Theta Burst Transcranial Magnetic Stimulation of Fronto-parietal Networks: Modulation by Mental State

NCT04010461 | Completed Results FDA Device

• 2 other identifiers: HUM00165239R21MH120633-01
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to improve understanding of the way transcranial magnetic stimulation (TMS), a form of non-invasive brain stimulation, affects the brain. The study hypothesis that when theta burst stimulation (TBS) is applied during a controlled mental state, network changes will be facilitated, compared to stimulation when mental state is uncontrolled. This study will focus on the dorsolateral prefrontal cortex (dlPFC) and the associated frontoparietal network (FPN), which subserves cognitive control - the ability to flexibly adapt and regulate behavior, an ability known to be impaired in neuropsychiatric conditions such as depression and dementia. Healthy volunteers that qualify for this study will have psychological assessments and cognitive measures (due to Covid, some of these were done via teleconference), as well as functional Magnetic Resonance Imaging (fMRI) scans, completed after administration of TMS. Participants will be asked to come in for a total of five visits that include; a screening and assessment visit; a baseline functional magnetic resonance imaging (fMRI) scan, followed by TMS session; Visits 3, 4, and 5 will be the experimental TMS session, followed by fMRI scan.

Conditions

Healthy

Keywords

functional magnetic resonance imaging; Transcranial Magnetic Stimulation; dorsolateral prefrontal cortex

Outcome Measures

Primary Outcomes (4)

• 2-back Minus 1-back Blood Oxygen Level-Dependent (BOLD) Activation, Voxelwise in FPN

  Fronto-parietal network (FPN) defined by BOLD change while subject performed the n-back working memory task, contrasting high (2-back) versus low (1-back) loads. Using the SPM12 package, data were normalized per standard, open source routines. Using a General Linear Model framework, a model was estimated with regressors (after convolution with hemodynamic response function) for 2-back \& 1-back conditions for each subject to predict BOLD change each day (arm).For analysis of group effects, second-level, between-subject analyses on normalized images of the 2-back minus 1-back beta estimate from the first level were entered into regression models, with mean frame displacement as a co-variate of no-interest to test contrasts between the arms/interventions. Using a FPN mask, the eigenvalues from the second-level estimates were extracted and entered into the analysis as an outcome measure. Note: eigenvalues are arbitrary units. Larger values indicate more BOLD signal.

  60 minutes after TMS during fMRI

• Frontoparietal Network (FPN) Connectivity to Dorsolateral Prefrontal Cortex (dlPFC) Theta Burst Stimulation (TBS) Target

  Analysis of resting-state connectivity was performed used the CONN toolbox, using standard techniques to demonstrate connectivity between a spherical seed placed on each participant's locus of dlPFC stimulation, and the rest of the brain. Connectivity (correlations of BOLD signal) was first calculated for each participant, and then spatially averaged in MNI brain space, between participants. A 'cluster' of connectivity was identified, only if the number of voxels (thresholded at P \<0.001) exceeded the count of 25. The outcome measure here is a count of the number of clusters exceeding this threshold, across all subjects. It represents significant connectivity between the site of stimulation and that cluster in the brain, for all subjects.

  60 minutes after TMS during fMRI

• Cerebral Blood Flow (rCBF) at Stimulation Target

  Regional cerebral blood flow measured at the site of theta burst stimulation (TBS) in milliliters per 100 mg tissue per minute

  15 minutes after TMS during fMRI

• Accuracy to 2-back

  Correct responses to letter stimuli, as a percentage of all responses

  60 minutes after TMS during fMRI

Secondary Outcomes (4)

• 2-back Minus 1-back BOLD Activation, Voxelwise in Whole Brain

  60 minutes after TMS during fMRI

• Measure Cerebral Blood Flow (rCBF) in FPN

  15 minutes after TMS during fMRI

• Median Reaction Time (RT) in 2-back

  60 minutes after TMS during fMRI

• D-prime in 2-back

  60 minutes after TMS during fMRI

Study Arms (3)

TMS to dlPFC, without a concurrent task

EXPERIMENTAL

TMS (intermittent theta burst stimulation) will be applied to the dlPFC, when subjects are in a resting state

