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Background and ObjectivesEnlarged perivascular spaces (ePVS) have been identified as a key signature of glymphatic system dysfunction in neurological conditions. The incidence and clinical implications of ePVS after traumatic brain injury (TBI) are not yet understood. We investigated whether individuals with chronic moderate-severe TBI had an increased burden of ePVS, and whether ePVS burden is modulated by the presence of focal lesions, older brain age, and poorer sleep quality. We examined whether increased burden of ePVS was associated with poorer cognitive and emotional outcomes.MethodsUsing a cross-sectional design, participants with a single moderate-severe chronic TBI (sustained ≥ 10 years ago) were recruited from an inpatient rehabilitation program. Control participants were recruited from the community. Participants underwent 3T brain MRI, neuropsychological assessment, and clinical evaluations. ePVS burden in white matter was quantified using automated segmentation. The relationship between number of ePVS, group membership, focal lesions, brain age, current sleep quality, and outcome was modelled using negative binomial and linear regressions.ResultsThis study included 100 participants with TBI (70% male;M= 56.8 years), and 75 control participants (54.3% male;M= 59.8 years). The TBI group had a significantly greater burden of ePVS (prevalence ratio rate (PRR) = 1.29,p= 0.013, CI95%[1.05, 1.57]). The presence of bilateral lesions was associated with greater ePVS burden (PRR= 1.41,p= 0.021, CI95%[1.05, 1.90]). There was no association between ePVS burden, sleep quality (PRR= 1.01,p= 0.491, CI95%[0.98, 1.048]) and sleep duration (PRR= 1.03,p= 0.556, CI95%[0.92, 1.16]). ePVS was associated with verbal memory (β = -0.42,p= 0.006, CI95%[-0.72, -0.12]), but not with other cognitive domains. Burden of ePVS was not associated with emotional distress (β = -0.70,p= 0.461, CI95%[-2.57, 1.17) or brain age (PRR= 1.00,p= 0.665, CI95%[0.99, 1.02]).DiscussionTBI is associated with a greater burden of ePVS, especially when there have been bilateral brain lesions. ePVS was associated with reduced verbal memory performance. ePVS may indicate ongoing impairments in glymphatic system function in the chronic post-injury period.

Neuroimaging data analysis often requires purpose-built software, which can be challenging to install and may produce different results across computing environments. Beyond being a roadblock to neuroscientists, these issues of accessibility and portability can hamper the reproducibility of neuroimaging data analysis pipelines. Here, we introduce the Neurodesk platform, which harnesses software containers to support a comprehensive and growing suite of neuroimaging software (https://www.neurodesk.org/). Neurodesk includes a browser-accessible virtual desktop environment and a command line interface, mediating access to containerized neuroimaging software libraries on various computing platforms, including personal and high-performance computers, cloud computing and Jupyter Notebooks. This community-oriented, open-source platform enables a paradigm shift for neuroimaging data analysis, allowing for accessible, flexible, fully reproducible, and portable data analysis pipelines.

Anxiety and depression are two of the most common forms of psychopathology experienced after traumatic brain injury (TBI), yet there is a scarcity of studies validating measures of anxiety and depression for use with this population. Using symmetrical bifactor modeling, we evaluated whether the Hospital Anxiety and Depression Scale (HADS) reliably differentiated anxiety and depression in 874 adults with moderate-severe TBI. There was a dominant general distress factor accounting for 84% of the systematic variance in the HADS total score. The specific anxiety and depression factors accounted for little residual variance in their respective subscale scores (12% and 20%, respectively), and overall, minimal bias was found in using the HADS as a unidimensional measure. Further, in a subsample (n=184), the HADS subscales did not clearly discriminate between formal anxiety and depressive disorders diagnosed via semi-structured clinical interview. Results were consistent when accounting for degree of disability, non-English speaking background, and time post-injury. In conclusion, variance in HADS scores after TBI predominately reflects a single underlying latent variable. Clinicians and researchers working with individuals with TBI should exercise caution in interpreting the individual HADS subscales, instead considering using the total score as a more valid measure of general distress.

