# Enhancing Sleep Spindle Activity through Thalamic TI-TES:  Neuromodulatory Foundations for Targeting Thalamocortical Dysfunction in Schizophrenia

> **NIH MH R21** · UNIVERSITY OF WISCONSIN-MADISON · 2026 · $427,625

## Abstract

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

## Key facts

- **NIH application ID:** 11217604
- **Project number:** 1R21MH141540-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Larissa Elena Regina Albantakis
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** MH
- **Fiscal year:** 2026
- **Award amount:** $427,625
- **Award type:** 1
- **Project period:** 2026-04-01T00:00:00 → 2028-03-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11217604

## Citation

> US National Institutes of Health, RePORTER application 11217604, Enhancing Sleep Spindle Activity through Thalamic TI-TES:  Neuromodulatory Foundations for Targeting Thalamocortical Dysfunction in Schizophrenia (1R21MH141540-01). Retrieved via AI Analytics 2026-07-04 from https://api.ai-analytics.org/grant/nih/11217604. Licensed CC0.

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