# Multi-Scale Cortical Dynamics in Human Epilepsy

> **NIH NIH R01** · BROWN UNIVERSITY · 2021 · $358,933

## Abstract

ABSTRACT
Epilepsy is one of the most common neurological disorders affecting ~65 million people worldwide. Of those,
25-35% are not responsive to pharmacological treatment, despite the development of new antiepileptic drugs
in the previous decades. One of the main barriers hindering the development of better therapies for epileptic
seizures, such as closed-loop neuromodulation for seizure prevention and abatement, is the lack of
understanding of how seizures initiate, spread and terminate over cortical and subcortical regions. Progress
thus far has been hampered by the challenge of measuring in humans neural activity at the multiple scales of
ensembles of single neurons and large-scale brain networks. In addition, most previous studies have focused
on biophysical mechanisms for seizure initiation at seizure onset zones. An overlooked aspect of focal seizures
is the formation/maintenance of local and large-scale pathological neuronal networks and the time-varying
susceptibility of brain dynamics to seizure initiation and spread (generalization). We hypothesize that these
pathological multiscale networks are maintained via the recurring activation of epileptiform spatiotemporal
patterns not only during seizures but also during interictal and preictal periods. We will address these problems
in patients with pharmacologically intractable focal epilepsy by recording ensemble of single-neurons via
intracortical 96-microelectrode arrays (96-MEA, 4 mm X 4 mm) and large-scale brain networks via intracranial
EEGs (Truccolo et al., 2011, 2014; Wagner et al., 2015). Neural activity at these multiple levels will be
recorded continuously 24hr/day, over a period of ~1-2 weeks. Furthermore, we will determine the association
between recurrent pathological patterns and changes in the brain's susceptibility to spread of excitation and
seizures by actively probing neural dynamics with a recently developed real-time closed-loop intracranial
electrical stimulation platform (Sarma et al., 2016). Three specific AIMs will: (1) Test the hypothesis that
multiscale ictal patterns recur not only during seizures but also during interictal periods, becoming part of the
resting state networks' repertoire; (2) Test the hypothesis that precursor biomarkers of seizure initiation include
the reactivation of multiscale ictal network patterns; (3) Test the hypothesis that ictal pattern reactivation during
interictal periods is accompanied by increases in the brain's susceptibility to both local and large-scale spread
of excitation: probing neural dynamics with closed-loop electrical stimulation.

## Key facts

- **NIH application ID:** 10126913
- **Project number:** 5R01NS079533-09
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** WILSON TRUCCOLO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $358,933
- **Award type:** 5
- **Project period:** 2012-07-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10126913

## Citation

> US National Institutes of Health, RePORTER application 10126913, Multi-Scale Cortical Dynamics in Human Epilepsy (5R01NS079533-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10126913. Licensed CC0.

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