IntroductionPsychopathology following traumatic brain injury (TBI) is a common and debilitating consequence that is often associated with reduced functional and psychosocial outcomes. There is a lack of evidence regarding the neural underpinnings of psychopathology following TBI, and whether there may be transdiagnostic neural markers that are shared across traditional psychiatric diagnoses. The aim of this systematic review and meta-analysis is to examine the association of MRI-derived markers of brain structure and function with both transdiagnostic and specific psychopathology following moderate-severe TBI.Methods and analysisA systematic literature search of Embase (1974–2022), Ovid MEDLINE (1946–2022) and PsycINFO (1806–2022) will be conducted. Publications in English that investigate MRI correlates of psychopathology characterised by formal diagnoses or symptoms of psychopathology in closed moderate-severe TBI populations over 16 years of age will be included. Publications will be excluded that: a) evaluate non-MRI neuroimaging techniques (CT, PET, MEG, EEG); b) comprise primarily a paediatric cohort; c) comprise primarily penetrating TBI. Eligible studies will be assessed against a modified Joanna Briggs Institute Critical Appraisal Instrument and data will be extracted by two independent reviewers. A descriptive analysis of MRI findings will be provided based on qualitative synthesis of data extracted. Quantitative analyses will include a meta-analysis and a network meta-analysis where there is sufficient data available.Ethics and disseminationEthics approval is not required for the present study as there will be no original data collected. We intend to disseminate the results through publication to a high-quality peer-reviewed journal and conference presentations on completion.PROSPERO registration numberCRD42022358358Article SummaryStrengths and limitations of this study:This is a comprehensive review of MRI markers of psychopathology among adults with moderate – severe traumatic brain injuries.We will investigate neural correlates across the spectrum of psychopathology rather than focusing on specific diagnoses, allowing for transdiagnostic investigations of brain structure and function alterations after TBI with comorbid psychopathology.We will be restricting eligible studies to English language.We will capture pre-injury psychopathology where data are available and analyse the associations with post-injury psychopathology and neural correlates.

Neuroimaging data analysis often requires purpose-built software, which can be challenging to install and may produce different results across computing environments. Beyond being a roadblock to neuroscientists, these issues of accessibility and portability can hamper the reproducibility of neuroimaging data analysis pipelines. Here, we introduce the Neurodesk platform, which harnesses software containers to support a comprehensive and growing suite of neuroimaging software (https://www.neurodesk.org/). Neurodesk includes a browser-accessible virtual desktop environment and a command line interface, mediating access to containerized neuroimaging software libraries on various computing platforms, including personal and high-performance computers, cloud computing and Jupyter Notebooks. This community-oriented, open-source platform enables a paradigm shift for neuroimaging data analysis, allowing for accessible, flexible, fully reproducible, and portable data analysis pipelines.

The field of genomics is the principal avenue in the ongoing development of precision/personalised medicine for a variety of health conditions. However, relating genes to outcomes is notoriously complex, especially when considering that other variables can change, or moderate, gene-outcome associations. Here, we comprehensively discuss moderation of gene-outcome associations in the context of traumatic brain injury (TBI), a common, chronically debilitating, and costly neurological condition that is under complex polygenic influence. We focus our narrative review on single nucleotide polymorphisms (SNPs) of three of the most studied genes (apolipoprotein E, brain-derived neurotrophic factor, and catechol-O-methyltransferase) and on three demographic variables believed to moderate associations between these SNPs and TBI outcomes (age, biological sex, and ethnicity). We speculate on the mechanisms which may underlie these moderating effects, drawing widely from biomolecular and behavioural research (n = 175 scientific reports) within the TBI population (n = 72) and other neurological, healthy, ageing, and psychiatric populations (n = 103). We conclude with methodological recommendations for improved exploration of moderators in future genetics research in TBI and other populations.

This study aimed to examine the impact of break duration between consecutive shifts, time of break onset, and prior shift duration on total sleep time (TST) between shifts in heavy vehicle drivers (HVDs), and to assess the interaction between break duration and time of break onset. The sleep (actigraphy and sleep diaries) and work shifts (work diaries) of 27 HVDs were monitored during their usual work schedule for up to 9 weeks. Differences in TST between consecutive shifts and days off were assessed. Linear mixed models (followed by pairwise comparisons) assessed whether break duration, prior shift duration, time of break onset, and the interaction between break duration and break onset were related to TST between shifts. Investigators found TST between consecutive shifts (mean [SD] 6.38 [1.38] h) was significantly less than on days off (mean [SD] 7.63 [1.93] h; p 0.001). Breaks starting between 12:01 and 8:00 a.m. led to shorter sleep (p 0.05) compared to breaks starting between 4:01 and 8:00 p.m. Break durations up to 7, 9, and 11 h (Australian and European minimum break durations) resulted in a mean (SD) of 4.76 (1.06), 5.66 (0.77), and 6.41 (1.06) h of sleep, respectively. The impact of shift duration prior to the break and the interaction between break duration and time of break were not significant. HVDs' sleep between workdays is influenced independently by break duration and time of break onset. This naturalistic study provides evidence that current break regulations prevent sufficient sleep duration in this industry. Work regulations should evaluate appropriate break durations and break onset times to allow longer sleep opportunities for HVDs.

