Neuro-MoD: Neuroplasticity With Motor Development

Harnessing Early Neuroplasticity in Infants With Perinatal Brain Injury: A Study of Combined Transcutaneous Auricular Vagal Nerve Stimulation (taVNS) Paired With Constraint Induced Movement Therapy (CIMT) and Transcranial Magnetic Stimulation (TMS)

This study is for infants and toddlers between 8 and 24 months old who use one arm and/or hand differently following a perinatal brain injury. This is a time when investigators think they can best help improve how the brain controls movement. Investigators are testing whether the combination of transcutaneous auricular vagus nerve stimulation (taVNS) with 40 hours of constraint-induced movement therapy (CIMT) can help infants move their weaker arm and hand better and make the brain pathways for movement stronger.

Study Overview

• Status: Not yet recruiting
• Conditions: Perinatal Brain Injury
• Intervention / Treatment: Behavioral: Constraint-Induced Movement Therapy (CIMT); Device: Transcutaneous auricular vagus nerve stimulation (taVNS)

Detailed Description

Primary Objective • To evaluate the feasibility of using spTMS to elicit motor-evoked potentials (MEPs) in infants with hemiplegic cerebral palsy (CP) due to perinatal brain injury and to determine whether baseline MEP characteristics predict motor response to a 40-hour intervention combining taVNS with CIMT.

Exploratory Objective:

• To investigate neuroplastic changes in cortical motor circuitry associated with taVNS-paired CIMT by examining longitudinal changes in MEP topography and corresponding motor function.

• Study Type: Interventional
• Enrollment (Estimated): 8
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Bernadette Gillick, PhD, MSPT; Phone Number: 608-262-7457; Email: bgillick@wisc.edu
• Study Contact Backup: Name: Arun Karumattu Manattu, PhD; Phone Number: 608-381-2699; Email: karumattuman@wisc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Infants aged 8 to 24 months, diagnosed with hemiplegia or with an evident unilateral upper-limb weakness due to perinatal brain injury
• Gross Motor Function Classification System (GMFCS) level I-IV
• Infants who have not received previous CIMT in the preceding 3 months
• Able to make consecutive appointments for assessments and intervention over 2 weeks, and complete the 3-month follow-up.

Exclusion Criteria:

• GMFCS level V
• Prior CIMT within the past 3 months
• Severe motor impairment/quadriplegic involvement.
• Uncontrolled seizure disorders, cardiomyopathy, severe congenital malformations,
• significant sensory impairments, or conditions preventing safe participation in therapy sessions

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: Infants and Toddlers with Perinatal Brain Injury; Therapy sessions in this study will take 4 hours a day, 5 days a week for 2 weeks (40 hours total CIMT). Sticker like sensors (electrodes) are placed just inside and outside the child's left earlobe at the start of the session to deliver the taVNS. During daily therapy sessions, the taVNS will be on whenever the child moves their free arm, for up to 2.5 minutes at a time.

