Loss of the ipsilateral silent period in amyotrophic lateral sclerosis is associated with reduced white matter integrity in the motor section of the corpus callosum.

Objective: Interhemispheric neurons in the motor section of the corpus callosum have an inhibitory effect on neurons of the contralateral motor cortex. Three quarters of patients with amyotrophic laterals sclerosis (ALS) show impaired transcallosal inhibition. We aimed to investigate whether structural changes co-occur with this functional impairment and to explore its phenotypic correlates.

Methods: The demographic, clinical, and neuropsychological data of 127 ALS patients were analysed. Transcallosal inhibition was assessed with an ipsilateral silent period (iSP) protocol using transcranial magnetic stimulation. Patients were categorised based on an iSP response or its loss, and the groups were characterised by demographic, clinical, and neuropsychological variables. Diffusion-weighted images from a subset of 63 patients were analysed using tractography, and white matter (WM) structural integrity metrics were compared across groups.

Results: 54 % of patients displayed iSP loss. The average free-water-corrected fractional anisotropy values within the callosal tract between the primary motor cortices were lower for patients with iSP loss compared to patients with an iSP response. There were no group differences based on other diffusivity metrics. The groups did not differ regarding any of the demographic, clinical, or neuropsychological variables.

Interpretation: We found reduced WM integrity in the motor section of the corpus callosum that differentiated ALS patients with iSP loss from patients with an iSP response, but with a small effect size. Nevertheless, the underlying pathological substrate and potential genetic drivers for these structural and functional changes in a subset of ALS patients remain to be satisfactorily investigated.