Service needs and barriers to care five or more years after moderate to severe TBI among Veterans.

PRIMARY OBJECTIVE: The objective of this paper is to identify the most frequent service needs, factors associated with needs, and barriers to care among Veterans and service members five or more years after moderate to severe traumatic brain injury (TBI). RESEARCH DESIGN: Survey administered via telephone 5-16 years after injury (median eight years) and subsequent acute inpatient rehabilitation at a regional Veterans Affairs (VA) medical centre. METHODS AND PROCEDURES: Participants were 119 Veterans and military personnel, aged 23-70 (median 35), 90% male. Demographics, injury characteristics, service needs, whether needs were addressed, barriers to care, health and general functioning were assessed. MAIN OUTCOMES AND RESULTS: The most frequent needs were for help with memory, information about available services and managing stress. Obtaining information about services was the most consistently un-addressed need; managing stress was the most consistently addressed need. Cognitive and psychiatric symptoms and alienation from community were associated with needs going un-addressed. Participants treated after an expansion of TBI services at the study site reported fewer un-addressed needs. Not knowing where to get help was the most common barrier to care. CONCLUSION: Repeated outreach, assessment of needs and education about available services are needed throughout Veterans' lifespan after moderate to severe TBI.

Prospective Tracking and Analysis of Traumatic Brain Injury in Veterans and Military Personnel.

OBJECTIVE: To describe the ongoing Clinical Tracking Form (CTF) study of the Defense and Veterans Brain Injury Center (DVBIC). DESIGN: Prospective longitudinal study. Data at baseline and postinjury are collected on participants through interview and questionnaire, review of medical records, and periodic follow-ups throughout their lifetime. SETTING: A regional DVBIC site located at a Veterans Affairs Medical Center. PARTICIPANTS: Participants (N=211; age range, 18-75y) were enrolled between January 1, 2005, and December 31, 2012, at a regional DVBIC site. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Injury information, functioning, and psychological health. RESULTS: Sixty percent of 211 participants were identified as having severe traumatic brain injuries (TBIs), 14% moderate TBIs, and 26% mild TBIs. Of these 211 participants, 79% sustained closed head injuries, 15% penetrating head injuries, and 6% were not reported. Comparing the severity of TBI in combat versus stateside situations, most of the mild injuries (71%) occurred in combat locations, while most of the severe injuries (62%) occurred in the United States. Among those injured in combat, blast-related TBIs (82%) greatly outnumbered non-blast-related TBIs, regardless of severity. CONCLUSIONS: The CTF study serves as a significant resource of data to understand the effect and outcomes of TBI in the military population. The lifelong experience of military veterans across the full spectrum of TBI and recovery will be recorded through the CTF, and will translate into more informed clinical decisions and educational efforts to guide future research pathways.

Long-term outcomes after moderate-to-severe traumatic brain injury among military veterans: Successes and challenges.

OBJECTIVE: To assess long-term outcomes after traumatic brain injury (TBI) among veterans and service members. SETTING: Regional Veterans Affairs medical centre. PARTICIPANTS: One hundred and eighteen veterans and military personnel, aged 23-70 years (median = 35 years), 90% male, had moderate-to-severe TBI (82% in coma > 1 day, 85% amnesic > 7 days), followed by acute interdisciplinary rehabilitation 5-16 years ago (median = 8 years). DESIGN: Cross-sectional analysis of live interviews conducted via telephone. MAIN MEASURES: TBI follow-up interview (occupational, social, cognitive, neurologic and psychiatric ratings), Community Integration Questionnaire, Disability Rating Scale (four indices of independent function) and Satisfaction with Life Scale. RESULTS: At follow-up, 52% of participants were working or attending school; 34% ended or began marriages after TBI, but the overall proportion married changed little. Finally, 22% were still moderately-to-severely disabled. However, 62% of participants judged themselves to be as satisfied or more satisfied with life than before injury. Injury severity, especially post-traumatic amnesia, was correlated with poorer outcomes in all functional domains. CONCLUSIONS: After moderate-severe TBI, most veterans assume productive roles and are satisfied with life. However, widespread difficulties and functional limitations persist. These findings suggest that veteran and military healthcare systems should continue periodic, comprehensive follow-up evaluations long after moderate-to-severe TBI.