This prospective controlled study examined long-term trajectories of neuropsychological performance in individuals with traumatic brain injury (TBI) compared to healthy controls, and the impact of IQ, age at injury, time since injury, and injury severity on change over time. Fifty-three individuals with moderate to severe TBI (60.37% male

Objective This study compared traumatic brain injury (TBI) outcomes from 2 cohorts: the National Institute on Disability, Independent Living, and Rehabilitation Research Traumatic Brain Injury Model Systems (TBIMS) in the United States and Longitudinal Head Injury Outcome Study conducted in Victoria, Australia, by the Monash Epworth Rehabilitation Research Centre (MERRC). Design Cohort study with 1- and 2-year follow-up. Setting Acute trauma care and inpatient rehabilitation with follow-up. Participants Patients (N=1056) with moderate-severe TBI admitted in 2000-2012 to inpatient rehabilitation after motor vehicle–related collisions, who completed follow-up, were matched using 1:2 matching algorithm based on age at injury, days of posttraumatic amnesia, and years education, resulting in groups of 352 (MERRC) and 704 patients (TBIMS). Intervention The cohorts had received acute trauma care and inpatient rehabilitation for a median 38 (MERRC) or 33 days (TBIMS). The MERRC group also had routine access to community-based support and rehabilitation for return to work or school, attendant care, and home help as justified, funded by an accident compensation system, whereas the TBIMS cohort had variable access to these services. Main Outcome Measures Outcomes were assessed 1 and 2 years post injury in terms of employment, living situation, marital status, and Glasgow Outcome Scale-Extended (GOS-E) scores. Results At 2 years post injury, MERRC participants were more likely to be competitively employed. At both 1 and 2 years post injury, MERRC participants were more likely to be married and living independently. On GOS-E, the TBIMS group had higher percentages of patients in Lower Severe Disability/Vegetative State and Upper Good Recovery than MERRC participants, whereas the MERRC cohort had higher percentages of Lower Moderate Disability than TBIMS. Conclusions Findings may suggest that routine provision of community-based supports could confer benefits for long-term TBI outcomes. Further studies documenting rehabilitation services are needed to explore this.

Background and ObjectivesTraumatic brain injury (TBI) has been promoted as a risk factor for Alzheimer disease (AD). There is evidence of elevated β-amyloid (Aβ) and tau, the pathologic hallmarks of AD, immediately following TBI. It is not clear whether Aβ and tau remain elevated in the chronic period. To address this issue, we assessed Aβ and tau burden in long-term TBI survivors and healthy controls using PET imaging.MethodsUsing a cross-sectional design, we recruited individuals following a single moderate to severe TBI at least 10 years previously from an inpatient rehabilitation program. A demographically similar healthy control group was recruited from the community. PET data were acquired using 18F-NAV4694 (Aβ) and 18F-MK6240 (tau) tracers. Aβ deposition was quantified using the Centiloid scale. Tau deposition was quantified using the standardized uptake value ratio (SUVR) in 4 regions of interest (ROIs). As a secondary measure, PET scans were also visually read as positive or negative. We examined PET data in relation to time since injury and age at injury. PET data were analyzed in a series of regression analyses.ResultsThe sample comprised 87 individuals with TBI (71.3% male; 28.7% female; mean 57.53 years, SD 11.53) and 59 controls (59.3% male; 40.7% female; mean 60.34 years, SD 11.97). Individuals with TBI did not have significantly higher 18F-NAV4694 Centiloid values (p = 0.067) or 18F-MK6240 tau SUVRs in any ROI (p ≤ 0.001; SUVR greater for controls). Visual assessment was consistent with the quantification; individuals with TBI were not more likely than controls to have a positive Aβ (p = 0.505) or tau scan (p = 0.221). No associations were identified for Aβ or tau burden with time since injury (p = 0.057 to 0.332) or age at injury.DiscussionA single moderate to severe TBI was not associated with higher burden of Aβ or tau pathologies in the chronic period relative to healthy controls. Aβ and tau burden did not show a significant increase with years since injury, and burden did not appear to be greater for those who were older at the time of injury.

Highlights • Older age is associated with lower GABAergic inhibition in primary motor cortex (M1). • Lower GABAergic inhibition in M1 is associated with more persistent adaptation memory. • This explains why older age is associated with more persistent adaptation memory. • The way neurostimulation changes adaptation memory depends on M1 neurochemistry., Graphical abstract, Ageing disrupts the finely tuned excitation/inhibition balance (E:I) across cortex via a natural decline in inhibitory tone (γ-amino butyric acid, GABA), causing functional decrements. However, in young adults, experimentally lowering GABA in sensorimotor cortex enhances a specific domain of sensorimotor function: adaptation memory. Here, we tested the hypothesis that as sensorimotor cortical GABA declines naturally with age, adaptation memory would increase, and the former would explain the latter. Results confirmed this prediction. To probe causality, we used brain stimulation to further lower sensorimotor cortical GABA during adaptation. Across individuals, how stimulation changed memory depended on sensorimotor cortical E:I. In those with low E:I, stimulation increased memory; in those with high E:I stimulation reduced memory. Thus, we identified a form of motor memory that is naturally strengthened by age, depends causally on sensorimotor cortex neurochemistry, and may be a potent target for motor skill preservation strategies in healthy ageing and neurorehabilitation.