Behavioral: Constraint-Induced Movement Therapy (CIMT); CIMT involves placing a mitt constraint on the stronger arm and hand while encouraging your child to use the weaker arm and hand during intensive therapy sessions.; Device: Transcutaneous auricular vagus nerve stimulation (taVNS); Stimulates a nerve by the ear, called the vagus nerve, that may enhance learning motor skills.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants in whom MEPs can be elicited reliably at baseline (presence/absence)	Motor-evoked potentials (MEPs) are electrical responses recorded from a muscle following a brief magnetic pulse delivered to the brain using single-pulse transcranial magnetic stimulation (spTMS). This outcome measures the proportion of participants in whom a reliable MEP can be elicited at baseline and serves as a measure of the feasibility of assessing corticospinal connectivity in infants with perinatal brain injury.	baseline (Day 1)
Completion rate of spTMS sessions	This outcome measures the proportion of planned spTMS assessment sessions that are successfully completed at baseline, post-intervention, and 3-month follow-up. Completion rates will be used to evaluate the feasibility, tolerability, and practicality of conducting repeated spTMS assessments in infants and toddlers with perinatal brain injury.	baseline (Day 1), post-intervention (Day 12), 3 month follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline MEP Amplitude	MEP amplitude will be reported in millivolts (mV), measured from electromyography recordings of the target muscle.	baseline (Day 1), post-intervention (Day 12), 3 month follow-up
Percent change in Mini-Assisting Hand Assessment (mini-AHA) score from baseline to end of treatment	The mini-AHA evaluates how effectively infants with unilateral upper extremity impairment use their affected hand during bimanual play activities. Scores are reported on a standardized 0-100 scale, with higher scores indicating greater functional use of the affected hand and lower scores indicating less functional use.	baseline (Day 1), post-intervention (Day 12), 3 month follow-up
Change in Quality of Upper Extremity Skills Test (QUEST) score from baseline	This is a measure of movement, scored in several domains: dissociated movement (joint mobility), grasp (holding and manipulating objects), protective extension (reflex reactions), and weight bearing assessments. It is scored from 0 to 100 where higher scores mean better movement. Change in QUEST score from baseline will be used to assess changes in upper extremity function following the intervention.	baseline (Day 1), post-intervention (Day 12), 3 month follow-up
Bayley Scales of Infant Development (Bayley-4; Fine Motor subtest)	The Bayley Scales of Infant and Toddler Development, Fourth Edition (Bayley-4) Fine Motor subtest evaluates fine motor skills, including reaching, grasping, object manipulation, and hand-eye coordination. Scores are standardized based on age and range from 1 to 19, with a normative mean of 10 and standard deviation of 3. Scores in the range of 8-12 are generally considered within the typical range for age. Higher scores indicate more advanced motor development.	baseline (Day 1), post-intervention (Day 12), 3 month follow-up
Bayley Scales of Infant Development (Bayley-4; Gross Motor subtests)	The Bayley Scales of Infant and Toddler Development, Fourth Edition (Bayley-4) Gross Motor subtest evaluates gross motor skills, including posture, sitting, crawling, standing, walking, and other age-appropriate movement abilities. Scores are standardized based on age and range from 1 to 19, with a normative mean of 10 and standard deviation of 3. Scores in the range of 8-12 are generally considered within the typical range for age. Higher scores indicate more advanced motor development.	baseline (Day 1), post-intervention (Day 12), 3 month follow-up
Gross Motor Function Measure (GMFM-88)	The Gross Motor Function Measure-88 (GMFM-88) evaluates gross motor function across five domains: lying and rolling, sitting, crawling and kneeling, standing, and walking, running, and jumping. Items are scored on a 4-point scale and converted to dimension and total scores ranging from 0 to 100. Higher scores indicate better gross motor function and greater ability to perform age-appropriate motor activities.	baseline (Day 1), post-intervention (Day 12), 3 month follow-up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
MEP Amplitude	Motor-evoked potential (MEP) amplitude measures the strength of the muscle response produced after a brief magnetic pulse is applied to the brain using single-pulse transcranial magnetic stimulation (spTMS). Larger amplitudes indicate stronger communication between the brain and the target muscle. MEP amplitude will be reported in millivolts (mV).	baseline (Day 1), post-intervention (Day 12), 3 month follow-up
MEP Threshold	Motor-evoked potential (MEP) threshold is the minimum level of magnetic stimulation needed to produce a muscle response. Lower thresholds generally indicate that the pathway between the brain and muscle can be activated more easily. MEP threshold will be reported as a percentage of maximum stimulator output (%MSO).	baseline (Day 1), post-intervention (Day 12), 3 month follow-up
Cortical Map Topography	Cortical map topography describes the location and distribution of brain areas that produce muscle responses when stimulated using single-pulse transcranial magnetic stimulation (spTMS). Changes in the size, location, or organization of these areas over time may reflect changes in brain connectivity and neuroplasticity.	baseline (Day 1), post-intervention (Day 12), 3 month follow-up

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Investigators: Principal Investigator: Bernadette Gillick, PhD, MSPT, UW School of Medicine and Public Health

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: July 27, 2026
• First Submitted That Met QC Criteria: July 27, 2026
• First Posted (Actual): July 31, 2026

Study Record Updates

• Last Update Posted (Actual): July 31, 2026
• Last Update Submitted That Met QC Criteria: July 27, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: intracranial hemorrhage; perinatal stroke; Constraint-Induced Movement Therapy (CIMT); transcutaneous auricular vagus nerve stimulation (taVNS); hypoxic-ischemic encephalopathy (HIE); hemiplegic cerebral palsy (CP); motor-evoked potentials (MEPs); Single Pulse Transcranial Magnetic Stimulation (spTMS)
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Hemorrhage; Brain Ischemia; Signs and Symptoms, Respiratory; Hypoxia, Brain; Hypoxia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hypoxia-Ischemia, Brain; Intracranial Hemorrhages; Therapeutics; Physical Therapy Modalities; Exercise Therapy; Rehabilitation; Constraint Induced Movement Therapy
• Other Study ID Numbers: 2026-0790; ICTR Pilot Award (Other Identifier: UW Madison); Protocol Version 6/17/26 (Other Identifier: UW Madison); SMPH/Pediatrics/Dev & Reh Med (Other Identifier: UW Madison)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes