Resting-State fMRI Metrics in Acute Sport-Related Concussion and Their Association with Clinical Recovery: A Study from the NCAA-DOD CARE Consortium

Abstract

There has been a recent call for longitudinal cohort studies to track the physiological recovery of sport-related concussion (SRC) and its relationship with clinical recovery. Resting-state functional magnetic resonance imaging (rs-fMRI) has shown potential for detecting subtle changes in brain function after SRC. We investigated the effects of SRC on rs-fMRI metrics assessing local connectivity (regional homogeneity; REHO), global connectivity (average nodal strength), and the relative amplitude of slow oscillations of rs-fMRI (fractional amplitude of low-frequency fluctuations; fALFF). Athletes diagnosed with SRC (n = 92) completed visits with neuroimaging at 24-48 h post-injury (24 h), after clearance to begin the return-to-play (RTP) progression (asymptomatic), and 7 days following unrestricted RTP (post-RTP). Noninjured athletes (n = 82) completed visits yoked to the schedule of matched injured athletes and served as controls. Concussed athletes had elevated symptoms, worse neurocognitive performance, greater balance deficits, and elevated psychological symptoms at the 24-h visit relative to controls.These deficits were largely recovered by the asymptomatic visit. Concussed athletes still reported elevated psychological symptoms at the asymptomatic visit relative to controls. Concussed athletes also had elevated REHO in the right middle and superior frontal gyri at the 24-h visit that returned to normal levels by the asymptomatic visit. Additionally, REHO in these regions at 24 h predicted psychological symptoms at the asymptomatic visit in concussed athletes. Current results suggest that SRC is associated with an acute alteration in local connectivity that follows a similar time course as clinical recovery. Our results do not indicate strong evidence that concussion-related alterations in rs-fMRI persist beyond clinical recovery.

Task-related functional magnetic resonance imaging activations in patients with acute and subacute mild traumatic brain injury: A coordinate-based meta-analysis

“…Taken together, altered recruitment of the right MFG after mTBI may represent an over-arching disruption in modulating attention. These findings are also consistent with resting-state fMRI studies in concussion and mTBI, which have observed altered functional connectivity in the right MFG (Meier et al., 2019) as well as other regions that mediate internally-oriented processes (Zhu et al., 2015; Militana et al., 2016; Borich et al, 2015).…”

A roadmap of brain recovery in a mouse model of concussion: insights from neuroimaging

“…Our results of initial increased functional connectivity associated with significant motor-balance deficits were consistent with some smaller studies that showed significant rsfMRI changes associated with post-concussion symptoms [ 34 , 36 , 37 , 102 ]; the trends and networks most frequently involved in studies were reduced connectivity in the posterior DMN [ 34 , 102 ], increased connectivity in the anterior DMN [ 34 , 102 ], reduced anti-correlation among networks with anti-correlation relationships [ 102 ], and decreased local intrinsic functional connectivity in the SN [ 36 , 37 ], in the lateralised cognitive control network [ 37 ], and in regions related with motor, sensorimotor, attention, and phonological processing [ 36 ]. On the other hand, Meier et al reported short-term elevated local intrinsic functional connectivity in regions associated with the DMN that normalised upon symptom recovery [ 39 ]. Other studies in humans have also found persistent rsfMRI changes beyond symptom recovery [ 35 , 103 , 104 ], with one study reporting no significant changes to rsfMRI connectivity when symptoms were highest, but ongoing rsfMRI changes after symptoms had recovered [ 103 ].…”

“…At 8 days post-injury, a global increase in functional connectivity was seen with improving symptoms, which recovered by 15 days post-injury [ 38 ]. Similarly, Meier et al reported increased local intrinsic functional connectivity in the right middle and superior frontal gyri at 24–48 h post-injury, which were normalised at 7 days and 6 months post-medical-clearance [ 39 ]. To the best of the authors’ knowledge no functional imaging study combining stimulus-evoked functional MRI and rsfMRI were published in a mouse model of closed-head injury.…”

Resting‐State Power and Regional Connectivity After Pediatric Mild Traumatic Brain Injury

“…Similarly, adult studies have also reported decreased thalamic fALFF 23 days postinjury, 46 region-dependent increases and decreases acutely, 47 or null findings in fALFF in a relatively large cohort of adult athletes with acute concussion. 15 These discrepancies could be due to differences in age, injury mechanism, or time since injury between the studies, all of which likely affect BOLD imaging metrics postinjury. 16 Of particular relevance, inconsistencies between our findings and prior adult studies could also be explained by the dynamic and highly plastic nature of the developing brain.…”

“…Foremost, they do not require multiple corrections for familywise error if looking across multiple regions and may better account for the heterogeneous nature of mTBI at the local level. Although previous studies have examined ReHo and fALFF alterations in both sport and emergency department (ED) samples of adult mTBI patients, 8,14,15 there is a lack of data using these parameters to characterize the effects of mTBI in children. 16 The first aim of our study was to examine whether ReHo or fALFF were affected and subsequently recovered in a large cohort of pmTBI at subacute (SA;~1 week) and early chronic (EC;~4 months) postinjury periods relative to age-and sexmatched healthy controls (HCs).…”