Facilitating successful return to work (RTW) is a key rehabilitation objective following traumatic brain injury (TBI). This study modelled early (within 6 months) and late (7-34 months) RTW by leveraging a large and comprehensive compensation database. The sample comprised 666 participants with TBI, the majority of whom sustained a moderate or severe injury caused by a motor vehicle accident. Early RTW was more likely for individuals who were pre-morbidly employed in a managerial or professional occupation (odds ratio [OR] = 2.1, confidence interval [CI] = 1.29-3.37), and those who experienced shorter post-traumatic amnesia (PTA) (OR = 0.96, CI = 0.94-0.98). RTW was less likely in the late phase for individuals who were older (hazard ratio [HR] = 0.99, CI = 0.98-1.00), experienced longer PTA (HR = 0.98, CI = 0.97-0.99), had an abdominal injury (HR = 0.90, CI = 0.67-1.21) and used more specialist practitioner (HR = 0.99, standard error [SE] = 0.98-1.00) and analgesic services (HR = 0.91, CI = 0.82-1.00). Conversely, RTW in the late phase was more likely for individuals using a greater number of specialist RTW supports (HR = 1.03, CI = 1.01-1.05). Patterns of early service utilization may therefore contribute to prediction of RTW outcome. It is encouraging that RTW was more likely for individuals using vocational supports.

The overwhelming focus of research on memory following traumatic brain injury (TBI) has been on anterograde amnesia, and very little attention has been paid to retrograde amnesia. There is evidence to suggest that retrograde autobiographical memory deficits exist after severe TBI, although there have been no prospective studies of autobiographical memory in a representative sample of moderate to severe cases recruited from hospital admissions.The purpose of the present study was to report changes in autobiographical memory performance among a group of patients soon after emergence from posttraumatic amnesia (PTA) and at the 6-month follow-up compared with a healthy control (HC) group. The authors also examined associations with anterograde memory function and community integration to assist in understanding the functional impact of autobiographical memory deficits and potential underlying mechanisms. The Autobiographical Memory Interview and the Rey Auditory Verbal Learning Test were used as measures of retrograde and anterograde memory, respectively, and the Community Integration Questionnaire was used as a measure of functional outcome in the TBI group.The results demonstrated that both personal semantic and episodic autobiographical memory scores were impaired following emergence from PTA and at the 6-month follow-up. Only subtle differences emerged in change over time in different injury severity groups. Recent retrograde memory function was associated with anterograde memory performance, which supports some degree of overlap in underlying mechanisms.The findings suggest that autobiographical memory deficits are prevalent following moderate to severe TBI and warrant consideration in rehabilitation.

Highlights • Adults with TBI show abnormal brain activation in canonical working memory networks. • Increased task load associated with behavioural deficits and greater activity in DMN. • Hyper- and hypo-activation are evident during encoding and maintenance, respectively. • Working memory deficits may reflect impaired capacity to reallocate neural resources., Impaired working memory is a common and disabling consequence of traumatic brain injury (TBI) that is caused by aberrant brain processing. However, little is known about the extent to which deficits are perpetuated by specific working memory subprocesses. Using a combined functional magnetic resonance imaging (fMRI) and working memory paradigm, we tested the hypothesis that the pattern of brain activation subserving working memory following TBI would interact with both task demands and specific working memory subcomponents: encoding, maintenance, and retrieval. Forty-three patients with moderate-severe TBI, of whom 25 were in the acute phase of recovery (M = 2.16 months, SD = 1.48 months, range = 0.69 – 6.64 months) and 18 in the chronic phase of recovery (M = 23.44 months, SD = 6.76 months, range = 13.35 – 34.82 months), were compared with 38 demographically similar healthy controls. Behaviourally, we found that working memory deficits were confined to the high cognitive load trials in both acute (P = 0.006) and chronic (P = 0.024) cohorts. Furthermore, results for a subset of the sample (18 chronic TBI and 17 healthy controls) who underwent fMRI revealed that the TBI group showed reduced brain activation when simply averaged across all task trials (regardless of cognitive load or subcomponent). However, interrogation of the subcomponents of working memory revealed a more nuanced pattern of activation. When examined more closely, patterns of brain activity following TBI were found to interact with both task demands and the working memory subcomponent: increased activation was observed during encoding in the left inferior occipital gyrus whereas decreased activation was apparent during maintenance in the bilateral cerebellum and left calcarine sulcus. Taken together, findings indicate an inability to appropriately modulate brain activity according to task demand that is specific to working memory encoding and maintenance.