Device: TMS; Behavioral: n-back working memory task

TMS to vertex, without concurrent task

EXPERIMENTAL

TMS (intermittent theta burst stimulation) will be applied to the cerebral vertex, when subjects are in a resting state

Device: TMS; Behavioral: n-back working memory task

TMS to dlPFC, during task

EXPERIMENTAL

TMS (intermittent theta burst stimulation) will be applied to the dlPFC, when subjects are engaged in the n-back working memory task

Device: TMS; Behavioral: n-back working memory task

Interventions

TMS DEVICE

Intermittent theta burst stimulation TMS applied to the cortex to excite cerebral cortex

Also known as: intermittent theta burst stimulation (iTBS)

TMS to dlPFC, during task; TMS to dlPFC, without a concurrent task; TMS to vertex, without concurrent task

n-back working memory task BEHAVIORAL

Subjects perform an executive function task, in which they view the serial presentation of letters and decide whether or not a letter matches a letter presented 'n' letters back (2 letters or 1 letter)

TMS to dlPFC, during task; TMS to dlPFC, without a concurrent task; TMS to vertex, without 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 can not be pregnant or trying to become pregnant
• Ability to tolerate small, enclosed spaces without anxiety
• Size compatible with scanner gantry, e. g. men over 6 feet tall that weigh more than 250 lbs, men under 6 feet tall that weigh over 220 lbs, women over 5'11" tall that weigh more than 220 lbs, or women under 5'10" tall that weigh more than 200 lbs. Subjects of these weights or greater typically have difficult fitting into the fMRI scanner properly
• Ability and willingness to give informed consent to participate
• Alcohol or drug dependence (if in remission for greater than 5 years)

You may not qualify if:

• History of past or current mental illness (except simple phobias)
• History of closed head injury, for example, loss of consciousness \> approximately 5 minutes, hospitalization, neurological sequela;
• Metals, implants or metallic substances within or on the body that might cause adverse effects to the subject in a strong magnetic field, or interfere with image acquisition (for example; aneurysm clips, retained particles or metal workers with exposures, neurostimulators, foil-backed transdermal patches, carotid or cerebral stents, cerebral spinal fluid (CSF) shunts; magnetic dental implants, ferromagnetic ocular implants, pacemakers, and automatic implantable defibrillators).
• Prescription or non-prescription, with psychotropic effects (birth control medications allowed)
• First-degree family members with a history of epilepsy
• History of serious neurological illness or current medical condition that could compromise brain function, such as liver failure

Sponsors & Collaborators

• University of Michigan: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48170, United States

Location

Related Publications (1)

• Taylor SF, Lee TG, Jonides J, Tso IF, Hernandez-Garcia L. Theta Burst Transcranial Magnetic Stimulation of Fronto-Parietal Networks: Modulation by Mental State. J Psychiatr Brain Sci. 2020;5:e200011. doi: 10.20900/jpbs.20200011. Epub 2020 May 26.

  PMID: 32613082 DERIVED

Limitations and Caveats

Because of technical problems, performance measure for accuracy and d-prime were not available for 24 subjects in the 'Active' condition.

Results Point of Contact

• Title: Stephan Taylor
• Organization: University of Michigan

sftaylor@med.umich.edu

(734) 936-4955

Study Officials

• Stephan Taylor, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: All subjects will receive all interventions in a cross-over design. The three intervention sessions (visits 3, 4 \& 5) will be given in counter-balanced order, stratified by gender. Subjects will be blind to the nature of the questions being asked; however, they will be told that different stimulation paradigms will be used, which will be evident to the subjects as they go through the procedures.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry

Model Details: All participants will have 3 MRI sessions subsequent to the baseline visit and these will occur in a counterbalanced order.

Study Record Dates

• First Submitted: July 3, 2019
• First Posted: July 8, 2019
• Study Start: November 11, 2019
• Primary Completion: March 29, 2022
• Study Completion: March 29, 2022
• Last Updated: October 6, 2023
• Results First Posted: October 6, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: De-identified data will be entered into the NDA 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 NDA.

Locations

US (1)