Normal aging and Parkinson's disease are associated with the functional decline of distinct frontal-striatal circuits

Aleksandra Gruszka,Adam Hampshire,Roger A Barker,Adrian M Owen

doi:10.1016/j.cortex.2017.05.020

Abstract

Impaired ability to shift attention between stimuli (i.e. shifting attentional ‘set’) is a well-established part of the dysexecutive syndrome in Parkinson's Disease (PD), nevertheless cognitive and neural bases of this deficit remain unclear. In this study, an fMRI-optimised variant of a classic paradigm for assessing attentional control (Hampshire and Owen 2006) was used to contrast activity in dissociable executive circuits in early-stage PD patients and controls. The results demonstrated that the neural basis of the executive performance impairments in PD is accompanied by hypoactivation within the striatum, anterior cingulate cortex (vACC), and inferior frontal sulcus (IFS) regions. By contrast, in aging it is associated with hypoactivation of the anterior insula/inferior frontal operculum (AI/FO) and the pre-supplementary motor area (preSMA). Between group behavioural differences were also observed; whereas normally aging individuals exhibited routine-problem solving deficits, PD patients demonstrated more global task learning deficits. These findings concur with recent research demonstrating model-based reinforcement learning deficits in PD and provide evidence that the AI/FO and IFS circuits are differentially impacted by PD and normal aging.

Highlights

Idiopathic Parkinson's Disease (PD) is a common neurodegenerative condition, in which the prevalent motor features, namely: bradykinesia, rigidity and resting tremor are frequently accompanied by impairments of executive functioning that closely resemble difficulties seen in clinical groups with known damage to frontal cortex
Mean Response times (RTs) were recorded for each of the types of subject response, namely: ID and ED shifts committed both while working out the correct target, first response following a set change, first response following a reversal of reward contingency, first correct response to a target, and late correct response to a target
Cross group analyses were conducted for the same contrasts, in order to identify which brain regions were affected under which conditions in PD relative to controls

Summary

Introduction

Idiopathic Parkinson's Disease (PD) is a common neurodegenerative condition, in which the prevalent motor features, namely: bradykinesia, rigidity and resting tremor are frequently accompanied by impairments of executive functioning that closely resemble difficulties seen in clinical groups with known damage to frontal cortex This so-called ‘dysexecutive syndrome’ is evident even from the early stages of the disease (Foltynie, Brayne, Robbins, & Barker, 2004) and includes deficits of working memory, planning, attentional control and set-shifting performance (Gotham, Brown, & Marsden, 1988; Grossman, Crino, Reivich, Stern, & Hurtig, 1992; Lees & Smith, 1983; Morris et al, 1988; Owen et al, 1992; Taylor, Saint-Cyr, & Lang, 1986). Previous functional imaging studies exploring dysexecutive syndrome in PD have provided supporting evidence for a role of disruption in the nigrostriatal (Owen, Doyon, Dagher, Sadikot, & Evans, 1998), mesocortical (Cools, Stefanova, Barker, Robbins, & Owen, 2002; Mattay et al, 2002), or both of these pathways (Monchi, Petrides, Mejia-Constain, & Strafella, 2007), possibly depending on the extent to which the striatum is involved along with COMT genotype and drug therapy (Fallon et al, 2015; Williams-Gray, Hampshire, Barker, & Owen, 2008)

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