Oxytocin differentially modulates macroscale functional hierarchy in development
Poster No:
298
Submission Type:
Abstract Submission
Authors:
Jessica Royer1, Philipp Kanske2, Katrin Preckel3, Boris Bernhardt1, Frieder Paulus4, Sören Krach4, Annalina Mayer4
Institutions:
1McGill University, Montreal, Canada, 2Technische Universität Dresden, Dresden, Germany, 3Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, 4University of Lübeck, Lübeck, Germany
First Author:
Co-Author(s):
Introduction:
Autism spectrum disorder (ASD) is characterized by atypical sensory and socio-cognitive processing. Previous work has linked symptom profiles to a disruption of macroscale functional hierarchies characterized by reduced segregation of unimodal and transmodal systems [1]. In parallel, several studies have suggested a role of oxytocin circuits in regulating behavioural and neural phenotypes of ASD. However, findings on the modulatory role of oxytocin on local brain activity and functional connectivity have been mixed, motivating explorations of system-level effects [2-4]. The present work assessed oxytocin-induced shifts in the topography of macroscale functional connectome organization in ASD and neurotypical controls (NT).
Methods:
We studied 32 NT adults and 31 adults with a diagnosis of ASD (all male) recruited as part of a multisite, randomized, double-blind, placebo-controlled, crossover study examining the effect of a single 24-IU dose of intranasally-administered oxytocin on brain function (Fig1). Groups were well matched in age (ASD mean age=26.77±4.72 years; NT mean age=26.81±4.41 years; TAGE=-0.03, p>0.05) and full-scale IQ (ASD mean=108.32±14.28; NT mean=110.84±11.27; TFSIQ=-0.78, p>0.05). Participants underwent a T1-weighted (1mm isovoxels) and resting-state functional imaging (3mm isovoxels) at 3Tesla. Functional timeseries were pre-processed using fMRIprep v23.2.1 and sampled along each participant's native cortical surface through procedures implemented in micapipe v0.2.3 [5-7]. Cortical surfaces were resampled to the fsLR template (downsampled to ~10k vertices). Vertex timeseries were cross-correlated and underwent Fisher R-to-Z transformation. We generated individual-specific functional connectome gradients using BrainSpace and aligned each gradient to a normative template [8,9]. Mixed effects models were implemented via BrainStat [10] and findings were corrected for multiple comparisons using random field theory.
·Figure 1
Results:
Principal gradient topographies (G1: unimodal-transmodal gradient) averaged according to group and treatment conditions are shown in Fig2A. Consistent with prior work [1], we found a significant main effect of group showing reduced differentiation of G1 in ASD relative to NT. ASD participants showed significant increases in gradient scores in right postcentral (pFWE<0.001) and left lateral temporal regions (pFWE=0.009; Fig2B). Stratifying G1 scores according to intrinsic network communities [11] highlighted an upwards shift of vertices composing the somatomotor network and a downward shift of vertices in the default mode network in ASD relative to NT. The main effect of treatment (oxytocin vs. placebo) was non-significant. We found a significant group x treatment interaction on G1, with a significant cluster in the posterior insula (pFWE=0.007; Fig2C). This effect was seemingly driven by a decrease in G1 scores in NT in the oxytocin condition relative to placebo, while this region's position along G1 was relatively stable in both treatment conditions in ASD. Post hoc comparisons of this cluster's functional connectivity revealed a significant group x treatment interaction. Specifically, the administration of oxytocin in NT increased this region's connectivity strength to several subregions of unimodal sensory as well as dorsal and ventral attention networks, particularly in the contralateral hemisphere (pFWE<0.001).
·Figure 2
Conclusions:
In addition to replicating compressions of the functional hierarchy in ASD, the present work highlights subtle interaction between developmental trajectories and the administration of intranasal oxytocin. This effect targeted the posterior insula, a node at the interface of somatomotor and salience networks implicated in interoceptive processing. Considering the posited role of impaired interoception in the behavioural phenotypes of ASD [12], future work will assess the relevance of neural effects with respect to individual symptom profiles.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism) 1
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural)
Task-Independent and Resting-State Analysis
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Anatomy and Functional Systems
Physiology, Metabolism and Neurotransmission:
Physiology, Metabolism and Neurotransmission Other 2
Keywords:
ADULTS
Autism
Cortex
FUNCTIONAL MRI
Systems
Other - Oxytocin
1|2Indicates the priority used for review
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