Assessment of story comprehension deficits after brain damage

A story comprehension task was specifically developed for the clinical diagnosis of text comprehension deficits. The performance of 49 healthy control participants on qualitatively different Yes/No questions confirmed that both salience and explicitness of information had an impact on question difficulty. An unselected group of brain damaged patients (n = 96) made more errors, particularly on questions about implicit information. The subgroup of patients with left-hemispheric vascular aetiology (n = 18) had particular difficulties with stated details, patients with right-hemispheric vascular aetiology (n = 12) with implicit main ideas, and patients with traumatic brain injury (n = 34) were most impaired on implicit information. Correlations with neuropsychological test scores also confirmed that the questions successfully tapped different subprocesses of comprehension. Performance on implicit main ideas was correlated with tests of executive functions, whereas the performance on the other three question types was correlated with long-term memory and verbal learning. These results suggest that the story comprehension test is a useful diagnostic tool for neuropsychological assessment.     

Neuropharmacological modulation of cognitive deficits after brain damage

PURPOSE OF REVIEW: This review discusses recent studies that have implications for potential neuropharmacological interventions which target cognitive deficits resulting from traumatic brain injury or stroke. RECENT FINDINGS: An important new study concerning the activity of N-methyl-D-aspartate (NMDA) receptors after brain injury reveals that previous influential hypotheses about an increase in glutamate triggering neuronal death may need to be revised. Furthermore, the study suggests that cognitive function may be best preserved by stimulation of NMDA receptors with agonists rather than by the use of antagonists, as previously believed. Investigations of animal models of stroke and traumatic brain injury have further demonstrated the possibility of intervening in the acute and sub-acute stages to protect specific brain systems, such as preservation of the cholinergic system (via cholinesterase inhibitors) and hippocampal neurons (via a D2 agonist). Clinical trials in humans indicate it is also possible to target these neurotransmitter systems to enhance cognitive performance in patients with chronic deficits. In particular, recent studies demonstrated that it is possible to ameliorate the effects of two common cognitive syndromes, visual neglect and aphasia. SUMMARY: Cognitive deficits are an extremely common consequence of either traumatic brain injury or stroke. Recent studies demonstrate the potential for using neuropharmacological intervention after acquired brain injury to prevent or ameliorate the effects of cognitive impairments. These treatments, however, are still in their preliminary stages and further research is required to identify the most effective compounds.     

Neuroimmune aspects of brain damage after focal ischemia

We have studied the level of products of nitrosative stress, immunoglobulins, and antibodies against nitrated proteins in the cerebrospinal fluid (CSF) and in the neocortex of rats 24 hours after focal ischemia. In the acute stage after ischemia, the level of metabolites of nitric oxide, nitrate, and nitrite, significantly increased in the CSF and in the ischemic neocortex of the animals. In addition, in the CSF of rats, the level of immunoglobulins (Ig) significantly increased and the nitrotyrosine-BSA binding was enhanced. Immunochemical staining of the sections of the brain by anti-rat Ig antibodies revealed their presence in the ischemic focus but not in the contralateral hemisphere. In the ischemic hemisphere in some Ig-positive cells, we observed colocalization of staining with the pro-apoptotic protein Bax. At this stage, in the ischemic hemisphere a membrane attack complex, the product of the terminal stage of complement activation, was detected by immunohistochemistry. Thus, the development of an immune response during the acute stage after experimental stroke is associated with some features of apoptotic cell death and seems to a certain extent to be modulated by nitrosative stress products, such as proteins modified by nitration.     

Tacrolimus, a potential neuroprotective agent, ameliorates ischemic brain damage and neurologic deficits after focal cerebral ischemia in nonhuman primates.

Tacrolimus (FK506), an immunosuppressive drug, is known to have potent neuroprotective activity and attenuate cerebral infarction in experimental models of stroke. Here we assess the neuroprotective efficacy of tacrolimus in a nonhuman primate model of stroke, photochemically induced thrombotic occlusion of the middle cerebral artery (MCA) in cynomolgus monkeys. In the first experiment, tacrolimus (0.01, 0.032, or 0.1 mg/kg) was intravenously administered immediately after MCA occlusion, and neurologic deficits and cerebral infarction volumes were assessed 24 hours after the ischemic insult. Tacrolimus dose-dependently reduced neurologic deficits and infarction volume in the cerebral cortex, with statistically significant amelioration of neurologic deficits at 0.032 and 0.1 mg/kg and significant reduction of infarction at 0.1 mg/kg. In the second experiment, the long-term efficacy of tacrolimus on neurologic deficits and cerebral infarction was assessed. Vehicle-treated monkeys exhibited persistent and severe deficits in motor and sensory function for up to 28 days. A single intravenous bolus injection of tacrolimus (0.1 or 0.2 mg/kg) produced long-lasting amelioration of neurologic deficits and significant reduction of infarction volume. In conclusion, we have provided compelling evidence that a single dose of tacrolimus not only reduces brain infarction but also ameliorates long-term neurologic deficits in a nonhuman primate model of stroke, strengthening the view that tacrolimus might be beneficial in treating stroke patients.     

