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

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. 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. 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). SICI and SICI are uncorrelated measures of motor cortical inhibitory functions which are useful as distinct, unequally affected, measures of disinhibition in ALS. Examining both SICI and SICI may facilitate more comprehensive characterisation of motor cortical disinhibition in ALS.