Age-Related Decreases in Interhemispheric Resting-State Functional Connectivity and Their Relationship With Executive Function

Jizheng Zhao; Peter Manza; Corinde Wiers; Huaibo Song; Puning Zhuang; Jun Gu; Yinggang Shi; Gene-Jack Wang; Dongjian He

doi:10.3389/fnagi.2020.00020

Age-Related Decreases in Interhemispheric Resting-State Functional Connectivity and Their Relationship With Executive Function

Front Aging Neurosci. 2020 Feb 26:12:20. doi: 10.3389/fnagi.2020.00020. eCollection 2020.

Authors

Jizheng Zhao^{1

2

3}, Peter Manza⁴, Corinde Wiers⁴, Huaibo Song^{1

2

3}, Puning Zhuang^{1

2

3}, Jun Gu⁵, Yinggang Shi¹, Gene-Jack Wang⁴, Dongjian He^{1

2

3}

Affiliations

¹ College of Mechanical and Electronic Engineering, Northwest A&F University, Yangling, China.
² Key Laboratory of Agricultural Internet of Things, Ministry of Agriculture, Yangling, China.
³ Shaanxi Key Laboratory of Agricultural Information Perception and Intelligent Service, Yangling, China.
⁴ Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, United States.
⁵ Department of Endocrinology, First Affiliated Hospital of Hebei North University, Zhangjiakou, China.

Abstract

Age-related alterations of functional brain networks contribute to cognitive decline. Current theories indicate that age-related intrinsic brain functional reorganization may be a critical marker of cognitive aging. Yet, little is known about how intrinsic interhemispheric functional connectivity changes with age in adults, and how this relates to critical executive functions. To address this, we examined voxel-mirrored homotopic connectivity (VMHC), a metric that quantifies interhemispheric communication, in 93 healthy volunteers (age range: 19-85) with executive function assessment using the Delis-Kaplan Executive Function System (D-KEFS) scales. Resting functional MRI data were analyzed to assess VMHC, and then a multiple linear regression model was employed to evaluate the relationship between age and the whole-brain VMHC. We observed age-related reductions in VMHC of ventromedial prefrontal cortex (vmPFC) and hippocampus in the medial temporal lobe subsystem, dorsal anterior cingulate cortex and insula in salience network, and inferior parietal lobule in frontoparietal control network. Performance on the color-word inhibition task was associated with VMHC of vmPFC and insula, and VMHC of vmPFC mediated the relationship between age and CWIT inhibition reaction times. The percent ratio of correct design scores in design fluency test correlated positively with VMHC of the inferior parietal lobule. The current study suggests that brain interhemispheric functional alterations may be a promising new avenue for understanding age-related cognitive decline.

Keywords: Delis-Kaplan executive function system; executive function; frontoparietal control network; medial temporal lobe subsystem; mediation analysis; salience network; voxel-mirrored homotopic connectivity.