A single- and paired-pulse TMS-EEG investigation of the N100 and long interval cortical inhibition in autism spectrum disorder

Kirkovski, M.; Hill, A. T.; Rogasch, N. C.; Saeki, T.; Fitzgibbon, B. M.; Yang, J.; Do, M.; Donaldson, P. H.; Albein-Urios, N.; Fitzgerald, P. B.; Enticott, P. G.

doi:10.1101/2021.01.06.425653

bioRxiv · 10.1101/2021.01.06.425653

A single- and paired-pulse TMS-EEG investigation of the N100 and long interval cortical inhibition in autism spectrum disorder

Kirkovski, M.·Hill, A. T.·Rogasch, N. C.·Saeki, T.·Fitzgibbon, B. M.·Yang, J.·Do, M.·Donaldson, P. H.·Albein-Urios, N.·Fitzgerald, P. B.·Enticott, P. G.

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Abstract

BackgroundThere is evidence to suggest a disruption of gamma-aminobutyric acid (GABA) in autism spectrum disorder (ASD), but findings are mixed. Concurrent electroencephalography and transcranial magnetic stimulation (TMS-EEG) provides a novel method by which to probe GABA-mediated cortical inhibition. MethodsWith a particular focus on GABAB-ergic mechanisms, we investigated the N100 peak of the TMS evoked potential (TEP), as well as long interval cortical inhibition (LICIEEG) in adults with ASD (n = 23; 12 female) without intellectual disability, and a neurotypical comparison group (n =22; 12 female) matched for age, sex, and IQ. Seventy-five single-(spTMS) and 75 paired-(ppTMS; 100 ms inter-stimulus-interval) pulses were applied to the right primary motor cortex (M1), right temporoparietal junction (TPJ), and right dorsolateral prefrontal cortex (DLPFC) while EEG was recorded from 20 scalp electrodes. Additionally, electromyography (EMG) was used to investigate corticospinal inhibition following ppTMS to M1 (LICIEMG). ResultsThere were no group differences in the N100 amplitude or latency following spTMS. LICI outcomes following ppTMS, as measured by either EEG or EMG, also did not differ between groups. These findings were further supported by Bayesian analyses, which provided weak-moderate support for the null hypothesis. LimitationsData presented here reflect adults without intellectual disability, and the generalisability of these results is therefore limited. ConclusionsThe findings of this study argue against GABAB-ergic impairment in adults with ASD without intellectual disability, at least at the cortical regions examined. Further research investigating these mechanisms in ASD at various ages, with varying degrees of symptomatology, and at different brain sites is an important factor in understating the role of GABA in the neuropathophysiology of ASD.

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Kirkovski, M., Hill, A. T., Rogasch, N. C., Saeki, T., Fitzgibbon, B. M., Yang, J., Do, M., Donaldson, P. H., Albein-Urios, N., Fitzgerald, P. B., Enticott, P. G.. 2021-01-08. A single- and paired-pulse TMS-EEG investigation of the N100 and long interval cortical inhibition in autism spectrum disorder. https://doi.org/10.1101/2021.01.06.425653

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