The dynamically neurodiverse human brain: Measuring excitatory-inhibitory dynamics and identifying homeostatic differences in autistic and non-autistic people

Abstract

AbstractBrain 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 multiple neurodevelopmental conditions, such as autism; and are consequently targets for pharmacological support options. Yet, E-I measures of neurotransmitter levels or receptors in the living human brain (such as Magnetic Resonance Spectroscopy or Positron Emission Tomography) are expensive and/or invasive and do not capture dynamics. The determine if a candidate metric captures a neurosignalling system, the system must be challenged and changes observed objectively. This is basis of animal study designs. The aperiodic 1/f exponent of the EEG power spectrum is sensitive to E-I perturbations in animals but, more work is needed to translate to humans. Therefore, we tested the hypotheses that i) the aperiodic 1/f exponent of resting-state EEG in humans changes following a pharmacological E-I challenge with arbaclofen, a GABABreceptor agonist; and ii) dynamic responsivity to GABAergic challenge is different in a neurodevelopmental condition associated with E-I differences, namely autism. As predicted, in both groups the aperiodic 1/f exponent significantly increased following a high (30mg) dose of arbaclofen. However, an aperiodic exponent increase was also elicited at a lower (15mg) dose of arbaclofen in autistic but not non-autistic individuals. Hence, in humans, the aperiodic 1/f exponent captures E-I dynamics and autistic brains are dynamically different compared to non-autistic brains. We suggest that our results can be explained by homeostatic differences E-I regulation between groups.