Feasibility of group telerehabilitation for individuals with chronic acquired brain injury: integrating clinical care and research.

BACKGROUND: Acquired brain injury (ABI) is a leading cause of lifelong disability, but access to treatment in the chronic stages has significant barriers. Group-based, remotely delivered neurorehabilitation reduces costs, travel barriers, and infection risk; however, its feasibility for patients with ABI is not well-established. OBJECTIVES: To investigate the feasibility of remotely group-based cognitive and mood therapies for persons with chronic ABI. METHODS: Three hundred and eighty-eight adults with chronic ABI participated in group tele-neurorehabilitation modules comprising Cognitive Behavioral Therapy, Goal Management Training®, Relaxation and Mindfulness Skills Training, and/or a novel Concussion Education & Symptom Management program. Assessments comprised quantitative metrics, surveys, as well as qualitative semi-structured interviews in a subset of participants. RESULTS: High retention, adherence, and satisfaction were observed. Facilitators of treatment included accessibility, cost-effectiveness, and convenience. Adoption of technology was high, but other people's technological interruptions were a barrier. Self-reported benefits specific to group-based format included improved mood, stress management, coping, interpersonal relationships, cognitive functioning, and present-mindedness. CONCLUSIONS: The present study examined chronic ABI patients' perceptions of telerehabilitation. Patients found remotely delivered, group-based mood, and cognitive interventions feasible with easy technology adoption. Group format was considered a benefit. Recommendations are provided to inform design of remotely delivered ABI programs.

Group-based mood and cognitive telerehabilitation is feasible for persons with chronic acquired brain injury, with high reported satisfaction.Screening for technical proficiency and providing ongoing technical support improves therapy adherence and retention.Integration of clinical care and research is feasible for delivering remote therapies to persons with brain injury.

Moderate-Severe TBI as a Progressive Disorder: Patterns and Predictors of Cognitive Declines in the Chronic Stages of Injury.

BACKGROUND: Moderate-severe traumatic brain injury (TBI) has been associated with progressive cognitive decline in the chronic injury stages in a small number of studies. OBJECTIVE: This study aimed to (i) replicate our previous findings of decline from 1 to 3+ years post-injury in a larger, non-overlapping sample and (ii) extend these findings by examining the proportion of decliners in 2 earlier time windows, and by investigating novel predictors of decline. METHODS: N = 48 patients with moderate-severe TBI underwent neuropsychological assessment at 2, 5, 12 months, and 30+ months post-injury. We employed the Reliable Change Index (RCI) to evaluate decline, stability and improvement across time and logistic regression to identify predictors of decline (demographic/cognitive reserve; injury-related). RESULTS: The proportions of patients showing decline were: 12.5% (2-5 months post-injury), 17% (5-12 months post-injury), and 27% (12-30+ months post-injury). Measures of verbal retrieval were most sensitive to decline. Of the predictors, only left progressive hippocampal volume loss from 5 to 12 months post-injury significantly predicted cognitive decline from 12 to 30+ months post-injury. CONCLUSIONS: Identical to our previous study, 27% of patients declined from 12 to 30+ months post-injury. Additionally, we found that the further from injury, the greater the proportion of patients declining. Importantly, earlier progressive hippocampal volume loss predicted later cognitive decline. Taken together, the findings highlight the need for ongoing research and treatment that target these deleterious mechanisms affecting patients in the chronic stages of moderate-severe TBI.

Towards PPG-based anger detection for emotion regulation.

