Thalamocortical interactions and the effect of thalamic stimulation on sleep oscillations

PROJECT SUMMARY The thalamus plays a key role supporting sleep. The thalamus is also a target for therapeutic electrical stimulation, but the effect of thalamic stimulation on sleep has not been investigated. We hypothesize that thalamic stimulation could both elicit and disrupt sleep oscillations, particularly spindles, depending on stimulation location and timing. We also hypothesize that thalamic stimulation affects sleep integrity. We will study two unique complementary patient groups to obtain direct evidence in humans of how thalamic stimulation affects sleep. First, in 50 patients with medication refractory epilepsy with semi-chronic depth-electrodes clinically implanted to delineate their epileptic focus, we will compare stimulation delivered to the thalamus and to other regions. We will assess the spatial extent across the brain of stimulation evoked spindles under each condition. Then, with our closed-loop system, spindles will be detected, and stimulation delivered in real-time. We will study under which circumstances stimulation disrupts spindles. We expect thalamic stimulation to have a broad effect compared to a local effect of neocortical stimulation. We will also relate spindle disruption to other oscillations. In another 25 patients with chronically implanted stimulator devices in the thalamus (to control their epileptic seizures) we will study their brain activity following therapeutic thalamic stimulation during sleep at home. We will evaluate whether stimulation evokes spindles and produces micro-arousals. For therapeutic thalamic stimulation to fully benefit the patients, it is necessary to understand the effect of stimulation on sleep oscillations and whether there are consequences for sleep integrity. This project is the first step to unravel the effect of thalamic stimulation on sleep oscillations in humans. This will improve our understanding of the thalamus as relay of sleep oscillations and provide for the first-time direct evidence in humans of the implications of chronic thalamic stimulation for sleep. This new direction for research is essential for understanding current therapies and moving toward new therapies for a wide range of neurological and neuropsychological disorders.