Cognitive rehabilitation interventions for executive function: moving from bench to bedside in patients with traumatic brain injury

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.     

Association between cognitive impairments and obsessive-compulsive spectrum presentations following traumatic brain injury

This study examined the association between self-reported obsessive-compulsive spectrum symptomatology and cognitive performance in a sample of patients with traumatic brain injury (TBI). Twenty-four adults with a moderate-severe TBI accessing a community brain injury rehabilitation service were recruited. Age ranged between 19 and 69 years. Participants completed a battery of neuropsychological tasks assessing memory, executive functioning, and speed of information processing. Self-report questionnaires assessing obsessive-compulsive (OC) symptoms and obsessive-compulsive personality disorder (OCPD) traits were also completed. Correlational analyses revealed that deficits in cognitive flexibility were associated with greater self-reported OC symptomatology and severity. Greater OC symptom severity was significantly related to poorer performance on a visual memory task. Verbal memory and speed of information processing impairments were unrelated to OC symptoms. Performance on tasks of memory, executive functioning, and speed of information processing were not associated with OCPD traits. Overall, results indicate that greater OC symptomatology and severity were associated with specific neuropsychological functions (i.e., cognitive flexibility, visual memory). OCPD personality traits were unrelated to cognitive performance. Further research is needed to examine the potential causal relationship and longer-term interactions between cognitive sequelae and obsessive-compulsive spectrum presentations post-TBI.     

Theory of mind following traumatic brain injury: the role of emotion recognition and executive dysfunction

A number of studies have now documented that traumatic brain injury (TBI) is associated with deficits in the recognition of basic emotions, the capacity to infer mental states of others (theory of mind), as well as executive functioning. However, no study to date has investigated the relationship between these three constructs in the context of TBI. In the current study TBI participants (N=16) were compared with demographically matched healthy controls (N=17). It was found that TBI participants' recognition of basic emotions, as well as their capacity for mental state attribution, was significantly reduced relative to controls. Performance on both of these measures was strongly correlated in the healthy control, but not in the TBI sample. In contrast, in the TBI (but not the control) sample, theory of mind was substantially correlated with performance on phonemic fluency, a measure of executive functioning considered to impose particular demands upon cognitive flexibility and self-regulation. These results are consistent with other evidence indicating that deficits in some aspects of executive functioning may at least partially underlie deficits in social cognition following TBI, and thus help explain the prevalence of social dysfunction in TBI.     

Executive dysfunction following traumatic brain injury: neural substrates and treatment strategies

Executive dysfunction is among the most common and disabling aspects of cognitive impairment following traumatic brain injury (TBI), and may include deficits in reasoning, planning, concept formation, mental flexibility, aspects of attention and awareness, and purposeful behavior. These impairments are generally attributed to frontal systems dysfunction, due either to direct insult to the frontal lobes or to disruption of their connections to other brain regions. Evaluation of executive deficits typically includes neuropsychological assessment, though adjunctive interviews can be critical in detecting subtle dysexecutive symptoms that may not be apparent on standardized testing. Rehabilitation programs emphasizing cognitive-behavioral approaches to the retraining of planning and problem-solving skills can be effective in ameliorating identified executive deficits. In addition, pharmacological approaches may be useful in addressing aspects of executive dysfunction. This review summarizes the nature of executive deficits following TBI, their neuroanatomical substrates, selected assessment and treatment strategies, and recent research findings and trends.     

Social dysdecorum following severe traumatic brain injury: loss of implicit social knowledge or loss of control?

The purpose of the present study was to investigate two theoretical frameworks for understanding acquired deficits in social behavior in individuals with severe traumatic brain injury (TBI). Recent research has found that brain injury can lead to impairments in implicit processes including social cognition. Impairments in implicit social cognition have been recently advanced as an explanation for acquired social deficits, as implicit social cognition is hypothesized to mediate the processing and understanding of often subtle, nonverbal cues in social interactions. In contrast, the executive dysfunction account posits that deficits in higher order cognitive functions, such as attention, planning ability, and mental flexibility, are the locus for acquired deficits in social cognition and behavior. To test these two theories, 22 participants with severe TBI and 25 matched controls were administered a measure of implicit social cognition (Implicit Association Test, IAT), as well as two measure of explicit social attitudes and a range of executive functioning measures. The TBI participants were found to perform normally on the IAT and explicit measures of gender stereotyping but demonstrated executive deficits. Performance on the IAT and executive functions were correlated. Performance in general did not fit well with the implicit social cognition explanation for social dysdecorum following TBI. More evidence was found to support the executive account.     

