Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| R21MH129653 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
Not provided
Not provided
Not provided
Not provided
The objective of this study is to examine the effect of intermittent theta-burst transcranial magnetic stimulation (iTBS) targeting the reward circuit.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| rmPFC-iTBS | Experimental | Transcranial magnetic stimulation delivered to the rostral 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. |
|
| Inion-iTBS | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| transcranial magnetic stimulation | Device | Transcranial magnetic stimulation delivered to the scalp targeting medial prefrontal cortex |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Anhedonia Post-intervention and Washout | change in self-reported anhedonia from baseline averaged across post-intervention and post-washout 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, one-hour post-intervention, one-week post-intervention |
| 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 and Washout Measured Via EEG | change in reward positivity from baseline averaged across immediately post-intervention and post-washout assessed via the EEG event-related potential (ERP) to feedback over FCz in microvolts | baseline, immediately post-intervention, one-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 |
| 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 (arbitrary units). More positive values indicate greater activation relative to baseline (more reward-related signal). | baseline, 15 minutes post-intervention |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| FSU MRI Facility | Tallahassee | Florida | 32306 | United States |
Behavioral and imaging data will be shared
Within a year following publication of findings
Behavioral and imaging data will be accessible from https://nda.nih.gov/edit\_collection.html?id=4341 by NDA users
Not provided
After enrollment, participants complete 1) a baseline functional MRI scan to determine targets for transcranial magnetic stimulation (TMS), and 2) motor thresholding to determine intensity of TMS. Participants are not assigned to arms if they cannot perform the task inside the MRI scanner (e.g. due to claustrophobia), if they cannot tolerate TMS (e.g., due to discomfort), and if they have contraindications for MRI or TMS (e.g., pro-epileptic medications, neurological conditions).
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | rmPFC-iTBS Then Inion-iTBS | Transcranial magnetic stimulation: Transcranial magnetic stimulation delivered to the scalp targeting specific brain structures via stereotactic guidance. Each visit consists of 600 pulses delivered in 2 second trains of 50 Hz bursts every 5 Hz with 8 seconds in-between trains at 80% of resting motor threshold to one target. For a given target, stimulation was performed once a day for 5 consecutive days. A 9 day washout period followed prior to stimulating the alternate target. This arm completed transcranial magnetic stimulation to the rostromedial prefrontal cortex (rmPFC) first followed by the inion. |
| FG001 | Inion-iTBS Then rmPFC-iTBS | Transcranial magnetic stimulation: Transcranial magnetic stimulation delivered to the scalp targeting specific brain structures via stereotactic guidance. Each visit consists of 600 pulses delivered in 2 second trains of 50 Hz bursts every 5 Hz with 8 seconds in-between trains at 80% of resting motor threshold to one target. For a given target, stimulation was performed once a day for 5 consecutive days. A 9 day washout period followed prior to stimulating the alternate target. This arm completed transcranial magnetic stimulation to the inion first followed by the rostromedial prefrontal cortex (rmPFC). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | rmPFC-iTBS Then Inion-iTBS | Transcranial magnetic stimulation: Transcranial magnetic stimulation delivered to the scalp targeting specific brain structures via stereotactic guidance. Each visit consists of 600 pulses delivered in 2 second trains of 50 Hz bursts every 5 Hz with 8 seconds in-between trains at 80% of resting motor threshold to one target. For a given target, stimulation was performed once a day for 5 consecutive days. A 9 day washout period followed prior to stimulating the alternate target. This arm completed transcranial magnetic stimulation to the rostromedial prefrontal cortex (rmPFC) first followed by the inion. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Anhedonia Post-intervention and Washout | change in self-reported anhedonia from baseline averaged across post-intervention and post-washout measured using the score on the Dimensional Anhedonia Rating Scale (DARS); score range is 0-68 with higher scores meaning better outcomes (less anhedonia) | 4 participants with incomplete data were not analyzed. 16 participants who did not complete the study were not analyzed. | Posted | Mean | Standard Error | Scores on a scale | baseline, one-hour post-intervention, one-week post-intervention |
|
From enrollment until the end of washout, up to 5 weeks
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | rmPFC-iTBS Then Inion-iTBS | Transcranial magnetic stimulation: Transcranial magnetic stimulation delivered to the scalp targeting specific brain structures via stereotactic guidance. Each visit consists of 600 pulses delivered in 2 second trains of 50 Hz bursts every 5 Hz with 8 seconds in-between trains at 80% of resting motor threshold to one target. For a given target, stimulation was performed once a day for 5 consecutive days. A 9 day washout period followed prior to stimulating the alternate target. This arm completed transcranial magnetic stimulation to the rostromedial prefrontal cortex (rmPFC) first followed by the inion. |
