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Recognizing and managing the effects of cerebral concussion is very challenging, given the discrete symptomatology. Most individuals with sports-related concussion will not score below 15 on the Glasgow Coma Scale, but will present with rapid onset of short-lived neurological impairment, demonstrating no structural changes on traditional magnetic resonance imaging (MRI) and computed tomography (CT) scans. The return-to-play decision is one of the most difficult responsibilities facing the physician, and so far this decision has been primarily based on neurological examination, symptom checklists, and neuropsychological (NP) testing. Diffusion tensor imaging (DTI) may be a more objective tool to assess the severity and recovery of function after concussion. We assessed white matter (WM) fiber tract integrity in varsity level college athletes with sports-related concussion without loss of consciousness, who experienced protracted symptoms for at least 1 month after injury. Evaluation of fractional anisotropy (FA) and mean diffusivity (MD) of the WM skeleton using tract-based spatial statistics (TBSS) revealed a large cluster of significantly increased MD for concussed subjects in several WM fiber tracts in the left hemisphere, including parts of the inferior/superior longitudinal and fronto-occipital fasciculi, the retrolenticular part of the internal capsule, and posterior thalamic and acoustic radiations. Qualitative comparison of average FA and MD suggests that with increasing level of injury severity (ranging from sports-related concussion to severe traumatic brain injury), MD might be more sensitive at detecting mild injury, whereas FA captures more severe injuries. In conclusion, the TBSS analysis used to evaluate diffuse axonal injury of the WM skeleton seems sensitive enough to detect structural changes in sports-related concussion.

The extent of structural injury in sports-related concussion (SRC) is central to the course of recovery, long-term effects, and the decision to return to play. In the present longitudinal study, we used diffusion tensor imaging (DTI) to assess white matter (WM) fiber tract integrity within 2 days, 2 weeks, and 2 months of concussive injury. Participants were right-handed male varsity contact-sport athletes (20.2±1.0 years of age) with a medically diagnosed SRC (no loss of consciousness). They were compared to right-handed male varsity non-contact-sport athletes serving as controls (19.9±1.7 years). We found significantly increased radial diffusivity (RD) in concussed athletes (n=12; paired t-test, tract-based spatial statistics; p<0.025) at 2 days, when compared to the 2-week postinjury time point. The increase was found in a cluster of right hemisphere voxels, spanning the posterior limb of the internal capsule (IC), the retrolenticular part of the IC, the inferior longitudinal fasciculus, the inferior fronto-occipital fasciculus (sagittal stratum), and the anterior thalamic radiation. Post-hoc, univariate, between-group (controls vs. concussed), mixed-effects analysis of the cluster showed significantly higher RD at 2 days (p=0.002), as compared to the controls, with a trend in the same direction at 2 months (p=0.11). Results for fractional anisotropy (FA) in the same cluster showed a similar, but inverted, pattern; FA was decreased at 2 days and at 2 months postinjury, when compared to healthy controls. At 2 weeks postinjury, no statistical differences between concussed and control athletes were found with regard to either RD or FA. These results support the hypothesis of increased RD and reduced FA within 72 h postinjury, followed by recovery that may extend beyond 2 weeks. RD appears to be a sensitive measure of concussive injury.

Avoiding recurrent injury in sports-related concussion (SRC) requires understanding the neural mechanisms involved during the time of recovery after injury. The decision for return-to-play is one of the most difficult responsibilities facing the physician, and so far this decision has been based primarily on neurological examination, symptom checklists, and neuropsychological (NP) testing. Functional magnetic resonance imaging (fMRI) may be an additional, more objective tool to assess the severity and recovery of function after concussion. The purpose of this study was to define neural correlates of SRC during the 2 months after injury in varsity contact sport athletes who suffered a SRC. All athletes were scanned as they performed an n-back task, for n=1, 2, 3. Subjects were scanned within 72 hours (session one), at 2 weeks (session two), and 2 months (session three) post-injury. Compared with age and sex matched normal controls, concussed subjects demonstrated persistent, significantly increased activation for the 2 minus 1 n-back contrast in bilateral dorsolateral prefrontal cortex (DLPFC) in all three sessions and in the inferior parietal lobe in session one and two (α≤0.01 corrected). Measures of task performance revealed no significant differences between concussed versus control groups at any of the three time points with respect to any of the three n-back tasks. These findings suggest that functional brain activation differences persist at 2 months after injury in concussed athletes, despite the fact that their performance on a standard working memory task is comparable to normal controls and normalization of clinical and NP test results. These results might indicate a delay between neural and behaviorally assessed recovery after SRC.

