Epidemiology of Comorbid Conditions Among Adults 50 Years and Older With Traumatic Brain Injury.

OBJECTIVES: Aging individuals with traumatic brain injury (TBI) experience multiple comorbidities that can affect recovery from injury. The objective of this study was to describe the most commonly co-occurring comorbid conditions among adults 50 years and older with TBI. SETTING: Level I Trauma centers. PARTICIPANTS: Adults 50 years and older with moderate/severe TBI enrolled in the TBI-Model Systems (TBI-MS) from 2007 to 2014 (n = 2134). DESIGN: A TBI-MS prospective cohort study. MAIN MEASURES: International Classification of Disease-9th Revision codes collapsed into 45 comorbidity categories. Comorbidity prevalence estimates and trend analyses were conducted by age strata (50-54, 55-64, 65-74, 75-84, ≥85 years). A dimension reduction method, Treelet Transform, classified clusters of comorbidities that tended to co-occur. RESULTS: The 3 most commonly occurring comorbid categories were hypertensive disease (52.6/100 persons), other diseases of the respiratory system (51.8/100 persons), and fluid component imbalances (43.7/100 persons). Treelet Transform classified 3 clusters of comorbid codes, broadly classified as (1) acute medical diseases/infections, (2) chronic conditions, and (3) substance abuse disorders. CONCLUSION: This study provides valuable insight into comorbid conditions that co-occur among adults 50 years and older with TBI and provides a foundation for future studies to explore how specific comorbidities affect TBI recovery.

Post-traumatic epilepsy associations with mental health outcomes in the first two years after moderate to severe TBI: A TBI Model Systems analysis.

PURPOSE: Research suggests that there are reciprocal relationships between mental health (MH) disorders and epilepsy risk. However, MH relationships to post-traumatic epilepsy (PTE) have not been explored. Thus, the objective of this study was to assess associations between PTE and frequency of depression and/or anxiety in a cohort of individuals with moderate-to-severe TBI who received acute inpatient rehabilitation. METHODS: Multivariate regression models were developed using a recent (2010-2012) cohort (n=867 unique participants) from the TBI Model Systems (TBIMS) National Database, a time frame during which self-reported seizures, depression [Patient Health Questionnaire (PHQ)-9], and anxiety [Generalized Anxiety Disorder (GAD-7)] follow-up measures were concurrently collected at year-1 and year-2 after injury. RESULTS: PTE did not significantly contribute to depression status in either the year-1 or year-2 cohort, nor did it contribute significantly to anxiety status in the year-1 cohort, after controlling for other known depression and anxiety predictors. However, those with PTE in year-2 had 3.34 times the odds (p=.002) of having clinically significant anxiety, even after accounting for other relevant predictors. In this model, participants who self-identified as Black were also more likely to report clinical symptoms of anxiety than those who identified as White. PTE was the only significant predictor of comorbid depression and anxiety at year-2 (Odds Ratio 2.71; p=0.049). CONCLUSIONS: Our data suggest that PTE is associated with MH outcomes 2years after TBI, findings whose significance may reflect reciprocal, biological, psychological, and/or experiential factors contributing to and resulting from both PTE and MH status post-TBI. Future work should consider temporal and reciprocal relationships between PTE and MH as well as if/how treatment of each condition influences biosusceptibility to the other condition.

Genetic Variation in the Vesicular Monoamine Transporter: Preliminary Associations With Cognitive Outcomes After Severe Traumatic Brain Injury.

INTRODUCTION: Traumatic brain injury (TBI) frequently results in impaired cognition, a function that can be modulated by monoaminergic signaling. Genetic variation among monoaminergic genes may affect post-TBI cognitive performance. The vesicular monoamine transporter-2 (VMAT2) gene may be a novel source of genetic variation important for cognitive outcomes post-TBI given VMAT2's role in monoaminergic neurotransmission. OBJECTIVE: To evaluate associations between VMAT2 variability and cognitive outcomes post-TBI. METHODS: We evaluated 136 white adults with severe TBI for variation in VMAT2 using a tagging single nucleotide polymorphism (tSNP) approach (rs363223, rs363226, rs363251, and rs363341). We show genetic variation interacts with assessed cognitive impairment (cognitive composite [Comp-Cog] T-scores) to influence functional cognition (functional independence measure cognitive [FIM-Cog] subscale] 6 and 12 months postinjury. RESULTS: Multivariate analyses at 6 months postinjury showed rs363226 genotype was associated with Comp-Cog (P = .040) and interacted with Comp-Cog to influence functional cognition (P < .001). G-homozygotes had the largest cognitive impairment, and their cognitive impairment had the greatest adverse effect on functional cognition. DISCUSSION: We provide the first evidence that genetic variation within VMAT2 is associated with cognitive outcomes after TBI. Further work is needed to validate this finding and elucidate mechanisms by which genetic variation affects monoaminergic signaling, mediating differences in cognitive outcomes.

