Cortical rTMS as a Treatment for Depression

Summary

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.

Detailed Description

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 depression, 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 depression's most common comorbidities. Thus, it is clear that we need a better understanding of the therapeutic mechanisms using non-invasive brain stimulation (e.g., TMS) treatment to the OFC as applied to patients with depression. As such, we 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 patients with depression.

Eligibility Criteria

Interventions