Dataset Information

Distributed brain co-processor for tracking spikes, seizures and behaviour during electrical brain stimulation.

ABSTRACT: Early implantable epilepsy therapy devices provided open-loop electrical stimulation without brain sensing, computing, or an interface for synchronized behavioural inputs from patients. Recent epilepsy stimulation devices provide brain sensing but have not yet developed analytics for accurately tracking and quantifying behaviour and seizures. Here we describe a distributed brain co-processor providing an intuitive bi-directional interface between patient, implanted neural stimulation and sensing device, and local and distributed computing resources. Automated analysis of continuous streaming electrophysiology is synchronized with patient reports using a handheld device and integrated with distributed cloud computing resources for quantifying seizures, interictal epileptiform spikes and patient symptoms during therapeutic electrical brain stimulation. The classification algorithms for interictal epileptiform spikes and seizures were developed and parameterized using long-term ambulatory data from nine humans and eight canines with epilepsy, and then implemented prospectively in out-of-sample testing in two pet canines and four humans with drug-resistant epilepsy living in their natural environments. Accurate seizure diaries are needed as the primary clinical outcome measure of epilepsy therapy and to guide brain-stimulation optimization. The brain co-processor system described here enables tracking interictal epileptiform spikes, seizures and correlation with patient behavioural reports. In the future, correlation of spikes and seizures with behaviour will allow more detailed investigation of the clinical impact of spikes and seizures on patients.

SUBMITTER: Sladky V

PROVIDER: S-EPMC9217965 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Distributed brain co-processor for tracking spikes, seizures and behaviour during electrical brain stimulation.

Sladky Vladimir V Nejedly Petr P Mivalt Filip F Brinkmann Benjamin H BH Kim Inyong I St Louis Erik K EK Gregg Nicholas M NM Lundstrom Brian N BN Crowe Chelsea M CM Attia Tal Pal TP Crepeau Daniel D Balzekas Irena I Marks Victoria S VS Wheeler Lydia P LP Cimbalnik Jan J Cook Mark M Janca Radek R Sturges Beverly K BK Leyde Kent K Miller Kai J KJ Van Gompel Jamie J JJ Denison Timothy T Worrell Gregory A GA Kremen Vaclav V

Brain communications 20220506 3

Early implantable epilepsy therapy devices provided open-loop electrical stimulation without brain sensing, computing, or an interface for synchronized behavioural inputs from patients. Recent epilepsy stimulation devices provide brain sensing but have not yet developed analytics for accurately tracking and quantifying behaviour and seizures. Here we describe a distributed brain co-processor providing an intuitive bi-directional interface between patient, implanted neural stimulation and sensing ...[more]

PMID: 35755635

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Project description:Objective.Electrical deep brain stimulation (DBS) is an established treatment for patients with drug-resistant epilepsy. Sleep disorders are common in people with epilepsy, and DBS may actually further disturb normal sleep patterns and sleep quality. Novel implantable devices capable of DBS and streaming of continuous intracranial electroencephalography (iEEG) signals enable detailed assessments of therapy efficacy and tracking of sleep related comorbidities. Here, we investigate the feasibility of automated sleep classification using continuous iEEG data recorded from Papez's circuit in four patients with drug resistant mesial temporal lobe epilepsy using an investigational implantable sensing and stimulation device with electrodes implanted in bilateral hippocampus (HPC) and anterior nucleus of thalamus (ANT).Approach.The iEEG recorded from HPC is used to classify sleep during concurrent DBS targeting ANT. Simultaneous polysomnography (PSG) and sensing from HPC were used to train, validate and test an automated classifier for a range of ANT DBS frequencies: no stimulation, 2 Hz, 7 Hz, and high frequency (>100 Hz).Main results.We show that it is possible to build a patient specific automated sleep staging classifier using power in band features extracted from one HPC iEEG sensing channel. The patient specific classifiers performed well under all thalamic DBS frequencies with an average F1-score 0.894, and provided viable classification into awake and major sleep categories, rapid eye movement (REM) and non-REM. We retrospectively analyzed classification performance with gold-standard PSG annotations, and then prospectively deployed the classifier on chronic continuous iEEG data spanning multiple months to characterize sleep patterns in ambulatory patients living in their home environment.Significance.The ability to continuously track behavioral state and fully characterize sleep should prove useful for optimizing DBS for epilepsy and associated sleep, cognitive and mood comorbidities.