Self-awareness and neurobehavioral outcomes, 5 years or more after moderate to severe brain injury.

OBJECTIVE: To examine self-awareness 5 years or more after traumatic brain injury (TBI) and its relation to outcomes. PARTICIPANTS: Sixty-two adults with moderate to severe TBI and significant other (SO) informants (family or close friend). SETTING: Regional veterans medical center. MAIN MEASURES: TBI Follow-up Interview, Community Integration Questionnaire, Satisfaction with Life Scale, and Caregiver Burden Inventory. DESIGN: Five to 16 years after acute inpatient rehabilitation, separate staff contacted and interviewed subjects and SOs. Subject awareness was defined as inverse subject-SO discrepancy scores. RESULTS: Subjects significantly underreported neurologic symptoms and overreported their work and home functioning; their self-ratings of emotional distress and social functioning did not differ from SO ratings. Employment was associated with greater self-awareness of cognitive deficits, even after controlling for injury severity. Subjects' life-satisfaction was associated with better self-reported neurologic functioning, which frequently did not agree with SO ratings. Caregiver burden was worse as SOs perceived subjects as having worse symptoms and poorer work and social integration. CONCLUSIONS: Impaired self-awareness remains evident more than 5 years after TBI. People with TBI are more likely to gain employment when they are aware of their cognitive deficits and abilities. However, subjective quality of life, for subjects and SOs, was related to their own perception of the TBI outcomes.

Low maternal hemoglobin during pregnancy and diminished neuromotor and neurocognitive performance in offspring with schizophrenia.

OBJECTIVE: Previous research has linked maternal anemia during pregnancy with increased risk for schizophrenia in offspring. However, no study has sought to determine whether this early insult leads to a more severe form of the disorder, characterized by worsened motor and neurocognitive functioning. METHOD: Subjects were 24 cases diagnosed with schizophrenia and 22 controls from the Developmental Insult and Brain Anomaly in Schizophrenia (DIBS) study. Hemoglobin values were measured throughout pregnancy. Among offspring, psychiatric diagnoses were determined through semi-structured interviews and medical records review and comprehensive neurocognitive assessment batteries were conducted in adulthood. RESULTS: Results indicated that among cases decreases in maternal hemoglobin led to significant decreases in scores on the Grooved Pegboard test, the Finger Tapping test and the Wechsler Adult Intelligent Scales (WAIS) information subtest. In contrast, controls only exhibited decreases in performance on the California Verbal Learning Test (CVLT) long-delay recall after fetal exposure to lower hemoglobin. There were also significant interactions between hemoglobin and case status for all of the motor tasks. CONCLUSIONS: These findings support the hypothesis that fetal exposure to decreases in maternal hemoglobin is related to preferentially poorer neuromotor function among cases compared to controls, as well as general intellectual difficulties among cases. Controls were relatively unaffected by decreased maternal hemoglobin, which suggests that liability to schizophrenia renders cases susceptible to the deleterious influences of in utero exposure to decreases in maternal hemoglobin.

Association of maternal genital and reproductive infections with verbal memory and motor deficits in adult schizophrenia.

Maternal exposure to genital and reproductive infections has been associated with schizophrenia in previous studies. Impairments in several neuropsychological functions, including verbal memory, working memory, executive function, and fine-motor coordination occur prominently in patients with schizophrenia. The etiologies of these deficits, however, remain largely unknown. We aimed to assess whether prospectively documented maternal exposure to genital/reproductive (G/R) infections was related to these neuropsychological deficits in offspring with schizophrenia and other schizophrenia spectrum disorders. The cases were derived from a population-based birth cohort; all cohort members belonged to a prepaid health plan. Cases were assessed for verbal memory, working memory, executive function, and fine-motor coordination. Compared to unexposed cases, patients exposed to maternal genital/reproductive infection performed more poorly on verbal memory, fine-motor coordination, and working memory. Stratification by race revealed associations between maternal G/R infection and verbal memory and fine-motor coordination for case offspring of African-American mothers, but not for case offspring of White mothers. Significant infection-by-race interactions were also observed. Although independent replications are warranted, maternal G/R infections were associated with verbal memory and motor function deficits in African-American patients with schizophrenia.

