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Traumatic brain injury (TBI) triggers progressive neurodegeneration resulting in brain atrophy that continues months-to-years following injury. However, a comprehensive characterization of the spatial and temporal evolution of TBI-related brain atrophy remains incomplete. Utilizing a sensitive and unbiased morphometry analysis pipeline optimized for detecting longitudinal changes, we analyzed a sample consisting of 37 individuals with moderate-severe TBI who had primarily high-velocity and high-impact injury mechanisms. They were scanned up to three times during the first year after injury (3 months, 6 months, and 12 months post-injury) and compared with 33 demographically matched controls who were scanned once. Individuals with TBI already showed cortical thinning in frontal and temporal regions and reduced volume in the bilateral thalami at 3 months post-injury. Longitudinally, only a subset of cortical regions in the parietal and occipital lobes showed continued atrophy from 3 to 12 months post-injury. Additionally, cortical white matter volume and nearly all deep gray matter structures exhibited progressive atrophy over this period. Finally, we found that disproportionate atrophy of cortex along sulci relative to gyri, an emerging morphometric marker of chronic TBI, was present as early as 3 month post-injury. In parallel, neurocognitive functioning largely recovered during this period despite this pervasive atrophy. Our findings demonstrate msTBI results in characteristic progressive neurodegeneration patterns that are divergent across regions and scale with the severity of injury. Future clinical research using atrophy during the first year of TBI as a biomarker of neurodegeneration should consider the spatiotemporal profile of atrophy described in this study., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

This study aimed to empirically evaluate the hierarchical structure of the Coma Recovery Scale-Revised (CRS-R) rating scale categories and their alignment with the Aspen consensus criteria for determining disorders of consciousness (DoC) following a severe brain injury. CRS-R data from 262 patients with DoC following a severe brain injury were analyzed applying the partial credit Rasch Measurement Model. Rasch Analysis produced logit calibrations for each rating scale category. Twenty-eight of the 29 CRS-R rating scale categories were operationalized to the Aspen consensus criteria. We expected the hierarchical order of the calibrations to reflect Aspen consensus criteria. We also examined the association between the CRS-R Rasch person measures (indicative of performance ability) and states of consciousness as determined by the Aspen consensus criteria. Overall, the order of the 29 rating scale category calibrations reflected current literature regarding the continuum of neurobehavioral function: category 6 "Functional Object Use" of the Motor item was hardest for patients to achieve; category 0 "None" of the Oromotor/Verbal item was easiest to achieve. Of the 29 rating scale categories, six were not ordered as expected. Four rating scale categories reflecting the Vegetative State (VS)/Unresponsive Wakefulness Syndrome (UWS) had higher calibrations (reflecting greater neurobehavioral function) than the easiest Minimally Conscious State (MCS) item (category 2 "Fixation" of the Visual item). Two rating scale categories, one reflecting MCS and one not operationalized to the Aspen consensus criteria, had higher calibrations than the easiest eMCS item (category 2 "Functional: Accurate" of the Communication item). CRS-R person measures (indicating amount of neurobehavioral function) and states of consciousness, based on Aspen consensus criteria, showed a strong correlation (r s  = 0.86; p  < 0.01). Our study provides empirical evidence for revising the diagnostic criteria for MCS to also include category 2 "Localization to Sound" of the Auditory item and for Emerged from Minimally Conscious State (eMCS) to include category 4 "Consistent Movement to Command" of the Auditory item.

Summary: Brain injury resulting in coma may evolve into a prolonged disorder of consciousness, including the vegetative and minimally conscious states. Early detection of emerging consciousness has positive prognostic significance, and improvement in consciousness at any point may indicate the potential for meaningful communication and environmental control. Despite the importance of accurate assessment of consciousness, research indicates that as many as 40% of patients with a disorder of consciousness may be assessed incorrectly. Assessment of consciousness is challenging for many reasons, including the fact that consciousness cannot be measured directly but must be inferred from patterns of behavioral activity, that many patients have confounding deficits and treatments that may mask consciousness, and that patient performance may be highly variable over time. In this manuscript, we discuss strategies for optimizing patient status during assessment and review a number of structured assessment approaches that can be used. The available assessment techniques vary in their length and cost, and the expertise required to use them. Which of these approaches is most applicable to a given acute or subacute setting will vary with the volume of patients with a disorder of consciousness and the available resources. Importantly, lack of consciousness in the acute setting should not be used to justify the withdrawal of care or denial of rehabilitation services., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 by the American Clinical Neurophysiology Society.)

Importance: Traumatic brain injury (TBI) leads to 2.9 million visits to US emergency departments annually and frequently involves a disorder of consciousness (DOC). Early treatment, including withdrawal of life-sustaining therapies and rehabilitation, is often predicated on the assumed worse outcome of disrupted consciousness., Objective: To quantify the loss of consciousness, factors associated with recovery, and return to functional independence in a 31-year sample of patients with moderate or severe brain trauma., Design, Setting, and Participants: This cohort study analyzed patients with TBI who were enrolled in the Traumatic Brain Injury Model Systems National Database, a prospective, multiyear, longitudinal database. Patients were survivors of moderate or severe TBI who were discharged from acute hospitalization and admitted to inpatient rehabilitation from January 4, 1989, to June 19, 2019, at 1 of 23 inpatient rehabilitation centers that participated in the Traumatic Brain Injury Model Systems program. Follow-up for the study was through completion of inpatient rehabilitation., Exposures: Traumatic brain injury., Main Outcomes and Measures: Outcome measures were Glasgow Coma Scale in the emergency department, Disability Rating Scale, posttraumatic amnesia, and Functional Independence Measure. Patient-related data included demographic characteristics, injury cause, and brain computed tomography findings., Results: The 17 470 patients with TBI analyzed in this study had a median (interquartile range [IQR]) age at injury of 39 (25-56) years and included 12 854 male individuals (74%). Of these patients, 7547 (57%) experienced initial loss of consciousness, which persisted to rehabilitation in 2058 patients (12%). Those with persisting DOC were younger; had more high-velocity injuries; had intracranial mass effect, intraventricular hemorrhage, and subcortical contusion; and had longer acute care than patients without DOC. Eighty-two percent (n = 1674) of comatose patients recovered consciousness during inpatient rehabilitation. In a multivariable analysis, the factors associated with consciousness recovery were absence of intraventricular hemorrhage (adjusted odds ratio [OR], 0.678; 95% CI, 0.532-0.863; P = .002) and intracranial mass effect (adjusted OR, 0.759; 95% CI, 0.595-0.968; P = .03). Functional improvement (change in total functional independence score from admission to discharge) was +43 for patients with DOC and +37 for those without DOC (P = .002), and 803 of 2013 patients with DOC (40%) became partially or fully independent. Younger age, male sex, and absence of intraventricular hemorrhage, intracranial mass effect, and subcortical contusion were associated with better functional outcome. Findings were consistent across the 3 decades of the database., Conclusions and Relevance: This study found that DOC occurred initially in most patients with TBI and persisted in some patients after rehabilitation, but most patients with persisting DOC recovered consciousness during rehabilitation. This recovery trajectory may inform acute and rehabilitation treatment decisions and suggests caution is warranted in consideration of withdrawing or withholding care in patients with TBI and DOC.

