# Progressive resistance exercise and dystonia pathophysiology.

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2023 · $510,564

## Abstract

PROJECT ABSTRACT
Dystonia is a debilitating movement disorder characterized by involuntary muscle contractions with abnormal
and repetitive movements, postures, or both. The current treatments for dystonia, consisting of oral
medications, botulinum toxin injections, and deep brain stimulation surgery, fail to improve symptoms in more
than a third of patients despite optimal management. The improvements are often unpredictable. Recent
studies found exercise therapy primarily involving muscle stretching, muscle relaxation, and range of motion
exercises, when added to optimal medical management, further improved symptoms of focal cervical dystonia.
But the clinical outcomes were noted to be variable and modest. These studies did not investigate the
pathophysiological underpinnings that could explain the variability of treatment outcomes. They did not
include progressive resistance training that has the potential to induce central brain changes. The main goal of
this proposal is to investigate the brain adaptation effects for progressive resistance exercise-focused cervical
and shoulder training (PERFECT) in patients with focal cervical dystonia, which is the most common form of
dystonia. We will use functional MRI (fMRI) and transcranial magnetic stimulation (TMS) techniques for
understanding the pathophysiological underpinnings. We will randomize patients into PERFECT plus
standard-of-care (SOC) group and SOC alone group. Participants in the PERFECT + SOC group will perform
personal-trainer-guided exercises twice a week for six months. Participants in the SOC group will continue
receiving standard pharmacological therapies at stable doses, and they will not exercise. We will use fMRI and
TMS techniques to examine brain effects. We hypothesize that the PERFECT program in focal cervical dystonia
will improve the functioning of dystonia circuitries involving the sensorimotor cortex. In Aim 1, we will
determine the brain adaptation changes in response to PERFECT at six months compared to baseline with
fMRI. We will record seed-based functional connectivity and bold oxygen level-dependent signal in the
sensorimotor network. In Aim 2, we will determine the brain adaptation changes in response to PERFECT at
six months compared to baseline with TMS. We will use a TMS-based paired associative stimulation protocol to
measure sensorimotor plasticity and compare. We will monitor the TMS-based resting motor threshold; motor
evoked potential, intracortical inhibition, and intracortical facilitation as additional measures. In Aim 3, we will
determine whether the brain adaptation response relates to clinical and functional change. We will assess with
blinded dystonia ratings, cognition and mood measures, muscle strength, physical functioning capacity. The
outcomes of this proposal will (1) test whether a 6-month long resistance exercise is viable, (2) identify
physiological brain markers that are responsive to effects of resistance exercise and are specific to dys...

## Key facts

- **NIH application ID:** 10691544
- **Project number:** 5R01NS122943-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Aparna Wagle Shukla
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $510,564
- **Award type:** 5
- **Project period:** 2022-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10691544

## Citation

> US National Institutes of Health, RePORTER application 10691544, Progressive resistance exercise and dystonia pathophysiology. (5R01NS122943-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10691544. Licensed CC0.

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