Brain State-dependent Stimulation to Improve Movement

NCT05103176 | Completed Results

• 2 other identifiers: HUM001866371R21NS118055-01A1
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

Repetitive transcranial magnetic stimulation (rTMS) is a powerful tool to non-invasively modulate brain circuits, brain plasticity, and behavior. This proposal will test the hypothesis that controlling behavioral state during focal multi-day rTMS of a brain region involved in grasping movements will enhance the functional specificity of the neuromodulation action among distributed brain regions involved in voluntary motor control and concomitantly improve manual dexterity. Results from this study will be used to optimize rTMS therapy for individuals with neuromotor impairments by controlling behavioral state to improve the efficacy of rTMS treatment. Healthy volunteers that qualify for this study will have motor skill assessments and basic neuromotor testing (using neurophysiology with TMS and functional Magnetic Resonance Imaging (fMRI) scans). Participants will be asked to come in for up to nine sessions that include 1 screening session, 5 consecutive daily rTMS sessions and 3 assessment sessions with resting-state and task-based fMRI, neurophysiology with TMS, and hand motor tasks over the course of 3-4 weeks.

Conditions

Healthy

Keywords

fMRI; TMS; brain stimulation; theta burst; posterior parietal cortex; motor control; grasping

Outcome Measures

Primary Outcomes (4)

• Percentage Change in the Time to Complete the Nine-hole Peg Test (9-HPT) to Immediate Post-intervention

  9-hole peg test (9-HPT) is a manual dexterity measure in which a participant must place 9 pegs in board with 9 holes, and remove all 9 pegs upon the insertion of all 9 pegs. This is completed with one peg at a time, and only one hand is used. For our study, only the right hand was used. The performance is estimated as the time required to complete the task (seconds). A lower time in seconds is indicative of a better score. For percent change in performance, a higher positive percent is indicative improved performance.

  Baseline and immediately post-intervention (session 6, up to Day 15), up to 30 minutes

• Percentage Change in Amplitude of Motor Evoked Potential (MEP) to Immediate Post-intervention.

  Motor cortical excitability is measured by electromyography using MEPs (motor evoked potentials) elicited by TMS (Transcranial magnetic stimulation) to a motor hotspot determined before collection of baseline (baseline occurs before intervention) MEP (motor evoked potential) collection. It was assessed in session 1, 3, 4, 5, 6, and 7, although only session 6 is reported here. An increase in MEPs (motor evoked potentials) is indicative of increased cortical excitability. A positive increase in MEP (motor evoked potential) percent change is indicative of increased cortical excitability.

  Baseline and immediately post-intervention (session 6, up to Day 15), up to 60 minutes

• Change From Baseline Functional Connectivity to PPC Stimulation Target Within the Cortical Grasping Network to Immediate Post-intervention.

  Resting-state connectivity of low frequency BOLD (blood oxygenation level dependent) fluctuations for a seed at the PPC (posterior parietal cortex). The original analysis was a time-series correlation (Pearson's R) of resting state fMRI data between two regions of interest. The Z-score a Fisher's r-to-z transform. 0 for the Z value means that the pearson's correlation was also 0, positive means positive correlation and negative means it was a negative correlation. Therefore, standard deviations above the mean represented greater connectivity between the regions of interest. There were no clinically relevant thresholds to consider. The two time points being compared were scans from session 2 and session 7.

  Baseline (scan acquired during session 2) and immediate post-intervention (scan acquired after intervention during session 7, up to day 20), up to 60 minutes

• Change From Baseline Blood Oxygen Level-Dependent (BOLD) Activation, Voxelwise in the Cortical Grasp Network to Immediate Post-intervention.

  Parietal-frontal cortical grasping network defined by BOLD change during precision force-tracking task. t-test statistics were acquired for BOLD activation (estimated with univariate GLMs within each individual) from scans pre and post (session 2 and 7) with free surfer software. We ran univariate GLMs for each session for each individual that gave regression coefficients (beta values) for each voxel. We calculated a t-stat for each of those beta-values (each person and session we have a t-stat for our contrast of interest at each voxel). We averaged these across region of interest for each person/session. We ran another paired t-test at the group level to test pre vs post differences. SD shows t-stat variability across people in respective groups. A t-stat of 0 shows no BOLD change, a large positive t-stat shows increase BOLD change (increased connectivity, better outcome), and a large negative t-stat shows decrease BOLD change (decreased connectivity, worse outcome) pre vs post.

  Baseline (scan acquired during session 2) and immediate post-intervention (scan acquired after intervention during session 7, up to day 20), up to 60 minutes

Secondary Outcomes (12)

• Percentage Change in the Time to Complete the Nine-hole Peg Test (9-HPT) to 1-week Post-intervention

  Baseline and 1-week post intervention (session 8 or 9, approximately 1 week after session 7, up to day 30), up to 30 minutes

• Percentage Change in Amplitude of Motor Evoked Potential (MEP) to 1-week Post-intervention.

  Baseline and 1-week post-intervention (during session 8 or 9, approximately 1 week after session 7, up to day 30), up to 60 minutes

• Change From Baseline Functional Connectivity to PPC Stimulation Target Within the Cortical Grasping Network to 1-week Post-intervention.

  Baseline (scan acquired during session 2) and 1-week post-intervention (scan during session 8 or 9, approximately 1 week after session 7, up to day 30), up to 60 minutes

• Change From Baseline Blood Oxygen Level-Dependent (BOLD) Activation, Voxelwise in the Cortical Grasp Network to 1-week Post-intervention.

