A neurotransmitter-related and age-stable modular integration abnormality of reward circuit in ASD
Poster No:
1426
Submission Type:
Abstract Submission
Authors:
Chen Yang1, Zhi Ma1, Qiang Dong1, Rong Zhang1, Yu Chen1, Dan Chen2, Yu-Feng Zang3, Li-Xia Yuan4
Institutions:
1Hangzhou Normal University, Hangzhou, Zhejiang, 2Zhejiang University School of Medicine, Hangzhou, Zhejiang, 3Hangzhou normal university, Hangzhou, China, 4Hangzhou Normal University, Hangzhou, Zhejiang Province
First Author:
Co-Author(s):
Introduction:
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with social communication impairments as a core symptom(Pelphrey, Shultz, Hudac, & Vander Wyk, 2011). Social dysfunction in ASD is associated with the social brain(Gotts et al., 2012; Muller & Fishman, 2018), which encompasses four specific subnetworks, i.e., reward-related system (RRS) (Bickart, Hollenbeck, Barrett, & Dickerson, 2012; Chevallier, Kohls, Troiani, Brodkin, & Schultz, 2012), theory of mind (ToM) network(Mar, 2011; Schurz, Radua, Aichhorn, Richlan, & Perner, 2014), mirror neuron system (MNS) (Babiloni et al., 2017; Molenberghs, Cunnington, & Mattingley, 2012), and face perception network (FPN) (Cohen Kadosh, Cohen Kadosh, Dick, & Johnson, 2011; Duchaine & Yovel, 2015). However, the relationship between neural mechanisms of social dysfunction and modular integration of these subnetworks within the social brain remains unclear in ASD.
Methods:
To define the four subnetworks in the social brain, related meta-analytic activation maps were obtained from Neurosynth(Yarkoni, Poldrack, Nichols, Van Essen, & Wager, 2011). The participation coefficient (PC) (Guimerà & Nunes Amaral, 2005) was applied to explore the abnormal modular integration of the four subnetworks in 298 ASD participants and 348 typically developing (TD) controls from the Autism Brain Imaging Data Exchange (ABIDE) I dataset. Then, its association with clinical symptoms was investigated with Pearson's or Spearman's partial correlation. Furthermore, to explore the molecular underpinnings of the dysfunctional modular integration in ASD, its associations with neurotransmitter densities were obtained with spatial correlation(Dukart et al., 2021). Additionally, age effect on aberrant modular integration was estimated with linear regression models. Finally, we assess the reproducibility of our results from a meta-perspective using the ABIDE II dataset.
Results:
ASD patients exhibited increased integration of the RRS (p = 7.10×10-6, Cohen's d = 0.36, Bonferroni corrected) relative to TDs, which were attributed to increased inter‐modular connections between the RRS and FPN as well as MNS. The increased integration of the RRS was positively correlated with Social Responsiveness Scale (SRS) total scores (r = 0.18, p = 0.003, FDR corrected). Furthermore, increased modular integration of the RRS was negatively associated with the neurotransmitters such as 5HT1a (r = -0.64, p = 0.005, FDR corrected) and GABAa (r = -0.67, p = 0.005, FDR corrected). Additionally, a significant main effect of age and diagnosis on the modular integration of RRS were revealed. Finally, the replicated meta-analysis demonstrated similar modular integration disruption of RRS in ASD.
·Modular participation coefficient alterations in ASD
·A symptom-related, neurotransmitter-associated, and age-stable modular integration abnormality of reward circuit in ASD
Conclusions:
We revealed a symptom-related, neurotransmitter-associated, age-stable, and reproducible modular integration abnormality of reward circuit in ASD. Our study supported the excitatory-inhibitory balance theory of ASD and may shed light on the development of new intervention strategies for social impairments of ASD.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism)
Emotion, Motivation and Social Neuroscience:
Social Cognition
Social Neuroscience Other 2
Modeling and Analysis Methods:
fMRI Connectivity and Network Modeling 1
Task-Independent and Resting-State Analysis
Keywords:
Autism
FUNCTIONAL MRI
Neurotransmitter
Social Interactions
1|2Indicates the priority used for review
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