Department of Psychology, Westfälische Wilhelms-Universität, 48149, Münster, Germany.
Institute of Neuroscience and Medicine (INM3), Cognitive Neuroscience, Research Centre Jülich, 52425, Jülich, Germany.
Brain Struct Funct. 2018 Jun;223(5):2097-2111. doi: 10.1007/s00429-018-1616-2. Epub 2018 Jan 27.
Parkinson's disease (PD), which is caused by degeneration of dopaminergic neurons in the midbrain, results in a heterogeneous clinical picture including cognitive decline. Since the phasic signal of dopamine neurons is proposed to guide learning by signifying mismatches between subjects' expectations and external events, we here investigated whether akinetic-rigid PD patients without mild cognitive impairment exhibit difficulties in dealing with either relevant (requiring flexibility) or irrelevant (requiring stability) prediction errors. Following our previous study on flexibility and stability in prediction (Trempler et al. J Cogn Neurosci 29(2):298-309, 2017), we then assessed whether deficits would correspond with specific structural alterations in dopaminergic regions as well as in inferior frontal cortex, medial prefrontal cortex, and the hippocampus. Twenty-one healthy controls and twenty-one akinetic-rigid PD patients on and off medication performed a task which required to serially predict upcoming items. Switches between predictable sequences had to be indicated via button press, whereas sequence omissions had to be ignored. Independent of the disease, midbrain volume was related to a general response bias to unexpected events, whereas right putamen volume correlated with the ability to discriminate between relevant and irrelevant prediction errors. However, patients compared with healthy participants showed deficits in stabilisation against irrelevant prediction errors, associated with thickness of right inferior frontal gyrus and left medial prefrontal cortex. Flexible updating due to relevant prediction errors was also affected in patients compared with controls and associated with right hippocampus volume. Dopaminergic medication influenced behavioural performance across, but not within the patients. Our exploratory study warrants further research on deficient prediction error processing and its structural correlates as a core of cognitive symptoms occurring already in early stages of the disease.
帕金森病（PD）是由中脑多巴胺能神经元变性引起的，导致包括认知能力下降在内的异质临床表现。由于多巴胺能神经元的相位信号被提议通过表示主体期望与外部事件之间的不匹配来指导学习，因此我们在这里研究了无轻度认知障碍的运动不能-僵硬 PD 患者是否在处理相关（需要灵活性）或不相关（需要稳定性）预测误差方面存在困难。在我们之前关于预测中的灵活性和稳定性的研究（Trempler 等人，J Cogn Neurosci 29(2):298-309, 2017）之后，我们评估了缺陷是否与多巴胺能区域以及下额叶皮层、内侧前额叶皮层和海马体的特定结构改变相对应。21 名健康对照者和 21 名正在接受和不接受药物治疗的运动不能-僵硬 PD 患者进行了一项需要连续预测即将到来项目的任务。需要通过按钮按下指示可预测序列之间的切换，而必须忽略序列遗漏。独立于疾病，中脑体积与对意外事件的一般反应偏向相关，而右侧壳核体积与区分相关和不相关预测误差的能力相关。然而，与健康参与者相比，患者在稳定对不相关预测误差方面表现出缺陷，与右侧下额叶回和左侧内侧前额叶皮层的厚度相关。由于相关预测误差导致的灵活更新在患者中也受到影响，与右侧海马体体积相关。与对照组相比，多巴胺能药物影响了患者的行为表现，而不是影响了患者内部的表现。我们的探索性研究表明，作为疾病早期出现的认知症状核心的预测误差处理及其结构相关性值得进一步研究。
