Probabilistic thresholding of functional connectomes: application to schizophrenia

Abstract

Functional connectomes are commonly analysed as sparse graphs, constructed by thresholding cross-correlations between regional neurophysiological signals. Thresholding generally retains the strongest edges (correlations), either by retaining edges surpassing a given absolute weight, or by constraining the edge density. The latter (more widely used) method risks inclusion of false positive edges at high edge densities and exclusion of true positive edges at low edge densities. Here we apply new wavelet-based methods, which enable construction of probabilistically-thresholded graphs controlled for type I error, to a dataset of resting-state fMRI scans of 56 patients with schizophrenia and 71 healthy controls. By thresholding connectomes to fixed edge-specific P value, we found that functional connectomes of patients with schizophrenia were more dysconnected than those of healthy controls, exhibiting a lower edge density and a higher number of (dis)connected components. Furthermore, many participants connectomes could not be built up to the fixed edge densities commonly studied in the literature (~5-30%), while controlling for type I error. Additionally, we showed that the topological randomisation previously reported in the schizophrenia literature is likely attributable to \"non-significant\" edges added when thresholding connectomes to fixed density based on correlation. Finally, by explicitly comparing connectomes thresholded by increasing P value and decreasing correlation, we showed that probabilistically thresholded connectomes show decreased randomness and increased consistency across participants. Our results have implications for future analysis of functional connectivity using graph theory, especially within datasets exhibiting heterogenous distributions of edge weights (correlations), between groups or across participants.