The thalamus plays a key role in supporting sleep and is also a target of therapeutic stimulation. This project investigates when, where, and how electrical stimulation delivered to the thalamus in humans elicits or disrupts sleep oscillations. This research is a first step to better understand how current neuromodulation therapies affect sleep and may help advance toward new therapies to improve sleep for a wide range of neurological and neuropsychological disorders.

The thalamus plays a key role in supporting sleep. The thalamus is also increasingly used as a stimulation therapeutic target, but the effect of thalamic stimulation on sleep has not been investigated.

We hypothesize that electrical stimulation delivered to the thalamus in humans could both elicit and disrupt sleep oscillations, such as spindles, depending on the timing and location of stimulation. We propose a study to obtain direct evidence in humans of how thalamic stimulation affects sleep.

We will test the hypothesis that stimulation during a thalamic sleep spindle disrupts it, while stimulation outside evokes a response resembling a k-complex followed by a spindle. Participants will be patients with refractory epilepsy who have semi-chronically implanted depth electrodes in the thalamus and other brain regions (~100) as part of the pre-surgical clinical work-up. We will detect spindles and stimulate during or outside oscillations using a real-time closed-loop system that we developed. Simultaneously recording across the brain will comprehensively map the effect and extent of thalamic stimulation on sleep oscillations.

This will be the first step to unravel the effect of thalamic stimulation on sleep oscillations and maintenance. This will increase our understanding of the thalamus as a relay of sleep oscillations and could have profound implications to ensure good sleep quality for the increasing number of people implanted with therapeutic stimulation.

Inclusion Criteria:

• Patients getting intracranial recordings for clinical purposes who, as part of that plan, will receive thalamic electrodes.

Exclusion Criteria:

• previous extensive resection or large atrophy

De-identified intracranial EEG recordings will be collated across participants. Data used in the results publication will be shared.

Beginning 1 year after publication with no end date

We will share electrophysiological data with the scientific community via the Data Archive for the BRAIN Initiative (DABI), or another NIH-approved database, where we will offer access to our database of neural activity.