Long-interval intracortical inhibition is similar in people with and without amyotrophic lateral sclerosis

Long-interval intracortical inhibition, measured using transcranial magnetic stimulation, provides a non-invasive measure of spinal inhibition at interstimulus intervals below 100 ms and of GABA-B-mediated motor cortical inhibition at interstimulus intervals of 100-200 ms. To date, only a few small studies have investigated if long-interval intracortical inhibition is affected in amyotrophic lateral sclerosis. None have employed threshold tracking protocols or investigated multiple induced current directions. In this study, we aimed to determine if long-interval intracortical inhibition (i) differs between people with amyotrophic lateral sclerosis and healthy controls; (ii) relates to motor symptom severity, disease duration or survival time in those with amyotrophic lateral sclerosis; or (iii) relates to intracortical facilitation or short-interval intracortical inhibition. Employing automated threshold tracking during paired-pulse transcranial magnetic stimulation of the precentral gyrus, long-interval intracortical inhibition was recorded in 30 people with amyotrophic lateral sclerosis [9 female, 21 male, median (range) age: 63.5 (41-79) years] and 45 healthy controls [16 female, 29 male, median (range) age: 57 (34-76) years]. Long-interval intracortical inhibition was recorded with interstimulus intervals of 50, 100, 150 and 200 ms using posterior-to-anterior induced current (LICI_PA), and with interstimulus intervals of 150 and 200 ms using anterior-to-posterior induced current (LICI_AP). In subcohorts of both healthy controls and people with amyotrophic lateral sclerosis, short-interval intracortical inhibition was recorded with interstimulus intervals of 1 and 3 ms using posterior-to-anterior induced current and 3 ms using anterior-to-posterior current. Intracortical facilitation was recorded with an interstimulus interval of 10 ms using posterior-to-anterior induced current. No differences were found between those with and without amyotrophic lateral sclerosis in long-interval intracortical inhibition magnitude (P ≥ 0.44, Hedge's g ≤ 0.14) or in the interstimulus interval at which maximal long-interval intracortical inhibition occurs (P = 0.68, χ2 = 1.5). In those with amyotrophic lateral sclerosis, no statistically significant correlations were identified between long-interval intracortical inhibition measures and disease duration or functional rating scale scores. Statistically significant positive correlations were observed between LICI_PA recorded with 100 and 150 ms interstimulus intervals, and between LICI_PA recorded with 150 and 200 ms interstimulus intervals, but not between LICI_PA and LICI_AP measures or between long-interval intracortical inhibition and short-interval intracortical inhibition or intracortical facilitation. Our findings indicate that disinhibition manifested in this disease is primarily not mediated via changes in the cortical GABA-Bergic or spinal circuitry which underpins long-interval intracortical inhibition measures. As LICI_PA and LICI_AP measures show minimal covariation, it is possible that these measures are underpinned by distinct aspects of motor cortical inhibition.