Insomnia following traumatic brain injury: a review

Sleep disturbances after a traumatic brain injury (TBI) have received very little scientific attention despite the fact that several studies indicate that they may occur in 30% to 70% of patients. For individuals with TBI, problems falling asleep or maintaining sleep can exacerbate other symptoms such as pain, cognitive deficits, fatigue, or irritability. Sleep disturbances can thus compromise the rehabilitation process and the ability to return to work. This article reviews the evidence on the epidemiology, etiology, and treatment of insomnia in the context of TBI and proposes areas for future research. Prevalence estimates of insomnia complaints in TBI patients are summarized. Potential etiological factors (i.e., lesions to the nervous system, anxiety) and possible consequences of insomnia (i.e., fatigue, cognitive problems) in the context of TBI are discussed. Finally, pharmacological and psychological treatments previously shown effective to treat insomnia in healthy individuals are discussed as valuable treatment options for TBI patients. Increased knowledge about the high prevalence, diagnosis, and potential etiological factors of insomnia following TBI may promote a better identification, evaluation, and treatment of sleeping difficulties in this population.     

Persistent cognitive dysfunction after traumatic brain injury: A dopamine hypothesis

Traumatic brain injury (TBI) represents a significant cause of death and disability in industrialized countries. Of particular importance to patients the chronic effect that TBI has on cognitive function. Therapeutic strategies have been difficult to evaluate because of the complexity of injuries and variety of patient presentations within a TBI population. However, pharmacotherapies targeting dopamine (DA) have consistently shown benefits in attention, behavioral outcome, executive function, and memory. Still it remains unclear what aspect of TBI pathology is targeted by DA therapies and what time-course of treatment is most beneficial for patient outcomes. Fortunately, ongoing research in animal models has begun to elucidate the pathophysiology of DA alterations after TBI. The purpose of this review is to discuss clinical and experimental research examining DAergic therapies after TBI, which will in turn elucidate the importance of DA for cognitive function/dysfunction after TBI as well as highlight the areas that require further study.     

Executive function and coping at one-year post traumatic brain injury

The purpose of this study was to examine the relationship between executive function and coping at one-year-post traumatic brain injury (TBI). TBI and matched control groups completed a coping questionnaire and a neuropsychological test series. In the TBI group, better executive performance was related to the use of problem focused coping (considered more adaptive). Conversely, lower executive performance was related to the use of emotion focused coping (considered more maladaptive). Planned hierarchical regression showed that executive function contributed significantly to the use of problem focused coping above and beyond pre-morbid intelligence and injury severity. Implications for cognitive rehabilitation are discussed.     

Longitudinal study of objective and subjective cognitive performance and psychological distress in OEF/OIF Veterans with and without traumatic brain injury

Objective: To describe changes in post-deployment objective and subjective cognitive performance in combat Veterans over 18 months, relative to traumatic brain injury (TBI) status and psychological distress. Method: This prospective cohort study examined 500 Veterans from Upstate New York at four time points, six months apart. TBI status was determined by a structured clinical interview. Neuropsychological instruments focused on attention, memory, and executive functions. Subjective cognitive complaints were assessed with the Neurobehavioral Symptom Inventory (NSI). A psychological distress composite included measures of post-traumatic stress disorder (PTSD), depression, and generalized anxiety. Results: Forty-four percent of the sample was found to have sustained military-related TBI, 97% of which were classified as mild (mTBI), with a mean time since injury of 41 months. Veterans with TBI endorsed moderate cognitive symptoms on the NSI. In contrast to these subjective complaints, mean cognitive test performance was within normal limits at each time point in all domains, regardless of TBI status. Multilevel models examined effects of TBI status, time, and psychological distress. Psychological distress was a strong predictor of all cognitive domains, especially the subjective domain. Substantial proportions of both TBI+ and TBI? groups remained in the clinically significant range at the initial and final assessment for all three distress measures, but the TBI+ group had higher proportions of clinically significant cases. Conclusions: Objective cognitive performance was generally within normal limits for Veterans with mTBI across all assessments. Psychological distress was elevated and significantly related to both objective and subjective cognitive performance.     