The temporal lobes are critical for episodic memories and are preferentially affected following a traumatic brain injury (TBI). As such, episodic memory difficulties are common following TBI; however, the underlying neural changes that precipitate or maintain these difficulties in the early phase of recovery remains poorly understood. Here, we use functional magnetic resonance imaging (fMRI) to interrogate the relationship of temporal lobe activation in response to face, scene, and animal stimuli. Twenty-five patients with moderate to severe TBI were recruited an average of 2 months’ post-injury and compared with 21 demographically similar healthy controls. Findings indicate that memory for faces was preferentially impaired, compared to scene and animal stimuli. Decreased activity in temporal lobe structures was present for both face (right transverse temporal gyrus) and scene stimuli (right fusiform gyrus), but not for animals. Greater activation in these structures was associated with better long-term recognition. These findings provide evidence to suggest that TBI: a) preferentially affects memory for complex stimuli such as faces and scenes, and b) causes aberrant neuronal processes despite lack of evidence of significant impairment in behavioural performance. The mechanisms underpinning these findings are discussed in terms of differences in verbalisation during encoding and reduced neural efficiency.

Stroke is the largest cause of complex disability in adults. Approximately half of right-hemisphere stroke survivors suffer spatial neglect–an inability to voluntarily orient to people or objects in contralesional space. Neglect is a significant impediment to successful community reintegration. Prism adaptation (PA) is a promising behavioural intervention that can alleviate symptoms of spatial neglect. PA induces a leftward pointing bias–the prism after-effect (AE). In neglect, the prism AE generalises to improve other sensory, motor, and cognitive domains. Although the formation of an AE is a key index in neglect, we do not yet know where it is formed in the brain. Here, we used a novel computational fMRI-based approach to study, for the first time, the brain circuits that mediate the formation of PA in stroke survivors and age matched controls. Healthy individuals (n = 17) and stroke patients (n = 11) performed prism adaptation during fMRI. Temporal signatures of memory formation were extracted from the behavioural data using a state-space model and regressed against the fMRI data. This revealed that, in both groups, fMRI signal in left sensorimotor cortex correlated with the gradual formation of the prism after-effect during adaptation. This indicates that the sensorimotor cortex may be a useful target for neuromodulation that aims to improve the persistence of therapeutic prism after effects.

Ageing disrupts the finely tuned excitation/inhibition balance (E:I) across cortex, driven by a natural decline in inhibitory tone (γ-amino butyric acid, GABA). This causes functional decrements. However, in young adults, experimentally lowering GABA in sensorimotor cortex enhances adaptation memory. Therefore, using a cross-sectional design, here we tested the hypothesis that as sensorimotor cortical GABA declines naturally with age, adaptation memory would increase, and the former would explain the latter. Results confirmed this prediction. To probe causality, we used brain stimulation to further lower sensorimotor cortical GABA during adaptation. Across individuals, how stimulation changed memory depended on sensorimotor cortical E:I. In those with low E:I, stimulation increased memory; in those with high E:I stimulation reduced memory. Thus, we identify a form of motor memory that improves naturally with age, depends causally on sensorimotor cortex neurochemistry, and may be a potent target for motor skill preservation strategies in healthy ageing and neurore-habilitation.

The temporal lobes are critical for episodic memories and are preferentially affected following a traumatic brain injury (TBI). As such, episodic memory difficulties are common following TBI; however, the underlying neural changes that precipitate or maintain these difficulties in the early phase of recovery remains poorly understood. Here, we use functional magnetic resonance imaging (fMRI) to interrogate the relationship of temporal lobe activation in response to face, scene, and animal stimuli. Twenty-five patients with moderate to severe TBI were recruited an average of 2 months’ post-injury and compared with 21 demographically similar healthy controls. Findings indicate that memory for faces was preferentially impaired, compared to scene and animal stimuli. Decreased activity in temporal lobe structures was present for both face (right transverse temporal gyrus) and scene stimuli (right fusiform gyrus), but not for animals. Greater activation in these structures was associated with better long-term recognition. These findings provide evidence to suggest that TBI: a) preferentially affects memory for complex stimuli such as faces and scenes, and b) causes aberrant neuronal processes despite lack of evidence of significant impairment in behavioural performance. The mechanisms underpinning these findings are discussed in terms of differences in strategy use and reduced neural efficiency.

