PROJECT SUMMARY Sleep spindle deficits are a promising biomarker and therapeutic target for schizophrenia spectrum disor- der (SSD), as they reflect underlying dysfunction in thalamocortical circuits. However, current non-invasive neuromodulation techniques lack the depth and precision to directly target deep brain structures like the thala- mus, where sleep spindles are generated. Temporal interference transcranial electric stimulation (TI-TES) of- fers a novel approach to selectively stimulate deep brain regions, such as the thalamus, while minimizing elec- tric fields elsewhere. Additionally, TI-TES permits simultaneous stimulation and high-density EEG (hdEEG) ac- quisition during sleep, a combination pioneered by the research team. Supported by preliminary data, the over- all objective of this project is to demonstrate that TI-TES can effectively target thalamic circuits and enhance sleep spindle activity in healthy subjects during non-rapid eye movement (NREM) sleep. Specifically, this pro- ject aims to 1) identify the optimal TI-TES parameters (frequency, location) for enhancing spindle frequency activity (SFA), and 2) determine the differential effects of thalamic TI-TES on fast and slow spindle subtypes, slow waves, and SO-spindle coupling. The central hypothesis is that slow and fast spindle subtypes can be selectively enhanced by modulating the location and frequency of thalamic TI-TES. The rationale for this pro- ject is that focal thalamic stimulation could restore normal spindle activity in SSD patients in a personalized manner, potentially improving thalamocortical connectivity and addressing broader neurobiological deficits. To achieve these aims, personalized, multipolar TI-TES combined with hdEEG will be applied to healthy subjects during the N2 sleep stages of a 90 min afternoon nap. Each participant will undergo bilateral thalamic stimulation at three target locations (broad thalamic, anterior, posterior) across separate nap sessions in a ran- d