Psychological consequences of brain injury

Interpersonal functioning deficits: temporary or stable characteristics of depressed individuals?

To assess selected cognitive functions of persons with traumatic brain injury using a computer-simulated virtual reality environment. A computer-simulated virtual kitchen was used to assess the ability of 30 patients with brain injury and 30 volunteers without brain injury to process and sequence information. The overall assessment score was based on the number of correct responses and the time needed to complete daily living tasks. Identical daily living tasks were tested and scored in participants with and without brain injury. Each subject was evaluated twice within 7 to 10 days. A total of 30 tasks were categorized as follows: information processing, problem solving, logical sequencing, and speed of responding. Persons with brain injuries consistently demonstrated a significant decrease in the ability to process information (P = 0.04-0.01), identify logical sequencing (P = 0.04-0.01), and complete the overall assessment (P < 0.01), compared with volunteers without brain injury. The time needed to process tasks, representing speed of cognitive responding, was also significantly different between the two groups (P < 0.01). A computer-generated virtual reality environment represents a reproducible tool to assess selected cognitive functions and can be used as a supplement to traditional rehabilitation assessment in persons with acquired brain injury.

Background: Interpersonal skills deficits and dysfunctional metacognitive beliefs have been implicated in the etiology and maintenance of depression. This study aimed to investigate the association between changes in these skills deficits and change in depressive symptoms over the course of treatment with Cognitive Behavioral Analysis System of Psychotherapy (CBASP) and Metacognitive Therapy (MCT).Methods: In this prospective, parallel group observational study, data was collected at baseline and after 8 weeks of an intensive day clinic psychotherapy program. Based on a shared decision between patients and clinicians, patients received either CBASP or MCT. Ninety patients were included in the analyses (CBASP: age M = 38.7, 40.5% female, MCT: age M = 44.7, 43.3% female). Interpersonal deficits were assessed with the short-form of the Luebeck Questionnaire for Recording Preoperational Thinking (LQPT-SF) and the Impact Message Inventory (IMI-R). Metacognitive beliefs were assessed with the Metacognition Questionnaire-30 (MCQ-30). The Quick Inventory of Depressive Symptomatology (QIDS-SR16) was utilized to assess depressive symptoms. A regression analysis was conducted to assess variables associated with outcome. ANCOVAs were utilized to investigate whether improvement in skills deficits is dependent on type of treatment received.Results: Improvements in preoperational thinking and increases in friendly-dominant behavior were associated with change in depressive symptoms. There was no association between reductions in dysfunctional metacognitive beliefs and a decrease in depressive symptoms. While both treatment groups showed significant improvements in interpersonal and metacognitive skills, there was no significant between-group difference in the change scores for either of these skills.Conclusion: Our findings suggest that changes in interpersonal skills seem to be of particular relevance in the treatment of depression. These results have to be replicated in a randomized-controlled design before firm conclusions can be drawn.

The human entorhinal-hippocampal circuitry is characterized by an information-specific functional organization where two routes, that are preferentially connected to the parahippocampal cortex or the perirhinal and retrosplenial cortices, divide the entorhinal cortex as well as hippocampal subiculum and CA1 subregions.

