The effect of stimulus presentation rate on syntax test performance in brain-injured adolescents

Abstract

The purpose of this study was to explore how testing procedure influences performance after traumatic brain injury, and how this influence varies as a function of the subject's information-processing abilities. Twelve brain-injured subjects completed three versions of the Listening/Grammar subtest of the Test of Adolescent Language. In the first condition, sentences were presented at 2-s intervals, in the second at 4-s intervals, and in the third at variable intervals controlled by the subject. Scores in each condition were correlated with measures of working memory strorage and processing ability. Performance in the 2-s condition was significantly influenced by working memory processing ability, whereas performance in the 4-s condition was significantly influenced by working memory storage ability. Both aspects of working memory contributed to performance in the variable condition, although only processing was significant. As a group, subjects with better working memory processing ability preferred the variable interval condition, which allowed greater flexibility, while subjects with poor processing ability found it more difficult. The results are discussed in terms of clinical assessment and intervention.     

Head injury and dementia

PURPOSE OF REVIEW: The link between head injury and dementia/Alzheimer's disease is controversial. This review discusses some recent epidemiological, human autopsy and experimental studies on the relationship between traumatic head injury and dementia. RECENT FINDINGS: Recent epidemiological studies have shown that head injury is a risk factor for the development of dementia/Alzheimer's disease, whereas others have not. After experimental brain trauma the long-term accumulation of amyloid beta peptide suggests that neurodegeneration is influenced by apolipoprotein E epsilon 4, and after human brain injury both amyloid beta peptide deposition and tau pathology are seen, even in younger patients. Amyloid beta peptide levels in the cerebrospinal fluid and the overproduction of beta amyloid precursor protein in humans and animals after traumatic brain injury are increased. Repeated mild head trauma in both animals and humans accelerates amyloid beta peptide accumulation and cognitive impairment. Retrospective autopsy data support clinical studies suggesting that severe traumatic brain injury with long-lasting morphological residuals are a risk factor for the development of dementia/Alzheimer's disease. The influence of the apolipoprotein E genotype on the prognosis of traumatic brain injury is under discussion. SUMMARY: Although epidemiological studies and retrospective autopsy data provide evidence that a later cognitive decline may occur after severe traumatic brain injury, the relationship between dementia after head/brain trauma and apolipoprotein E status is still ambiguous. Both human postmortem and experimental studies showing apolipoprotein beta deposition and tau pathology after head injury support the link between traumatic brain injury and dementia, and further studies are warranted to clarify this relationship.     

Traumatic brain injury and grey matter concentration: a preliminary voxel based morphometry study

BACKGROUND: Magnetic resonance imaging (MRI) studies have shown diffuse cerebral atrophy following traumatic brain injury. In the past, quantitative volumetric analysis of these changes was carried out by manually tracing specific regions of interest. In contrast, voxel based morphometry (VBM) is a fully automated technique that allows examination of the whole brain on a voxel by voxel basis. OBJECTIVE: To use VBM to evaluate changes in grey matter concentration following traumatic brain injury. METHODS: Nine patients with a history of traumatic brain injury (ranging from mild to severe) about one year previously were compared with nine age and sex matched healthy volunteers. T1 weighted three dimensional MRI images were acquired and then analysed with statistical parametric mapping software (SPM2). The patients with traumatic brain injury also completed cognitive testing to determine whether regional grey matter concentration correlated with a measure of attention and initial injury severity. RESULTS: Compared with controls, the brain injured patients had decreased grey matter concentration in multiple brain regions including frontal and temporal cortices, cingulate gyrus, subcortical grey matter, and the cerebellum. Decreased grey matter concentration correlated with lower scores on tests of attention and lower Glasgow coma scale scores. CONCLUSIONS: Using VBM, regions of decreased grey matter concentration were observed in subjects with traumatic brain injury compared with well matched controls. In the brain injured patients, there was a relation between grey matter concentration and attentional ability.     

