The visual thalamus has been extensively studied in terms of its anatomical organization, connectivity patterns, and basic neural response properties. However, its role in perception and cognition has remained poorly understood. The present application is a competing renewal submission for our grant ?Functions of the thalamus in perception and cognition? (RO1-EY017699). Work during the previous funding period has (i) characterized the topographic organization and functional response properties of the human pulvinar using high-resolution functional magnetic resonance imaging (fMRI) and (ii) defined a functional role of the macaque pulvinar in spatial selective attention using simultaneous multi-site recordings. The present application extends this work to investigate a causal role for the macaque pulvinar in attentional control. The pulvinar is the largest nucleus in the primate thalamus and is considered a higher-order thalamic nucleus, because it forms input- output loops almost exclusively with the cortex. From an anatomical perspective, the pulvinar is ideally positioned to regulate the transmission of information to the cortex and between cortical areas to influence perceptual and cognitive processes. Evidence from lesion studies in humans and monkeys demonstrate a critical involvement of the pulvinar in a number of fundamental cognitive functions, including orienting responses and the exploration of visual space, the filtering of unwanted information, and visually-guided behavior. Our studies during the last funding cycle have begun to establish neural correlates that may underlie some of these cognitive functions. We showed that the indirect pulvino-cortical connectivity appears to facilitate information transfer between areas in visual cortex. The proposed project will extend this work by probing the hypothesis that the pulvinar is an integral subcortical part of a large-scale attentional control network. Using a multi-modal methods approach that includes simultaneous multi-site recordings, neuroimaging, and reversible inactivation in monkeys trained on an Eriksen flanker task, we will pursue three specific aims. First, we will systematically characterize attentional modulation and functional interactions across pulvinar subdivisions by simultaneously recording from dozens of single- and multi-units using linear microelectrode arrays. Second, we will probe the idea that the pulvinar coordinates interactions within the fronto-parietal attention control network, thus acting as a temporal coordinator, by simultaneously recording from FEF, LIP and their interconnected projection zone in dorsal pulvinar. And third, we will probe a causal role for the pulvinar in attentional control. By reversibly inactivating dorsal pulvinar under MR-guidance and performing simultaneous recordings from FEF and LIP in our spatial attention task we will investigate local effects and interactions across the fronto- parietal network in relation to behavior. The significance of the proposed research is that it will further our understanding of the functions of thalamo-cortical interactions in perception and cognition using an innovative approach that combines cutting edge neuroimaging techniques with intracranial electrophysiology.
The proposed research is relevant to public health because it aims at advancing our understanding of neural mechanisms underlying selective attention, which is one of the most fundamental cognitive abilities for guiding behavior. This becomes strikingly clear when attentional selection mechanisms fail, such as in individuals afflicted with ADHD, visuo-spatial hemineglect that is often observed following stroke, and schizophrenia. Progress in understanding the basic mechanisms of selective attention is a first necessary step in developing effective treatment strategies for attentional deficits.
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