A Connectome-wide Functional Signature of Trait Anger

Abstract

Past research on the brain correlates of trait anger has been limited by small sample sizes, a focus on relatively few regions-of-interest, and poor test-retest reliability of functional brain measures. To address these limitations, we conducted a data-driven analysis of variability in connectome-wide functional connectivity in a sample of 1,048 young adult volunteers. Multi-dimensional matrix regression analysis showed that self-reported trait anger maps onto variability in the whole-brain functional connectivity patterns of three brain regions that serve action-related functions: bilateral supplementary motor area (SMA) and the right lateral frontal pole. We then demonstrate trait anger modulates the functional connectivity of these regions with canonical brain networks supporting somatomotor, affective, self-referential, and visual information processes. Our findings offer novel neuroimaging evidence for interpreting trait anger as a greater propensity to provoked action, supporting ongoing efforts to understand its utility as a potential transdiagnostic marker for disordered states characterized by aggressive behavior.

Keywords: Amygdala; CWAS; Connectivity; Trait anger; fMRI.

Figure 1.

Data-driven MDMR analysis identified three regions with whole-brain functional connectivity patterns significantly associated with trait anger (left panel). Connectome-wide functional connectivity patterns for each MDMR-derived seed region as a function of trait anger (middle panel). Relative involvement of seven canonical functional networks to each connectivity pattern (right panel). Values farther toward the outer circle indicate greater functional connectivity to the corresponding network in high trait anger. Note that the brain maps in the middle panel were not thresholded thereby allowing for full visualization of all information relevant to the MDMR step, as they were performed post hoc to the family-wise error-controlled MDMR findings and thus do not represent independent statistical tests.

Figure 2.

Seed-based analysis using amygdala ROIs (left panel) showed that high trait anger was associated with hyperconnectivity of the amygdala with a network of cortical and subcortical brain regions (right panel). Results shown here are visualized with a statistical threshold ofp < 0.05, corrected for multiple comparisons across the whole brain. No brain regions survived this threshold when the left centromedial amygdala was used as a seed region. Note: dACC (dorsal anterior cingulate cortex), dmPFC (dorsomedial prefrontal cortex), FPm (medial frontal pole), NAcc (nucleus accumbens), MFG (middle frontal gyrus), SMA (supplementary motor area), TP (temporal pole)