Compensatory neural mechanisms in cognitively unimpaired Parkinson disease

ObjectiveCognitive impairments in Parkinson disease (PD) are thought to be caused in part by dopamine dysregulation. However, even when nigrostriatal dopamine neuron loss is severe enough to cause motor symptoms, many patients remain cognitively unimpaired. It is unclear what brain mechanisms allow these patients to remain cognitively unimpaired despite substantial dopamine dysregulation. MethodsThirty‐one cognitively unimpaired PD participants off dopaminergic medications were scanned using functional magnetic resonance imaging while they performed a working memory task, along with 23 controls. We first compared the PD off medication (PD_OFF) group with controls to determine whether PD participants engage compensatory frontostriatal mechanisms during working memory. We then studied the same PD participants on dopaminergic medications to determine whether these compensatory brain changes are altered with dopamine. ResultsControls and PD showed working memory load‐dependent activation in the bilateral putamen, anterior–dorsal insula, supplementary motor area, and anterior cingulate cortex. Compared to controls, PD_OFF showed compensatory hyperactivation of bilateral putamen and posterior insula, and machine learning algorithms identified robust differences in putamen activation patterns. Compared to PD_OFF, the PD on medication group showed reduced compensatory activation in the putamen. Loss of compensatory hyperactivation on dopaminergic medication correlated with slow...
Source: Annals of Neurology - Category: Neurology Authors: Tags: Research Article Source Type: research