Conceptual model and cluster analysis of behavioral symptoms in two cohorts of adults with traumatic brain injuries.

INTRODUCTION: Behavioral changes often occur after moderate-to-severe traumatic brain injury (TBI) and can lead to poor health, psychosocial functioning, and quality of life. Challenges in evaluating these behaviors often result from the complexity and variability in the way they are conceptualized and defined. We propose and test a conceptual model that is specific to behavioral symptoms after TBI, to serve as a basis for better assessment and treatment. We hypothesized that clusters of individuals, with unique emotional, cognitive, and behavioral characteristics, would emerge that would illustrate this conceptual model. METHODS: We conducted model-based cluster analyses in two cohorts, 6-months post-injury (n = 79) and >6 months post-injury (n = 62), of adults with moderate-to-severe TBI to explore the face validity of our conceptual model by evaluating how participants clustered with regard to emotional (Patient Health Questionnaire 9, Positive and Negative Affect Schedule), cognitive (neuropsychological test battery), and frontal behavioral (Frontal Systems Behavior Scale) symptoms. RESULTS: In each cohort, unique clusters of participants emerged that differed significantly with regard to emotional state, cognition, and behavior (ps<.05). Those 6-months post-injury clustered along a general continuum of symptom severity in emotional and behavioral symptom domains, from no impairment to severe impairment. Clusters in the chronic cohort (>6 months) demonstrated a more complex pattern of symptoms; the most severe behavioral symptoms occurred in the context of severe emotional symptoms, even in the absence of cognitive impairment. However, problematic behavioral symptoms were also present in the context of severe cognitive impairment, even in the absence of emotional symptoms. CONCLUSIONS: Emotional, cognitive, and behavioral characteristics were represented as expected, based on the proposed conceptual model of behavior. This conceptual model provides the basis for evaluating behavioral changes after moderate-to-severe TBI and identifying modifiable targets and relevant subpopulations for behavioral intervention, with the goal of improved evidence-based personalized medicine for this population.

COMT and ANKK1 Genetics Interact With Depression to Influence Behavior Following Severe TBI: An Initial Assessment.

OBJECTIVE: Genetic variations in the dopamine (DA) system are associated with cortical-striatal behavior in multiple populations. This study assessed associations of functional polymorphisms in the ankyrin repeat and kinase domain (ANKK1; Taq1a) and catechol-O-methyltransferase (COMT; Val158Met) genes with behavioral dysfunction following traumatic brain injury (TBI). PARTICIPANTS: This was a prospective study of 90 survivors of severe TBI recruited from a level 1 trauma center. MAIN MEASURES: The Frontal Systems Behavior Scale, a self- or family report questionnaire evaluating behavior associated with frontal lobe dysfunction, was completed 6 and 12 months postinjury. Depression was measured concurrently with the Patient Health Questionnaire-9. Study participants were genotyped for Val158Met and Taq1a polymorphisms. RESULTS: No statistically significant behavioral differences were observed by Taq1a or Val158Met genotype alone. At 12 months, among those with depression, Met homozygotes (Val158Met) self-reported worse behavior than Val carriers (P = .015), and A2 homozygotes (Taq1a) self-reported worse behavior than A1 carriers (P = .028) in bivariable analysis. Multivariable models suggest an interaction between depression and genetic variation with behavior at 12 months post-TBI, and descriptive analysis suggests that carriage of both risk alleles may contribute to worse behavioral performance than carriage of either risk allele alone. CONCLUSION: In the context of depression, Val158Met and Taq1a polymorphisms are individually associated with behavioral dysfunction 12 months following severe TBI, with preliminary evidence suggesting cumulative, or perhaps epistatic, effects of COMT and ANKK1 on behavioral dysfunction.

