重复经颅磁刺激治疗精神分裂症工作记忆缺陷的研究进展

精神分裂症患者存在明显的工作记忆缺陷,影响其功能及预后,但目前尚无有效干预手段治疗精神分裂症的工作记忆缺陷.重复经颅磁刺激(rTMS)是一种非侵入性干预手段,基础及临床研究提示rTMS对精神分裂症的工作记忆缺陷可能具有改善作用,但是现有的研究结果并不能反映rTMS对精神分裂症工作记忆缺陷的治疗全貌及真实情况.因此,对rTMS治疗进行深入研究不仅有助于阐明精神分裂症的工作记忆缺陷机制,同时也能为精神分裂症认知功能缺陷的治疗提供新的治疗途径,改善患者的功能及预后.     

精神分裂症患者的工作记忆障碍

工作记忆 (workingmemory)是近年来认知神经科学研究的一个热点。用工作记忆的模式来解释人类的认知活动 ,发现工作记忆不仅仅作为信息的暂存 ,而且与语言理解能力、有目的行为、自我监察、注意分配、计划及推理等有关。近年来研究发现精神分裂症患者的工作记忆存在缺陷 ,研究者推测它可能是精神分裂症神经认知缺陷中核心的障碍 ,与精神分裂症发病机理有关。现对近年来精神分裂症工作记忆障碍的研究作一综述。工作记忆与精神分裂症精神分裂症存在神经认知功能的损害 ,而且这种损害绝大部分在那些首发未经治疗的精神分裂症患者中就已表现出来…     

精神分裂症认知功能障碍的新疗法--认知矫正治疗

一、认知矫正治疗产生的背景目前研究显示认知功能障碍已经成为精神分裂症的主要症状之一 ,也是影响患者社会功能康复和疾病预后的重要因素[1] 。目前 ,认为精神分裂症的认知功能障碍存在四种类型[2 4] :注意障碍 ,记忆障碍 ,抽象思维障碍 ,信息整合障碍。在精神分裂症所致的认知障碍中 ,报道最多的是前额叶的执行功能障碍[5] 。目前 ,针对精神分裂症认知功能损害的治疗手段大致可以分为两大类 :(1)药物治疗。传统抗精神病药对认知功能有进一步损害 ,而新型抗精神病药 (如利培酮等 )对认知功能的改善作用优于前者[6] ;但对精神分裂症残余症…     

精神分裂症工作记忆的研究进展

精神分裂症伴有大量的认知功能损害,目前认为工作记忆损伤是精神分裂症患者的主要特征,本文回顾了近几年有关精神分裂症工作记忆的损伤及神经影像学改变研究进展,以及药物对于改善工作记忆的作用。     

多巴胺受体与前额叶皮层的认知功能

前额叶皮层是指额叶中央前回和中央旁小叶以前的广大皮层 ,既包括半球的背外侧面 ,又包括其内侧面和眶面 ,具有丰富的皮层间和皮层下交互纤维联系。前额叶在人的注意力、排除干扰能力、思维、逻辑推理、行为计划、组织、工作记忆等脑高级认知功能中起重要作用。前额叶皮层功能紊乱与许多精神症状有关 ,如 :精神分裂症、注意缺陷多动障碍等 [1～ 3 ] 。目前大量研究都支持精神分裂症的认知功能障碍与前额叶多巴胺 (DA)的异常有关。研究表明 :中脑大脑皮层 (额叶、扣带回 ) DA系统主要参与认知功能。本文综述了近年来 DA受体与前额叶皮层认…     

工作记忆的脑功能定位研究

工作记忆是一项重要认知功能 ,对于人类高级认知功能具有重要作用 ,也是神经影像学常用的研究方法。目前较多研究均认为工作记忆与额叶有关 ,本文综述了其脑功能定位的有关研究 ,并介绍了精神分裂症的工作记忆研究成果     

