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.     

Cognitive and psychological flexibility after a traumatic brain injury and the implications for treatment in acceptance-based therapies: A conceptual review

This paper provides a selective review of cognitive and psychological flexibility in the context of treatment for psychological distress after traumatic brain injury, with a focus on acceptance-based therapies. Cognitive flexibility is a component of executive function that is referred to mostly in the context of neuropsychological research and practice. Psychological flexibility, from a clinical psychology perspective, is linked to health and well-being and is an identified treatment outcome for therapies such as acceptance and commitment therapy (ACT). There are a number of overlaps between the constructs. They both manifest in the ability to change behaviour (either a thought or an action) in response to environmental change, with similarities in neural substrate and mental processes. Impairments in both show a strong association with psychopathology. People with a traumatic brain injury (TBI) often suffer impairments in their cognitive flexibility as a result of damage to areas controlling executive processes but have a positive response to therapies that promote psychological flexibility. Overall, psychological flexibility appears a more overarching construct and cognitive flexibility may be a subcomponent of it but not necessarily a pre-requisite. Further research into therapies which claim to improve psychological flexibility, such as ACT, needs to be undertaken in TBI populations in order to clarify its utility in this group.     

Diffuse axonal injury due to traumatic brain injury alters inhibition of imitative response tendencies

It is well known that traumatic brain injury particularly affects the frontal lobes. Consequently, patients often suffer from executive dysfunction and behavioral disturbances. Accordingly, our study aimed at investigating patients after traumatic brain injury with two tasks involving different functional processes and structural networks supported by the frontal lobes. Two paradigms were applied: the Stroop color-word task and a task in which subjects had to inhibit imitative response tendencies. We selected a patient group solely with diffuse axonal injury, as this type of injury is homogenous and is correlated with cognitive dysfunction more than focal contusions. To evaluate long-term effects most relevant for rehabilitation, we selected a patient group whose brain injuries dated back several years. Our results show that patients with diffuse axonal injury inhibited imitative responses more successfully than control subjects, whereas executive processes examined with the Stroop task were unaltered. Interestingly, impairments were tightly correlated both with the length of the post-traumatic amnesia predicting outcome in traumatic brain injury and with behavioral disturbances. Impairments in the imitation-inhibition task may indicate alterations in an anterior frontomedian neural network even years after traumatic brain injury.     

Frontal cortex as the central executive of working memory: time to revise our view

For historical reasons (Bianchi, 1895; Harlow, 1968; Luria, 1966; Shallice, 1982), a specific link between the central executive of working memory and the frontal cortex was originally suggested by Baddeley (1986). This review discusses the evidence against such a univocal link. Two executive processes investigated in neuropsychology are discussed: inhibition (WCST, Stroop, proactive interference, go-no go, Stop signal and the Hayling test) and dual-task management. The evidence reviewed demonstrates (i) that executive processes involve links between different brain areas, not exclusively with the frontal cortex, (ii) that patients with no evidence of frontal damage present with executive deficits, and (iii) that patients with frontal lesions do not always show executive deficits. In conclusion, this review suggests that it is time for a more dynamic and flexible view of the neural substrate of executive processes to be considered. It also confirms, as recently suggested by Baddeley (1996, 1998a, 1998b), that the study of frontal patients cannot be used as a primary source of evidence to understand CE functions.     

