Study explores how brain disruption may foster schizophrenia

September 26, 2012
Credit: Shutterstock

(Medical Xpress)—A team led by Yale researchers has used pharmacological neuroimaging and computational modeling to examine large-scale functional organization in the human brain. Their novel approach has yielded important insights about how disruption of a specific molecular signaling mechanism within neural systems may contribute to symptoms of schizophrenia. The results are reported online ahead of print in the Proceedings of the National Academy of Sciences.

Previous studies on this topic have been limited to processes in local circuits; however, cognition involves large-scale with multiple interacting regions. The current study suggests that coordination of these large-scale systems depends on the proper functioning of glutamate – a key .

"While neuroimaging alone has aided our understanding of higher cognitive function, it cannot reveal cellular-level mechanisms in humans. The addition of pharmacology and computational modeling help us start to see a more complete picture," said Alan Anticevic, PhD, associate research scientist in psychiatry at the Yale School of Medicine and lead author of the study. "This deeper understanding could lead to better treatment of such as schizophrenia."

The team found that a balance of excitatory and inhibitory function in the is vital for optimal large-scale network coordination and cognition, and that inhibitory neurons play a crucial role in producing the that may occur in individuals with schizophrenia.

Study explores how brain disruption may foster schizophrenia
Glutamate and computational principles of anti-correlated neural systems. Pictured is a parameter space of a biophysically-realistic computational model of working memory, with hypothesized neural system effects of N-methyl-D-aspartate receptor antagonism.

Additionally, for the first time, the team elucidated the link between drug effects and behavior using a mathematical model that was built from the level of cells. Perturbing the balance of neuronal inhibition inside the model closely matched experimental observations.

Philip Corlett, PhD, assistant professor of psychiatry, and John Krystal, MD, Robert L. McNeil Jr. Professor of Translational Research and chair of psychiatry, share senior authorship. The team's state-of-the-art mathematical models were developed by John Murray, a PhD student in physics at Yale, and Xiao-Jing Wang, PhD, professor of neurobiology, of psychology, and of physics at Yale, both of whom are co-authors of the study.

"These results provide the exciting possibility of understanding psychiatric symptoms at the levels of individual cells, neural systems, and human behavior," said Corlett. Krystal added, "Such translational approaches ultimately offer the promise for rationally-devised treatments for psychiatric conditions."

Explore further: The neuroscience of choosing: Can we understand how the brain makes decisions?

More information: www.pnas.org/content/early/2012/09/25/1208494109.abstract

Related Stories

Recommended for you

Precise control of brain circuit alters mood

June 23, 2016

By combining super-fine electrodes and tiny amounts of a very specific drug, Duke University researchers have singled out a circuit in mouse brains and taken control of it to dial an animal's mood up and down.

Research shows how visual perception slows with age

June 21, 2016

Grandparents may be some of the best storytellers around, in the sense that they usually have plenty of stories to tell. What they're not always as good at, however, is staying on topic when they regale others with their ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.