工作记忆的脑功能定位研究

工作记忆是一项重要认知功能，对于人类高级认知功能具有重要作用。也是神经影像学常用的研究方法，目前较多研究均认为工作记忆与额叶有关，本文综述了其脑功能定位的有关研究。并介绍了精神分裂症的工作记忆研究成果。     

首发精神分裂症患者治疗前后脑功能磁共振成像的研究

目的 利用功能磁共振成像(fMRI)探讨首发精神分裂症患者利培酮治疗前后认知功能激发图像的特点。方法 18例首发精神分裂症患者治疗前进行倒背数字作业的fMRI检查,经利培酮[(3.8±0.9)mg/d]治疗(57±9)d后复查fMRI(16例)。用阳性和阴性症状量表(PANSS)及治疗中需处理的不良反应症状量表评价精神症状的严重程度及不良反应。结果 (1)利培酮治疗后的PANSS减分率为(50±22)％,有效率为72％。(2)治疗前倒背数字作业激活范围较广泛,包括额叶、顶叶及颞叶等脑区。(3)左侧额上回治疗前激活脑区计数为4,治疗后计数为12,治疗前后激活脑区计数的差异有非常显著性(P=0.009);左侧额叶腹外侧面治疗前激活平均体积为(15±38)个体素,治疗后激活平均体积为(67±76)个体素,治疗前后的差异有显著性(P=0.046)。结论 首发精神分裂症患者在发病初期就存在工作记忆缺陷,这种缺陷可能与左侧额上回及额下回激活低下有关,利培酮治疗可改善患者的工作记忆缺陷。     

精神分裂症的失言识别能力与眶额叶损伤关系的研究

目的通过失言识别的神经心理学研究,初步了解精神分裂症患者社会认知障碍的脑机制。方法应用失言识别的神经心理学实验,对正常人(n=40)、精神分裂症(n=36)、眶额叶损伤(n=15)以及前额叶背外侧损伤(n=13)患者进行对照研究。结果分裂症患者的失言识别得分较正常对照组及前额叶背外侧损伤患者有显著性差异;与眶额叶损伤患者无明显差异。与前额叶背外侧损伤患者相比,眶额叶损伤患者失言识别有明显障碍。结论分裂症患者失言识别能力明显受损,可能与眶额叶功能异常有关。     

工作记忆缺陷在首发精神分裂症早期诊断中的作用

目的探讨在不同认知负荷下首发精神分裂症患者的工作记忆损伤及其与症状学和社会功能的关系,为精神分裂症的早期诊断提供参考。方法纳入2016年9月-2017年7月在广州医科大学附属脑科医院门诊就诊且符合《精神障碍诊断与统计手册(第4版)》(DSM-IV)精神分裂症诊断标准的首发精神分裂症患者32例,同时纳入健康人员35例作为对照组,采用阳性和阴性症状量表(PANSS)及个体和社会功能量表(PSP)对患者组的临床症状进行评估,两组均完成面孔和房屋的延迟匹配样本任务,测量其视觉工作记忆,分析其与临床症状的相关性。结果精神分裂症患者的面孔和房屋工作记忆均受损(F均16,P0.01)。在房屋工作记忆的准确性上,患者组和对照组之间的差异随记忆负荷增大而减小(F均9,P0.01)。患者组工作记忆的表现与病程、症状严重程度、抗精神病药物剂量无相关性(P均0.05)。结论首发精神分裂症患者存在视觉工作记忆缺陷,而面孔工作记忆缺陷不易受认知负荷的影响,可能可作为精神分裂症早期诊断的依据之一。     

