Altered lateralization of the cingulum in deployment-related traumatic brain injury: An ENIGMA military-relevant brain injury study.

Traumatic brain injury (TBI) in military populations can cause disruptions in brain structure and function, along with cognitive and psychological dysfunction. Diffusion magnetic resonance imaging (dMRI) can detect alterations in white matter (WM) microstructure, but few studies have examined brain asymmetry. Examining asymmetry in large samples may increase sensitivity to detect heterogeneous areas of WM alteration in mild TBI. Through the Enhancing Neuroimaging Genetics Through Meta-Analysis Military-Relevant Brain Injury working group, we conducted a mega-analysis of neuroimaging and clinical data from 16 cohorts of Active Duty Service Members and Veterans (n = 2598). dMRI data were processed together along with harmonized demographic, injury, psychiatric, and cognitive measures. Fractional anisotropy in the cingulum showed greater asymmetry in individuals with deployment-related TBI, driven by greater left lateralization in TBI. Results remained significant after accounting for potentially confounding variables including posttraumatic stress disorder, depression, and handedness, and were driven primarily by individuals whose worst TBI occurred before age 40. Alterations in the cingulum were also associated with slower processing speed and poorer set shifting. The results indicate an enhancement of the natural left laterality of the cingulum, possibly due to vulnerability of the nondominant hemisphere or compensatory mechanisms in the dominant hemisphere. The cingulum is one of the last WM tracts to mature, reaching peak FA around 42 years old. This effect was primarily detected in individuals whose worst injury occurred before age 40, suggesting that the protracted development of the cingulum may lead to increased vulnerability to insults, such as TBI.

Novel Psychiatric Disorder 6 Months After Traumatic Brain Injury in Children and Adolescents.

OBJECTIVE: To investigate the factors predictive of novel psychiatric disorders in the interval 0-6 months following traumatic brain injury (TBI). METHODS: Children ages 5-14 years consecutively hospitalized for mild to severe TBI at five hospitals were recruited. Participants were evaluated at baseline (soon after injury) for pre-injury characteristics including psychiatric disorders, socioeconomic status (SES), psychosocial adversity, family function, family psychiatric history, and adaptive function. In addition to the psychosocial variables, injury severity and lesion location detected with acquisition of a research MRI were measured to develop a biopsychosocial predictive model for development of novel psychiatric disorders. Psychiatric outcome, including occurrence of a novel psychiatric disorder, was assessed 6 months after the injury. RESULTS: The recruited sample numbered 177 children, and 141 children (80%) returned for the six-month assessment. Of the 141 children, 58 (41%) developed a novel psychiatric disorder. In univariable analyses, novel psychiatric disorder was significantly associated with lower SES, higher psychosocial adversity, and lesions in frontal lobe locations, such as frontal white matter, superior frontal gyrus, inferior frontal gyrus, and orbital gyrus. Multivariable analyses found that novel psychiatric disorder was independently and significantly associated with frontal-lobe white matter, superior frontal gyrus, and orbital gyrus lesions. CONCLUSION: The results demonstrate that occurrence of novel psychiatric disorders following pediatric TBI requiring hospitalization is common and has identifiable psychosocial and specific biological predictors. However, only the lesion predictors were independently related to this adverse psychiatric outcome.

Novel Oppositional Defiant Disorder 12 Months After Traumatic Brain Injury in Children and Adolescents.

OBJECTIVE: The investigators examined the factors predictive of novel oppositional defiant disorder in the 6-12 months following traumatic brain injury (TBI). METHODS: Children ages 5-14 years old who experienced a TBI were recruited from consecutive admissions to five hospitals. Participants were evaluated soon after injury (baseline) for preinjury characteristics, including psychiatric disorders, adaptive function, family function, psychosocial adversity, family psychiatric history, socioeconomic status, and injury severity, to develop a biopsychosocial predictive model for development of novel oppositional defiant disorder. MRI analyses were conducted to examine potential brain lesions. Psychiatric outcome, including that of novel oppositional defiant disorder, was assessed 12 months after injury. RESULTS: Although 177 children were recruited for the study, 120 children without preinjury oppositional defiant disorder, conduct disorder, or disruptive behavior disorder not otherwise specified (DBD NOS) returned for the 12-month assessment. Of these 120 children, seven (5.8%) exhibited novel oppositional defiant disorder, and none developed conduct disorder or DBD NOS in the 6-12 months postinjury. Novel oppositional defiant disorder was significantly associated with lower socioeconomic status, higher psychosocial adversity, and lower preinjury adaptive functioning. CONCLUSIONS: These results demonstrate that novel oppositional defiant disorder following TBI selectively and negatively affects an identifiable group of children. Both proximal (preinjury adaptive function) and distal (socioeconomic status and psychosocial adversity) psychosocial variables significantly increase risk for this outcome.

