Department of Psychology, University of Michigan, Ann Arbor, MI 48109, United States.
Department of Radiology, University of Michigan, Ann Arbor, MI 48109, United States; Department of Neurology, University of Michigan, Ann Arbor, MI 48109, United States; Morris K. Udall Center of Excellence for Parkinson's Disease Research, University of Michigan, Ann Arbor, MI 48109, United States; Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI 48109, United States.
Neuroimage. 2019 Apr 15;190:94-106. doi: 10.1016/j.neuroimage.2018.01.021. Epub 2018 Jan 11.
Executive functions are complex both in the cognitive operations involved and in the neural structures and functions that support those operations. This complexity makes executive function highly vulnerable to the detrimental effects of aging, brain injury, and disease, but may also open paths to compensation. Neural compensation is often used to explain findings of additional or altered patterns of brain activations by older adults or patient populations compared to young adults or healthy controls, especially when associated with relatively preserved performance. Here we test the hypothesis of an alternative form of compensation, between different neuromodulator systems. 135 patients with Parkinson's Disease (PD) completed vesicular monoamine transporter type2 (VMAT2) and acetylcholinesterase PET scanning to assess the integrity of nigrostriatal dopaminergic, thalamic cholinergic, and cortical cholinergic pathways, and a behavioral test (Stroop + task-switching) that puts high demands on conflict processing, an important aspect of executive control. Supporting the compensatory hypothesis, regression models controlling for age and other covariates revealed an interaction between caudate dopamine and cortical cholinergic integrity: Cortical cholinergic integrity was a stronger predictor of conflict processing in patients with relatively low caudate dopaminergic function. These results suggest that although frontostriatal dopaminergic function plays a central role in executive control, cholinergic systems may also make an important contribution. The present results suggest potential pathways for remediation, and that the appropriate interventions for each patient may depend on their particular profile of decline. Furthermore, they help to elucidate the brain systems that underlie executive control, which may be important for understanding other disorders as well as executive function in healthy adults.
执行功能在涉及的认知操作以及支持这些操作的神经结构和功能方面都非常复杂。这种复杂性使执行功能极易受到衰老、脑损伤和疾病的不利影响，但也可能为代偿提供途径。神经代偿通常用于解释与年轻人或健康对照组相比，老年人或患者群体的大脑活动出现额外或改变模式的发现，尤其是当与相对保留的表现相关时。在这里，我们测试了不同神经调质系统之间存在另一种代偿形式的假设。135 名帕金森病（PD）患者完成了囊泡单胺转运体 2（VMAT2）和乙酰胆碱酯酶 PET 扫描，以评估黑质纹状体多巴胺能、丘脑胆碱能和皮质胆碱能通路的完整性，以及一项行为测试（Stroop+任务转换），该测试对冲突处理提出了很高的要求，冲突处理是执行控制的一个重要方面。支持代偿假说，控制年龄和其他协变量的回归模型显示出尾状核多巴胺和皮质胆碱能完整性之间的相互作用：在尾状核多巴胺能功能相对较低的患者中，皮质胆碱能完整性是冲突处理的更强预测因子。这些结果表明，尽管额纹状体多巴胺能功能在执行控制中起着核心作用，但胆碱能系统也可能做出重要贡献。目前的结果表明了修复的潜在途径，并且每个患者的适当干预措施可能取决于他们特定的衰退模式。此外，它们有助于阐明执行控制的大脑系统，这对于理解其他疾病以及健康成年人的执行功能可能很重要。
