Supplementary motor area driving changes of structural brain network in blepharospasm

Abstract

Blepharospasm is traditionally thought to be a movement disorder that results from basal ganglia dysfunction. Recently, accumulating morphometric studies have revealed structural alterations outside the basal ganglia, such as in the brainstem, cerebellum, and sensorimotor cortex, suggesting that blepharospasm may result from network disorders. However, the temporal and causal relationships between structural alterations, and whether there are disease duration-related hierarchical structural changes in these patients remain largely unknown. Structural magnetic resonance imaging was performed in 62 patients with blepharospasm, 62 patients with hemifacial spasm, and 62 healthy controls to assess the structural alterations using voxel-based morphology and structural covariance networks. The use of the causal structural covariance network, modularity analysis, and functional decoding were subsequently performed to map the causal effect of gray matter change pattern, hierarchical topography, and functional characterizations of the structural network throughout the disease duration of blepharospasm. Greater gray matter volume in the left and right supplementary motor areas was identified in patients with blepharospasm compared to that in patients with hemifacial spasm and healthy controls, whereas no significant difference was identified between patients with hemifacial spasm and healthy controls. In addition, increased gray matter volume covariance between the right supplementary motor area and right brainstem, left superior frontal gyrus, left supplementary motor area, and left paracentral gyrus was found in patients with blepharospasm compared to healthy controls. Further causal structural covariance network, modularity analysis, and functional decoding showed that the right supplementary motor area served as a driving core in patients with blepharospasm, extending greater gray matter volume to areas in the cortico-basal ganglia-brainstem motor pathway and cortical regions in the vision-motor integration pathway. Taken together, our results suggest that the right supplementary motor area is an early and important pathologically impaired region in patients with blepharospasm. With a longer duration of blepharospasm, increased gray matter volume extends from the right supplementary motor area to the cortico-basal ganglia motor and visual-motor integration pathways, showing a hierarchy of structural abnormalities in the disease progression of blepharospasm, which provides novel evidence to support the notion that blepharospasm may arise from network disorders and is associated with a wide range of gray matter abnormalities.

The pathogenesis of blepharospasm

“…DTI is a non-invasive method that can effectively observe and evaluate the ultrastructure of WM. Numerous previous studies have reported abnormal GM structures in the basal ganglia, sensorimotor cortex, and cerebellum of patients with blepharospasm ( 66 , 68 ). For example, Martino et al ( 69 ) performed VBM on 25 patients with primary blepharospasm and on 24 healthy controls.…”

“…When interpreting the results of a VBM study, the location of the abnormality is of paramount importance. A comparative study of 62 patients and 62 age/sex matched healthy subjects found that, with an increase in the duration of blepharospasm, the volume of GM increased from the right supplementary motor area (SMA) to the cortical–basal ganglia motor and visual–motor integration pathways, suggesting that blepharospasm is associated with extensive GM structural abnormalities ( 66 ). Another meta-analysis, involving 129 patients with blepharospasm and 144 healthy controls, showed an increase in GM in the bilateral precentral and postcentral gyri, SMA, and bilateral paracenter lobules in patients with blepharospasm, which provides a new concept of blepharospasm as a type of brain network dysfunction ( 67 ).…”

Progressive thalamic nuclear atrophy in blepharospasm and blepharospasm-oromandibular dystonia

“…In our previous study on BSP, we used a causal structural covariance network (caSCN) to identify two pathways derived by the supplementary motor area—one to areas in the cortico–basal ganglia–brainstem motor pathway and the other to cortical regions in the vision–motor integration pathway. 36 Specifically, the volumes of abnormal thalamic nuclei in patients with BSP were ranked according to JRS and duration, as well as in patients with BSP and with BOD together. These rankings, although not derived from true longitudinal MRIs of the same patients, functioned as a ‘pseudo-time series’ to characterize disease progression.…”

Progressive increase of brain gray matter volume in individuals with regular soccer training

“…This methodological extension has yielded significant insights, especially in characterizing the flow of brain information in various neurological conditions. For instance, in temporal lobe epilepsy, schizophrenia, Parkinson’s disease, and Alzheimer’s disease, GCA has demonstrated its utility in elucidating complex brain dynamics 13 – 15 . These applications underscore the versatility and robustness of GCA in diverse research contexts.…”