Subgrouping and structural brain connectivity of Parkinson's disease – past studies and future directions

Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder associated with several motor and non-motor dysfunctions. The wide variety of clinical features often leads to divergent symptom progressions. Most PD studies have attempted subgrouping based on clinical features to help understand the disease etiology and thereby contribute toward specific treatment. However, clinical symptoms have proven to be overlapping, arbitrary, and non-reliable in several cases, often biasing the deciphered subgroups. Moreover, the prodromal phase complicates diagnosis and subgrouping as it is characterized by limited clinical symptom expression. Hence, recent studies have used data-driven machine learning and deep learning methods to data-mine the heterogeneity and obtain subgroups. Structural Magnetic Resonance Imaging (sMRI) is a non-invasive approach for visualization and analysis of anatomical tissue properties of brain. It has enabled the detection of brain abnormalities and is a potential modality for subgrouping.

This review article starts with a comprehensive discussion of clinical symptoms-based and data-driven structural neuroimaging-based subgrouping approaches in PD. Secondly, we summarize the work done in brain connectivity studies using structural MRI for PD. We give an overview of mathematical definitions, connectivity metrics, brain connectivity software, and widespread network atlases. Finally, we discuss the inherent challenges and give practical suggestions on selecting methods that could be attempted for subgrouping and connectivity analysis using structural MRI data for future Parkinson's research.