Working memory brain activation following severe traumatic brain injury

Functional magnetic resonance imaging (fMRI) has shown that brain activation during performance of working memory (WM) tasks under high memory loads is altered in adults with severe traumatic brain injury (TBI) relative to uninjured subjects (Perlstein et al., 2004; Scheibel et al., 2003). Our study attempted to equate TBI patients and orthopedically injured (OI) subjects on performance of an N-Back task that used faces as stimuli. To minimize confusion in TBI patients that was revealed in pilot work, we presented the memory conditions in two separate tasks, 0- versus 1-back and 0- versus 2-back. In the 0- versus 1-back task, OI subjects activated bilateral frontal areas more extensively than TBI patients, and TBI patients activated posterior regions more extensively than OI subjects. In the 0- versus 2-back task, there were no significant differences between the groups. Analysis of changes in activation over time on 1-back disclosed that OI subjects had decreases in bilateral anterior and posterior regions, while TBI patients showed activation increases in those and other areas over time. In the 2-back condition, both groups showed decreases over time in fusiform and parahippocampal gyri, although the OI group also showed increases over time in frontal, parietal, and temporal areas not seen in the TBI patients. The greatest group differences were found in the 1-back condition, which places low demand on WM. Although the extent of activation in the 2-back condition did not differ between the two groups, deactivation in the 2-back condition was seen in the OI patients only, and both groups' patterns of activation over time varied, suggesting a dissociation between the TBI and OI patients in recruitment of neural areas mediating WM.     

Cancelling planned actions following mild traumatic brain injury

Mild traumatic brain injury (mTBI) leads to a variety of attentional, cognitive, and sensorimotor deficits. An important aspect of behavior that intersects each of these functions is the ability to cancel a planned action. Thus, the purpose of this study was to determine the effects of mTBI on the ability to perform a countermanding saccade task. In this task, participants were asked to generate a saccade to a target appearing in peripheral vision, but to inhibit saccade execution if an auditory stop signal was presented. The delay between the appearance of the peripheral target and the presentation of the auditory stop signal was varied between 0 and 125ms. We found that the change in the probability of cancelling the saccade as a function of this delay was no different between participants with mTBI tested within 2 days of their injury and matched controls. However, saccadic reaction times and the stop signal reaction time were unexpectedly faster in the participants with mTBI and, furthermore, they inaccurately inhibited saccades during 15% of the trials with no stop signal. Taken together, this data suggests that the ability to cancel planned actions is subtly yet adversely affected by mTBI.     

A meta-analysis of task-related influences in prospective memory in traumatic brain injury

Prospective memory is the ability to remember to do something in the future and it is essential to every-day functional independence. Traumatic brain injury is associated with frequent and persistent prospective memory deficits. This study presents a review and meta-analysis investigating the effects of task parameters on prospective memory performance of individuals with TBI. Individual studies using continuous behavioural measures of prospective memory with a sample of adults with TBI and matched controls were included. Consistent with previous research, a random effects meta-analysis indicated that TBI groups demonstrated lower prospective memory performance than control groups (d?=?1.10, SE?=?0.12, 95% CI?=?0.86–1.34). In addition, we found that type of prospective memory cue, saliency of cues, and complexity of the ongoing task significantly moderated the difference in prospective memory performance between TBI and control groups. These findings suggest that prospective memory task parameters should be considered in the assessment of prospective memory in individuals with cognitive impairment. In addition, considering the influence of these task parameters would be useful to develop effective compensatory strategies to reduce prospective memory failures.     

