# Focal thalamocortical circuit dysfunction mediates motor and cognitive deficits in developmental epilepsy

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $706,515

## Abstract

Project Summary / Abstract
Benign epilepsy with centrotemporal spikes (BECTS) is the most common focal childhood epilepsy syndrome,
characterized by a transient period of seizures and abundant epileptiform spikes arising from the sensorimotor
cortex during non-REM (NREM) sleep. Recent findings indicate that BECTS is a developmental disorder with a
wider range of severity than previously appreciated. In addition to seizures, children have deficits in attention
and motor coordination. The motor and cognitive symptoms in BECTS exist on a spectrum of severity, clinically
and genetically overlapping with severe epileptic encephalopathies, which are characterized by permanent and
progressive declines in cerebral function coincident with sleep activated spikes. There are currently no proven
treatment strategies to address the neuropsychological deficits in BECTS or other epileptic encephalopathies.
Several lines of evidence, including our preliminary findings, suggest a dysfunction in thalamocortical circuitry
drives the motor and cognitive abnormalities in BECTS. First, thalamocortical structural circuits are abnormal in
BECTS. Second, children with BECTS have reduced sleep spindles, oscillations that are critical for memory
consolidation during NREM sleep and generated and propagated by thalamocortical circuitry. Third,
thalamocortical sensory gating is impaired in children with centrotemporal spikes, like those observed in
BECTS. Effective dampening or “gating” of irrelevant sensory information prior to reaching the cortex, mediates
performance on attentional tasks. Despite this evidence, the relationship between thalamocortical
electrophysiology, connectivity, and cognitive symptoms in BECTS has not been investigated. The long term
goal of this project is to test the hypothesis that focal thalamocortical circuit dysfunction mediates the
motor and cognitive symptoms in BECTS. Our interdisciplinary team - consisting of a pediatric
epileptologist, a neuropsychologist, and a computational neuroscientist – will use validated experimental
paradigms and computational tools to collect and analyze multimodal data to link thalamocortical circuit
abnormalities to cognitive deficits in children with BECTS. First, we will determine whether children with
BECTS show abnormal sleep spindle activity that relates to impaired sleep-dependent memory consolidation.
Second, we will determine whether impaired sensory gating and thalamocortical connectivity relate to impaired
attention in BECTS. Third, we will test the impact of medication and closed loop auditory stimulation on
thalamocortical spindles, gating, and cognitive function in BECTS. Completion of the proposal goals will
represent significant progress towards understanding the pathophysiological mechanisms underlying cognitive
dysfunction in BECTS, and the identification of new targets and approaches for treating cognitive deficits in
BECTS and related epileptic encephalopathies.
.

## Key facts

- **NIH application ID:** 9944733
- **Project number:** 1R01NS115868-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Catherine J Chu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $706,515
- **Award type:** 1
- **Project period:** 2020-05-15 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9944733

## Citation

> US National Institutes of Health, RePORTER application 9944733, Focal thalamocortical circuit dysfunction mediates motor and cognitive deficits in developmental epilepsy (1R01NS115868-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9944733. Licensed CC0.

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