Investigating cognitive functions mediated by ventral and dorsal striatum

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Cognitive neuroscience aims to uncover neural substrates of cognitive processes. Most studies of cognition focus on the cerebral cortex. Subcortical structures are increasingly implicated in these functions, however. Evidence is accruing that the striatum?the input region of a group of subcortical nuclei termed the basal ganglia?supports a range of cognitive processes. The dorsal striatum (DS)-comprised of the bulk of the caudate nucleus and putamen-and the ventral striatum (VS)-constituting the nucleus accumbens and most ventral aspects of the caudate and putamen-seem to support different cognitive functions. This is possibly due to the fact that DS and VS have differing dopaminergic supplies, the substantia nigra pars compacta (SNc) for the former and the ventral tegmental area (VTA) for the latter. The DS and VS also have almost non-overlapping cortical projections. The distinctiveness of these striatal subgregions potentially account for the heterogeneity of striatal functions. Outlining cognitive functions of striatum (Aim 1), and delineating the nigrostriatal and mesolimbic/mesocortical dopaminergic systems (Aim 2) are primary goals of the proposed research. Ultimately, this research will inform theories of cognition and behaviour. We will extend our investigations of cognitive functions mediated by the striatum, as well as clarify differences in the nigrostriatal versus mesolimbic/mesocortical dopaminergic systems. To this point, though highly consistent, our initial results vis-à-vis DS and VS functions have arisen through behavioural tests in different participant groups, sometimes tested off and on DA-replacement medication with 3T MRI. Activity in dopaminergic systems are inferred from patterns of behaviour in relation to the larger literature and/or interpreting blood-oxygenation-level-dependent (BOLD) signal as a proxy for DA release and receptor stimulation. Complexity and moment-to-moment fluctuations within DA systems warrant investigation of these questions with complementary and more precise imaging techniques. In Experiment 1 we will pursue more detailed investigation using pre- and post-synaptic DA ligands in positron emission tomography (PET). Finally, in Experiments 2 & 3 we aim to explore structural and functional activity/connectivity within DA pathways with 7T MRI. Across these experiments we will explore the following hypotheses. Hypothesis 1: VS mediates general learning, including non-associative, explicit encoding of single items. Hypothesis 2: DS does not underlie learning but appears in contexts where decisions require integration of information and deliberation. Hypothesis 3: In humans, patterns of activity and projections within DArgic pathways from SNc and VTA to subregions of DS, VS, and cortex are more nuanced than currently appreciated. We expect to understand differences in DArgic systems using presynaptic and postsynaptic DA ligands in PET/MRI and using 7T MRI.