Investigating cognitive functions mediated by ventral and dorsal striatum

认知神经科学旨在揭示认知过程的神经基础。大多数关于认知的研究集中在大脑皮层。然而，皮层下结构越来越多地参与这些功能。越来越多的证据表明纹状体？一组被称为基底神经节的皮质下核的输入区？支持一系列认知过程。背纹状体（DS）——由大部分尾状核和壳核组成——和腹侧纹状体（VS）——构成伏隔核和尾状核和壳核的大部分腹侧部分——似乎支持不同的认知功能。这可能是由于DS和VS有不同的多巴胺能供应，前者是黑质致密部（SNc），后者是腹侧被盖区（VTA）。DS和VS也有几乎不重叠的皮层突起。这些纹状体亚区的独特性可能解释了纹状体功能的异质性。概述纹状体的认知功能（Aim 1），以及描述黑质纹状体和中边缘/中皮层多巴胺能系统（Aim 2）是本研究的主要目标。最终，这项研究将为认知和行为理论提供信息。我们将扩展纹状体介导的认知功能的研究，并阐明黑质纹状体与中边缘/中皮质多巴胺能系统的差异。在这一点上，虽然高度一致，但我们对-à-vis DS和VS功能的初步结果是通过不同参与者组的行为测试产生的，有时测试了da替代药物和3T MRI。多巴胺能系统的活性是从与大量文献相关的行为模式和/或解释血氧水平依赖（BOLD）信号作为DA释放和受体刺激的代理来推断的。数据分析系统的复杂性和实时波动需要用互补和更精确的成像技术来研究这些问题。在实验1中，我们将在正电子发射断层扫描（PET）中使用突触前和突触后的DA配体进行更详细的研究。最后，在实验2和3中，我们的目标是利用7T MRI探索DA通路中的结构和功能活性/连通性。通过这些实验，我们将探索以下假设。假设1:VS介导一般学习，包括单个项目的非联想、显式编码。假设2：动态决策不是学习的基础，而是出现在需要整合信息和深思熟虑的决策环境中。假设3：在人类中，从SNc和VTA到DS、VS和皮层亚区的daric通路的活动模式和投射比目前所认识的更加微妙。我们希望在PET/MRI和7T MRI中使用突触前和突触后DA配体来了解daric系统的差异。

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.