精神分裂症患者工作记忆不同认知成分的fMRI研究

目的：采用事件相关功能磁共振成像（ER-fMRI）探讨精神分裂症患者与正常对照组执行工作记忆不同认知成分即编码、维持和提取过程的神经机制差别。方法：使用fMRI技术,观察16名正常受试者和20名精神分裂症患者在执行Sternberg项目认知任务（SIRT）的编码、维持和提取过程时的激活脑区。结果：与正常组比较,患者组工作记忆不同认知过程的执行脑区激活程度增加,编码期激活增加脑区为右侧楔前叶,维持期激活增加脑区为左侧PMA、左侧DLPFC、右侧楔前叶及左侧VLPFC,提取期激活增加脑区为左侧PMA,而且患者组还激活了更多皮层下结构、初级运动皮层及左侧颞叶语言相关脑区。结论：精神分裂症患者工作记忆编码、维持和提取成分的一些执行脑区皮层效率功能低下。     

精神分裂症患者任务诱发去激活的fMRI研究

目的：任务诱发去激活（Task induced deactivation,TID）皮层区是静息态脑功能的“默认”模式相关脑区,可能与自我定向思维活动有关。本文探讨精神分裂症患者中线TID脑区是否出现变化,以及TID脑区与患者情感状态、行为学表现间的相关性。材料与方法：15例精神分裂症患者和15例与之匹配的正常对照组执行2-back工作记忆任务时行全脑BOLD-fMRI扫描,对每个受试者进行PANAS量表评定。结果：与正常组比较,患者组2-back任务中反应时间（RT）延长,前额叶内侧皮层（MPFC）、后内侧皮层（PMC）脑区TID效应降低,负性情绪评分增加;患者组MPFC区TID与RT、负性情绪评分呈负相关。结论：精神分裂症患者在认知任务执行中存在着认知-情感之间注意资源转移效率障碍,这可能是精神分裂症患者认知功能障碍的神经机制之一。     

首发精神分裂症患者威斯康星卡片分类测验中的脑功能障碍研究

目的:探讨首发未服药精神分裂症患者进行威斯康星卡片分类测验(WCST)操作时的脑功能状态特点。方法:20名健康受试者(对照组)和20名首发未服药精神分裂症患者(患者组)操作WCST和颜色卡片分类测验(CCST)时进行脑功能磁共振成像(fMRI),比较2组激活脑区的激活体积。结果:对照组WCST和CCST功能图像相减获得的脑活动功能图像显示,激活主要分布在双侧前额叶,尤其是背外侧部以及顶叶后下部皮质和前扣带回。患者组WCST操作成绩较对照组差,有显著性差异(P<0.01)。与对照组相比,患者组的左侧前额叶背外侧部、左前扣带回皮质激活低下,左顶叶后下部皮质激活增加(P<0.01或0.05)。结论:双侧前额叶,尤其是背外侧部,以及顶叶后下部皮质和前扣带回皮质参与WCST操作的高级认知过程。精神分裂症患者在未治疗前就存在执行功能缺陷,其前额叶和扣带回功能低下,可能与患者执行功能障碍相关;后顶叶皮质功能亢进,可能对前额叶功能低下有补偿作用。     

精神分裂症空间工作记忆任务的fMRI研究

目的采用fMRI技术探讨精神分裂症患者空间工作记忆损害的神经机制。方法收集18例精神分裂症患者和18名正常受试者进行空间n-back任务的fMRI扫描。采用SPM 8进行数据预处理和统计分析,单样本t-检验用于分析两组各自脑激活结果,双样本t-检验用于工作记忆相关脑激活的组间比较。采用FDR方法进行多重比较校正。利用SPSS 17.0软件对工作记忆任务中的行为学结果 (正确率和反应时间)进行组间比较。结果与对照组相比,精神分裂症患者空间工作记忆任务反应时间延长(882.00±50.31)ms,正确率下降(83.60±2.90)%(P0.05)。精神分裂症患者在n-back空间工作记忆任务时所激活的脑区分布与对照组基本一致,主要包括双侧前额皮层、颞顶叶皮层及部分基底核团。但组间比较显示精神分裂症患者多个脑区激活强度及范围明显增加,包括双侧前额皮层背外侧、双侧后顶叶皮层、右侧中央前回、左侧颞中回、右扣带回和双侧小脑(FDR校正,P0.05)。结论执行空间工作记忆任务时精神分裂症患者脑区激活增加,但行为学表现下降,提示患者脑区活动效率低下,可能是工作记忆能力损害的神经基础。     