The guest editors of this journal are pleased to introduce this special issue on the mechanisms of perinatal brain injury. The purpose of this issue is to highlight recent developments toward our understanding of both grey and white matter injury in the perinatal brain. Over the last decade, there has been significant advancement in our understanding of the mechanisms underlying this injury. The progression of the field stems from many factors including: (1) the development and refinement of experimental models; (2) advances in modern imaging technologies, such as magnetic resonance imaging and diffusion tensor imaging; (3) detailed characterization of the injury, both in human and animals, on the anatomical, cellular, and subcellular levels and (4) identification of the developmental factors that underlie the vulnerability of the perinatal brain to such injury. Here we present nine review and two research articles that together highlight these advancements, as summarized below. It has been our honor to work with each of the contributing scientists, and we thank them for their commitment to this Special Issue. The review by C. Thornton et al. summarizes our current understanding of the “Molecular mechanisms of perinatal brain injury,” with a focus on mitochondrial functional impairment and apoptotic events during the secondary injury phase. The authors also present the most up-to-date intervention strategies targeting the different stages of brain injury. V. Ten and A. Starkov further explore the role of mitochondria in hypoxic-ischemic (H-I) injury and provide evidence for the mitochondrial production of reactive oxygen species as a pathogenic mechanism underlying this injury. The authors summarize experimental data delineating mitochondrial sources of reactive oxygen species and their specific targets in neonatal animals. Necrotic cell death is well documented in H-I brain injury and is traditionally thought uncontrollable. In another review, R. Chavez-Valdez et al. introduce the recently identified RIP1/3 kinase dependent programmed necrosis pathway to the field of neonatal brain injury and propose an apoptosis-necrosis cell death “continuum” for cellular degeneration. The authors highlight experimental evidence supporting a prominent role of programmed necrosis in neonatal H-I brain injury. Another paper by C. Hill and R. Fitch explores the underlying basis of the increased vulnerability of male infants to H-I injury and their increased incidence of cognitive deficits associated with that injury. The authors discuss hormonal factors underlying these differences as well as sex-specific differences in H-I-induced cell death pathways. In the review by K. Buller et al., the effects of perinatal H-I injury on the serotonergic system are summarized. The potential use of anti-inflammatory interventions to alleviate this injury is also discussed. Disruption of this neurotransmitter system may underlie the cardiorespiratory, cognitive, and attention deficits observed in survivors of prematurity. Changing the focus from H-I injury to inflammation and infection, C. Mallard and X. Wang summarize clinical and experimental evidence for neonatal sepsis and increased vulnerability of the immature brain and discuss the involvement of Toll-like receptors (TLRs) in perinatal brain injury. Continuing in the area of inflammation and infection, R. McAdams and S. Juul address the initiation and activation of cytokines and inflammatory cells in the perinatal brain and their detrimental short and long-term consequences. They highlight the importance of understanding the dynamic structure of the blood brain barrier, as well as the relatively unknown mechanisms that impair its integrity allowing immune cells direct access to the brain. In the first of two research articles, D. Selip et al. characterize, in a rodent model of H-I, the spectrum of grey matter damage in association with the white matter damage once thought to be dominant in H-I injury. The authors characterize the regional susceptibility to H-I injury in terms of the inflammatory response, white matter injury and myelin loss, neuronal degeneration, and axonal injury. Our second research article by K. Shrivastava et al. provides an extensive characterization of the glia/inflammatory response following H-I using a common model of injury thought to spare the contralateral hemisphere. This study extends our knowledge of this model by characterizing a subtle inflammatory response in the contralateral brain, and provides important information regarding the timing of the insult in relationship to the initiation of inflammatory signaling cascades. The paper by V. Biran et al. highlights a novel area of the brain—the cerebellum—that has emerged as an important attribute of perinatal brain injury through imaging studies. This review provides an extensive detailed analysis of cerebellar development, and the implications of disrupting its normal maturation as a consequence of perinatal brain injury. Finally H. Kinney and J. Volpe stress the importance of developing and using animal models with a careful consideration of human perinatal brain development and injury. This paper emphasizes the need to model perinatal brain injury as an encephalopathy of prematurity characterized by a combination of both grey and white matter lesions.

Being highly self-efficacious is a key factor in successful chronic disease self-management. It is unknown whether neuropsychological rehabilitation improves self-efficacy in managing the consequences of brain injury. To investigate whether levels of general and brain injury specific self-efficacy and quality of life (QoL) increased after neuropsychological rehabilitation and whether cognitive performance was associated with self-efficacy. We conducted a retrospective clinical cohort study of 62 patients with acquired brain injury and cognitive complaints with measurements before start and after completion of treatment. QoL was measured with the visual analogue scale (EQ VAS) of the EuroQol (EQ-5D); self-efficacy with the TBI Self-efficacy Questionnaire (SEsx) and the General Self-efficacy Scale (GSES). Cognitive performance was measured as a compound score of tests for memory, attention and information processing speed. Self-efficacy for managing brain injury-specific symptoms and QoL increased significantly after neuropsychological rehabilitation. Both general and brain injury-specific self-efficacy were positively associated with QoL after completion of the programme. Cognitive performance was not associated with self-efficacy for managing brain injury-specific symptoms nor with general self-efficacy. Self-efficacy and QoL improve after treatment. Further research is needed to identify the specific ingredients responsible for improvement of self-efficacy in patients with cognitive complaints.

