Substrates for Post-Stroke Arm Rehabilitation (SPARk)

Defining the Neurological Substrates of Proximal Upper Extremity Motor Control and Recovery After Stroke

Difficulty moving the arm is very common and a major cause of disability after stroke. Although rehabilitation therapies (i.e., occupational and physical therapy) are the most common treatments used to improve arm motor function, it remains unknown how therapy actually changes brain pathways after stroke. This project seeks to generate fundamental knowledge about brain pathways that allow people to move their arm after stroke and how these pathways change with rehabilitation; we expect this knowledge to translate to new therapies to reduce stroke-related disability.

We plan to enroll N = 50 patients with moderate to severe difficulty moving their arm after ischemic or hemorrhage stroke during the subacute period (3 to 6 months post stroke) into either 30 hours over 6 weeks of Arm Basis Training (a protocolized form of occupational therapy targeting motor control) or usual care. We will perform kinematic motor assessments, neuroimaging, and neurophysiology before and after therapy in order to test the hypothesis that intensive, target training improves arm motor control and induces corresponding anatomical and physiological changes of associated brain pathways.

Study Overview

• Status: Recruiting
• Conditions: Stroke; Stroke Rehabilitation; Neurorecovery
• Intervention / Treatment: Behavioral: Arm Basis Training

Detailed Description

Strokes commonly damage motor pathways in the brain which leads to "hemiparesis", the collective term given to the syndrome of motor dysfunction after stroke. Upper extremity hemiparesis is comprised of both loss of abilities (negative signs- weakness and loss of dexterity or fractionated motor control) and intrusion of abnormal movements (positive signs- spasticity, abnormal resting postures, and synergies).

Recent work from our group and others shows that components of motor hemiparesis are dissociable: they can be separated and each map onto different and specific brain pathways. In this proposal, we focus on one specific component of post-stroke hemiparesis: proximal upper extremity motor control. Proximal upper extremity motor control can be measured as the ability to individuate and coordinate shoulder and elbow movements. We ask (i) where does proximal upper extremity motor control localize in the post-stroke brain? (ii) can we improve motor control with a specific form of targeted, high-dose, high-intensity therapy? And (iii) does therapy lead to corresponding changes in anatomy and physiology of brain pathways? Our central hypothesis is that intensive, targeted training improves proximal upper extremity motor control and induces corresponding anatomical and physiological changes of the corticospinal tract. To test this hypothesis, we will conduct three specific aims: (1) Determine baseline relationships between the corticospinal tract and proximal upper extremity motor control, (2) Define changes in proximal upper extremity motor control induced by targeted rehabilitation training, and (3) Define changes in corticospinal tract anatomy and physiology induced by targeted rehabilitation training. We leverage a clinical trial design of N = 50 patients with moderate-severe hemiparesis randomized to two groups: Arm Basis Training (a protocolized form of occupational therapy targeting motor control) versus usual care. Before and after six weeks of therapy, all patients will undergo kinematic assessment of motor control, diffusion magnetic resonance imaging to assess corticospinal tract axon density, and transcranial magnetic stimulation to assess corticospinal excitability. Dr. Lin, an acute care neurologist with neurorehabilitation and neuroscience training and the Director of the MGH Neurorecovery Clinic, will lead the project and bring together a world-class team of investigators and consultants, supported by the rich and multidisciplinary environment at Massachusetts General Hospital, Harvard Medical School, and collaborating institutions. This project is a mechanistic and hypothesis-driven investigation of the neuroanatomic and neurophysiologic signatures of a specific component of hemiparesis, proximal upper extremity motor control, and its response to targeted rehabilitation. The unique integration of kinematics, neuroanatomy, and neurophysiology in patients after stroke will transform stroke rehabilitation with a precision approach that targets brain structure and function.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Caroline Lambert, BA; Phone Number: 617-726-1311; Email: celambert@mgh.harvard.edu
• Study Contact Backup: Name: Julie DiCarlo, MS; Phone Number: 617-726-1311; Email: jdicarlo2@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Laboratory for Translational Neurorecovery, Center for Neurotechnology and Neurorecovery, Massachusetts General Hospital
      • Contact: Caroline Lambert; Phone Number: 617-726-1311; Email: celambert@mgh.harvard.edu
      • Contact: Julie DiCarlo; Phone Number: 617-726-1311; Email: jdicarlo2@mgh.harvard.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• first time unilateral ischemic or hemorrhagic stroke occurring within the 3-6 months
• upper extremity motor impairment as measured by the Upper Extremity Fugl-Meyer Assessment (UE-FMA) Score <= 44
• ability to participate in a 6-week intensive upper extremity intervention in English as determined by a licensed occupational therapist.