Objectives: Severe brain injury is often accompanied by painful comorbidities and by concurrent limitations in the ability to report pain. Assessment of nociception aids diagnosis and helps balance reduction in suffering with avoidance of sedating medications. Existing assessment methods confound patients' level of consciousness with the intensity of nociception, complicating pain assessment as consciousness evolves. We sought to develop a measure of nociception that is independent of the level of consciousness., Materials and Methods: We identified 15 behavioral and physiological items likely to be sensitive to nociception. We rated noncommunicative patients with traumatic brain injury in 4 different activities predicted to modulate nociception, on each of 2 days, one randomly chosen for acetaminophen administration. The level of consciousness and level of agitation were also measured., Rasch Analysis: Rasch analysis was used to assess item fit to an underlying dimension of nociception., Results: Five items that demonstrated poor fit to the dimension were removed. The 10 remaining items demonstrated acceptable fit. Scores were significantly influenced by activity and analgesic treatment and were largely independent of measures of consciousness and agitation. Accurate scores could be obtained in about 10 minutes and were robust to missing data., Discussion: The results provide evidence that the Brain Injury Nociception Assessment Measure (BINAM) is reliable and feasible to administer. It can assess the intensity of nociception largely independent of the level of consciousness. Further research is warranted on the impact of BINAM use on the care of patients with severe traumatic brain injury.

Rehabilitation is a key service component in the context of significant brain injury, yet many of the treatments and services employed in rehabilitation are not based on rigorous evidence. Treatment research in rehabilitation, like in other fields of healthcare, relies on a developmental sequence of studies that address different questions, including safety, proof of principle, definitive efficacy, and real-world effectiveness. Each of these steps faces challenges specific to the rehabilitation domain, where many treatments are nonpharmacologic, and outcomes of interest are highly varied and complex. This chapter frames the research questions addressed by different phases of treatment research, identifies some of the particular challenges in answering these questions, and takes a hypothetical treatment through the sequence to illustrate the process., (© 2015 Elsevier B.V. All rights reserved.)

Objective: To examine person, injury, and treatment characteristics associated with recovery trajectories of people with severe traumatic brain injury (TBI) during inpatient rehabilitation., Design: Observational prospective longitudinal study., Setting: TBI rehabilitation units., Participants: Adults (N=206) with severe nonpenetrating TBI admitted directly to inpatient rehabilitation from acute care. Participants were excluded for prior disability and intentional etiology of injury., Interventions: Naturally occurring treatments delivered within comprehensive multidisciplinary teams were recorded daily in 15-minute units provided to patients and family members, separately., Main Outcome Measures: Motor and cognitive FIM were measured on admission, discharge, and every 2 weeks in between and were analyzed with individual growth curve methodology., Results: Inpatient recovery was best modeled with linear, cubic, and quadratic components: relatively steep recovery was followed by deceleration of improvement, which attenuated prior to discharge. Slower recovery was associated with older age, longer coma, and interruptions to rehabilitation. Patients admitted at lower functional levels received more treatment, and more treatment was associated with slower recovery, presumably because treatment was allocated according to need. Therefore, effects of treatment on outcome could not be disentangled from effects of case mix factors., Conclusions: FIM gain during inpatient recovery from severe TBI is not a linear process. In observational studies, the specific effects of treatment on rehabilitation outcomes are difficult to separate from case mix factors that are associated with both outcome and allocation of treatment., (Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Traumatic brain injury (TBI) is likely to disrupt structural network properties due to diffuse white matter pathology. The present study aimed to detect alterations in structural network topology in TBI and relate them to cognitive and real-world behavioral impairment. Twenty-two people with moderate to severe TBI with mostly diffuse pathology and 18 demographically matched healthy controls were included in the final analysis. Graph theoretical network analysis was applied to diffusion tensor imaging (DTI) data to characterize structural connectivity in both groups. Neuropsychological functions were assessed by a battery of psychometric tests and the Frontal Systems Behavior Scale (FrSBe). Local connection-wise analysis demonstrated reduced structural connectivity in TBI arising from subcortical areas including thalamus, caudate, and hippocampus. Global network metrics revealed that shortest path length in participants with TBI was longer compared to controls, and that this reduced network efficiency was associated with worse performance in executive function and verbal learning. The shortest path length measure was also correlated with family-reported FrSBe scores. These findings support the notion that the diffuse form of neuropathology caused by TBI results in alterations in structural connectivity that contribute to cognitive and real-world behavioral impairment.

Objective: To examine possible changes in Glasgow Coma Scale (GCS) scores related to changes in emergency management, such as intubation and chemical paralysis, and the potential impact on outcome prediction., Participants: 10 228 patients from the Traumatic Brain Injury Model Systems national database., Design: Retrospective study examining 5-year epochs from 1987 to 2012., Main Measures: GCS score assessed in the Emergency Department (GCS scores for intubated, but not paralyzed, patients were estimated with a formula using 2 of the 3 GCS components), Outcome: Functional Independence Measure (FIM) assessed at rehabilitation admission., Results: The rate of intubation prior to GCS scoring averaged 43% and did not increase across time. However, a clear increase over time was observed in the use of paralytics or heavy sedatives, with 27% of patients receiving this intervention in the most recent epoch. Estimated GCS scores classified 69% of intubated patients as severely brain injured and 8% as mildly injured. The GCS accounted for a modest, yet consistent, amount of variability (approximately 5%-7%) in FIM scores during most epochs., Conclusions: Given the frequency of intubation and/or paralysis following brain injury in this sample, estimating GCS or exploring other means to gauge injury severity is beneficial, particularly because a portion likely did not sustain severe brain injury. There is no evidence for declining predictive utility of the GCS over time.

The purpose of this study was to determine whether there are underlying dimensions common among traditional traumatic brain injury (TBI) severity indices and, if so, the extent to which they are interchangeable when predicting short-term outcomes. This study had an observational design, and took place in United States trauma centers reporting to the National Trauma Data Bank (NTDB). The sample consisted of 77,470 unweighted adult cases reported to the NTDB from 2007 to 2010, with International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) TBI codes. There were no interventions. Severity indices used were the Emergency Department Glasgow Coma Scale (GCS) Total score and each of the subscales for eye opening (four levels), verbal response (five levels), and motor response (six levels); the worst Abbreviated Injury Scale (AIS) severity score for the head (six levels); and the worst Barell index type (three categories). Prediction models were computed for acute care length of stay (days), intensive care unit length of stay (days), hospital discharge status (alive or dead), and, if alive, discharge disposition (home versus institutional). Multiple correspondence analysis (MCA) indicated a two dimensional relationship among items of severity indexes. The primary dimension reflected overall injury severity. The second dimension seemed to capture volitional behavior without the capability for cogent responding. Together, they defined two vectors around which most of the items clustered. A scale that took advantage of the order of items along these vectors proved to be the most consistent index for predicting short-term health outcomes. MCA provided useful insight into the relationships among components of traditional TBI severity indices. The two vector pattern may reflect the impact of injury on different cortical and subcortical networks. Results are discussed in terms of score substitution and the ability to impute missing values.

Individuals 65 years of age and over have the highest rates of traumatic brain injury (TBI)-related hospitalizations and deaths, and older adults (defined variably across studies) have particularly poor outcomes after TBI. The factors predicting these outcomes remain poorly understood, and age-specific care guidelines for TBI do not exist. This study provides an overview of TBI in older adults using data from the National Trauma Data Bank (NTDB) gathered between 2007 and 2010, evaluates age group-specific trends in rates of TBI over time using U.S. Census data, and examines whether routinely collected information is able to predict hospital discharge status among older adults with TBI in the NTDB. Results showed a 20-25% increase in trauma center admissions for TBI among the oldest age groups (those >=75 years), relative to the general population, between 2007 and 2010. Older adults (>=65 years) with TBI tended to be white females who have incurred an injury from a fall resulting in a "severe" Abbreviated Injury Scale (AIS) score of the head. Older adults had more in-hospital procedures, such as neuroimaging and neurosurgery, tended to experience longer hospital stays, and were more likely to require continued medical care than younger adults. Older age, injury severity, and hypotension increased the odds of in-hospital death. The public health burden of TBI among older adults will likely increase as the Baby Boom generation ages. Improved primary and secondary prevention of TBI in this cohort is needed.