BACKGROUND: Anger dyscontrol is a common issue after traumatic brain injury (TBI). With the growth of wearable physiological sensors, there is new potential to facilitate the rehabilitation of such anger in the context of daily life. This potential, however, depends on how well physiological markers can distinguish changing emotional states and for such markers to generalize to real-world settings. Our study explores how wearable photoplethysmography (PPG), one of the most widely available physiological sensors, could be used detect anger within a heterogeneous population. METHODS: This study collected the TRIEP (Toronto Rehabilitation Institute Emotion-Physiology) dataset, which comprised of 32 individuals (10 TBI), exposed to a variety of elicitation material (film, pictures, self-statements, personal recall), over two day sessions. This complex dataset allowed for exploration into how the emotion-PPG relationship varied over changes in individuals, endogenous/exogenous drivers of emotion, and day-to-day differences. A multi-stage analysis was conducted looking at: (1) times-series visual clustering, (2) discriminative time-interval features of anger, and (3) out-of-sample anger classification. RESULTS: Characteristics of PPG are largely dominated by inter-subject (between individuals) differences first, then intra-subject (day-to-day) changes, before differentiation into emotion. Both TBI and non-TBI individuals showed evidence of linear separable features that could differentiate anger from non-anger classes within time-interval analysis. However, what is more challenging is that these separable features for anger have various degrees of stability across individuals and days. CONCLUSION: This work highlights how there are contextual, non-stationary challenges to the emotion-physiology relationship that must be accounted for before emotion regulation technology can perform in real-world scenarios. It also affirms the need for a larger breadth of emotional sampling when building classification models.

Longitudinal Patterns of Functional Connectivity in Moderate-to-Severe Traumatic Brain Injury.

Longitudinal neuroimaging studies aid our understanding of recovery mechanisms in moderate-to-severe traumatic brain injury (TBI); however, there is a dearth of longitudinal functional connectivity research. Our aim was to characterize longitudinal functional connectivity patterns in two clinically important brain networks, the frontoparietal network (FPN) and the default mode network (DMN), in moderate-to-severe TBI. This inception cohort study of prospectively collected longitudinal data used resting-state functional magnetic resonance imaging (fMRI) to characterize functional connectivity patterns in the FPN and DMN. Forty adults with moderate-to-severe TBI (mean ± standard deviation [SD]; age = 39.53 ± 16.49 years, education = 13.92 ± 3.20 years, lowest Glasgow Coma Scale score = 6.63 ± 3.24, sex = 70% male) were scanned at approximately 0.5, 1-1.5, and 3+ years post-injury. Seventeen healthy, uninjured participants (mean ± SD; age = 38.91 ± 15.57 years, education = 15.11 ± 2.71 years, sex = 29% male) were scanned at baseline and approximately 11 months afterwards. Group independent component analyses and linear mixed-effects modeling with linear splines that contained a knot at 1.5 years post-injury were employed to investigate longitudinal network changes, and associations with covariates, including age, sex, and injury severity. In patients with TBI, functional connectivity in the right FPN increased from approximately 0.5 to 1.5 years post-injury (unstandardized estimate = 0.19, standard error [SE] = 0.07, p = 0.009), contained a slope change in the opposite direction, from positive to negative at 1.5 years post-injury (estimate = -0.21, SE = 0.11, p = 0.009), and marginally declined afterwards (estimate = -0.10, SE = 0.06, p = 0.079). Functional connectivity in the DMN increased from approximately 0.5 to 1.5 years (estimate = 0.15, SE = 0.05, p = 0.006), contained a slope change in the opposite direction, from positive to negative at 1.5 years post-injury (estimate = -0.19, SE = 0.08, p = 0.021), and was estimated to decline from 1.5 to 3+ years (estimate = -0.04, SE = 0.04, p = 0.303). Similarly, the left FPN increased in functional connectivity from approximately 0.5 to 1.5 years post-injury (estimate = 0.15, SE = 0.05, p = 0.002), contained a slope change in the opposite direction, from positive to negative at 1.5 years post-injury (estimate = -0.18, SE = 0.07, p = 0.008), and was estimated to decline thereafter (estimate = -0.04, SE = 0.03, p = 0.254). At approximately 0.5 years post-injury, patients showed hypoconnectivity compared with healthy, uninjured participants at baseline. Covariates were not significantly associated in any of the models. Findings of early improvement but a tapering and possible decline in connectivity thereafter suggest that compensatory effects are time-limited. These later reductions in connectivity mirror growing evidence of behavioral and structural decline in chronic moderate-to-severe TBI. Targeting such declines represents a novel avenue of research and offers potential for improving clinical outcomes.