Association between cognitive impairments and anxiety disorders following traumatic brain injury

This study examined the association between cognitive impairment and anxiety disorders following traumatic brain injury (TBI). Sixty-six participants recruited from a rehabilitation hospital completed the Structured Clinical Interview for the DSM–IV (Diagnostic and Statistical Manual of Mental Disorders–Fourth Edition) and cognitive tests at one year post injury. Prevalence of anxiety disorder was 27.3%. Logistic regression analyses revealed that the attention/working memory, information processing, and executive functions models were significantly associated with anxiety disorder. The memory model was not significant. Processing speed emerged as the strongest model associated with anxiety disorder. The role of cognitive impairment in the etiology of anxiety disorders after TBI is discussed, and treatment implications are explored.     

CXCL12与创伤性颅脑损伤后神经细胞凋亡的相关性

创伤性颅脑损伤（TBI）后的神经细胞凋亡是继发性TBI中最严重的病理生理变化，是临床上致残、致死率高的重要原因。有效控制神经细胞凋亡是治疗TBI的关键，直接关系到TBI患者的预后。CXCL12是一类具有趋化活性的细胞因子，在中枢神经系统有广泛的表达，在神经保护、神经功能调节、神经细胞发生和神经炎症反应中起着关键作用。随着研究的不断深入，发现CXCL12与TBI后神经细胞凋亡有着密切的联系。本文就CXCL12与TBI后神经细胞凋亡关系的研究进展展开综述。     

Functional anatomy of neuropsychological deficits after severe traumatic brain injury

BACKGROUND: Neurobehavioral disorders after severe traumatic brain injury (TBI) are poorly correlated with focal lesions detected by structural neuroimaging techniques such as CT scan or MRI. OBJECTIVE: To explore the relationships between regional cerebral glucose metabolism at rest, as measured by PET, and neurobehavioral status after severe TBI at the subacute stage. METHODS: Thirteen patients without focal structural lesion on MRI were studied. Neuropsychological assessment included tests of memory, attention and speed of information processing, and executive functions, and a global neurobehavioral assessment. Regional cerebral glucose metabolism at rest was measured with (18F)-fluorodeoxyglucose and PET. RESULTS: A close link was found between cognitive and behavioral disorders and decreased cortical metabolism in prefrontal and cingulate cortex. Tests of memory and executive functions significantly correlated with regional metabolism in the mesial and lateral prefrontal cortex and the cingulate gyrus. Behavioral disorders correlated significantly with mesial prefrontal and cingulate metabolisms. CONCLUSION: These results suggest a predominant role of prefrontal and cingulate dysfunction in cognitive and behavioral disorders of patients with severe traumatic brain injury, even in the absence of focal structural lesion of the brain. Further cognitive functional activation research using PET or functional MRI might help clarify the relative contributions of both areas to dysfunction.     

Tonic and phasic alertness training: a novel treatment for executive control dysfunction following mild traumatic brain injury

Many individuals with traumatic brain injury (TBI) suffer difficulty regulating fundamental aspects of attention (focus, sustained attention) and may also exhibit hypo- or hyper-states of alertness. Deficits in the state of attention may underlie or exacerbate higher order executive dysfunction. Recent studies indicate that computerized cognitive training targeting attentional control and alertness can ameliorate attention deficits evident in patients with TBI or acquired brain injury. The current study examined whether improvements in attentional state following training can also influence performance on higher-order executive function and mood in individuals with mild TBI (mTBI). The current study examined five patients with executive control deficits as a result of mTBI, with or without persistent anxiety. Three patients engaged in ~5 hours of an executive control training task targeting inhibitory control and sustained attention; two additional patients were re-tested following the same period of time. Performance on standard neuropsychological measures of attention, executive function, and mood were evaluated pre- and post-training. The results indicate that tonic and phasic alertness training may improve higher-order executive function and mood regulation in individuals with TBI.     

