The role of trauma-related distractors on neural systems for working memory and emotion processing in posttraumatic stress disorder

The relevance of emotional stimuli to threat and survival confers a privileged role in their processing. In PTSD, the ability of trauma-related information to divert attention is especially pronounced. Information unrelated to the trauma may also be highly distracting when it shares perceptual features with trauma material. Our goal was to study how trauma-related environmental cues modulate working memory networks in PTSD. We examined neural activity in participants performing a visual working memory task while distracted by task-irrelevant trauma and non-trauma material. Recent post-9/11 veterans were divided into a PTSD group (n = 22) and a trauma-exposed control group (n = 20) based on the Davidson trauma scale. Using fMRI, we measured hemodynamic change in response to emotional (trauma-related) and neutral distraction presented during the active maintenance period of a delayed-response working memory task. The goal was to examine differences in functional networks associated with working memory (dorsolateral prefrontal cortex and lateral parietal cortex) and emotion processing (amygdala, ventrolateral prefrontal cortex, and fusiform gyrus). The PTSD group showed markedly different neural activity compared to the trauma-exposed control group in response to task-irrelevant visual distractors. Enhanced activity in ventral emotion processing regions was associated with trauma distractors in the PTSD group, whereas activity in brain regions associated with working memory and attention regions was disrupted by distractor stimuli independent of trauma content. Neural evidence for the impact of distraction on working memory is consistent with PTSD symptoms of hypervigilance and general distractibility during goal-directed cognitive processing.     

骨形态发生蛋白4转基因治疗大鼠的胫骨缺损

目的:观察基因工程技术构建人骨形态发生蛋白4复制缺陷腺病毒的成骨效果。方法:实验于2006-03/08在安徽医科大学第一附属医院实验动物中心完成。实验分组:选取普通级雄性SD大鼠30只,体质量(200±10)g,全部动物胫骨上端部分分别造成8mm×5mm长方形缺损。采用自身对照法,右侧骨缺损为实验组,左侧骨缺损为对照组。实验组植入人骨形态发生蛋白4复制缺陷腺病毒复合明胶海绵,对照组植入单纯明胶海绵。实验评估:术后分别于4,6,8周麻醉后处死10只动物,取材行X线、组织病理、免疫组织化学、透视电镜检查,观察成骨情况。结果:纳入30只大鼠,全部进入结果分析。①大鼠胫骨缺损X线、组织病理学检查结果:术后8周实验组和对照组骨缺损均得到修复,但实验组无论从成骨时间、成骨效果、新生骨量等方面都要优于对照组。其中各时间点实验组骨密度明显高于对照组,差异有显著性意义[4周:(95.91±16.33),(87.93±11.52);6周:(128.34±10.64),(102.41±9.81);8周:(138.36±10.49),(121.56±9.63);P<0.01]。各时间点实验组新生骨占骨缺损面积比明显高于对照组,差异有显著性意义[4周:(41.39±5.65)%,(26.58±5.62)%;6周:(80.35±7.25)%,(65.41±6.52)%;8周:(96.45±2.76)%,(82.22±7.30)%;P<0.01]②术后4周免疫组织化学染色结果:实验组软骨及骨痂内呈强阳性反应,而对照组骨痂内骨形态发生蛋白4表达微弱。结论:人骨形态发生蛋白4重组腺病毒具有良好的成骨活性,骨形态发生蛋白4直接转基因治疗能够加快骨缺损的修复。     

Virtual reality measures in neuropsychological assessment: a meta-analytic review

Objective: Virtual reality-based assessment is a new paradigm for neuropsychological evaluation, that might provide an ecological assessment, compared to paper-and-pencil or computerized neuropsychological assessment. Previous research has focused on the use of virtual reality in neuropsychological assessment, but no meta-analysis focused on the sensitivity of virtual reality-based measures of cognitive processes in measuring cognitive processes in various populations. Method: We found eighteen studies that compared the cognitive performance between clinical and healthy controls on virtual reality measures. Results: Based on a random effects model, the results indicated a large effect size in favor of healthy controls (g = .95). For executive functions, memory and visuospatial analysis, subgroup analysis revealed moderate to large effect sizes, with superior performance in the case of healthy controls. Participants’ mean age, type of clinical condition, type of exploration within virtual reality environments, and the presence of distractors were significant moderators. Conclusions: Our findings support the sensitivity of virtual reality-based measures in detecting cognitive impairment. They highlight the possibility of using virtual reality measures for neuropsychological assessment in research applications, as well as in clinical practice.     