Objective: To compare the rate and nature of rehospitalization in a cohort of patients enrolled in the National Institute on Disability and Rehabilitation Research Traumatic Brain Injury Model Systems (TBIMS) who have disorders of consciousness (DOC) at the time of rehabilitation admission with those in persons with moderate or severe traumatic brain injury (TBI) but without DOC at rehabilitation admission., Design: Prospective observational study., Setting: Inpatient rehabilitation within TBIMS with annual follow-up., Participants: Of 9028 persons enrolled from 1988 to 2009 (N=9028), 366 from 20 centers met criteria for DOC at rehabilitation admission and follow-up data, and another 5132 individuals met criteria for moderate (n=769) or severe TBI (n=4363)., Interventions: Not applicable., Main Outcome Measures: Participants and/or their family members completed follow-up data collection including questions about frequency and nature of rehospitalizations at 1 year postinjury. For the subset of participants with DOC, additional follow-up was conducted at 2 and 5 years postinjury., Results: The DOC group demonstrated an overall 2-fold increase in rehospitalization in the first year postinjury relative to those with moderate or severe TBI without DOC. Persons with DOC at rehabilitation admission have a higher rate of rehospitalization across several categories than persons with moderate or severe TBI., Conclusions: Although the specific details of rehospitalization are unknown, greater injury severity resulting in DOC status on rehabilitation admission has long-term implications. Data highlight the need for a longitudinal approach to patient management., (Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the incidence of medical complications in patients with recent traumatic disorders of consciousness (DOCs)., Design: Data on adverse events in a placebo controlled trial of amantadine hydrochloride revealed no group difference, which allowed these events to be reanalyzed descriptively as medical complications experienced by the 2 groups collectively., Setting: Eleven clinical facilities in the United States, Denmark, and Germany with specialty rehabilitation programs for patients with DOCs., Participants: Patients (N=184) with nonpenetrating traumatic brain injury enrolled from acute inpatient rehabilitation programs between 4 and 16 weeks postinjury., Interventions: Participants were randomized to receive 200 to 400mg of amantadine hydrochloride or placebo daily for 4 weeks, and followed for an additional 2 weeks. Adverse events were recorded and categorized with respect to their nature, timing, and severity., Main Outcome Measure: Number, type, and severity of medical complications occurring during the 6-week study interval., Results: A total of 468 medical complications were documented among the patients (.40 events per week per patient). More than 80% of patients experienced at least 1 medical complication, and 41 of these were defined as serious adverse events. New medical complications declined over time in rehabilitation and were not dependent on time since injury. Hypertonia, agitation/aggression, urinary tract infection, and sleep disturbance were the most commonly reported problems. Hydrocephalus, pneumonia, gastrointestinal problems, and paroxysmal sympathetic hyperactivity were the most likely to be severe., Conclusions: Patients with DOCs have a high rate of medical complications early after injury. Many of these complications require brain injury expertise for optimal management. Active medical management appears to contribute to the reduction in new complications. An optimal system of care for DOC patients must provide expert medical management in the early weeks after injury., (Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To characterize the 5-year outcomes of patients with traumatic brain injury (TBI) not following commands when admitted to acute inpatient rehabilitation., Design: Secondary analysis of prospectively collected data from the National Institute on Disability and Rehabilitation Research-funded Traumatic Brain Injury Model Systems (TBIMS)., Setting: Inpatient rehabilitation hospitals participating in the TBIMS program., Participants: Patients (N=108) with TBI not following commands at admission to acute inpatient rehabilitation were divided into 2 groups (early recovery: followed commands before discharge [n=72]; late recovery: did not follow commands before discharge [n=36])., Interventions: Not applicable., Main Outcome Measures: FIM items., Results: For the early recovery group, depending on the FIM item, 8% to 21% of patients were functioning independently at discharge, increasing to 56% to 85% by 5 years postinjury. The proportion functioning independently increased from discharge to 1 year, 1 to 2 years, and 2 to 5 years. In the late recovery group, depending on the FIM item, 19% to 36% of patients were functioning independently by 5 years postinjury. The proportion of independent patients increased significantly from discharge to 1 year and from 1 to 2 years, but not from 2 to 5 years., Conclusions: Substantial proportions of patients admitted to acute inpatient rehabilitation before following commands recover independent functioning over as long as 5 years, particularly if they begin to follow commands before hospital discharge., (Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Over the last decade, research on patients with disorders of consciousness (DOC) has suggested that their prognosis for functional recovery early after injury is surprisingly positive, particularly for those with traumatic etiologies; that meaningful recovery proceeds for longer intervals than previously appreciated; and that such individuals are often medically complex and challenging to manage. However, access to intensive specialty rehabilitation is limited for most individuals with DOC in the United States. The evolving understanding of DOC calls for a reconsideration of appropriate models of care. This collection of articles provides insight into the functional recovery of individuals with DOC, new tools for assessing prognosis, and the patterns of comorbidity that complicate the recovery process. In addition, models of care from the United States and Europe that attempt to address the needs of patients as well as their caregivers are presented., (Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: To develop reliable coding for five treatment ingredients hypothesized to be "active" in a scheduled telephone intervention (STI) for traumatic brain injury (TBI); to examine factors associated with delivery of ingredients over the first year post-injury., Method: Operational definitions of directive and non-directive action planning; TBI education; reinforcement; and reframing, were refined until kappa >0.80 across multiple coders. Codes were assigned for presence/absence of ingredients in 253 recorded calls delivered to 49 participants in a randomized controlled trial on effects of STI versus usual care. Using multivariate analyses, we tested hypotheses about effects of TBI severity, time and other factors on delivery of ingredients., Results: Longitudinal analyses revealed that TBI education decreased over time, as expected. Non-directive action planning increased over time, according to hypotheses; unexpectedly, directive action planning did not concurrently decline. Reinforcement and reframing both increased over time, with reframing also increasing with TBI severity. Therapist differences were pronounced, despite extensive supervision designed to promote uniform treatment delivery., Conclusions: Reliable operational definitions of therapist behavior for each ingredient were achieved, but at the sacrifice of sensitivity in the coding scheme. Behavioral operational definitions of ingredients may be useful for treatment specification, for therapist training and supervision, and for testing hypotheses about the strength of specific components within the "black box" of rehabilitation., Implications for Rehabilitation: Operationally defining active ingredients of rehabilitation can allow measurement of adherence to specified treatment protocols, and can facilitate the study of the relationship between delivery of specific ingredients and resulting outcomes. In this study, there were strong differences in delivery of ingredients by different clinicians despite frequent joint supervision and a shared treatment philosophy. Defining active ingredients in advance may help focus training and supervision on specific clinician behaviors that convey key ingredients of treatment. Complex treatments such as counseling, where the therapist's behavior is partly determined by the client's behavior and vice versa, are particularly challenging to define operationally since the opportunity to deliver certain ingredients varies with the problems the client presents and the way they are presented.

