The role of sleep quality on white matter integrity and concussion symptom severity in adolescents

Abstract

Background: Sleep problems are common after concussion; yet, to date, no study has evaluated the relationship between sleep, white matter integrity, and post-concussion symptoms in adolescents. Using self-reported quality of sleep measures within the first 10 days of injury, we aimed to determine if quality of sleep exerts a main effect on white matter integrity in major tracts, as measured by diffusion Magnetic Resonance Imaging (dMRI), and further examine whether this effect can help explain the variance in post-concussion symptom severity in 12- to 17.9-year-old adolescents.

Methods: dMRI data were collected in 57 concussed adolescents (mean age[SD] = 15.4[1.5] years; 41.2 % female) with no history of major psychiatric diagnoses. Severity of post-concussion symptoms was assessed at study entry (mean days[SD] = 3.7[2.5] days since injury). Using the Pittsburgh Sleep Quality Index (PSQI), concussed adolescents were divided into two groups based on their quality of sleep in the days between injury and scan: good sleepers (PSQI global score ≤ 5; N = 33) and poor sleepers (PSQI global score > 5; N = 24). Neurite Orientation Dispersion and Dispersion Index (NODDI), specifically the Neurite Density Index (NDI), was used to quantify microstructural properties in major tracts, including 18 bilateral and one interhemispheric tract, and identify whether dMRI differences existed in good vs poor sleepers. Since the interval between concussion and neuroimaging acquisition varied among concussed adolescents, this interval was included in the analysis along with an interaction term with sleep groups. Regularized regression was used to identify if quality of sleep-related dMRI measures correlated with post-concussion symptom severity. Due to higher reported concussion symptom severity in females, interaction terms between dMRI and sex were included in the regularized regression model. Data collected in 33 sex- and age-matched non-concussed controls (mean age[SD] = 15.2[1.5]; 45.5 % female) served as healthy reference and sex and age were covariates in all analyses.

Results: Relative to good sleepers, poor sleepers demonstrated widespread lower NDI (18 of the 19 tracts; FDR corrected P < 0.048). This group effect was only significant with at least seven days between concussion and neuroimaging acquisition. Post-concussion symptoms severity was negatively correlated with NDI in four of these tracts: cingulum bundle, optic radiation, striato-fronto-orbital tract, and superior longitudinal fasciculus I. The multiple linear regression model combining sex and NDI of these four tracts was able to explain 33.2 % of the variability in symptom severity (F[7,49] = 4.9, P < 0.001, Adjusted R² = 0.332). Relative to non-concussed controls, poor sleepers demonstrated lower NDI in the cingulum bundle, optic radiation, and superior longitudinal fasciculus I (FDR corrected P < 0.040).

Conclusions: Poor quality of sleep following concussion is associated with widespread lower integrity of major white matter tracts, that in turn helped to explain post-concussion symptom severity in 12-17.9-year-old adolescents. The effect of sleep on white matter integrity following concussion was significant after one week, suggesting that acute sleep interventions may need this time to begin to take effect. Our findings may suggest an important relationship between good quality of sleep in the days following concussion and integrity of major white matter tracts. Moving forward, researchers should evaluate the effectiveness of sleep interventions on white matter integrity and clinical outcomes following concussion.

Keywords: Adolescence; Concussion; Diffusion MRI; Post-concussion symptoms; Sleep; White matter.

Fig. 1

White matter tracts associated with quality of sleep following concussion.

Fig. 2

Between-group differences in white matter tracts associated with post-concussion symptoms.