Abnormal functional connectivity of the reward network in autism spectrum disorder

2027 

Abstract Submission 

Chen Yang¹, Xing-Ke Wang², Shengzhi Ma¹, Li Nathan³, Qiu-Rong Zhang¹, Wen-Qiang Dong¹, Yu-Feng ZANG⁴, Li-Xia Yuan⁵

¹Hangzhou Normal University, Hangzhou, Zhejiang Province, ²State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, BeiJing, ³University of Western Ontario, London, Ontario, ⁴The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang Province, ⁵Zhejiang University, Hangzhou, Zhejiang Province

Chen Yang  
Hangzhou Normal University
Hangzhou, Zhejiang Province

Xing-Ke Wang  
State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University
Beijing, BeiJing

Shengzhi Ma  
Hangzhou Normal University
Hangzhou, Zhejiang Province

Li Nathan  
University of Western Ontario
London, Ontario

Qiu-Rong Zhang  
Hangzhou Normal University
Hangzhou, Zhejiang Province

Wen-Qiang Dong  
Hangzhou Normal University
Hangzhou, Zhejiang Province

Yu-Feng ZANG  
The Affiliated Hospital of Hangzhou Normal University
Hangzhou, Zhejiang Province

Li-Xia Yuan  
Zhejiang University
Hangzhou, Zhejiang Province

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with social communication impairments as a core symptom (Sarmiento 2020). The social motivation hypothesis proposes that the social deficits of ASD are related to reward system dysfunction (Clements et al. 2018). Converging evidence indicates that brain abnormalities in ASD involve atypical functional connectivity (FC) (Picci et al. 2016). However, the abnormalities of FC patterns of the reward network in ASD have not been systematically explored yet, and the effects of age, gender and subtype on reward-related FC are largely unknown.

The reward network was defined as eight regions of interest (ROIs) per hemisphere, including the nucleus accumbens (NAc) (Janouschek et al. 2021), caudate (McNaughton et al. 2023), putamen (Kohls et al. 2018), anterior cingulate cortex (ACC) (Keifer et al. 2021), ventromedial prefrontal cortex (vmPFC) (Müller et al. 2018), orbitofrontal cortex (OFC) (Martins et al. 2021), amygdala (Janouschek et al. 2021), and insula (Gu et al. 2019). We computed both the ROI-wise resting-state FC within the reward network and the seed-based whole-brain voxel-wise FC of each ROI in 298 participants with ASD and 348 typically developing (TD) controls available through the Autism Brain Imaging Data Exchange I dataset. A two-sample t-test was applied to obtain the aberrant FCs and their relationship with clinical symptoms was explored using Pearson's correlation or Spearman's correlation. In addition, Neurosynth Image Decoder was used to generate word clouds verifying the cognitive functions of the aberrant pathways. Furthermore, a three-way multivariate analysis of variance (MANOVA) was conducted to examine the effects of gender, subtype and age on the atypical FCs.

For the within network analysis, the left ACC showed weaker FCs with both the right amygdala and left NAc in ASD compared with TD, which were negatively correlated with the Autism Diagnostic Observation Schedule (ADOS) total scores and Social Responsiveness Scale (SRS) total scores respectively. For the whole-brain analysis, weaker FC (i.e., FC between the left vmPFC and the left calcarine gyrus, and between the right vmPFC and the left precuneus) accompanied by stronger FC (i.e., FC between the left caudate and the right insula) were exhibited in ASD relative to TD, which were positively associated with the SRS motivation scores. Automated decoding of these aberrant FCs further verified their cognitive implications are related to social cognition, such as emotion, motivation, sensation, memory, and mentalizing. The three-way MANOVA analysis revealed the main effect of age on the abnormal FC between the left vmPFC and the left calcarine gyrus, main effect of subtype on the abnormal FC between the right vmPFC and the left precuneus, main effect of age and age-by-gender interaction on FC between the left caudate and the right insula.

Our findings highlight the crucial role of abnormal FC patterns of the reward network in the core social deficits of ASD, which have the potential to reveal new biomarkers for ASD. The increasing insight into gender, subtype and age-related FC changes in reward circuit may advance the development of more effective interventions.

Neurodevelopmental/ Early Life (eg. ADHD, autism) ²

Social Cognition

fMRI Connectivity and Network Modeling

Task-Independent and Resting-State Analysis ¹

Autism

FUNCTIONAL MRI

Other - reward network