Brain and Mind Institute, University of Western Ontario London, Ontario, Canada.
Faculty of Law, University of Ottawa Ottawa, Ontario, Canada.
Ann Clin Transl Neurol. 2014 Jun;1(6):390-400. doi: 10.1002/acn3.62. Epub 2014 May 16.
Understanding cognition mediated by the striatum can clarify cognitive deficits in Parkinson's disease (PD). Previously, we claimed that dorsal striatum (DS) mediates cognitive flexibility. To refute the possibility that variation in cognitive effort confounded our observations, we reexamined our data to dissociate cognitive flexibility from effort. PD provides a model for exploring DS-mediated functions. In PD, dopamine-producing cells supplying DS are significantly degenerated. DS-mediated functions are impaired off and improved on dopamine replacement medication. Functional magnetic resonance imaging (fMRI) can confirm striatum-mediated functions.
Twenty-two PD patients, off-on dopaminergic medication, and 22 healthy age-matched controls performed a number selection task. Numerical distance between number pairs varied systematically. Selecting between two numbers that are closer versus distant in magnitude is more effortful: the symbolic distance effect. However, selecting between closer versus distant number pairs is equivalent in the need to alter attention or response strategies (i.e., cognitive flexibility). In Experiment 2, 28 healthy participants performed the same task with simultaneous measurement of brain activity with fMRI.
The symbolic distance effect was equivalent for PD versus control participants and across medication sessions. Furthermore, symbolic distance did not correlate with DS activation using fMRI. In this dataset, we showed previously that integrating conflicting influences on decision making is (1) impaired in PD and improved by dopaminergic therapy and (2) associated with preferential DS activation using fMRI.
These findings support the notion that DS mediates cognitive flexibility specifically, not merely cognitive effort, accounting for some cognitive deficits in PD and informing treatment.
了解纹状体介导的认知可以阐明帕金森病（PD）的认知缺陷。以前，我们声称背侧纹状体（DS）介导认知灵活性。为了反驳认知努力的变化混淆了我们的观察结果的可能性，我们重新检查了我们的数据，以将认知灵活性与努力区分开来。PD 为探索 DS 介导的功能提供了模型。在 PD 中，供应 DS 的产生多巴胺的细胞显著退化。DS 介导的功能在多巴胺替代药物治疗时受损，在治疗时改善。功能磁共振成像（fMRI）可确认纹状体介导的功能。
22 名 PD 患者，停用-启用多巴胺能药物治疗，以及 22 名年龄匹配的健康对照者进行了数字选择任务。数字对之间的数值距离系统地变化。选择两个在大小上更近或更远的数字比选择两个在大小上更近或更远的数字更费力：符号距离效应。但是，在需要改变注意力或反应策略（即认知灵活性）时，选择更近或更远的数字对是等效的。在实验 2 中，28 名健康参与者进行了相同的任务，同时使用 fMRI 测量大脑活动。
PD 与对照组参与者以及在药物治疗期间的符号距离效应是等效的。此外，符号距离与使用 fMRI 的 DS 激活无关。在这个数据集，我们以前曾表明，整合对决策的冲突影响是（1）在 PD 中受损，并且在多巴胺能治疗时改善，以及（2）与使用 fMRI 的优先 DS 激活相关。
这些发现支持了这样一种观点，即 DS 专门介导认知灵活性，而不仅仅是认知努力，解释了 PD 中的一些认知缺陷，并为治疗提供了信息。
