HealthyBrainSTIMNCT05103176
Brain State-dependent Stimulation to Improve Movement
A study testing TMS and Object directed grasping in people with Healthy, run by University of Michigan at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- TMS and Object directed grasping
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Feb 2022to 31 May 2023
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
- MRI specific exclusion criteria: Any relevant history of open-heart surgery, artificial heart valve, brain aneurysm surgery, braces or extensive dental work, cataract surgery or lens implant, or artificial limb or joint. History of foreign metallic object in the body such as bullets, BB's, pellets, shrapnel, or metalwork fragments. Claustrophobia, have uncontrollable shaking, or cannot lie still for one hour.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Leveraging Behavioral State to Enhance Specificity of Non-invasive Brain Stimulation on Motor Circuits
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.
Read the detailed description
This study will examine a particular type of rTMS, known as theta burst stimulation (TBS), which has been shown to induce longer lasting effects than other forms of rTMS, making TBS an important tool for therapeutic applications. While TBS provides relatively focal stimulation, effects on the brain occur through interconnected networks in ways that are poorly understood. Moreover, stimulation is highly state-dependent, and the use of rTMS in most therapeutic settings, such as the treatment of motor impairments, leaves behavioral state uncontrolled. Augmenting rTMS therapy by inducing specific behavioral states is an attractive idea for improving therapeutic rTMS, but the relevant knowledge base is sparse. To address this critical gap, this exploratory R21 proposal will examine the effects of TBS and behavioral state on brain and motor behavior. The investigators will test the broad hypothesis that when TBS is applied during a controlled behavior state, motor function will be facilitated, compared to stimulation when behavioral state is uncontrolled. The investigators will focus on the posterior parietal cortex (PPC), and associated parietofrontal circuits, which subserve skilled grasp control, an ability known to be impaired in stroke, traumatic brain injury, and other motor disorders. The investigators will collect functional magnetic resonance imaging (fMRI), neurophysiological measures with TMS, and behavioral measures in all subjects for three different interventions.
In Aim 1, the investigators will show improvement in action performance by manipulating the behavioral state during PPC stimulation.
In Aim 2, the investigators will demonstrate modulation of neurophysiological aftereffects of PPC stimulation on motor output by manipulating behavioral state.
In Aim 3, the investigators will assess the relationship between brain connectivity, plasticity and behavior in response to the behavioral state during brain stimulation.
Impact: Results will provide insights into the effects of rTMS and behavioral state on the brain and behavior. This knowledge will lay a mechanistic foundation for future studies to show how controlling behavioral state during rTMS can improve therapeutic efficacy in neurological disorders.
- Conditions
- Healthy
- Being tested
- TMS, Object directed grasping
- Keywords
- fMRI, TMS, brain stimulation, theta burst, posterior parietal cortex, motor control, grasping
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMSDevice
Also called MagPro X100 TMS system
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.
Object directed graspingBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| To PPC, with concurrent task | Experimental | This arm will receive intermittent theta bust stimulation to the PPC site while subjects perform a grasp task Receives: 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 Receives: 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 Receives: Device: TMS; Behavioral: Object directed grasping |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
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.
Measured: 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.
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. 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.
Measured: 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.
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.
Measured: 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.
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 8/9) 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.
Measured: 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.
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.
Measured: 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 Whole Brain to 1-week 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 8/9) 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.
Measured: 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
Percentage Change in Accuracy to Precision Force-tracking Task to Immediate Post-intervention
The force tracking task measures one's ability to regulate their grip force. For this task, the participant must adjust their grip of an object to move the cursor in order to correspond with a constantly moving target. The outcome of this measure is the squared distance (error) from the cursor to the target in the precision force-tracking task, estimated as the root mean squared error (RMSE). A lower root mean squared error (RMSE) is indicative of better performance and better ability of a participant to regulate their grip force. A higher percent change in root mean squared error (RMSE) accuracy is indicative of better performance and better ability of a participant to regulate their grip force. It was assessed in session 2, 7, and 8/9, although only session 2 and 7 are reported here.
Measured: Baseline(during fMRI during session 2) and immediate post-intervention (during fMRI following stimulation during session 7, up to day 20), up to 60 minutes
Percentage Change in Accuracy to Precision Force-tracking Task to 1-week Post-intervention
The force tracking task measures one's ability to regulate their grip force. For this task, the participant must adjust their grip of an object to move the cursor in order to correspond with a constantly moving target. The outcome of this measure is the squared distance (error) from the cursor to the target in the precision force-tracking task, estimated as the root mean squared error (RMSE). A lower root mean squared error (RMSE) is indicative of better performance and better ability of a participant to regulate their grip force. A higher percent change in root mean squared error (RMSE) accuracy is indicative of better performance and better ability of a participant to regulate their grip force. It was assessed in session 2, 7, and 8/9, although only session 2 and 8/9 are reported here.