Erratum to: Hippocampal Atrophy is Associated with Psychotic Symptom Severity Following Traumatic Brain Injury.

[This corrects the article DOI: 10.1093/braincomms/fcab026.].

Hippocampal atrophy is associated with psychotic symptom severity following traumatic brain injury.

Psychosis is a rare, but particularly serious sequela of traumatic brain injury. However, little is known as to the neurobiological processes that may contribute to its onset. Early evidence suggests that psychotic symptom development after traumatic brain injury may co-occur with hippocampal degeneration, invoking the possibility of a relationship. Particularly regarding the hippocampal head, these degenerative changes may lead to dysregulation in dopaminergic circuits, as is reported in psychoses due to schizophrenia, resulting in the positive symptom profile typically seen in post-injury psychosis. The objective of this study was to examine change in hippocampal volume and psychotic symptoms across time in a sample of moderate-to-severe traumatic brain injury patients. We hypothesized that hippocampal volume loss would be associated with increased psychotic symptom severity. From a database of n = 137 adult patients with prospectively collected, longitudinal imaging and neuropsychiatric outcomes, n = 24 had complete data at time points of interest (5 and 12 months post-traumatic brain injury) and showed increasing psychotic symptom severity on the Personality Assessment Inventory psychotic experiences subscale of the schizophrenia clinical scale across time. Secondary analysis employing stepwise regression with hippocampal volume change (independent variable) and Personality Assessment Inventory psychotic symptom change (dependent variable) from 5 to 12 months post-injury was conducted including age, sex, marijuana use, family history of schizophrenia, years of education and injury severity as control variables. Total right hippocampal volume loss predicted an increase in the Personality Assessment Inventory psychotic experiences subscale (F (1, 22) = 5.396, adjusted R 2 = 0.161, P = 0.030; ß = -0.017, 95% confidence interval = -0.018, -0.016) as did volume of the right hippocampal head (F (1, 22) = 5.764, adjusted R 2 = 0.172, P = 0.025; ß = -0.019, 95% confidence interval = -0.021, -0.017). Final model goodness-of-fit was confirmed using k-fold (k = 5) cross-validation. Consistent with our hypotheses, the current findings suggest that hippocampal degeneration in the chronic stages of moderate-to-severe traumatic brain injury may play a role in the delayed onset of psychotic symptoms after traumatic brain injury. These findings localized to the right hippocampal head are supportive of a proposed aetiological mechanism whereby atrophy of the hippocampal head may lead to the dysregulation of dopaminergic networks following traumatic brain injury; possibly accounting for observed clinical features of psychotic disorder after traumatic brain injury (including prolonged latency period to symptom onset and predominance of positive symptoms). If further validated, these findings may bear important clinical implications for neurorehabilitative therapies following traumatic brain injury.

Relationship Between Cognition and Gait at 2- and 12-Months Post-Traumatic Brain Injury.

Background: A common and debilitating challenge experienced by people with TBI is gait-associated mobility impairment and persisting cognitive impairments. Cognitive and physical impairments are often addressed independently during rehabilitation, however, increasing evidence links cognitive and motor processes more closely. Objectives: (1) To determine if correlations exist between measures of cognitive and gait recovery, post-TBI. (2) To investigate the predictive power of cognition at 2-months on gait outcomes at 12-months post-TBI. Methods: In this secondary, longitudinal study of cognitive and neural recovery, data from 93 participants admitted to an inpatient neurorehabilitation program were analyzed. Spatiotemporal gait variables [velocity, step time variability (STV), step length variability (SLV)] were collected along with cognitive variables [Trail Making Test-B (TMT-B), Digit Span-Forward (DS-F)]. Spearman's correlation coefficients were calculated between gait and cognitive variables. Multilinear and step wise regression analyses were calculated to determine predictive value of cognitive variables at 2-months on gait performance at 12-months-post TBI. Results: At 2-months post-injury, TMT-B was significantly correlated with gait velocity and STV; and DS-F was significantly correlated with velocity. At 12-months post-injury, TMT-B and DS-F was still significant correlated with velocity. TMT-B at 2-months was correlated with SLV and STV at 12-months; and DS-F correlated significantly with velocity. Regression models showed TMT-B at 2-months predicting STV, SLV, and velocity at 12-months. Conclusions: Significant associations and predictions between physical and cognitive recovery post-TBI were observed in this study. Future directions may consider a "neural internetwork" model as a salient rehabilitation approach in TBI that integrates physical and cognitive functions.

