Voxel-mirrored homotopic connectivity in upper motor neuron-dominant amyotrophic lateral sclerosis is associated with different spread directions.

By adopting the method of voxel-mirrored homotopic connectivity (VMHC), the correlation of the synchrony of spontaneous neural functional activities between symmetrical regions is determined to be mediated by the corpus callosum (CC). This study investigated differences in homotopic functional connectivity (FC) across distinct symptom spread directions in individuals with upper motor neuron-dominant amyotrophic lateral sclerosis (UMN-D ALS). The UMN-D ALS patients were categorized into two groups on the basis of the direction of symptom spread-horizontal spread (group H) and vertical spread (group V). Indices of interhemispheric functional and structural changes are derived via analyses of VMHC and probabilistic fiber tracking. The VMHC analysis of grey matter revealed that the intergroup differences in the superior frontal gyrus (SFG) were greater in group H than in groups V and HC (voxel P < 0.05, cluster P < 0.05, GRF corrected). According to CC-based VMHC analysis, group H had greater VMHC values than did group V (45 mm³ vs. 18 mm³ at a voxel-level threshold of P < 0.05, uncorrected). In UMN-D ALS, the results of VMHC analysis vary with different spread directions. In group H, homotopic FC significantly increased, possibly associated with early bilateral limb involvement and subsequent compensatory increases in the SFG. These results contribute to the understanding of the relationship between brain function and symptom evolution in individuals with ALS.