Abnormal distraction and load-specific connectivity during working memory in cognitively normal Parkinson's disease

Abstract

Visuospatial working memory impairments are common in Parkinson's disease (PD), yet the underlying neural mechanisms are poorly understood. The present study investigated abnormalities in context-dependent functional connectivity of working memory hubs in PD. Cognitively normal PD and control participants underwent fMRI while performing a visuospatial working memory task. To identify sources of dysfunction, distraction, and load-modulated connectivity were disentangled for encoding and retrieval phases of the task. Despite normal working memory performance in PD, two features of abnormal connectivity were observed, one due to a loss in normal context-related connectivity and another related to upregulated connectivity of hubs for which the controls did not exhibit context-dependent connectivity. During encoding, striatal-prefrontal coupling was lost in PD, both during distraction and high memory loads. However, long-range connectivity of prefrontal, medial temporal and occipital hubs was upregulated in a context-specific manner. Memory retrieval was characterized by different aberrant connectivity patterns, wherein precuneus connectivity was upregulated during distraction, whereas prefrontal couplings were lost as memory load approached capacity limits. Features of abnormal functional connectivity in PD had pathological and compensatory influences as they correlated with poorer working memory or better visuospatial skills. The results offer new insights into working memory-related signatures of aberrant cortico–cortical and corticostriatal functional connections, which may portend future declines in different facets of working memory.