The scale of neurodegeneration in moderate-to-severe traumatic brain injury: a systematic review protocol.

BACKGROUND: Our understanding of recovery after moderate-to-severe traumatic brain injury (TBI) has shifted. Until recently, it was presumed that following a period of acute neurological vulnerability, the brain remained stable in the chronic stages of injury. However, recent research has shown neurodegeneration in the chronic stages of moderate-to-severe TBI, challenging the assumption of neurological stability. While there is extensive evidence that neurodegeneration occurs, debate remains regarding the scale and timing. This systematic review will evaluate the scale and timelines of neurodegeneration in adult patients with moderate-to-severe TBI. METHODS: Literature searches will be conducted in six electronic databases (from inception onwards), including MEDLINE, EMBASE, PsycINFO, CINAHL, SportDiscus, and Cochrane Central Register of Controlled Trials. We will include observational studies that examine neurodegenerative changes within a single sample of TBI patients or studies that compare neuroimaging outcomes between TBI patients and healthy controls. Our primary outcome is structural neuroimaging, and our secondary outcome is diffusion tensor imaging for detection of post-injury white matter changes. All screening, data extraction, and study quality appraisal will be performed independently by the same two study members. It is expected that a narrative summary of the literature will be produced. If feasible, we will conduct a random-effects meta-analysis. However, given the expected heterogeneity between studies (with respect to, for example, timing of imaging, regions imaged) we do not expect to perform a meta-analysis; rather, a narrative synthesis of our findings is expected to be performed. DISCUSSION: Understanding the scale and timelines of neurodegeneration in moderate-to-severe TBI (as well as which brain areas are most vulnerable to chronic declines) can inform intervention research designed to offset such changes. This may help improve patient outcome following moderate-to-severe TBI and, in turn, reduce the burden of the injury. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019117548.

Comprehensive Neuropsychiatric and Cognitive Characterization of Former Professional Football Players: Implications for Neurorehabilitation.

Objectives: To identify novel targets for neurorehabilitation of people with a remote history of multiple concussions by: (1) comprehensively characterizing neuropsychiatric and cognitive functioning in former professional football players, with a focus on executive functions; (2) distinguishing concussion-related findings from pre-morbid/cohort characteristics of professional football players; and, (3) exploring the relationship between executive functions and neuropsychiatric symptoms. Participants: Sixty-one high-functioning former professional football players and 31 age- and sex-matched control participants without history of concussion or participation in contact sports. Design: Between-groups analyses. Main measures: Neuropsychiatric. Personality Assessment Inventory (PAI) clinical scales plus the Aggression treatment consideration scale; the Mini International Neuropsychiatric Interview (MINI). Cognitive. Comprehensive clinical neuropsychological battery assessing domains of verbal and visuospatial attention; speed of processing and memory; current and estimated pre-morbid IQ; and, executive functioning, including two experimental measures that were novel for this population (i.e., response inhibition and inconsistency of responding on a go/no-go task). Results: (1) Compared to control participants, former professional football players scored significantly higher on the PAI Depression, Mania, and Aggression scales, and significantly lower on response inhibition. (2) Relative to controls, former players with >3 concussions ( x ¯ = 6 . 1 ), but not former players with ≤ 3 concussions ( x ¯ = 2 . 0 ), showed (i) significantly higher scores on the PAI Depression scale, (ii) significantly more MINI clinical diagnoses overall, and manic/hypomanic episodes specifically, and (iii) significantly poorer executive function. (3) Mediation analysis revealed that concussion exposure had a significant indirect effect on PAI Depression, Mania, and Aggression via inconsistency of responding on the go/no-go task. Conclusions: Notable impairments to neuropsychiatric functioning and worse performance on a sensitive experimental measure of executive function were observed; these were related to both concussion history and pre-morbid (cohort) factors. Therefore, neuropsychiatric and executive functioning should be carefully assessed in those with a remote history of multiple concussions. Moreover, former players' neuropsychiatric symptoms were associated with inconsistency of responding; this suggests that treatments targeted at response inconsistency could help to mitigate neuropsychiatric dysfunction.