The global burden of mortality and morbidity caused by traumatic brain injury (TBI) is significant, and the heterogeneity of TBI patients and the relatively small sample sizes of most current neuroimaging studies is a major challenge for scientific advances and clinical translation. The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Adult moderate/severe TBI (AMS-TBI) working group aims to be a driving force for new discoveries in AMS-TBI by providing researchers world-wide with an effective framework and platform for large-scale cross-border collaboration and data sharing. Based on the principles of transparency, rigor, reproducibility and collaboration, we will facilitate the development and dissemination of multiscale and big data analysis pipelines for harmonized analyses in AMS-TBI using structural and functional neuroimaging in combination with non-imaging biomarkers, genetics, as well as clinical and behavioral measures. Ultimately, we will offer investigators an unprecedented opportunity to test important hypotheses about recovery and morbidity in AMS-TBI by taking advantage of our robust methods for large-scale neuroimaging data analysis. In this consensus statement we outline the working group’s short-term, intermediate, and long-term goals. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

OBJECTIVE This study aimed to investigate the association between white matter tracts and multiple aspects of attention and working memory deficits in a relatively acute traumatic brain injury (TBI) sample. METHOD Neuropsychological measures of attention and working memory were administered to 20 participants with complicated mild-to-very severe TBI and 20 control participants. Tract-based spatial statistics was used to assess fractional anisotropy (FA) and mean diffusivity (MD) of white matter tracts for 15 TBI participants and 20 controls. RESULTS When compared to controls, participants with TBI were found to have lower FA (p

To identify predictors of treatment response to cognitive behavior therapy (CBT) for sleep disturbance following acquired brain injury (ABI).Classification and regression tree (CART) analysis was conducted on individual patient data from two pilot randomized controlled trials (RCTs): one in traumatic brain injury (TBI), the other in stroke. The combined sample comprised 32 participants; 15 receiving CBT and 17 allocated to treatment as usual (TAU). The outcome was reliable improvement on the Pittsburgh Sleep Quality Index (PSQI).Study group was a statistically significant predictor of outcome, with CBT participants more likely to achieve reliable improvements than TAU (OR = 4.88, p = 0.042). Study group (CBT vs. TAU) exhibited an area under the ROC curve (AUROC) of 69%. In separate CART analyzes, verbal memory (CVLT-II45.5), age (47.5) and baseline depression (HADS-D 6) predicted positive outcomes in CBT recipients. Each of these variables added a small (∼5%) but not statistically significant amount to AUROC over study group.In this ABI sample, better memory, younger age, and higher baseline depression were associated with positive treatment response to CBT although individually these variables were not better than group alone in predicting outcomes. The present findings generate hypotheses for further investigation in future studies. Implications for rehabilitation Cognitive behavior therapy improves sleep quality over treatment as usual in persons with acquired brain injury. Individuals who are younger in age with better memory and co-morbid symptoms of depression are more likely to respond to the treatment. These findings are based on a small sample and can be considered hypothesis generating for future clinical studies.

Traumatic brain injury (TBI) is associated with an elevated frequency of mood disorders that may, in part, be explained by changes in white-matter microstructure. This study is the first to examine the relationship between mood disorders and white-matter pathology in a sample of patients with mild to severe TBI using a standardized psychiatric interview. This study reports on a sub-sample of 29 individuals recruited from a large prospective study that examined the evolution of psychiatric disorders following complicated, mild to severe TBI. Individuals with TBI were also compared with 23 healthy control participants. Individuals were invited to complete the Structured Clinical Interview for DSM-IV Disorders (SCID) to diagnose psychiatric disorders. Participants who developed a mood disorder within the first 3 years were categorized into a TBI-Mood group. Diffusion tensor tractography assessed white matter microstructure using atlas-based tract-averaged and along-tract approaches. Fractional anisotropy (FA) was used as the measure of white-matter microstructure. TBI participants with and without a mood disorder did not differ in regard to injury severity and other background factors. Nevertheless, TBI participants diagnosed with a mood disorder displayed significantly lower tract-averaged FA values for the right arcuate fasciculus (p = 0.011), right inferior longitudinal fasciculus (p = 0.009), and anterior segments I (p = 0.0004) and II (p = 0.007) of the corpus callosum, as well as the left (p = 0.014) and right (p = 0.015) fronto-occipital longitudinal fasciculi. The pattern of white matter disruption identified in the current study provides further support for a neurobiological basis of post-TBI mood disorders. Greater understanding of individuals' underlying neuropathology may enable better characterization and prediction of mood disorders. Integration of neuropathology may also inform the potential efficacy of pharmacological and psychological interventions.