Back to table of contents Previous article Next article Book ReviewsFull AccessCognitive Rehabilitation: An Integrative Neuropsychological ApproachMichelle Kornbleuth, Ph.D.Michelle KornbleuthSearch for more papers by this author, Ph.D.Published Online:1 Aug 2002AboutSectionsView EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail In the past, research about the efficacy of treatment and rehabilitation for individuals who suffered acquired or traumatic brain injuries was limited. However, a surge of research and literature over the past ten years has opened up possibilities for both clinicians and clients. Clinicians need to keep abreast of the advances in technology and treatment that help to further their understanding of clients with cognitive difficulties.In 1989, McKay Moore Sohlberg and Catherine A. Mateer published Introduction to Cognitive Rehabilitation: Theory and Practice. The need for a text that both reviews the literature to date on cognitive functioning and provides a comprehensive overview of theory has encouraged these authors to produce a second book to address the growth in the field of cognitive rehabilitation and neuropsychology.The new book thoroughly examines a variety of cognitive disorders (some developmental, others a result of acquired and/or traumatic injuries) and informs the experienced clinician, as well as the layperson, about the anatomy and etiology of a disorder, the relationship between the brain and behavior, and the type of treatment that best suits the problem. This book addresses the behavioral, cognitive, and emotional aspects of brain functioning required to practice effectively and efficiently in cognitive neuropsychology and rehabilitation. It is recommended for all practitioners who work with individuals with brain injury, as well as for students.Within the context of advances in cognitive rehabilitation, Part I introduces theories, models, and disorders associated with cognitive impairments, along with the principles of cognitive rehabilitation, new perspectives shaping the field, including advances in technology, emphasis on empowerment, functional approaches to treatment, and the impact of emotions on treatment. Recovery and assessment procedures are specifically defined.Part II comprehensively reviews the theories, assessment procedures, and approaches to treating and managing the areas of cognitive functioning, such as attention, memory, awareness, communication, and executive functioning, that can be affected by brain injury. Along with realistic case examples, the authors provide practical questionnaires, exercises, tasks, and worksheets, including a handout on attention strategies, tasks to assess for executive functioning, charts to record daily thoughts, and specific strategies and instructions for classroom accommodations for children with cognitive impairments.It is noteworthy that the authors discuss realistically the important issue of reduced awareness in relation to an individual's ability to benefit from treatment. Interviewing tips, including specific questions, are provided to assess self-awareness and adaptive functioning skills. In addition, they provide functional suggestions to increase awareness in clients, and they emphasize the importance of support networks, specifically family members. Interventions for psychological sequelae of a brain injury, as well as approaches to working with children and individuals with mild brain injury, are covered in Parts III and IV. Greater coverage of the research and literature on the benefits of neuropsychiatry of traumatic brain injury would be helpful, but this is a minor criticism.The authors' new work has expanded to cover the growing field of cognitive rehabilitation. It presents the research and clinical interests pertinent to questions of brain–behavior relationships in children and adults, with a range of disabilities, at a variety of levels of functioning. It is highly recommended as an adjunct to other texts on rehabilitation, cognitive deficits, and neuroanatomy for neurologists, neuropsychologists, psychologists, psychiatrists, social workers, speech and occupational therapists, caseworkers, and students. Dr. Kornbleuth is a clinical psychologist affiliated with Lenox Hill Hospital, New York, NY.By McKay Moore Sohlberg and Catherine A. Mateer, New York, Guilford Press, 2001, 492 pages, ISBN 1-57230-613-0, $55.00 FiguresReferencesCited byDetailsCited ByNone Volume 14Issue 3 August 2002Pages 352-352 Metrics History Published online 1 August 2002 Published in print 1 August 2002

Objective : This study examined psychiatric sequelae of traumatic brain injuries in outpatients and their relation to functional disability. Method : Fifty consecutive outpatients with traumatic brain injuries who came to a brain injury rehabilitation clinic for initial evaluation were examined for DSM-III-R diagnoses with the use of the National Institute of Mental Health Diagnostic Interview Schedule. The patients completed the Medical Outcomes Study Health Survey to assess functional disability and a questionnaire to assess postconcussion symptoms and self-perceptions of the severity of their brain injuries and cognitive functioning. Results : Thirteen (26%) of the patients had current major depression, and an additional 14 (2 8%) reported a first-onset major depressive episode after the injury that had resolved. Twelve (24%) had current generalized anxiety disorder, and four (8%) reported current substance abuse. The group with depression and/or anxiety was significantly more impaired than the nondepressed/nonanxious patients according to the Medical Outcomes Study Health Survey measures of emotional role functioning, mental health, and general health perceptions. The depressed/anxious group also rated their injuries as significantly more severe and their cognitive functioning as significantly worse, despite the lack of significant differences in objective measures of severity of injury and Mini-Mental State examination scores. The depressed patients reported significantly more postconcussion symptoms that were increasing in severity over time. Conclusions : Depression and anxiety are common in outpatients with traumatic brain injuries. Patients with depression or anxiety are more functionally disabled and perceive their injury and cognitive impairment as more severe. Depressed patients report more increasingly severe postconcussion symptoms.

