Perugini Alessandra, Basso Michele A
Joaquin Fuster Laboratory of Cognitive Neuroscience, Department of Psychiatry and Biobehavioral Sciences, Department of Neurobiology, and The Semel Institute for Neuroscience and Human Behavior and the Brain Research Institute, David Geffen School of Medicine, University of California , Los Angeles, California.
J Neurophysiol. 2018 Mar 1;119(3):849-861. doi: 10.1152/jn.00761.2017. Epub 2017 Nov 22.
Both cognitive and motor symptoms in people with Parkinson's disease (PD) arise from either too little or too much dopamine (DA). Akinesia stems from DA neuronal cell loss, and dyskinesia often stems from an overdose of DA medication. Cognitive behaviors typically associated with frontal cortical function, such as working memory and task switching, are also affected by too little or too much DA in PD. Whether motor and cognitive circuits overlap in PD is unknown. In this article, we show that whereas motor performance improves in people with PD when on dopaminergic medication compared with off medication, perceptual decision-making based on previously learned information (priors) remains impaired whether on or off medications. To rule out effects of long-term DA treatment and dopaminergic neuronal loss such as occur in PD, we also tested a group of people with dopa-unresponsive focal dystonia, a disease that involves the basal ganglia, like PD, but has motor symptoms that are insensitive to dopamine treatment and is not thought to involve frontal cortical DA circuits, unlike PD. We found that people with focal dystonia showed intact perceptual decision-making performance but impaired use of priors in perceptual decision-making, similar to people with PD. Together, the results show a dissociation between motor and cognitive performance in people with PD and reveal a novel cognitive impairment, independent of sensory and motor impairment, in people with focal dystonia. The combined results from people with PD and people with focal dystonia provide mechanistic insights into the role of basal ganglia non-dopaminergic circuits in perceptual decision-making based on priors.
帕金森病(PD)患者的认知和运动症状均源于多巴胺(DA)过少或过多。运动不能源于DA神经元细胞丢失,而运动障碍通常源于DA药物过量。通常与额叶皮质功能相关的认知行为,如工作记忆和任务切换,在PD中也会受到DA过少或过多的影响。在PD中,运动和认知回路是否重叠尚不清楚。在本文中,我们表明,与未服用多巴胺能药物时相比,PD患者在服用多巴胺能药物时运动表现有所改善,但基于先前学习信息(先验信息)的感知决策无论是否服药均仍受损。为了排除长期DA治疗和多巴胺能神经元丢失(如在PD中发生的情况)的影响,我们还测试了一组多巴无反应性局灶性肌张力障碍患者,这种疾病与PD一样累及基底神经节,但其运动症状对多巴胺治疗不敏感,且与PD不同,一般认为不涉及额叶皮质DA回路。我们发现,局灶性肌张力障碍患者的感知决策表现完好,但在感知决策中对先验信息的利用受损,这与PD患者类似。总之,这些结果表明PD患者的运动和认知表现存在分离,并揭示了局灶性肌张力障碍患者存在一种独立于感觉和运动障碍的新型认知障碍。PD患者和局灶性肌张力障碍患者的综合结果为基底神经节非多巴胺能回路在基于先验信息的感知决策中的作用提供了机制性见解。