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

## TL;DR

This study found no significant differences in long-interval intracortical inhibition between people with amyotrophic lateral sclerosis and healthy controls, suggesting that this type of inhibition is not affected by the disease.

## Contribution

The study is the first to use threshold tracking protocols and investigate multiple current directions in long-interval intracortical inhibition in amyotrophic lateral sclerosis.

## Key findings

- No differences were found in long-interval intracortical inhibition magnitude between people with amyotrophic lateral sclerosis and healthy controls.
- Long-interval intracortical inhibition measures did not correlate with disease duration or symptom severity in amyotrophic lateral sclerosis.
- LICIPA and LICIAP measures showed minimal covariation, suggesting they reflect distinct aspects of motor cortical inhibition.

## Abstract

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 (LICIPA), and with interstimulus intervals of 150 and 200 ms 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 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 LICIPA recorded with 100 and 150 ms interstimulus intervals, and between LICIPA recorded with 150 and 200 ms interstimulus intervals, but not between LICIPA and LICIAP 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 LICIPA and LICIAP measures show minimal covariation, it is possible that these measures are underpinned by distinct aspects of motor cortical inhibition.

Long-interval intracortical inhibition, measured using paired-pulse transcranial magnetic stimulation, provides a non-invasive measure of GABA-Bergic cortical inhibition at interstimulus intervals of 100–200 ms or spinal inhibition at a 50 ms interstimulus interval. McMackin et al. report no significant difference in these measures between people with amyotrophic lateral sclerosis and healthy controls.

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