Objectives: To (1) develop a standardized interview for telephone administration, (2) assess the psychometric properties of this interview format (Disability Rating Scale-Postacute Interview [DRS-PI]), and (3) identify additional items to reduce skew., Design: Prospective cohort assessment study., Setting: Not applicable., Participants: Participants (N=406; 287 individuals with traumatic brain injury [TBI], 119 caregivers) in the U.S. TBI Model Systems national database during 1- to 20-year telephone follow-up., Interventions: Not applicable., Main Outcome Measures: Original Disability Rating Scale (DRS) and DRS-PI variations. DRS-PI questions were developed by consensus of the study investigators; item scores were derived from responses to questions by algorithm. Unnecessary questions were pruned., Results: The DRS-PI correlated highly with the original DRS (intraclass correlation, .91) and demonstrated satisfactory construct validity and internal consistency (person separation/reliability, 2.51/.86; item separation/reliability, 16.72/1.00; Cronbach α=.83). Both versions showed substantial skew. For the original DRS, 42% of scores were 0 or 1; for DRS-PI, 44%. Adding several items to the DRS-PI including actual employment status further improved its psychometric properties (person separation/reliability, 3.10/.91; item separation/reliability, 21.42/1.00; Cronbach α=.92) and reduced skew. For the Expanded DRS-PI, 18% of scores were 0 or 1., Conclusions: The DRS-PI provides an efficient method to ensure standardized administration of, and correlates highly with, the original DRS. The addition of several new items including actual employment status mitigates skew in postacute samples., (Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Given that traumatic brain injury (TBI) results in chronic alteration of baseline cerebral perfusion, a perfusion functional MRI (fMRI) method that dissociates resting- and task-related cerebral blood flow (CBF) changes can be useful in noninvasively investigating the neural correlates of cognitive dysfunction and recovery in TBI., Objective: The authors used continuous arterial spin-labeled (ASL) perfusion fMRI to characterize CBF at rest and during sustained-attention and working-memory tasks., Methods: A total of 18 to 21 individuals with moderate to severe TBI and 14 to 18 demographically matched healthy controls completed 3 continuous 6-minute perfusion fMRI scans (resting, visual sustained attention, and 2-back working memory)., Results: For both tasks, TBI participants showed worse behavioral performance than controls. Voxelwise neuroimaging analysis of the 2-back task found that group differences in task-induced CBF changes were localized to bilateral superior occipital cortices and the left superior temporal cortex. Whereas controls deactivated these areas during task performance, TBI participants tended to activate these same areas. These regions were among those found to be disproportionately hypoperfused at rest after TBI. For both tasks, the control and TBI groups showed different patterns of correlation between performance and task-related CBF changes., Conclusions: ASL perfusion fMRI demonstrated differences between individuals with TBI and healthy controls in resting perfusion and in task-evoked CBF changes as well as different patterns of performance-activation correlation. These results are consistent with the notion that sensory/attentional modulation deficits contribute to higher cognitive dysfunction in TBI.

Rationale: Methylphenidate (MPH), the most widely prescribed psychostimulant to treat many neuropsychiatric conditions, is reported to improve attention and speed of processing in survivors of traumatic brain injury (TBI). The neural correlate of this efficacy, however, remains unclear., Objective: Using perfusion functional magnetic resonance imaging (fMRI) as a biomarker of regional neural activity, the current study aimed to examine the neural correlates of single-dose (0.3 mg/kg) MPH administration in a randomized double-blind placebo-controlled crossover study design., Methods: Twenty-three individuals with moderate to severe TBI were tested on two occasions approximately 1 week apart. Perfusion fMRI scanning was carried out at rest and while participants performed cognitive tasks requiring sustained attention and working memory., Results: Behaviorally, MPH significantly improved both accuracy and reaction time (RT) in the sustained attention task but only RT in the working memory task. A trend of global reduction of cerebral blood flow by MPH was observed in all task conditions including resting. Voxel-wise whole-brain analysis revealed an interaction effect of drug by condition (MPH-placebo X task-rest) for the sustained attention task in the left posterior superior parietal cortex and parieto-occipital junction (BA 7/19). The magnitude of drug-related deactivation of this area during task performance was correlated with improvement in RT., Conclusion: Suppression of activity in this area during task performance may reflect a compensatory mechanism by which MPH ameliorates attention impairments in TBI.

Measures of structure and process in health care have been shown to be associated with care outcomes in prior research. Two articles in this issue propose measures of structure and process that may be relevant to pediatric traumatic brain injury rehabilitation. This commentary considers how these potential measures may be related to the actual treatments and services that ultimately affect patient outcomes., (Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Amantadine hydrochloride is one of the most commonly prescribed medications for patients with prolonged disorders of consciousness after traumatic brain injury. Preliminary studies have suggested that amantadine may promote functional recovery., Methods: We enrolled 184 patients who were in a vegetative or minimally conscious state 4 to 16 weeks after traumatic brain injury and who were receiving inpatient rehabilitation. Patients were randomly assigned to receive amantadine or placebo for 4 weeks and were followed for 2 weeks after the treatment was discontinued. The rate of functional recovery on the Disability Rating Scale (DRS; range, 0 to 29, with higher scores indicating greater disability) was compared over the 4 weeks of treatment (primary outcome) and during the 2-week washout period with the use of mixed-effects regression models., Results: During the 4-week treatment period, recovery was significantly faster in the amantadine group than in the placebo group, as measured by the DRS score (difference in slope, 0.24 points per week; P=0.007), indicating a benefit with respect to the primary outcome measure. In a prespecified subgroup analysis, the treatment effect was similar for patients in a vegetative state and those in a minimally conscious state. The rate of improvement in the amantadine group slowed during the 2 weeks after treatment (weeks 5 and 6) and was significantly slower than the rate in the placebo group (difference in slope, 0.30 points per week; P=0.02). The overall improvement in DRS scores between baseline and week 6 (2 weeks after treatment was discontinued) was similar in the two groups. There were no significant differences in the incidence of serious adverse events., Conclusions: Amantadine accelerated the pace of functional recovery during active treatment in patients with post-traumatic disorders of consciousness. (Funded by the National Institute on Disability and Rehabilitation Research; ClinicalTrials.gov number, NCT00970944.).

Few studies address the course of recovery from prolonged disorders of consciousness (DOC) after severe traumatic brain injury (TBI). This study examined acute and long-term outcomes of persons with DOC admitted to acute inpatient rehabilitation within the National Institute on Disability and Rehabilitation Research (NIDRR) TBI Model Systems Programs (TBIMS). Of 9028 persons enrolled from 1988 to 2009, 396 from 20 centers met study criteria. Participants were primarily male (73%), Caucasian (67%), injured in motor vehicle collision (66%), with a median age of 28, and emergency department Glasgow Coma Scale (GCS) score of 3. Participant status was evaluated at acute rehabilitation admission and discharge and at 1, 2, and 5 years post-injury. During inpatient rehabilitation, 268 of 396 (68%) regained consciousness and 91 (23%) emerged from post-traumatic amnesia (PTA). Participants demonstrated significant improvements on GCS (z=16.135, p≤0.001) and Functional Independence Measure (FIM) (z=15.584, p≤0.001) from rehabilitation admission (median GCS=9; FIM=18) to discharge (median GCS=14; FIM=43). Of 337 with at least one follow-up visit, 28 (8%) had died by 2.1 years (mean) after discharge. Among survivors, 66 (21%) improved to become capable of living without in-house supervision, and 63 demonstrated employment potential using the Disability Rating Scale (DRS). Participants with follow-up data at 1, 2, and 5 years post-injury (n=108) demonstrated significant improvement across all follow-up evaluations on the FIM Cognitive and Supervision Rating Scale (p<0.01). Significant improvements were observed on the DRS and FIM Motor at 1 and 2 years post-injury (p<0.01). Persons with DOC at the time of admission to inpatient rehabilitation showed functional improvement throughout early recovery and in years post-injury.