Novel Oppositional Defiant Disorder 6 Months After Traumatic Brain Injury in Children and Adolescents.

OBJECTIVE: The investigators aimed to assess predictive factors of novel oppositional defiant disorder (ODD) among children and adolescents in the first 6 months following traumatic brain injury (TBI). METHODS: Children ages 5-14 years who experienced a TBI were recruited from consecutive admissions to five hospitals. Testing of a biopsychosocial model that may elucidate the development of novel ODD included assessment soon after injury (baseline) of preinjury characteristics, including psychiatric disorders, adaptive function, family function, psychosocial adversity, family psychiatric history, socioeconomic status, injury severity, and postinjury processing speed (which may be a proxy for brain injury). MRI analyses were also conducted to examine potential brain lesions. Psychiatric outcome, including that of novel ODD, was assessed 6 months after the injury. RESULTS: A total of 177 children and adolescents were recruited for the study, and 134 who were without preinjury ODD, conduct disorder, or disruptive behavior disorder not otherwise specified (DBD NOS) returned for the 6-month assessment. Of those who returned 6 months postinjury, 11 (8.2%) developed novel ODD, and none developed novel conduct disorder or DBD NOS. Novel ODD was significantly associated with socioeconomic status, preinjury family functioning, psychosocial adversity, and processing speed. CONCLUSIONS: These findings show that an important minority of children with TBI developed ODD. Psychosocial and injury-related variables, including socioeconomic status, lower family function, psychosocial adversity, and processing speed, significantly increase risk for this outcome.

Risk factors for decline in cognitive performance following deployment-related mild traumatic brain injury: A preliminary report.

Thorough identification of risk factors for delayed decline in cognitive performance following combat-related mild traumatic brain injury (mTBI) is important for guiding comprehensive post-deployment rehabilitation. In a sample of veterans who reported at least one deployment-related mTBI, preliminary results indicate that factors including a history of loss of consciousness over 1 min, current obesity and hypertension, and Black race were more prevalent in those with decreased scores on a measure of memory function. These factors should be considered by clinicians and researchers working with current and former military personnel.

Diffusion Tensor Imaging Correlates of Resilience Following Adolescent Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI) is associated with considerable mortality and morbidity in adolescents, but positive outcomes are possible. Resilience is the concept that some individuals flourish despite significant adversity. OBJECTIVE: To determine if there is a relationship between resilience-promoting factors that are known to promote resilience and white matter (WM) microstructure 1 year after complicated mild TBI or moderate or severe TBI that is sustained by adolescents. METHOD: We examined the relationship between performance on a self-report measure of resilience-promoting factors and WM integrity assessed by diffusion tensor imaging in a group of adolescents who had sustained either a TBI (n = 38) or an orthopedic injury (OI) (n = 23). RESULTS: Immediately following injury, the individuals with TBI and the OI controls had comparable levels of resilience-promoting factors; however, at 1 year post injury, the TBI group endorsed fewer resilience-promoting factors and exhibited WM disruption compared with the OI controls. The individuals with TBI who had more resilience-promoting factors at 1 year post injury exhibited increased WM integrity, but the OI controls did not. Findings were particularly strong for the following structures: anterior corona radiata, anterior limb of the internal capsule, and genu of the corpus callosum-structures that are implicated in social cognition and are frequently disrupted after TBI. Relationships were notable for caregiver and community-level resilience-promoting factors. CONCLUSION: The current findings are some of the first to indicate neurobiological evidence of previously noted buffering effects of resilience-promoting factors in individuals with TBI.

Role of deployment-related mTBI and resilience in perceived participation limitations among Veterans.

Problems with social functioning are common following combat deployment, and these may be greater among individuals with a history of traumatic brain injury (TBI). The present investigation examined the impact of mild TBI (mTBI), deployment-related characteristics, and resilience on perceived participation limitations among combat Veterans. This was a cross-sectional study of 143 participants with a history of at least one deployment-related mTBI (TBI group) and 80 without a history of lifetime TBI (Comparison group). Self-report measures of participation, resilience, posttraumatic stress disorder (PTSD) symptoms, and combat exposure were administered. In addition, each participant completed a structured interview to assess lifetime TBI history. The groups did not differ in basic demographics, but significant differences were found for perceived limitations in participation, the presence of PTSD symptoms, and intensity of combat exposure. A stepwise model indicated a significant effect of resilience on reported limitations in participation (adjusted R2 = 0.61). Individuals with higher resiliency reported a higher degree of social participation, and this effect was stronger in the TBI group. Deployment-related characteristics, including intensity of combat exposure, did not have a significant effect (adjusted R2 = 0.28) on social participation. The role of resilience should be recognized within post-deployment transition and rehabilitation programs.

