Towards network-guided neuromodulation for epilepsy

Brain, Journal Year: 2022, Volume and Issue: 145(10), P. 3347 - 3362

Published: June 30, 2022

Abstract Epilepsy is well-recognized as a disorder of brain networks. There growing body research to identify critical nodes within dynamic epileptic networks with the aim target therapies that halt onset and propagation seizures. In parallel, intracranial neuromodulation, including deep stimulation responsive neurostimulation, are well-established expanding reduce seizures in adults focal-onset epilepsy; there emerging evidence for their efficacy children generalized-onset seizure disorders. The convergence these advancing fields driving an era ‘network-guided neuromodulation’ epilepsy. this review, we distil current literature on network mechanisms underlying neurostimulation We discuss modulation key ‘propagation points’ epileptogenic network, focusing primarily thalamic nuclei targeted clinical practice. These include (i) anterior nucleus thalamus, now clinically approved site open loop stimulation, increasingly neurostimulation; (ii) centromedian both epilepsies. briefly associated other neuromodulation targets, such pulvinar piriform cortex, septal area, subthalamic nucleus, cerebellum others. report synergistic findings garnered from multiple modalities investigation have revealed structural functional points — scalp invasive EEG, diffusion MRI. also recordings implanted devices which provide us data aiming modulate. Finally, review continuing evolution network-guided epilepsy accelerate progress towards two translational goals: use pre-surgical analyses determine patient candidacy by providing biomarkers predict efficacy; deliver precise, personalized effective antiepileptic prevent arrest through mapping each patients’ individual

Language: Английский

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Delineating epileptogenic networks using brain imaging data and personalized modeling in drug-resistant epilepsy

Science Translational Medicine, Journal Year: 2023, Volume and Issue: 15(680)

Published: Jan. 25, 2023

Precise estimates of epileptogenic zone networks (EZNs) are crucial for planning intervention strategies to treat drug-resistant focal epilepsy. Here, we present the virtual epileptic patient (VEP), a workflow that uses personalized brain models and machine learning methods estimate EZNs aid surgical strategies. The structural scaffold patient-specific whole-brain network model is constructed from anatomical T1 diffusion-weighted magnetic resonance imaging. Each node equipped with mathematical dynamical simulate seizure activity. Bayesian inference sample optimize key parameters using functional stereoelectroencephalography recordings patients’ seizures. These together their determine given patient’s EZN. Personalized were further used predict outcome surgeries. We evaluated VEP retrospectively 53 patients VEPs reproduced clinically defined precision 0.6, where physical distance between regions identified by was small. Compared resected 25 who underwent surgery, showed lower false discovery rates in seizure-free (mean, 0.028) than non–seizure-free 0.407). now being an ongoing clinical trial (EPINOV) expected 356 prospective

Language: Английский

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Seizure Diaries and Forecasting With Wearables: Epilepsy Monitoring Outside the Clinic

Frontiers in Neurology, Journal Year: 2021, Volume and Issue: 12

Published: July 13, 2021

It is a major challenge in clinical epilepsy to diagnose and treat disease characterized by infrequent seizures based on patient or caregiver reports limited duration testing. The poor reliability of self-reported seizure diaries for many people with well-established, but these records remain necessary care therapeutic studies. A number wearable devices have emerged, which may be capable detecting seizures, recording data, alerting caregivers. Developments non-invasive sensors measure accelerometry, photoplethysmography (PPG), electrodermal activity (EDA), electromyography (EMG), other signals outside the traditional environment able identify seizure-related changes. Non-invasive scalp electroencephalography (EEG) minimally invasive subscalp EEG allow direct measurement activity. However, significant network computational infrastructure needed continuous, secure transmission data. large volume data acquired necessitates computer-assisted review detection reduce burden human reviewers. Furthermore, user acceptability such must paramount consideration ensure adherence long-term device use. Such can tonic-clonic identification semiologies non-EEG wearables an ongoing challenge. Identification electrographic systems has recently been demonstrated over long (>6 month) durations, this shows promise accurate, objective records. While ability detect forecast from ambulatory intracranial established, not acceptable individuals epilepsy. Recent studies show promising results probabilistic forecasts risk electronic seizures. There also predictive value individuals' symptoms, mood, cognitive performance. forecasting requires perpetual use monitoring, increasing importance system's users. concurrent confirmation are lacking currently. This describes current evidence challenges essential components remote monitoring systems, explores feasibility impending via systems.

Language: Английский

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Circadian Rhythms, Disease and Chronotherapy

Journal of Biological Rhythms, Journal Year: 2021, Volume and Issue: 36(6), P. 503 - 531

Published: Sept. 22, 2021

Circadian clocks are biological timing mechanisms that generate 24-h rhythms of physiology and behavior, exemplified by cycles sleep/wake, hormone release, metabolism. The adaptive value is evident when internal body daily environmental mismatched, such as in the case shift work jet lag or even mistimed eating, all which associated with physiological disruption disease. Studies animal human models have also unraveled an important role functional circadian modulating cellular organismal responses to cues (ex., food intake, exercise), pathological insults (e.g. virus parasite infections), medical interventions medication). With growing knowledge molecular underlying pathophysiology, it becoming possible target for disease prevention treatment. In this review, we discuss recent advances research potential therapeutic applications take patient into account treating

Language: Английский

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The pilocarpine model of mesial temporal lobe epilepsy: Over one decade later, with more rodent species and new investigative approaches

Neuroscience & Biobehavioral Reviews, Journal Year: 2021, Volume and Issue: 130, P. 274 - 291

Published: Aug. 23, 2021

Language: Английский

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Seizure Forecasting Using a Novel Sub-Scalp Ultra-Long Term EEG Monitoring System