Objective: To evaluate the effect of a Scheduled Telephone Intervention (STI) compared with usual care (UC) on function, health/emotional status, community/work activities, and well-being at 1 and 2 years after traumatic brain injury (TBI)., Design: Two group, randomized controlled trial., Setting: Telephone contacts with subjects recruited in inpatient rehabilitation., Participants: Eligible subjects (N=433) with TBI (age>16y) were randomly assigned to STI plus UC (n=210) or UC (n=223) at discharge. STI subjects (n=169) completed the outcome at year 1 (118 at year 2) and 174 UC subjects at year 1 (123 at year 2)., Interventions: STI subjects received calls at 2 and 4 weeks and 2, 3, 5, 7, 9, 12, 15, 18, and 21 months consisting of brief training in problem solving, education, or referral., Main Outcome Measures: A composite outcome at 1 year was the primary endpoint. Analysis on intent-to-treat basis used linear regression adjusted for site, Glasgow Coma Scale, race/ethnicity, age, FIM, sex, and Disability Rating Scale (DRS). Secondary analyses were conducted on individual and composite measures (FIM, DRS, community participation indicators, Glasgow Outcome Scale [Extended], Short Form-12 Health Survey, Brief Symptom Inventory-18, EuroQOL, and modified Perceived Quality of Life)., Results: No significant differences were noted between the groups at years 1 or 2 for primary (P=.987 regression for year 1, P=.983 for year 2) or secondary analyses., Conclusions: This study failed to replicate the findings of a previous single center study of telephone-based counseling. While telephone mediated treatment has shown promise in other studies, this model of flexible counseling in problem solving and education for varied problems was not effective over and above usual care., (Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Cognitive and behavioral sequelae of traumatic brain injury (TBI) interfere with the rehabilitation process and are among the most important sources of long-term disability. Many psychoactive drugs that have been studied in other patient populations are widely used to treat these deficits, but rigorous evidence of their efficacy in TBI is lacking. Use of psychoactive medications in the early post-injury period may appear to be clinically effective, because of the confounding effects of natural recovery. Even single subject assessment methods have limited ability to disentangle drug effects from natural recovery in this period because of the rapid pace and variability of recovery, requiring the application of more traditional parallel group controlled designs. However, the prevalent use of unproven psychoactive drugs in clinical practice can promote a culture of intervention that makes enrollment in controlled studies more challenging. For these reasons, we argue that the early use of unproven psychoactive medications after TBI should be limited, that placebo controlled group studies should be encouraged, and that single subject methods can be most productively used in later periods when natural recovery has slowed.

The National Institute of Neurologic Disorders and Stroke, Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury, National Institute on Disability and Rehabilitation Research, and Defense and Veterans Brain Injury Center jointly supported an effort to develop common data elements (CDEs, ie, consensus-based content domains of importance and recommended ways to measure them) for research on traumatic brain injury and psychological health. The authors served as participants in this effort as well as editors of the resulting articles. This article describes the current status of this multiagency endeavor, the obstacles encountered, and possible directions for future development. Challenges that occurred within the working groups that developed the CDE recommendations and similarities and differences among the articles that describe those recommendations were reviewed. Across all of the working groups, there were challenges in striking a balance between specificity in recommendations to researchers and the need to tailor the selection of variables to specific study aims. The domains addressed by the different working groups varied in the research available to guide the selection of important content areas to be measured and the specific tools for measuring them. The working groups also addressed this challenge in somewhat different ways. The CDE effort must enhance consensus among researchers with similar interests while not stifling innovation and scientific rigor. This will require regular updating of the recommendations and may benefit from more standardized criteria for the selection of important content areas and measurement tools across domains., (Copyright © 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To examine congruence between participant (P) and significant other (SO) reports on societal participation in 3 objective domains (economic, community, and social activities) and subjective satisfaction with participation at 1 year after traumatic brain injury (TBI)., Participants: Ninety-seven persons with moderate to severe TBI and their SOs (27 spouses/partners, 47 parents, 23 other relatives/friends)., Main Outcome Measure: Community Participation Indicators questionnaire, divided into Objective (Economic, Community, Social) and Subjective (Satisfaction) subscales., Design: Prospective correlational study., Results: P-SO congruence differed by domain of participation, with Economic and Community indicators showing higher agreement than Social and Satisfaction items. Congruence was not affected by P-SO relationship or whether the pair lived together. However, pairs who spent at least daily time together had significantly higher agreement on Satisfaction items than pairs who were together less often. Congruence was not predicted by SOs' self-reported degree of awareness of Ps' concerns. Severity of TBI, within the range represented in this sample, had no effect on P-SO congruence in any domain., Conclusion: In research on participation after TBI, proxy report may be an acceptable substitute for missing participant report on productivity and community activity outcomes. However, proxy responses should be used with caution for questions about social activities and degree of satisfaction with participation.

Non-invasive measurement of resting state cerebral blood flow (CBF) may reflect alterations of brain structure and function after traumatic brain injury (TBI). However, previous imaging studies of resting state brain in chronic TBI have been limited by several factors, including measurement in relative rather than absolute units, use of crude spatial registration methods, exclusion of subjects with substantial focal lesions, and exposure to ionizing radiation, which limits repeated assessments. This study aimed to overcome those obstacles by measuring absolute CBF with an arterial spin labeling perfusion fMRI technique, and using an image preprocessing protocol that is optimized for brains with mixed diffuse and focal injuries characteristic of moderate and severe TBI. Resting state CBF was quantified in 27 individuals with moderate to severe TBI in the chronic stage, and 22 demographically matched healthy controls. In addition to global CBF reductions in the TBI subjects, more prominent regional hypoperfusion was found in the posterior cingulate cortices, the thalami, and multiple locations in the frontal cortices. Diffuse injury, as assessed by tensor-based morphometry, was mainly associated with reduced CBF in the posterior cingulate cortices and the thalami, where the greatest volume losses were detected. Hypoperfusion in superior and middle frontal cortices, in contrast, was associated with focal lesions. These results suggest that structural lesions, both focal and diffuse, are the main contributors to the absolute CBF alterations seen in chronic TBI, and that CBF may serve as a tool to assess functioning neuronal volume. We also speculate that resting reductions in posterior cingulate perfusion may reflect alterations in the default-mode network, and may contribute to the attentional deficits common in TBI.

Development of rehabilitation treatments and services that are effective and supported by rigorous evidence is a long and multi-step process. Although there are similarities between this process and that used in pharmaceutical development, the sequence involved in developing this evidence in rehabilitation is more complex and less linear. The specific steps involved depend on a variety of factors including the location of the target of treatment within the International Classification of Functioning, Disability, and Health (ICF; World Health Organisation, 2006), the degree to which the treatment is guided by an underlying theory, the availability of animal models, and the plausibility of safety concerns. Similarly, the research designs chosen and the setting of the research vary both by treatment target and by maturity of the programme of evidence development. A full picture of the appropriate role and anticipated impact of specific rehabilitation treatments can benefit from a marriage between rehabilitation research (which seeks to understand how to change specific aspects of function), and enablement/disablement research (which seeks to understand how changes in one part of the ICF framework affect functioning elsewhere). Although the specific steps involved in a programmatic approach to rehabilitation treatment research vary, development of evidence about all treatments can benefit from a systematic programmatic approach in which each step seeks to answer specific questions and set the stage for subsequent investigation.

Attention deficits are nearly ubiquitous after traumatic brain injury (TBI). In the subacute phase of moderate to severe TBI, these deficits may be difficult to measure with the precision needed to predict outcomes, assess degree of recovery, and monitor treatment response. This article reports the findings of four studies, three observational and one a randomized, controlled treatment trial of methylphenidate (MP), designed to provide construct validation of the Moss Attention Rating Scale (MARS), an observational measure of attention dysfunction following TBI. One hundred seven participants with moderate to severe TBI were enrolled during treatment on an inpatient rehabilitation unit. MARS scores were provided independently by four rehabilitation disciplines (Physical, Occupational and Speech Therapies and Nursing). Results indicated that the MARS: (1) is more strongly related to concurrent measures of cognitive versus physical disability, supporting its validity as a measure of cognition, (2) is more strongly related to concurrent psychometric measures of attention versus measures thought to rely less on attention, supporting its validity as a measure of attention; and (3) predicts 1-year outcomes of TBI better than psychometric measures of attention. However, the MARS (4) was not differentially affected by MP versus placebo treatment. Results support the construct validity and utility of the MARS, with further research needed to clarify its role in treatment outcome assessment.

