreatment seizures were 0.30-fold less likely to be treatment resistant than those with very frequent seizures (hazard ratio, 0.30; 95% CI, 0.14-0.64; P = .002; Holm-Bonferroni-corrected P = .006). Participants with self-reported comorbid psychological disorders were 1.78-fold more likely to be treatment resistant than those without (relative risk, 1.78; 95% CI, 1.26-2.52; P = .001). Conclusions and Relevance: In the Human Epilepsy Project multicenter prospective cohort study, most people with newly diagnosed focal epilepsy took more than a year and more than 1 ASM to become seizure free. Drug resistance can be identified earlier in those with frequent pretreatment seizures, and a history of psychiatric comorbidities at epilepsy diagnosis is an important prognostic factor. Trial Registration: ClinicalTrials.gov Identifier: NCT02126774.

Putting MINDSET Action Plans into Action (P2-9.010)

Neurology · 2025-04-07

To describe integration of the MINDSET decision aid with individualized interventions in a comprehensive epilepsy clinic.

Status Epilepticus Protocol Variation Across Accredited National Association of Epilepsy Centers Members

Neurology · 2025-05-16 · 3 citations

OBJECTIVES: Status epilepticus (SE) is a neurologic emergency that requires urgent recognition and medical management. SE management remains heterogeneous across centers. METHODS: We analyzed SE treatment protocols from level 3 and level 4 epilepsy centers. Discrete data including stabilization measures, timing of treatment phases, medications, doses, and routes of administration were collected from each protocol and described using frequency for categorical variables and median for continuous variables. The distribution of treatment times and dosing were compared with the AES guideline. RESULTS: A total of 256 SE treatment protocols were included. Only 66% of SE protocols detailed treatment times. Doses below recommendations occurred in 4% of protocols for initial benzodiazepine (BZD) and 14% for first non-BZD medications. Infusion therapy was outlined in 61% of protocols. DISCUSSION: Despite the importance of timeliness in SE management, one third of institutional protocols did not specify treatment times. This analysis of US hospital inpatient SE protocols provides expert opinion regarding infusion therapy management and highlights gaps and targets for improvement in SE treatment.

Data driven physical activity quantification using chest strap-based heart rate measurements: the Antwerp Activity Index

European Heart Journal · 2025-11-01

Abstract Background The introduction of wearable heart rate monitors (HRMs) could enable continuous, transmural, and objective tracking of physical activity (PA). Despite the widespread availability of HR monitors, translating HR data into meaningful, personalized metrics that effectively quantify PA remains an ongoing challenge. Aims To develop and evaluate a novel HR-based score, the Antwerp Activity Index (AAI), for quantifying PA. To determine the optimal daily AAI threshold for classifying active days. Methods This prospective study involved participants from two groups (cardiac rehabilitation and healthy individuals) who wore a Polar H10 chest strap during PA for 12 to 14 weeks. The HR data collected from this HRM was transmitted via an application programming interface (API) to our secure database, where it could be used to calculate the daily Antwerp Activity Index (AAI). The percentage of heart rate reserve (%HRR) was used to determine moderate (≥40-69 %HRR) and vigorous (≥70-100 %HRR) intensity activity zones. Active days were classified based on a predefined threshold of ≥21.43 minutes (i.e. 150 min/week divided by 7) of moderate to vigorous activity (MVA), as recommended by the World Health Organisation (WHO). Minutes spent in the moderate zone counted as 1 MVA-minute, while minutes in the vigorous zone counted double (1 minute = 2 MVA-minutes). The optimal daily AAI threshold to predict active days was determined using Receiver Operating Characteristic Curve – Area Under the Curve analysis (ROC-AUC). Performance of the threshold is evaluated using sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV). Results The average time of device usage was 11.70±6.7 weeks. A total of 146 participants (73.5% male; 48.4±13.4 years old) collected at least 1 AAI value. The median daily AAI value was 73.4 (IQR: 24.7). The AAI score exhibited a strong positive correlation with MVA duration (Spearman's rank correlation coefficient, SCC: 0.961; p<.001). The median AAI score on active days significantly differed from the median AAI score on non-active days (80.6 vs. 50.9; p<.001). ROC curve analysis calculated an ideal AAI threshold of 67.5 with a ROC-AUC of 0.98. This threshold showed high sensitivity (96.0%), high specificity (91.8%), and high accuracy (94.4%) in predicting active days based on WHO criteria. Conclusions The AAI score provides a robust, HR-based method for objectively classifying daily PA levels. Its strong correlation with time spent in MVA zones and its high predictive performance suggest that it can serve as a valuable tool for real-time activity monitoring in both clinical and general populations.