Mild, moderate and severe: terminology implications for clinical and experimental traumatic brain injury.

PURPOSE OF REVIEW: When describing clinical or experimental traumatic brain injury (TBI), the adjectives 'mild,' 'moderate' and 'severe' are misleading. 'Mild' clinical TBI frequently results in long-term disability. 'Severe' rodent TBI actually resembles mild or complicated mild clinical TBI. RECENT FINDINGS: Many mild TBI patients appear to have recovered completely but have postconcussive symptoms, deficits in cognitive and executive function and reduced cerebral blood flow. After moderate TBI, 31.8% of patients died or were discharged to skilled nursing or hospice. Among survivors of moderate and severe TBI, 44% were unable to return to work. On MRI, 88% of mild TBI patients have evidence of white matter damage, based on measurements of fractional anisotropy and mean diffusivity/apparent diffusion coefficient. After sports concussion, clinically recovered patients have abnormalities in functional connectivity on functional MRI. Methylphenidate improved fatigue and cognitive impairment and, combined with cognitive rehabilitation, improved memory and executive functioning. In comparison to clinical TB, because the entire spectrum of experimental rodent TBI, although defined as moderate or severe, more closely resembles mild or complicated mild clinical TBI. SUMMARY: Many patients after mild or moderate TBI suffer long-term sequelae and should be considered a major target for translational research. Treatments that improve outcome in rodent TBI, even when the experimental injuries are defined as severe, might be most applicable to mild or moderate TBI.

Pain and chronic mild traumatic brain injury in the US military population: a Chronic Effects of Neurotrauma Consortium study.

PRIMARY OBJECTIVES: To describe the association between mild traumatic brain injury (mTBI) and pain intensity and pain interference outcomes while accounting for potential confounders and mediators including environmental factors and comorbidities in a cohort of US Veterans of the Iraq and Afghanistan wars. RESEARCH DESIGN: Cross-sectional snapshot of baseline data from a prospective, longitudinal study. METHODS: Effects of mTBI on pain intensity and pain interference were compared between participants with or without mTBI exposure. Data were analysed using covariate-adjusted regression analyses as well as structural equation modelling (SEM) methods to assess the robustness of findings across different modelling assumptions. As results of the two approaches were consistent with respect to the overall association between mTBI exposure and pain, the results focus primarily on the SEM findings. RESULTS: The mTBI exposed group reported significantly greater indices of post-traumatic stress disorder (PTSD), depression, anxiety and sleep disturbance. After accounting for other factors, mTBI exposure was significantly, but indirectly associated with the pain interference and pain intensity outcomes. CONCLUSIONS: mTBI is strongly associated with pain intensity and pain interference in this sample. However, the effect appears to be mediated by other common mTBI comorbidities: PTSD, depression, anxiety and sleep disturbance.

Chronic Effects of Neurotrauma Consortium (CENC) multicentre study interim analysis: Differences between participants with positive versus negative mild TBI histories.

OBJECTIVES: Compare characteristics and outcomes of combat-exposed military personnel with positive versus negative mild traumatic brain injury (mTBI) histories. SETTING: Recruitment was from registration lists and ambulatory clinics at four veterans administration hospitals. PARTICIPANTS: Consented veterans and service members completing initial evaluation by September 2016 (n = 492). DESIGN: Observational with cross-sectional analyses. MAIN MEASURES: Multimodal assessments including structured interviews, record review, questionnaires, neuroendocrine labs and neurocognitive and sensorimotor performance. RESULTS: In unadjusted comparisons to those absent lifetime mTBI, the mTBI positive group (84%) had greater combat exposure, more potential concussive events, less social support and more comorbidities, including asthma, sleeping problems and post-traumatic stress disorder. They also fared worse on all sensory and pain symptom scores and self-reported functional and global outcomes. They had poorer scores on Wechsler Adult Intelligence Scale-IV coding (processing speed), TMT-B (visual-motor integration and executive function) and two posturography subtests, but were otherwise equal to TBI negative participants on neurocognitive and sensorimotor testing and neuroendocrine levels. CONCLUSIONS: Although differences in characteristics exist which were not adjusted for, participants with historical mTBI have greater symptomatology and life functioning difficulties compared with non-TBI. Performance measures were less dissimilar between groups. These findings will guide further research within this accruing cohort.