Longitudinal Recovery of Executive Control Functions After Moderate-Severe Traumatic Brain Injury: Examining Trajectories of Variability and Ex-Gaussian Parameters.

BACKGROUND: Executive control deficits are deleterious and enduring consequences of moderate-severe traumatic brain injury (TBI) that disrupt everyday functioning. Clinically, such impairments can manifest as behavioural inconsistency, measurable experimentally by the degree of variability across trials of a reaction time (RT) task (also known as intraindividual variability [IIV]). Growing research on cognition after TBI points to cognitive deterioration in the chronic stages postinjury. OBJECTIVE: To examine the longitudinal recovery of RT characteristics (IIV and more detailed ex-Gaussian components, as well as the number of impulsively quick responses) following moderate-severe TBI. METHODS: Seventy moderate-severe TBI patients were assessed at 2, 5, 12, and 24+ months postinjury on a go/no-go RT task. RT indices (ex-Gaussian parameters mu and sigma [mean and variability of the normal distribution component], and tau [extremely slow responses]; mean, intraindividual coefficient of variation [ICV], and intraindividual standard deviation [ISD]) were analyzed with repeated-measures multivariate analysis of variance. RESULTS: ICV, ISD, and ex-Gaussian tau significantly decreased (ie, improved) over time in the first year of injury, but worsened from 1 to 2+ years, as did the frequency of extremely fast responses. These quadratic patterns were accentuated by age and shown primarily in tau (extremely slow) and extremely fast (impulsive) responses. CONCLUSIONS: The pattern of early recovery followed by decline in executive control function is consistent with growing evidence that moderate-severe TBI is a progressive and degenerative disorder. Given the responsiveness to treatment of executive control deficits, elucidating the trajectory and underpinnings of inconsistent behavioral responding may reveal novel prognostic and clinical management opportunities.

Motor Function in Former Professional Football Players with History of Multiple Concussions.

The objective of this study was to assess the incidence of motor impairment in former professional Canadian Football League (ex-CFL) players with multiple concussions. We investigated motor symptoms and signs in 45 ex-CFL players with multiple concussions and 25 age- and education-matched healthy controls with no history of concussion. Neurological assessment included items from the SCAT3 (Sport Concussion Assessment Tool 3) and the Unified Parkinson's Disease Rating Scale part III (UPDRS-Part III). A performance-based measurement of manual motor function was undertaken using the Grooved Pegboard test. Cognition was measured with patient-reported outcomes for memory, executive and behavioral symptoms as well as performance-based measures of memory and executive function. Symptoms of anxiety and depression were measured using the Personality Assessment Inventory. There was no significant difference between the ex-CFL players and controls on the UPDRS-Part III scores, and neither group reported clinically significant motor complaints. Ex-CFL players did not perform differently from control subjects on the Grooved Pegboard test. In contrast, with regard to cognitive and mood testing, players were more symptomatic: The ex-CFL players reported significantly more memory (77.8% vs. 16%, respectively, p < 0.001), executive (53.3% vs. 8%, respectively, p < 0.001), and behavioral symptoms (66.7% vs. 20%, respectively, p < 0.001). No significant differences were found when comparing ex-CFL players and controls in performance on memory and executive tests. In summary, in a group of retired CFL players who self-reported declines in memory, executive and behavioral symptoms, no motor symptoms were reported and no motor signs were detected.

