Stanford Psychiatry and University of Iowa awarded grant for research aiming to improve efficacy of rTMS for treatment-resistant depression

November 17, 2023

Corey Keller, MD, PhD

We are excited to announce that Stanford Psychiatry’s Corey Keller, Assistant Professor of Psychiatry and Behavioral Sciences, has received a grant from the National Institute of Mental Health for research to characterize the key markers of the brain’s response to repetitive transcranial magnetic stimulation (rTMS). Dr. Keller is joined by co-principal investigator Dr. Aaron Boes at the University of Iowa.

Depression is the leading cause of disability worldwide and of disease burden in the U.S., and up to a third of individuals with depression experience treatment-resistant depression. The development of an effective non-pharmacological option for treatment-resistant depression using rTMS represents a major advance in the field, but it’s still unknown why about half of patients do not benefit from the treatment.

One of the major barriers to optimizing rTMS and improving the percentage of patients who benefit from it is a lack of understanding about the basic mechanisms of how and why rTMS works. Prior work in this field has been limited by relying heavily on non-invasive measures of brain activity — like functional MRI, EEG, and behavior — to assess the underlying mechanisms of rTMS. These methods have inherent limitations in spatiotemporal resolution.

This project will use a novel approach that combines invasive and noninvasive methods to evaluate the effects of rTMS with much higher spatiotemporal resolution than has been possible to date. Using surgically implanted intracranial electrodes, the study team will record directly from the human brain during the administration of stimulation protocols used to treat depression. Those measures will help understand the mechanism of current treatments, develop new treatments, and improve treatment efficacy.

“The goal of this proposal is to characterize the key markers of the brain’s response to repeated doses of TMS with high resolution using invasive brain recordings in humans, and relate these brain markers to noninvasive recordings,” write Dr. Keller and Dr. Boes. “These markers will improve our understanding of TMS and can be used to optimize and enhance clinical efficacy for depression and other psychiatric disorders.”

The overarching goal of Dr. Keller’s team in the Laboratory for Personalized Neurotherapeutics is to improve brain stimulation treatment for neurological and psychiatric disease. His lab focuses on understanding the neural mechanisms of how brain stimulation technologies alter brain circuits in an effort to develop novel, personalized, and more effective brain stimulation treatments. Recent publications related to this work include “Personalized Repetitive Transcranial Magnetic Stimulation for Depression” and “Reliability and Validity of Transcranial Magnetic Stimulation-Electroencephalography Biomarkers,” both published in the journal Biological Psychiatry: Cognitive Neuroscience and Neuroimaging.

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