Structural brain alterations in schizophrenia following fetal exposure to the inflammatory cytokine interleukin-8.

BACKGROUND: Maternal infection during pregnancy has been repeatedly associated with increased risk for schizophrenia. Nevertheless, most viruses do not cross the placenta; therefore, the damaging effects to the fetus appear to be related to maternal antiviral responses to infection (e.g. proinflammatory cytokines). Fetal exposure to the proinflammatory cytokine interleukin-8 (IL-8) has been significantly associated with risk of schizophrenia in offspring. This study sought to determine the association between fetal exposure to IL-8 and structural brain changes among schizophrenia cases and controls. METHODS: Subjects were 17 cases diagnosed with schizophrenia from the Developmental Insult and Brain Anomaly in Schizophrenia (DIBS) study. Psychiatric diagnoses were determined among offspring with semi-structured interviews and medical records review. IL-8 was determined from assays in archived prenatal sera and volumetric analyses of neuroanatomical regions were obtained from T1-weighted magnetic resonance imaging in adulthood. Eight controls were included for exploratory purposes. RESULTS: Among cases, fetal exposure to increases in IL-8 was associated with significant increases in ventricular cerebrospinal fluid, significant decreases in left entorhinal cortex volumes and significant decreases in right posterior cingulate volumes. Decreases that approached significance also were found in volumes of the right caudate, the putamen (bilaterally), and the right superior temporal gyrus. No significant associations were observed among controls. CONCLUSION: Fetal exposure to elevations in maternal IL-8 led to structural neuroanatomic alterations among cases in regions of the brain consistently implicated in schizophrenia research. In utero exposure to elevations in IL-8 may partially account for brain disturbances commonly found in schizophrenia.

Cognitive decline in schizophrenia from childhood to midlife: a 33-year longitudinal birth cohort study.

BACKGROUND: We examined cognitive deficits before and after onset of schizophrenia in a longitudinal study that: 1) covers a long time interval; 2) minimizes test unreliability by including the identical measure at both childhood and post-onset cognitive assessments; and 3) minimizes bias by utilizing a population-based sample in which participants were selected neither for signs of illness in childhood nor for being at risk for schizophrenia. METHODS: Participants in the present study, Developmental Insult and Brain Anomaly in Schizophrenia (DIBS), were ascertained from an earlier epidemiologic study conducted in Oakland, CA. The original version of the Peabody Picture Vocabulary Test (PPVT), a test of receptive vocabulary, was administered at age 5 or 9 and repeated as part of the DIBS study at an average age of 40. There were 10 DIBS cases with DSM-IV schizophrenia or schizoaffective disorder and 15 demographically similar DIBS controls with both child and adult PPVT scores. RESULTS: Cases scored significantly lower than controls in childhood (d=0.95) and adulthood (d=1.67). Residualized scores indicating the number of SDs above or below one's predicted adult score revealed a mean case-control difference of -1.51SDs, consistent with significant relative decline over time among the cases (p<0.0013). CONCLUSIONS: In this prospective study, individuals who developed adult schizophrenia manifested impaired receptive vocabulary during childhood and further relative deterioration (or lack of expected improvement) between childhood and midlife. Limitations should also be acknowledged, including the small sample size and the fact that we cannot be certain when the continued deterioration took place.

Prenatal exposure to maternal infection and executive dysfunction in adult schizophrenia.

