Unearthing the mechanisms of responsive neurostimulation for epilepsy

Communications Medicine, Journal Year: 2023, Volume and Issue: 3(1)

Published: Nov. 16, 2023

Responsive neurostimulation (RNS) is an effective therapy for people with drug-resistant focal epilepsy. In clinical trials, RNS results in a meaningful reduction median seizure frequency, but the response highly variable across individuals, many receiving minimal or no benefit. Understanding why this variability occurs will help improve use of therapy. Here we advocate reexamination assumptions made about how reduces seizures. This now possible due to large patient cohorts having used device, some long-term. Two foundational have been that device's intracranial leads should target focus/foci directly, and stimulation be triggered only detected epileptiform activity. Recent studies called into question both hypotheses. Here, discuss these exciting new suggest future approaches selection, lead placement, device programming could outcomes.

Language: Английский

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Circadian changes in aperiodic activity are correlated with seizure reduction in patients with mesial temporal lobe epilepsy treated with responsive neurostimulation

Epilepsia, Journal Year: 2024, Volume and Issue: 65(5), P. 1360 - 1373

Published: March 22, 2024

Abstract Objectives Responsive neurostimulation (RNS) is an established therapy for drug‐resistant epilepsy that delivers direct electrical brain stimulation in response to detected epileptiform activity. However, despite overall reduction seizure frequency, clinical outcomes are variable, and few patients become seizure‐free. The aim of this retrospective study was evaluate aperiodic electrophysiological activity, associated with excitation/inhibition balance, as a novel electrographic biomarker aid early prognostication the RNS. Methods We identified intractable mesial temporal lobe who were implanted RNS System between 2015 2021 at University Utah. parameterized neural power spectra from intracranial recordings during first 3 months following implantation into periodic components. then correlated circadian changes parameters baseline most recent follow‐up. Results Seizure significantly patient's average change day/night exponent ( r = .50, p .016, n 23 patients) oscillatory alpha .45, .042, across recordings. reached its maximum nighttime hours (12 a.m. 6 a.m.) responders (i.e., least 50% seizures). Significance These findings suggest modulation broadband activity therapy. This marker has potential identify likely respond Furthermore, we propose less may be related dysfunction balance interconnected role epilepsy, sleep, memory.

Language: Английский

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Hippocampal network activity forecasts epileptic seizures

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(10), P. 2787 - 2790

Published: July 12, 2024

Language: Английский

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Gauging and controlling excitability in cortical disorders

Current Opinion in Neurology, Journal Year: 2025, Volume and Issue: 38(2), P. 140 - 150

Published: Feb. 17, 2025

Cortical excitability, defined as the cortex's responsiveness to incoming stimuli, is a fundamental concept in neuroscience and targetable mechanism for controlling brain dysfunctions such epilepsy, well other neurological psychiatric disorders. In this review, we delineate boundaries between physiological pathological highlighting recent theoretical, experimental, translational advances relevant human Specifically, describe dynamic regulation of cortical excitability propose practical means monitor its known fluctuations guide therapeutic interventions. From conceptual standpoint, last decade research on has benefited from dynamical systems theory, which studies behavior nonlinear (here, cortex) their resilience perturbations different conditions variable excitability). We review how relationships were verified series studies. also natural these may open windows vulnerability expression dysfunctions. then turn practicalities measuring monitoring latent that must be actively probed. Practical gauging likely have broad applicability. To enable new developments clinical practice, principled design pharmacological neurostimulation therapies leverage current understanding dynamics.

Language: Английский

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Explainable and Responsible AI in Neuroscience

Published: March 3, 2025

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State-dependent effects of responsive neurostimulation depend on seizure localization

Brain, Journal Year: 2024, Volume and Issue: 148(2), P. 521 - 532

Published: July 25, 2024

Brain-responsive neurostimulation (RNS) is firmly ensconced among treatment options for drug-resistant focal epilepsy, but over a quarter of patients treated with the RNS® System do not experience meaningful seizure reduction. Initial titration RNS therapy typically similar all patients, raising possibility that response might be enhanced by consideration patient-specific variables. Indeed, small, single-centre studies have yielded preliminary evidence effectiveness depends on brain state during which stimulation applied. The generalizability these findings remains unclear, however, and it unknown whether state-dependent effects responsive are also stratified location onset zone where delivered. We aimed to determine evident in large, diverse, multi-centre cohort clinical trial participants test differ between mesiotemporal neocortical epilepsies. Eighty-one 256 across 31 centres trials met criteria inclusion this retrospective study. Risk states were defined relation phases daily multi-day cycles interictal epileptiform activity thought likelihood. found probabilities risk transitions depended parameter being changed, starting stimulated region. Changes two commonly adjusted parameters, charge density frequency, produced opposite depending localization. Greater variance acute was explained bipolar epilepsies monopolar Variability individuals may relate, at least partly, fact current paradigms account fully fluctuations or locations simulation sites. State-dependence electrical inform development next-generation closed-loop devices can detect changes deliver adaptive, localization-specific patterns maximize therapeutic effects.