Objectives:Anecdotal reports suggest that following traumatic brain injury (TBI) retrograde memories are initially impaired and recover in order of remoteness. However, there has been limited empirical research investigating whether a negative gradient in retrograde amnesia—relative preservation of remote over recent memory—exists during post-traumatic amnesia (PTA) compared with the acute phase post-emergence. This study used a repeated-measures design to examine the pattern of personal semantic (PS) memory performance during PTA and within two weeks of emergence to improve understanding of the nature of the memory deficit during PTA and its relationship with recovery.Methods:Twenty patients with moderate-severe TBI and 20 healthy controls (HCs) were administered the Personal Semantic Schedule of the Autobiographical Memory Interview. The TBI group was assessed once during PTA and post-emergence. Analysis of variance was used to compare the gradient across lifetime periods during PTA relative to post-emergence, and between groups.Results:PS memory was significantly lower during PTA than post-emergence from PTA, with no relative preservation of remote memories. The TBI group was still impaired relative to HCs following emergence from PTA. Lower overall PS memory scores during PTA were associated with increased days to emerge from PTA post-interview.Conclusions:These results suggest a global impairment in PS memory across lifetime periods particularly during PTA, but still present within 2 weeks of emergence from PTA. PS memory performance may be sensitive to the diffuse nature of TBI and may, therefore, function as a clinically valuable indicator of the likely time to emerge from PTA. (JINS, 2018,24, 1064–1072)

Prospective monitoring of posttraumatic amnesia (PTA) status is recommended following traumatic brain injury (TBI). Use of patients' subjective reports is, however, still common and necessary in some circumstances. It is therefore important to understand how patients' self-reported first memories relate to prospective measures and how reliable these reports remain over time. In the present study, patients with moderate-severe TBI in PTA were asked about their first and last memories surrounding the injury daily and were administered the Westmead Post-Traumatic Amnesia Scale (WPTAS). Following PTA emergence, a semistructured interview was used to ascertain participants' reports of return of continuous memory after the injury, as well as their last preinjury memory. This interview was repeated six months later, along with the Community Integration Questionnaire to measure functional outcome and the Rey Auditory Verbal Learning Test to measure anterograde memory. The temporal order of recovery of WPTAS variables and subjective reports was determined, and consistency of subjective reports over time was examined using bivariate correlation and intraclass correlation coefficients (ICCs). Findings suggested that patients' reports of return of continuous memory aligned most closely with return of consistent orientation, and occurred significantly earlier than attainment of criterion on the WPTAS. Reported first memories were significantly later at follow-up (i.e., greater days post injury) and the ICC was not suggestive of adequate clinical reliability. Last memory reports were slightly more reliable, with 71% of cases remaining in the same band at follow-up. Demographic and injury-related variables were not significantly associated with the discrepancy between reports. The variability in patients' reports over time highlights the importance and value of prospective PTA monitoring.

OBJECTIVE:: To examine the validity of the Alcohol Use Disorders Identification Test (AUDIT) and the Drug Abuse Screening Test (DAST)-2 widely recommended rating scales-in a traumatic brain injury (TBI) population at 24 months following injury. The Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders was used as the gold standard criterion. SETTING:: TBI rehabilitation program at Epworth Hospital, Victoria, Australia. PARTICIPANTS:: A total of 113 individuals, 87 males and 26 females, with complicated mild to severe TBI. DESIGN:: Prospective study documenting substance use following TBI. MAIN MEASURES:: AUDIT, DAST, and Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders. RESULTS:: In individuals with TBI, a cutoff score of 11 on the AUDIT may be the most appropriate indicator of an alcohol use disorder whereas a cutoff score of 6 on the DAST may be the most appropriate indicator of drug use disorder. Both screening measures demonstrated excellent diagnostic accuracy at 24 months following injury. CONCLUSION:: The optimal cutoff score for the AUDIT may need to be elevated for use following TBI. Nevertheless, both the AUDIT and the DAST are suitable measures for assessing substance use following TBI. Given the importance of uniformity in postinjury assessment, the AUDIT and the DAST may serve as future screening standards in TBI research. Language: en

