Cognitive Thalamus

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PROJECT SUMMARY The Pulvinar (PUL) and Mediodorsal (MD) nuclei are higher order thalamic structures that are known to play critical roles in various cognitive domains. However, the precise mechanisms are unknown, with theories suggesting their role in either gating or facilitating functional connectivity across their cortical targets. Imoprtantly, recent evidence from schizophrenia patients suggests that these higher order thalamic-cortical interactions are perturbed and may even be causative to disease etiology. In this Center, we have assembled a group of investigators who will utilize behavior, electrophysiology, imaging in human and non-human animals to 1. Identify cognitive functional organization principles of higher-order thalamic nuclei in interacting with cortex; 2. Translate thalamic functionality from animal models to the healthy and diseased human brain; and 3. Develop a biologically plausible model for the human higher-order thalamus. The Center will be divided into 5 Scientific Projects and 3 Cores. Project 1 (PI Usrey) will combine electrophysiology and optical perturbations to study interactions between PUL and early visual cortical areas during attentional processing. Project 2 (PI Kastner) will take a large-scale network approach in the macaque to study interactions between the primate-specific mdPUL subdivision and fronto-parietal networks in attention, and also study interactions between the MD and frontal cortical areas in hierarchical reasoning and task switching. Project 3 (PI Halassa) will combine optical perturbations, electrophysiology and disease modeling in Tupaia to study interactions between PUL regulation of dorsal vs. ventral stream selection in attention, and MD regulation of frontal cortical interactions in hierarchical reasoning. Project 4 (PI Collins/Arcaro) will combine functional neuroimaging and behavior in humans to interrogate PUL and MD engagement with their cortical partners in attention and hierarchical reasoning, respectively. This will begin an exciting endeavor of determining what types of higher order thalamic contributions to cognition have expanded in the human brain. Project 5 (PI Woodward) will examine behavior-brain relationships (attention-PUL and decision making-MD) in schizophrenia patients, where the structural integrity of higher order thalamic connectivity to cortical partners is known to be impaired. Core A (PIs Kastner, Halassa and Usrey) will administratively manage this Center and involve important outreach and training activities. Core B (PI Chen) will provide analytical support for all projects and streamline data collection, curation and sharing across PIs with common format, as well as allow for data sharing with the broader community. Core C (PI Kopell) will generate computational models that will be iteratively refined by the collected data and provide testable prediction on an ongoing basis. Altogether, successful launching of this Center promises to provide new frameworks for the neural circuitry underlying cognitive processing and how the thalamus may be a target for enhancing cognition in schizophrenia.