轻度颅脑损伤患者的执行功能研究

背景 颅脑损伤常遗留神经精神的损害,包括认知功能损害、精神病性障碍和行为问题等.认知功能损害是颅脑损伤后常见的后遗问题,其中执行功能是一个十分重要的维度.轻度颅脑损伤一直被认为是脑遭受外力打击后出现的暂时的脑功能障碍,无肉眼可见的器质性损害.近年来这一传统的观点受到质疑,目前国内外一些学者认为轻度颅脑损伤是一种弥漫性的脑损伤.关于轻度颅脑损伤患者的神经心理学研究是众多研究者争论的焦点,观点不一致.本研究对恢复期的颅脑损伤患者进行执行功能评定,目的是探讨轻度颅脑损伤患者的执行功能状况.方法 对159例因交通事故造成颅脑外伤的幸存者于损伤后3～6个月医疗终结后进行执行功能评定,并与68例正常人对照.病例组的入组标准为①年龄16～65岁;②文化程度小学及以上文化,能理解执行功能测验的内容;③右利手;④有明确的脑损伤史;⑤检查前4周内未使用抗精神病药物或其他影响中枢神经系统功能的药物;⑥资料齐全;⑦自愿参加本研究.正常对照组的入组标准为①年龄16～65岁;②文化程度小学及以上文化,能理解认知功能测验的内容;③右利手;④自愿参加本研究.排除标准为①以往有脑损伤史、脑部疾患史、精神疾病史者;②精神发育迟滞者;③严重的躯体疾患者;④有药物、酒精或其他影响中枢神经系统功能的物质滥用史者;⑤色盲、色弱者;⑥对测验不合作或不能有效完成测验者.病例组分组根据颅脑损伤伤情评定的国际标准格拉斯哥昏迷计分法将病例组分成三组轻度脑损伤组78例(49.1%)GCS评分15～13分,伤后昏迷时间＜20 min;中度脑损伤组52例(32.7%)GCS评分12～9分,伤后昏迷时间20 min至6 h;重度脑损伤组29例(18.2%)GCS评分8～6分,伤后昏迷时间＞6 h.测验包括韦氏智力测验中的木块拼图测验、STROOP测验、威斯康辛卡片分类测验-改良版(M-WCST)和词汇的流畅性测验,比较轻度颅脑损伤与中、重度颅脑损伤患者的测验成绩,以及CT/MRI有无阳性发现患者的测验成绩,分析与执行功能有关的因素.结果 轻度颅脑损伤患者所有的测验成绩均低于正常对照组,其差异达到显著性水平(P＜0.01).而与中度损伤组的成绩比较则没有显著性差异(P＞0.05).在轻度组与重度组的比较中,除STROOP测验和WCST的分类个数外,其余测验成绩均存在显著性差异(P＜0.05).CT/MRI结果为阳性的病例中,不同脑损伤程度组间的执行功能检测成绩除木块拼图测验外均不具有显著性差异;CT/MRI结果为阴性的病例中,结果显示不同脑损伤程度组间的执行功能测验成绩没有显著性差异(P＞0.05).相关分析显示木块拼图和词汇流畅性两个测验成绩与脑损伤程度呈负相关(P＜0.05).年龄和执行功能呈负相关,受教育程度与执行功能呈正相关.结论 轻度颅脑损伤患者在医疗终结时仍然存在执行功能损害.我们在伤残评定中应对轻度颅脑损伤患者予以重视,同时要注意综合多方面的检测结果考虑.     

Effect of traumatic brain injury on control and suppression of inhibition processes

Recent hypotheses have renewed discussion on the mechanisms linking executive functions and working memory in patients with traumatic brain injury. In this context, we studied the control and suppression functions of inhibition processes. Results obtained with a suppression paradigm showed that the traumatic brain injury patient makes a number of suppression errors and that suppression responses imply an important temporal loss in this population.     

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.     

Executive function in traumatic brain injury and obsessive–compulsive disorder: An overlap?

Thirteen individuals with traumatic brain injury, 13 individuals with obsessive-compulsive disorder (OCD) and 10 normal controls were compared on neuropsychological measures of executive function. Individuals with a traumatic brain injury performed significantly poorer than the other two groups on a test measuring visuo-spatial strategy. Although the traumatic brain injury group made more errors on a test of maze learning and the OCD group less than the control group, this did not reach statistical significance. No support for an overlap in executive dysfunction in traumatic brain injury and OCD was found. It may be that the 'error prevention system' in the brain was influenced in a contrasting way by executive dysfunction in these disorders. This difference may reveal itself clinically in impulsivity/perseveration and slowness, respectively. Further studies were needed to test this hypothesis.     

Self-awareness after acquired and traumatic brain injury

Self-awareness deficits are common after acquired and (traumatic) brain injury (ABI), particularly in social behaviour, yet the underlying cognitive and neuroanatomical structures supporting social self-awareness are not fully understood. This paper reviews the current literature on prevalence, type and severity of self-awareness deficits in ABI. Neuropsychological and neuroanatomical models are reviewed and theoretical frameworks are examined. We summarise results of a case-control comparison of 20 ABI patients with and 20 ABI patients without behavioural disturbance. Our research found that lack of social self-awareness predicts behavioural disturbance in acquired and traumatic brain injury independent of cognitive and executive function. Theory of mind ability was related to self-awareness and a possible role for metacognition and affective processes in self-awareness is discussed to account for social self-awareness deficits.     

