Charles E. Kaufman Foundation

2020 New Investigator Grant

Anna Schapiro, Ph.D.  Assistant Professor, Department of Psychology, University of Pennsylvania

Mechanisms of generalization: The role of neural inhibitory processes and time of day. 


Our focus and ability to do various tasks fluctuates across the day, with performance on tasks that require inhibition and cognitive control known to be best at our “on-peak” times — typically morning for older adults and evening for younger adults. Recent evidence indicates an intriguing flip side of this circadian coin. Tasks that require creativity and generalization seem to be better at “off-peak” times. What fluctuates in our brain to produce these changes? We hypothesize that circadian-related changes in the concentration of gamma-aminobutyric acid (GABA), the brain’s primary inhibitory neurotransmitter, may be the key. High concentrations of GABA suppress neural activity, which can facilitate cognitive control. Low concentrations of GABA cause activity to spread between neurons more easily, which may allow us to see connections between ideas that would otherwise appear unrelated. New technology using noninvasive magnetic resonance imaging allows us to measure at high spatial resolutions the concentration of GABA within the human brain. We will track changes in GABA across the day in humans and evaluate its effects on both neural activity and on cognition. We will also simulate these effects in a biologically realistic neural network model. The work will create new bridges between human neurobiology and high-level cognition, establishing methods that can be used broadly for relating neurotransmitter levels to neural activity. It has the potential to lead to fundamental new insights into the neural mechanisms that underlie our daily experience. 

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