Higher exosomal phosphorylated tau and total tau among veterans with combat-related repetitive chronic mild traumatic brain injury.

OBJECTIVE: The objective of the study is to measure plasma and exosomal levels of tau, phosphorylated tau (p-tau), and amyloid beta (Aß) in Veterans with historical mild traumatic brain injury (mTBI) and chronic neuropsychological symptoms. METHODS: Tau, p-tau, Aß40, and Aß42 were measured by ultrasensitive immunoassay in plasma and exosomes from 195 Veterans enrolled in the Chronic Effects of Neurotrauma Consortium Multicenter Observational Study. Protein biomarkers were compared among groups with and without mTBI with loss of consciousness (LOC) or post-traumatic amnesia (PTA), and also in those with and without repetitive (≥3) mTBI (rTBI) compared to those with 0 (TBI-neg) and 1-2 mTBI. RESULTS: There were no differences in measures of plasma and exosomal protein levels among mTBI with LOC or PTA, mTBI with alteration of consciousness only or TBI-neg. Exosomal tau and exosomal p-tau were elevated in rTBI compared to those with 2 or fewer mTBIs and TBI-neg (p < 0.05). Elevations of exosomal tau and p-tau significantly correlated with post-traumatic and post-concussive symptoms, with exosomal tau also relating specifically to cognitive, affective, and somatic post-concussive symptoms (p < 0.05). CONCLUSION: rTBI is associated with elevations of exosomal p-tau and exosomal tau, suggesting that blood-based exosomes may provide a peripheral source of informative, centrally derived biomarkers in remote mTBI and that rTBI may contribute to chronic neuropsychological symptoms.

Functional brain connectivity and cortical thickness in relation to chronic pain in post-911 veterans and service members with mTBI.

OBJECTIVES: Investigate the relation of chronic pain interference to functional connectivity (FC) of brain regions and to cortical thickness in post-911 Veterans and Service Members (SMs) who sustained a mild traumatic brain injury (mTBI). METHODS: This is an observational study with cross-sectional analyses. A sample of 65 enrollees completing initial evaluation at a single site of the Chronic Effects of Neurotrauma Consortium (CENC) reported pain interference ratings on the TBI QOL. Functional connectivity and cortical thickness were measured. RESULTS: Severity of pain interference was negatively related to FC of the default mode network (DMN), i.e., participants who reported more severe pain interference had less FC between mesial prefrontal cortex and posterior regions of the DMN including posterior cingulate cortex and precuneus. Cortical thickness of specific regions was positively related to severity of pain interference. CONCLUSION: The more that pain was perceived to interfere with daily life, the less the FC between regions in a network associated with self-referential thought and mind wandering. Although cortical thickness in specific brain regions was positively related to severity of pain interference, follow-up longitudinal data, control group data, and study of individual differences in this cohort will expand this initial report and replicate these findings.

The Neuropsychology of Traumatic Brain Injury: Looking Back, Peering Ahead.

The past 50 years have been a period of exciting progress in neuropsychological research on traumatic brain injury (TBI). Neuropsychologists and neuropsychological testing have played a critical role in these advances. This study looks back at three major scientific advances in research on TBI that have been critical in pushing the field forward over the past several decades: The advent of modern neuroimaging; the recognition of the importance of non-injury factors in determining recovery from TBI; and the growth of cognitive rehabilitation. Thanks to these advances, we now have a better understanding of the pathophysiology of TBI and how recovery from the injury is also shaped by pre-injury, comorbid, and contextual factors, and we also have increasing evidence that active interventions, including cognitive rehabilitation, can help to promote better outcomes. The study also peers ahead to discern two important directions that seem destined to influence research on TBI over the next 50 years: the development of large, multi-site observational studies and randomized controlled trials, bolstered by international research consortia and the adoption of common data elements; and attempts to translate research into health care and health policy by the application of rigorous methods drawn from implementation science. Future research shaped by these trends should provide critical evidence regarding the outcomes of TBI and its treatment, and should help to disseminate and implement the knowledge gained from research to the betterment of the quality of life of persons with TBI. (JINS, 2017, 23, 806-817).

Chronic Effects of Blast-Related TBI on Subcortical Functional Connectivity in Veterans.

