Microstructural Degeneration of the Corpus Callosum in Parkinson's Disease with Unilateral Onset: A Free-Water Imaging Study

Background: Motor symptom laterality is an important clinical feature of PD that not only manifests as lateral limb dysfunction but also affects the nonmotor symptoms and the prognosis in PD patients. Previous studies suggested that the compensatory mechanisms in the dominant hemisphere of the brain may be an underlying explanation. The corpus callosum (CC) is the largest fiber connecting the two hemispheres of the brain. Considering the CC as the pointcut may help elucidate the mechanisms underlying how motor symptom laterality affects nonmotor symptoms and prognosis in PD patients. Purpose: To explore microstructural degeneration of the CC in PD patients with unilateral motor symptom onset and evaluate its relationship with motor and nonmotor performance. Methods: In this study, 201 right-handed PD patients with unilateral motor symptom onset (91 patients with left-onset [LPD] and 110 with right-onset [RPD]) and 100 right-handed healthy controls (HC) were included. A bitensor model of diffusion tensor imaging was applied to analyze free water (FW) as well as fractional anisotropy (FA_T) and mean diffusivity (MD_T) of the tissue compartment after correcting FW. These provide noninvasive in vivo measures of white matter integrity and pathological processes including atrophy, edema, and neuroinflammation. The CC was divided into halves along the median sagittal line, and each half was manually divided into five functional segments. A total of 10 subregions were obtained and numbered in sequence. The laterality index was calculated to quantify the asymmetry of the CC and its segments. A general linear model was used to compare among groups, and partial correlation analysis was performed to explore the relationships between the diffusion parameters of CC subregions and clinical manifestations. Results: Compared with HC, FW and FA_T of the bilateral CC were decreased in the LPD group, whereas MD_T in the right hemisphere was increased. In the LPD group, FA_T of all CC subregions except for subregions 1, 3, and 6 was significantly lower than HC, and MD_T in the anterior and posterior segments of the CC (CC subregions 1, 5-7, and 10) was significantly higher than HC. In the RPD group, FA_T of subregion 7 was significantly decreased and MD_T was increased than HC. Laterality index analysis of the CC indicated significant interhemispheric FA_T asymmetry in the anterior and middle in the RPD group, with a more significant reduction in the right CC. Moreover, degeneration of the CC and its subregions was related to motor and nonmotor symptoms in PD. Conclusions: More extensive CC damage was observed in the LPD group than in the RPD group. Additional, asymmetrical damage was observed in the anterior and middle segments of the CC in the RPD group, suggesting that differences in callosal degeneration patterns may be a potential mechanism underlying how asymmetrical motor symptoms affect the nonmotor symptoms and prognosis in PD.