Transcranial Magnetic Stimulation
Conditions
Brief summary
The objective of this study is to examine the effect of intermittent theta-burst transcranial magnetic stimulation (iTBS) targeting the reward circuit.
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.
Interventions
DEVICEtranscranial magnetic stimulation
Transcranial magnetic stimulation delivered to the scalp targeting medial prefrontal cortex
Sponsors
Florida State University
National Institute of Mental Health (NIMH)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Anhedonia Post-intervention and Washout | baseline, one-hour post-intervention, one-week post-intervention | 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) |
| Change in Anhedonia Post-intervention | baseline, 1 hour 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) |
| Change in Anhedonia Post-washout | baseline, 1 week post-intervention | 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) |
| Change in RewP Post-intervention and Washout Measured Via EEG | baseline, immediately post-intervention, one-week post-intervention | 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 |
| Change in RewP Post-intervention Measured Via EEG | baseline, immediately post-intervention | change in reward positivity from baseline immediately following the intervention assessed via the EEG event-related potential (ERP) to feedback over FCz in microvolts |
| Change in RewP Post-washout Measured Via EEG | baseline, 1 week post-intervention | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Reward Activation Measured Via fMRI | baseline, 15 minutes post-intervention | 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). |
| Change in Reward Connectivity Measured Via fMRI | baseline, 15 minutes post-intervention | 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. |
Countries
United States
Participant flow
Pre-assignment details
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).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 23.8116 Years STANDARD_DEVIATION 7.85582 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 11 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 46 Participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 34 |
| other Total, other adverse events | 0 / 35 | 0 / 34 |
| serious Total, serious adverse events | 0 / 35 | 0 / 34 |
Outcome results
None listed