OBJECTIVES: Blast explosions are the most frequent mechanism of traumatic brain injury (TBI) in recent wars, but little is known about their long-term effects. METHODS: Functional connectivity (FC) was measured in 17 veterans an average of 5.46 years after their most serious blast related TBI, and in 15 demographically similar veterans without TBI or blast exposure. Subcortical FC was measured in bilateral caudate, putamen, and globus pallidus. The default mode and fronto-parietal networks were also investigated. RESULTS: In subcortical regions, between-groups t tests revealed altered FC from the right putamen and right globus pallidus. However, following analysis of covariance (ANCOVA) with age, depression (Center for Epidemiologic Studies Depression Scale), and posttraumatic stress disorder symptom (PTSD Checklist - Civilian version) measures, significant findings remained only for the right globus pallidus with anticorrelation in bilateral temporal occipital fusiform cortex, occipital fusiform gyrus, lingual gyrus, and cerebellum, as well as the right occipital pole. No group differences were found for the default mode network. Although reduced FC was found in the fronto-parietal network in the TBI group, between-group differences were nonsignificant after the ANCOVA. CONCLUSIONS: FC of the globus pallidus is altered years after exposure to blast related TBI. Future studies are necessary to explore the trajectory of changes in FC in subcortical regions after blast TBI, the effects of isolated versus repetitive blast-related TBI, and the relation to long-term outcomes in veterans. (JINS, 2016, 22, 631-642).

Quantitative structural neuroimaging of mild traumatic brain injury in the Chronic Effects of Neurotrauma Consortium (CENC): Comparison of volumetric data within and across scanners.

BACKGROUND: An important component of the multicentre Chronic Effects of Neurotrauma Consortium (CENC) project is the development of improved quantitative magnetic resonance imaging (MRI) methods, including volumetric analysis. Although many studies routinely employ quality assurance (QA) procedures including MR and human phantoms to promote accuracy and monitor site differences, few studies perform rigorous direct comparisons of these data nor report findings that enable inference regarding site-to-site comparability. These gaps in evaluating cross-site differences are concerning, especially given the well-established differences that can occur between data acquired on scanners with different manufacturer, hardware or software. METHODS: This study reports findings on (1) a series of studies utilizing two MR phantoms to interrogate machine-based variability using data collected on the same magnet, (2) a human phantom repeatedly imaged on the same scanner to investigate within-subject, within-site variability and (3) a human phantom imaged on three different scanners to examine within subject, between-site variability. RESULTS: Although variability is relatively minimal for the phantom scanned on the same magnet, significantly more variability is introduced in a human subject, particularly when regions are relatively small or multiple sites used. CONCLUSION: Vigilance when combining data from different sites is suggested and that future efforts address these issues.

Computer-automated focus lateralization of temporal lobe epilepsy using fMRI.

PURPOSE: To compare the performance of computer-automated diagnosis using functional magnetic resonance imaging (fMRI) interictal graph theory (CADFIG) to that achieved in standard clinical practice with MRI, for lateralizing the affected hemisphere in temporal lobe epilepsy (TLE). MATERIALS AND METHODS: Interictal resting state fMRI and high-resolution MRI were performed on 14 left and 10 right TLE patients. Functional topology measures were calculated from fMRI using graph theory, and used to lateralize the epileptogenic hemisphere using quadratic discriminant analysis. Leave-one-out cross-validation prediction accuracy of CADFIG was compared to performance based on expert manual analysis (MA) of MRI, using video EEG as the "gold standard" for focus lateralization. RESULTS: CADFIG correctly lateralized 95.8% (23/24) of cases, compared to 66.7% (16/24) with expert MA of MRI. Combining MA with CADFIG allowed all cases (24/24) to be correctly lateralized. CADFIG correctly identified the affected hemisphere for all patients (8/8) where MRI failed to lateralize. CONCLUSION: CADFIG based on fMRI lateralized the affected hemisphere in TLE with superior performance compared to expert MA of MRI. These results demonstrate that functional patterns in fMRI can be used with automated machine learning for diagnostic lateralization in TLE. Addition of fMRI-based tests to existing protocols for identifying the affected hemisphere in presurgical assessment can improve diagnostic accuracy and surgical outcome in TLE.

Personality Change Due to Traumatic Brain Injury in Children and Adolescents: Neurocognitive Correlates.

