Long interval intracortical inhibition is similar in people with and without Amyotrophic Lateral Sclerosis

Abstract Long interval intracortical inhibition (LICI), measured using transcranial magnetic stimulation, provides a non-invasive measure of spinal inhibition at interstimulus intervals below 100ms and of GABA-B-mediated motor cortical inhibition at interstimulus intervals of 100-200ms. To date, only a few small studies have investigated if LICI 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 LICI (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, LICI 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). LICI was recorded with interstimulus intervals of 50, 100, 150 and 200ms using posterior-to-anterior induced current (LICIPA), and with interstimulus intervals of 150 and 200ms using anterior-to-posterior induced current (LICIAP). In subcohorts of both healthy controls and people with amyotrophic lateral sclerosis, short interval intracortical inhibition was recorded with interstimulus intervals of 1 and 3ms using posterior-to-anterior induced current and 3ms using anterior-to-posterior current. Intracortical facilitation was recorded with an interstimulus interval of 10ms using posterior-to-anterior induced current. No differences were found between those with and without amyotrophic lateral sclerosis in LICI magnitude (p≥0.44, Hedge’s g≤0.14) or in the interstimulus interval at which maximal LICI occurs (p=0.68, χ2=1.5). In those with amyotrophic lateral sclerosis, no statistically significant correlations were identified between LICI measures and disease duration or functional rating scale scores. Statistically significant positive correlations were observed between LICIPA recorded with 100 and 150ms interstimulus intervals, and between LICIPA recorded with 150ms and 200ms interstimulus intervals, but not between LICIPA and LICIAP measures or between LICI 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 LICI measures. As LICIPA and LICIAP measures show minimal covariation, it is possible that these measures are underpinned by distinct aspects of motor cortical inhibition.