Recovery of episodic memory subprocesses in mild and complicated mild traumatic brain injury at 1 and 12 months post injury

Introduction: Episodic memory complaints are commonly reported after traumatic brain injury (TBI). The contributions of specific memory subprocesses (encoding, consolidation, and retrieval), however, are not well understood in mild TBI (mTBI). In the present study, we evaluated subprocesses of episodic memory in patients with mTBI using the item-specific deficit approach (ISDA), which analyzes responses on list learning tasks at an item level. We also conducted exploratory analyses to evaluate the effects of complicated mTBI (comp-mTBI) on memory. Method: We compared episodic verbal memory performance in mTBI (n = 92) at approximately 1 and 12 months post TBI, as well as in a healthy comparison (HC) group (n = 40) at equivalent time points. Episodic memory was assessed using the California Verbal Learning Test–2nd Edition (CVLT–II), and both standard CVLT–II scores and ISDA indices were evaluated. Results: Compared to the HC group, the mTBI group showed significantly poorer encoding and learning across time, as measured by ISDA and CVLT–II. Further analyses of these mTBI subgroups [(noncomplicated mTBI (NC-mTBI, n = 77) and comp-mTBI (n = 15)], indicated that it was the comp-mTBI group who continued to demonstrate poorer encoding ability than the HC group. When the patient groups were directly compared, the NC-mTBI group improved slightly on the ISDA Encoding Deficit Index. While the comp-mTBI group worsened slightly over time, their poorer encoding ability was not likely clinically meaningful. Conclusions: These findings indicate that, while the NC-mTBI and HC groups’ performances were comparable by 12 months, a primary, long-term deficit in encoding of auditory verbal information remained problematic in the comp-mTBI group.     

Antisaccades and remembered saccades in mild traumatic brain injury

The most common site of focal lesions after mild traumatic brain injury (MTBI) is the frontal lobe. This lobe, however, is difficult to examine clinically. Neuroimaging is not performed routinely and usually shows normal results in uncomplicated trauma. Antisaccades (AS) and remembered saccades (RS) are neuro-ophthalmological tests of frontal function. This study examined whether there are disturbances of latency time or error rate of AS and RS in patients within 24 h after MTBI. Eye movements were studied with infrared-oculography. Data were obtained prospectively from 25 patients. An additional group of 6 patients with MTBI and alcohol intoxication were also examined. No statistical differences in AS or RS, either for errors or for latency time, were found between a group of age-matched controls and the patients, except in the group of alcohol-intoxicated MTBI patients. Our findings indicate that visual reflex inhibition and initiation of voluntary saccades were not disturbed in the nonintoxicated patients. It is hypothesized that the responsible frontal area was not affected. It is concluded that error rate and latency time of AS and RS are inappropriate measures for evaluating acute MTBI. Received: 27 July 1998/Received in revised form: 8 February 1999/Accepted: 6 September 1999     

Perceived importance of prospective memory failures in adults with traumatic brain injury

Prospective memory (PM) is the ability to carry out an intended action in the future. Failures in PM are often observed as more frequent in individuals with traumatic brain injury (TBI) than controls. However, it remains unknown how individuals with TBI and their significant others perceive the importance of these PM problems. In the current study, four groups (38 TBI, 34 TBI-other, 34 controls, 31 control-other) were recruited to report on the perceived importance of PM failures using Part B of the Comprehensive Assessments of Prospective Memory (CAPM). Individuals with TBI perceived PM failures as being more important than did their significant others. Controls' ratings did not differ from their significant others. There were no statistically significant differences in rated importance for PM problems involving the basic activities of daily living (BADL) component and those involving the instrumental activities of daily living (IADL) component. Implications of the results are discussed in terms of the motivation of people with TBI.     

Prospective memory intervention using visual imagery in individuals with brain injury

Prospective memory deficits are common after brain injury and can create impediments to independent living. Most approaches to management of such deficits are compensatory, such as the use of notebooks or electronic devices. While these can be effective, a restorative approach, in theory, could lead to greater generalisation of treatment. In the current study a metacognitive technique, using visual imagery, was employed under conditions of rote repetition and spaced retrieval. Treatment was provided in an AB-BA crossover design with A as the active treatment and B as a no-treatment attention control to 20 individuals with brain injury. A group of 20 healthy participants served to control for effects of re-testing. Individuals with brain injury demonstrated improvement on the main outcome measure of prospective memory, the Memory for Intentions Screening Test, only after the active treatment condition. In addition, some generalisation of treatment was measured in daily life. Moreover, treatment gains were maintained for one year after treatment was completed.     

