Responsive manipulation of neural circuit pathology by fully implantable, front-end multiplexed embedded neuroelectronics

Responsive neurostimulation is increasingly required to probe neural circuit function and treat neuropsychiatric disorders. We introduce a multiplex-then-amplify (MTA) scheme that, in contrast to current approaches (which necessitate an equal number of amplifiers as number of channels), only requires one amplifier per multiplexer, significantly reducing the number of components and the size of electronics in multichannel acquisition systems. It also enables simultaneous stimulation of arbitrary waveforms on multiple independent channels. We validated the function of MTA by developing a fully implantable, responsive embedded system that merges the ability to acquire individual neural action potentials using conformable conducting polymer-based electrodes with real-time onboard processing, low-latency arbitrary waveform stimulation, and local data storage within a miniaturized physical footprint. We verified established responsive neurostimulation protocols and developed a network intervention to suppress pathological coupling between the hippocampus and cortex during interictal epileptiform discharges. The MTA design enables effective, self-contained, chronic neural network manipulation with translational relevance to the treatment of neuropsychiatric disease.

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Distributed Brain Co-Processor for Neurophysiologic Tracking and Adaptive Stimulation: Application to Drug Resistant Epilepsy

10.1101/2021.03.08.434476 ◽

2021 ◽

Author(s):

Vladimir Sladky ◽

Petr Nejedly ◽

Filip Mivalt ◽

Benjamin H. Brinkmann ◽

Inyong Kim ◽

...

Keyword(s):

Data Storage ◽

Brain Stimulation ◽

Open Loop ◽

Natural Environments ◽

Drug Resistant ◽

Embedded Computing ◽

Epileptiform Discharges ◽

Interictal Epileptiform Discharges ◽

Drug Resistant Epilepsy

AbstractElectrical brain stimulation is a proven therapy for epilepsy, but long-term seizure free outcomes are rare. Early implantable devices were developed for open-loop stimulation without sensing, embedded computing or adaptive therapy. Recent device advances include sensing and closed-loop responsive stimulation, but these clinically available devices lack adequate computing, data storage and patient interface to concisely catalog behavior, seizures, and brain electrophysiology, despite the critical importance of these details for epilepsy management. Here we describe the first application of a distributed brain co-processor providing an intuitive, bi-directional interface between device implant, patient & physician, and implement it in human and canine patients with epilepsy living in their natural environments. Automated behavioral state tracking (awake and sleep) and electrophysiologic classifiers for interictal epileptiform discharges and electrographic seizures are run on local hand-held and distributed cloud computing resources to guide adaptive electrical stimulation. These algorithms were first developed and parameterized using long-term retrospective data from 10 humans and 11 canines with epilepsy and then implemented prospectively in two pet canines and one human with drug resistant epilepsy as they naturally navigate their lives in society.One Sentence SummaryWe created a distributed brain co-processor for continuous neurophysiologic tracking and controlling adaptive brain stimulation to treat epilepsy.

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Prognostic Significance of Interictal Epileptiform Discharges in Newly Diagnosed Seizure Disorders

Yearbook of Neurology and Neurosurgery ◽

10.1016/j.yneu.2011.04.009 ◽

2011 ◽

Vol 2011 ◽

pp. 195

Author(s):

G.N. Breningstall

Keyword(s):

Prognostic Significance ◽

Newly Diagnosed ◽

Seizure Disorders ◽

Epileptiform Discharges ◽

Interictal Epileptiform Discharges

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Prevalence of Interictal Epileptiform Discharges in Children Less Than One Year of Age Referred for Polysomnography

The Neurodiagnostic Journal ◽

10.1080/21646821.2015.1043224 ◽

2015 ◽

Vol 55 (2) ◽

pp. 122-132

Author(s):

Adetayo Adeleye ◽

Alice W. Ho ◽

Alberto Nettel-Aguirre ◽

Valerie Kirk ◽

Jeffrey Buchhalter

Keyword(s):

Epileptiform Discharges ◽

Interictal Epileptiform Discharges ◽

One Year

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Zero-crossing patterns reveal subtle epileptiform discharges in the scalp EEG

Scientific Reports ◽

10.1038/s41598-021-83337-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jan Pyrzowski ◽

Jean- Eudes Le Douget ◽

Amal Fouad ◽

Mariusz Siemiński ◽

Joanna Jędrzejczak ◽

...