两种荧光显微成像系统亚细胞定位的对比

目的:应用高分辨率荧光显微成像系统采集细胞器探针图像,并与激光共聚焦显微成像系统进行对比。方法:实验于2003-05/2004-01在解放军总医院完成。①实验材料:鼠肺毛细血管内皮细胞株(1H11)由上海复旦张江生物公司提供;荧光探针Rhodamine-123,Lucifer Yellow,DiOC6[3],BODIPY(美国Sigma公司)。②细胞培养及荧光探针染色:细胞培养采用含体积分数为0.2胎牛血清的低糖DMEM培养基,密度5×107L-1。选择Rhodamine-123作为细胞线粒体特异性荧光探针,选择DiOC6[3]作为细胞内质网特异性荧光探针,选择BODIPY作为细胞高尔基体特异性荧光探针,选择Lucifer Yellow作为细胞溶酶体探针。前3个探针在完全避光条件下与培养的细胞共同孵育0.5h,后者则共同孵育15h。③高分辨率荧光成像系统的图像采集:线粒体荧光图像采集,选取经Rhodamine-123共孵育完成的细胞,选择激发滤色镜为BP460-490,吸收滤色镜为BA515,分光镜为DM500,另加一绿通道液晶滤光片,激发出Rhodamine-123的荧光。电荷耦合器件采集图像并送入计算机。重复上述步骤,采用DiOC6[3]标记内质网,BODIPY标记高尔基体,Lucifer Yellow标记细胞溶酶体,激发条件同Rhodamine-123。分别采集同一视野靶细胞DiOC6[3]、BODIPY或Lucifer Yellow的荧光图像,完成全部图像采集并储存在计算机中。④激光共聚焦显微成像系统的图像采集:选择经4种探针染色的靶细胞,使用氩离子激光器在488nm激发Rhodamine-123,Rhodamine-123荧光通过配置有530/60-G发射滤光片的通道1探测。重复上述步骤,在488nm激发DiOC6[3]和BODIPY,在457nm激发Lucifer yellow,3种荧光均由通道1探测,后2个探针的发射滤光片的配置为515/30-G,DiOC6[3]选择530/60-G。由光电倍增管接收信号并传输入计算机成像。结果:①高分辨率荧光成像系统所采集图像,靶细胞中由荧光探针Rhodamine-123染色的线粒体呈多个典型的小棒状或卵圆状,聚集在核周;Lucifer yellow染色的溶酶体呈多个非对称球型,在胞浆内随机分布,颗粒尺寸通常大于线粒体;荧光探针DiOC6[3]着色的内质网占据胞浆的很大空间,以囊状聚集为特征;BODIPY特异性地结合在高尔基体上,荧光图像显示围绕在细胞核周围呈条索状。②与高分辨率荧光成像系统比较,激光共聚焦显微成像系统所采集的图像其荧光强度基本相同,但分辨率低、细节显示模糊、胞浆中细胞器的准确分布信息和形态特征显示效果欠佳。结论:两种荧光显微成像系统均可采集到细胞器探针的荧光图像。但高分辨率荧光成像系统采集的荧光图像具有细节清晰、分辨度高、准确显示胞浆中细胞器的分布信息和形态特征等优点。     

Causality between local field potentials of the subthalamic nucleus and electromyograms of forearm muscles in Parkinson’s disease

Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson’s disease, although its precise mechanisms remain poorly understood. To gain further insight into the mechanisms underlying deep brain stimulation, we analysed the causal relationship between forearm muscle activity and local field potentials derived from the subthalamic nucleus. In 19 patients suffering from Parkinson’s disease of the akinetic‐rigid subtype, we calculated the squared partial directed coherence between muscles of the contralateral forearm and the subthalamic nucleus or zona incerta during both a rest and a hold condition of the arm. For both recording regions, data analysis revealed that, during the rest condition, electromyographic activity was significantly more often ‘Granger‐causal’ for the local field potentials than the opposite causation. In contrast, during the hold condition, no significant difference was found in the occurrence of causalities. Contrary to the existing basal ganglia model and the current concept of Parkinson’s disease pathophysiology, we found the subthalamic nucleus to receive more ‘afferences’ than it emitted ‘efferences’, suggesting that its role is more complex than a simple driving nucleus in the basal ganglia loop. Therefore, the effect of deep brain stimulation in the subthalamic nucleus could, at least in part, result from a blockade of pathological afferent input.     

Penetration of doripenem in human brain: an observational microdialysis study in patients with acute brain injury

Concentration-time profiles of unbound doripenem were determined by microdialysis in the cerebral interstitium of five patients with acute brain injury. The ratio of the area under the concentration-time curve in brain to that in plasma (AUC(brain)/AUC(plasma)) was 0.17 in one patient and 0.01 in the remaining four patients. Based on the percentage of the dosing interval during which the doripenem concentration exceeded a certain minimum inhibitory concentration (T>MIC), a value of ≥35% of the dosing interval was reached for pathogens with MICs up to 0.05 mg/L. The present data indicate that breakpoints based on concentrations of doripenem in plasma may overestimate antimicrobial activity in brain parenchyma.