Brain dopaminergic modulation associated with executive function in Parkinson's disease

Abstract

The progressive development of deficits in executive functions, including action planning, is a well-known complication of Parkinson's disease. A dysfunction of the prefrontal lobe, which is known to be involved in the control of inhibitory processes, could explain the difficulties in initiating behavior or inhibiting ongoing actions in patients with PD. The strong dopaminergic innervation of the prefrontal cortex raises questions about the putative effects of dopa therapy on this cognitive impairment. In the present study, we used fMRI to examine the functional influence of dopa therapy on neural activity during a go/no-go task in nine patients with and without levodopa treatment and in matched controls. Whereas the patient and control subjects exhibited the same performance during the go/no-go task, different patterns of brain activation were observed depending on the dopaminergic status. The drug-off state was characterized by more widely distributed brain activity, mainly in the bilateral caudate. Levodopa did not fully restore normal brain activation and induced changes in the pattern of cingulate cortex activity, which was more pronounced in the rostral part in the drug-off state and in the caudal part after levodopa intake. These results support the idea of a critical role for dopamine in the control of executive functions in patients with PD.