Joshua C. Brown, MD, PhD
Medical Director, Transcranial Magnetic Stimulation (TMS) Service
Director of Transcranial Magnetic Stimulation Research, Division of Depression and Anxiety Disorders
Director, Brain Stimulation Mechanisms Laboratory
- Assistant Professor of Psychiatry
Biography
Joshua C. Brown, MD, PhD, is a psychiatrist, neurologist, and neuroscientist. He is medical director of the Transcranial Magnetic Stimulation (TMS) Service and director of TMS research in the Division of Depression and Anxiety Disorders at McLean Hospital. Dr. Brown is also director of the Brain Stimulation Mechanisms Laboratory at McLean and an assistant professor of Psychiatry at Harvard Medical School.
Dr. Brown is internationally recognized for his work on the synaptic mechanisms of TMS, pharmacologic augmentation of TMS, and TMS parameter selection. He is the founding editor-in-chief of the new journal, Transcranial Magnetic Stimulation, and is the president-elect of the Clinical TMS Society.
The Brain Stimulation Mechanisms Laboratory (BSML) at McLean Hospital is focused on understanding the neuronal mechanisms of transcranial magnetic stimulation (TMS) and leveraging these mechanisms to improve TMS effectiveness through parameter selection and pharmacologic augmentation strategies.
TMS is a tool capable of modulating brain activity in targeted networks, most likely subserved by changes in the synapse, such as long-term potentiation (LTP) and long-term depression (LTD). Dr. Brown’s lab has done much of the seminal work to understand the synaptic mechanisms of conventional 10-Hz rTMS in humans.
Using neurophysiology and pharmacology, the lab discovered that 10-Hz rTMS exhibits properties consistent with LTP, such as excitatory shifts in input-output curves, apparent occlusion of compound facilitation during intracortical facilitation protocols and homeostatic depression in response to intracortical inhibition protocols.
NMDA receptor activation was sufficient to enhance these effects, and NMDA receptor antagonism knocked down these effects. GABA receptor activation did not support the alternative hypothesis of “cutting the brakes” with 10Hz rTMS. These effects were also impaired in chronic caffeine users and enhanced in those with extensive use or practice involving the motor cortex.
These mechanistic studies are an extension of Brown’s earlier fundamental animal work demonstrating that BRAG1, which has mutations causing X-linked intellectual disorder (XLID), acts as a molecular consolidator of memory through removal of less-stable GluA1-type AMPA receptors for continuously recycling GluA2 receptors. His efforts to enhance TMS effects were preceded by his work with mice overexpressing neurogranin—a protein causally implicated in schizophrenia and Alzheimer’s disease (AD)—revealed the capacity to not only restore, but to enhance brain function.
Brown and his staff use multimodal approaches to investigate TMS mechanisms, including receptor modulation with pharmacology, non-invasive brain stimulation, neurobehavioral tasks, clinical scales, and neurophysiology approaches, EMG-based motor-evoked potentials (MEPs), and EEG-based TMS-evoked potentials. The lab emphasizes collaboration with psychotherapists and functional neuroimagers and efforts to assess neurotransmitter levels through magnetic resonance spectroscopy (MRS).
- Tracy Barbour, MD, Massachusetts General Hospital
- Joan Camprodon, MD, PhD, Massachusetts General Hospital
- Linda Carpenter, MD, Butler Hospital/Brown University School of Medicine
- Leo Chen, MD, Monash University, Australia
- Kevin Clancy, PhD, McLean Hospital
- Marc L. Copersino, PhD, ABPP-CP, McLean Hospital
- Jeff Daskalakis, MD, PhD, University of California San Diego
- Daniel G. Dillon, PhD, McLean Hospital
- Nick Folk, PhD, Beth Israel Deaconess Medical Center
- Michael Frank, PhD, Brown University
- Peter Fried, PhD, Beth Israel Deaconess Medical Center
- Mark George, MD, Medical University of South Carolina
- Carolina Haass-Koffler, PharmD, PhD, Brown University
- Mark A. Halko, PhD, McLean Hospital
- Alex McGirr, MD, PhD, University of Calgary, Canada
- Robert C. Meisner, MD, McLean Hospital
- Recep Ozdemir, PhD, Beth Israel Deaconess Medical Center
- Kerry J. Ressler, MD, PhD, McLean Hospital
- Alexander Rotenberg, MD, PhD, Boston Children’s Hospital
- Stephen J. Seiner, MD, McLean Hospital
- Mo Shafi, MD, PhD, Beth Israel Deaconess Medical Center
- Mohamed Sherif, MD, PhD, Brown University School of Medicine
- Shan Siddiqi, MD, Brigham and Women’s Hospital
- Joseph Taylor, MD, PhD, Brigham and Women’s Hospital
- Brian Theyel, MD, PhD, Brown University School of Medicine
- Jenna M. Traynor, PhD, McLean Hospital
- Stefan Vestring, MD, PhD, University of Freiburg, Germany
- Andreas Vlachos, MD, PhD, University of Freiburg, Germany
- Agustin G. Yip, MD, PhD, McLean Hospital
Brown JC, Petersen, A, Zhong L, Himelright, ML, Murphy, JA, Walikonis RS, Gerges NZ. Bi-directional regulation of synaptic transmission by BRAG1/IQSEC2 and its requirement in long-term depression. Nature Communications. 2016;24:7:11080.
Brown JC, DeVries WH, Korte JE, Sahlem GL, Bonilha L, Short EB, George MS. NMDA receptor partial agonist, d-cycloserine, enhances 10 Hz rTMS-induced motor plasticity, suggesting long-term potentiation (LTP) as underlying mechanism. Brain Stimulation. 2020;13:530-532.
Brown JC, Higgins ES, George MS. Synaptic plasticity 101: The story of the AMPA receptor for the brain stimulation practitioner. Neuromodulation. 2021;25(8):1289-1298.
Education & Training
- 2002 BS in Psychology, University of Utah
- 2013 PhD in Neurobiology, Medical College of Wisconsin
- 2014 MD, Medical College of Wisconsin
- 2014-2015 Internship, Internal Medicine, Medical University of South Carolina
- 2015-2020 Residency in Psychiatry and Neurology, Medical University of South Carolina
- 2018-2020 DART Research Fellowship, Brain Stimulation Laboratory, Medical University of South Carolina
- 2017-2020 Interventional Psychiatry Track, Medical University of South Carolina
- 2016 Medical License, State of South Carolina
- 2020 Medical License, State of Rhode Island and Providence Plantations
- 2022 Psychiatry, American Board of Psychiatry and Neurology
- 2023 Medical License, Board of Registration in Medicine, Commonwealth of Massachusetts