Molecular targets for treating cognitive dysfunction in schizophrenia

Cognitive impairment is a core feature of schizophrenia as deficits are present in the majority of patients, frequently precede the onset of other positive symptoms, persist even with successful treatment of positive symptoms, and account for a significant portion of functional impairment in schizophrenia. While the atypical antipsychotics have produced incremental improvements in the cognitive function of patients with schizophrenia, overall treatment remains inadequate. In recent years, there has been an increased interest in developing novel strategies for treating the cognitive deficits in schizophrenia, focusing on ameliorating impairments in working memory, attention, and social cognition. Here we review various molecular targets that are actively being explored for potential drug discovery efforts in schizophrenia and cognition. These molecular targets include dopamine receptors in the prefrontal cortex, nicotinic and muscarinic acetylcholine receptors, the glutamatergic excitatory synapse, various serotonin receptors, and the gamma-aminobutyric acid (GABA) system.     

Neural changes following cognitive remediation therapy for schizophrenia

Patients with schizophrenia experience cognitive impairments that relate to poorer social functioning even after amelioration of positive symptoms. Pharmacological treatment and cognitive remediation are the two important therapeutic approaches for cognitive impairment in schizophrenia. Cognitive remediation therapy (CRT) for schizophrenia improves cognitive functioning and induces neuroplasticity, but different approaches and durations of CRT and different neuroimaging devices have led to varying results in meta‐analyses. The objective of this review was to explore the impact of CRT on neurobiology. Several studies have provided evidence of increased activation in the frontal brain regions, such as the prefrontal cortex, anterior cingulate cortex, and parietal and occipital regions during working memory or executive function tasks after CRT. Two studies have shown alterations in resting‐state connectivity between the prefrontal cortex and temporal regions. Two studies have reported that CRT induces changes in gray matter volume in the hippocampus. Further, one study observed that patients who had received CRT had elevated fractional anisotropy in the basal ganglia. We conclude that neuroimaging studies assessing CRT in patients with schizophrenia showed functional, structural, and connectivity changes that were positively correlated with cognitive improvements despite heterogeneous CRT approaches. Future studies that combine multiple modalities are required to address the differences, effects of intrinsic motivation, and pharmacological augmentation of CRT. Further understanding of the biological basis might lead to predictions of the CRT response in patients with schizophrenia and contribute to identification of schizophrenia patients for future interventions.     

恢复期精神分裂症患者的认知功能障碍

目的：研究恢复期精神分裂症患者认知功能损害特点。方法：对２６例病情已达显著进步以上的精神分裂症患者及２５例健康者评定认知功能障碍的状况。结果：所有实验组患者与对照组相比较,在注意、记忆及信息整合与执行功能方面均有不同程度缺损。结论：认知功能障碍是精神分裂症的核心症状之一,以阳、阴性症状为主的临床诊疗标准存在一定的限制性,应增补认知功能和评定内容。     

The effects of 7-week cognitive training in patients with vascular cognitive impairment,no dementia (the Cog-VACCINE study): A randomized controlled trial

IntroductionEvidence for the efficacy of cognitive training in patients with subcortical vascular cognitive impairment no dementia is still lacking.MethodsA randomized, active controlled design using multidomain, adaptive, computerized cognitive training for 30 minutes, 5 days/week for 7 weeks. Assessments included global cognitive function and executive function (primary outcomes) and brain functional connectivity and structural changes (secondary outcomes).ResultsSixty patients were randomized across three medical centers in Beijing. At the end of the intervention, the cognitive training group showed significant improvement in Montreal Cognitive Assessment relative to the active control group (P = .013) and significantly increased functional connectivity between the left dorsolateral prefrontal cortex and medial prefrontal cortex, which was significantly correlated with Montreal Cognitive Assessment change (P = .017).DiscussionComputerized cognitive training significantly improved global cognitive function, which was supported by the improved brain plasticity. Incorporation of biomarkers should be implemented in cognitive training trials.     

