Noninvasive Modulation of Motivational Brain Regions in Healthy Volunteers

NCT04972786 | Completed Results DMC FDA Device

• 1 other identifier: 20-623
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

21 healthy control participants will be recruited. On Day 1 they will complete reward-guided decision making tasks and questionnaires followed by a functional magnetic resonance imaging (fMRI) scan. On Days 2 and 3 they will receive repetitive transcranial magnetic stimulation (rTMS) targeting a specific part of the brain called the dorsal anterior cingulate cortex (dACC) or sham stimulation, and will then repeat a subset of the same decision making tasks and fMRI sequences. If brain stimulation modifies decision making and dACC activity, it could represent a novel way of treating patients with neural circuit deficits that impede motivated behavior. Of particular relevance to the current trial, this rTMS study will run in parallel with a study of apathy (i.e., diminished motivation) in patients with traumatic brain injury (TBI), with the goal of eventually leading to a patient-centered trial of rTMS treatment for this disruptive neuropsychiatric symptom.

Conditions

Traumatic Brain Injury

Outcome Measures

Primary Outcomes (6)

• dACC BOLD Signal (After Active rTMS Session)

  Encoding of trial-by-trial immediate expected value (IEV) in dorsal anterior cingulate cortex (dACC) region-of-interest that was targeted with rTMS. Expressed in units of BOLD % signal change. This primary outcome reflects IEV encoding in this region immediately after active rTMS.

  30 minutes post-rTMS

• Immediate Expected Value (IEV; After Active rTMS Visit)

  A normative computational model (POMDP) is run to fit behavioral performance on a 3-armed bandit reinforcement learning task. Weighting of immediate expected value (IEV) on this model can be generated for each subject, indicating the degree to which they relied on immediate value to drive their decisions. This between-subjects IEV parameter reflects a standardized coefficient from a multinomial logistic regression (softmax) model. Higher values indicate a greater tendency to rely on IEV when making choices.

  30 minutes post-rTMS

• Effort-Based Discounting (After Active rTMS)

  Participants make a series of effort - value tradeoff decisions on our Effort-Based Decision-Making task. Values reflect a standardized coefficient of the random subject-level intercept from a hierarchical logistic regression model fit with an interaction term, between effort and value, to index "effort-based discounting" of reward (i.e., the degree to which increases in effort level change the motivational salience of reward value on decisions). Higher values indicate a greater tendency to de-value rewards based on increasing effort level.

  30 minutes post-rTMS

• dACC BOLD Signal (After Sham rTMS Session)

  Encoding of trial-by-trial immediate expected value (IEV) in dorsal anterior cingulate cortex (dACC) region-of-interest that was targeted with rTMS. Expressed in units of BOLD % signal change. This primary outcome reflects IEV encoding in this region immediately after sham rTMS.

  30 minutes post-rTMS

• Immediate Expected Value (IEV; After Sham rTMS Visit)

  A normative computational model (POMDP) is run to fit behavioral performance on a 3-armed bandit reinforcement learning task. Weighting of immediate expected value (IEV) on this model can be generated for each subject, indicating the degree to which they relied on immediate value to drive their decisions. This between-subjects IEV parameter reflects a standardized coefficient from a multinomial logistic regression (softmax) model. Higher values indicate a greater tendency to rely on IEV when making choices.

  30 minutes post-rTMS

• Effort-Based Discounting (After Sham rTMS)

  Participants make a series of effort - value tradeoff decisions on our Effort-Based Decision-Making task. Values reflect a standardized coefficient of the random subject-level intercept from a hierarchical logistic regression model fit with an interaction term, between effort and value, to index "effort-based discounting" of reward (i.e., the degree to which increases in effort level change the motivational salience of reward value on decisions). Higher values indicate a greater tendency to de-value rewards based on increasing effort level.

  30 minutes post-rTMS

Study Arms (2)

Sham rTMS

SHAM COMPARATOR

Participants will receive sham rTMS for 10-20 minutes.

Device: Repetitive Transcranial Magnetic Stimulation

Active rTMS

ACTIVE COMPARATOR

Participants will receive active rTMS for 10-20 minutes.

Device: Repetitive Transcranial Magnetic Stimulation

Interventions

Repetitive Transcranial Magnetic Stimulation DEVICE

TMS pulses will be delivered through an air-cooled coil in either a figure-eight or double-cone shape, with the latter being particularly useful for targeting deeper structures such as dACC. The first phase of the TMS protocol will involve a standardized motor-thresholding procedure, wherein peripheral responses evoked by single TMS pulses are recorded via an electromyographic recording device. In this phase, the TMS coil's stimulation intensity is titrated to a level that is comfortable yet effective at reliably exciting neuronal populations orthogonal to the coil (50% motor-evoked potentials ≥50 microvolts; typical duration≈20-40 mins). Then repetitive TMS (rTMS) will be administered to a pre-determined cortical target based on the individual's pre-TMS fMRI scan using a Localite Neuronavigation system (duration≈10-20 mins). The rTMS protocol will involve the delivery of a train of TMS pulses over a cortical target prior to performance of behavioral tasks during a post-rTMS fMRI scan.

Active rTMS; Sham rTMS

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• or more years of education
• ability to provide informed consent independently

You may not qualify if:

• Non-fluency in English
• Prior history of seizure
• contraindications to MRI (metal in the body)
• history of substance abuse (excluding moderate alcohol/cannabis usage)
• medical diagnosis of psychosis or mania

Sponsors & Collaborators

• University of New Mexico: lead

Study Sites (1)

University of New Mexico Domenici Hall

Albuquerque, New Mexico, 87131, United States

Location

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Results Point of Contact

• Title: Dr. Jeremy Hogeveen
• Organization: University of New Mexico

jhogeveen@unm.edu

773-941-2182

Study Officials

• Jeremy Hogeveen, PhD

  University of New Mexico

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Magventure rTMS device enables double blinding. Participant group assignment will be blind to the participant, investigator, and outcomes assessor until all subject data has been collected, at which point the group assignment will be unblinded.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Sham versus active rTMS to dACC

Study Record Dates

• First Submitted: July 13, 2021
• First Posted: July 22, 2021
• Study Start: August 1, 2021
• Primary Completion: June 21, 2023
• Study Completion: June 21, 2023
• Last Updated: July 16, 2024
• Results First Posted: July 16, 2024

Record last verified: 2024-06

Locations

US (1)