Neuroimaging Detectable Differences between Parkinson's Disease Motor Subtypes: A Systematic Review

Background: The neuroanatomical substrates of Parkinson's disease (PD) with tremor-dominance (TD) and those with non-tremor dominance (nTD), postural instability and gait difficulty (PIGD), and akinetic-rigid (AR) are not fully differentiated. A better understanding of symptom specific pathoanatomical markers of PD subtypes may result in earlier diagnosis and more tailored treatment. Here, we aim to give an overview of the neuroimaging literature that compared PD motor subtypes. Methods: A systematic literature review on neuroimaging studies of PD subtypes was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Search terms submitted to the PubMed database included: "Parkinson's disease", "MRI" and "motor subtypes" (TD, nTD, PIGD, AR). The results are first discussed from macro to micro level of organization (i.e., (1) structural; (2) functional; and (3) molecular) and then by applied imaging methodology. Findings: Several neuroimaging methods including diffusion imaging and positron emission tomography (PET) distinguish specific PD motor subtypes well, although findings are mixed. Furthermore, our review demonstrates that nTD-PD patients have more severe neuroalterations compared to TD-PD patients. More specifically, nTD-PD patients have deficits within striato-thalamo-cortical (STC) circuitry and other thalamocortical projections related to cognitive and sensorimotor function, while TD-PD patients tend to have greater cerebello-thalamo-cortical (CTC) circuitry dysfunction. Conclusions: Based on the literature, STC and CTC circuitry deficits seem to be the key features of PD and the subtypes. Future research should make greater use of multimodal neuroimaging and techniques that have higher sensitivity in delineating subcortical structures involved in motor diseases.