Project description:Demand-controlled deep brain stimulation (DBS) appears to be a promising approach for the treatment of Parkinson's disease (PD) as revealed by computational, pre-clinical and clinical studies. Stimulation delivery is adapted to brain activity, for example, to the amount of neuronal activity considered to be abnormal. Such a closed-loop stimulation setup might help to reduce the amount of stimulation current, thereby maintaining therapeutic efficacy. In the context of the development of stimulation techniques that aim to restore desynchronized neuronal activity on a long-term basis, specific closed-loop stimulation protocols were designed computationally. These feedback techniques, e.g., pulsatile linear delayed feedback (LDF) or pulsatile nonlinear delayed feedback (NDF), were computationally developed to counteract abnormal neuronal synchronization characteristic for PD and other neurological disorders. By design, these techniques are intrinsically demand-controlled methods, where the amplitude of the stimulation signal is reduced when the desired desynchronized regime is reached. We here introduce a novel demand-controlled stimulation method, pulsatile multisite linear delayed feedback (MLDF), by employing MLDF to modulate the pulse amplitude of high-frequency (HF) DBS, in this way aiming at a specific, MLDF-related desynchronizing impact, while maintaining safety requirements with the charge-balanced HF DBS. Previously, MLDF was computationally developed for the control of spatio-temporal synchronized patterns and cluster states in neuronal populations. Here, in a physiologically motivated model network comprising neurons from subthalamic nucleus (STN) and external globus pallidus (GPe), we compare pulsatile MLDF to pulsatile LDF for the case where the smooth feedback signals are used to modulate the amplitude of charge-balanced HF DBS and suggest a modification of pulsatile MLDF which enables a pronounced desynchronizing impact. Our results may contribute to further clinical development of closed-loop DBS techniques.

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Project description:Electrical brain stimulation (EBS) is a trendy new technique used to change brain function and treat neurological, psychiatric and psychological disorders. We were curious whether the published literature, which is dominated by positive results, reflects the experience of researchers using EBS. Specifically, we wanted to know whether researchers are able to reproduce published EBS effects and whether they engage in, but fail to report, questionable research practices. We invited 976 researchers to complete an online survey. We also audited 100 randomly-selected published EBS papers. A total of 154 researchers completed the survey. Survey respondents had a median of 3 [1 to 6, IQR] published EBS papers (1180 total) and 2 [1 to 3] unpublished ones (380 total). With anodal and cathodal EBS, the two most widely used techniques, 45-50% of researchers reported being able to routinely reproduce published results. When asked about how study sample size was determined, 69% of respondents reported using the sample size of published studies, while 61% had used power calculations, and 32% had based their decision on pilot data. In contrast, our audit found only 6 papers where power calculations were used and a single paper in which pilot data was used. When asked about questionable research practices, survey respondents were aware of other researchers who selectively reported study outcomes (41%) and experimental conditions (36%), adjusted statistical analysis to optimise results (43%), and engaged in other shady practices (20%). Fewer respondents admitted to engaging in these practices themselves, although 25% admitted to adjusting statistical analysis to optimize results. There was strong agreement that such practices should be reported in research papers; however, our audit found only two such admissions. The present survey confirms that questionable research practices and poor reproducibility are present in EBS studies. The belief that EBS is effective needs to be replaced by a more rigorous approach so that reproducible brain stimulation methods can be devised and applied.

Dataset Information

Distributed brain co-processor for tracking spikes, seizures and behaviour during electrical brain stimulation.

Publications

Distributed brain co-processor for tracking spikes, seizures and behaviour during electrical brain stimulation.

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