Neural correlates of cognitive control deficits in pediatric mild traumatic brain injury

Abstract

There is a growing body of research showing that cerebral pathophysiological processes triggered by pediatric mild traumatic brain injury (pmTBI) may extend beyond the usual clinical recovery timeline. It is paramount to further unravel these processes, because the possible long-term cognitive effects resulting from ongoing secondary injury in the developing brain are not known. In the current fMRI study, neural processes related to cognitive control were studied in 181 patients with pmTBI at sub-acute (SA; ~1 week) and early chronic (EC; ~4 months) stages post-injury. Additionally, a group of 162 age- and sex-matched healthy controls (HC) were recruited at equivalent time points. Proactive (post-cue) and reactive (post-probe) cognitive control were examined using a multimodal attention fMRI paradigm for either congruent or incongruent stimuli. To study brain network function, the triple-network model was used, consisting of the executive and salience networks (collectively known as the cognitive control network), and the default mode network. Additionally, whole-brain voxel-wise analyses were performed. Decreased deactivation was found within the default mode network at the EC stage following pmTBI during both proactive and reactive control. Voxel-wise analyses revealed sub-acute hypoactivation of a frontal area of the cognitive control network (left pre-supplementary motor area) during proactive control, with a reversed effect at the EC stage after pmTBI. Similar effects were observed in areas outside of the triple-network during reactive control. Group differences in activation during proactive control were limited to the visual domain, whereas for reactive control findings were more pronounced during the attendance of auditory stimuli. No significant correlations were present between task-related activations and (persistent) post-concussive symptoms. In aggregate, current results show alterations in neural functioning during cognitive control in pmTBI up to 4 months post-injury, regardless of clinical recovery. We propose that subacute decreases in activity reflect a general state of hypo-excitability due to the injury, while early chronic hyperactivation represents a compensatory mechanism to prevent default mode interference and to retain cognitive control.

Keywords: BOLD; cognition; concussion; task fMRI.

FIGURE 1

Flowchart of enrollment, inclusion, data quality assurance, and attrition for patients with pediatric mild traumatic brain injury (pmTBI) and healthy controls (HC). Asterisks indicate the total number of participants who were eligible to return, computed as the sum of participants with usable functional magnetic resonance imaging data from the multimodal attention task and those with quality assurance issues.

FIGURE 2

Results from the primary analyses. (a) The following networks of interest (NOI) were examined: default mode network (DMN), executive network (EN), and salience network (SN). (b) Differences in DMN activity were observed during the attend‐visual cues condition between pediatric mild traumatic brain injury (pmTBI) and healthy controls (HC) at the early chronic (EC) but not sub‐acute (SA) visit. (c) Group differences in DMN activity during the attend‐auditory probes condition were similarly only present at the EC visit. Asterisks show significant (post hoc) comparisons.

FIGURE 3

Patients showed significantly higher percent signal change (PSC) in the default mode network (DMN) for the peak phase of the hemodynamic response function during the attend‐auditory probes condition.

FIGURE 4

Results from secondary whole‐brain voxel‐wise analyses. (a) Significantly decreased activation in the left‐pre‐supplementary motor area (pre‐SMA) in pediatric mild traumatic brain injury (pmTBI) versus healthy controls (HC) during attend‐visual cues at the sub‐acute (SA) visit, with a reversed effect at the early chronic (EC) visit. (b) Significant group differences for the peak, but not late peak phase of the hemodynamic response function in the left premotor cortex during the attend‐visual probes condition. (c) Group differences for a cluster in the right cerebellum (lobules VI/VIIa) that was only significant at the EC visit (pmTBI > HC), as well as for the right middle temporal gyrus that was significant at both visits (pmTBI < HC at SA, and pmTBI > HC at EC). Asterisks show significant (post hoc) comparisons.