TY  - JOUR
AU  - Grumbach, Pascal
AU  - Kasper, Jan
AU  - Hipp, Joerg F.
AU  - Forsyth, Anna
AU  - Valk, Sofie L.
AU  - Muthukumaraswamy, Suresh
AU  - Eickhoff, Simon B.
AU  - Schilbach, Leonhard
AU  - Dukart, Juergen
TI  - Local activity alterations in individuals with autism correlate with neurotransmitter properties and ketamine-induced brain changes
JO  - Nature Communications
VL  - 16
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - FZJ-2025-04144
SP  - 8248
PY  - 2025
AB  - 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.
LB  - PUB:(DE-HGF)16
DO  - DOI:10.1038/s41467-025-63857-6
UR  - https://juser.fz-juelich.de/record/1047195
ER  -