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

Highlights

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  SICI measured using posterior-to-anterior induced current direction (SICI _PA) has been reported to be lower in ALS.

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  We find both SICI _PA and SICI recorded with anterior-to-posterior induced current direction (SICI _AP) are lower in ALS.

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  SICI _PA and SICI _AP do not correlate in ALS or controls, indicating that they reflect distinct physiological processes.

Abstract

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 _3ms was also recorded using a coil orientation which induces anterior-posterior (AP)-directed current across the motor cortex.

Results

At group level, SICI _3ms-PA (AUROC = 0.7), SICI _3ms-AP (AUROC = 0.8) and SICI _1ms (AUROC = 0.66) were substantially lower in those with ALS, although there was considerable interindividual heterogeneity. Averaging across interstimulus intervals (ISIs) marginally improved SICI _PA 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 _3ms-AP alone. SICI _3ms-AP and SICI _3ms-PA did not significantly correlate (rho = 0.19, p = 0.313), while SICI _1ms-PA and SICI _3ms-PA did (rho = 0.37, p = 0.006). Further, those with ALS with the lowest SICI _3ms-PA were not those with the lowest SICI _3ms-AP. ICF was similar between groups (AUROC = 0.50).

Conclusions

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

Significance

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