Objectives We compared the integrity of white matter (WM) microstructure to the course of recovery in athletes who sustained one sports‐related concussion (SRC), assessing individual longitudinal changes in WM fiber tracts following SRC using pre‐ and post‐injury measurements. Materials and Methods Baseline diffusion tensor imaging (DTI) scans and neuropsychological tests were collected on 53 varsity contact‐sport college athletes. Participants (n = 13) who subsequently sustained an SRC underwent DTI scans and neuropsychological testing at 2 days, 2 weeks, and 2 months following injury. Results Relying on tract‐based spatial statistics (TBSS) analyses, we found that radial diffusivity (RD) and mean diffusivity (MD) were significantly increased at 2 days post‐injury compared to the same‐subject baseline (corrected p < 0.02). These alterations were visible in anterior/posterior WM regions spanning both hemispheres, demonstrating a diffuse pattern of injury after concussion. Implicated WM fiber tracts at 2 days include the following: right superior/inferior longitudinal fasciculus; right/left inferior fronto‐occipital fasciculus; right corticospinal tract; right acoustic radiation; right/left anterior thalamic radiations; right/left uncinate fasciculus; and forceps major/minor. At 2 weeks post‐injury, persistently elevated RD and MD were observed solely in prefrontal portions of WM fiber tracts (using same‐subject contrasts). No significant differences were found for FA in any of the post‐injury comparisons to baseline. Plots of individual subject RD and MD in prefrontal WM demonstrated homogenous increases from baseline to just after SRC; thereafter, trajectories became more variable. Most subjects’ diffusivity values remained elevated at 2 months post‐injury relative to their own baseline. Over the 2‐month period after SRC, recovery of WM fiber tracts appeared to follow a posterior‐to‐anterior trend, paralleling the posterior–anterior pattern of WM maturation previously identified in the normal population. Conclusion These results suggest greater vulnerability of prefrontal regions to SRC, underline the importance of an individualized approach to concussion management, and show promise for using RD and MD for imaging‐based diagnosis of SRC. In this study, we tracked the course of white matter (WM) tract recovery in athletes who have sustained one sports‐related concussion (SRC) by comparing baseline diffusion tensor imaging (DTI) scans to scans collected 2 days, 2 weeks, and 2 months post‐injury. We found that radial diffusivity (RD) and mean diffusivity (MD) were significantly increased at 2 days post‐injury compared to baseline scans and for most subjects, elevated RD and MD persisted at both 2 weeks and 2 months post‐injury. Over the 2‐month period following SRC, we observed WM fiber tract recovery to be individualized and to follow a posterior‐to‐anterior trend, mirroring the posterior‐to‐anterior pattern of WM maturation previously identified in the normal population.

Objective To define neural correlates of SRC during the 2 month post-injury period using a working memory (WM) task and fMRI and correlate these to clinical measures. Design Longitudinal fMRI study assessing subject's brain activation as they perform a N-back task (N=1 to 3) consisting of 30 randomised blocks. Setting Varsity collegiate athletes were recruited from high-risk sports teams. Images were acquired on a 3T Siemens Skyra scanner. Subjects All athletes were evaluated prospectively within 48 h, 2, 8 weeks postinjury on SCAT2 and hybrid NP battery (ImPACT, paper and pencil tests). 15 right-handed, varsity contact sport athletes who sustained a SRC were scanned at 72 h, 2 and 8 weeks post injury. 15 uninjured control athletes were scanned at baseline and 2 weeks. Outcome Measures Post-hoc, whole brain t tests of the 2–1 contrast were performed using FSL-FEAT (mixed effects modelling, z>2.3, corrected p=0.05). Results Across all 3 sessions, concussed athletes demonstrated significantly increased activation in the right dorsolateral prefrontal cortex (DLPFC). In session 1, concussed subjects demonstrated increased activation in additional areas: left DLPFC and bilateral inferior parietal. In all 3 sessions, no significant between group differences were observed in subjects performance for all 3 N-back task conditions. Conclusions Functional brain activation differences persist at 8 weeks post injury in concussed athletes, despite the fact that their performance on a WM task is comparable to normal controls and normalisation of clinical/hybrid NP tests. These results might indicate a delay between neural and behaviorally-assessed recovery. Acknowledgements This research was supported by NJBIR Grant 10-3217-BIR-E-0 AMSSM Grant 005548 Goldstein Family Fund.