Decreased prefrontal cortex activity in mild traumatic brain injury during performance of an auditory oddball task

Up to one-third of patients with mild traumatic brain injury (TBI) demonstrate persistent cognitive deficits in the ‘executive’ function domain. Mild TBI patients have shown prefrontal cortex activity deficits during the performance of executive tasks requiring active information maintenance and manipulation. However, it is unclear whether these deficits are related to the executive processes themselves, or to the degree of mental effort. To determine whether prefrontal deficits also would be found during less effortful forms of executive ability, fMRI images were obtained on 31 mild TBI patients and 31 control participants during three-stimulus auditory oddball task performance. Although patients and controls had similar topographical patterns of brain activity, region-of-interest analysis revealed significantly decreased activity in right dorsolateral prefrontal cortex for mild TBI patients during target stimulus detection. Between-group analyses found evidence for potential compensatory brain activity during target detection and default-mode network dysfunction only during the detection of novel stimuli.     

Complement Drives Synaptic Degeneration and Progressive Cognitive Decline in the Chronic Phase after Traumatic Brain Injury

Cognitive deficits following traumatic brain injury (TBI) remain a major cause of disability and early-onset dementia, and there is increasing evidence that chronic neuroinflammation occurring after TBI plays an important role in this process. However, little is known about the molecular mechanisms responsible for triggering and maintaining chronic inflammation after TBI. Here, we identify complement, and specifically complement-mediated microglial phagocytosis of synapses, as a pathophysiological link between acute insult and a chronic neurodegenerative response that is associated with cognitive decline. Three months after an initial insult, there is ongoing complement activation in the injured brain of male C57BL/6 mice, which drives a robust chronic neuroinflammatory response extending to both hemispheres. This chronic neuroinflammatory response promotes synaptic degeneration and predicts progressive cognitive decline. Synaptic degeneration was driven by microglial phagocytosis of complement-opsonized synapses in both the ipsilateral and contralateral brain, and complement inhibition interrupted the degenerative neuroinflammatory response and reversed cognitive decline, even when therapy was delayed until 2 months after TBI. These findings provide new insight into our understanding of TBI pathology and its management; and whereas previous therapeutic investigations have focused almost exclusively on acute treatments, we show that all phases of TBI, including at chronic time points after TBI, may be amenable to therapeutic interventions, and specifically to complement inhibition.SIGNIFICANCE STATEMENT There is increasing evidence of a chronic neuroinflammatory response after traumatic brain injury (TBI), but little is known about the molecular mechanisms responsible for triggering and maintaining chronic inflammation. We identify complement, and specifically complement-mediated microglial phagocytosis of synapses, as a pathophysiological link between acute insult and a chronic neurodegenerative response, and further that this response is associated with cognitive decline. Complement inhibition interrupted this response and reversed cognitive decline, even when therapy was delayed until 2 months after injury. The data further support the concept that TBI should be considered a chronic rather than an acute disease condition, and have implications for the management of TBI in the chronic phase of injury, specifically with regard to the therapeutic application of complement inhibition.     

Executive functioning and the application of social skills following traumatic brain injury

Many adults with a traumatic brain injury (TBI) are less competent conversationalists following their injury. Reduced conversational competency is a clinically significant problem. It is associated with a variety of adverse psychosocial outcomes following TBI. Unfortunately, direct attempts to improve the conversational competency of adults with TBI using social skills training has had limited success. This article applies McFall's (1982) social skills model to conversational competency following TBI. This social skills model is based on two critical assumptions. First, in order to be judged socially competent, a person needs to possess the social skills required in a given social context. Second, that social competence requires the ability to apply social skills flexibly according to the rules of social interaction. It is argued that the inability to flexibly apply behaviour according to rules (executive dysfunction) could account for many characteristics of conversation following TBI. This argument is illustrated through the detailed application of Norman and Shallice's (1986) theory of executive functioning to research on conversational behaviour following TBI. It is concluded that fostering appropriate social environments, and providing support are more likely to be effective than remedial social skills training.     