Personality change due to traumatic brain injury (PC) in children is an important psychiatric complication of injury and is a form of severe affective dysregulation. This study aimed to examine neurocognitive correlates of PC. The sample included 177 children 5-14 years old with traumatic brain injury who were enrolled from consecutive admissions to five trauma centers. Patients were followed up prospectively at baseline and at 6 months, and they were assessed with semistructured psychiatric interviews. Injury severity, socioeconomic status, and neurocognitive function (measures of attention, processing speed, verbal memory, IQ, verbal working memory, executive function, naming/reading, expressive language, motor speed, and motor inhibition) were assessed with standardized instruments. Unremitted PC was present in 26 (18%) of 141 participants assessed at 6 months postinjury. Attention, processing speed, verbal memory, IQ, and executive function were significantly associated with PC even after socioeconomic status, injury severity, and preinjury attention deficit hyperactivity disorder were controlled. These findings are a first step in characterizing concomitant cognitive impairments associated with PC. The results have implications beyond brain injury to potentially elucidate the neurocognitive symptom complex associated with mood instability regardless of etiology.

Psychiatric disorders in children and adolescents 24 months after mild traumatic brain injury.

This study aimed to better understand the occurrence of novel psychiatric disorders (NPDs) in children with mild traumatic brain injury (mTBI) in relation to preinjury variables, injury-related variables, and concurrent neurocognitive outcome. Eighty-seven children aged 5-14 years who had experienced mTBI were studied from consecutive hospital admissions with semistructured psychiatric interviews soon after injury (baseline). Fifty-four children were reassessed 24 months postinjury. Standardized instruments were used to evaluate injury severity, lesion characteristics, preinjury variables (lifetime psychiatric disorder, family psychiatric history, family function, socioeconomic status, psychosocial adversity, adaptive function, and academic function), and finally, postinjury neurocognitive and adaptive function. At 24 months postinjury, NPDs had occurred in 17 of 54 (31%) participants. NPD at 24 months was related to frontal white matter lesions and was associated with estimated preinjury reading, preinjury adaptive function, and concurrent deficits in reading, processing speed, and adaptive function. These findings extend earlier reports that the psychiatric morbidity after mTBI in children is more common than previously thought, and moreover, it is linked to preinjury individual variables and injury characteristics and is associated with postinjury adaptive and neurocognitive functioning.

Sport and nonsport etiologies of mild traumatic brain injury: similarities and differences.

Mild traumatic brain injury (mTBI) has recently gained appreciation as a significant public health problem, which has highlighted just how little is known about its proximal and long-term effects. A major challenge in the study of mTBI is the heterogeneity of the condition. Research on mTBI has historically separated sport and nonsport etiologies, and the extent to which research from one of these samples translates to the other is unclear. This review examines the literature on mTBI, with a focus on comparing sport and nonsport etiologies with regard to the latest research on biomechanics, pathophysiology, neurocognitive effects, and neuroimaging. Issues of particular relevance to sports injuries, such as exercise, repetitive injuries, subconcussive blows, and chronic injury effects, are also reviewed.

A Longitudinal Investigation of Sleep Quality in Adolescents and Young Adults After Mild Traumatic Brain Injury.

OBJECTIVE AND BACKGROUND: We examined sleep-related problems in adolescents and young adults after a mild traumatic brain injury (MTBI) or orthopedic injury. We extended the analysis of data from a study of early emotional and neuropsychological sequelae in these populations (McCauley et al. 2014. J Neurotrauma. 31:914). METHODS: We gave the Pittsburgh Sleep Quality Index to 77 participants with MTBI, 71 with orthopedic injury, and 43 non-injured controls. The age range was 12 to 30 years. We tested sleep quality within 96 hours of injury and at 1- and 3-month follow-up. Participants also completed measures of pain and fatigue, drug and alcohol use, and post-traumatic stress symptoms. RESULTS: Older participants (mean age=25 years) in the MTBI group exhibited a sharp increase in sleep-related symptoms between the baseline assessment and 1 month, and still had difficulties at 3 months. Younger participants with MTBI (mean age=15 years) and older participants with an orthopedic injury had modest increases in sleep difficulties between baseline and 1 month. The participants with MTBI also had more clinically significant sleep difficulties at all 3 assessments. At 3 months, Pittsburgh Sleep Quality Index scores in younger participants with MTBI and all participants with orthopedic injury did not differ significantly from the non-injured controls'. The controls had no significant change in their sleep symptoms during the 3 months. CONCLUSIONS: Sleep difficulties in young adults may persist for ≤3 months after MTBI and exceed those after orthopedic injury. Clinicians should seek and treat sleep-related problems after MTBI.