Traumatic brain injury and schizophrenia in members of schizophrenia and bipolar disorder pedigrees

OBJECTIVE: Schizophrenia following a traumatic brain injury could be a phenocopy of genetic schizophrenia or the consequence of a gene-environment interaction. Alternatively, traumatic brain injury and schizophrenia could be spuriously associated if those who are predisposed to develop schizophrenia have greater amounts of trauma for other reasons. The authors investigated the relationship between traumatic brain injury and psychiatric diagnoses in a large group of subjects from families with at least two biologically related first-degree relatives with schizophrenia, schizoaffective disorder, or bipolar disorder. METHOD: The Diagnostic Interview for Genetic Studies was used to determine history of traumatic brain injury and diagnosis for 1,275 members of multiplex bipolar disorder pedigrees and 565 members of multiplex schizophrenia pedigrees. RESULTS: Rates of traumatic brain injury were significantly higher for those with a diagnosis of schizophrenia, bipolar disorder, and depression than for those with no mental illness. However, multivariate analysis of within-pedigree data showed that mental illness was related to traumatic brain injury only in the schizophrenia pedigrees. Independent of diagnoses, family members of those with schizophrenia were more likely to have had traumatic brain injury than were members of the bipolar disorder pedigrees. The members of the schizophrenia pedigrees also failed to show the gender difference for traumatic brain injury (more common in men than in women) that was expected and was present in the bipolar disorder pedigrees. Subjects with a schizophrenia diagnosis who were members of the bipolar disorder pedigrees (and thus had less genetic vulnerability to schizophrenia) were less likely to have had traumatic brain injury (4.5%) than were subjects with schizophrenia who were members of the schizophrenia pedigrees (and who had greater genetic vulnerability to schizophrenia) (19.6%). CONCLUSIONS: Members of the schizophrenia pedigrees, even those without a schizophrenia diagnosis, had greater exposure to traumatic brain injury compared to members of the bipolar disorder pedigrees. Within the schizophrenia pedigrees, traumatic brain injury was associated with a greater risk of schizophrenia, consistent with synergistic effects between genetic vulnerability for schizophrenia and traumatic brain injury. Posttraumatic-brain-injury schizophrenia in multiplex schizophrenia pedigrees does not appear to be a phenocopy of the genetic disorder.     

Effect of the dopamine D2 receptor T allele on response latency after mild traumatic brain injury

OBJECTIVE: The authors tested the hypothesis that the dopamine D2 receptor T allele (formerly described as the A1 allele) would be associated with poorer performance on memory and attention tasks following mild traumatic brain injury. METHOD: Thirty-nine patients with mild traumatic brain injury and 27 comparison subjects were genotyped. All subjects completed memory and attention tests, including the California Verbal Learning Test recognition task and the Continuous Performance Test. RESULTS: In both groups the T allele was associated with poorer performance on the California Verbal Learning Test recognition task. There was also a significant diagnosis-by-allele interaction on measures of response latency (Continuous Performance Test): the subjects with mild traumatic brain injury and the T allele had the worst performance. CONCLUSIONS: Genetic polymorphisms modulating central dopaminergic tone can affect cognitive outcome following mild traumatic brain injury.     

An fMRI study of canonical and noncanonical word order in German

Understanding a complex sentence requires the processing of information at different (e.g., phonological, semantic, and syntactic) levels, the intermediate storage of this information and the unification of this information to compute the meaning of the sentence information. The present investigation homed in on two aspects of sentence processing: working memory and reanalysis. Event-related functional MRI was used in 12 healthy native speakers of German, while they read sentences. Half of the sentences had unambiguous initial noun-phrases (masculine nominative, masculine accusative) and thus signaled subject-first (canonical) or object-first (noncanonical) sentences. Noncanonical unambiguous sentences were supposed to entail greater demand on working memory, because of their more complex syntactic structure. The other half of the sentences had case-ambiguous initial noun-phrases (feminine gender). Only the second unambiguous noun-phrase (eighth position in the sentences) revealed, whether a canonical or noncanonical word order was present. Based on previous data it was hypothesized that ambiguous noncanonical sentences required a recomputation of the sentence, as subjects would initially commit to a subject first reading. In the respective contrasts two main areas of brain activation were observed. Unambiguous noncanonical sentences elicited more activation in left inferior frontal cortex relative unambiguous canonical sentences. This was interpreted in conjunction with the greater demands on working memory in the former condition. For noncanonical ambiguous relative to canonical ambiguous sentences, an activation of the left supramarginal gyrus was revealed, which was interpreted as a reflection of the reanalysis-requirements induced by this condition.     

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.     