The authors outline the process for developing the International Classification of Functioning, Disability, and Health (ICF) Core Sets for traumatic brain injury (TBI). ICF Core Sets are selections of categories of the ICF that identify relevant categories of patients affected by specific diseases. Comprehensive and brief ICF Core Sets for TBI should become useful for clinical practice and for research. The final definition of the ICF Core Sets for TBI will be determined at an ICF Core Sets Consensus Conference, which will integrate evidence from preliminary studies. The development of ICF Core Sets is an inclusive and open process and rehabilitation professionals are invited to participate.

Objectives: The common hypnotic, zolpidem, has been reported to temporarily restore consciousness to individuals in the chronic vegetative state. In drug responders, repeated dosing appears to maintain consciousness. The frequency of such responses, however, is unknown and is important both to guide clinical use and to plan further research on the mechanisms underlying drug response. The objectives of this study were to obtain an estimate of the frequency of clinically significant responses among individuals with disorders of consciousness, to determine whether less obvious drug responses are present among "nonresponders," and to identify clinical features characteristic of zolpidem responders., Design: Participants were individuals in the vegetative or minimally conscious state at least 1 month after brain injury. Each participant was studied individually in a double-blind, placebo-controlled, crossover design, once on zolpidem (10 mg per feeding tube) and once on placebo. Each assessment involved baseline administration of the Coma Recovery Scale-Revised, followed immediately by administration of the study drug, followed by 5 hourly readministrations of the Coma Recovery Scale-Revised. A replication pair of assessments was available for drug responders., Results: : One of 15 participants (6.7%) demonstrated a clinically significant response, which altered his assessment from the vegetative state to the minimally conscious state, and this result was repeated in the replication assessment. The remaining 14 participants showed no evidence of a subclinical response to the drug., Conclusion: These results confirm that clinically significant responses to zolpidem among individuals with disorders of consciousness do occur in a minority of patients and can be replicated. Failure to find a trend toward improved performance on zolpidem among nonresponders suggests a bimodal rather than a graded response to the drug. The fact that only one drug responder was identified in this small study prevents assessment of features characteristic of drug responders.

Objectives: To investigate predictors of recovery from the vegetative state (VS) and minimally conscious state (MCS) after brain injury as measured by the widely used Disability Rating Scale (DRS) and to explore differences in rate of recovery and predictors of recovery during inpatient rehabilitation in patients with non-traumatic (NTBI) and traumatic brain injury (TBI)., Design: Longitudinal observational cohort design and retrospective comparison study, in which an initial DRS score was collected at the time of study enrollment. Weekly DRS scores were recorded until discharge from the rehabilitation center for both NTBI and TBI patients., Setting: Seven acute inpatient rehabilitation facilities in the United States and Europe with specialized programs for VS and MCS patients (the Consciousness Consortium)., Participants: One hundred sixty-nine patients with a non-traumatic (N=50) and a traumatic (N=119) brain injury who were in the VS or MCS states., Interventions: Not applicable., Main Outcome Measures: DRS score at 13 weeks after injury; change in DRS score over 6 weeks post-admission; and time until commands were first followed (for patients who did not show command-following at or within 2 weeks of admission)., Results: Both time between injury and enrollment and DRS score at enrollment were significant predictors of DRS score at week 13 post-injury but the main effect of etiology only approached significance. Etiology was however a significant predictor of the amount of recovery observed over the 6 weeks following enrollment. Time between injury and enrollment was also a good predictor of this outcome, but not DRS score at enrollment. For the time until commands were first followed, patients with better DRS scores at enrollment, and those with faster early rates of change recovered command following sooner than those with worse DRS scores or slower initial rates of change. The etiology was not a significant predictor for this last outcome. None of these predictive models explained sufficient variance to allow their use in individual clinical decision making., Conclusions: Time post-injury and DRS score at enrollment are predictors of early recovery among patients with disorders of consciousness, depending on the outcome measure chosen. Etiology was also a significant predictor in some analyses, with traumatically injured patients recovering more than those with non-traumatic injuries. However, the hypothesized interaction between etiology and time post-injury did not reach significance in any of the analyses suggesting that, within the time frame studied, the decline in prognosis with the passage of time was similar in the two groups.

Rationale and Objectives: Diffusion tensor (DT) and T1 structural magnetic resonance images provide unique and complementary tools for quantifying the living brain. We leverage both modalities in a diffeomorphic normalization method that unifies analysis of clinical datasets in a consistent and inherently multivariate (MV) statistical framework. We use this technique to study MV effects of traumatic brain injury (TBI)., Materials and Methods: We contrast T1 and DT image-based measurements in the thalamus and hippocampus of 12 TBI survivors and nine matched controls normalized to a combined DT and T1 template space. The normalization method uses maps that are topology-preserving and unbiased. Normalization is based on the full tensor of information at each voxel and, simultaneously, the similarity between high-resolution features derived from T1 data. The technique is termed symmetric normalization for MV neuroanatomy (SyNMN). Voxel-wise MV statistics on the local volume and mean diffusion are assessed with Hotelling's T(2) test with correction for multiple comparisons., Results: TBI significantly (false discovery rate P < .05) reduces volume and increases mean diffusion at coincident locations in the mediodorsal thalamus and anterior hippocampus., Conclusions: SyNMN reveals evidence that TBI compromises the limbic system. This TBI morphometry study and an additional performance evaluation contrasting SyNMN with other methods suggest that the DT component may aid normalization quality.

Objective: To determine whether older persons are at increased risk for progressive functional decline after traumatic brain injury (TBI)., Design: Longitudinal cohort study., Setting: Traumatic Brain Injury Model Systems (TBIMS) rehabilitation centers., Participants: Subjects enrolled in the TBIMS national dataset., Interventions: Not applicable., Main Outcome Measures: Disability Rating Scale (DRS), FIM instrument cognitive items, and the Glasgow Outcome Scale-Extended., Results: Participants were separated into 3 age tertiles: youngest (16-26y), intermediate (27-39y), and oldest (> or =40y). DRS scores were comparable across age groups at admission to a rehabilitation center. The oldest group was slightly more disabled at discharge from rehabilitation despite having less severe acute injury severity than the younger groups. Although DRS scores for the 2 younger groups improved significantly from year 1 to year 5, the greatest magnitude of improvement in disability was seen among the youngest group. In addition, after dividing patients into groups according to whether their DRS scores improved (13%), declined (10%), or remained stable (77%) over time, the likelihood of decline was found to be greater for the 2 older groups than for the youngest group. A multiple regression model showed that age has a significant negative influence on DRS score 5 years post-TBI after accounting for the effects of covariates., Conclusions: This study supported our primary hypothesis that older patients show greater decline over the first 5 years after TBI than younger patients. In addition, the greatest amount of improvement in disability was observed among the youngest group of survivors. These results suggest that TBI survivors, especially older patients, may be candidates for neuroprotective therapies after TBI.

