Bidirectional Correlations Between Dopaminergic Function and Motivation in Parkinson's Disease

Area of Science:

• Neuroscience
• Radiology
• Psychiatry

Background:

• Parkinson disease (PD) is associated with motivational alterations, including impulse control disorders (ICDs) and apathy.
• The neurobiological underpinnings of these motivational changes, particularly the role of striatal dopamine function, require further elucidation.

Purpose of the Study:

• To investigate the relationship between striatal dopaminergic function and motivational alterations in Parkinson disease.
• To compare vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DaT) imaging in PD patients with ICDs, apathy, or neither.

Main Methods:

• Vesicular monoamine transporter 2 (VMAT2) PET imaging (18F-AV133) and dopamine transporter (DaT) scans were analyzed from the Parkinson's Progression Markers Initiative (PPMI) database.
• Apathy and ICDs were assessed using the Movement Disorders Society-revised Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP).
• Analysis of variance (ANOVA) and log-linear mixed-effects (LME) regression were used to model striatal binding ratios (SBRs) with neurobehavioral metrics.

Main Results:

• Significant groupwise differences in VMAT2 binding were observed in the right anterior putamen, right posterior putamen, and right caudate.
• The impulse control disorder (ICD) group showed elevated right striatal VMAT2 binding, while the apathy group exhibited reduced binding compared to controls.
• Normalizing VMAT2 with DaT SBR strengthened bidirectional correlations, with high VMAT2/DaT associated with ICDs and low VMAT2/DaT associated with apathy.

Conclusions:

• Striatal presynaptic dopaminergic function, as measured by VMAT2 and DaT imaging, is implicated in the neurobiological basis of motivational dysregulation in Parkinson disease.
• Findings suggest a spectrum of dopaminergic function, from high in ICDs to low in apathy, contributing to distinct motivational phenotypes in PD.