Dopaminergic modulation of neural correlates of working memory in Parkinson’s Disease

Abstract

ObjectiveBrain mechanisms underlying performance of working memory (WM) vary according to domain specific requirements of the WM task. In Parkinson’s Disease (PD) domain specific WM tasks can be differentially affected. MethodWe investigated the pattern of brain activation during performance of domain specific working memory tasks in nine patients with early PD before (OFF-state) and after challenge with 200mg of levodopa (ON-state) by functional Magnetic Resonance Imaging (fMRI) using two variants of a phonological and one visual delayed matched to sample task paradigm. Eleven healthy volunteers were studied with the same protocol once. ResultsBehavioural data showed no significant difference of accuracy in performance of the WM tasks between PD and healthy controls. During performance of the verbal WM task fMRI revealed reduced activity within the left middle frontal gyrus, right cerebellum and left posterior inferior temporal gyrus in patients with PD. These abnormalities could be reversed by levodopa. In contrast, reduced activity within the right prefrontal cortex, that was found during visuospatial WM performance remained unchanged after levodopa administration. ConclusionsOur findings demonstrate altered brain activity in PD during verbal and visuospatial WM tasks and show different responses of these disturbed WM networks to levodopa.