# Mechanism of CMPf Deep Brain Stimulation for Tourette Syndrome

> **NIH NIH F31** · MAYO CLINIC ROCHESTER · 2021 · $45,520

## Abstract

PROJECT SUMMARY
Tourette syndrome (TS) is a neurodevelopmental disorder characterized by the chronic presence of both motor
and vocal tics. Recent epidemiologic studies show over 100,000 school children are affected by this syndrome,
often with associated behavioral comorbidities that interfere with scholastic performance and social
development. While primarily a disease of childhood that improves with age, a subset of patients are refractory
to medication and continue to be afflicted into adulthood. Deep brain stimulation (DBS) has emerged as a
treatment option for these severely affected patients and while many targets for DBS therapy have been
identified, the primary target is the centromedian-parafascicular complex (CMPf) of the thalamus. The largest
Tourette’s DBS clinical trial to date targeting the CMPf found a 52% reduction in the Yale Global Tic Severity
Scale, a promising result that shows its potential. Despite this clinical benefit, the neurobiological mechanism
by which DBS of the CMPf alleviates symptoms of TS is not understood. Previous studies have implicated
increased extracellular dopamine levels in the striatum with the pathophysiology of this disease and our
preliminary results using fast scan cyclic voltammetry (FSCV) during CMPf DBS suggest the CMPf can
modulate these levels. These findings indicate that DBS of the CMPf may alter extracellular striatal dopamine
levels and this may be correlated with reduced tic behavior. To test this, we seek to elucidate if CMPf
stimulation leads to a dopaminergic response in the dorsal striatum. We will employ optogenetic and electrical
stimulation to do so and record extracellular levels of phasic and tonic changes in dopamine with FSCV and
multiple cyclic square wave voltammetry, respectively. A rat model of TS will be employed to characterize the
effects of CMPF DBS on extracellular striatal dopamine levels and tic behavior. Pharmacological manipulations
will be applied to mechanistically assess if CMPf stimulation-evoked changes in dopamine release are required
for amelioration of TS-related tic behavior.

## Key facts

- **NIH application ID:** 10128201
- **Project number:** 5F31NS115202-02
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Aaron Elliott Rusheen
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10128201

## Citation

> US National Institutes of Health, RePORTER application 10128201, Mechanism of CMPf Deep Brain Stimulation for Tourette Syndrome (5F31NS115202-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10128201. Licensed CC0.

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