Objective: To examine the interrater agreement and responsiveness to change of the Moss Attention Rating Scale (MARS), 22-item version, during acute inpatient rehabilitation after traumatic brain injury (TBI)., Design: Observational study of clinician ratings (physical therapy [PT], occupational therapy [OT], speech-language pathology [SLP], nursing) of each patient's attentional function at 2 points in time, near the time of admission and near the time of discharge from inpatient rehabilitation., Setting: Dedicated acute inpatient brain injury rehabilitation program., Participants: Inpatients (N=149) with moderate to severe TBI (58% enrolled in the National Institute on Disability Rehabilitation Research-funded Traumatic Brain Injury Model System); age 16 years or older; receiving OT, PT, SLP, and nursing care on the inpatient TBI rehabilitation unit; and having Rancho Los Amigos Levels of Cognitive Functioning Scale scores of IV (confused/agitated) or higher at enrollment. Patients were excluded if they had premorbid history of attention-deficit hyperactivity disorder, major psychiatric disorder (eg, bipolar), or neurologic impairment (eg, stroke)., Interventions: Not applicable., Main Outcome Measure: Scores on the MARS (22-item version) and its 3 factor scores., Results: Intraclass correlations among ratings from PT, OT, and SLP ranged from .69 to .78 at the initial assessment and .67 to .72 at the follow-up assessment. Agreement between nursing and the other disciplines was somewhat lower (at initial assessment, .59-.68; at follow-up, .48-.59), although still substantial. Agreement for 2 of the factor scores (restlessness and/or distractibility, initiation) was similar but agreement for the third factor (consistent and/or sustained attention) was lower (.25-.27). The total MARS scores were highly significantly improved (P<.001) at follow-up compared with initial assessment (mean, 27.6d between ratings; median, 21d; range, 4-125d) for each of the rating disciplines, with change scores ranging from 7.8 points (OT) to 13.1 points (nursing). Factor scores also improved significantly during the same interval. When different occupational therapists provided the initial and follow-up OT ratings, these follow-up ratings were significantly lower, but this pattern was not seen among other rating disciplines., Conclusions: The 22-item MARS showed good interrater agreement among PT, OT, and SLP and lower but still acceptable agreement between nursing and the other disciplines. Two of the 3 factor scores also showed good agreement. The 22-item total score and all 3 factor scores were highly sensitive to change occurring during inpatient rehabilitation. These results show that the 22-item MARS is a reliable instrument for the observational rating of attentiveness in an acute TBI rehabilitation sample. Lower agreement between nursing and the other disciplines suggests that the less structured environment of the nursing unit compared with therapy sessions reduces interrater agreement. The utility of the factor scores, particularly the least reliable sustained and/or consistent attention factor, requires additional investigation. Further research on construct validity and impact of the use of the MARS on clinical practice are warranted.

Traumatic brain injury (TBI) is one of the most common causes of long-term disability. Despite the importance of identifying neuropathology in individuals with chronic TBI, methodological challenges posed at the stage of inter-subject image registration have hampered previous voxel-based MRI studies from providing a clear pattern of structural atrophy after TBI. We used a novel symmetric diffeomorphic image normalization method to conduct a tensor-based morphometry (TBM) study of TBI. The key advantage of this method is that it simultaneously estimates an optimal template brain and topology preserving deformations between this template and individual subject brains. Detailed patterns of atrophies are then revealed by statistically contrasting control and subject deformations to the template space. Participants were 29 survivors of TBI and 20 control subjects who were matched in terms of age, gender, education, and ethnicity. Localized volume losses were found most prominently in white matter regions and the subcortical nuclei including the thalamus, the midbrain, the corpus callosum, the mid- and posterior cingulate cortices, and the caudate. Significant voxel-wise volume loss clusters were also detected in the cerebellum and the frontal/temporal neocortices. Volume enlargements were identified largely in ventricular regions. A similar pattern of results was observed in a subgroup analysis where we restricted our analysis to the 17 TBI participants who had no macroscopic focal lesions (total lesion volume >1.5 cm(3)). The current study confirms, extends, and partly challenges previous structural MRI studies in chronic TBI. By demonstrating that a large deformation image registration technique can be successfully combined with TBM to identify TBI-induced diffuse structural changes with greater precision, our approach is expected to increase the sensitivity of future studies examining brain-behavior relationships in the TBI population.

Objective: To evaluate the effects of bromocriptine on a variety of aspects of attention, ranging from laboratory-based impairment measures to caregiver ratings and work productivity, in individuals after traumatic brain injury., Design: Twelve adults with moderate to severe traumatic brain injury and attention complaints in the postacute phase of recovery were enrolled in a 6-wk double-blind, placebo-controlled, crossover study of bromocriptine, titrated to a dose of 5 mg twice a day. A wide range of attentional measures was administered weekly, including computerized and paper-and-pencil tests of attention, videotaped records of individual work in a distracting environment, real-time observational scoring of attentiveness in a classroom environment, and caregiver and clinician ratings of attentiveness. Data from these 12 participants were used to identify attentional dimensions suggestive of a treatment effect for independent replication., Results: The effects of bromocriptine on 13 previously identified attentional factors and 13 individual performance scores were assessed via the Wilcoxon signed ranks test, using a relaxed probability cutoff of 0.20 to select those to be studied in a larger replication sample. Only two factor scores and one individual score met the cutoff, and all of these showed trends toward worse performance on bromocriptine than on placebo. A more detailed investigation of bromocriptine's effect on divided attention was also conducted, but the previously reported finding of a beneficial effect on this domain was not replicated. Blood pressure was marginally lower on bromocriptine than on placebo. In view of the lack of cognitive benefit and the fact that several participants experienced possible or probable drug side effects, we did not pursue a larger replication at this drug dose., Conclusions: Bromocriptine in a dose of 5 mg, given twice a day to individuals with attentional complaints after TBI, does not seem to enhance attentional skills, and it may be associated with an excess of adverse events. It is not clear whether intermittent dosing or lower doses might confer benefit.

Objective: To examine the relationship between gender and cognitive recovery 1 year following traumatic brain injury (TBI)., Methods: Patients with blunt TBI were identified from the TBI Model Systems of Care National Database, multi-centre cohort study. The included patients (n = 325) were 16-45 years at injury, admitted to an acute care facility within 24 hours, received inpatient rehabilitation, had documented admission Glasgow Coma Scale (GCS) scores, completed neuropsychological follow-up 1 year post-injury and did not report pre-morbid learning problems. Multivariate analyses of variance examined the unadjusted association between gender and six cognitive domains examining attention/working memory, verbal memory, language, visual analytic skills, problem-solving and motor functioning. Analyses of covariance models were constructed to determine if confounding factors biased the observed associations., Results: Females performed significantly better than males on tests of attention/working memory and language. Males outperformed females in visual analytic skills. Gender remained significantly associated with performance in these areas when controlling for confounding variables., Conclusions: These results suggest a better cognitive recovery of females than males following TBI. However, future studies need to include non-TBI patients to control for possible pre-injury gender-related differences, as well as to conduct extended follow-ups to determine the stability of the observed differences.

Objective: To determine the effects of methylphenidate (MPH) on command following and yes/no communication in brain injured patients with severe disorders of consciousness (DOC)., Design: A meta-analysis of a series of single-subject repeated crossover trials, using doses ranging from 7.5 to 25 mg (median dose: 10 mg), generally given twice a day. A Wilcoxon signed ranks test was performed, comparing mean responsiveness and accuracy by drug condition. Drug effect sizes were calculated for the full group and for participant subgroups of interest., Results: No significant effect of MPH was seen on either responsiveness or on accuracy in the whole group. None of the patient subgroups examined showed a substantial drug effect size., Conclusions: This study did not identify a clinically meaningful effect of MPH in the doses used on responsiveness or accuracy in standardized command-following protocols in the overall study group of patients with severe DOC, or in any subgroup that was assessed. Because MPH has been shown to have some positive effects in higher-level patients with TBI, more research is needed to define the types of individuals with TBI who do and do not benefit from this drug, and/or the dose that provides optimal benefit.

Purpose: To examine experiences among individuals in the USA with traumatic brain injury (TBI) regarding their access to and use of the Internet, problems encountered, and desire for improved Internet access and skills., Method: An in-depth survey was administered as a semi-structured interview to 80 individuals at least 3 months post moderate to severe TBI., Results: Two-thirds of respondents reported having a computer at home, but only half had access to the Internet. Fewer than half were Internet users, as compared to 60% users in the USA population at the time of the survey. However, Internet activities engaged in by users in this sample were comparable to those of the overall population. There was a strong interest in using the Internet among non-users. Most respondents expressed a strong desire for coaching or other training to enhance or develop Internet skills. Reported reasons for Internet non-use in this sample were lack of access and knowledge, versus lack of interest as in the general population., Conclusions: The high interest in using and learning more about the Internet supports the development of interventions to mprove Internet skills for people with TBI.