The psychological, neurochemical and functional neuroanatomical mediators of the effects of positive and negative mood on executive functions

In this review we evaluate the cognitive and neural effects of positive and negative mood on executive function. Mild manipulations of negative mood appear to have little effect on cognitive control processes, whereas positive mood impairs aspects of updating, planning and switching. These cognitive effects may be linked to neurochemistry: with positive mood effects mediated by dopamine while negative mood effects may be mediated by serotonin levels. Current evidence on the effects of mood on regional brain activity during executive functions, indicates that the prefrontal cortex is a recurrent site of integration between mood and cognition. We conclude that there is a disparity between the importance of this topic and awareness of how mood affects, executive functions in the brain. Most behavioural and neuroimaging studies of executive function in normal samples do not explore the potential role of variations in mood, yet the evidence we outline indicates that even mild fluctuations in mood can have a significant influence on neural activation and cognition.     

Dysexecutive syndromes in neurologic disease

Damage to the frontal structures may lead to a diverse set of changes in cognitive, behavioral, or emotional domains. While lesion studies have demonstrated distinct impairments related to pathology in different frontal regions, it is clear that the frontal lobe syndrome is not restricted to damage to frontal regions. Therefore, the broad range of impairments in executive functioning evident in neurologic disease is often referred to as the dysexecutive syndrome. This review provides an overview of how executive functioning has been traditionally defined and measured. The components of executive function such as planning, cognitive flexibility and set-shifting, initiation and self-generation, response inhibition, serial ordering and sequencing, are discussed with respect to traditional measures and neural substrates. This is followed by profiles of frontal-executive dysfunction in aging, traumatic brain injury, frontotemporal dementia, and Parkinson's disease. Since no one specific neurologic disorder has a predilection to damage isolated to the frontal lobes, profiles of the dysexecutive syndrome are related to damage to several regions in addition to the frontal lobes. Finally, there is a discussion of ecological validity and the impact of executive deficits on everyday functioning. The recent development of executive tests with greater ecological validity is reviewed and discussed, and suggestions for future directions for research are provided.     

Executive function,self-regulation and attribution in acquired brain injury: A scoping review

Impairments in executive function, self-regulation and attribution individually have been implicated in impairment in goal-directed behaviour, resulting in reduced participation in daily activities by individuals with brain injury. There is minimal literature that explicitly addresses the relationships among these constructs, how these may be affected by brain injury and the implications for rehabilitation. The objectives of this study were to determine what is known about the relationship between executive function, self-regulation and attribution, and to understand how these inter-relationships affect goal-directed behaviour in adults with acquired brain injury. A scoping review of the cognitive neuroscience, neuropsychology, rehabilitation, educational and social psychology literature from 1985 to 2011 was performed. The identified literature provided definitions of the constructs and insight into the relationships between them according to their neural underpinnings and theoretical models. These data also provided for the development of a new model illustrating the hypothesised relationships between constructs. This review and the model developed, suggest that attribution may play an important role in executive function and self-regulation. Rehabilitation interventions that address formulation of appropriate attributions should be considered in conjunction with those targeting self-regulation and executive function for individuals with brain injury.     

Short- and long-term social outcomes following pediatric traumatic brain injury.

The social outcomes of pediatric traumatic brain injury (TBI) were examined in a prospective, longitudinal study that included 53 children with severe TBI, 56 with moderate TBI, and 80 with orthopedic injuries, recruited between 6 and 12 years of age. Child and family functioning were assessed at baseline, at 6- and 12-month follow-ups, and at an extended follow-up a mean of 4 years post injury. Growth curve analyses revealed that pediatric TBI yields negative social outcomes that are exacerbated by family environments characterized by lower socioeconomic status, fewer family resources, and poorer family functioning. After controlling for group membership, age, race, socioeconomic status, and IQ, path analyses indicated that long-term social outcomes were accounted for in part by specific neurocognitive skills, including executive functions and pragmatic language, and by social problem-solving. Deficits in these domains among children with TBI are likely to reflect damage to a network of brain regions that have been implicated in social cognition.     

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.     

Multiple fregoli delusions after traumatic brain injury.

A 61 year old man after a traumatic brain injury resulting in right frontal and left temporoparietal contusions developed florid Fregoli-type misidentifications. Extensive neuropsychological testing demonstrated significant deficits in executive and memory functions. The patient's neuropsychological profile closely resembled that seen in previously reported patients with Capgras syndrome. Our findings are consistent with the hypothesis that a combination of executive and memory deficits may account for cases of delusional misidentification associated with brain lesions. However, the form which the delusion takes may be influenced by other factors including motivation.     

