A Quantitative Data-Driven Analysis (QDA) Framework for Resting-state fMRI: a Study of the Impact of Adult Age

Abstract

Purpose The objective of this study is to introduce a new quantitative data-driven analysis (QDA) framework for the analysis of resting-state fMRI (R-fMRI) and use it to investigate the effect of adult age on resting-state functional connectivity (RFC). Methods Whole-brain R-fMRI measurements were conducted on a 3T clinical MRI scanner in 227 healthy adult volunteers (N=227, aged 18-74 years old, male/female=99/128). With the proposed QDA framework we derived two types of voxel-wise RFC metrics: the connectivity strength index (CSI) and connectivity density index (CDI) utilizing the convolutions of the cross-correlation (CC) histogram with different kernels. Furthermore, we assessed the negative and positive portions of these metrics separately. Results With the QDA framework we found age-related declines of RFC metrics in the superior and middle frontal gyrus (MFG), posterior cingulate cortex (PCC), right insula and inferior parietal lobule (IPL) of the default mode network (DMN), which resembles previously reported results using other types of RFC data processing methods. Importantly, our new findings complement previously undocumented results in the following aspects: 1) the PCC and right insula are anti-correlated and tend to manifest simultaneously declines of both the negative and positive connectivity strength with subjects’ age; 2) separate assessment of the negative and positive RFC metrics provides enhanced sensitivity to the aging effect; 3) the sensorimotor network depicts enhanced negative connectivity strength with the adult age. Conclusion The proposed QDA framework can produce threshold-free, voxel-wise analysis of R-fMRI data the RFC metrics. The detected adult age effect is largely consistent with previously reported studies using different R-fMRI analysis approaches. Moreover, the separate assessment of the negative and positive contributions to the RFC metrics can enhance the RFC sensitivity and clarify some of the mixed results in the literature regarding to the DMN and sensorimotor network involvement in adult aging. Highlights A quantitative data-driven analysis (QDA) framework was proposed to analysis resting-state fMRI data. Threshold-free resting-state functional connectivity (RFC) metrics were derived to assess brain changes with adult age. Separate assessment of the positive and negative correlations improve sensitivity of the RFC metrics. The posterior cingulate and right insula cortices are anti-correlated and tend to manifest declines in both the negative and positive connectivity strength with adult age. Negative connectivity strength enhances with adult age in sensorimotor network.