Considering dynamic nature of the brain: the clinical importance of connectivity variability in machine learning...

The brain connectivity of resting-state fMRI (rs-fMRI) represents an intrinsic state of brain architecture, and it has been used as a useful neural marker for detecting psychiatric conditions as well as for predicting psychosocial characteristics. However, most studies using brain connectivity have focused more on the strength of functional connectivity over time (static-FC) but less attention to temporal characteristics of connectivity changes (FC-variability). The primary goal of the current study was to investigate the effectiveness of using the FC-variability in classifying an individual's pathological characteristics from others and predicting psychosocial characteristics. In addition, the current study aimed to prove that benefits of the FC-variability are reliable across various analysis procedures. To this end, three open public large resting-state fMRI datasets including individuals with Autism Spectrum Disorder (ABIDE; N = 1249), Schizophrenia disorder (COBRE; N = 145), and typical development (NKI; N = 672) were utilized for the machine learning (ML) classification and prediction based on their static-FC and the FC-variability metrics. To confirm the robustness of FC-variability utility, we benchmarked the ML classification and prediction with various brain parcellations and sliding window parameters. As a result, we found that the ML performances were significantly improved when the ML included FC-variability features in classifying pathological populations from controls (e.g., individuals with autism spectrum disorder vs. typical development) and predicting psychiatric severity (e.g., score of autism diagnostic observation schedule), regardless of parcellation selection and sliding window size. Additionally, the ML performance deterioration was significantly prevented with FC-variability features when excessive features were inputted into the ML models, yielding more reliable results. In conclusion, the current finding proved the usefulness of the FC-variability and its reliability.