Objective To evaluate the effect of hydrogen (H2) inhalation on brain injury in septic mice.Methods One hundred and eighty male ICR mice,aged 6-8 weeks,weighing 20-25 g,were randomly divided into 4 groups (n =45 each) using a random number table:sham operation group (SH group),H2 group,sepsis group (S group) and sepsis + H2 group (S + H2 group).Sepsis was produced by cecal ligation and puncture (CLP) in chloral hydrate-anesthetized mice.H2 and S + H2 groups inhaled 2％ H2 for 1 h starting from 1 and 6 h after CLP.At 7,12 and 24 h after CLP,6 mice in each group were sacrificed and brains were removed for determination of Evans Blue (EB) and water contents in brain tissues.Another 6 mice in each group were chosen at 7,12 and 24 h after CLP,blood samples were obtained,the mice were then sacrificed and brains were removed to measure the concentrations of tumor necrosis factor-α (TNF-α),high mobility group protein B1 (HMGB1) and interleukin-10 (IL-10) in serum and brain tissues by ELISA.Three mice in each group were sacrificed at 24 h after LPS and brains were removed for microscopic examination of pathological changes in hippocampal CA1 region.Six mice in each group were sacrificed at 24 h after LPS and brains were removed for determination of the expression of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in brain tissues by Western blot.Results Compared with SH group,the contents of EB and water in brain tissues were significantly increased,and the levels of TNF-α,HMGB1 and IL-10 in serum and brain tissues were increased at 7,12 and 24 h after CLP,and the expression of Nrf2 and HO-1 in brain tissues was up-regulated at 24 h after CLP in S and CLP + H2 groups,and no significant difference was found in the index above in H2 group.Compared with S group,the contents of EB and water in brain tissues were significantly decreased,the levels of TNF-α and HMGB1 in serum and brain tissues were decreased and the level of IL-10 in serum and brain tissues was increased at 7,12 and 24 h after CLP,and the expression of Nrf2 and HO-1 in brain tissues was up-regulated at 24 h after CLP and the pathological changes were attenuated in group CLP + H2.Conclusion H2 inhalation can attenuate brain injury in septic mice and the mechanism is related to activation of Nrf2/ARE signaling pathway and inhibition of inflammatory responses. Key words: Hydrogen ; Sepsis ; Brain injuries

To investigate which category in the "Kihon Checklist" developed by the Japanese Ministry of Health, Labor and Welfare can predict functional decline for community-dwelling elderly people at a 2-year follow up. We compared comprehensive geriatric assessment (CGA) between "specified elderly individuals" at high risk of requiring long-term care insurance (LTCI) and "uncertified elderly people" (neither certified under LTCI nor "specified"), and also compared CGA between the risk group and non-risk group, in subcategories of the "Kihon Checklist", such as physical strength, nutrition/oral function, overall low score on questions 1-20, houseboundness, cognitive function, and depression risk. The study population consisted of 527 elderly participants aged 75 years and older in a cross-sectional study, and 382 in a longitudinal study. CGA was assessed for basic and higher functional activities of daily living (ADL), depressive symptoms, and quality of life (QOL). The Student's t-test was used in the cross-sectional study and ANOVA with repeated measures was used in the longitudinal analysis. In the cross-sectional study, the risk group had lower functions in all CGA items than the non-risk group in all subcategories of the "Kihon Checklist." In the longitudinal study, Tokyo Metropolitan Institute of Gerontology Index of Competence scores and its three subscales declined in the risk group both in physical and cognitive subcategories compared with the non-risk group, whereas only one or two subscales of Tokyo Metropolitan Institute of Gerontology Index of Competence declined in "specified" and the other two subcategories of the Kihon Checklist In both cross-sectional and longitudinal studies, the assessment of physical strength and cognitive function was more useful to detect frail elderly.

BackgroundThe cryopreservation and thawing processes are known to induce many deleterious effects in cells and might be detrimental to several cell types. There is an inherent variability in cellular responses among cell types and within individual cells of a given population with regard to their ability to endure the freezing and thawing process. The aim of this study was to evaluate the fate of cryopreserved cells within an optical cryo apparatus, the individual-cell-based cryo-chip (i3C), by monitoring several basic cellular functional activities at the resolution of individual cells.ResultsIn the present study, U937 cells underwent the freezing and thawing cycle in the i3C device. Then a panel of vital tests was performed, including the number of dead cells (PI staining), apoptotic rate (Annexin V staining), mitochondrial membrane potential (TMRM staining), cytoplasm membrane integrity and intracellular metabolism (FDA staining), as well as post-thawing cell proliferation assays. Cells that underwent the freezing - thawing cycle in i3C devices exhibited the same functional activity as control cells. Moreover, the combination of the multi-parametric analysis at a single cell resolution and the optical and biological features of the device enable an accurate determination of the functional status of individual cells and subsequent retrieval and utilization of the most valuable cells.ConclusionsThe means and methodologies described here enable the freezing and thawing of spatially identifiable cells, as well as the efficient detection of viable, specific, highly biologically active cells for future applications.