Acute Trauma Factor Associations With Suicidality Across the First 5 Years After Traumatic Brain Injury.

OBJECTIVE: To determine whether severity of head and extracranial injuries (ECI) is associated with suicidal ideation (SI) or suicide attempt (SA) after traumatic brain injury (TBI). DESIGN: Factors associated with SI and SA were assessed in this inception cohort study using data collected 1, 2, and 5 years post-TBI from the National Trauma Data Bank and Traumatic Brain Injury Model Systems (TBIMS) databases. SETTING: Level I trauma centers, inpatient rehabilitation centers, and the community. PARTICIPANTS: Participants with TBI from 15 TBIMS Centers with linked National Trauma Data Bank trauma data (N=3575). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: SI was measured via the Patient Health Questionnaire 9 (question 9). SA in the last year was assessed via interview. ECI was measured by the Injury Severity Scale (nonhead) and categorized as none, mild, moderate, or severe. RESULTS: There were 293 (8.2%) participants who had SI without SA and 109 (3.0%) who had SA at least once in the first 5 years postinjury. Random effects logit modeling showed a higher likelihood of SI when ECI was severe (odds ratio=2.73; 95% confidence interval, 1.55-4.82; P=.001). Drug use at time of injury was also associated with SI (odds ratio=1.69; 95% confidence interval, 1.11-2.86; P=.015). Severity of ECI was not associated with SA. CONCLUSIONS: Severe ECI carried a nearly 3-fold increase in the odds of SI after TBI, but it was not related to SA. Head injury severity and less severe ECI were not associated with SI or SA. These findings warrant additional work to identify factors associated with severe ECI that make individuals more susceptible to SI after TBI.

Effects of Depression and Antidepressant Use on Cognitive Deficits and Functional Cognition Following Severe Traumatic Brain Injury.

OBJECTIVE: To use a Rehabilomics framework to evaluate relations hips between post-traumatic brain injury (TBI) depression (PTD) and potential associated factors, including antidepressant use, on cognitive recovery following severe TBI. PARTICIPANTS: Severe TBI survivors (n = 154), recruited from a level 1 trauma center. DESIGN: Prospective cohort study with assessments at 6 and 12 months postinjury. MAIN MEASURES: Patient Health Questionnaire-9 (PTD symptoms); cognitive composite score from a neuropsychological assessment battery (cognitive impairment); and Functional Independence Measure-Cognition (FIM-Cog, self-reported functional cognition). RESULTS: Individuals with and without PTD did not differ with respect to cognitive impairment. However, antidepressant use, regardless of PTD status, was associated with cognitive impairment. Individuals with PTD reported lower FIM-Cog scores at both time points compared with those without PTD. In a post hoc longitudinal analysis, individuals with late-onset PTD had worse cognitive impairment. CONCLUSION: These results suggest that antidepressant use impairs cognition among individuals without PTD. Also, PTD did not directly affect cognitive impairment but may affect functional cognitive limitations through self-evaluation and apathy/motivation factors.

Persistent Hypogonadotropic Hypogonadism in Men After Severe Traumatic Brain Injury: Temporal Hormone Profiles and Outcome Prediction.

OBJECTIVE: To (1) examine relationships between persistent hypogonadotropic hypogonadism (PHH) and long-term outcomes after severe traumatic brain injury (TBI); and (2) determine whether subacute testosterone levels can predict PHH. SETTING: Level 1 trauma center at a university hospital. PARTICIPANTS: Consecutive sample of men with severe TBI between 2004 and 2009. DESIGN: Prospective cohort study. MAIN MEASURES: Post-TBI blood samples were collected during week 1, every 2 weeks until 26 weeks, and at 52 weeks. Serum hormone levels were measured, and individuals were designated as having PHH if 50% or more of samples met criteria for hypogonadotropic hypogonadism. At 6 and 12 months postinjury, we assessed global outcome, disability, functional cognition, depression, and quality of life. RESULTS: We recruited 78 men; median (interquartile range) age was 28.5 (22-42) years. Thirty-four patients (44%) had PHH during the first year postinjury. Multivariable regression, controlling for age, demonstrated PHH status predicted worse global outcome scores, more disability, and reduced functional cognition at 6 and 12 months post-TBI. Two-step testosterone screening for PHH at 12 to 16 weeks postinjury yielded a sensitivity of 79% and specificity of 100%. CONCLUSION: PHH status in men predicts poor outcome after severe TBI, and PHH can accurately be predicted at 12 to 16 weeks.