Higher Anxiety Symptoms Predict Progressive Hippocampal Atrophy in the Chronic Stages of Moderate to Severe Traumatic Brain Injury.

BACKGROUND: In the chronic stages of moderate-severe traumatic brain injury (TBI), progressive hippocampal volume loss-continuing well after acute neurological insults have resolved-has now been well documented. Previous research in other populations suggests that elevated anxiety symptoms are associated with compromise to the medial temporal lobes. OBJECTIVE: To examine whether higher anxiety symptoms predict greater hippocampal volume loss in moderate-severe TBI. METHODS: We conducted an analysis of prospectively collected, longitudinal behavioral and magnetic resonance imaging (MRI) data from 5 to 12 to 30 months post-injury. Eighty participants were included in the study, with anxiety symptom and MRI data collected at a minimum of 2 time points. Correlational and bivariate latent difference score (with imputation) analyses were used to examine the relationship of Beck Anxiety Inventory scores with hippocampal volume loss, while controlling for depressive symptoms and total brain volume. RESULTS: Analyses revealed that higher anxiety symptoms at 5 and at 12 months following moderate-severe TBI predicted significant later volume loss in the right hippocampal complex and the right hippocampal head. Right hippocampal volume and volume change did not predict subsequent anxiety scores or anxiety change scores. CONCLUSIONS: These novel findings implicate anxiety symptoms as a possible predictor of progressive hippocampal volume loss in the chronic stages of moderate-severe TBI.

Feasibility of online self-administered cognitive training in moderate-severe brain injury.

PURPOSE: Cognitive environmental enrichment (C-EE) offers promise for offsetting neural decline that is observed in chronic moderate-severe traumatic brain injury (TBI). Brain games are a delivery modality for C-EE that can be self-administered over the Internet without therapist oversight. To date, only one study has examined the feasibility of self-administered brain games in TBI, and the study focused predominantly on mild TBI. Therefore, the primary purpose of the current study was to examine the feasibility of self-administered brain games in moderate-severe TBI. A secondary and related purpose was to examine the feasibility of remote monitoring of any C-EE-induced adverse symptoms with a self-administered evaluation tool. METHOD: Ten patients with moderate-severe TBI were asked to complete 12 weeks (60 min/day, five days/week) of online brain games with bi-weekly self-evaluation, intended to measure any adverse consequences of cognitive training (e.g., fatigue, eye strain). RESULTS: There was modest weekly adherence (42.6% ± 4.4%, averaged across patients and weeks) and 70% patient retention; of the seven retained patients, six completed the self-evaluation questionnaire at least once/week for each week of the study. CONCLUSIONS: Even patients with moderate-severe TBI can complete a demanding, online C-EE intervention and a self-administered symptom evaluation tool with limited therapist oversight, though at daily rate closer to 30 than 60 min per day. Further self-administered C-EE research is underway in our lab, with more extensive environmental support. Implications for Rehabilitation Online brain games (which may serve as a rehabilitation paradigm that can help offset the neurodegeneration observed in chronic TBI) can be feasibly self-administered by moderate-to-severe TBI patients. Brain games are a promising therapy modality, as they can be accessed by all moderate-to-severe TBI patients irrespective of geographic location, clinic and/or therapist availability, or impairments that limit mobility and access to rehabilitation services. Future efficacy trials that examine the effect of brain games for offsetting neurodegeneration in moderate-to-severe TBI patients are warranted.

Envisioning future cognitive telerehabilitation technologies: a co-design process with clinicians.

