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Local activity alterations in individuals with autism correlate with neurotransmitter properties and ketamine-induced brain changes

Author

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  • Pascal Grumbach

    (Research Centre Juelich; Wilhelm-Johnen-Straße 1
    Heinrich Heine University Duesseldorf; Bergische Landstraße 2)

  • Jan Kasper

    (Research Centre Juelich; Wilhelm-Johnen-Straße 1
    Heinrich Heine University Duesseldorf; Moorenstraße 5)

  • Joerg F. Hipp

    (F. Hoffmann–La Roche Ltd.)

  • Anna Forsyth

    (Grafton)

  • Sofie L. Valk

    (Research Centre Juelich; Wilhelm-Johnen-Straße 1
    Heinrich Heine University Duesseldorf; Moorenstraße 5
    Max Planck School of Cognition; Stephanstraße 1A
    Max Planck Institute for Human Cognitive and Brain Sciences; Stephanstraße 1A)

  • Suresh Muthukumaraswamy

    (Grafton)

  • Simon B. Eickhoff

    (Research Centre Juelich; Wilhelm-Johnen-Straße 1
    Heinrich Heine University Duesseldorf; Moorenstraße 5)

  • Leonhard Schilbach

    (LVR-Klinikum Duesseldorf, Heinrich Heine University Duesseldorf; Bergische Landstraße 2
    Ludwig Maximilians University Munich; Nußbaumstraße 7)

  • Juergen Dukart

    (Research Centre Juelich; Wilhelm-Johnen-Straße 1
    Heinrich Heine University Duesseldorf; Moorenstraße 5)

Abstract

Autism is a neurodevelopmental condition associated with altered resting-state brain function. An increased excitation-inhibition ratio is discussed as a pathomechanism but in-vivo evidence of disturbed neurotransmission underlying functional alterations remains scarce. We compare local resting-state brain activity and neurotransmitter co-localizations between autism (N = 405, N = 395) and neurotypical controls (N = 473, N = 474) in two independent cohorts and correlate them with excitation-inhibition changes induced by glutamatergic (ketamine) and GABAergic (midazolam) medication. Autistic individuals exhibit consistent reductions in local activity, particularly in default mode network regions. The whole-brain differences spatially overlap with glutamatergic and GABAergic, as well as dopaminergic and cholinergic neurotransmission. Functional changes induced by NMDA-antagonist ketamine resemble the spatial pattern observed in autism. Our findings suggest that consistent local activity alterations in autism reflect widespread disruptions in neurotransmission and may be resembled by pharmacological modulation of the excitation-inhibition balance. These findings advance understanding of the neurophysiological basis of autism. Trial registration number: ACTRN12616000281493

Suggested Citation

  • Pascal Grumbach & Jan Kasper & Joerg F. Hipp & Anna Forsyth & Sofie L. Valk & Suresh Muthukumaraswamy & Simon B. Eickhoff & Leonhard Schilbach & Juergen Dukart, 2025. "Local activity alterations in individuals with autism correlate with neurotransmitter properties and ketamine-induced brain changes," Nature Communications, Nature, vol. 16(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63857-6
    DOI: 10.1038/s41467-025-63857-6
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