Dopaminergic Modulation of Medial Prefrontal Cortex Deactivation in Parkinson Depression.

Anders H Andersen,Charles D Smith,Lee X Blonder,Richard J Kryscio,Catherine A Martin,John T Slevin,Frederick A Schmitt

doi:10.1155/2015/513452

Abstract

Parkinson's disease (PD) is associated with emotional abnormalities. Dopaminergic medications ameliorate Parkinsonian motor symptoms, but less is known regarding the impact of dopaminergic agents on affective processing, particularly in depressed PD (dPD) patients. The aim of this study was to examine the effects of dopaminergic pharmacotherapy on brain activation to emotional stimuli in depressed versus nondepressed Parkinson disease (ndPD) patients. Participants included 18 ndPD patients (11 men, 7 women) and 10 dPD patients (7 men, 3 women). Patients viewed photographs of emotional faces during functional MRI. Scans were performed while the patient was taking anti-Parkinson medication and the day after medication had been temporarily discontinued. Results indicate that dopaminergic medications have opposite effects in the prefrontal cortex depending upon depression status. DPD patients show greater deactivation in the ventromedial prefrontal cortex (VMPFC) on dopaminergic medications than off, while ndPD patients show greater deactivation in this region off drugs. The VMPFC is in the default-mode network (DMN). DMN activity is negatively correlated with activity in brain systems used for external visual attention. Thus dopaminergic medications may promote increased attention to external visual stimuli among dPD patients but impede normal suppression of DMN activity during external stimulation among ndPD patients.

Highlights

Parkinson’s disease (PD) is characterized by tremor, muscular rigidity, and bradykinesia
A companion FreeSurfer analysis of the structural MRI scans did not show any significant differences in medial prefrontal cortex brain region volume between the groups of nondepressed and depressed PD patients adjusted for age and education
We found that dopaminergic medications used to treat PD have opposite effects in two regions of the prefrontal cortex depending upon whether or not the patient suffers from depression

Summary

Introduction

Parkinson’s disease (PD) is characterized by tremor, muscular rigidity, and bradykinesia. Individuals with PD experience nonmotor symptoms, such as impairments in cognitive and emotional processing, including depression, anxiety, and apathy (see Blonder and Slevin [1] for a review). Dopaminergic drugs show considerable efficacy in treating PD motor symptoms, dopaminergic pharmacotherapy may have variable effects on cognitive and affective processing depending upon the mood state of the PD patient. Blonder et al [2] found that depressed PD (dPD) patients performed more poorly on neuropsychological tests of working memory and facial affect recognition while on dopaminergic medications than while off. Functional neuroimaging studies of dPD patients have shown abnormalities in the caudate, orbitofrontal cortex, medial frontal cortex, anterior cingulate, limbic system, and thalamus [3,4,5,6,7].

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