Altering Default Mode Network Activity With Transcranial Focused Ultrasound to Reduce Depressive Symptoms

Depression is a leading cause of disability worldwide, affecting roughly 21 million adults. Repetitive Negative Thought (RNT) has been identified as a potential maintaining factor in depression, such that those who exhibit higher degrees of RNT endorse greater symptoms. Research also suggests that the Default Mode Network (DMN), responsible for self-referential processing, plays an important role in depression wherein it has been linked to RNT. In depressed individuals, this network appears to be hyper-connected, or "too connected", within itself which, in turn, is thought to promote RNT. Half of depressed individuals are treatment-resistant, creating a critical need to identify more effective interventions derived from a better mechanistic understanding of the development and maintenance of depression. Non-invasive Transcranial-Focused Ultrasound Stimulation (tFUS) is promising for the treatment of depression. tFUS directs a low-intensity (nonthermal) focused ultrasound beam that passes safely through the skull. Compared to other noninvasive neuromodulation approaches, tFUS can target deeper brain regions with high spatial precision. The present study is an exploratory non-blinded single treatment study to investigate whether tFUS targeting a major hub of the DMN, the anterior-medial prefrontal cortex, can improve depression symptoms and reduce RNT. Twenty depressed individuals with high RNT (75th percentile) will complete up to eleven ultrasound sessions targeting the anterior medial prefrontal cortex, a hub of the brain's default mode network that has been found to be hyper-connected in depression. MRI scans will be obtained before the first and after the last ultrasound sessions. Based on previous literature, it is predicted that depression interview ratings and self-report symptoms will decrease after the intervention, and also that DMN connectivity will decrease following intervention.