Impact of rTMS on Abnormal Cortical fMRI in Patients With Dystonia

The Effect of Repetitive Trans-cranial Magnetic (rTMS) Stimulation on Abnormal Cortical Hubs Identified by Functional Magnetic Resonance in Subjects With Dystonia.

By tracking resting-state fMRI scans, we aim to discover how repetitive transcranial magnetic stimulation (rTMS) changes brain connectivity in individuals with dystonia.

Study Overview

• Status: Recruiting
• Conditions: Dystonia Disorder
• Intervention / Treatment: Device: Transcranial Magnetic Stimulation

Detailed Description

Dystonia is a neurological movement disorder characterized by spontaneous involuntary muscle contractions that cause repetitive twisting motions. These involuntary movements affect various body regions, including the face (blepharospasm), jaw (bruxism, oromandibular dystonia), head and neck (torticollis), voice box (laryngeal spasm), hands (writer's cramp), or as multiple body segments simultaneously. Dystonia lacks defining neuropathological change, making diagnosis challenging, and rendering symptom management incomplete. Advanced imaging techniques, particularly spatial covariance analysis and graph theory computations have revealed insights into dystonia's underlying brain networks. This approach shows that the relative strength of the metabolic function at each brain region (called "hubs") regulates information flow within the network and between the network and the rest of the brain. The identification of accessible cortical hubs as integral parts of the dystonia network raises new therapeutic possibilities though non-invasive techniques. Continuous theta-burst stimulation (cTBS), a modified form of rTMS that mimics natural brain rhythms (theta 4-8Hz), can effectively inhibit the cortical hyperactivity in targeted hubs with shorter treatment times than traditional approaches. The rationale for this proposed pilot experiment is to combine advanced analysis of standard neuroimaging to refine target location for a test of whether the application of non-invasive rTMS (in the form of cTBS) modulates abnormal cortical regions or the entire brain network, or both, as these networks underlie dystonia.

Our PET investigations of patients with dystonia (DYT1 carriers both symptomatic and non-symptomatic) have identified hyperactive subcortical regions including the lentiform nuclei, cerebellum, and supplementary motor cortex. The dystonia-related brain metabolic networks that we generated with PET scanning, can now be generated with rs-fMRI, a less invasive technique that avoids radiation exposure and blood sampling. Graph Theory analysis indicates that the bilateral motor cortex (spanning the inter-hemispheric sulcus) and the left pre-motor region serve as critical hyperactive hubs. We hypothesize that modulating these hubs will disrupt the information flow in patients with dystonia. Using frameless stereotaxic optical system (Polaris Vicra, BrainSight 2.2), we can precisely target these cortical hubs with cTBS, the inhibitory form of rTMS.

We are encouraged by recent studies that showed that a single cTBS run (40sec) precisely targeted significantly modified brain networks in patients with dystonia.

Ameliorating dystonia has been one of the most controversial and challenging topics in treating hyperkinetic movement disorders, because it is difficult to estimate the overall whole brain responses after focal alterations caused by brain stimulation techniques. Our approach offers several innovations:

1. Enhanced and personalized hypermetabolic cortical hub identification.
2. Use of independent component analysis and graph theory to optimize location for cTBS delivery.
3. Individual response to the single cTBS stimulation site will be used for customized modeling of the TMS effect.

Although previous attempts to use TMS to improve dystonia have been inconsistent, our precisely targeted approach may improve outcomes. Success with this method could expand TMS application beyond its established use in depression to other neurological disorders. The shift from PET to rs-fMRI for network mapping represents a significant advance, making the technique/treatment more accessible and easier on patients.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Bruce T Volpe, MD; Phone Number: 516-562-3384; Email: bvolpe1@northwell.edu
• Study Contact Backup: Name: Celina B Fernandez, MS; Phone Number: 516-562-3646; Email: cfernandez14@northwell.edu

Study Locations

• United States
  • New York
    • Manhasset, New York, United States, 11030
      • Recruiting
      • Northwell Health/Feinstein Institutes
      • Contact: Celina B Fernandez, MS; Phone Number: 516-562-3646; Email: cfernandez14@northwell.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female
• 18 and 80 years of age.
• Patients who manifest dystonia - sustained involuntary movement of the head, neck, trunk or limbs.
• The dystonia may be spontaneous or genetic, specifically DYT1 or DYT6 and then only those patients who are demonstrating dystonia. The patient/subject will have a normal neurological exam except for dystonia.

Exclusion Criteria:

• Heredodegenrative dystonia of the type DYT8,9 or 10.
• Past history of head trauma, stroke, epilepsy, demyelinating disease
• Hypertension in excess of 160mmHg systolic and 90mmHg diastolic
• Congestive heart failure
• Diabetes
• Past psychiatric conditions: e.g., depression
• Systemic metabolic disease: e.g., Wilson's disease, progressive neurodegenerative disease (like supranuclear palsy or corticobasal ganglionic degeneration)
• Magnetizable incorporated metal parts - like pacemakers
• History or diagnosis of Parkinson's disease
• Presence of myoclonus
• No previous surgery for dystonia
• Long term exposure to benzodiazepines, neuroleptics or anticonvulsants
• No botulinum toxin within 12 weeks of baseline assessment and fMRI.
• Moderate to severe cognitive impairment (judged by a minimental status of <24.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Active rTMS Arm; We will investigate how repetitive transcranial magnetic stimulation (rTMS) affects brain networks in patients with dystonia by measuring changes in resting state-functional magnetic resonance images (rs-fMRI).

Device: Transcranial Magnetic Stimulation; Continuous theta-burst stimulation (cTBS), a modified form of rTMS that mimics natural brain rhythms (theta 4-8Hz), can effectively inhibit the cortical hyperactivity in targeted hubs with shorter treatment times than traditional approaches. The rationale for this proposed pilot experiment is to combine advanced analysis of standard neuroimaging to refine target location for a test of whether the application of non-invasive rTMS (in the form of cTBS) modulates abnormal cortical regions or the entire brain network, or both, as these networks underlie dystonia. This pilot study will provide the basis for a controlled study to test the effectiveness and robustness of any positive influence that TMS might have on the patients' dystonia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluating rs-fMRI Changes Following rTMS Treatment	The primary objective is to identify and modify replicable brain networks in dystonia patients using rs-fMRI. These networks reflect underlying disease processes, clinical symptomatology or both. The primary endpoint is change in the rs-fMRI derived network after rTMS treatment for two or four weeks, or both. We expect there to be changes at two and four weeks. We will then analyze the robustness of these changes in the repeat fMRI one week after treatment ends. Initially, identification and validation of the dystonia pattern from the resting state MRI will occur; it is a task with which we are familiar and is detailed in our recent manuscript.	Two to four weeks.

Collaborators and Investigators

• Sponsor: Northwell Health

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: May 29, 2026
• First Submitted That Met QC Criteria: May 29, 2026
• First Posted (Actual): June 4, 2026

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Transcranial Magnetic Stimulation, Heperkinetic Movement Disorder,Truncal (Axial) Dystonia, Abnormal Posture,Contractions of the chest, back,abdominal muscles
• Additional Relevant MeSH Terms: Neurologic Manifestations; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Dyskinesias; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Dystonia; Dystonic Disorders; Therapeutics; Magnetic Field Therapy; Transcranial Magnetic Stimulation
• Other Study ID Numbers: 25-0951

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No