A Dopamine Pathway Gene Risk Score for Cognitive Recovery Following Traumatic Brain Injury: Methodological Considerations, Preliminary Findings, and Interactions With Sex.

OBJECTIVES: With evidence of sexual dimorphism involving the dopamine (DA)-pathway, and the importance of DA pathways in traumatic brain injury (TBI) recovery, we hypothesized that sex × DA-gene interactions may influence cognition post-TBI. PARTICIPANTS: Adult survivors of severe TBI (n = 193) consecutively recruited from a level 1 trauma center. DESIGN: Risk allele assignments were made for multiple DA pathway genes using a sex-specific stratified approach. Genetic risk alleles, and their impacts on cognition, were assessed at 6 and 12 months postinjury using unweighted, semiweighted, and weighted gene risk score (GRS) approaches. MAIN MEASURES: A cognitive composite score generated from 8 standardized neuropsychological tests targeting multiple cognitive domains. RESULTS: A significant sex × gene interaction was observed at 6 and 12 months for ANKK1 rs1800497 (6M: P = .002, 12M: P = .001) and COMT rs4680 (6M: P = .048; 12M: P = .004); DRD2 rs6279 (P = .001) and VMAT rs363226 (P = .043) genotypes were independently associated with cognition at 6 months, with trends for a sex × gene interaction at 12 months. All GRS methods were significant predictors of cognitive performance in multivariable models. Weighted GRS multivariate models captured the greatest variance in cognition: R = 0.344 (6 months); R = 0.441 (12 months), significantly increasing the variance captured from the base prediction models. CONCLUSIONS: A sex-specific DA-pathway GRS may be a valuable tool when predicting cognitive recovery post-TBI. Future work should validate these findings and explore how DA-pathway genetics may guide therapeutic intervention.

Preliminary Associations Between Brain-Derived Neurotrophic Factor, Memory Impairment, Functional Cognition, and Depressive Symptoms Following Severe TBI.

UNLABELLED: Background Traumatic brain injury (TBI) often leads to mood and cognitive complications, affecting functional recovery. Understanding neurobiological alterations common in post-TBI depression (PTD) and cognition may identify novel biomarkers for TBI complications. Brain-derived neurotrophic factor (BDNF) is a likely target based on evidence of reduced BDNF signaling in experimental TBI and depression models and its role in learning and memory. Objective To evaluate BDNF as a biomarker for PTD, cognitive impairment, and functional cognition in a prospective cohort with severe TBI. Methods Participants with TBI (n = 113) were evaluated for PTD (Patient Health Questionnaire-9 [PHQ-9]), cognitive impairment (cognitive composite score), and functional cognition (Functional Independence Measure-Cognition, FIM-Cog). BDNF levels were measured in cerebrospinal fluid and serum at 0 to 6 days postinjury and in serum at 6 and 12 months postinjury. RESULTS: Serum BDNF was reduced after TBI versus controls at all time points. Acute serum BDNF positively correlated with memory composites (6 months: r = 0.43, P = .019, n = 30; 12 months: r = 0.53, P = .005, n = 26) and FIM-Memory scores (6 months: r = 0.35, P = .019, n = 45; 12 months: r = 0.38, P = .018, n = 38). Acute serum BDNF negatively correlated with 12-month PHQ-9 scores (r = -0.38; P = .044; n = 29). At 12 months, chronic serum BDNF tended to be lower in participants with PTD (P = .07) and correlated with PHQ-9 scores (r = -0.41; P = .019; n = 32). Conclusions Acute BDNF associations with memory recovery may implicate hippocampal damage/degeneration. Comparatively, BDNF associations with PTD status were not as strong as associations with PTD severity. Further investigation may delineate longitudinal BDNF patterns, and BDNF responsive treatments, reflecting mood and cognitive recovery following TBI.

Trajectories of life satisfaction after traumatic brain injury: Influence of life roles, age, cognitive disability, and depressive symptoms.