Exclusion Criteria:

• bilateral stroke
• unstable medical status affecting functional status
• pre-stroke upper extremity injury or conditions that limited use
• visual or auditory impairment limiting ability to participate in study procedures

• significant aphasia (NIHSS sub-item 9 > 1) or cognitive (NIHSS 1a or 1b or

  1c > 1) deficits

• known or expected inability to maintain follow-up through the study intervention and post- assessment
• contraindications to MRI
• contraindications to TMS
• known history of uncontrolled seizure disorder.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm Basis Training; This program is a systematic training regimen specifically designed to improve proximal motor control for patients with severe upper extremity hemiparesis. The core principles of the Arm Basis Training Program focus on rebuilding the fundamental capacity for specific and selective motor control before progressing to more complex motor patterns.	Behavioral: Arm Basis Training; This program is a systematic training regimen specifically designed to improve proximal motor control for patients with severe upper extremity hemiparesis. The core principles of the Arm Basis Training Program focus on rebuilding the fundamental capacity for specific and selective motor control before progressing to more complex motor patterns.
No Intervention: Usual Care Occupational Therapy; Usual care occupational therapy. Participants will be asked to keep logs of the therapy they receive.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Kinematic Measure of Upper Extremity Motor Control	Kinematic measures of Upper Extremity Motor Control include joint individuation index (a measure of how well joints can move independently of other joints) and shoulder-elbow coordination (a measure of how normal a point-to-point planar reaching movement is)	Pre- and post- 6 weeks of therapy
Change in Corticospinal Tract Axon Density on MRI	High-resolution diffusion MR neuroimaging will be performed, from which corticospinal tract axon density will be calculated	Pre- and post- 6 weeks of therapy
Change in Corticospinal Tract Neurophysiology	The primary neurophysiologic measure of interest will be MEP presence or absence at proximal upper extremity muscles. If MEP positive, secondary measures of corticospinal excitability will be the MEP recruitment curve slope as well as MEP amplitude (at 100% MSO).	Pre- and post- six weeks of therapy

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: David J Lin, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2025
• Primary Completion (Estimated): April 30, 2030
• Study Completion (Estimated): April 30, 2030

Study Registration Dates

• First Submitted: May 22, 2025
• First Submitted That Met QC Criteria: May 22, 2025
• First Posted (Actual): May 31, 2025

Study Record Updates

• Last Update Posted (Actual): March 11, 2026
• Last Update Submitted That Met QC Criteria: March 8, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: motor control; neurorecovery; stroke rehabilitation; upper limb kinematics; corticospinal tract
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke
• Other Study ID Numbers: 2025P000641; R01NS142153 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will release raw behavior, imaging, and physiology data sets with relevant de-identified data to the database ~12 months after we have finished a portion of the project with enough sample size for publication. We will give database access to investigators who contact us about specific projects or analyses and/or are willing to enter into the same data sharing, authorship, and human subject data protection protocols that binds our multi-institutional collaboration, and agree to work closely with us to ensure that these complex data are analyzed with complete understanding of the experimental conditions under which they were collected.; We will also release annotated, preprocessed datasets from this grant that form the basis for published manuscripts two years after their initial (online) publication date. We will make data available to individuals who agree to a data-sharing agreement.
• IPD Sharing Time Frame: May 2031 -
• IPD Sharing Access Criteria: We will give database access to investigators who contact us about specific projects or analyses and/or are willing to enter into the same data sharing, authorship, and human subject data protection protocols that binds our multi-institutional collaboration, and agree to work closely with us to ensure that these complex data are analyzed with complete understanding of the experimental conditions under which they were collected.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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