Randomized double-blind placebo-controlled trials have been argued to provide the strongest test of efficacy and, as such, are important tools for advancing the evidence base supporting rehabilitation treatment. However, such trials present difficult ethical issues, because one group, by definition, receives no treatment for the condition being studied. In the case of an experimental treatment that is available only within a research protocol, a 50% chance of receiving the desired treatment may be sufficient to motivate enrollment. However, many rehabilitation treatments that need further study are available outside of research protocols and are perceived as low risk, making the advantages of research participation less clear and the task of weighing the pros and cons of research participation more difficult. In this article, we discuss a placebo-controlled trial currently underway in which this issue is combined with a number of other complicating factors, such as the inability of study participants to provide their own informed consent, and the catastrophic nature of the disability under study. We examine whether other research designs could successfully answer efficacy questions in this area, and we discuss the ethical and psychosocial issues involved in planning the trial and seeking enrollment.

Objective: To examine characteristics and diversity among vocational treatment services in model programs for traumatic brain injury (TBI) rehabilitation., Setting: Vocational or postacute treatment components of 16 TBI Model System (TBIMS) centers., Participants: Vocational director/coordinator from each TBIMS surveyed in semistructured phone interview., Measure: Survey of vocational services for people with TBI, with about 100 closed and open-ended questions on vocational assessments; pre- and postjob placement treatments; program philosophies; funding; and integration of cognitive, behavioral, family, and medical rehabilitation interventions., Results: Great diversity was found among the vocational services of the 16 TBIMS. Programs fell into 3 clusters emphasizing medical rehabilitation services, supported employment, or a combination of these with an emphasis on case management. Job coaching was identified as a key intervention, but there was great variability in intensity, availability, and funding of coaching services., Conclusion: Diversity in vocational services appears related to funding differences and "parallel evolution" rather than strong treatment philosophy or scientific evidence base. Multicenter research on effectiveness or establishment of best practices in vocational rehabilitation after TBI must deal with substantial existing variability in treatment models and specific interventions, and must examine the relationship of treatment variations to case-mix factors.

There is currently a lack of evidence-based guidelines to guide the pharmacological treatment of neurobehavioral problems that commonly occur after traumatic brain injury (TBI). It was our objective to review the current literature on the pharmacological treatment of neurobehavioral problems after traumatic brain injury in three key areas: aggression, cognitive disorders, and affective disorders/anxiety/ psychosis. Three panels of leading researchers in the field of brain injury were formed to review the current literature on pharmacological treatment for TBI sequelae in the topic areas of affective/anxiety/ psychotic disorders, cognitive disorders, and aggression. A comprehensive Medline literature search was performed by each group to establish the groups of pertinent articles. Additional articles were obtained from bibliography searches of the primary articles. Group members then independently reviewed the articles and established a consensus rating. Despite reviewing a significant number of studies on drug treatment of neurobehavioral sequelae after TBI, the quality of evidence did not support any treatment standards and few guidelines due to a number of recurrent methodological problems. Guidelines were established for the use of methylphenidate in the treatment of deficits in attention and speed of information processing, as well as for the use of beta-blockers for the treatment of aggression following TBI. Options were recommended in the treatment of depression, bipolar disorder/mania, psychosis, aggression, general cognitive functions, and deficits in attention, speed of processing, and memory after TBI. The evidence-based guidelines and options established by this working group may help to guide the pharmacological treatment of the person experiencing neurobehavioral sequelae following TBI. There is a clear need for well-designed randomized controlled trials in the treatment of these common problems after TBI in order to establish definitive treatment standards for this patient population.

Executive function mediated by prefrontally driven distributed networks is frequently impaired by traumatic brain injury (TBI) as a result of diffuse axonal injury and focal lesions. In addition to executive cognitive functions such as planning and working memory, the effects of TBI impact social cognition and motivation processes. To encourage application of cognitive neuroscience methods to studying recovery from TBI, associated reorganization of function, and development of interventions, this article reviews the pathophysiology of TBI, critiques currently employed methods of assessing executive function, and evaluates promising interventions that reflect advances in cognitive neuroscience. Brain imaging to identify neural mechanisms mediating executive dysfunction and response to interventions following TBI is also discussed.

Objective: This study compared the accuracy of artificial neural networks to multiple regression and classification and regression trees in predicting outcomes of 1,644 patients in the Traumatic Brain Injury Model Systems database 1 year after injury., Methods: Data from rehabilitation admission were used to predict discharge scores on the Functional Independence Measure, the Disability Rating Scale, and the Community Integration Questionnaire., Results: Artificial neural networks did not demonstrate greater accuracy in predicting outcomes than did the more widely used method of multiple regression. Both of these methods outperformed classification and regression trees., Conclusion: Because of the sophisticated form of multiple regression with splines that was used, firm conclusions are limited about the relative accuracy of artificial neural networks compared to more widely used forms of multiple regression.

Objectives: To investigate the factor structure of disordered attention in moderate to severe, acute traumatic brain injury (TBI) and to use factor analysis and item response theory to further validate and refine an observational rating scale of attention for clinical and research purposes., Design: Multicenter inception cohort., Setting: Inpatient rehabilitation units., Participants: Patients with TBI (N=372) consecutively admitted to 8 Traumatic Brain Injury Model System centers within 2 weeks prior to observation, who consistently followed commands and who were on stable doses of all psychotropic medications for a 3-day rating period., Interventions: Not applicable., Main Outcome Measure: Participants were rated independently by treating occupational and physical therapists at an average of 1 month postinjury on the Moss Attention Rating Scale (MARS), a 45-item, Likert-type scale of attention-related behavior., Results: Exploratory and confirmatory factor analyses revealed 3 correlated factors of disordered attention, interpreted as restlessness/distractibility, initiation, and sustained/consistent attention. Item response (Rasch) analysis was used to eliminate redundant items and to fill gaps in item difficulty. The resulting MARS consists of 22 items that can produce 3 factor scores and a total score that covers the broad construct of disordered attention., Conclusions: The factor-scored MARS has potential utility as a quantitative observational method with which to assess and study different dimensions of disordered attention in acute TBI, and to monitor change over time and treatment response within these dimensions.

Objective: To describe evidence grading methods employed in the systematic reviews in this special series of articles. To provide an overview of results of these reviews to critique the quality of rehabilitation research. To identify issues in the application of evidence grading methods to rehabilitation., Design: Conceptual review of evidence-based practice and evidence grading methods. English-language research studies on rehabilitation of persons with spinal cord injury, traumatic brain injury, and burn for the 5-yr period of 1999-2004 were reviewed using methods of the American Academy of Neurology supplemented by Cochrane criteria and summarized., Results: Rehabilitation has a shortage of high-level studies. The number of level 1 treatment studies was quite limited (five in spinal cord injury, 15 in traumatic brain injury, 12 in burn rehabilitation), as was the number of level 2 studies (26, 4, and 2, respectively). Despite the large number of correlational studies published, the number of high-level (1 or 2) diagnostic and prognostic studies was surprisingly limited (34, 11, and 5, respectively). The rate of production of high-level studies is rapidly increasing. Problems were encountered in applying standard evidence criteria to complex issues encountered in some studies, suggesting limitations and issues in evidence grading methodology., Conclusions: Rehabilitation needs more high-level studies. Some improvements in research methodology are relatively affordable (e.g., improved blinding), whereas others are expensive (e.g., large randomized controlled trials). Lower-level investigations reporting promising results need to be followed by more definitive, higher-level trials.