OBJECTIVES: (a) Identify life satisfaction trajectories after moderate to severe traumatic brain injury (TBI); (b) establish a predictive model for these trajectories across the first 5 years postinjury; and (c) describe differences in these life satisfaction trajectory groups, focusing on age, depressive symptoms, disability, and participation in specific life roles. RESEARCH METHOD: Analysis of the longitudinal TBI Model Systems National Database was performed on data collected prospectively at 1-, 2-, and 5-years post-TBI. Participants (n = 3,012) had a moderate to severe TBI and were 16 years old and older. RESULTS: Four life satisfaction trajectories were identified across the first 5 years postinjury, including: stable satisfaction, initial satisfaction declining, initial dissatisfaction improving, and stable dissatisfaction. Age, depressive symptoms, cognitive disability, and life role participation as a worker, leisure participant, and/ or religious participant at 1-year postinjury significantly predicted trajectory group membership. Life role participation and depressive symptoms were strong predictors of life satisfaction trajectories across the first 5 years post-TBI. CONCLUSIONS: The previously documented loss of life roles and prevalence of depression after a moderate to severe TBI make this a vulnerable population for whom low or declining life satisfaction is a particularly high risk. Examining individual life role participation may help to identify relevant foci for community-based rehabilitation interventions or supports.

Pilot feasibility of an mHealth system for conducting ecological momentary assessment of mood-related symptoms following traumatic brain injury.

OBJECTIVE: This study assessed pilot feasibility and validity of a mobile health (mHealth) system for tracking mood-related symptoms after traumatic brain injury (TBI). DESIGN: A prospective, repeated measures design was used to assess compliance with daily ecological momentary assessments (EMA) conducted via a smartphone application over an 8-week period. METHODS: An mHealth system was developed specifically for individuals with TBI and utilized previously validated tools for depressive and anxiety symptoms (Patient Health Questionnaire-9, Generalized Anxiety Disorder-7). Feasibility was assessed in 20 community-dwelling adults with TBI via an assessment of compliance, satisfaction and usability of the smartphone applications. The authors also developed and implemented a clinical patient safety management mechanism for those endorsing suicidality. RESULTS: Participants correctly completed 73.4% of all scheduled assessments, demonstrating good compliance. Daily assessments took <2 minutes to complete. Participants reported high satisfaction with smartphone applications (6.3 of 7) and found them easy to use (6.2 of 7). Comparison of assessments obtained via telephone-based interview and EMA demonstrated high correlations (r = 0.81-0.97), supporting the validity of conducting these assessments via smartphone application in this population. CONCLUSIONS: EMA conducted via smartphone demonstrates initial feasibility among adults with TBI and presents numerous opportunities for long-term monitoring of mood-related symptoms in real-world settings.

Affective state and community integration after traumatic brain injury.

Previous studies investigating the relationship between affective state and community integration have focused primarily on the influence of depression and anxiety. In addition, they have focused on frequency of participation in various activities, failing to address an individual's subjective satisfaction with participation. The purpose of this study was to examine how affective state contributes to frequency of participation and satisfaction with participation after traumatic brain injury among participants with and without a current major depressive episode. Sixty-four community-dwelling participants with a history of complicated mild-to-severe traumatic brain injury participated in this cross-sectional cohort study. High positive affect contributed significantly to frequency of participation (ß = 0.401, P = 0.001), and both high positive affect and low negative affect significantly contributed to better satisfaction with participation (F2,61 = 13.63, P < 0.001). Further investigation to assess the direction of these relationships may better inform effective targets for intervention. These findings highlight the importance of assessing affective state after traumatic brain injury and incorporating a subjective measure of participation when considering community integration outcomes.

Brief report of affective state and depression status after traumatic brain injury.