Keyword(s):

Normal Subjects ◽

Intracranial Eeg ◽

Zero Crossing ◽

Temporal Precision ◽

Scalp Eeg ◽

Epileptiform Discharges ◽

Interictal Epileptiform Discharges ◽

Eeg Recordings ◽

Patients With Epilepsy ◽

Low Amplitude

AbstractClinical diagnosis of epilepsy depends heavily on the detection of interictal epileptiform discharges (IEDs) from scalp electroencephalographic (EEG) signals, which by purely visual means is far from straightforward. Here, we introduce a simple signal analysis procedure based on scalp EEG zero-crossing patterns which can extract the spatiotemporal structure of scalp voltage fluctuations. We analyzed simultaneous scalp and intracranial EEG recordings from patients with pharmacoresistant temporal lobe epilepsy. Our data show that a large proportion of intracranial IEDs manifest only as subtle, low-amplitude waveforms below scalp EEG background and could, therefore, not be detected visually. We found that scalp zero-crossing patterns allow detection of these intracranial IEDs on a single-trial level with millisecond temporal precision and including some mesial temporal discharges that do not propagate to the neocortex. Applied to an independent dataset, our method discriminated accurately between patients with epilepsy and normal subjects, confirming its practical applicability.

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Detection of Intracranial Signatures of Interictal Epileptiform Discharges from Concurrent Scalp EEG

International Journal of Neural Systems ◽

10.1142/s0129065716500167 ◽

2016 ◽

Vol 26 (04) ◽

pp. 1650016 ◽

Cited By ~ 11

Author(s):

Loukianos Spyrou ◽

David Martín-Lopez ◽

Antonio Valentín ◽

Gonzalo Alarcón ◽

Saeid Sanei

Keyword(s):

Detection Algorithm ◽

The Other ◽

Intracranial Eeg ◽

Scalp Eeg ◽

Epileptiform Discharges ◽

Interictal Epileptiform Discharges ◽

Scalp Electroencephalogram ◽

Patients With Epilepsy ◽

Electrical Activities ◽

The Brain

Interictal epileptiform discharges (IEDs) are transient neural electrical activities that occur in the brain of patients with epilepsy. A problem with the inspection of IEDs from the scalp electroencephalogram (sEEG) is that for a subset of epileptic patients, there are no visually discernible IEDs on the scalp, rendering the above procedures ineffective, both for detection purposes and algorithm evaluation. On the other hand, intracranially placed electrodes yield a much higher incidence of visible IEDs as compared to concurrent scalp electrodes. In this work, we utilize concurrent scalp and intracranial EEG (iEEG) from a group of temporal lobe epilepsy (TLE) patients with low number of scalp-visible IEDs. The aim is to determine whether by considering the timing information of the IEDs from iEEG, the resulting concurrent sEEG contains enough information for the IEDs to be reliably distinguished from non-IED segments. We develop an automatic detection algorithm which is tested in a leave-subject-out fashion, where each test subject’s detection algorithm is based on the other patients’ data. The algorithm obtained a [Formula: see text] accuracy in recognizing scalp IED from non-IED segments with [Formula: see text] accuracy when trained and tested on the same subject. Also, it was able to identify nonscalp-visible IED events for most patients with a low number of false positive detections. Our results represent a proof of concept that IED information for TLE patients is contained in scalp EEG even if they are not visually identifiable and also that between subject differences in the IED topology and shape are small enough such that a generic algorithm can be used.

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