  Baseline (scan acquired during session 2) and 1-week post-intervention (scan during session 8 or 9, approximately 1 week after session 7, up to day 30), up to 60 minutes

• Change From Baseline Blood Oxygen Level-Dependent (BOLD) Activation, Voxelwise in Whole Brain to Immediate Post-intervention.

  Baseline (scan acquired during session 2) and immediate post-intervention (scan acquired after intervention during session 7, up to day 20), up to 60 minutes

Study Arms (3)

To PPC, with concurrent task

EXPERIMENTAL

This arm will receive intermittent theta bust stimulation to the PPC site while subjects perform a grasp task

Device: TMS; Behavioral: Object directed grasping

To PPC, without a concurrent task

EXPERIMENTAL

This arm will receive intermittent theta bust stimulation to the PPC site without a concurrent task

Device: TMS

To vertex, with concurrent task

EXPERIMENTAL

This arm will receive intermittent theta bust stimulation to the vertex site (control condition) while subjects perform a grasp task

Device: TMS; Behavioral: Object directed grasping

Interventions

TMS DEVICE

A MagPro X100 magnetic stimulator with a 90mm figure-8 coil (MC-B70, MagVenture Inc.) will be utilized to deliver brain stimulation. All participants will receive five consecutive days of stimulation. The 3-minute session of intermittent Theta Burst Stimulation (iTBS) will consist of 10 bursts of high-frequency stimulation (a 2 s train of 3 biphasic waveform pulses at 50 Hz repeated every 200 ms at 80% AMT) repeated every 10 s for a total of 190 s (600 pulses) to the target area. The target area will be located using BrainSight2 neuronavigation system. The baseline structural scan obtained during the scan 1 will be utilized for this localization process.

Also known as: MagPro X100 TMS system

To PPC, with concurrent task; To PPC, without a concurrent task; To vertex, with concurrent task

Object directed grasping BEHAVIORAL

Subjects will perform a precision grip with the right hand towards either a small or large target object positioned in front of them. The illumination of an LED (green or red) will instruct the subject to plan a precision grip towards either a small or large target object positioned in front of them. After \~1 second, the LED will extinguish and cue subjects to execute the intended object-directed hand action. The presentation of the visual stimuli will be synchronized with the iTBS stimulation, which will occur 800ms before the onset of every "GO" cue in order to modulate cortical activity during both the planning and execution phase of the action.

To PPC, with concurrent task; To vertex, with concurrent task

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Women of child bearing age cannot be pregnant or trying to become pregnant
• Ability to tolerate small, enclosed spaces without anxiety
• Ability and willingness to give informed consent to participate
• No history of neurological disorder
• Right handed
• English speaking

You may not qualify if:

• Are left-handed
• Are younger than 18 or older than 50 years old
• Women who are pregnant, suspect they are pregnant, or are attempting to become pregnant
• Have metal anywhere in the head, excluding the mouth
• Have a pacemaker, deep brain stimulator, vagus nerve stimulator or any other medically implanted device
• Have cochlear hearing implants
• Are taking GABAergic, NDMA-receptor antagonist, or other drug known to influence neural receptors
• Have any of the below conditions that would put participants at increased risk of having a seizure: a personal or family history of seizure/epilepsy, taking prescription drugs that lower the threshold for seizures, recent history of excessive alcohol consumption, history of alcohol addiction/dependence, recent history of recreational drug use, history of drug addiction/dependence
• Have been diagnosed with any of the following: a stroke, brain hemorrhage, brain tumor, encephalitis, multiple sclerosis, Parkinson's disease or Alzheimer's disease, depression in the past 6 months, attention deficit disorder, schizophrenia, manic depressive (bipolar) disorder, normal pressure hydrocephalus or increased intra-cranial pressure, diabetes requiring insulin treatment, any serious heart disorder or liver disease
• Have had a migraine in the past month

Sponsors & Collaborators

• University of Michigan: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48170, United States

Location

Results Point of Contact

• Title: Dr. Michael Vesia, Assistant Professor
• Organization: University of Michigan

mvesia@umich.edu

734 763-3905

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Subjects will be randomly assigned to one of the 3 arms of the study. Subjects will be blind to which arm they are in, however, will be aware of what is involved within each of the arms.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Movement Science

Model Details: The investigators will use a randomized block design with up to 65 subjects in up to nine sessions. The first session will screen subjects before enrolling subjects into study. Three sessions will collect functional magnetic resonance imaging (fMRI) scans, neurophysiological measures with TMS, and behavioral measures. After a baseline testing session, subsequent sessions over five days will entail rTMS, followed by two assessments to evaluate the effects of stimulation on brain and behavior. rTMS intervention sessions will consist of: (i) Posterior Parietal Cortex (PPC) stimulation alone, (ii) PPC stimulation paired with a grasp task or (iii) vertex stimulation (as a control condition) paired with a grasp task. Duration of study: Approximately 3-4 weeks (depending upon scheduling)

Study Record Dates

• First Submitted: October 19, 2021
• First Posted: November 2, 2021
• Study Start: February 15, 2022
• Primary Completion: May 31, 2023
• Study Completion: May 31, 2023
• Last Updated: April 4, 2025
• Results First Posted: April 4, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Within 1 year of the conclusion of the study
• Access Criteria: No additional access restrictions will be placed on the de-identified data beyond those that are standard for the NIH.

Locations

US (1)