OBJECTIVE: To examine the relationship between affective state (positive and negative affect) and depression status among adults with chronic traumatic brain injury (TBI). RESEARCH METHOD: This is a cross-sectional cohort study of community-dwelling adults with chronic TBI (n = 64) that assesses the relationship between affective state (positive and negative affect), using the Positive and Negative Affect Schedule (PANAS), and depression status, categorized as no depression, history of depressive episode, and current depressive episode, using the Primary Care Evaluation of Mental Disorders (PRIME-MD). RESULTS: Affective state differed significantly across depression status groups for both positive affect (F (2, 61) = 5.10, p = .009) and negative affect (F ( 2, 61) = 8.19, p = .001). Participants with no depression reported higher positive affect (M = 35.67, SD = 9.08) than those with a current depressive episode (M = 27.64, SD = 8.59, p = .007) and lower negative affect (M = 14.52, SD = 5.08) than those with a history of a depressive episode (M = 20.21, SD = 5.08, p = .006) and those with a current depressive episode (M = 22.29, SD = 6.21, p = .001). CONCLUSIONS: Poor affective state, including both low positive affect and high negative affect, is associated with depression diagnosis. High negative affect is present, even in the absence of a current depressive episode, after TBI. These data highlight the need to assess affective state in addition to screening for mood disorders among adults with chronic TBI.

Corpus callosum integrity and neuropsychological performance after traumatic brain injury: a diffusion tensor imaging study.

OBJECTIVES: (1) Detailed analysis of diffusion tensor imaging (DTI) parameters (fractional anisotropy and radial diffusivity) to evaluate white matter integrity in the corpus callosum (CC), and (2) examine correlations between DTI data and performance on multiple measures of cognitive functioning. PARTICIPANTS: Twelve individuals with a history of complicated mild, moderate, or severe traumatic brain injury (TBI) who were an average of 1.7 years postinjury and 12 control participants. MAIN MEASURES: Standardized and experimental neuropsychological tests; detailed analysis of DTI parameters. RESULTS: The TBI group demonstrated DTI values suggesting decreased white matter integrity and correlations with severity of injury. Both groups showed correlations between DTI parameters and cognitive measures, with more significant correlations observed for the TBI group. White matter changes in the CC were evident chronically and were related to severity of injury. CONCLUSIONS: Diffusion tensor imaging parameters suggesting disruptions in white matter in the CC may be implicated in impaired performance, both in terms of cognitive tasks and reaction time, after TBI.

Mobile phone text messaging to assess symptoms after mild traumatic brain injury and provide self-care support: a pilot study.

PURPOSE: To examine whether patients with mild traumatic brain injury (mTBI) receiving text messaging-based education and behavioral support had fewer and less severe postconcussive symptoms than those not receiving text-message support. Our secondary objective was to determine the feasibility of using text messaging to assess daily symptoms and provide support to patients with mTBI. DESIGN: Randomized controlled trial with 14-day follow-up. PARTICIPANTS: Convenience sample of 43 adult emergency department patients with mTBI. INTERVENTION: Fourteen days of timed SMS (short-message service) symptom assessments (9 AM: headaches; 1 PM: difficulty concentrating; 5 PM: irritability or anxiety) with self-care support messages. MAIN MEASURES: SMS symptom reports, Rivermead Postconcussion Symptoms Questionnaire. RESULTS: Compared with the control group, intervention participants trended to lower odds of reporting headaches (odds ratio [OR] = 0.38; 95% confidence interval [CI]: 0.07-1.99), concentration difficulty (OR = 0.32; 95% CI: 0.04-2.24), and irritability or anxiety (OR = 0.33; 95% CI: 0.05-2.35). There were also trends of lower mean scores for headaches (0.99 vs 1.19; P = .5), difficulty concentrating (0.88 vs 1.23; P = .2), and irritability/anxiety (1.00 vs 1.62; P = .06). There were high response rate to SMS symptom assessments and high satisfaction with the intervention. CONCLUSION: Those receiving the text messaging-based education and support had fewer and less severe postconcussive symptoms than the controls but none of the differences reached statistical significance. Further evaluation of more robust mobile interventions and larger sample of participants are still needed.

Unique contribution of fatigue to disability in community-dwelling adults with traumatic brain injury.