Relation of executive functioning and social communication measures to functional outcomes following traumatic brain injury

Neuropsychologists are increasingly asked to provide recommendations regarding functional abilities based on test results, particularly within the rehabilitation setting. Yet, the empirical basis for making such recommendations is limited. The current study examines relationships between executive functioning and social communication measures and concurrently measured occupational and social integration outcomes. Participants were 121 individuals with traumatic brain injury (TBI) recruited from participants in a longitudinal study of outcome following TBI who had all received comprehensive brain injury rehabilitation. As part of a larger study designed to evaluate social communication abilities following TBI, participants completed measures of executive functioning, affect perception, perceived communication ability, and functional outcome. After adjusting for age, education, and performance on executive functioning measures, social communication performance accounted for a unique 5.6% of the variance in occupational outcomes and 7.9% of variance in social integration outcomes. Executive functioning performance accounted for a unique 13.3% of the variance in occupational functioning and 16.0% of explained variance in social integration. These results provide evidence of the value of executive functioning and social communication measures in the prediction of functional outcomes. Additionally, such results provide preliminary support for the addition of social communication measures to assessment of TBI in neuropsychological practice.     

Mindfulness-based Cognitive Therapy: Benefits in Reducing Depression Following a Traumatic Brain Injury

Context Current therapies for traumatic brain injury (TBI) include pharmacotherapy, psychotherapy, and cognitive rehabilitation. Unfortunately, psychological and emotional issues regularly go untreated in individuals with TBI even after they receive treatment for physical, behavioral, and cognitive issues. Mindfulness-based cognitive therapy (MBCT) may offer new rehabilitation opportunities for individuals with TBI. Objective To demonstrate the efficacy of MBCT in the treatment of clinically diagnosed depression in a TBI population. Design The research team measured depression, pain frequency and intensity, energy levels, health status, and function preintervention and postintervention. Setting The research team conducted the study at the Ottawa Hospital Rehabilitation Centre, Ontario, Canada. Participants The research team recruited 23 participants from two sources: (1) the brain injury program at the hospital and (2) the local head-injury association. Twenty participants completed the study. Intervention The intervention was 8 weeks in length, with a 90-minute MBCT session once a week. The research team based the specific content of the study's intervention on a combination of Kabat-Zinn's manualized mindfulness-based stress reduction program and Segal and colleague's manual for MBCT. Outcome Measures The research team determined statistical significance using paired t-tests for continuous outcomes and the McNemar chi-square test for dichotomous categorical outcomes. They also calculated effect sizes for all depression measures. Results Postintervention, the study found that MBCT significantly reduced (P < .050) depression symptoms on all scales compared to baseline. The study demonstrated medium to large effect sizes for each depression measure. Participants indicated reduced pain intensity (P = .033) and increased energy levels (P = .004). No significant changes occurred in anxiety symptoms, pain frequency, and level of functioning postintervention. Conclusion MBCT was efficacious in reducing depression in the TBI population, providing ample rationale for further research with more robust designs. This study marks an important step toward the development and provision of MBCT on a wider scale to support the rehabilitation efforts of people who have depression symptoms following TBI. (Adv Mind Body Med. 2012;26(1):14-20.).     

A systematic review of recommended modifications of CBT for people with cognitive impairments following brain injury

Due to diverse cognitive, emotional and interpersonal changes that can follow brain injury, psychological therapies often need to be adapted to suit the complex needs of this population. The aims of the study were to synthesise published recommendations for therapy modifications following brain injury from non-progressive traumatic, vascular, or metabolic causes and to determine how often such modifications have been applied to cognitive behavioural therapy (CBT) for post-injury emotional adjustment problems. A systematic review and narrative synthesis of therapy modifications recommended in review articles and reported in intervention studies was undertaken. Database and manual searches identified 688 unique papers of which eight review articles and 16 intervention studies met inclusion criteria. The review articles were thematically analysed and a checklist of commonly recommended modifications composed. The checklist items clustered under themes of: therapeutic education and formulation; attention; communication; memory; and executive functioning. When this checklist was applied to the intervention studies, memory aids and an emphasis on socialising patients to the CBT model were most frequently reported as adaptations. It was concluded that the inconsistent reporting of psychological therapy adaptations for people with brain injury is a barrier to developing effective and replicable therapies. We present a comprehensive account of potential modifications that should be used to guide future research and practice.