重型颅脑损伤患者精神障碍的临床分析

目的 探讨重型颅脑损伤后精神障碍的发生率、表现形式及影响因素。方法 以深圳市1999年10月1日至2000年9月30日因交通事故所致重型颅脑损伤的183例幸存者为研究对象,在颅脑损伤治疗后（平均6个月）,由2名精神科副主任医师根据中国精神疾病分类方案与诊断标准第2版修订本对这些伤者的精神状态进行评估。结果 （1）在183例中,罹患各类精神障碍者共165例,发生率为90．2％,其中智能障碍者为142例（77．6％）。（2）在183例,中度及其以上智力损伤者为29例（15．8％）。（3）有智力损伤组的脑干损伤、颅内血肿及≥3个脑叶损伤的比例高于无智力损伤组（P＜0．01）;伴有精神障碍组的平均年龄（P＜0．05）、脑干损伤（P＜0．05）及≥3个脑中损伤（P＜0．01）的比例高于无精神病性障碍组;有人格改变组额叶损伤、开颅清除血肿并减压治疗的比例高于无人格改变组（P＜0．01）。结论 重型颅脑损伤后精神障碍的发生率较高,应引起有关临床学科的重视。     

The costs of freedom: an ERP -- study of non-canonical sentences.

OBJECTIVES: The present investigation explored the electrophysiological correlates of working memory during sentence comprehension.METHODS: Event-related brain potentials (ERP) were recorded from 29 channels in 22 subjects, while they read German sentences having subject-first (canonical) or object-first (non-canonical) word orders.RESULTS: Three different ERP effects were observed: a negativity (maximum at Fc5) differentiating unambiguous object-first and subject-first sentences, interpreted as reflecting the demands of the object-first sentences on working memory; a second negativity (maximum at F7) to the subject noun-phrase in object-first sentences, interpreted as indicating retrieval of verbal material. Finally, a parietal positivity was found for ambiguous sentences that turned out to have a non-canonical word order, which was interpreted as indicating revision and reevaluation processes.CONCLUSIONS: The present data underscore the different roles of working memory in comprehension.     

Brain lesions in patients visiting a memory clinic with postconcussional sequelae after mild to moderate brain injury

Postconcussional disorder after a relatively mild head injury is common. Although a partial organic etiology is presumed, little imaging evidence exists for this assumption. In this study, patients with mild to moderate brain injury (median Glasgow Coma Scale score of 14) had more parenchymal brain lesions than control subjects (P=0.02). Additionally, the authors investigated the potential of quantifying brain injury by the magnetization transfer ratio (MTR). The curve amplitude of the MTR histogram was used as a measure of normal white matter. Patients had a lower curve amplitude than control subjects (P=0.008). This study provides evidence of persistent traumatic brain alterations in patients who sustained a relatively mild traumatic brain injury.     

Morphometric MRI findings in the thalamus and brainstem in children after moderate to severe traumatic brain injury

Generalized whole brain volume loss is well documented in moderate to severe traumatic brain injury. Whether this atrophy occurs in the thalamus and brainstem has not been systematically studied in children. Magnetic resonance imaging (MRI) quantitative analysis was used to investigate brain volume loss in the thalamus and brainstem in 16 traumatic brain injury subjects (age range 9-16 years) compared with 16 age and demo-graphically matched controls. Based on multiple analysis of covariance, controlling for age and head size, reduced volume in the thalamus and the midbrain region of the brainstem were found. General linear model analyses revealed a relation between processing speed on a working memory task and midbrain and brain stem volumes. Reduced volume in thalamic and brainstem structures were associated with traumatic brain injury. Reduction in midbrain and thalamic volume is probably a reflection of the secondary effects of diffuse axonal injury and reduction in cortical volume from brain injury.     

Changes in social emotion recognition following traumatic frontal lobe injury

Changes in social and emotional behaviour have been consistently observed in patients with traumatic brain injury. These changes are associated with emotion recognition deficits which represent one of the major barriers to a successful familiar and social reintegration. In the present study, 32 patients with traumatic brain injury, involving the frontal lobe, and 41 ageand education-matched healthy controls were analyzed. A Go/No-Go task was designed, where each participant had to recognize faces representing three social emotions (arrogance, guilt and jealousy). Results suggested that ability to recognize two social emotions (arrogance and jealousy) was significantly reduced in patients with traumatic brain injury, indicating frontal lesion can reduce emotion recognition ability. In addition, the analysis of the results for hemispheric lesion location (right, left or bilateral) suggested the bilateral lesion sub-group showed a lower accuracy on all social emotions.     

