Fiber-Specific White Matter Alterations in Parkinson's Disease

Abstract

Background: Disruption of brain circuits, including the basal ganglia network, is one of the core mechanisms of Parkinson’s disease(PD). Understanding the structural connection alterations in PD is the key for relevant treatment. Although, due to methodological limitations, most previous studies suffered from the difficulty of locating white matter damages to specific fiber tracts. In the present study, we aimed to demonstrate tract-specific white matter structural changes and its relationship with clinical symptoms. Methods: Nighty-eight PD patients(41 patients were at early stage and 57 were at middle stage) and 76 healthy controls were enrolled and underwent brain magnetic resonance imaging and neuropsychological tests. We implemented the fixel-based analysis method to investigate both micro- and macro-structural changes in the white matter fibers of PD patients, and to investigate their correlation with clinical symptoms. Findings: We found decreased fiber density(FD) of the corpus callosum and increased FD of the cortical spinal tract in PD patients comparing to healthy controls. We also found increased fiber-bundle cross-section(FC) of the superior cerebellar peduncle of PD patients. Further region-of-interest analysis showed that FD values of the corpus callosum in PD patients were negatively correlated with UPDRS-III scores(r=0.001, p=-0.334), HAMD-17 scores(r=0.043, p=-0.205) and HAMA scores(r=0.02, p=-0.234). Also, log transformed FC values of superior cerebellar peduncle were negatively correlated with HAMD-17 scores(r=0.013, p=-0.251) and positively correlated with MMSE scores(r=0.002, p=0.312). Interpretation: PD patients had both decreased and increased white matter integrity within specific fiber bundles. Additionally, these white matter alterations were different across disease stages, suggesting complex pathological and compensatory changes during the development of PD. Funding Statement: This study was supported by the 13th Five-year Plan for National Key Research and Development Program of China (Grant No. 2016YFC1306600), the Health Foundation for Creative Talents in Zhejiang Province (2016). Declaration of Interests: The authors have no conflicts of interest to declare. Ethics Approval Statement: All the subjects had signed written informed consent forms before participating in the study. This research was approved by the Medical Ethics Committee of 2nd Affiliated Hospital, Zhejiang University.