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Optogenetic Manipulation of Neural Circuits During Monitoring Sleep/wakefulness States in Mice
Published on: June 19, 2019
Closed-loop modulation of sleep in children undergoing intracranial recordings
Simeon M Wong1, Vicki Li1, Karim Mithani2
1Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Neurosciences & Mental Health Program, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.
Insights
Phase-targeted auditory stimulation (PTAS) enhances slow-wave sleep (SWS) in children with epilepsy. This non-invasive approach also reduces seizures and improves cognitive function.
Area of Science:
- Neuroscience
- Sleep Medicine
- Pediatric Neurology
Background:
- Epilepsy disrupts sleep, creating a cycle where poor sleep increases seizure risk.
- Slow-wave sleep (SWS) impairment affects cognitive, immune, and metabolic functions in children with epilepsy.
Purpose of the Study:
- To investigate the efficacy of phase-targeted auditory stimulation (PTAS) for improving sleep and reducing seizures in pediatric epilepsy.
- To assess the impact of PTAS on cognitive performance in children with epilepsy.
Main Methods:
- A randomized cross-over study involving 27 children with epilepsy undergoing monitoring.
- Utilized scalp, intracranial, and thalamic recordings to deliver PTAS timed to endogenous slow oscillations.
- Assessed changes in SWS power, interictal epileptiform discharges, and cognitive performance.
Main Results:
- PTAS significantly enhanced SWS power, particularly in thalamic, frontal, and auditory regions.
- Auditory stimulation suppressed interictal epileptiform discharges from 0.4 to <0.1 spikes/min.
- Cognitive performance on a response inhibition task improved significantly, from 76% to 95% accuracy.
Conclusions:
- Closed-loop auditory stimulation effectively modulates sleep architecture and suppresses pathological brain activity in pediatric epilepsy.
- PTAS offers a non-invasive, physiologically informed strategy to address sleep disturbances and cognitive deficits in children with epilepsy.
Abstract:
Children with epilepsy suffer a vicious cycle in which disturbed sleep heightens seizure susceptibility, while seizures further disrupt sleep quality, particularly impairing the slow-wave sleep (SWS) critical for cognitive, immune, and metabolic function. We present a phase-targeted auditory stimulation (PTAS) system that delivers stimuli timed to endogenous slow oscillations. In 27 children undergoing epilepsy monitoring with simultaneous scalp, intracranial, and thalamic recordings, PTAS significantly enhances SWS power, with maximal effects on thalamic, frontal, and auditory regions in a randomized cross-over protocol. Stimulation also suppresses interictal epileptiform discharges (from 0.4 to <0.1 spikes/min) and improves cognitive performance on a response inhibition task (from 76% to 95% accuracy). These results provide direct intracranial evidence that closed-loop auditory stimulation modulates sleep architecture, suppresses pathological activity, and enhances cognition. PTAS represents a physiologically informed, non-invasive approach for addressing both neurophysiological and cognitive comorbidities in pediatric epilepsy.
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