Alzheimer’s disease (AD) is a degenerative neurological disease that primarily affects the elderly. Drug therapy is the main strategy for AD treatment, but current treatments suffer from poor efficacy and a number of side effects. Non-drug therapy is attracting more attention and may be a better strategy for treatment of AD. Hypoxia is one of the important factors that contribute to the pathogenesis of AD. Multiple cellular processes synergistically promote hypoxia, including aging, hypertension, diabetes, hypoxia/obstructive sleep apnea, obesity, and traumatic brain injury. Increasing evidence has shown that hypoxia may affect multiple pathological aspects of AD, such as amyloid-beta metabolism, tau phosphorylation, autophagy, neuroinflammation, oxidative stress, endoplasmic reticulum stress, and mitochondrial and synaptic dysfunction. Treatments targeting hypoxia may delay or mitigate the progression of AD. Numerous studies have shown that oxygen therapy could improve the risk factors and clinical symptoms of AD. Increasing evidence also suggests that oxygen therapy may improve many pathological aspects of AD including amyloid-beta metabolism, tau phosphorylation, neuroinflammation, neuronal apoptosis, oxidative stress, neurotrophic factors, mitochondrial function, cerebral blood volume, and protein synthesis. In this review, we summarized the effects of oxygen therapy on AD pathogenesis and the mechanisms underlying these alterations. We expect that this review can benefit future clinical applications and therapy strategies on oxygen therapy for AD.

Treatments to improve outcomes following severe traumatic brain injury (TBI) are limited but may benefit from understanding subacute-chronic brain protein profiles and identifying biomarkers suitable for use in this time. Acute alterations in the well-known TBI biomarkers glial fibrillary acidic protein (GFAP), αII-spectrin, and their breakdown products (BDPs) have been well established, but little is known about the subacute-chronic post-injury profiles of these biomarkers. Thus, the current study was designed to determine the extended profile of these TBI-specific biomarkers both in brain tissue and cerebral spinal fluid (CSF). Protein abundance was evaluated in brain tissue samples taken from regions of interest and in CSF at 24 h, 3 days, 7 days, 1 month, and 3 months following severe TBI in rats. Results showed increased full length GFAP (GFAP-FL) and GFAP-BDPs starting at 24 h that remained significantly elevated in most brain regions out to 3 months post-injury. However, in CSF, neither GFAP-FL nor GFAP-BDPs were elevated as a consequence of injury. Regional-specific reduction in αII-spectrin was evident in brain tissue samples from 24 h through 3 months. In contrast, SBDP-145/150 was robustly elevated in most brain regions and in CSF from 24 h through 7 days. Correlation analyses revealed numerous significant relationships between proteins in CSF and brain tissue or neurological deficits. This work indicates that TBI results in chronic changes in brain protein levels of well-known TBI biomarkers GFAP, αII-spectrin, and their BDPs and that SBDP-145/150 may have utility as an acute-chronic biomarker.

In Memoriam

In multiple sclerosis (MS), pronounced neurodegeneration manifests itself as cerebral gray matter (GM) atrophy, which is associated with cognitive and physical impairments. Microstructural changes in GM estimated by diffusion kurtosis imaging (DKI) may reveal neurodegeneration that is undetectable by conventional structural MRI and thus serve as a more sensitive marker of disease progression. The primary objective was to investigate the relationships between morphological and diffusional properties in cerebral GM and physical and cognitive performance in relapsing-remitting MS (RRMS) patients. A secondary objective was to investigate the relationship between GM microstructure and white matter (WM) injury, estimated by the volume of WM lesions. Sixty-seven RRMS patients performed the brief repeatable battery of neuropsychological tests (BRB-N), the 6-minute walk test (6MWT), the six spot step test (SSST), and underwent MRI scans using structural and DKI protocols. GM volumetrics and DKI measurements were analyzed in the cortex and deep GM structures using a general linear model with demographics, physical- and cognitive performance as covariates. Mean diffusivity (MD) in the cortex was associated with the SSST, 6MWT, information processing, global cognitive performance, and volume of WM lesions. In addition, thalamic volume was associated with SSST (r2 = 0.21, 6MWT (r2 = 0.18), information processing (r2 = 0.21), and WM lesion volume (r2 = 0.60). Cortical diffusion and thalamic volume are associated with walking and cognitive performance in RRMS patients and are highly affected by the presence of WM lesions.