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Updated: May 17, 2026
Dynamic Clamp Methods to Investigate Impaired Neuronal Excitability Associated with Autism
Published on: October 17, 2025
Dynamic excitatory-inhibitory differences in autistic and non-autistic adults: Evidence from a pharmacological
Claire Louise Ellis1,2, Jumana Ahmad1,2,3, Alexia Zoumpoulaki4
1Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK.
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.