OBJECTIVE: Executive dysfunction is one of the most prominent and functionally important cognitive deficits in schizophrenia. Although strong associations have been identified between executive impairments and structural and functional prefrontal cortical deficits, the etiological factors that contribute to disruption of this important cognitive domain remain unclear. Increasing evidence suggests that schizophrenia has a neurodevelopmental etiology, and several prenatal infections have been associated with risk of this disorder. The authors examined whether prenatal infection is associated with executive dysfunction in patients with schizophrenia. METHOD: The authors assessed the relationship between serologically documented prenatal exposure to influenza and toxoplasmosis and performance on the Wisconsin Card Sorting Test and the Trail Making Test, part B (Trails B), as well as other measures of executive function, in 26 patients with schizophrenia from a large and well-characterized birth cohort. RESULTS: Patients who were exposed to infection in utero committed significantly more total errors on the Wisconsin Card Sorting Test and took significantly more time to complete the Trails B than unexposed patients. Exposed patients also exhibited deficits on figural fluency, letter-number sequencing, and backward digit span. CONCLUSIONS: Prenatal infections previously associated with schizophrenia are related to impaired performance on the Wisconsin Card Sorting Test and Trails B. The pattern of results suggests that cognitive set-shifting ability may be particularly vulnerable to this gestational exposure. Further work is needed to elucidate the specificity of prenatal infection to these executive function measures and to examine correlates with neuroanatomic and neurophysiologic anomalies.

Prenatal infection and cavum septum pellucidum in adult schizophrenia.

Increased length of the cavum septum pellucidum (CSP) and in utero infection are each associated with increased risk of schizophrenia. Hence, we examined whether prenatal infections are related to CSP length in schizophrenia patients. In a well-characterized birth cohort, in utero infection was assessed using serologic biomarkers or physician diagnoses. Magnetic resonance images were acquired, and CSP length was quantified by a standard protocol. In utero infection was associated with increased CSP length in exposed schizophrenia cases compared to unexposed cases, suggesting that prenatal infection plays a role in a neurodevelopmental morphologic anomaly that has been related previously to schizophrenia.

The potential utility of driving simulators in the cognitive rehabilitation of combat-returnees with traumatic brain injury.

A large number of Operation Enduring Freedom/Operation Iraqi Freedom returnees are seeking DOD and VA rehabilitative care for war-related traumatic brain injury (TBI). This article reviews evidence on the utility of driving simulators as tools for assessment and training in TBI rehabilitation. Traditionally, cognitive rehabilitation has been shown to improve specific cognitive skills. However, there are few studies and only weak evidence to show that these gains transfer to everyday activities. Theoretically, modern driving simulators may be useful in cognitive rehabilitation because they can systematically present realistic and interesting tasks that approximate driving activities, while automatically monitoring performance. The use of simulation technology for patients with TBI provides cognitive stimulation in an ecologically compatible setting, without the risks associated with a corresponding real-world experience. The utility, limitations, and future directions for the use of driving simulator in the rehabilitation of patients with war-related TBI are discussed.

Simultaneous measurement of perceptual and motor cortical potentials: implications for assessing information processing in traumatic brain injury.

OBJECTIVE: Psychomotor slowing is a common manifestation of traumatic brain injury. Previous electrophysiological studies of traumatic brain injury have focused on abnormal attentional and perceptual responses to incoming stimuli. We hypothesize that traumatic brain injury is also associated with abnormal cortical components of motor execution. DESIGN: To test this hypothesis, we analyzed event-related potentials of 22 subjects (11 with a history of severe traumatic brain injury and 11 age-matched healthy subjects) during oddball discrimination tasks. In addition to the usual stimulus-locked averaging of electrophysiological data to reveal cognitive components, such as the P300, we also analyzed subjects' response-locked data to reveal motor potential waveforms. To focus on generalized effects across modality, analyses were performed on composite measures from both auditory and visual event-related potentials. RESULTS: (1) Traumatic brain injury subjects had abnormal P300 responses (with reduced amplitude and prolonged latency) in both sensory modalities. (2) Traumatic brain injury subjects' motor potential waveforms showed significantly reduced amplitude in both sensory modalities. (3) Abnormalities in P300 latency, amplitude, and motor potential amplitude (effect sizes = 1.2-1.5 SD) were greater than behavioral slowing, as measured by reaction times (0.7 SD). (4) P300 latency and motor potential amplitude together accounted for much of the reaction time prolongation (r = 0.73). CONCLUSIONS: This study demonstrates the value of concurrently analyzing stimulus-locked and response-locked event-related potential data to evaluate cortical components of perceptual and motor processing. The present findings indicate that patients with traumatic brain injury have impairments in both the perceptual interpretation of incoming stimuli and the execution of motor responses and that both abnormalities contribute to psychomotor slowing in patients with traumatic brain injury.

