Fronto-striatal atrophy correlates of inhibitory dysfunction in Parkinson's disease versus behavioural variant frontotemporal dementia

Introduction: Impulsive behaviours commonly manifest in treated Parkinson's disease (PD) patients, and, are typically viewed as sequelae of dopaminergic therapy. However, recent evidence shows that impulsivity in those patients may not only depend on medication status. Instead, there is the suggestion that dopaminergic therapy interacts with existing neuroanatomical and/or neurochemical abnormalities, to produce impulsive behaviour in certain vulnerable patients.

Methods: In this study, we investigated whether grey matter atrophy in fronto-striatal brain regions contributes to inhibitory dysfunction - a key feature of impulsive behaviour - in PD. Importantly, we contrasted 25 PD patients with 11 behavioural variant frontotemporal dementia (bvFTD) patients, who have well-established inhibitory dysfunction and related grey matter atrophy. We employed a questionnaire to assess impulsive behaviours (Barrett Impulsiveness Scale), and measures of verbal inhibitory function (Hayling Test) and response inhibitory function (a go/no-go task). Behavioural analyses were conducted to examine performance in the PD and bvFTD patients and in 15 healthy controls. Scores on the verbal and response inhibition tasks were also entered as covariates in a region of interest voxel-based morphometry analysis, to determine the grey matter correlates.

Results: PD patients showed impairments in inhibitory function, though to a milder degree than bvFTD patients. In the Parkinson's sample, frontal atrophy (namely, orbitofrontal and right inferior frontal cortex) was shown to correlate with verbal disinhibition, and striatal atrophy (right nucleus accumbens) was associated with response disinhibition, whereas a more distributed pattern of fronto-striatal atrophy was associated with the bvFTD patients' performance on inhibitory measures.

Conclusions: These results provide the first evidence that disinhibition in PD is related to fronto-striatal grey matter atrophy. Our study adds support to the hypothesis that impulsivity in PD is not solely mediated by dopaminergic medication effects, but that fronto-striatal structural abnormalities contribute to impulsive behaviours in these patients.