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

Roisin McMackin; Yasmine Tadjine; Antonio Fasano; Matthew Mitchell; Mark Heverin; Friedemann Awiszus; Bahman Nasseroleslami; Richard G Carson; Orla Hardiman

doi:10.1016/j.cnp.2024.03.001

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

Clin Neurophysiol Pract. 2024 Mar 13:9:120-129. doi: 10.1016/j.cnp.2024.03.001. eCollection 2024.

Authors

Affiliations

¹ Discipline of Physiology, School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Ireland.
² Academic Unit of Neurology, School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Ireland.
³ Department of Orthopaedic Surgery, Otto-von-Guericke University, Magdeburg, Germany.
⁴ Trinity College Institute of Neuroscience and School of Psychology, Trinity College Dublin, University of Dublin, Ireland.
⁵ School of Psychology, Queen's University Belfast.
⁶ Beaumont Hospital, Dublin, Ireland.

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.

Keywords: Amyotrophic lateral sclerosis; Coil orientation; Intracortical facilitation; Short-interval intracortical inhibition; Threshold tracking; Transcranial magnetic stimulation.