Cognitive impairment in relation to depression,anxiety and virological response in hepatitis C patients in Egypt

Abstract

Objective. Cognitive impairment commonly occurs in hepatitis C virus (HCV) patients. The objective of this study was to estimate the prevalence and sociodemographic and clinical correlates of cognitive impairment in HCV patients before and after 12 weeks of interferon treatment in comparison with a control group. Methods. Hundred and sixteen consecutive HCV patients were included in the study and divided into treated and untreated groups. All patients were assessed using sociodemographic and clinical questionnaire, Montreal Cognitive Assessment Scale (MOCA) and Hospital Anxiety and Depression Scale (HADS) before and after 12 weeks of treatment or observation. Results. Thirty-eight percent of treated patients showed cognitive impairment at baseline, which increased to 69% after 12 weeks of interferon treatment. This cognitive impairment was reflected in the total MOCA score and in visuo-constructional skills, attention, concentration, working memory, language, and short-term memory, which was not shown by untreated group after 12 weeks of observation. Cognitive impairment was associated with low education, but not with depression, anxiety, or virological response. Conclusions. Cognitive impairment is common in HCV patients and increases significantly after interferon treatment. It is not related to depression or anxiety in HCV patients. Future research should focus on prevention, treatment and outcome of cognitive impairment in HCV patients, particularly those receiving interferon therapy.     

Temporally anticorrelated brain networks during working memory performance reveal aberrant prefrontal and hippocampal connectivity in patients with schizophrenia

Functional neuroimaging studies on cognitive dysfunction in schizophrenia have suggested regional brain activation changes in the dorsolateral prefrontal cortex and the medial temporal lobe. However, less is known about the functional coupling of these areas during cognitive performance. In this study, we used functional magnetic resonance imaging, a verbal working memory (WM) task and multivariate statistical techniques to investigate the functional coupling of temporally anticorrelated neural networks during cognitive processing in patients with schizophrenia (n = 16) compared to healthy controls (n = 16). Independent component analysis identified 18 independent components (ICs) among which two ICs were selected for further analyses. These ICs included temporally anticorrelated networks which were most highly associated with the delay period of the task in both healthy controls and patients with schizophrenia. Functional network abnormalities in patients with schizophrenia were detected within a “task-positive” lateral frontoparietal network, where increased functional connectivity was found in bilateral dorsolateral prefrontal regions. In addition, aberrant functional coupling of the hippocampal cortex in patients with schizophrenia was detected within a “task-negative” medial frontotemporal network. In patients with schizophrenia, functional connectivity indices in the left dorsolateral prefrontal cortex and the right hippocampal cortex were positively correlated with accuracy during the WM task, while the connectivity strength in the right dorsolateral prefrontal cortex was negatively correlated with measures of symptom severity. These data suggest that within two temporally anticorrelated network states, patients with schizophrenia exhibit increased and persistent dorsolateral prefrontal and hippocampal connectivity during WM performance.     

Relation of prefrontal cortex dysfunction to working memory and symptoms in schizophrenia.

OBJECTIVE: The dorsolateral prefrontal cortex has been implicated in both working memory and the pathophysiology of schizophrenia. A relationship among dorsolateral prefrontal cortex activity, working memory dysfunction, and symptoms in schizophrenia has not been firmly established, partly because of generalized cognitive impairments in patients and task complexity. Using tasks that parametrically manipulated working memory load, the authors tested three hypotheses: 1) patients with schizophrenia differ in prefrontal activity only when behavioral performance differentiates them from healthy comparison subjects, 2) dorsolateral prefrontal cortex dysfunction is associated with poorer task performance, and 3) dorsolateral prefrontal cortex dysfunction is associated with cognitive disorganization but not negative or positive symptoms. METHOD: Seventeen conventionally medicated patients with schizophrenia and 16 healthy comparison subjects underwent functional magnetic resonance imaging while performing multiple levels of the "n-back" sequential-letter working memory task. RESULTS: Patients with schizophrenia showed a deficit in physiological activation of the right dorsolateral prefrontal cortex (Brodmann's area 46/9) in the context of normal task-dependent activity in other regions, but only under the condition that distinguished them from comparison subjects on task performance. Patients with greater dorsolateral prefrontal cortex dysfunction performed more poorly. Dorsolateral prefrontal cortex dysfunction was selectively associated with disorganization symptoms. CONCLUSIONS: These results are consistent with the hypotheses that working memory dysfunction in patients with schizophrenia is caused by a disturbance of the dorsolateral prefrontal cortex and that this disturbance is selectively associated with cognitive disorganization. Further, the pattern of behavioral performance suggests that dorsolateral prefrontal cortex dysfunction does not reflect a deficit in the maintenance of stimulus representations per se but points to deficits in more associative components of working memory.     

