“…29,33 If we take these results together, our data support the hypothesis of an active and at least partially independent bilateral cortical process of degeneration with secondary damage to the CC, particularly in its midbody, known to be significantly involved in the process of axonal degeneration in ALS 34 and substantially formed by interhemispheric fibers connecting the motor cortices, as also demonstrated by diffusion tensor tractography. 35 According to previous neuropathologic findings, 27,34,36 ALS degenerative changes in the cerebral cortex mainly involve motor areas, though recent whole-brain voxel-based morphometry analyses have largely reported GM abnormalities even in extramotor regions. 12,14,15,20,31,37 Thereby, the trends of MD and RD changes, which largely overlapped in our patients in both the genu and splenium of the CC, may represent an increase in the extracellular volume secondary to axonal loss associated with injury to the myelin sheaths, as previously reported in human and animal models of demyelination and axonal degeneration.…”