Self and other in schizophrenia: a cognitive neuroscience perspective.

OBJECTIVE: Recent basic science data indicate that in healthy individuals, self-referential processing and social cognition rely on common neural substrates. The authors assessed self-referential source memory and social cognition in a large sample of schizophrenia outpatients and healthy comparison subjects in order to compare how these critical processes are associated in the two groups. METHOD: Ninety-one schizophrenia outpatients and 30 healthy comparison subjects were assessed on measures of basic social cognition and source memory for previously learned word items: self-generated, externally presented, and new words. Partial correlations and multiple regression analysis were used to test the association between social cognition measures and source memory performance and the contributions of source memory and general cognitive abilities to a social cognition composite score. RESULTS: Schizophrenia patients demonstrated significantly lower source memory for self-generated items (self-referential source memory) relative to comparison subjects but showed intact external source memory. In both groups, self-referential source memory and social cognition showed strong correlations. When the effects of general cognitive abilities were controlled for, these correlations were attenuated in the schizophrenia patients. Regression analysis revealed discrepancies between groups in the cognitive functions contributing to social cognition performance. CONCLUSIONS: Impaired self-referential source memory represents a unique cognitive deficit in schizophrenia. Moreover, the strong association between self-referential source memory and social cognition seen in healthy subjects is reduced in schizophrenia and is moderated by general cognitive abilities. Impairments in the neurocognitive system that underlies both self-referential and social cognition provide a parsimonious explanation for the disturbances in the sense of self and other that characterize schizophrenia.

A neurocognitive model of borderline personality disorder: effects of childhood sexual abuse and relationship to adult social attachment disturbance.

Borderline personality disorder (BPD) is a paradigmatic disorder of adult attachment, with high rates of antecedent childhood maltreatment. The neurocognitive correlates of both attachment disturbance and maltreatment are both presently unknown in BPD. This study evaluated whether dimensional adult attachment disturbance in BPD is related to specific neurocognitive deficits, and whether childhood maltreatment is related to these dysfunctions. An outpatient BPD group (n=43) performed nearly 1 SD below a control group (n=26) on short-term recall, executive, and intelligence functions. These deficits were not affected by emotionally charged stimuli. In the BPD group, impaired recall was related to attachment-anxiety, whereas executive dysfunction was related to attachment-avoidance. Abuse history was correlated significantly with executive dysfunction and at a trend level with impaired recall. Neurocognitive deficits and abuse history exhibited both independent and interactive effects on adult attachment disturbance. These results suggest that (a) BPD patients' reactivity in attachment relationships is related to temporal-limbic dysfunction, irrespective of the emotional content of stimuli, (b) BPD patients' avoidance within attachment relationships may be a relational strategy to compensate for the emotional consequences of frontal-executive dysregulation, and (c) childhood abuse may contribute to these neurocognitive deficits but may also exert effects on adult attachment disturbance that is both independent and interacting with neurocognitive dysfunction.

Program development and defining characteristics of returning military in a VA Polytrauma Network Site.

The conflicts in Iraq and Afghanistan have resulted in a new generation of combat survivors with complex physical injuries and emotional trauma. This article reports the initial implementation of the Polytrauma Network Site (PNS) clinic, which is a key component of the Department of Veterans Affairs (VA) Polytrauma System of Care and serves military personnel returning from combat. The PNS clinic in Palo Alto, California, is described to demonstrate the VA healthcare system's evolving effort to meet the clinical needs of this population. We summarize the following features of this interdisciplinary program: (1) sequential assessment, from initial traumatic brain injury screening throughout our catchment area to evaluation by the PNS clinic team, and (2) clinical evaluation results for the first 62 clinic patients. In summary, this population shows a high prevalence of postconcussion symptoms, posttraumatic stress, poor cognitive performance, head and back pain, auditory and visual symptoms, and problems with dizziness or balance. An anonymous patient feedback survey, which we used to fine-tune the clinic process, reflected high satisfaction with this new program. We hope that the lessons learned at one site will enhance the identification and treatment of veterans with polytrauma across the country.