Perceptual aberration and schizotypy: a cautionary note

This study assessed 51 college students for associations between Continuous Performance Test performance and schizotypy scale scores. Results suggest that perceptual aberration scores, while generally correlated with overall schizotypy scores, may not be adequate as a single-criterion measure of schizotypy.     

Risperidone attenuates brain damage after focal cerebral ischemia in vivo

Since their introduction, atypical neuroleptic agents have been discovered to have some beneficial effects beyond their effectiveness as neuroleptic drugs. Among these initially unexpected effects are their potential effects as mood stabilizers in bipolar disorder and their efficacy in improving long-term outcome in schizophrenia. These effects recently raised the question whether these drugs may also have some neuroprotective effect in the brain. To examine this matter, in this study we evaluated the neuroprotective effect of risperidone after permanent focal cerebral ischemia. Anaesthetized male C57BL/6j mice were submitted to permanent thread occlusion of the middle cerebral artery (MCA). Risperidone (0.1, 1 or 10 mg/kg) or vehicle was applied intraperitoneally just after permanent ischemia. Twenty-four hours after permanent ischemia, brain injury was evaluated by triphenyltetrazolium chloride staining (TTC). Risperidone (0.1, 1 and 10 mg/kg) showed significant neuroprotection after permanent focal cerebral ischemia.     

Olanzapine attenuates brain damage after focal cerebral ischemia in vivo

Atypical antipsychotic drugs are widely used in the treatment of schizophrenia. These agents are discovered to have some additional beneficial effects beyond their effectiveness as antipsychotic drugs. Among these initially unexpected effects are their potential effects as mood stabilizers in bipolar disorder and their efficacy in improving long-term outcome in schizophrenia. These effects recently raised the question whether these drugs may also have some neuroprotective effect in the brain. To examine this matter, in this study we evaluated the neuroprotective effect of olanzapine after permanent focal cerebral ischemia. Anaesthetized male C57BL/6j mice were submitted to permanent thread occlusion of the middle cerebral artery (MCA). Olanzapine (0.1 and 1 mg/kg) or vehicle was applied intraperitoneally just after permanent ischemia. Twenty-four hours after permanent ischemia, brain injury was evaluated by triphenyltetrazolium chloride staining (TTC). Olanzapine (0.1 and 1 mg/kg) showed significant neuroprotection after permanent focal cerebral ischemia.     

On telling your fruit from your vegetables: a consideration of category-specific deficits after brain damage

This paper is concerned with single case studies of brain-damaged patients who have selective problems in recognizing and naming stimuli from specific categories (such as fruits and vegetables). We focus on the relevance of these studies for understanding how stimuli are normally recognized and named. To increase the relevance of such studies, we suggest that investigators need to develop more detailed process models of particular behaviours. Impairments can then be understood in terms of deficits to specific processes in the model.     

Prolonged deficits after focal inhibitory seizures

Introduction: Seizures are most commonly associated with positive phenomena such as tonic, clonic or myoclonic movements, automatisms, paresthesias and hallucinations. Negative phenomena, however, are not an uncommon manifestation of seizure activity. Examples of negative seizure phenomena include speech arrest, aphasia, amaurosis, amnesia, numbness, deafness, neglect and atonic seizures. Less commonly described in the literature are focal inhibitory motor seizures. Methods and Results: Two patients presenting with rapidly progressive, prolonged hemiparesis, sensory neglect and hemi-visual field obscuration are described. Computed tomography (CT) and magnetic resonance imaging (MRI) of the brain did not reveal progression of known structural lesions or new lesions. The superficial cortex of the hemisphere contralateral to the hemiparesis and sensory neglect enhanced diffusely with gadolinium on T1-weighted MRI images. Electroencephalography demonstrated periodic lateralized epileptiform discharges (PLEDs) in one patient and lateralized suppression and slowing in the other patient. Single photon emission computed tomography (SPECT) revealed hyperperfusion in the hemisphere contralateral to the hemiparesis and sensory neglect. The changes seen on MRI and SPECT resolved with resolution of the symptoms. Conclusion: Taken together with the clinical history, the results from these investigations suggest focal inhibitory seizure as the underlying etiology. A review of the literature and investigations helpful in making this difficult diagnosis are provided.     

