Functions and thalamocortical interactions of macaque higher order thalamus in cognitive control

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PROJECT 2 SUMMARY Project 2 (P2) will specifically contribute to Center hypothesis 1 and 3 by investigating cognitive control functions of two higher order thalamic nuclei, the medio-dorsal pulvinar (mdPUL; a primate-specific part of the pulvinar) and the MD along with their cortical networks. Lesion studies in humans and non-human primates (NHP) indicate that particularly these nuclei, which are primarily interconnected with the vastly expanded association cortices, play an important role in cognitive control functions including executive functioning, attention, and working memory. Specifically, we will target a mdPul-fronto-parietal (frontal eye field, FEF; lateral intraparietal area, LIP) network in the Center’s “Attention-under-perceptual-uncertainty” (APU) task and an MD- PFC-ACC (dorsolateral prefrontal cortex, dlPFC; anterior cingulate cortex, ACC) network in the Center’s “Hierarchical Decision Making” (HDM) task. The former study will permit a direct comparison of sensory-related parts of pulvinar probed in the same task in P1 at the large-scale, in P3 at the circuit level, and in P4 at the network level with the primate-specific mdPul. The latter study will complement the circuit level (P3) and network level (P4) investigation of the same HDM task. The results of all three animal projects are expected to provide a mechanistic model for the indirect neural measures obtained with neuroimaging in healthy humans in P4 and how they may be altered in disease (P5). The outcomes will inform the computational modeling approach taken in Core B. Given the similar data structure of the NHP projects (P1, P2), the project leaders will closely collaborate with Core C to establish common preprocessing routines and analytical strategies, as well as probe and develop innovative novel strategies to characterize simultaneously acquired population recordings. In P2, we propose to perform simultaneous recordings from thalamus and interconnected cortical areas to test key hypotheses about the role of higher order thalamus in cognition. In Aim 1, we will investigate interactions of a mdPul-LIP-FEF network in monkeys trained on our APU task. Our hypothesis is that pulvinar computes signals that reflect decision uncertainty to control functional connectivity across cortical areas during attentional allocation. In Aim 2, we will target dlPFC, ACC and their projection zones in MD in monkeys trained on our HDM task. Our hypothesis is that MD represents rule mapping uncertainty and will modulate ACC-dlPFC interactions based on such representation. In Aim 3, we will characterize differences and commonalities in thalamic computations and thalamocortical interactions of the circuits investigated in aims 1 and 2 to identify possible general functional organization principles that emerge regardless of the specific thalamocortical circuit that a nucleus is part of or the cognitive operations supported by it. Collectively, the expected outcomes for P2 will provide essential information towards a mechanistic and biologically plausible model for human thalamus function.