Heart rate variability interacts with recovery of resting-state connectivity in amygdala circuitry and the persistence of symptoms after sport-related concussion

Abstract

We investigated longitudinal trajectories of resting-state fMRI (rsfMRI), autonomic function, and graded symptoms after sport-related concussion (SRC). Limbic circuitry may be particularly vulnerable to traumatic brain injury, which could explain the affective and autonomic dysfunction that some patients develop. Relatively few studies have performed longitudinal rsfMRI analyses in concussion and fewer have combined imaging with autonomic and symptom data. We leveraged published limbic rsfMRI networks centered on the amygdala that include core affective and autonomic structures to test whether athletes with SRC would have altered connectivity, and that network recovery would be related to measures of autonomic function and symptom persistence. We compared rsfMRI connectivity of amygdala networks in college athletes with SRC (N = 31, female = 14) at three time points after concussion (T1 = 4 days, T2 = 10-14 days, T3 = 2-3 months) and matched controls with no concussion (in-sport control [ISC] N = 36, female = 17). SRCs show greater amygdala network connectivity as compared to ISCs (T1 p = 0.003, T2 p = 0.014) that normalizes over time (T3 p = 0.182). However, SRCs with higher versus lower heart rate variability (HRV), as measured by pNN50 at T1, have opposing trajectories of connectivity. That is, SRCs with higher HRV have connectivity that starts high and normalizes over time (T1 p = 0.001, T2 p = 0.055, T3 p = 0.576) whereas SRCs with lower HRV have connectivity that increases over time (T1 p = 0.429, T2 p = 0.050, T3 p = 0.002). Furthermore, SRCs with greatest connectivity at T3, presumably the least recovered, have the most symptoms on the Graded Symptom Checklist at ∼3 months (r = 0.635, p = 0.001). Heightened connectivity of amygdala circuitry acutely after a concussion and its normalization over time may be protective, and with HRV, may be a biomarker of symptom persistence.