Language: Английский

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Aperiodic activity as a biomarker of seizures and neuromodulation

Brain stimulation, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Mounting evidence suggests the efficacy of neuromodulation for epilepsy is mediated by network remodeling and neural state. Epilepsy related pathophysiology has been associated with variation in aperiodic exponent, which describes inverse relationship between frequency power linked to synaptic-level processes. This study sought assess relationships periodic activity, disease state, responsive stimulation. Chronic intracranial EEG was recorded from 13 patients undergoing neurostimulation epilepsy. Recordings containing clinician-annotated seizures, stimulation triggered device-detected interictal epileptiform activity (IEA), stimulation-free periods were analyzed. Multidien IEA cycles identified, recordings classified cycle phase. Power spectra parameterized into components using an established algorithm. The exponent larger during seizures pre-stimulation intervals than recordings, decreased following A rise observed 12 hours preceding seizures. Larger rising phase multidien cycles. Periodic alpha beta intervals, high-risk (rising and/or peak) phases, whereas theta gamma exhibited variable relationships. did not change after or before any studied band. positively instantaneous state severity negatively therapeutic Aperiodic may emerge as a practical biomarker treatment response guide

Language: Английский

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Epileptiform Activity and Seizure Risk Follow Long‐Term Non‐Linear Attractor Dynamics

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 7, 2025

Abstract Many biological systems display circadian and slow multi‐day rhythms, such as hormonal cardiac cycles. In patients with epilepsy, these cycles also manifest cyclical fluctuations in seizure propensity. However, symptoms are consequences of the complex interactions between underlying physiological, pathophysiological, external causes. Therefore, identifying an accurate model system that governs rhythms allows for a more reliable risk forecast targeted interventions. The primary aim is to develop personalized strategy inferring long‐term trajectories epileptiform activity and, consequently, individual undergoing ECoG sampling via implantable neurostimulation devices. To achieve this goal, Hankel alternative view Koopman (HAVOK) analysis adopted approximate linear representation nonlinear propensity dynamics. HAVOK framework leverages theory delay‐embedding decompose chaotic dynamics into leading delay‐embedded coordinates driven by low‐energy coordinate (i.e., forcing). findings reveal topology attractors cycles, showing seizures tend occur regions manifold strongly Moreover, it demonstrated identified forcings short periods up few days accurately predicts patients' slower which improves forecasting.

Language: Английский

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Interictal intracranial EEG asymmetry lateralizes temporal lobe epilepsy

Brain Communications, Journal Year: 2024, Volume and Issue: 6(5)

Published: Jan. 1, 2024

Abstract Patients with drug-resistant temporal lobe epilepsy often undergo intracranial EEG recording to capture multiple seizures in order lateralize the seizure onset zone. This process is associated morbidity and ends postoperative recurrence. Abundant interictal (between-seizure) data are captured during this process, but these currently play a small role surgical planning. Our objective was predict laterality of zone using patients epilepsy. We performed retrospective cohort study (single-centre for model development; two-centre validation). studied undergoing at University Pennsylvania (internal cohort) Medical South Carolina (external between 2015 2022. developed logistic regression several features derived from recent publications. compared concordance model-predicted side surgery good poor outcomes. Forty-seven (30 female; ages 20–69; 20 left-sided, 10 right-sided 17 bilateral onsets) were analysed development internal validation. Nineteen (10 23–73; 5 right-sided, 4 bilateral) external The cross-validated area under curve trained spike rates 0.83 predicting left-sided 0.68 onset. Balanced accuracies 79.3% 78.9% left- predictions, respectively. predicted higher outcome. replicated finding that right harder distinguish separate modality resting-state functional MRI. In conclusion, signatures distinct across lateralities. Left-sided onsets easier than onsets. A on accurately identifies zones predicts potential clinical application findings could be either support or oppose hypothesis unilateral when deciding pursue resection ablation as opposed device implantation.

Language: Английский

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Epileptiform activity and seizure risk follow long-term non-linear attractor dynamics

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 26, 2024

Abstract Many biological systems display circadian and slow multi-day rhythms, such as hormonal cardiac cycles. In patients with epilepsy, these cycles also manifest cyclical fluctuations in seizure propensity. However, symptoms are consequences of the complex interactions between underlying physiological, pathophysiological, external causes. Therefore, identifying an accurate model system that governs rhythms allows for a more reliable risk forecast targeted interventions. To achieve this goal, we adopt Hankel alternative view Koopman (HAVOK) analysis to approximate linear representation nonlinear propensity dynamics. The HAVOK framework leverages theory delay-embedding decompose chaotic dynamics into leading delay-embedded coordinates driven by low-energy coordinate (i.e., forcing). Our findings reveal topology attractors cycles, showing seizures tend occur regions manifold strongly Moreover, demonstrate identified forcings short periods up few days accurately predicts patients’ slower which improves forecasting.

Language: Английский

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