大鼠轻型颅脑损伤后星形胶质细胞与神经元的病理改变

目的 探讨轻型颅脑损伤（TBI）后神经元及星形胶质细胞改变的病理生理过程。方法 将24只成年SD大鼠随机分为轻型TBI组（n=18）和假手术组（n=6）,轻型TBI组又分为伤后3 h（n=6）、伤后24 h（n=6）、伤后72 h（n=6）三亚组。采用液压冲击法制作轻型TBI模型。采用胶质纤维酸性蛋白（GFAP）染色检测星形胶质细胞,采用Fluoro-Jade B（FJ-B）荧光染色检测变性神经元。结果 与假手术组相比,轻型TBI后3 h、24 h、72 h邻近顶叶皮质、海马CA2/3区GFAP阳性细胞数量均明显减少（P<0.05）;缺失区周围星形胶质细胞肿胀增生明显。FJ-B阳性神经元在损伤后3 h无明显增加（P>0.05）,伤后24 h皮层区FJ-B阳性神经元显著增加（P<0.05）,伤后72 h海马区FJ-B阳性神经元显著增加（P<0.05）。伤后72 h伤侧皮层区与海马区GFAP阳性细胞数和FJ-B阳性细胞数呈显著负相关（r=-0.8285,P<0.05）。结论 轻型TBI后星形胶质细胞超急性期（3 h）即出现损害和胶质反应,神经元则在急性期（24 h）至亚急性期（72 h）出现明显损害,星形胶质细胞缺失程度可以反应神经元损伤程度。     

Three versus seven days to return-to-work after mild traumatic brain injury: a randomized parallel-group trial with neuropsychological assessment

Although most patients with a mild traumatic brain injury (mTBI) recover within days to weeks, some experience persistent physical, cognitive and emotional symptoms, often described as post-concussion syndrome (PCS). The optimal recovery time including return-to-work (RTW) after mTBI is unclear. In this single-centre parallel-group trial, patients assigned three days (3D-group) or seven days (7D-group) sick leave were compared with a comprehensive neuropsychological test battery including the Post-Concussion Symptom Scale (PCSS) within one week, after three and 12 months post-injury. The influence of the effective time until RTW on post-concussional symptoms and cognitive performance was analysed. The 3D-group rated significantly higher mean scores in some PCSS symptoms, tended to fulfil diagnosis criteria of PCS more often and showed better cognitive performance in several neuropsychological test scores than the 7D-group at all three time-points of follow-up. Overall, patients returned to work 11.35 d post-injury, thus distinctly above both recommended sick leaves. There was a trend for longer sick leave in patients randomized into the 3D-group. Further analyses revealed that the group with an absolute RTW within one week showed lower symptom severity in fatigue at 3 and 12 months, less PCS and faster performance in fine motor speed at 12 months than the group with an absolute RTW after one week. Our data underline the heterogeneity of mTBI and show that acute and sub-acute symptoms are not prognostic factors for neuropsychological outcome at one year. Later, ability to work seems to be prognostic for long-term occurrence of PCS.     

Long term outcome following mild traumatic brain injury in Moroccan patients

Primary objectives

To describe the symptoms of chronic post-concussion syndrome (PCS) and to investigate the relationship between the persistence of these symptoms and different aspects of social life (return to work, quality of life, sport and leisure activities and family relationships) in Moroccan patients with mild traumatic brain injury (MTBI), one year after the trauma.

Methods

Forty-two adult patients who sustained MTBI were reviewed one year after trauma. We investigated the persistence of PCS by using the “Problem Checklist” questionnaire. We also assessed their quality of life using a visual analogue scale, and noted the changes in employment status, social activities and family relationships. Then, we examined whether there were significant relationships between these different data.

Results

More than half of the patients (n = 23, 54.8%) were found with persistent post-concussion symptoms at one year post-injury. Chronic PCS was significantly more common in married persons (p = 0.008) and significantly related to both non return to work (p ≤ 0.01), and QoL deterioration (p ≤ 0.001).

Conclusion

In this study, a large proportion of persons who sustained a MTBI experienced persistent symptoms up to one year after trauma. MTBI might have significant and lasting impact on the quality of life, which is to be verified by further studies.     

Effect of depression on cognition after mild traumatic brain injury in adults

Objective: The current study examined the effect of depression on cognitive test performance in a sample of adults seeking treatment for a mild traumatic brain injury (MTBI). We hypothesized that patients with greater depressive symptoms would perform worse on tasks of fluid cognition compared to those without depression, after controlling for potential confounds.

Method: Patients (N = 76) completed a brief cognitive test battery (NIH Toolbox Cognition Battery; NIHTB-CB) and a depression screening questionnaire (PHQ-9) at 11.7-weeks post injury (SD = 6.3 range 2–26). Cognitive scores were adjusted for age, education, gender, and race/ethnicity. Depressive symptoms were examined continuously and dichotomized as: (1) total PHQ-9 score of ≥ 10, the optimal cut-off for Major Depressive Disorder caseness from prior research, and (2) five or more symptoms of depression, including either depressed mood or anhedonia (i.e. DSM-5-based definition).

Results: Twenty-seven patients (35.5%) met DSM-5-based criteria for depression and 42 (55.3%) met criteria based on PHQ-9 > 10. Depression symptom severity correlated with lower fluid cognition composite scores [r = ?.22, p = .05] and contributed to the prediction of fluid cognition performance in a model that controlled for time since injury and crystallized cognitive abilities [F(3, 72) = 7.49, p < .001; R² = 20.6%]. Examining specific NIHTB-CB fluid subtests, the largest group differences were seen on processing speed (d = .40–.49), cognitive flexibility (d = .32–.36), and episodic memory (d = .20–.34). Depression severity was strongly associated with overall post-concussion symptom burden (r = .77, p < .001).

Conclusion: Depression is a common comorbidity and an important factor to consider when interpreting neurocognitive test performance in adults with concussion in a clinical setting.     

Correlation between standardized assessment of concussion scores and small-world brain network in mild traumatic brain injury

This study investigated the characteristics of the small-world brain network architecture of patients with mild traumatic brain injury (MTBI), and a correlation between brain functional connectivity network properties in the resting-state fMRI and Standardized Assessment of Concussion (SAC) parameters. The neurological conditions of 22 MTBI patients and 17 normal control individuals were evaluated according to the SAC. Resting-state fMRI was performed in all subjects 3 and 7 days after injury respectively. After preprocessing the fMRI data, cortex functional regions were marked using AAL90 and Dosenbach160 templates. The small-world network parameters and areas under the integral curves were computed in the range of sparsity from 0.01 to 0.5. Independent-sample t-tests were used to compare these parameters between the MTBI and control group. Significantly different parameters were investigated for correlations with SAC scores; those that correlated were chosen for further curve fitting. The clustering coefficient, the communication efficiency across in local networks, and the strength of connectivity were all higher in MTBI patients relative to control individuals. Parameters in 160 brain regions of the MTBI group significantly correlated with total SAC score and score for attention; the network parameters may be a quadratic function of attention scores of SAC and a cubic function of SAC scores. MTBI patients were characterized by elevated communication efficiency across global brain regions, and in local networks, and strength of mean connectivity. These features may be associated with brain function compensation. The network parameters significantly correlated with SAC total and attention scores.     

Functional magnetic resonance imaging of mild traumatic brain injury

Functional magnetic resonance imaging (fMRI) offers great promise for elucidating the neuropathology associated with a single or repetitive mild traumatic brain injury (mTBI). The current review discusses the physiological underpinnings of the blood-oxygen level dependent response and how trauma affects the signal. Methodological challenges associated with fMRI data analyses are considered next, followed by a review of current mTBI findings. The majority of evoked studies have examined working memory and attentional functioning, with results suggesting a complex relationship between cognitive load/attentional demand and neuronal activation. Researchers have more recently investigated how brain trauma affects functional connectivity, and the benefits/drawbacks of evoked and functional connectivity studies are also discussed. The review concludes by discussing the major clinical challenges associated with fMRI studies of brain-injured patients, including patient heterogeneity and variations in scan-time post-injury. We conclude that the fMRI signal represents a complex filter through which researchers can measure the physiological correlates of concussive symptoms, an important goal for the burgeoning field of mTBI research.     

Central nervous system microbleeds in the acute phase are associated with structural integrity by DTI one year after mild traumatic brain injury: A longitudinal study

Introduction

Several imaging modalities are under investigation to unravel the pathophysiological mystery of delayed performance deficits in patients after mild traumatic brain injury (mTBI). Although both imaging and neuropsychological studies have been conducted, only few data on longitudinal correlations of diffusion tensor imaging (DTI), susceptibility weighted imaging (SWI) and extensive neuropsychological testing exist.

Auditory evoked brain potentials as markers of chronic effects of mild traumatic brain injury in mid-life

ObjectiveAuditory event-related potential (ERP) correlates of pre-dementia in late-life may also be sensitive to chronic effects of mild traumatic brain injury (mTBI) in mid-life. In addition to mTBI history, other clinical factors may also influence ERP measures of brain function. This study’s objective was to evaluate the relationship between mTBI history, auditory ERP metrics, and common comorbidities.MethodsERPs elicited during an auditory target detection task, psychological symptoms, and hearing sensitivity were collected in 152 combat-exposed veterans and service members, as part of a prospective observational cohort study. Participants, with an average age of 43.6 years, were grouped according to positive (n = 110) or negative (n = 42) mTBI history. Positive histories were subcategorized into repetitive mTBI (3 + ) (n = 40) or non-repetitive (1–2) (n = 70).ResultsPositive history of mTBI was associated with reduced N200 amplitude to targets and novel distractors. In participants with repetitive mTBI compared to non-repetitive and no mTBI, P50 was larger in response to nontargets and N100 was smaller in response to nontargets and targets. Changes in N200 were mediated by depression and anxiety symptoms and hearing loss, with no evidence of a supplementary direct mTBI pathway.ConclusionsAuditory brain function differed between the positive and negative mTBI groups, especially for repetitive injury, which implicated more basic, early auditory processing than did any mTBI exposure. Symptoms of internalizing psychopathology (depression and anxiety) and hearing loss are implicated in mTBI’s diminished brain responses to behaviorally relevant and novel stimuli.SignificanceA mid-life neurologic vulnerability conferred by mTBI, particularly repetitive mTBI, may be detectable using auditory brain potentials, and so auditory ERPs are a target for study of dementia risk in this population.     

Mild traumatic brain injury and executive functions in school-aged children

Objective: This study sought to examine the effects of mild traumatic brain injury (TBI) on executive functions in school-aged children.

Participants and method: The prospective, longitudinal study involved 8–15 year old children, 186 with mild TBI and 99 with mild orthopaedic injuries (OI). They were administered the Stockings of Cambridge and Spatial Working Memory sub-tests from the Cambridge Neuropsychological Testing Automated Battery (CANTAB) ～10 days, 3 months and 12 months post-injury. Parents completed the Behavior Rating Inventory of Executive Functions (BRIEF) on each occasion, with ratings at the initial assessment intended to assess pre-morbid functioning retrospectively.

Results: On the CANTAB, the groups did not differ on the Stockings of Cambridge and the mild TBI group unexpectedly performed better than the OI group on Spatial Working Memory. On the BRIEF, children with mild TBI showed a marginally significant trend toward more problems than the OI group on the Metacognition Index composite. The only BRIEF sub-scale on which they demonstrated significantly more problems was Organization of Materials. The presence of intracranial abnormalities on MRI was associated with more problems on the BRIEF Organization of Materials sub-scale at 3 months, but other findings were not consistent with hypothesized effects of TBI severity. The CANTAB sub-tests were significant predictors of later ratings on the BRIEF, but accounted for modest variance.

Discussion: Children with mild TBI show limited evidence of deficits in executive functions, either cognitively or behaviourally, irrespective of injury characteristics. Cognitive tests of executive functions are modest predictors of ratings of executive functions in everyday life, for children both with and without mild TBI.     

