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@ARTICLE{Grumbach:1047195,
author = {Grumbach, Pascal and Kasper, Jan and Hipp, Joerg F. and
Forsyth, Anna and Valk, Sofie L. and Muthukumaraswamy,
Suresh and Eickhoff, Simon B. and Schilbach, Leonhard and
Dukart, Juergen},
title = {{L}ocal activity alterations in individuals with autism
correlate with neurotransmitter properties and
ketamine-induced brain changes},
journal = {Nature Communications},
volume = {16},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Springer Nature},
reportid = {FZJ-2025-04144},
pages = {8248},
year = {2025},
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.},
cin = {INM-7},
ddc = {500},
cid = {I:(DE-Juel1)INM-7-20090406},
pnm = {5251 - Multilevel Brain Organization and Variability
(POF4-525)},
pid = {G:(DE-HGF)POF4-5251},
typ = {PUB:(DE-HGF)16},
doi = {10.1038/s41467-025-63857-6},
url = {https://juser.fz-juelich.de/record/1047195},
}