Reward Circuit Targeted iTBS

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.

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