OBJECTIVE: To examine the unique contribution of fatigue to self-reported disability in community-dwelling adults with traumatic brain injury (TBI). DESIGN: A cross-sectional cohort design. SETTING: Community dwellings. PARTICIPANTS: Adults (N=50) with a history of mild to severe TBI were assessed. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: This study assessed the contribution of fatigue (Modified Fatigue Impact Scale) to disability (Mayo-Portland Adaptability Inventory), controlling for executive functions (Frontal Systems Behavior Scale), depression status (major depression in partial remission/current major depression/depressive symptoms or no history of depression), and initial injury severity (uncomplicated mild, complicated mild, moderate, or severe). RESULTS: Fatigue was found to contribute uniquely to the variance in self-reported disability (ß=.47, P<.001) after controlling for injury severity, executive functions, and depression status. The overall model was significant (F(4,45)=17.32, P<.001) and explained 61% of the variance in self-reported disability, with fatigue alone accounting for 12% of the variance in self-reported disability (F(1,45)=13.97, P<.001). CONCLUSIONS: Fatigue contributes uniquely to disability status among community-dwelling adults with chronic TBI, independent of injury severity, executive functions, and depression. Addressing fatigue through targeted interventions may help to improve self-perceived disability in this population.

Hemispheric and executive influences on low-level language processing after traumatic brain injury.

OBJECTIVE: The purpose of this study was to examine whether minor high-level language deficits found after traumatic brain injury (TBI) might be due to low-level language processing issues or executive control influences. A possible mechanism was also investigated. METHOD: Nineteen age- and education-matched healthy controls (16 M, 3 F) and 19 persons who had experienced a complicated mild, moderate or severe TBI between 1-3 years prior (16 M, 3 F; mean GCS = 9.44) participated in two computerized behavioural experiments utilizing two paradigms standard in the psycholinguistic literature (priming with lexical decision and verb generation), which included trials of greater and lesser executive demand. RESULTS: Response time and accuracy differences were found in both experiments, indicating deficits in single-word processing for the patient group. Disproportionate difficulty was found for trials which included an executive component. Right visual field (left hemisphere) preferences were found to be stronger in the TBI group than in controls. CONCLUSIONS: Results suggest that persons with TBI may have difficulties in processing single words alone, especially under conditions of increased executive demand, and that atypical patterns of hemispheric recruitment may be associated with these difficulties.

Encoding and recognition after traumatic brain injury: neuropsychological and functional magnetic resonance imaging findings.

Although impairment of episodic memory is common after traumatic brain injury (TBI), the complex nature of human memory suggests the need to study more than recall alone. For this reason, we are presenting an extension with additional analyses of persons reported in a previous publication ( Russell, Arenth, Scanlon, Kessler, & Ricker, 2011 ). We examined both the encoding and recognition components of an episodic memory paradigm containing both word and letter string blocks using functional magnetic resonance imaging (fMRI) and neuropsychological testing. This paradigm was completed by 12 persons with complicated mild, moderate, or severe TBI and 12 matched uninjured controls. Comparisons were made between groups and stimulus types. While task behavioral performance was not significantly different between groups, imaging results showed greater activation for the TBI group during the encoding portion of the task, while the control group exhibited more activation on the recognition portion. Observed areas of activation suggest that the TBI group may have used a less effective, but more automatic verbal strategy for encoding the nonpronounceable letter strings, while controls may have opted for more of a recognition-focused strategy. Group differences in California Verbal Learning Test-Second Edition (CVLT-II) performance supported these ideas, and further neuropsychological testing also suggested limitations in executive functioning in the TBI group that may have influenced performance. Implications for intervention are discussed.

CDP-choline as a biological supplement during neurorecovery: a focused review.

Cytidine 5'-diphosphocholine (CDP-choline or citicoline) is a highly bioavailable compound with potential benefits for aiding neural repair and increasing acetylcholine levels in the central and peripheral nervous system. As a result, many researchers have investigated the use of CDP-choline for various types of neurological insult or conditions, including stroke, traumatic brain injury, and Alzheimer disease. Despite the fact that the safety of the compound has been verified across multiple international studies, evidence for efficacy remains less clear. This may be attributable, at least in part, to several issues, including a lack of randomized clinical trials, a lack of availability of the compound in the United States, and statistical power issues in reported trials. In addition, the fact that CDP-choline has multiple potential points of therapeutic impact makes it an exciting treatment option in theory but also complicates the analysis of efficacy in the sense that multiple mechanisms and time points must be evaluated. Although some clinical conditions do not appear to benefit from CDP-choline treatment, the majority of findings to date have suggested at least minor benefits of treatment. In this review we will examine the evidence in the published literature pertaining to use of CDP-choline in rehabilitation populations and briefly consider the work yet to be done.