Cortical Inhibitory Alterations in Autism Spectrum Disorders: A TMS Study

Poster Presentation
Saturday, May 12, 2018: 11:30 AM-1:30 PM
Hall Grote Zaal (de Doelen ICC Rotterdam)
I. Bernardino1,2, A. Dionísio3, R. Monteiro3, I. Violante4 and M. Castelo-Branco5,6, (1)Institute for Nuclear Sciences Applied to Health (ICNAS), Coimbra, Portugal, (2)IBILI - Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine – University of Coimbra, Portugal, Coimbra, Portugal, (3)Institute of Nuclear Sciences Applied to Health, University of Coimbra, Coimbra, Portugal, (4)School of Psychology, Faculty of Health and Medical Sciences, University of Surrey, London, United Kingdom, (5)CIBIT & IBILI - Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine – University of Coimbra, Portugal, Coimbra, Portugal, (6)ICNAS - Produção Unipessoal Lda, Coimbra, Portugal
Background: Autism spectrum disorder (ASD) is a pervasive neurodevelopmental condition of considerable relevance in cognitive and clinical neuroscience because of its intriguing combination of symptoms, including marked impairments in social interaction and communication in the presence of repetitive stereotyped behavior. Although several studies have characterized the ASD phenotype, the nature of its pathophysiology remains unclear. Emerging evidence suggests that inhibitory GABA neurotransmission represents an important dysfunctional pathway in ASD. This led us to investigate whether alterations in the push-pull mechanism between physiological excitation and inhibition may be present in ASD and likely conduct to altered motor cortical excitability.

Objectives: We aimed to probe whether there are alterations in cortical excitability, including inhibition and facilitation, in the primary motor cortex (M1) on ASD patients, via the use of transcranial magnetic stimulation (TMS) well stablished protocols: paired-pulse (pp-TMS), input/output curves (I/O) and cortical silent period (CSP).

Methods: Data were acquired from 8 high-functioning (mean full-scale IQ 105) ASD patients (mean age ± SE = 21.56 ± 1.27) and 5 chronological age and full-scale IQ-matched control participants (mean age ± SE = 24.83 ± 1.54).

In pp-TMS, two magnetic pulses are applied, separated by variable inter-stimulus intervals (ISI) which can be associated to either cortical excitation or inhibition. Three protocols were implemented: short-interval intracortical inhibition (SICI) measuring cortical inhibition putatively mediated by GABAA receptors (ISIs= 1, 3, 5ms); intracortical facilitation (ICF) reflecting a mixture of excitatory (NMDA glutamate) and inhibitory (GABAA) effects (ISIs=10, 15, 20ms); and long-interval intracortical inhibition (LICI) showing inhibition mediated by GABAB receptors (ISIs= 50, 100, 150ms).

In I-O curve, TMS intensities at 90, 100, 110, 120, 130 and 140% of RMT were used. Ten pulses at each intensity were delivered in a randomized order.

Regarding CSP, a suprathreshold TMS pulse is given during voluntary muscle contraction producing a motor-evoked potential (MEP) followed by a period of EMG silence. Measures were obtained while participant maintained contraction of 20% of the maximal force, measured with a dynamometer. Ten CSPs were recorded using an intensity of 130% of RMT.

Results: Our preliminary results showed significant differences between groups regarding both relative and absolute cortical silent period measures. ASD patients revealed longer relative (M=159.75, SE=8.60) and absolute periods (M=117.11, SE=8.22) than controls (relative: M=129.45, SE=9.61; absolute: M=87.60, SE=9.04) (t-test; p=.038 and p=.034, respectively). Concerning paired-pulse, no significant differences were yet found (while we predict power to increase when additional participants are added), although a trend for higher values in ASD was shown for the 5ms interval, in SICI (t-test, p=.089). In the IO protocol, participants did not differ regarding curve slope, maximum MEP and S50, i.e. the stimulus intensity that produces a MEP amplitude of 50% of the maximum.

Conclusions: In this study, we found preliminary evidence of altered motor cortical excitability in ASD which seems to involve intracortical inhibitory pathways. These results are in line with previous findings reporting altered GABA neurotransmission in this pathology and suggest altered GABA-mediated cortical inhibition which possible underlies cognitive impairments present in ASD.