Investigating cognitive functions mediated by ventral and dorsal striatum

研究腹侧和背侧纹状体介导的认知功能

• 批准号: RGPIN-2019-07300
• 负责人: MacDonald, Penny
• 金额: $ 2.04万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=716685
• 关键词: Investigating; cognitive; functions; mediated; ventral

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 putamenand the ventral striatum (VS)constituting the nucleus accumbens and most ventral aspects of the caudate and putamenseem 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.

认知神经科学旨在揭示认知过程的神经基础。大多数认知研究都集中在大脑皮层。然而，皮质下结构越来越多地参与这些功能。 有证据表明纹状体？一组皮质下核团的输入区域称为基底神经节？支持一系列认知过程。背侧纹状体（DS）和腹侧纹状体（VS）分别由尾状核和壳核组成，而尾状核和壳核的大部分腹侧则支持不同的认知功能。 这可能是由于DS和VS具有不同的多巴胺能供应，前者的黑质背侧部（SNc）和后者的腹侧被盖区（VTA）。 DS和VS也有几乎不重叠的皮质投射。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（目标1），并划定黑质纹状体和中脑边缘/中皮层多巴胺能系统（目标2）的主要目标，拟议的研究。最终，这项研究将为认知和行为理论提供信息。 我们将扩大我们的调查认知功能介导的纹状体，以及澄清黑质纹状体与中脑边缘/中皮层多巴胺能系统的差异。在这一点上，尽管高度一致，但我们对DS和VS功能的初步结果是通过不同参与者组的行为测试得出的，有时使用3 T MRI进行DA替代药物的测试。 多巴胺能系统中的活性是从与较大文献相关的行为模式和/或将血氧水平依赖性（BOLD）信号解释为DA释放和受体刺激的代表来推断的。 DA系统内的复杂性和时刻到时刻的波动保证了这些问题的调查与补充和更精确的成像技术。 在实验1中，我们将进行更详细的调查，使用前和突触后DA配体的正电子发射断层扫描（PET）。最后，在实验2和3中，我们的目标是探索结构和功能活动/连接DA通路与7 T MRI。 在这些实验中，我们将探索以下假设。 假设1：VS介导一般学习，包括非联想，单一项目的显式编码。 假设2：DS并不是学习的基础，而是出现在决策需要整合信息和审议的背景下。 假设三：在人类中，从SNc和VTA到DS，VS和皮质的子区域的DArgic通路内的活动和投射模式比目前所认识的更加微妙。我们希望了解在DArgic系统中使用突触前和突触后DA配体在PET/MRI和使用7 T MRI的差异。