Dynamic excitatory-inhibitory differences in autistic and non-autistic adults: Evidence from a pharmacological challenge with arbaclofen

Ellis, Claire Louise, Ahmad, Jumana, Zoumpoulaki, Alexia ORCID: https://orcid.org/0000-0002-0810-0319, Dimitrov, Mihail, Velthuis, Hester E., Pereira, Andreia C., Wong, Nichol M. L., Ponteduro, Maria F., Kowalewski, Lukasz, Leonard, Alison, Garces, Pilar, Huang, Qiyun, Daly, Eileen, Murphy, Declan G. M. and McAlonan, Gráinne M. 2026. Dynamic excitatory-inhibitory differences in autistic and non-autistic adults: Evidence from a pharmacological challenge with arbaclofen. Journal of Psychopharmacology 10.1177/02698811261449378

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Abstract

Background: Brain function is the dynamic output of coordinated excitatory and inhibitory (E-I) activity. E-I alterations, arising from differences in excitatory glutamate and inhibitory GABA pathways, are implicated in the development and heterogeneity of autism, and are consequently targets for pharmacological support options. Existing tools, such as Magnetic Resonance Spectroscopy, are limited in capturing the dynamic nature of E-I regulation. The aperiodic 1/f exponent of the EEG power spectrum has shown sensitivity to E-I perturbations in animals and neurotypical humans, but its applicability to neurodiverse populations remains underexplored. Methods: Therefore, as proof-of-concept, this study tested the hypotheses that (i) the aperiodic 1/f exponent of resting-state EEG changes following a pharmacological E-I challenge with arbaclofen (STX209), a GABAB receptor agonist; and (ii) dynamic responsivity to GABAergic challenge is different in autism. Participants were 40 adults, 15 autistic. EEG was recorded at rest after randomised, double-blind administration of a placebo, 15 mg of arbaclofen, and 30 mg of arbaclofen. Aperiodic 1/f exponents were extracted. Results: As predicted, in both groups the aperiodic 1/f exponent significantly increased following a high (30 mg) dose of arbaclofen, replicating the effect observed in animals. Furthermore, a lower (15 mg) dose showed a different response pattern across groups, with aperiodic exponents tending to increase in autistic individuals but decrease in non-autistic individuals, suggesting differences in GABAergic responsivity. Conclusions: These findings support the aperiodic 1/f exponent as a metric for dynamic E-I regulation and provide preliminary evidence of distinct homeostatic E-I dynamics in autism.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Computer Science & Informatics
Publisher:	SAGE Publications
ISSN:	0269-8811
Date of First Compliant Deposit:	27 May 2026
Last Modified:	27 May 2026 09:45
URI:	https://orca.cardiff.ac.uk/id/eprint/187232

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