Structural Connectivity Related to Persistent Symptoms After Mild TBI in Adolescents and Response to Aerobic Training: Preliminary Investigation

Abstract

OBJECTIVE To quantify structural connectivity abnormalities in adolescents with mild traumatic brain injury (mTBI) and to investigate connectivity changes following aerobic training using graph theory and diffusion tensor imaging (DTI) tractography. SETTING Outpatient research setting. PARTICIPANTS Twenty two children (age: 15.83±1.77 years, 10 F) with 4–16 weeks of persistent symptoms after mTBI and a matched healthy comparison group. DESIGN Randomized clinical trial of aerobic training and stretching comparison combined with case-control comparison. MAIN MEASURES (1) Five global network measures: global efficiency (Eglob), mean local efficiency, modularity, normalized clustering coefficient (γ), normalized characteristic path length (λ), small-worldness (σ). (2) The self-reported Post-Concussion Symptom Inventory (PCSI) score. RESULTS At initial enrollment, adolescents with mTBI had significantly lower Eglob and higher γ, λ, and σ (all p<0.05) when compared to healthy peers. After the intervention, significant increased Eglob and decreased λ (both p<0.05) were found in the aerobic training group. Improvement in PCSI scores were significantly correlated with the Eglob increase and λ decrease in the aerobic training and λ decrease in the stretching comparison group (all p<0.05). CONCLUSION This pilot study showed initial evidence that structural connectivity analysis was sensitive to brain network abnormalities and may serve as an imaging biomarker in children with persistent symptoms after mTBI.

The structural connectome in traumatic brain injury: A meta-analysis of graph metrics

“…In one study, p-values and t-scores were used to estimate the effect size (Hellyer et al, 2015). For longitudinal GTA studies (Yuan et al, 2017a;Yuan et al, 2017b), only the baseline ('pre-training') comparisons between TBI and HCs were included. Two papers reported TBI connectivity data in separate subgroups, one according to severity level (Königs et al, 2017), and the other by post-traumatic complaints (van der Horn et al, 2016).…”

“…Six studies reported on small-worldness differences between TBI and HCs (Caeyenberghs et al, 2012;Caeyenberghs et al, 2014;Hellyer et al, 2015;Yuan et al, 2017a;Yuan et al, 2015;Yuan et al, 2017b), with no significant effect size overall; however, a trend was evident for larger values in TBI patients (g =0.794, p =0.06, I 2 =89.736%). Of the 158 patients in this analysis, 105 were moderate to severe; 108 acute patients were between 96 hours and 5.5 months post-injury, while 50 chronic patients were on average 4.6 years post-injury; and 84 were adults (average age: ~26.6 years) and 74 were paediatric (average age: ~11.8 years) at injury.…”

“…Clear rationales and a priori hypotheses regarding the specific choice of graph metrics (together with the expected direction of effect) was omitted in many of the studies analysed. For example, Yuan et al (2017b) ambiguously predicted that metrics would be "abnormal at baseline but would normalise after training". Only Yuan et al (2015) and Königs et al (2017) justified their choice of each graph metric.…”

“…Similarly, Kim et al (2014) found that longer path length in adults with moderatesevere TBI correlated with poorer higher-order cognitive processes like executive function and verbal learning. Since then, more research has suggested that graph metrics could be 'biomarkers' of TBI (e.g., Hellyer et al, 2015;Yuan et al, 2015;Yuan et al, 2017b).…”

Cognition and Intervention in Traumatic Brain Injury

“…In adolescents presenting TBI, global efficiency level, mean local efficiency scores, modularity, normalized clustering coefficient expression, normalized characteristic path length, a measure of structural connectivity abnormality, and small-worldness assessments, as well as Post-Concussion Symptom Inventory scoring, were all inferior to healthy control adolescents, but following aerobic training, global efficiency level was increased and normalized characteristic path length was decreased [25]. Also, the enhanced PostConcussion Symptom Inventory scores were correlated significantly with the global efficiency level improvements and normalized characteristic path length decrease.…”