Traumatic stress, brain changes, and memory deficits: a critical note

Memory deficits are frequently observed in posttraumatic stress disorder. According to some authors, these memory impairments are a result of hippocampal damage caused by traumatic stress. This article contains a critical review of studies on changes in hippocampal volume and memory performance in posttraumatic stress disorder. We conclude that most studies in this area suffer from methodological weaknesses and therefore do no allow for firm conclusions about the causal linkage among traumatic stress, hippocampal functioning, and memory. Suggestions for future research, circumventing methodological flaws, are given.     

细胞周期调控对局灶性缺血性脑损伤后的保护作用

目的通过抑制细胞周期素依赖激酶(Cyclindependentkinases,CDKS)来对神经元凋亡进行干预,以探讨细胞周期调控与细胞凋亡的关系。方法建立光化学法诱导大鼠局灶性脑缺血模型,并随机分为脑缺血组(对照组和干预组)和假手术组,采用HE染色显示梗死灶,并测定其面积占脑片面积百分率的平均值;通过TUNEL方法检测神经元凋亡;免疫印迹(Westernblot)观察损伤侧皮层周期素蛋白A(CyclinA)和周期素蛋白B1(CyclinB1)的表达。结果缺血后24h对照组梗死灶面积占脑片面积百分率的平均值明显大于干预组(P<0.05),缺血后梗死灶周围可见大量TUNEL阳性染色细胞,且对照组数量明显多于干预组(P<0.05),二者均多于假手术组(P<0.05);缺血后24h干预组大鼠NeuN TUNAL双标阳性表达率明显弱于对照组大鼠(P<0.05);Westernblot显示对照组CyclinA和CyclinB1的表达明显高于干预组(P<0.05)。结论细胞周期抑制剂可部分抑制缺血边缘区神经元的凋亡及减小脑梗死面积,这提示细胞周期调控可能参与了神经细胞的凋亡过程。     

Problem solving deficits after focal cerebral lesions

Verbal comprehension and naming, identification of categories, as well as problem solving on reasoning and sorting tasks were examined in 57 patients with focal brain lesions and 20 control patients. The results confirmed the prediction that frontal lobe lesions cause a more pronounced deficit in problem solving than posterior lesions. However, patients with left frontal lobe lesions showed verbal inefficiency which possibly disturbed their sorting on the basis of feedback, but the inferiority of the frontal lobe damaged patients on category identification was not secondary to this verbal deficit. As the patients with left posterior lesions did not have marked verbal deficits, the present findings should be confined to patients lacking severe aphasia, which may also disturb problem solving in patients with posterior lesions.     

Prolonged focal epilepsy and hypoxemia as a cause of focal brain damage: a case study.

A 48-year-old woman developed epilepsia partialis continue (EPC) involving the right arm and leg, which lasted for four weeks until she died. Systemic hypoxia associated with chronic obstructive pulmonary disease and acute pneumonia complicated her hospital course. At autopsy, diffuse cortical changes resembling the sequelae of ischemic anoxia were observed in the left cerebral hemisphere. The right cerebral hemisp here and cerebellum were minimally involved. No other significant pathological processes could be identified in the central nervous system, and the cerebrovascular system was free of obstructive lesions. It is proposed that the left-sided damage was precipitated by the increased metabolic demand of the cerebral cortex associated with the EPC, with which autoregulatory circulatory responses were unable to cope in a patient with underlying hypoxia.     

Right-sided representational neglect after left brain damage in a case without visuospatial working memory deficits

Brain damaged patients suffering from representational neglect (RN) fail to report, orient to, or verbally describe contra-lesional elements of imagined environments or objects. So far this disorder has only been reported after right brain damage, leading to the idea that only the right hemisphere is involved in this deficit. A widely accepted account attributes RN to a lateralized impairment in the visuospatial component of working memory. So far, however, this hypothesis has not been tested in detail. In the present paper, we describe, for the first time, the case of a left brain damaged patient suffering from right-sided RN while imagining both known and new environments and objects. An in-depth evaluation of her visuospatial working memory abilities, with special focus on the presence of a lateralized deficit, did not reveal any abnormality. In sharp contrast, her ability to memorize visual information was severely compromised. The implications of these results are discussed in the light of recent insights in the neglect syndrome.