Purpose Cognitive telerehabilitation is the concept of delivering cognitive assessment, feedback, or therapeutic intervention at a distance through technology. With the increase of mobile devices, wearable sensors, and novel human-computer interfaces, new possibilities are emerging to expand the cognitive telerehabilitation paradigm. This research aims to: (1) explore design opportunities and considerations when applying emergent pervasive computing technologies to cognitive telerehabilitation and (2) develop a generative co-design process for use with rehabilitation clinicians. Methods We conducted a custom co-design process that used design cards, probes, and design sessions with traumatic brain injury (TBI) clinicians. All field notes and transcripts were analyzed qualitatively. Results Potential opportunities for TBI cognitive telerehabilitation exist in the areas of communication competency, executive functioning, emotional regulation, energy management, assessment, and skill training. Designers of TBI cognitive telerehabilitation technologies should consider how technologies are adapted to a patient's physical/cognitive/emotional state, their changing rehabilitation trajectory, and their surrounding life context (e.g. social considerations). Clinicians were receptive to our co-design approach. Conclusion Pervasive computing offers new opportunities for life-situated cognitive telerehabilitation. Convivial design methods, such as this co-design process, are a helpful way to explore new design opportunities and an important space for further methodological development. Implications for Rehabilitation Designers of rehabilitation technologies should consider how to extend current design methods in order to facilitate the creative contribution of rehabilitation stakeholders. This co-design approach enables a fuller participation from rehabilitation clinicians at the front-end of design. Pervasive computing has the potential to: extend the duration and intensity of cognitive telerehabilitation training (including the delivery of 'booster' sessions or maintenance therapies); provide assessment and treatment in the context of a traumatic brain injury (TBI) patient's everyday life (thereby enhancing generalization); and permit time-sensitive interventions. Long-term use of pervasive computing for TBI cognitive telerehabilitation should take into account a patient's changing recovery trajectory, their meaningful goals, and their journey from loss to redefinition.

Negative neuroplasticity in chronic traumatic brain injury and implications for neurorehabilitation.

Based on growing findings of brain volume loss and deleterious white matter alterations during the chronic stages of injury, researchers posit that moderate-severe traumatic brain injury (TBI) may act to "age" the brain by reducing reserve capacity and inducing neurodegeneration. Evidence that these changes correlate with poorer cognitive and functional outcomes corroborates this progressive characterization of chronic TBI. Borrowing from a framework developed to explain cognitive aging (Mahncke et al., Progress in Brain Research, 157, 81-109, 2006a; Mahncke et al., Proceedings of the National Academy of Sciences of the United States of America, 103(33), 12523-12528, 2006b), we suggest here that environmental factors (specifically environmental impoverishment and cognitive disuse) contribute to a downward spiral of negative neuroplastic change that may modulate the brain changes described above. In this context, we review new literature supporting the original aging framework, and its extrapolation to chronic TBI. We conclude that negative neuroplasticity may be one of the mechanisms underlying cognitive and neural decline in chronic TBI, but that there are a number of points of intervention that would permit mitigation of this decline and better long-term clinical outcomes.

Scale and pattern of atrophy in the chronic stages of moderate-severe TBI.

BACKGROUND: Moderate-severe traumatic brain injury (TBI) is increasingly being understood as a progressive disorder, with growing evidence of reduced brain volume and white matter (WM) integrity as well as lesion expansion in the chronic phases of injury. The scale of these losses has yet to be investigated, and pattern of change across structures has received limited attention. OBJECTIVES: (1) To measure the percentage of patients in our TBI sample showing atrophy from 5 to 20 months post-injury in the whole brain and in structures with known vulnerability to acute TBI, and (2) To examine relative vulnerability and patterns of volume loss across structures. METHODS: Fifty-six TBI patients [complicated mild to severe, with mean Glasgow Coma Scale (GCS) in severe range] underwent MRI at, on average, 5 and 20 months post-injury; 12 healthy controls underwent MRI twice, with a mean gap between scans of 25.4 months. Mean monthly percent volume change was computed for whole brain (ventricle-to-brain ratio; VBR), corpus callosum (CC), and right and left hippocampi (HPC). RESULTS: (1) Using a threshold of 2 z-scores below controls, 96% of patients showed atrophy across time points in at least one region; 75% showed atrophy in at least 3 of the 4 regions measured. (2) There were no significant differences in the proportion of patients who showed atrophy across structures. For those showing decline in VBR, there was a significant association with both the CC and the right HPC (P < 0.05 for both comparisons). There were also significant associations between those showing decline in (i) right and left HPC (P < 0.05); (ii) all combinations of genu, body and splenium of the CC (P < 0.05), and (iii) head and tail of the right HPC (P < 0.05 all sub-structure comparisons). CONCLUSIONS: Atrophy in chronic TBI is robust, and the CC, right HPC and left HPC appear equally vulnerable. Significant associations between the right and left HPC, and within substructures of the CC and right HPC, raise the possibility of common mechanisms for these regions, including transneuronal degeneration. Given the 96% incidence rate of atrophy, a genetic explanation is unlikely to explain all findings. Multiple and possibly synergistic mechanisms may explain findings. Atrophy has been associated with poorer functional outcomes, but recent findings suggest there is potential to offset this. A better, understanding of the underlying mechanisms could permit targeted therapy enabling better long-term outcomes.

