Reduced neural connectivity but increased task-related activity during working memory in de novo Parkinson patients

Objective: Patients with Parkinson's disease (PD) often suffer from impairments in executive functions, such as working memory deficits. It is widely held that dopamine depletion in the striatum contributes to these impairments through decreased activity and connectivity between task-related brain networks. We investigated this hypothesis by studying task-related network activity and connectivity within a sample of de novo patients with PD, versus healthy controls, during a visuospatial working memory task. Methods: Sixteen de novo PD patients and 35 matched healthy controls performed a visuospatial n-back task while we measured their behavioral performance and neural activity using functional magnetic resonance imaging. We constructed regions-of-interest in the bilateral inferior parietal cortex (IPC), bilateral dorsolateral prefrontal cortex (DLPFC), and bilateral caudate nucleus to investigate group differences in task-related activity. We studied network connectivity by assessing the functional connectivity of the bilateral DLPFC and by assessing effective connectivity within the frontoparietal and the frontostriatal networks. Results: PD patients, compared with controls, showed trend-significantly decreased task accuracy, significantly increased task-related activity in the left DLPFC and a trend-significant increase in activity of the right DLPFC, left caudate nucleus, and left IPC. Furthermore, we found reduced functional connectivity of the DLPFC with other task-related regions, such as the inferior and superior frontal gyri, in the PD group, and group differences in effective connectivity within the frontoparietal network. Interpretation: These findings suggest that the increase in working memory-related brain activity in PD patients is compensatory to maintain behavioral performance in the presence of network deficits. Hum Brain Mapp 36:1554-1566, 2015. (c) 2015 Wiley Periodicals, Inc