Neostriatal Morphology in Parkinson's Disease: In Vivo Biomarkers of Disease Progression Stages and Clinical Symptoms

Background: Parkinson’s disease (PD) is associated with a wide range of clinical symptoms relating to frontostriato-pallido-thalamo-cortical circuits that traverse the neostriatum. The development of successful therapeutic interventions for PD will require a deeper knowledge of disease-related neurobiological changes that take place in the PD brain, the spatio-temporal course of these changes and improved understanding of the neural circuit basis of the clinical dysfunctions that characterize the disease. Objectives: We sought to investigate the morphological changes to the neostriatum in PD, how these changes manifest over the disease course and whether any morphological changes were correlated with measures of clinical function. Methods: The caudate nucleus and putamen were manually traced on 3-T T1-weighted magnetic resonance imaging scans of 74 probable PD participants and 27 controls. The three-dimensional object maps were then quantitatively analysed for volume and shape. Correlations of morphology with clinical function were investigated using the participant’s performance on a range of motor and non-motor tests. Findings: Bilateral caudate nuclei and putamina volumes were significantly smaller in the PD group compared to controls (5.5% reduction, p = 0.037 and 5.97% reduction, p = 0.039, respectively). Significant correlations were demonstrated between reduced putamina volumes and impairment in motor function as well as between reduced caudate nuclei volumes and impaired cognitive function. Conclusions: PD involves atrophic changes to the neostriatum that are related to clinical function. This research provides support for the neostriatum as a putative biomarker in PD and reiterates the important role of neural circuitry in PD