亚低温治疗重型外伤性颅脑损伤的临床对照观察

目的 比较亚低温治疗和常温治疗重型外伤性颅脑损伤的治疗效果,方法 50例重型颅脑损伤患者随机分为常温组26例和亚低温组24例.入院后病人均持续监测颅内压7 d.对照组维持正常体温,亚低温组入院后在3～7 h内将肛温降至33℃左右,并维持3～7 d.比较2组GCS评分、颅内压、临床预后指标.结果 在伤后第7天,亚低温组和...     

Factor analysis of the everyday memory questionnaire in persons with traumatic brain injury

Objectives: To investigate the factor structure of the Everyday Memory Questionnaire (EMQ) in persons with traumatic brain injury (TBI). Method: This was a secondary analysis of baseline data from two clinical trials targeting memory impairment after TBI. Participants were 169 persons with complicated mild, moderate, or severe TBI at an average of 41 months post-injury. They completed the EMQ via clinical interview. Exploratory factor analysis was conducted using a three-factor principal axis factoring estimation method with a polychoric correlation matrix and oblique rotation. Results: The three factors accounted for 49.2% of the variance, with moderate correlations observed among the factors. The three factors appeared to represent general everyday memory (prospective and episodic), conversational memory, and spatial or action memory. The three factors added significantly to the variance in age-corrected objective learning test scores predicted by injury severity, education, and sex. Conclusions: The three factors of the EMQ are consistent with the heterogeneity of memory impairments observed after TBI. The factor scores may be used to target treatments for impaired memory and to evaluate their effectiveness.     

亚低温在治疗急性颅脑创伤中的疗效和争议

二十世纪90年代初,国内外对亚低温脑保护的作用有了新认识。动物实验研究发现亚低温对实验性颅脑外伤具有显著的治疗保护作用。大多数前瞻性临床应用研究发现30～33℃亚低温能显著降低重型颅脑伤患者的死残率。但美国Clifton教授牵头的9个医学中心合作研究发现亚低温治疗组与对照组无统计学差异.仅能显著提高GCS 6～8分、年龄<45岁、伤后6h内达到亚低温水平的病人的治疗效果。最近一项欧州5家医院多中心前瞻性随机临床研究结果令人兴奋,他们研究证明亚低温对心跳骤停脑缺血缺氧病人有显著治疗保护作用。目前国内外有关亚低温治疗的争议焦点是亚低温治疗的指征、时间窗和时程。     

A rodent model of mild traumatic brain blast injury

One of the criteria defining mild traumatic brain injury (mTBI) in humans is a loss of consciousness lasting for less than 30 min. mTBI can result in long‐term impairment of cognition and behavior. In rats, the length of time it takes a rat to right itself after injury is considered to be an analog for human return to consciousness. This study characterized a rat mild brain blast injury (mBBI) model defined by a righting response reflex time (RRRT) of more than 4 min but less than 10 min. Assessments of motor coordination relying on beam‐balance and foot‐fault assays and reference memory showed significant impairment in animals exposed to mBBI. This study's hypothesis is that there are inflammatory outcomes to mTBI over time that cause its deleterious effects. For example, mBBI significantly increased brain levels of interleukin (IL)?1β and tumor necrosis factor‐α (TNFα) protein. There were significant inflammatory responses in the cortex, hippocampus, thalamus, and amygdala 6 hr after mBBI, as evidenced by increased levels of the inflammatory markers associated with activation of microglia and macrophages, ionized calcium binding adaptor 1 (IBA1), impairment of the blood–brain barrier, and significant neuronal losses. There were significant increases in phosphorylated Tau (p‐Tau) levels, a putative precursor to the development of neuroencephalopathy, as early as 6 hr after mBBI in the cortex and the hippocampus but not in the thalamus or the amygdala. There was an apparent correlation between RRRTs and p‐Tau protein levels but not IBA1. These results suggest potential therapies for mild blast injuries via blockade of the IL‐1β and TNFα receptors. © 2014 Wiley Periodicals, Inc.