Temporal stability of auditory event-related potentials in healthy individuals and patients with traumatic brain injury.

Historically, cognitive event-related potentials (ERPs) have received limited acceptance for clinical use due to lack of evidence for their reliability. However, recent advances in computer technology and artifact rejection methods have greatly enhanced the fidelity of ERP measurements. The present study examined the test-retest reliability of ERP measurement by using current data processing methods. We assessed the temporal stability of the most commonly used ERP paradigm, auditory pure-tone "odd ball" detection, and compared it with other commonly used clinical measures reported in the literature. Auditory ERPs were collected in 19 healthy subjects and 7 patients with traumatic brain injury at two time points, 2 days to 2 months apart. Test-retest reliability was calculated for four ERP components: N1, MMN (mismatch negativity), P3, and N4. In healthy subjects, temporal stabilities of these four commonly studied ERP components' amplitude measurements were moderate to high, with intraclass correlations ranging from 0.6 to 0.8. In contrast, in patients with traumatic brain injury, ERPs were stable only for the N1 component (intraclass correlation = 0.7).

The effects of increasing stimulus complexity in event-related potentials and reaction time testing: clinical applications in evaluating patients with traumatic brain injury.

This study compared the effectiveness of P300 event related potentials (ERPs) and reaction time (RT) in discriminating patients with traumatic brain injury (TBI) from healthy control subjects. In particular, we examined how the use of more complex, ecologically relevant stimuli may affect the clinical utility of these tasks. We also evaluated how length of posttraumatic amnesia (PTA) and loss of consciousness (LOC) related to P300 and RT measures in our patient sample. There were 22 subjects (11 patients with TBI and 11 age-matched healthy control subjects). Four stimulus detection procedures were used: two using simple, conventional stimuli (auditory tone discrimination, AT; visual color discrimination, VC), and two using complex, ecologically relevant stimuli in the auditory and visual modalities (auditory word category discrimination, AWC; visual facial affect discrimination, VFA). Our results showed that RT measures were more effective in identifying TBI patients when complex stimuli were used (AWC and VFA). On the other hand, ERP measures were more effective in identifying TBI patients when simple stimuli were used (AT and VC). We also found a remarkably high correlation between duration of PTA and P300 amplitude.

Social-emotion recognition in borderline personality disorder.

Borderline personality disorder (BPD) is characterized by interpersonal disturbances, but the neurocognitive aspects of these symptoms are poorly understood. We hypothesized that patients with BPD have impaired perception of emotional expressions, which are related to symptoms of interpersonal dysfunction. To control potential confounding factors, this study excluded subjects with comorbid diagnoses known to be associated with impaired affect perception. We tested 43 outpatients with BPD and 26 healthy controls on emotion recognition tasks (facial, prosodic, and integrated facial/prosodic), nonemotional facial feature recognition, and interpersonal antagonism (Buss-Durkee Hostility Index). Patients with BPD showed normal ability to recognize isolated facial or prosodic emotions but had impaired recognition of emotions in integrated facial/prosodic stimuli, as well as impaired discrimination of nonemotional facial features. In patients with BPD, impaired recognition of integrated emotional stimuli was associated with interpersonal antagonism, particularly suspiciousness and assaultiveness. These results suggest that patients with BPD have deficits in higher order integration of social information, which may be related to some of the more serious symptoms of the disorder.

Prognostic value of evoked and event-related potentials in moderate to severe brain injury.

Clinicians are often expected to project patients' clinical outcomes to allow effective planning for future care. This can be a challenge in patients with moderate to severe traumatic brain injury (TBI) who are often unable to participate reliably in clinical evaluations. With recent advances in computer instrumentation and signal processing, evoked potentials and event-related potentials show increasing promise as powerful tools for prognosticating the trajectory of recovery and ultimate outcome from the TBI. Short- and middle-latency evoked potentials can now effectively predict coma outcomes in patients with acute TBI. Long-latency event-related potential components hold promise in predicting recovery of higher order cognitive abilities.