Cerebral blood flow and autoregulation after pediatric traumatic brain injury

Traumatic brain injury is a global health concern and is the leading cause of traumatic morbidity and mortality in children. Despite a lower overall mortality than in adult traumatic brain injury, the cost to society from the sequelae of pediatric traumatic brain injury is very high. Predictors of poor outcome after traumatic brain injury include altered systemic and cerebral physiology, including altered cerebral hemodynamics. Cerebral autoregulation is often impaired after traumatic brain injury and may adversely impact the outcome. Although altered cerebrovascular hemodynamics early after traumatic brain injury may contribute to disability in children, there is little information regarding changes in cerebral blood flow and cerebral autoregulation after pediatric traumatic brain injury. This review addresses normal pediatric cerebral physiology and cerebrovascular pathophysiology after pediatric traumatic brain injury.     

The potential role of mitochondria in pediatric traumatic brain injury

Mitochondria play a central role in cerebral energy metabolism, intracellular calcium homeostasis and reactive oxygen species generation and detoxification. Following traumatic brain injury (TBI), the degree of mitochondrial injury or dysfunction can be an important determinant of cell survival or death. Literature would suggest that brain mitochondria from the developing brain are very different from those from mature animals. Therefore, aspects of developmental differences in the mitochondrial response to TBI can make the immature brain more vulnerable to traumatic injury. This review will focus on four main areas of secondary injury after pediatric TBI, including excitotoxicity, oxidative stress, alterations in energy metabolism and cell death pathways. Specifically, we will describe what is known about developmental differences in mitochondrial function in these areas, in both the normal, physiologic state and the pathologic state after pediatric TBI. The ability to identify and target aspects of mitochondrial dysfunction could lead to novel neuroprotective therapies for infants and children after severe TBI.     

Using magnetic resonance imaging to predict new learning outcome at 5 years after childhood traumatic brain injury

Memory and learning entail the recruitment of a number of neural areas, including the medial temporal lobes, temporal association areas, and prefrontal cortices. This study examined the effects of injury severity on long-term memory function in 55 children who sustained traumatic brain injury 5 years earlier and compared this with 17 healthy controls. It also investigated cortical damage and diffuse axonal injury and their association to memory and learning outcomes 5 years after traumatic brain injury. Children were administered memory tests of increasing complexity. Results indicated that injury severity affected aspects of complex memory, with no significant influence on working memory; that focal cortical damage was not predictive of working or complex memory, whereas diffuse axonal injury predicted outcome on complex memory tasks. Findings suggest that the implementation of diffuse axonal injury as an index of injury may assist in predicting memory outcome after childhood traumatic brain injury.     

Cognitive Impairments in Children with Nonidiopathic Temporal Lobe Epilepsy

Summary:  Ictal and interictal activities occurring in a mature brain can disorganize the neural network activity involved in one or various specific cognitive processes. In children, the situation might be more complex: the epileptic process occurs in a period when the cortex is still maturing and it may interfere with normal cerebral development. Although neural plasticity in children is greater than it is in adults, greater plasticity does not necessarily mean adaptive plasticity. Studies have shown that temporal lobe epilepsy in children is not systematically associated with global mental retardation. However, various difficulties in specific cognitive domains are more often found in children than in patients with adult-onset epilepsy. Language, memory, socioperceptive competence, and also executive functions, which can be impaired by the disruption of the temporofrontal circuit, are among such cognitive functions that need to be evaluated. Early detection of specific deficits is of primary importance for the implementation of appropriate remediation measures.     

Neuropsychology and clinical neuroscience of persistent post-concussive syndrome.

On the mild end of the acquired brain injury spectrum, the terms concussion and mild traumatic brain injury (mTBI) have been used interchangeably, where persistent post-concussive syndrome (PPCS) has been a label given when symptoms persist for more than three months post-concussion. Whereas a brief history of concussion research is overviewed, the focus of this review is on the current status of PPCS as a clinical entity from the perspective of recent advances in the biomechanical modeling of concussion in human and animal studies, particularly directed at a better understanding of the neuropathology associated with concussion. These studies implicate common regions of injury, including the upper brainstem, base of the frontal lobe, hypothalamic-pituitary axis, medial temporal lobe, fornix, and corpus callosum. Limitations of current neuropsychological techniques for the clinical assessment of memory and executive function are explored and recommendations for improved research designs offered, that may enhance the study of long-term neuropsychological sequelae of concussion.