Measured: Baseline(during fMRI during session 2) and 1-week post-intervention (during fMRI during session 8 or 9, about a week following last intervention, up to day 30), up to 60 minutes
Percentage Change in the Mean Choice Reaction Time to Immediate Post-intervention
The cRT (2-choice reaction time control task) is a measurement of visuomotor abilities that are non specific to the reach-to-grasp movement. The outcome for this measure is the mean reaction time for subjects responding in the cRT (2-choice reaction time control task), for correct responses. A lower mean reaction time in seconds is indicative of better visuomotor performance (non specific to the reach-to-grasp movement). A positive percent change in cRT (2-choice reaction time control task) is indicative of better visuomotor performance (non specific to the reach-to-grasp movement).
Measured: Baseline and immediately post-intervention (session 6, up to Day 15), up to 30 minutes
Percentage Change in the Mean Choice Reaction Time to 1-week Post-intervention
The cRT (2-choice reaction time control task) is a measurement of visuomotor abilities that are non specific to the reach-to-grasp movement. The outcome for this measure is the mean reaction time for subjects responding in the cRT (2-choice reaction time control task), for correct responses. A lower mean reaction time in seconds is indicative of better visuomotor performance (non specific to the reach-to-grasp movement). A positive percent change in cRT (2-choice reaction time control task) is indicative of better visuomotor performance (non specific to the reach-to-grasp movement).
Measured: 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 the Normalized Motor Evoked Potential (MEP) Size to Immediate Post-intervention.
Parietal-motor functional connectivity is measured by electromyography using MEPs (motor evoked potentials) elicited by dual-site TMS (Transcranial magnetic stimulation) to the motor hotspot and a parietal region determined at baseline (baseline occurs before intervention), while subjects perform an object-directed grasp/subjects are at rest. An increase in MEPs (motor evoked potentials) is indicative of increased cortical excitability. A positive increase in MEP (motor evoked potential) percent change, or normalized MEP (motor evoked potential), is indicative of increased cortical excitability. It was assessed in session 1, 3, 4, 5, 6, and 7, although only session 6 is reported here.
Measured: Baseline and immediately post-intervention (session 6, up to Day 15), up to 60 minutes
Percentage Change in the Normalized Motor Evoked Potential (MEP) Size to 1-week Post-intervention.
Parietal-motor functional connectivity is measured by electromyography using MEPs (motor evoked potentials) elicited by dual-site TMS (Transcranial magnetic stimulation) to the motor hotspot and a parietal region determined at baseline (baseline occurs before intervention), while subjects perform an object-directed grasp/subjects are at rest. An increase in MEPs (motor evoked potentials) is indicative of increased cortical excitability. A positive increase in MEP (motor evoked potential) percent change, or normalized MEP (motor evoked potential), is indicative of increased cortical excitability.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2021
- Study start15 Feb 2022
- Primary completion31 May 2023
- Study completion31 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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)
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Principal investigator, Michael Vesia, PhD, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05103176
- Sponsor's protocol ID
- HUM00186637
- Other IDs
- 1R21NS118055-01A1
- Acronym
- BrainSTIM
- Status last verified
- Mar 2025
- First submitted
- 19 Oct 2021
- Last updated
- 4 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The PI will share information about this/these trial(s) via timely registration, updates, and results reporting in ClinicalTrials.gov in accordance with NIH policy. De-identified data will be entered into the in ClinicalTrials.gov in accordance with NIH policy within 1 year of the conclusion of the study. In accord with NIH regulations, the investigators will make the data and relevant documentation available to other investigators upon acceptance of the main findings from the study for publication. The investigators will share analysis tools as they are developed. Because the collected data are to remain anonymous, only a subject number will identify all data. To further protect the privacy and confidentiality of the data, data and documentation will be made available only under a data-sharing agreement that provides for restrictions for the transferring of data to others and a commitment that the data will be used for research purposes only and not for a profit-making enterprise.
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Leveraging Behavioral State to Enhance Specificity of Non-invasive Brain Stimulation on Motor Circuits
- ClinicalTrials.gov ID
- NCT05103176
- Acronym / sponsor ID
- BrainSTIM / HUM00186637
- Conditions
- Healthy
- Keywords
- fMRI, TMS, brain stimulation, theta burst, posterior parietal cortex, motor control, grasping
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 15 Feb 2022 (actual)
- Primary completion
- 31 May 2023 (actual)
- Study completion
- 31 May 2023 (actual)
- First posted
- 2 Nov 2021 (actual)
- Results
- Posted 4 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study will examine a particular type of rTMS, known as theta burst stimulation (TBS), which has been shown to induce longer lasting effects than other forms of rTMS, making TBS an important tool for therapeutic applications. While TBS provides relatively focal stimulation, effects on the brain occur through interconnected networks in ways that are poorly understood. Moreover, stimulation is highly state-dependent, and the use of rTMS in most therapeutic settings, such as the treatment of motor impairments, leaves behavioral state uncontrolled. Augmenting rTMS therapy by inducing specific behavioral states is an attractive idea for improving therapeutic rTMS, but the relevant knowledge base is sparse. To address this critical gap, this exploratory R21 proposal will examine the effects of TBS and behavioral state on brain and motor behavior. The investigators will test the broad hypothesis that when TBS is applied during a controlled behavior state, motor function will be facilitated, compared to stimulation when behavioral state is uncontrolled. The investigators will focus on the posterior parietal cortex (PPC), and associated parietofrontal circuits, which subserve skilled grasp control, an ability known to be impaired in stroke, traumatic brain injury, and other motor disorders. The investigators will collect functional magnetic resonance imaging (fMRI), neurophysiological measures with TMS, and behavioral measures in all subjects for three different interventions.
