Brainmap: An evolving view of cognitive impairment in schizophrenia through functional, structural, and PET-MRI studies- Jashua Lawrence Roffman, MD

Wednesday, November 16, 2016 - 12:00 to 13:00

 

Abstract

Impairment in cognition, and specifically in working memory, are common and disabling symptoms of schizophrenia.  Many investigators consider the dorsolateral prefrontal cortex  (DLPFC) “ground zero” for cognitive impairment in schizophrenia, as this region is associated with altered working memory-related activation, connectivity, neurotransmitter signaling, and gene expression.  Disrupted prefrontal dopamine signaling, observed in several previous PET studies of schizophrenia patients, has been specifically linked to impaired working memory performance and altered prefrontal activation.  These findings are consistent with nonhuman primate studies that elaborate a critical role of prefrontal dopamine signaling in the “tuning” of pyramidal neurons to task-relevant stimuli.

However, some important gaps remain in our understanding of how cortical dopamine signaling and related prefrontal physiology contribute to schizophrenia.  Few fMRI studies of working memory abnormalities in schizophrenia adequately account for confounding effects of impaired task performance.   It has also remained unclear how variation in cortical D1 signaling scales up to influence cortical network function.  Finally, temporal variance in gene expression over the course of brain development may influence when – and where – the structural foundation of working memory is laid down.

Here, I will describe recent progress that we and others have made in each of these domains using multimodal imaging, drawing from both published and unpublished data.  First, event-related fMRI has helped us differentiate networks that underlie core working memory deficits in schizophrenia from those that simply reflect performance differences.  Second, using simultaneous PET-MRI with 11C NNC112, we have developed a more sophisticated understanding of how variation in cortical D1 signaling affects network dynamics underlying working memory performance.  Finally, leveraging data from the Brain Genomics Superstruct and BrainCloud data repositories, we have related variation in DLPFC thickness to development-specific patterns of ge

About the Speaker 

Dr. Joshua Roffman is a board certified psychiatrist and investigator in the MGH Schizophrenia Clinical and Research Program (SCRP). He is Assistant Professor of Psychiatry at Harvard Medical School and directs the Brain Genomics Laboratory at MGH. After graduating with high honors in neuroscience at Amherst College, Dr. Roffman completed his medical training at the University of Maryland, National Institutes of Health, and MGH-McLean Adult Psychiatry Residency Training Program. He was the recipient of early career awards from the Howard Hughes Medical Institute, National Institute of Mental Health (NIMH), and NARSAD/Brain & Behavior Research Foundation among others. His research is currently supported by NIMH, NARSAD, and MQ: Transforming Mental Health, where he was named one of the inaugural MQ Fellows.