Decoding and Modulating Affective Brain States

The study involves 11 visits over approximately 10 weeks, depending on scanner availability and scheduling. See below for the study schedule with a summary of the procedures:

• Visit 1: Screening Procedures (~3-4 hours). The first part of the screening will take place remotely (~1 hour). The investigators will begin by reviewing the Informed Consent Form (ICF). Participants who agree to participate and sign the ICF will then complete several questionnaires. Those who meet preliminary eligibility criteria based on the remote procedures will be invited for an in-person visit. The in-person screening will include a brief TMS demonstration (~20 minutes). If TMS is well tolerated, the visit will proceed to a comprehensive clinical interview (~2-3 hours) to assess current and past mental health history.
• Visit 2: Baseline MRI & Assessments (~2 hours). This visit will involve a 1-hour MRI scan, including both structural and functional sequences, and an assessment session with computerized tasks and questionnaires.
• Visit 3: MRI Scan with TMS (~2.5 hours). A second MRI scan will be conducted with concurrent TMS procedures. Participants will complete a mental task while interleaved rTMS is delivered at different frequencies. This scan will be used to determine the optimal stimulation frequency for each participant.
• Visits 4-6: First Neuromodulation Session (~1.5 hours each). Participants will receive rTMS using either the optimal or least optimal stimulation frequency. They will also complete two computerized tasks after rTMS, with questionnaires in between procedures.
• Visit 7: MRI Scan with TMS (~2 hours). This visit will be a shortened version of Visit 3, as some MRI scans and questionnaires will not need to be repeated.
• Visits 8-10: Second Neuromodulation Session (~1.5 hours each). These visits will mirror Visits 4-6. However, the TMS condition administered (optimal or suboptimal frequency) will be counterbalanced with the condition used during the first neuromodulation session. Visit 8 will be scheduled at least 2 weeks after Visit 7.
• Visit 11: MRI Scan with TMS (~2 hours). This visit will mirror Visit 7.

After completing all procedures, participants will receive the full study compensation. Payments may be issued earlier if participants request compensation after each visit or if they withdraw early.

Inclusion criteria

• 18-65 years old
• Patient Health Questionnaire (PHQ-9 score) = or > than 10
• Comprehension of instructions in the English language.
• Capacity to provide informed consent and follow study procedures.
• Availability for the duration of the study.

Exclusion criteria

• Diagnosis of bipolar disorder (as PI discretion), schizophrenia or other psychotic disorder
• Recent use of psychoactive medications or substances as determined by investigators
• History of neurological disorder or traumatic brain injury (other than mild)
• Unable to have an MRI scan, or current or prior medical condition that could interfere with the collection or interpretation of MRI data
• Unable to receive or tolerate TMS
• Implanted devices, such as an aneurysm clip or cardiac pacemaker
• History of stroke, epilepsy, or brain scarring
• Pregnant, nursing, or trying to become pregnant (self-attestation alone)

During this study, participants are asked to:

• Refrain from substance use (including marijuana and illicit drugs) for duration of the study (self-attestation alone).
• Abstain from alcohol for 24 hours before the MRI scans (self-attestation alone).
• Abstain from increasing caffeine intake or begin taking any new medications (self-attestation alone).