Frontiers in Neurology, Journal Year: 2021, Volume and Issue: 12

Published: Aug. 23, 2021

Accurate identification of seizure activity, both clinical and subclinical, has important implications in the management epilepsy. recognition activity is essential for diagnostic, forecasting purposes, but patient-reported seizures have been shown to be unreliable. Earlier work revealed accurate capture electrographic possible with an implantable intracranial device, less invasive electroencephalography (EEG) recording systems would optimal. Here, we present preliminary results detection a minimally sub-scalp device that continuously records EEG. Five participants refractory epilepsy who experience at least two clinically identifiable monthly implanted devices (Minder ® ), providing channels data from hemispheres brain. Data captured via behind-the-ear system, which also powers transferred wirelessly mobile phone, where it accessible remotely cloud storage. EEG recordings were compared recorded conventional system during 1-week ambulatory video-EEG monitoring session. Suspect epileptiform (EA) was detected using machine learning algorithms reviewed by trained neurophysiologists. Seizure demonstrated retrospectively utilizing cycles EA previous times. The procedures well-tolerated no significant complications reported. Seizures accurately identified on as visually confirmed periods concurrent scalp recordings. acquired allowed successfully undertaken. area under receiver operating characteristic curve (AUC score) achieved (0.88), comparable best score recent, state-of-the-art

Language: Английский

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Forecasting Seizure Likelihood With Wearable Technology

Frontiers in Neurology, Journal Year: 2021, Volume and Issue: 12

Published: July 15, 2021

The unpredictability of epileptic seizures exposes people with epilepsy to potential physical harm, restricts day-to-day activities, and impacts mental well-being. Accurate seizure forecasters would reduce the uncertainty associated but need be feasible accessible in long-term. Wearable devices are perfect candidates develop non-invasive, forecasts yet investigated long-term studies. We hypothesized that machine learning models could utilize heart rate as a biomarker for well-established cycles activity, addition other wearable signals, forecast high low risk periods. This feasibility study tracked participants' ( n = 11) rates, sleep, step counts using smartwatches occurrence smartphone diaries at least 6 months (mean 14.6 months, SD 3.8 months). Eligible participants had diagnosis refractory reported 20 135, 123) during recording period. An ensembled neural network model estimated either daily or hourly, retraining occurring on weekly basis additional data was collected. Performance evaluated retrospectively against rate-matched random area under receiver operating curve. A pseudo-prospective evaluation also conducted held-out dataset. Of 11 participants, were predicted above chance all (100%) an hourly ten (91%) forecast. average time spent (prediction time) before occurred 37 min 3 days Cyclic features added most predictive value forecasts, particularly circadian multiday cycles. can used produce patient-specific when biomarkers activity utilized.

Language: Английский

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Multiday cycles of heart rate are associated with seizure likelihood: An observational cohort study

EBioMedicine, Journal Year: 2021, Volume and Issue: 72, P. 103619 - 103619

Published: Oct. 1, 2021

Abstract

Background

Circadian and multiday rhythms are found across many biological systems, including cardiology, endocrinology, neurology, immunology. In people with epilepsy, epileptic brain activity seizure occurrence have been to follow circadian, weekly, monthly rhythms. Understanding the relationship between these cycles of excitability other physiological systems can provide new insight into causes cycles. The brain-heart link has previously considered in epilepsy research, potential implications for forecasting, therapy, mortality (i.e., sudden unexpected death epilepsy).

Methods

We report results from a non-interventional, observational cohort study, Tracking Seizure Cycles. This study sought examine heart rate seizures adults diagnosed uncontrolled (N=31) healthy adult controls (N=15) using wearable smartwatches mobile diaries over at least four months (M=12.0, SD=5.9; control M=10.6, SD=6.4). Cycles were detected continuous wavelet transform. Relationships measured distributions likelihood respect underlying cycle phase.

Findings

Heart all 46 participants (people controls), circadian (N=46), about-weekly (N=25) about-monthly (N=13) being most prevalent. Of 19 had 20 reported seizures, 10 significantly phase locked their

Interpretation

showed similarities may be comodulated likelihood. is relevant also cardiovascular disease. More broadly, understanding shed light on endogenous humans.

Funding

research received funding Australian Government National Health Medical Research Council (investigator grant 1178220), BioMedTech Horizons program, Epilepsy Foundation America's ‘My Gauge' grant.

Language: Английский

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Non-invasive transcranial brain modulation for neurological disorders treatment: A narrative review

Life Sciences, Journal Year: 2022, Volume and Issue: 307, P. 120869 - 120869

Published: Aug. 6, 2022

Language: Английский

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Circadian rhythms in the blood–brain barrier: impact on neurological disorders and stress responses

Molecular Brain, Journal Year: 2023, Volume and Issue: 16(1)

Published: Jan. 12, 2023

Circadian disruption has become more prevalent in society due to the increase shift work, sleep disruption, blue light exposure, and travel via different time zones. The circadian rhythm is a timed transcription-translation feedback loop with positive regulators, BMAL1 CLOCK, that interact negative CRY PER, regulate both central peripheral clocks. This review highlights functions of rhythm, specifically blood-brain barrier (BBB), during healthy pathological states. BBB highly selective dynamic interface composed CNS endothelial cells, astrocytes, pericytes, neurons, microglia form neurovascular unit (NVU). rhythms modulate integrity through regulating oscillations tight junction proteins, assisting NVU, modulating transporter functions. disruptions within have been observed stress responses several neurological disorders, including brain metastasis, epilepsy, Alzheimer's disease, Parkinson's disease. Further understanding these interactions may facilitate development improved treatment options preventative measures.

Language: Английский

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