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Dr. Keller is an Assistant Professor of Psychiatry and Behavioral Sciences at Stanford University and an Assistant Professor at the Veterans Affairs PaloAlto Health Care System (VAPAHCS). He is a member of Stanford Bio-X and the Wu Tsai Neurosciences Institute. Dr. Keller received his MD and PhD in neuroscience from the Medical Scientist Training Program at Albert Einstein College of Medicine. He completed his residency in psychiatry at Stanford University Medical Center focused on interventional psychiatry. Dr Keller has received several grants including the F31, T32, K23, DP5 Early Independence Award, SBIR, and R01 awards. He co-developed a fully automated non-invasive brain mapping technique used across industry and academia, and has run two clinical trials (NCT01829165 and NCT02843373) collecting over 1500 participants across ten clinical centers. Dr. Keller has extensive experience in the assessment and management of individuals with treatment-resistant depression. He has developed methodology for capturing the neurophysiology of human brain networks and the effect of stimulation through invasive and non-invasive electrophysiology. The overarching goal of Dr. Keller’s Laboratory, the Laboratory for Personalized Neurotherapeutics (kellerlab.stanford.edu) is to improve brain stimulation treatment for neurological and psychiatric disease. His lab focuses on understanding the neural mechanisms of how brain stimulation technologies induce alter brain circuits in an effort to develop novel, personalized, and more effective brain stimulation treatments. His lab combines invasive and noninvasive human electrophysiology to answer these critical questions.
The overarching goal of Dr. Keller’s Laboratory, the Laboratory for Personalized Neurotherapeutics (kellerlab.stanford.edu) 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. Specifically, his lab seeks to identify and apply individualized stimulation protocols to elicit precise and predictable long-term plasticity in order to alleviate psychiatric suffering. His lab combines invasive and noninvasive human electrophysiology to answer these critical questions. TMS is a non-invasive brain stimulation technique focused on normalizing dysfunctional brain networks and is FDA-approved for depression, OCD, migraines, and smoking cessation, with clinical trials underway for PTSD, addiction, and Alzheimers. Unfortunately, TMS is typically applied in a one-size-fits-all manner without reference to one’s biology, and as such we are in critical need for a personalized and more effective approach. Dr. Keller's seeks to improve Transcranial Magnetic Stimulation (TMS) and other brain stimulation techniques by better understanding the fundamental principles of human brain plasticity and building trans-diagnostic real-time monitoring platforms for personalized brain stimulation. Dr. Keller's lab performs translational research at the intersection of neuroscience, electrophysiology, brain stimulation, neuroengineering, psychiatry, and precision therapeutics. Their work suggests that brain-based biomarkers may be used to predict non-responders to TMS treatment, monitor brain networks during intervention, and be used to propose novel targets and treatment paradigms. This work has the expected outcome of producing novel stimulation treatments with enhanced specificity, plasticity, and efficacy. By increasing our understanding of the underlying mechanism and monitoring of brain changes during TMS, we will markedly increase the utility of these powerful techniques. Together, this work will help transform interventional psychiatry from an isolated (from a clinic perspective), one-size-fits-all treatment approach to one that focuses on targeting objective biomarkers and that is collaborative, large-scale, and automated, pushing the field into the age of personalized neuromodulation.Dr. Keller emphasizes an environment conducive to team-based learning in order to train the next generation of clinically-informed circuit neuroscientists, question the status quo with rigorous scientific experiments, and make important contributions in understanding how brain stimulation alters neural circuits and behavior and translate these findings to develop targeted, personalized, and more effective treatments.
Investigating the Neural Mechanisms of Repetitive Brain Stimulation With Invasive and Noninvasive Electrophysiology in Humans
Transcranial magnetic stimulation (TMS) is an effective treatment for depression, but
clinical outcome is suboptimal, partially because investigators are missing
biologically-grounded brain markers which show that TMS is modifying activity at the intended
target in the brain. 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. These markers
will improve the understanding of TMS and can be used to optimize and enhance clinical
efficacy for depression and other psychiatric disorders.
Stanford is currently not accepting patients for this trial.
For more information, please contact Jade Truong, (408) 840-3313.
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Probing the Dorsolateral Prefrontal Cortex and Central Executive Network for Improving Neuromodulation in Depression
Depression is a highly prevalent condition characterized by persistent low mood, energy, and
activity that can affect one's thoughts, mood, behavior, and sense of well-being. Repetitive
transcranial magnetic stimulation (rTMS), a non-invasive neuromodulatory technique, is an
effective treatment for depression when targeting the dorsolateral prefrontal cortex (dlPFC)
of the central executive network (CEN). However, remission rates are suboptimal and
individual methods to target the dlPFC are lacking. In this study, we will enroll 50 patients
with major depression and in a single rTMS 'dose,' prospective, randomized, double-blind,
cross-over design will assess whether rTMS targeted to an individual's central executive
network (CEN) assessed by single pulse TMS can enhance network modulation. If successful,
this work will lead to a clinical rTMS trial comparing this personalized targeting approach
against standard rTMS.
Closed-loop Optimized rTMS for Depression
Targeted and individualized treatments for mental health disorders are critically needed.
Repetitive transcranial magnetic stimulation (rTMS) represents the front-line of new and
innovative approaches to normalizing dysfunctional brain networks in those with mental
illness. rTMS is FDA-approved for depression and obsessive-compulsive disorder with clinical
trials underway for PTSD and addiction, among others. However, remission rates are suboptimal
and ideal stimulation parameters are unknown. We recently completed a randomized, double
blind clinical trial and a depression severity biomarker that predicts clinical outcome. The
overarching goal of this study is to develop the first broadly generalizable platform for
real-time biomarker monitoring and personalized rTMS treatment. We plan to recruit patients
with medication-resistant depression and in perform a four-phase, cross-over, double-blind,
placebo-controlled trial to 1) identify how standard and optimized rTMS patterns engage the
depression severity biomarker, and 2) determine the dose-response of these rTMS patterns.
Findings from this study will provide the basis for a double-blind, randomized clinical trial
comparing rTMS optimized to the individual against standard rTMS.
Brain-Based Biomarkers in Response to TMS in MDD
The overarching goal of this research program is to elucidate causal and directional neural
network- level abnormalities in depression, and how they are modulated by an
individually-tailored, circuit-directed intervention. By using concurrent TMS and EEG, the
investigators can overcome a major limitation of EEG - the inability to demonstrate
causality. Here, we plan to recruit patients with medication-resistant depression undergoing
rTMS treatment. At multiple time points, we will perform TMS-EEG to investigate the
excitability and connectivity profiles of brain networks and how they are modulated during
treatment. This study aims to provide objective brain network measures that can predict and
track clinical response to TMS treatment. Findings from this study will be utilized to
develop a novel, personalized treatment protocol based on individual brain networks.
Stanford is currently not accepting patients for this trial.
For more information, please contact Corey Keller, MD PhD, .