Cortical rTMS as a Treatment for Depression

The OFC is functionally connected to other cortical brain regions (e.g., prefrontal and parietal cortices) but also to subcortical areas in the dorsal striatum, a core reward circuitry region. The OFC is structurally connected to the medial forebrain bundle (MFB), deep brain stimulation (DBS) target for MDD, and the OFC may in fact be the mediator of anti-depressant effect. The functional connectivity between the OFC and those subcortical brain regions also plays an important role in addiction and suicide behaviors, which are MDD's most common comorbidities. Thus, it is clear that investigators need a better understanding of the therapeutic mechanisms using non-invasive brain stimulation (e.g., TMS) treatment to the OFC as applied to MDD patients. As such, the investigators propose to use a combination of interleaved TMS-fMRI, a novel method to observe and characterize causal manipulations of functional neural circuits, targeting the OFC and resting state fMRI to longitudinally study depressive symptoms and depression-related symptoms (e.g., addiction, suicidal behaviors) changes in MDD patients.

Inclusion criteria

• Be male or female aged 18-60 years old
• Meets MDD criteria
• Has depressive symptoms according to the Patients Health Questionnaire (PHQ)-9 or Hamilton Depression Rating Scale (HDRS) or Snaith-Hamilton Pleasure Scale (SHAPS)
• Be able to verbalize understanding of consent form, able to provide written informed consent, and verbalize willingness to complete study procedures
• Female subjects must be non-nursing and not pregnant at the times of fMRI experiments and TMS treatment
• 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)
• 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)

Exclusion criteria

• 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
• Unable to understand the design and requirements of the study
• Unable to sign informed consent for any reason
• Has an unstable medical condition, including AIDS, acute hepatitis, active TB, unstable cardiac disease, unstable diabetes, hepatic or renal insufficiency
• Female subjects who are pregnant or nursing
• 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
• 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.
• Non-English speaking subjects (we do not have the staff and/or resources to include other language).