Examining short interval intracortical inhibition with different transcranial magnetic stimulation-induced current directions in ALS.

Objective: To establish if induced current direction across the motor cortex alters the sensitivity of transcranial magnetic stimulation (TMS)-evoked short-interval intracortical inhibition (SICI) as an ALS biomarker.

Methods: Threshold tracking-TMS was undertaken in 35 people with ALS and 39 controls. Using a coil orientation which induces posterior-anterior (PA)-directed current across the motor cortex, SICI (1 ms and 3 ms interstimulus intervals) and intracortical facilitation (ICF, 10 ms interstimulus interval) were recorded. SICI was also recorded using a coil orientation which induces anterior-posterior (AP)-directed current across the motor cortex.

Results: At group level, SICI (AUROC = 0.7), SICI (AUROC = 0.8) and SICI (AUROC = 0.66) were substantially lower in those with ALS, although there was considerable interindividual heterogeneity. Averaging across interstimulus intervals (ISIs) marginally improved SICI sensitivity (AUROC = 0.76). Averaging SICI values across ISIs and orientations into a single SICI measure did not substantially improve sensitivity (AUROC = 0.81) compared to SICI alone. SICI and SICI did not significantly correlate (rho = 0.19, p = 0.313), while SICI and SICI did (rho = 0.37, p = 0.006). Further, those with ALS with the lowest SICI were not those with the lowest SICI. ICF was similar between groups (AUROC = 0.50).

Conclusions: SICI and SICI are uncorrelated measures of motor cortical inhibitory functions which are useful as distinct, unequally affected, measures of disinhibition in ALS.

Significance: Examining both SICI and SICI may facilitate more comprehensive characterisation of motor cortical disinhibition in ALS.