Reaction time after head injury: fatigue, divided and focused attention, and consistency of performance.

Three groups of patients who had suffered head injury were compared with matched control subjects on reaction time (RT) tasks. Group I consisted of outpatients previously hospitalised for head injury of wide ranging degrees of severity, assessed at varying intervals after injury. Group II was composed of non-hospitalised mildly concussed patients. Group III was made up of head injured patients of varying degrees of severity assessed 7-10 months after initial hospitalisation for their injury. The reaction time tests were graded in difficulty, from a simple RT response to a complex choice RT test. In addition, subjects were compared in their ability to ignore redundant information during one of the choice RT tests. The findings indicate that traumatic brain injury causes slower information processing, deficits in divided attention, an impairment of focused attention, and inconsistency of performance.     

Melatonin reduces traumatic brain injur y-induced oxidative stress in the cerebral cortex and blood of rats

Free radicals induced by traumatic brain injury have deleterious effects on the function and antioxidant vitamin levels of several organ systems including the brain. Melatonin possesses antioxidant effect on the brain by maintaining antioxidant enzyme and vitamin levels. We investigated the effects of melatonin on antioxidant ability in the cerebral cortex and blood of traumatic brain injury rats. Results showed that the cerebral cortex β-carotene, vitamin C, vitamin E, reduced glutathione, and erythrocyte reduced glutathione levels, and plasma vitamin C level were decreased by traumatic brain injury whereas they were increased following melatonin treatment. In conclusion, melatonin seems to have protective effects on traumatic brain injury-induced cerebral cortex and blood toxicity by inhibiting free radical formation and supporting antioxidant vitamin redox system.     

Sleep disturbance after mild traumatic brain injury: indicator of injury?

Mild traumatic brain injury (mTBI) is a complex entity with no known objective diagnostic markers. To test the hypothesis that sleep disturbances in the acute mTBI period can serve as an indicator of brain injury, the authors compared sleep polysomnograms (PSG) and sleep EEG power spectra (PS) data in seven mTBI subjects with seven age- and race-matched healthy-control subjects. The two groups differed significantly on PS measures, suggesting that mTBI can result in a disruption of sleep microarchitecture and, in theory, could be of use as a marker for brain injury. These pilot findings need to be replicated on larger samples.     

Inhibition of extracellular vesicle pathway using neutral sphingomyelinase inhibitors as a neuroprotective treatment for brain injury

Traumatic brain injury is a sudden trauma or blow on the head, and severe traumatic brain injury is a major cause of death and disability worldwide. The acute and chronic consequences following traumatic brain injury can lead to progressive secondary neurodegenerative changes and cognitive dysfunction. To date, there is no effective pharmaceutical products for the treatment to reduce secondary damage after brain injury. The discovery of extracellular vesicles has attracted considerable scientific attention due to their role in cell-to-cell communication. Extracellular vesicles have shown their potential to carry not only biological molecules but also as a drug delivery vehicle. As a carrier of molecular information, extracellular vesicles have been involved in physiological functions as well as in the modulation of immune responses. Here, we aim to provide new insights into the contrasting role of extracellular vesicles in the propagation of inflammatory responses after brain injury. As a carrier of pro-inflammatory molecules, their role as functional mediators in the pathophysiology of brain injury is discussed, addressing the inhibition of the extracellular vesicle pathway as an anti-inflammatory or neuroprotective approach to improve the outcome of both acute and chronic inflammation following brain injury. Here, we summarize therapeutic strategies to diminish the risk the neurodegeneration post brain injury and propose that neutral sphingomyelinase inhibitors could be used as potentially useful therapeutic agents for the treatment of brain injury associated neuroinflammation.     

MRI findings and Axis I and II psychiatric disorders after traumatic brain injury: a 30-year retrospective follow-up study

We studied the association between psychiatric disorders and the presence and location of traumatic lesions on magnetic resonance imaging (MRI) in 58 patients, on average, 30 years after traumatic brain injury. Axis I psychiatric disorders that had begun after the injury were assessed with the Schedules for Clinical Assessment in Neuropsychiatry (version 2.1), and Axis II disorders with the Structured Clinical Interview for DSM-III-R Personality Disorders. A 1.5-Tesla MRI scanner was used. One-third of the subjects had traumatic lesions visible on MRI. Only three psychiatric disorders, that is, delusional disorder, dementia, and the disinhibited type of organic personality syndrome, were significantly more common in subjects with contusions. Concerning the location of contusions, organic personality syndrome and its disinhibited subtype were associated with frontal lesions, and major depression was, surprisingly, inversely associated with temporal lesions. These results, which should be interpreted with caution due to the limited size of the study group, suggest that the majority of psychiatric disorders after traumatic brain injury are not closely related to the specific location or even the presence of contusions detectable with post-acute MRI.     