Not provided
Not provided
Due to a programming error, the rmPFC was mistargeted in 55 participants. For these participants, stimulation of the rmPFC was weaker than intended. This issue may have undermined the efficacy of the intervention.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Derek Nee | Florida State University | 8506441963 | dnee@fsu.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 3, 2024 | Oct 13, 2025 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Dec 14, 2022 | Oct 13, 2025 | ICF_001.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D050781 | Transcranial Magnetic Stimulation |
| ID | Term |
|---|---|
| D055909 | Magnetic Field Therapy |
| D013812 | Therapeutics |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| transcranial magnetic stimulation | Device | Transcranial magnetic stimulation delivered to the inion |
|
| 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 |
| 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 (z-scored correlation coefficient). More positive values indicate more positive correlations in BOLD signals between the ventral striatum and medial prefrontal cortex relative to baseline. | baseline, 15 minutes post-intervention |
| incidental MRI finding |
|
| could not tolerate rmPFC-iTBS |
|
| illness |
|
| BG001 | Inion-iTBS Then rmPFC-iTBS | Transcranial magnetic stimulation: Transcranial magnetic stimulation delivered to the scalp targeting specific brain structures via stereotactic guidance. Each visit consists of 600 pulses delivered in 2 second trains of 50 Hz bursts every 5 Hz with 8 seconds in-between trains at 80% of resting motor threshold to one target. For a given target, stimulation was performed once a day for 5 consecutive days. A 9 day washout period followed prior to stimulating the alternate target. This arm completed transcranial magnetic stimulation to the inion first followed by the rostromedial prefrontal cortex (rmPFC). |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | 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. |
|
|
|
| Primary | 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) | 4 participants with incomplete data were not analyzed. 16 participants who did not complete the study were not analyzed. | Posted | Mean | Standard Error | Scores on a scale | baseline, 1 hour post-intervention |
|
|
|
|
| Primary | 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) | 4 participants with incomplete data were not analyzed. 16 participants who did not complete the study were not analyzed. | Posted | Mean | Standard Error | Scores on a scale | baseline, 1 week post-intervention |
|
|
|
|
| Primary | Change in RewP Post-intervention and Washout Measured Via EEG | change in reward positivity from baseline averaged across immediately post-intervention and post-washout assessed via the EEG event-related potential (ERP) to feedback over FCz in microvolts | 3 participants who had incomplete data were not analyzed. 16 participants who did not complete the study were not analyzed. | Posted | Mean | Standard Error | microvolts | baseline, immediately post-intervention, one-week post-intervention |
|
|
|
|
| Secondary | 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 (arbitrary units). More positive values indicate greater activation relative to baseline (more reward-related signal). | 8 participants who had excessive head motion (root-mean square of framewise displacement > 0.3) were not analyzed. 2 participants with missing data were not analyzed. 16 participants who did not complete the study were not analyzed. | Posted | Mean | Standard Error | arbitrary units | baseline, 15 minutes post-intervention |
|
|
|
|
| Secondary | 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 (z-scored correlation coefficient). More positive values indicate more positive correlations in BOLD signals between the ventral striatum and medial prefrontal cortex relative to baseline. | 10 participants who had excessive head motion (root-mean square of framewise displacement > 0.3 in any visit) were not analyzed. 2 participants with missing data were not analyzed. 16 participants who did not complete the study were not analyzed. | Posted | Mean | Standard Error | z-scored correlation coefficient | baseline, 15 minutes post-intervention |
|
|
|
|
| Primary | 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 | 3 participants who had incomplete data were not analyzed. 16 participants who did not complete the study were not analyzed. | Posted | Mean | Standard Error | microvolts | baseline, immediately post-intervention |
|
|
|
|
| Primary | 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 | 3 participants who had incomplete data were not analyzed. 16 participants who did not complete the study were not analyzed. | Posted | Mean | Standard Error | microvolts | baseline, 1 week post-intervention |
|
|
|
|
| 0 |
| 35 |
| 0 |
| 35 |
| 0 |
| 35 |
| EG001 | Inion-iTBS Then rmPFC-iTBS | Transcranial magnetic stimulation: Transcranial magnetic stimulation delivered to the scalp targeting specific brain structures via stereotactic guidance. Each visit consists of 600 pulses delivered in 2 second trains of 50 Hz bursts every 5 Hz with 8 seconds in-between trains at 80% of resting motor threshold to one target. For a given target, stimulation was performed once a day for 5 consecutive days. A 9 day washout period followed prior to stimulating the alternate target. This arm completed transcranial magnetic stimulation to the inion first followed by the rostromedial prefrontal cortex (rmPFC). | 0 | 34 | 0 | 34 | 0 | 34 |
Not provided
Not provided