Structural white matter alterations as compensatory mechanisms in Parkinson's disease: A systematic review of diffusion tensor imaging studies

Compensation is described as normal or near to normal performance in Parkinson's disease (PD), despite the ongoing neural loss. Functional compensation typically proceeds in an inverse U-shaped manner: compensation initiates in the prodromal phase, followed by an increasing episode until plateauing and diminishes in the advanced stages of the disease. The first evidence of the structural compensation was reported by functional magnetic resonance imaging studies. Recent studies, which have used diffusion tensor imaging (DTI) as the basis for their investigation, have shown improved white matter diffusional properties both in motor- and non-motor-related structures in association with improved clinical scores in patients with PD. The majority of DTI studies have demonstrated microstructural compensation in the prodromal/early stages of PD at the regional scale. However, there have been reports of compensation in later stages of the disease and the whole-brain/network scale that are probably due to the heterogeneous nature of PD. Although serving as a promising beginning to characterize compensation, lots remain to be clarified in understanding the underlying mechanisms of compensation and its structural pattern in PD. The existing knowledge gap necessitates studies that their main research questions are focused on structural compensation. This requirement becomes more apparent because structural compensation evidence has mostly emerged from the post hoc analysis of data and incidental findings of studies. Thus, future studies are required to investigate compensatory microstructural changes in PD to clarify the exact underlying mechanisms. These studies would also provide a basis to develop clinical improvements in the early diagnosis and management of PD.