Reward Circuit Targeted iTBS

Manipulating the Reward Circuit With TMS

The objective of this study is to examine the effect of intermittent theta-burst transcranial magnetic stimulation (iTBS) targeting the reward circuit.

Study Overview

• Status: Recruiting
• Conditions: Transcranial Magnetic Stimulation
• Intervention / Treatment: Device: transcranial magnetic stimulation; Device: transcranial magnetic stimulation

Detailed Description

The study will examine the effect of medial prefrontal cortex (MPFC)-iTBS on the reward circuit, reward sensitivity, and anhedonia. The reward circuit will be assessed using functional MRI (fMRI) connectivity and activation during the Doors Task. Reward sensitivity will be assessed using an event-related potential called the reward positivity or RewP. The RewP will be measured using electroencephalography (EEG) during the Doors Task. Anhedonia will be measured using the Dimensional Anhedonia Ratings Scale (DARS).

The Doors Task was designed to examine reward processing in a simple, well-controlled paradigm. On each trial, participants select one of two doors. Gain (50 cents) or loss (25 cents) feedback is provided. Gains elicit a positive potential referred to as the RewP, while losses elicit a negative potential referred to as the feedback reward negativity (FRN). Gains also show increased activation in reward-related brain areas (e.g. ventral striatum) relative to losses in the fMRI signal.

Each participant will complete a baseline session including structural MRI, fMRI and EEG during the Doors task, and transcranial magnetic stimulation (TMS) motor thresholding. The ventral striatum (VS) will be identified on the structural MRI. The MPFC will be identified as a rostral-medial cortical area in prefrontal cortex with high connectivity to the VS. A control site, inion, will be identified using visual inspection of the skull.

Each participant will complete 2 weeks of iTBS sessions. Each week will target a different site (experimental: MPFC; control: inion). iTBS will be performed once a day for 5 consecutive days at each site, with order counter-balanced across participants in a cross-over design. 1 week of washout will follow each week of iTBS. At the end of each week, participants will perform the Doors task while being measured with EEG, and complete the DARS. At the end of the iTBS weeks, participants will also perform the Doors task while being measured with fMRI.

fMRI activation of the MPFC target and VS, and VS-MPFC fMRI connectivity will be compared at baseline, following the MPFC-iTBS week, and following the control-iTBS week. Changes specific to MPFC-iTBS will provide evidence of the effect of MPFC-iTBS on the reward circuit. The RewP and DARS will be compared at baseline, and after each week, respectively. Changes specific to MPFC-iTBS will provide evidence of the effect of MPFC-iTBS on the reward sensitivity and anhedonia. Changes that persist following washout will provide an indication of a lasting effect of MPFC-iTBS.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Derek Nee, PhD; Phone Number: 8506441963; Email: derek.evan.nee@gmail.com

Study Locations

• United States
  • Florida
    • Tallahassee, Florida, United States, 32306
      • Recruiting
      • FSU MRI Facility
      • Contact: Alecia Lapointe, MA; Phone Number: 850-644-1889; Email: alecia.lapointe@med.fsu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Right-handed
• Native English speaker or fluent by the age of 6
• Elevated self-reported anhedonia

Exclusion Criteria:

• Left-handed
• Metal in head
• Brain tumor, stroke, aneurysm, multiple sclerosis
• Active substance use disorder in last 3 months
• Dementia or other cognitive disorder making unable to engage in treatment
• History or diagnosis of schizophrenia, schizoaffective disorder, delusional disorder, or other psychiatic illness that precludes safe participation in trial
• Suicidal risk that precludes safe participation
• obsessive-compulsive disorder
• Inability to stop taking any mediation that significant lowers the seizure threshold (e.g. tricyclic antidepressants, clozapine, etc.)
• Severe traumatic brain injury
• Non-English speaker

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MPFC-iTBS; Transcranial magnetic stimulation delivered to the medial prefrontal cortex. 600 pulses delivered in 50 Hz bursts every 5 Hz for 2 seconds followed by 8 seconds of no stimulation repeated 20 times at 80% of resting motor threshold. Repeated daily for 5 consecutive days.	Device: transcranial magnetic stimulation; Transcranial magnetic stimulation delivered to the scalp targeting medial prefrontal cortex; Device: transcranial magnetic stimulation; Transcranial magnetic stimulation delivered to the inion
Active Comparator: Inion-iTBS; Transcranial magnetic stimulation delivered to the inion. 600 pulses delivered in 50 Hz bursts every 5 Hz for 2 seconds followed by 8 seconds of no stimulation repeated 20 times at 80% of resting motor threshold. Repeated daily for 5 consecutive days.	Device: transcranial magnetic stimulation; Transcranial magnetic stimulation delivered to the scalp targeting medial prefrontal cortex; Device: transcranial magnetic stimulation; Transcranial magnetic stimulation delivered to the inion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Anhedonia post-intervention	change in self-reported anhedonia from baseline immediately following the intervention measured using the score on the Dimensional Anhedonia Rating Scale (DARS); score range is 0-68 with higher scores meaning better outcomes (less anhedonia)	baseline, 1 hour post-intervention
Change in Anhedonia post-washout	change in self-reported anhedonia from baseline following a week of washout post-intervention measured using the score on the Dimensional Anhedonia Rating Scale (DARS); score range is 0-68 with higher scores meaning better outcomes (less anhedonia)	baseline, 1 week post-intervention
Change in RewP post-intervention measured via EEG	change in reward positivity from baseline immediately following the intervention assessed via the EEG event-related potential (ERP) to feedback over FCz in microvolts	baseline, immediately post-intervention
Change in RewP post-washout measured via EEG	change in reward positivity from baseline immediately following a week of washout post-intervention assessed via the EEG event-related potential (ERP) to feedback over FCz in microvolts	baseline, 1 week post-intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Reward activation measured via fMRI	change in reward-related activation in the ventral striatum assessed via the fMRI blood-oxygenation level dependent (BOLD) signal following feedback (this measure has no units)	baseline, 15 minutes post-intervention
Change in Reward connectivity measured via fMRI	change in fMRI connectivity between ventral striatum and medial prefrontal cortex assessed via correlations in the fMRI blood-oxygenation level dependent (BOLD) signal between these areas (this measure has no units)	baseline, 15 minutes post-intervention

Collaborators and Investigators

• Sponsor: Florida State University
• Collaborators: National Institute of Mental Health (NIMH)

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Anticipated): March 1, 2024
• Study Completion (Anticipated): April 30, 2024

Study Registration Dates

• First Submitted: July 1, 2022
• First Submitted That Met QC Criteria: July 15, 2022
• First Posted (Actual): July 21, 2022

Study Record Updates

• Last Update Posted (Actual): July 25, 2022
• Last Update Submitted That Met QC Criteria: July 20, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: STUDY00002776; R21MH129653 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Behavioral and imaging data will be shared
• IPD Sharing Time Frame: Within a year following publication of findings
• IPD Sharing Access Criteria: Behavioral and imaging data will be accessible from https://nda.nih.gov/edit_collection.html?id=4341 by NDA users
• IPD Sharing Supporting Information Type: Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes