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

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.

Resting State Functional Connectivity between Dorsal Attentional Network and Right Inferior Frontal Gyrus in Concussed and Control Adolescents.

Concussion among adolescents continues to be a public health concern. Yet, the differences in brain function between adolescents with a recent concussion and adolescents with no history of concussion are not well understood. Although resting state functional magnetic resonance imaging (fMRI) can be a useful tool in examining these differences, few studies have used this technique to examine concussion in adolescents. Here, we investigate the differences in the resting state functional connectivity of 52 adolescents, 38 with a concussion in the previous 10 days (mean age = 15.6; female = 36.8%), and 14 controls with no concussion history (mean age = 15.1; female = 57.1%). Independent component analysis and dual regression revealed that control adolescents had significantly greater functional connectivity between the dorsal attention network (DAN) and right inferior frontal gyrus (RIFG) compared to concussed adolescents (p-corrected < 0.001). Specifically, there was a positive DAN-RIFG connectivity in control, but not concussed, adolescents. Our findings indicate that concussion is associated with disrupted DAN-RIFG connectivity, which may reflect a general, nonspecific response to injury.

Vestibular/ocular motor symptoms in concussed adolescents are linked to retrosplenial activation.

Following concussion, adolescents often experience vestibular and ocular motor symptoms as well as working memory deficits that may affect their cognitive, academic and social well-being. Complex visual environments including school activities, playing sports, or socializing with friends may be overwhelming for concussed adolescents suffering from headache, dizziness, nausea and fogginess, thus imposing heightened requirements on working memory to adequately function in such environments. While understanding the relationship between working memory and vestibular/ocular motor symptoms is critically important, no previous study has examined how an increase in working memory task difficulty affects the relationship between severity of vestibular/ocular motor symptoms and brain and behavioural responses in a working memory task. To address this question, we examined 80 adolescents (53 concussed, 27 non-concussed) using functional MRI while performing a 1-back (easy) and 2-back (difficult) working memory tasks with angry, happy, neutral and sad face distractors. Concussed adolescents completed the vestibular/ocular motor screening and were scanned within 10 days of injury. We found that all participants showed lower accuracy and slower reaction time on difficult (2-back) versus easy (1-back) tasks (P-values < 0.05). Concussed adolescents were significantly slower than controls across all conditions (P < 0.05). In concussed adolescents, higher vestibular/ocular motor screening total scores were associated with significantly greater differences in reaction time between 1-back and 2-back across all distractor conditions and significantly greater differences in retrosplenial cortex activation for the 1-back versus 2-back condition with neutral face distractors (P-values < 0.05). Our findings suggest that processing of emotionally ambiguous information (e.g. neutral faces) additionally increases the task difficulty for concussed adolescents. Post-concussion vestibular/ocular motor symptoms may reduce the ability to inhibit emotionally ambiguous information during working memory tasks, potentially affecting cognitive, academic and social functioning in concussed adolescents.