The Tell on Telehealth

Epiliepsy currents/Epilepsy currents · 2024-05-30

Objective: Telehealth in epilepsy care is not new. During the COVID-19 public health emergency, telehealth became more readily used to deliver epilepsy care. However, a summarized guidance of use in caring for people with epilepsy utilizing telehealth is needed. Methods: Existing literature was reviewed to provide guidance on various aspects of telehealth. Billing aspects are reviewed. Recommendations and considerations along with benefits and barriers to telehealth are provided. Results: Telehealth can be a preferred delivery route of care for people with epilepsy in specific situations. Examples include psychiatric complaints, medication management, and follow-up visits for noncomplicated epilepsy care. In addition, telehealth is useful for patients who need postoperative visits, are not able to travel, or live in residential facilities. In-person care may be more suitable for patients who are medically complex, have language barriers or difficulty with resource access, hearing impaired, or have neurostimulation devices where remote monitoring or programming options are infeasible. Discussion: Telehealth care for people with epilepsy can be a useful and important method of care delivery. It should remain an option for providers to use in epilepsy clinical care. It is important for the neurology provider to understand the benefits, billing, and barriers to providing telehealth.

Barriers to Medication Adherence in People Living With Epilepsy

Neurology Clinical Practice · 2024-11-27 · 17 citations

Background and Objectives: Epilepsy affects approximately 1.2% of the US population, resulting in 3.4 million Americans with active epilepsy. Antiseizure medication (ASM) is considered the mainstay of treatment, effective for two-thirds of people with epilepsy (PWE), while at least one-third experience drug-resistant epilepsy. A significant percentage of PWE who are treated with ASMs report nonadherence to this type of medication, leading to potentially preventable seizures and the potential for being inappropriately classified as having drug-resistant epilepsy. Ongoing seizures are associated with increased morbidity, mortality, and health care costs, among other consequences. Recognizing when PWE struggle with ASM adherence is essential for creating effective interventions and prevention strategies to improve patient outcomes. Methods: As part of the Epilepsy Learning Healthcare System Registry, we collected data from 2020 through 2023 from 4,917 individuals seen at 8 epilepsy clinics in the United States. In this cross-sectional study, we used logistic regression analysis to examine the relationship between patient-reported seizure control (or provider-reported seizure control for some sites) and endorsed barriers to medication adherence. In addition, we explored potential associations with demographic variables such as sex, race, and ethnicity. The data analysis was conducted using R version 2023.06.1 + 524. Results: Overall, 18.4% (893/4,848) reported adherence barriers and 37.7% (1,447/3,834) reported seizure control, defined as no seizures for the preceding 12 months or longer. The most prevalent barriers were forgetting to take ASMs (48.2%), experiencing ASM side effects (29.2%), and feeling as if the ASMs were not helping in controlling seizures (21.3%). The PWE who reported adherence barriers had 0.6 lower odds of having seizure control compared with those who did not report barriers (95% CI 0.4-0.7) and 0.6 lower odds of having seizure control after adjusting for race, ethnicity, and sex (95% CI 0.5-0.7). Discussion: We observed significant barriers to medication adherence and inadequate seizure control among adult PWE across 8 centers in the United States. This study suggests that PWE might benefit from standardized screening for adherence barriers with behavioral strategies to address these barriers offered during clinical encounters to personalize care.

Response to Letters to the Editor by Gregory J, Rice K, McCarthy K, et al. 2023 Regarding: “Guidelines for Qualifications of Neurodiagnostic Personnel: A Joint Position Statement of the American Clinical Neurophysiology Society, the American Association of Neuromuscular & Electrodiagnostic Medicine, the American Society of Neurophysiological Monitoring, and ASET—The Neurodiagnostic Society”

Journal of Clinical Neurophysiology · 2024-02-01

Associations Between Testing and Treatment Pathways in a Case of Pediatric Nonlesional Epilepsy: A Census Survey of NAEC Center Directors

Journal of Child Neurology · 2024-10-25

Objective Epilepsy surgery is vital in managing of children with drug-resistant epilepsy. Noninvasive and invasive testing modalities allow for evaluation and treatment of children with drug-resistant epilepsy. Evidence-based algorithms for this process do not exist. This study examines expert response to a vignette of pediatric nonlesional epilepsy to assess associations in evaluation and treatment choices. Methods We analyzed annual report data and an epilepsy practice survey reported in 2020 from 135 pediatric epilepsy center directors in the United States. Characteristics of centers along with noninvasive and invasive testing and surgical treatment strategies were collected. Multivariable logistic regression modeling was performed. Results The response rate was 100% with 135 responses included in the analyses. Most used noninvasive testing modalities included Neuropsychology evaluation (90%), interictal brain fluorodeoxyglucose-positron emission tomography (85%), and functional magnetic resonance imaging (MRI) (72%) with nearly half obtaining genetic testing. Choosing functional MRI was associated with stereo electroencephalography (EEG) ( P = .025) and selecting Wada with subdural grid/strips ( P = .038). Directors from pediatric-only centers were more likely to choose stereo EEG as opposed to combined centers ( P = .042). Laser interstitial thermal therapy was almost 7 times as likely to be chosen as a treatment modality compared with open resection in dedicated pediatric centers (OR 6.96, P = .002). Significance In a vignette of nonlesional childhood drug-resistant epilepsy, epilepsy center directors’ patterns of noninvasive testing, invasive testing, and treatment were examined. Management choices were associated with pediatric versus combined pediatric/adult center characteristics. Expert opinions demonstrated equipoise in evaluation and management of children with drug-resistant epilepsy and the need for evidence-based management strategies.