We investigated the relationship between symptoms and rsfMRI connectivity between the insula and PFC in sport-related concussion (SRC).

Autonomic, affective, and nociceptive symptoms are common after SRC and have well-established relationships with central autonomic network (CAN) structures. We previously found that symptom persistence was positively correlated with hyperconnectivity between the medial amygdala and vmPFC/sgACC. We hypothesized that the insula might also display similar symptom-relevant hyperconnectivity.

We computed whole-brain seed-to-voxel connectivity from BOLD rsfMRI acquisitions at 3 timepoints after SRC (T1=1-4days, T2=10-14days, T3=2-3months) in collegiate athletes (N=31,female=14) and for two groups of healthy age- and gender-matched controls (in-sport, N=36,female=17; non-contact sport N=37,female=15). Twelve insula seed regions were selected from the Brainnetome 264 Atlas (voxel threshold uncorrected p<0.001, two-sided; cluster threshold FDR-corrected p<0.001). ANOVA followed by Tukey’s HSD was used to assess differences across group and time. Subject-level insula-PFC connectivity values (Fisher’sZ) were correlated with SCAT-3 graded symptom checklist (GSC) or Brief Symptom Inventory 18 (BSI-18) scores at each timepoint.

Compared to controls, SRC subjects displayed hyperconnectivity between 8 of 13 insula-PFC pairs at T1, hyperconnectivity between 2 of 13 insula-PFC pairs at T2, and hypoconnectivity between 8 of 13 insula-PFC pairs at T3. Among SRC subjects at T1, connectivity between right dorsal dysgranular insula and left frontal pole was negatively correlated with GSC and BSI-18 severity. Among SRC subjects at T3, connectivity between left ventral dysgranular/granular insula and right mPFC/dlPFC was positively correlated with GSC severity and the GSC cognitive subscale; connectivity between right ventral dysgranular/granular insula and left lateral frontal pole was negatively correlated with BSI-18 severity and BSI-18 depression and anxiety subscales.  

Acute hyperconnectivity between insula and PFC may be protective or compensatory after SRC. Chronic hyperconnectivity with the left insula may signal persistent cognitive symptoms; hypoconnectivity with the right insula may signal persistent affective symptoms.