Cell type- and circuit-specific error signals for cognitive flexibility

The brain forms expectations of future events and uses error signals arising from deviations in these expectations to update its internally stored model of the world. These expectations and their update through error signals are fundamental to many functions of the brain, including perception, decision-making, motor execution, and cognitive flexibility. Much past work has developed a foundation supporting this premise; however, the cellular and circuit mechanisms underlying error signaling and their use in updating expectations is not fully understood. The goal of the proposed research is to identify cell types and circuits that have specific functions for the signaling of errors and their use for learning. In the first aim, we will investigate if there are cell types that signal error updates across cortex and, if so, what role these signals play and how they may operate mechanistically. We hypothesize that a subtype of somatostatin inhibitory interneurons has a common, error-related function across cortical areas, tailored to the modality of each cortical area. We will test if this cell type’s activity correlates with error-related signals in the posterior parietal cortex, retrosplenial cortex, and visual cortex. Then, we will test if this cell type’s activity is necessary for neural and behavioral learning from error-related signals. Finally, we will examine how this cell type interacts with and changes the activity of neighboring neurons. In a second aim, we will investigate if there is a circuit for the signaling of errors in expected outcomes for cognitive flexibility. We hypothesize that the mediodorsal nucleus of the thalamus (MD) is critical for signaling outcome-related errors used to update rules linking sensation and action. First, we will survey activity across the brain to test whether MD is a focal point for these error-related signals. Second, we will test if the activity in MD is necessary for the cognitive flexibility underlying rule switching. Finally, we will investigate how MD’s signaling of errors in outcome expectations leads to updates in neural activity in cortical areas. Together, these studies will deepen our understanding of the mechanisms underlying how error-related signals are used to update the brain’s expectations of future events through the identification of specialized cell types and circuits for error-related signaling. Project Number: 1R01NS142028-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator: Christopher Harvey | Institution: HARVARD MEDICAL SCHOOL, BOSTON, MA | Award Amount: $579,740 | Activity Code: R01 | Study Section: Neuroscience of Basic Visual Processes Study Section[NBVP] View on NIH RePORTER: https://reporter.nih.gov/project-details/11294971