Patterns of brain dynamic functional connectivity are linked with attention-deficit/hyperactivity disorder-related behavioral and cognitive dimensions

Lekai Luo; Lizhou Chen; Yuxia Wang; Qian Li; Ning He; Yuanyuan Li; Wanfang You; Yaxuan Wang; Fenghua Long; Lanting Guo; Kui Luo; John A Sweeney; Qiyong Gong; Fei Li

doi:10.1017/S0033291723000089

Patterns of brain dynamic functional connectivity are linked with attention-deficit/hyperactivity disorder-related behavioral and cognitive dimensions

Psychol Med. 2023 Feb 7;53(14):1-12. doi: 10.1017/S0033291723000089. Online ahead of print.

Authors

Lekai Luo^{1

2}, Lizhou Chen^{1

3}, Yuxia Wang^{1

2}, Qian Li^{1

2}, Ning He⁴, Yuanyuan Li⁴, Wanfang You^{1

2}, Yaxuan Wang^{1

2}, Fenghua Long^{1

2}, Lanting Guo⁴, Kui Luo^{1

5}, John A Sweeney^{1

6}, Qiyong Gong^{1

7}, Fei Li^{1

2}

Affiliations

¹ Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, P.R. China.
² Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu 610041, Sichuan, P.R. China.
³ Functional and Molecular Imaging Key Laboratory of Sichuan University, Chengdu 610041, Sichuan, P.R. China.
⁴ Department of Psychiatry, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, P.R. China.
⁵ National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610041, Sichuan, P.R. China.
⁶ Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH 45219, USA.
⁷ Department of Radiology, West China Xiamen Hospital of Sichuan University, Xiamen 361021, Fujian, P.R China.

Abstract

Background: Attention-deficit/hyperactivity disorder (ADHD) is a clinically heterogeneous neurodevelopmental disorder defined by characteristic behavioral and cognitive features. Abnormal brain dynamic functional connectivity (dFC) has been associated with the disorder. The full spectrum of ADHD-related variation of brain dynamics and its association with behavioral and cognitive features remain to be established.

Methods: We sought to identify patterns of brain dynamics linked to specific behavioral and cognitive dimensions using sparse canonical correlation analysis across a cohort of children with and without ADHD (122 children in total, 63 with ADHD). Then, using mediation analysis, we tested the hypothesis that cognitive deficits mediate the relationship between brain dynamics and ADHD-associated behaviors.

Results: We identified four distinct patterns of dFC, each corresponding to a specific dimension of behavioral or cognitive function (r = 0.811-0.879). Specifically, the inattention/hyperactivity dimension was positively associated with dFC within the default mode network (DMN) and negatively associated with dFC between DMN and the sensorimotor network (SMN); the somatization dimension was positively associated with dFC within DMN and SMN; the inhibition and flexibility dimension and fluency and memory dimensions were both positively associated with dFC within DMN and between DMN and SMN, and negatively associated with dFC between DMN and the fronto-parietal network. Furthermore, we observed that cognitive functions of inhibition and flexibility mediated the relationship between brain dynamics and behavioral manifestations of inattention and hyperactivity.

Conclusions: These findings document the importance of distinct patterns of dynamic functional brain activity for different cardinal behavioral and cognitive features related to ADHD.

Keywords: Attention-deficit/hyperactivity disorder; cognitive function; dynamic functional connectivity; resting-state functional MRI; sparse canonical correlation analysis.