N200 latency and P300 amplitude in depressed mood post-traumatic brain injury patients

In order to examine the independent and combined effects of depressive symptoms and traumatic brain injury on event-related potential (ERP) components, we classified traumatic brain injury (TBI) patients as depressed and non-depressed mood according to their scores on the Zung Self-rating Depression Scale (SDS). Non-depressed mood post-traumatic brain injury patients (NondepTBI, n=9), depressed mood post-traumatic brain injury patients (DepTBI, n=26), and normal healthy control subjects (HC, n=10) were assessed for N100, N200, and P300 latencies and amplitudes by the auditory "oddball paradigm". DepTBI subjects had significantly prolonged N200 latency and low P300 amplitude compared with the NondepTBI and HC groups. A longer P300 latency in the NondepTBI and DepTBI than in the HC groups was found. A prolongation of N200 latency accompanied by low P300 amplitude may be a characteristic of post-traumatic brain injury patients with depressed mood. Prolonged P300 latency may be more closely associated with TBI than with depression, as it was significantly greater in both the DepTBI and NondepTBI, than in the HC group.     

Altered physiology of gastrointestinal vagal afferents following neurotrauma

The adaptability of the central nervous system has been revealed in several model systems.Of particular interest to central nervous system-injured individuals is the ability for neural components to be modified for regain of function. In both types of neurotrauma, traumatic brain injury and spinal cord injury, the primary parasympathetic control to the gastrointestinal tract, the vagus nerve, remains anatomically intact. However, individuals with traumatic brain injury or spinal cord injury are highly susceptible to gastrointestinal dysfunctions. Such gastrointestinal dysfunctions attribute to higher morbidity and mortality following traumatic brain injury and spinal cord injury. While the vagal efferent output remains capable of eliciting motor responses following injury, evidence suggests impairment of the vagal afferents. Since sensory input drives motor output, this review will discuss the normal and altered anatomy and physiology of the gastrointestinal vagal afferents to better understand the contributions of vagal afferent plasticity following neurotrauma.     

Vulnerability of the anterior commissure in moderate to severe pediatric traumatic brain injury

In relation to the adult brain, the immature brain might be more vulnerable to damage during and following traumatic brain injury, particularly in white-matter tracts. Given well-established evidence of corpus callosum atrophy, we hypothesized that anterior commissure volume (using quantitative magnetic resonance imaging [MRI]) in this structure would be decreased in children with moderate to severe traumatic brain injury relative to typically developing children. Second, given the purported role of the anterior commissure in interhemispheric axon conveyance between temporal lobes, we hypothesized that temporal lobe white matter, temporal lesion volume, and injury severity (Glasgow Coma Scale score) would be predictive of decreased anterior commissure cross-sectional volume in patients with traumatic brain injury. Finally, we wished to establish the relationship between the anterior commissure and the temporal stem, a major white-matter tract into the temporal lobes, using diffusion tensor imaging fiber-tracking maps for each patient. We also hypothesized that children with traumatic brain injury would exhibit decreased fractional anisotropy in relation to typically developing children in a fiber system including the anterior commissure and the temporal lobes. Decreased anterior commissure cross-sectional volume was observed in patients with traumatic brain injury, and, as predicted, anterior commissure and temporal white-matter volumes were positively related to each other and to higher Glasgow Coma Scale scores. Lesion volume was not independently predictive of anterior commissure volume in the overall model. Diffusion tensor imaging fractional anisotropy values differed between the groups for the temporal stem-anterior commissure system, with the traumatic brain injury group exhibiting decreased fractional anisotropy. The anterior commissure, like the corpus callosum, appears to be highly vulnerable to white-matter degenerative changes resulting from mechanisms such as the direct impact of trauma, progressive axonal injury as tissue in other brain regions atrophies, or myelin degeneration. This is the first systematic examination of anterior commissure atrophy following traumatic brain injury using in vivo quantitative MRI and diffusion tensor imaging fiber tracking in pediatric subjects.