Chronic traumatic encephalopathy and other neurodegenerative proteinopathies.

"Chronic traumatic encephalopathy" (CTE) is described as a slowly progressive neurodegenerative disease believed to result from multiple concussions. Traditionally, concussions were considered benign events and although most people recover fully, about 10% develop a post-concussive syndrome with persisting neurological, cognitive and neuropsychiatric symptoms. CTE was once thought to be unique to boxers, but it has now been observed in many different athletes having suffered multiple concussions as well as in military personal after repeated blast injuries. Much remains unknown about the development of CTE but its pathological substrate is usually tau, similar to that seen in Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). The aim of this "perspective" is to compare and contrast clinical and pathological CTE with the other neurodegenerative proteinopathies and highlight that there is an urgent need for understanding the relationship between concussion and the development of CTE as it may provide a window into the development of a proteinopathy and thus new avenues for treatment.

Environmental enrichment may protect against hippocampal atrophy in the chronic stages of traumatic brain injury.

OBJECTIVE: To examine the relationship between environmental enrichment (EE) and hippocampal atrophy in the chronic stages of moderate to severe traumatic brain injury (TBI). DESIGN: Retrospective analysis of prospectively collected data; observational, within-subjects. PARTICIPANTS: Patients (N = 25) with moderate to severe TBI. MEASURES: Primary predictors: (1) An aggregate of self-report rating of EE (comprising hours of cognitive, physical, and social activities) at 5 months post-injury; (2) pre-injury years of education as a proxy for pre-morbid EE (or cognitive reserve). PRIMARY OUTCOME: bilateral hippocampal volume change from 5 to 28 months post-injury. RESULTS: As predicted, self-reported EE was significantly negatively correlated with bilateral hippocampal atrophy (p < 0.05), with greater EE associated with less atrophy from 5 to 28 months. Contrary to prediction, years of education (a proxy for cognitive reserve) was not significantly associated with atrophy. CONCLUSION: Post-injury EE may serve as a buffer against hippocampal atrophy in the chronic stages of moderate-severe TBI. Clinical application of EE should be considered for optimal maintenance of neurological functioning in the chronic stages of moderate-severe TBI.

The influence of indirect and direct emotional processing on memory for facial expressions.

We used the remember-know procedure (Tulving, 1985 ) to test the behavioural expression of memory following indirect and direct forms of emotional processing at encoding. Participants (N=32) viewed a series of facial expressions (happy, fearful, angry, and neutral) while performing tasks involving either indirect (gender discrimination) or direct (emotion discrimination) emotion processing. After a delay, participants completed a surprise recognition memory test. Our results revealed that indirect encoding of emotion produced enhanced memory for fearful faces whereas direct encoding of emotion produced enhanced memory for angry faces. In contrast, happy faces were better remembered than neutral faces after both indirect and direct encoding tasks. These findings suggest that fearful and angry faces benefit from a recollective advantage when they are encoded in a way that is consistent with the predictive nature of their threat. We propose that the broad memory advantage for happy faces may reflect a form of cognitive flexibility that is specific to positive emotions.