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

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.

Functional Integration Between the Two Brain Hemispheres: Evidence From the Homotopic Functional Connectivity Under Resting State

“…Together, HoFC in lifespan indicated a global decrease related with age ( Zuo et al, 2010 ; Tzourio-Mazoyer et al, 2016 ). In specific regions, Zhao’s study found negative correlation, while Zuo’s study reported various development trajectories ( Zuo et al, 2010 ; Zhao et al, 2020 ). The discrepancies might be due to different statistical models in their studies, with a simple GLM in Zhao’s work and a more complicated one including both quadratic and cubic terms in Zuo’s work.…”

“… Gracia-Tabuenca et al (2018) discovered that the VMHC of the occipital fusiform gyrus and the lingual gyrus was negatively associated with the performance in visual long-term memory tasks. In addition, Zhao’s study found that the VMHC of the ventromedial prefrontal cortex and insula showed a negative linear relationship with the performance on the color-word inhibition task mainly about executive function ( Zhao et al, 2020 ).…”

“…Therefore, the exploration of functional integration between the two brain hemispheres should also start at earlier stages of brain development such as the fetal or neonatal stage. In most existing lifespan HoFC studies, the age range of subjects were disequilibrium and mostly located at young adults group ( Zuo et al, 2010 ; Tzourio-Mazoyer et al, 2016 ; Zhao et al, 2020 ). In future studies, it is warranted to map out lifespan trajectories of HoFC for different homologous regions, using a uniformly distributed lifespan cross-sectional or longitudinal data.…”

“…As demonstrated, HoFC is a robust feature with a peculiar interior distribution corresponding to the functional hierarchy, which does not follow the general law defined by the spatial distance ( Salvador et al, 2005 ; Stark et al, 2008 ; Tobyne et al, 2016 ). Meanwhile, it has been found to correlate with the performance of cognitive tasks, such as visuospatial attention ( Gracia-Tabuenca et al, 2018 ) and executive function ( Zhao et al, 2020 ). As summarized in Table 1 , a number of studies have achieved progress in functional integration between the two brain hemispheres by virtue of HoFC measurements under resting state.…”

Reorganization of brain structural networks in aging: A longitudinal study

“…It is also an important node of the DMN (Greicius et al, 2003). Previous aging studies have found age-related changes in the FC of this region and an association between these changes and cognitive decline in different domains, specifically, executive function (Lou et al, 2019;Zhao et al, 2020), semantic knowledge (Hoffman & Morcom, 2018), inhibitory control (Hu et al, 2018), and memory (Huo et al, 2018;Lamichhane et al, 2018). In line with our results, there is evidence of the loss of hub role for left IPC in aging, which was demonstrated using cortical thickness covariance networks (Carey et al, 2019).…”