Microstructural degeneration of the corpus callosum in Parkinson’s disease with unilateral onset: A free-water imaging study

Background The laterality of motor symptoms is an important clinical feature of PD, which is not only manifested as the lateral dysfunctions of limbs but also affects the non-motor symptoms and the prognosis in PD patients. Former studies suggested that the compensatory mechanisms in the dominant hemisphere of brain may be an underlying explanation. The corpus callosum (CC) is the largest fiber connecting the two hemispheres of brain. Considering CC as the pointcut may help to explore the mechanism of the laterality of motor symptoms affecting the non-motor symptoms and prognosis in PD patients. Purpose To explore microstructural degeneration of CC in PD patients with unilateral motor symptoms onset based on the bi-tensor model of diffusion imaging technology, and further explore the relationship with motor and non-motor performance. Methods A total of 201 right-handed PD patients with unilateral motor symptoms onset were included in this study, including 91 patients with left-onset (LPD) and 110 with right-onset (RPD), as well as 100 right-handed healthy controls (HC). A bi-tensor model of diffusion tensor imaging (DTI) was applied to obtain free-water (FW), as well as fractional anisotropy (FA _T ) and mean diffusivity (MD _T ) after correcting free-water. CC was divided into halves by the median sagittal line, and each was further divided into five functional segments manually according to the specific template. A total of 10 subregions were obtained and numbered in sequence. The laterality index (LI) was calculated to quantify the asymmetry of CC and its segments. The general linear model was used for the comparisons among groups, and then partial correlation analysis was performed to explore the relationship between the diffusion parameters of CC subregions and clinical manifestations. Results Compared with HC, FW and FA _T of CC in bilateral hemispheres were decreased in LPD group, while MD _T in right hemisphere was increased. In LPD group, FA _T of all CC subregions except for subregions 1, 3 and 6 were significantly lower than HC, and MD _T in anterior and posterior segments of CC (CC subregions 1, 5, 6, 7 and 10) were significantly higher than HC. In RPD group, FA _T of subregion 7 was significantly decreased and MD _T was increased than HC. The LI analysis of CC reflected significant interhemispheric FA _T asymmetry of the anterior and middle segments of CC in RPD group, with a more significant reduction in the right hemisphere of CC. Moreover, the degeneration in CC and its subregions was related to motor or non-motor symptoms in PD. Conclusions Extensive damage of CC was observed in LPD group than in RPD group, while asymmetrical damage was found in the anterior and middle segments of CC in RPD group, suggesting that differences in the patterns of callosal degeneration may be one of the potential mechanisms of asymmetrical motor symptoms affect the non-motor symptoms and prognosis in PD.