Overview

Depression is a leading cause of disability worldwide with a 19% lifetime prevalence in the United States. Dysfunctional reward processing is one of the core features of depression. Common treatments of depression include psychological therapies (e.g., cognitive behavioral therapy), medication (e.g., bupropion, sertraline) and psychological therapies and medication combined, but they may not address the function of the reward circuit in depression. These treatments often o not improve depressive symptoms in patients with depression who are classified as having treatment-resistant depression, and they may be unlikely to respond to further medication trials. Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation that enables us to selectively excite or inhibit neural activity. Multiple TMS pulses given consecutively are known as repetitive TMS (rTMS), and the primary clinical location for applying rTMS is the left dorsolateral prefrontal cortex (DLPFC) for treatment of depressive symptoms. Many of these studies have shown that rTMS to the DLPFC may result in decreased depressive symptoms, but is only partially effective (response and remission rates of 41.2 and 35.3%, respectively). This evidence supports the importance of evaluating the efficacy of rTMS in other brain regions, such as the orbitofrontal cortex (OFC), in the treatment of depressive symptoms rather than in the DLPFC.

Eligibility

Inclusion Criteria:

1. Be male or female aged 18-64 years old.
2. Has depressive symptoms according to the PHQ-9 or MADRS or HDRS or SHAPS
3. Be able to verbalize understanding of consent form, able to provide written informed consent, and verbalize willingness to complete study procedures
4. Female subjects must be non-nursing and not pregnant at the times of fMRI experiments and TMS treatment
5. Has no contraindications to MRI (pacemaker, cochlear implants, metal in eyes, other metal implants, etc.); Meets the pre-screening MRI questions provided by the Center for Advanced MR Imaging (CAMRI)
6. Has no contraindications to TMS (any types of non-removable metal in their head except the mouth, or within 12 inches of the coil, etc.); Meets the pre-screening TMS safety questionnaire (Transcranial Magnetic Stimulation Adult Safety Screen - TASS)
7. stabilized with medication treatments (e.g., methadone or buprenorphine) or abstinent from opioids if patients are seeking transition to naltrexone
8. urine toxicity test is negative for specific drugs (e.g., opioids)

Exclusion Criteria:

1. In the opinion of the clinician and/or the research team, be expected to fail to complete the study protocol due to not tolerable to receive TMS
2. Unable to understand the design and requirements of the study;
3. Unable to sign informed consent for any reason
4. Has an unstable medical condition, including AIDS, acute hepatitis, active TB, unstable cardiac disease, unstable diabetes, hepatic or renal insufficiency
5. Female subjects who are pregnant or nursing
6. Contraindications to MRI (pacemaker, cochlear implants, metal in the eye, other metal implants, etc.): Do not meet the pre-screening MRI questions provided by the CAMRI at BCM
7. Contraindications to TMS (any types of non-removable metal in their head except the mouth, or within 12 inches of the coil, etc.): Do not meet the pre-screening TMS safety questionnaire (TASS). Additional exclusion criteria for the TMS experiments are based on the recommendations described by the international consensus panel on brain stimulation
8. Non-English speaking subjects (we do not have the staff and/or resources to include other languages);
9. Unstable with medication treatments (e.g., methadone or buprenorphine)
10. urine toxicity test is positive for specific drugs (e.g., opioids)
11. currently on seizure medications (e.g., Depakote)