In Aim 1, the investigators will show improvement in action performance by manipulating the behavioral state during PPC stimulation.
In Aim 2, the investigators will demonstrate modulation of neurophysiological aftereffects of PPC stimulation on motor output by manipulating behavioral state.
In Aim 3, the investigators will assess the relationship between brain connectivity, plasticity and behavior in response to the behavioral state during brain stimulation.
Impact: Results will provide insights into the effects of rTMS and behavioral state on the brain and behavior. This knowledge will lay a mechanistic foundation for future studies to show how controlling behavioral state during rTMS can improve therapeutic efficacy in neurological disorders.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
- Model description
- 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)
| Arm | Type | Receives |
|---|---|---|
| To PPC, with concurrent task | Experimental | Device: TMS, Behavioral: Object directed graspingThis arm will receive intermittent theta bust stimulation to the PPC site while subjects perform a grasp task |
| To PPC, without a concurrent task | Experimental | Device: TMSThis arm will receive intermittent theta bust stimulation to the PPC site without a concurrent task |
| To vertex, with concurrent task | Experimental | Device: TMS, Behavioral: Object directed graspingThis arm will receive intermittent theta bust stimulation to the vertex site (control condition) while subjects perform a grasp task |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TMSAlso: MagPro X100 TMS systemA 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. | Device | To PPC, with concurrent task, To PPC, without a concurrent task, To vertex, with concurrent task |
| Object directed graspingSubjects 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. | Behavioural | To PPC, with concurrent task, To vertex, with concurrent task |
Primary outcome
Percentage Change in the Time to Complete the Nine-hole Peg Test (9-HPT) to Immediate Post-intervention
Time frame: Baseline and immediately post-intervention (session 6, up to Day 15), up to 30 minutes
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.
Percentage Change in Amplitude of Motor Evoked Potential (MEP) to Immediate Post-intervention.
Time frame: Baseline and immediately post-intervention (session 6, up to Day 15), up to 60 minutes
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.
Change From Baseline Functional Connectivity to PPC Stimulation Target Within the Cortical Grasping Network to Immediate Post-intervention.
Time frame: 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
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.
Change From Baseline Blood Oxygen Level-Dependent (BOLD) Activation, Voxelwise in the Cortical Grasp Network to Immediate Post-intervention.
Time frame: 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
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.
12 secondary outcomes
Percentage Change in the Time to Complete the Nine-hole Peg Test (9-HPT) to 1-week Post-intervention
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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 Whole Brain to 1-week Post-intervention.
Time frame: 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
Percentage Change in Accuracy to Precision Force-tracking Task to Immediate Post-intervention
Time frame: Baseline(during fMRI during session 2) and immediate post-intervention (during fMRI following stimulation during session 7, up to day 20), up to 60 minutes
Percentage Change in Accuracy to Precision Force-tracking Task to 1-week Post-intervention
Time frame: Baseline(during fMRI during session 2) and 1-week post-intervention (during fMRI during session 8 or 9, about a week following last intervention, up to day 30), up to 60 minutes
Percentage Change in the Mean Choice Reaction Time to Immediate Post-intervention
Time frame: Baseline and immediately post-intervention (session 6, up to Day 15), up to 30 minutes
Percentage Change in the Mean Choice Reaction Time to 1-week Post-intervention
Time frame: 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 the Normalized Motor Evoked Potential (MEP) Size to Immediate Post-intervention.
Time frame: Baseline and immediately post-intervention (session 6, up to Day 15), up to 60 minutes
Percentage Change in the Normalized Motor Evoked Potential (MEP) Size to 1-week Post-intervention.
Time frame: 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
Results and safety
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Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. The PI will share information about this/these trial(s) via timely registration, updates, and results reporting in ClinicalTrials.gov in accordance with NIH policy. De-identified data will be entered into the in ClinicalTrials.gov in accordance with NIH policy within 1 year of the conclusion of the study. In accord with NIH regulations, the investigators will make the data and relevant documentation available to other investigators upon acceptance of the main findings from the study for publication. The investigators will share analysis tools as they are developed. Because the collected data are to remain anonymous, only a subject number will identify all data. To further protect the privacy and confidentiality of the data, data and documentation will be made available only under a data-sharing agreement that provides for restrictions for the transferring of data to others and a commitment that the data will be used for research purposes only and not for a profit-making enterprise.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing TMS and Object directed grasping in people with Healthy, run by University of Michigan at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage Change in the Time to Complete the Nine-hole Peg Test (9-HPT) to Immediate Post-intervention (time frame: Baseline and immediately post-intervention (session 6, up to Day 15), up to 30 minutes). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2025; AzTrials last refreshed its copy on 27 Oct 2026.