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"...antidepressant...and cognitive behavioral therapy...induce post-treatment effects in brain networks...these are correlative...Conducting TMS in the fMRI scanner allows the demonstration of direct causal effects in real time. I am very excited to see this work move forward."
— Yvette Sheline, MD, McLure Professor of Psychiatry, Radiology, Neurology; University of Pennsyvlania Perelman School of Medicine

Desmond Oathes, PhD

Assistant Professor
University of Pennsylvania Perelman School of Medicine

Mental illness including depression, anxiety, substance abuse, and suicide has affected many members of my family, my friends, and my patients. I enjoy doing basic neuroscientific research but what really motivates me to spend late hours in the lab is the hope that I can contribute to a new treatment for patients with mental health problems who may be starting to lose hope that they can find something or someone to help them.

Summary

There is already an FDA approved noninvasive brain stimulation treatment for depression using Transcranial Magnetic Stimulation (TMS) but this treatment does not use state of the art neuroimaging to individualize and optimize treatment. In fact, there is now substantial evidence to suggest that we are not targeting the BEST brain area to treat depression with TMS. Also, there is no currently approved TMS treatment for anxiety though we have excellent neuroimaging evidence to guide new treatment targets. There are existing brain surgery interventions designed to treat very depressed and anxious patients because it is believed that the brain areas most abnormal for these conditions lie deep in the brain. Our ongoing work suggests that it is possible to reach these deep brain areas via interconnected circuits at the surface of the brain that are accessible to non-invasive brain stimulation. This means that we may be able to reach deep brain areas to treat them without surgery or anesthesia. If we can achieve results comparable to neurosurgical interventions but using our non-invasive methods, it would thus be a major achievement benefiting patients.

We are going to choose several potential targets on the surface of the brain whose activity is correlated in time with the deeper brain targets of interest for depression (subgenual cingulate cortex) and anxiety (amygdala). Then we will interleave pulses of TMS with functional recordings of brain activity (functional MRI; fMRI) to determine which non-invasive brain stimulation target BEST influences the deeper brain area. This will give us a unique, brain based and highly individualized target for each individual.

Why is this important?

Using an individual's actual brain activity to guide a novel noninvasive brain stimulation treatment of this kind has never been done. Similarly, the excellent brain imaging research done over many decades has so far yielded NO new treatments in mental health.

We feel that this project will be the critical step needed to determine novel brain targets to treat anxiety and depression with non-invasive brain stimulation. Our group represents cutting edge neuroscientists and clinicians (psychologists and psychiatrists) who have mastered the techniques required by this project and that only a handful of other labs in the world could accomplish. Ultimately, we see this approach to combining brain stimulation with functional brain recording to be a critical bridge between neuroscientific research and novel treatments for a wide variety of brain disorders.

Who will benefit?

Patients for whom there is evidence for a brain basis to their disorders but especially patients with a diagnosis of a depressive disorder or an anxiety disorder.

Budget

The budget will be used for MRI scan time at Penn, participant reimbursement/remuneration, and associated study supplies.