Impaired planning in Parkinson's disease is reflected by reduced brain activation and connectivity

Abstract

ObjectiveParkinson's disease (PD) often entails impairments of executive functions, such as planning. Although widely held that these impairments arise from dopaminergic denervation of the striatum, not all executive functions are affected early on, and the underlying neural dynamics are not fully understood. In a combined longitudinal and cross‐sectional study, we investigated how planning deficits progress over time in the early stages of PD compared to matched healthy controls. We used functional magnetic resonance imaging (fMRI) to identify accompanying neural dynamics.MethodsSeventeen PD patients and 20 healthy controls performed a parametric Tower of London task at two time points separated by ∼3 years (baseline and follow‐up). We assessed task performance longitudinally in both groups; at follow‐up, a subset of participants (14 patients, 19 controls) performed a parallel version of the task during fMRI. We performed meta‐analyses to localize regions‐of‐interest (ROIs), that is, the bilateral dorsolateral prefrontal cortex (DLPFC), inferior parietal cortex, and caudate nucleus, and performed group‐by‐task analyses and within‐group regression analyses of planning‐related neural activation. We studied task‐related functional connectivity of seeds in the DLPFC and caudate nucleus.ResultsPD patients, compared with controls, showed impaired task performance at both time‐points, while both groups showed similar performance reductions from baseline to follow‐up. Compared to controls, patients showed lower planning‐related brain activation together with decreased functional connectivity.ConclusionThese findings support the notion that planning is affected early in the PD disease course, and that this impairment in planning is accompanied by decreases in both task‐related brain activity and connectivity. Hum Brain Mapp 36:3703–3715, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Functional connectivity alterations in Parkinson’s disease during the stop-signal task

“…Seed-based analyses of task- related functional connectivity are therefore likely to show desynchronization of these seed regions with other brain areas with progression of PD. Our results are also consistent with our previous finding of lower connectivity between the DLPFC and IPL in the same sample of medicated PD patients during planning in the Tower of London Task [13].…”

“…GPPI allows for the analysis of functional connectivity between brain regions in the context of a specific task by adding psychophysiological interactions as regressors to the model [12]. Based on our own previous gPPI studies in this sample [13] and studies from others [14, 15], we further hypothesized that task-related functional connectivity during the stop-signal task would be lower in PD patients compared with well-matched healthy subjects.…”

Disrupted Nodal and Hub Organization Account for Brain Network Abnormalities in Parkinson’s Disease

“…PD patients often show executive dysfunction due to a disruption of the fronto-striatal dopamine system (Gratwicke et al, 2015). In addition, structural (Koshimori et al, 2015) and functional (Trujillo et al, 2015; Wu et al, 2015) changes in this cortical area and their association with cognitive impairment have been reported consistently in these patients (Koshimori et al, 2015). …”

Partial lesion of the nigrostriatal dopamine pathway in rats impairs egocentric learning but not spatial learning or behavioral flexibility.

“…PD patients show prefrontal-dependent impairments in the Wisconsin Card Sorting Task (Bowen et al, 1975), spatial working memory (Bradley et al, 1989; Owen et al, 1992, 1997), attentional set shifting (Downes et al, 1989; Owen et al, 1997; Cools et al, 2001; Kehagia et al, 2009), the Stroop task (Brown & Marsden, 1991), and planning tasks (Morris et al, 1988; Owen et al, 1992; Trujillo et al, 2015). Tasks targeting orbitofrontal function, such as reversal learning, have produced inconsistent results (e.g., Swainson et al, 2000; Peterson et al, 2009; Poletti et al, 2011).…”