Recognizing and managing the effects of cerebral concussion is very challenging, given the discrete symptomatology. Most individuals with sports-related concussion will not score below 15 on the Glasgow Coma Scale, but will present with rapid onset of short-lived neurological impairment, demonstrating no structural changes on traditional magnetic resonance imaging (MRI) and computed tomography (CT) scans. The return-to-play decision is one of the most difficult responsibilities facing the physician, and so far this decision has been primarily based on neurological examination, symptom checklists, and neuropsychological (NP) testing. Diffusion tensor imaging (DTI) may be a more objective tool to assess the severity and recovery of function after concussion. We assessed white matter (WM) fiber tract integrity in varsity level college athletes with sports-related concussion without loss of consciousness, who experienced protracted symptoms for at least 1 month after injury. Evaluation of fractional anisotropy (FA) and mean diffusivity (MD) of the WM skeleton using tract-based spatial statistics (TBSS) revealed a large cluster of significantly increased MD for concussed subjects in several WM fiber tracts in the left hemisphere, including parts of the inferior/superior longitudinal and fronto-occipital fasciculi, the retrolenticular part of the internal capsule, and posterior thalamic and acoustic radiations. Qualitative comparison of average FA and MD suggests that with increasing level of injury severity (ranging from sports-related concussion to severe traumatic brain injury), MD might be more sensitive at detecting mild injury, whereas FA captures more severe injuries. In conclusion, the TBSS analysis used to evaluate diffuse axonal injury of the WM skeleton seems sensitive enough to detect structural changes in sports-related concussion. [PUBLICATION ABSTRACT]

Autism is a neurodevelopmental disorder characterized by communication deficits, abnormal social interactions, and restrictive or repetitive interests and behaviors. Although autism research is an emerging field, the cause and cure remain unknown. Previous studies suggest an abnormal brain growth pattern in autism with near normal brain volume at birth, enlargement during early childhood, slowed growth during adolescence, and again, near normal brain volume during adulthood. Early brain growth abnormalities may negatively affect maturing brain areas. This leads to microscopic differences in white matter tract structure and organization which is undetectable by traditional MRI methods. By focusing on the less studied adult autistic population, the current diffusion tensor imaging study uses brain water diffusion to probe tissue organization and assess structural alterations resulting from an abnormal brain growth pattern. Typical diffusion imaging studies focus on central white matter regions to evaluate damage. The current study maps damage throughout the entire cerebral cortex using a post-processing method. In this method, subcortical diffusivity measures from white matter directly underlying the cortex are mapped to the overlying cortex. These interface maps were thoroughly investigated through a region of interest (ROI) and a voxelwise approach. Both analyses provide complementary results, finding similar areas of increased diffusivity in autistic individuals, such as middle temporal and inferior frontal areas. However, each analysis also reports several unique results. In the ROI case, autistic individuals additionally display significantly increased diffusivity in the left inferior temporal region and bilateral occipital cortex. In the voxelwise case, autistic individuals additionally display significantly increased diffusivity in the left inferior parietal lobule, bilateral precuneus, and bilateral insula. A subsequent surface-based analysis allowed visualization of these differences on the entire three dimensional cortical surface. The apparent differences between analyses are due to their inherent methodology. ROI analysis identifies larger diffusivity changes and is capable of detecting areas that may vary among subjects in their anatomical location within a region, while the voxelwise analysis finds smaller areas of change. Importantly, all identified areas are implicated in autism. Interestingly, the analyses collectively report more mean diffusivity (MD), parallel diffusivity (λ||), and perpendicular diffusivity (λ⊥) differences compared to fractional anisotropy (FA) for autistic individuals, suggesting greater MD sensitivity to diffusivity differences at the gray/white matter interface. A simple diffusion simulation was carried out to investigate relative FA and MD changes for slight modifications of parallel axonal tract organization. Due to greater FA variability and similar relative FA and MD changes, results indicate that MD is a more sensitive measure, further supporting the previous ROI, voxelwise, and surface analyses’ findings. Interface maps are potential tools for clinically diagnosing autism. Autistic and control interface diffusion data was classified using two different automated techniques, the Earth Mover’s Distance Metric and the Center of Mass. Initial investigation on the small sample size yields promising results with 13 out of 16 individuals classified correctly. This suggests the use of interface maps as biomarkers in the automated diagnosis and classification of autism.