Stanford Psychiatry researcher receives grant to advance understanding of functions and mechanisms of spontaneous cortical activity

June 13, 2023

Anish Mitra, MD, PhD

Congratulations to Stanford Psychiatry’s Anish Mitra, who was awarded a grant from the National Institute of Mental Health for a new project titled “Predictive Functions and Neural Mechanisms of Spontaneous Cortical Activity.”

Dr. Mitra is a postdoctoral scholar working with research mentors Karl Deisseroth, D.H. Chen Professor of bioengineering and of psychiatry and behavioral sciences, and Nolan Williams, associate professor of psychiatry and behavioral sciences, on projects that use imaging and brain stimulation techniques to investigate the mechanisms underlying organized patterns in brain-wide activity.

The goal of this study is to address knowledge gaps regarding spontaneous cortical circuits (SCS), which is when the mammalian cortex is spontaneously active in the absence of external stimuli. Dr. Mitra will build on his previous research in order to:

  • Investigate how specific interneuron types contribute to SCS
  • Test the causal influence of predictive SCS over perceptual decisions through a closed-loop behavior
  • Apply optogenetic modulation of neural activity to test the role of a specific cortical area, the retrosplenial cortex, in driving predictive SCS

“Spontaneous brain activity drives dramatic variability in both neural and perceptual responses to identical sensory stimuli,” said Dr. Mitra. “My proposal applies cutting-edge technologies to reveal the predictive functions and basic circuit mechanisms underlying spontaneous cortical states, with the ultimate goal of generating novel insights into how resting state activity contributes to psychiatric illness.”

Initially dismissed as neural noise, pioneering work established that these internal brain states produced by spontaneous activity are highly structured and responsible for the dramatic variability in both neural and perceptual responses to the same sensory stimulus. The discovery that varying spontaneous activity drives different responses to identical stimuli suggested that altered perceptions of the environment across psychiatry could derive from aberrant SCS.

“Ongoing resting state [functional magnetic resonance imaging] studies continue to search for reproducible links between SCS and psychiatric diagnoses, including schizophrenia, depression, and PTSD, among others,” said Dr. Mitra, “Yet our fundamental understanding of the cognitive processes and circuit mechanisms underlying SCS remains limited.”

Dr. Mitra is a recipient of the Burroughs Wellcome Fund’s 2023 Career Awards for Medical Scientists. These awards, bestowed annually, recognize outstanding early-career researchers who have demonstrated exceptional promise in the field of medical science. A total of 12 individuals have been selected for their remarkable contributions to biomedical research and their potential to make significant advancements in the field. Recent publications written by Dr. Mitra and colleagues include “Targeted neurostimulation reverses a spatiotemporal biomarker of treatment-resistant depression,” published in the journal Proceedings of the National Academy of Sciences of the United States of America.

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