Abstracts

Rationale: Sleep plays a fundamental role in numerous aspects of child and adolescent health and well-being. In children with epilepsy, the relationship between seizures and sleep is complex and bidirectional. Adequate sleep is essential for seizure control and conversely, epilepsy is associated with sleep fragmentation, leading to a cycle of sleep deprivation, particularly involving the deepest and most restorative stages of the sleep cycle.

While efforts to optimize sleep have historically focused on prioritizing sleep hygiene, neural-based neuromodulation has recently been proposed to directly enhance the restorative properties of sleep. In particular, enhancement of slow wave sleep—characterized by periods of high-amplitude, low-frequency neuronal oscillations—has been shown to improve memory consolidation, metabolic regulation, and immune function. To date, the ability to modulate sleep in the epileptic brain remains elusive.

Methods: Here, we present a novel closed-loop system to modulate sleep slow waves in children with epilepsy. The phase-targeted acoustic stimulation (PTAS) system consists of a real-time wavelet convolution estimator to track dominant neural oscillations during sleep, personalized to each individual child’s brain. The algorithm runs on a bedside tablet computer and processes EEG data streamed live from a wireless OpenBCI Cyton amplifier. Personalized to each child's endogenous sleep slow waves, PTAS was then delivered precisely timed to slow oscillation phase. We deployed the PTAS system in 30 children with simultaneous scalp and intracranial electrodes. Children were recruited from the Epilepsy Monitoring Unit at the Hospital for Sick Children, and underwent two or more nights of counterbalanced stimulation and withheld stimulation, with daily neurocognitive testing with the Go/Nogo response inhibition task both before and after PTAS.


Results: We found that delivery of the acoustic stimulus on the up-phase of the slow oscillations resulted in potentiation of sleep slow oscillations relative to the delivery on the down-phase on scalp EEG and in specific cortical regions that were sampled intracranially, namely, the thalamus, auditory cortex, cingulate gyrus, and midline frontal regions during sleep. Up-phase PTAS resulted in a significant reduction in interictal epileptiform activity during sleep (N2: p< 0.001, N3: p=0.007). The use of PTAS the previous night significantly improved accuracy on the Go/Nogo response inhibition task (p=0.002), a cognitive domain that is highly dependent on sleep quality.