To examine pre- and post-injury self-reported driver behaviour and safety in individuals with traumatic brain injury (TBI) who returned to driving after occupational therapy driver assessment and on-road rehabilitation.A self-report questionnaire, administered at an average of 4.5 years after completing an on-road driver assessment, documenting pre- and post-injury crash rates, near-crashes, frequency of driving, distances driven, driving conditions avoided and navigation skills, was completed by 106 participants, who had either passed the initial driver assessment (pass group n = 74), or required driver rehabilitation, prior to subsequent assessments (rehabilitation group n = 32).No significant difference was found between pre- and post-injury crash rates. Compared to pre-injury, 36.8% of drivers reported limiting driving time, 40.6% drove more slowly, 41.5% reported greater difficulty with navigating and 20.0% reported more near-crashes. The rehabilitation group (with greater injury severity) was significantly more likely to drive less frequently, shorter distances, avoid: driving with passengers, busy traffic, night and freeway driving than the pass group.Many drivers with moderate/severe TBI who completed a driver assessment and rehabilitation program at least 3 months post-injury, reported modifying their driving behaviour, and did not report more crashes compared to pre-injury. On-road driver training and training in navigation may be important interventions in driver rehabilitation programs.Driver assessment and on-road retraining are important aspects of rehabilitation following traumatic brain injury. Many drivers with moderate/severe TBI, reported modifying their driving behaviour to compensate for ongoing impairment and continued to drive safely in the longer term. Navigational difficulties were commonly experienced following TBI, suggesting that training in navigation may be an important aspect of driver rehabilitation.

The aim of this study was to examine the rate and causes of mortality following mild to severe traumatic brain injury (TBI) rehabilitation and to develop a multivariate prognostic model of mortality. We conducted a cohort study of 3341 individuals with mild to severe TBI followed-up from a post-acute inpatient rehabilitation center. Rate of death and survival between one and 26 years following injury were examined using standardized mortality ratios (SMRs) and prognostic models developed using Cox regression. A mortality rate of 9.3% was observed and an overall SMR of 1.04 (95% confidence interval [CI]=1.04-1.05). A statistically significant elevated SMR of 1.20 (95% CI=1.06-1.37) was observed for males, and both males and females had an elevated risk of death from external causes. Females also were found to have a significantly elevated SMR of 5.02 (95% CI=1.36-12.80) for intentional self-harm. Individuals ages 15-44 had a two-fold increase in mortality, compared with the general population. The multivariate Cox model indicated that increased risk of mortality was associated with older age, being male, being unemployed prior to injury, having a history of stroke, alcohol use, mental health issues, and back injury sustained in the accident. Premorbid lifestyle factors exerted a greater influence on mortality following TBI, compared with injury-related factors. This risk was especially prominent for younger individuals, who died primarily due to external causes. These findings highlight the need for interventions that address premorbid issues, such as substance abuse and mental health issues.

Objective To examine the stability of employment between 1 and 3 years following traumatic brain injury (TBI) and to identify the variables associated with continued employment throughout this time span. Participants This study included 236 individuals with predominantly moderate to very severe TBI, who had received rehabilitation in the context of a no-fault accident compensation system. Participants were eligible for the current study if they were employed before injury and reported their employment status at 1, 2, and 3 years following their injury as part of a longitudinal head injury outcome study. Results Only 44% of participants remained employed at each of the 3 years following TBI. There was also substantial transition into and out of employment across the 3 years. Significantly greater instability in employment was reported by individuals who were machinery operators or laborers before injury, had a longer duration of posttraumatic amnesia, reported more cognitive difficulties, and were less mobile 1 year following their injury. Conclusion A number of important factors determine the likelihood of achieving stability in employment following TBI. Findings from the current study support the continued need to identify ways in which physical as well as cognitive changes contribute to employment following TBI. Further examination is needed to identify possible compensatory strategies or job modifications to maximize the likelihood of job retention.

Objective To examine assessment outcomes and factors associated with passing an occupational therapy (OT) on-road driver assessment after traumatic brain injury (TBI). Design Retrospective analysis of outcomes of on-road driver assessment completed by persons with TBI over an 8-year period. Setting Inpatient and outpatient rehabilitation hospital. Participants A consecutive sample of individuals (N=207) with mild to severe TBI who completed an on-road driver assessment and were assessed at least 3 months postinjury. Intervention Not applicable. Main Outcome Measure Outcome of on-road driver assessment. Results Of the drivers with TBI, 66% (n=137) passed the initial on-road driver assessment (pass group), whereas 34% (n=70) required on-road driver rehabilitation and/or ≥1 on-road assessment (rehabilitation group). After driver rehabilitation, only 3 participants of the group did not resume driving. Participants who were men, had shorter posttraumatic amnesia (PTA) duration, had no physical and/or visual impairment, and had faster reaction times were significantly more likely to be in the pass group. In combination, these variables correctly classified 87.6% of the pass group and 71.2% of the rehabilitation group. Conclusions PTA duration proved to be a better predictor of driver assessment outcome than Glasgow Coma Scale score. In combination with the presence of physical/visual impairment and slowed reaction times, PTA could assist clinicians to determine referral criteria for OT driver assessment. On-road driver rehabilitation followed by on-road reassessment were associated with a high probability of return to driving after TBI.