Measuring changes in functional status among patients with schizophrenia: the link with cognitive impairment

Cognitive impairment associated with schizophrenia (CIAS) includes neuropsychological deficits in attention, working memory, verbal learning, and problem solving. These deficits have been shown to be linked to impairment in functional status (eg, social behavior, work performance, and activities of daily living) among patients with schizophrenia in cross-sectional studies. Less is known about the relationship between cognitive and functional change over time, such as potential functional implications of treatment-related improvement in CIAS. The purpose of this review is to summarize research on the association between change in CIAS and change in functional status, to discuss responsiveness of functional outcomes measures, and to provide recommendations for future research and measure development. Nine longitudinal studies were located on the link between CIAS and functional status, and 8 functional outcomes measures were used across these studies. The 9 studies offer initial support for a link between change in cognitive function and change in functional status. However, inconsistent findings across studies indicate that available research is preliminary, and substantial questions remain unanswered. Shortcomings of functional status measures are noted: most instruments were not developed for the target population, and none have demonstrated responsiveness to cognitive change among schizophrenic patients. It is recommended that new functional outcome measures be developed that are specifically designed to be responsive to change in cognition, with domains previously shown to be related to cognitive ability. When creating new functional outcomes measures for assessment of patients with schizophrenia, responsiveness to change in CIAS should be evaluated as part of the development and validation process.     

Repeated methamphetamine treatment impairs recognition memory through a failure of novelty-induced ERK1/2 activation in the prefrontal cortex of mice.

BACKGROUND: Recent clinical studies have suggested that chronic use of methamphetamine (METH) induces long-term cognitive deficits. To clarify the mechanism of METH-induced cognitive impairment, we investigated the effect of METH on cognitive function in mice. METHODS: Mice were repeatedly administered METH for 7 days, and their cognitive function was assessed using a novel-object recognition task. Therapeutic effects of clozapine and haloperidol on METH-induced cognitive impairment were investigated. Western blotting and specific inhibitors were employed to determine the role of extracellular signal-regulated kinase 1/2 (ERK1/2). RESULTS: Repeated METH treatment induced an impairment of recognition of novel objects and behavioral sensitization. These effects persisted for at least 28 days after the drug withdrawal. Clozapine, but not haloperidol, reduced METH-induced cognitive impairment. Hyperphosphorylation of ERK1/2 was found in the prefrontal cortex of mice exposed to the novel objects, but was abolished in mice treated with METH. Inhibition of ERK1/2 by the microinjection of PD98059 into the prefrontal cortex resulted in cognitive impairment. CONCLUSIONS: These results suggest that repeated METH treatment induces cognitive impairment, which is associated with the dysfunction of the ERK1/2 pathway in the prefrontal cortex.     

长春西汀对认知功能障碍的疗效观察

目的：探讨长春西汀对恢复期精神裂症患者认知功能障碍的治疗作用。方法：对31例疗效已达显著进步以上的精神分裂症患者，随机分为研究组（16例）和对照组（15例），在予长春西汀治疗前、后、对两组患者分别评定其认知障碍及脑血流状况，进行分析。结果：研究组治疗前后有显著好转，而对照组差异无显著性。结论：长春西汀对改善精神分裂症患者的认知障碍有益。