缺陷型精神分裂症患者认知功能的研究

目的 探讨缺陷型精神分裂症患者认知功能的变化.方法 采用Stroop测验、连线测试(TMT)、范畴流利测验对35例缺陷型精神分裂症、61例非缺陷型精神分裂症、59例健康志愿者进行测评.结果 缺陷型、非缺陷型精神分裂症组的所有神经心理测验均差于正常对照组(P＜0.05).缺陷型精神分裂症除Stroop色词测验外,其他的神经心理测验成绩与非缺陷型精神分裂症相比差异均有统计学意义[分别为(122.53±69.05),(318.30±203.74),(45.49±21.74),(28.86±12.95),(14.37±5.06),(P＜0.05)].除Stroop色词测验外,SDS阴性症状分、SANS量表分与其他神经心理测验均呈显著相关(P＜0.05或0.01).结论 精神分裂症存在广泛的认知功能损害,而缺陷型精神分裂症作为一种独立亚型,可能存在更严重的额叶损伤.     

汉字情景记忆时皮层定位的fMRI研究

目的探讨用功能磁共振成像(fMRI)检测汉字情景记忆时皮层定位的价值及皮层定位的双侧不对称性.方法 10名健康右利手成人,以高频双字汉字作为刺激任务,行全脑fMRI,确定激活皮层的定位.结果汉字情景记忆时双侧多个脑区有激活,但两侧激活脑区不完全对称,编码加工时主要激活脑区为左侧纹外区和左侧颞叶梭状回,而提取加工时左侧顶叶楔前叶、左侧前额叶背外侧显著激活.结论汉字情景记忆时左右大脑半球激活区存在不对称性,fMRI可对此种功能皮层进行准确定位.     

精神分裂症幻听患者静息态脑功能低频振幅研究

目的运用静息态功能磁共振成像(fM RI)中的低频振幅(ALFF)参量评价精神分裂症幻听相关的神经元自发活动改变。方法纳入精神分裂症幻听组患者16例,非幻听组患者17例。采集所有研究对象的静息态fM RI数据并通过后处理计算得到ALFF值,比较精神分裂症幻听组和非幻听组ALFF组间存在差异的脑区;采用阳性与阴性症状量表(PANSS)对精神分裂症症状进行评估,分析差异脑区ALFF值和幻听症状的相关性。结果与非幻听组比较,幻听组ALFF显著降低的脑区主要位于枕叶皮层,ALFF显著升高的脑区有左侧角回、缘上回、颞上回。左侧角回的ALFF值与幻听症状评分呈正相关关系(P=0.006,R=0.550),枕叶皮层的ALFF值与幻听症状评分呈负相关关系(P=0.007,R=-0.53)。结论精神分裂症幻听患者的静息态自发脑功能活动异常可能与听觉语言处理皮层过度激活及视觉信息处理功能受损有关。     

注意缺陷障碍患儿注视作业时的功能性磁共振成像分析

目的应用功能性磁共振成像研究正常儿童及注意缺陷障碍（ADHD）患儿在进行注视作业测验时其额、颞叶等皮质区激活状况的差异。方法使用美国GE 1．5T Sigma Horizon LX超导型磁共振仪对19名正常儿童及17例ADHD患儿于注视作业测试时进行fMRI检查。结果（1）正常儿童和ADHD患儿激活脑区范围均较广泛，两组激活脑区在额叶、颞叶、顶叶、枕叶及扣带回部位的分布情况大体相同（P〉0．05）。（2）正常儿童与ADHD患儿激活脑区计数如下，左额上回分别为15个和6个，右额上回分别为16个和5个，右额中回分别为16个和8个，左额下回分别为15个和5个，2组对象上述部位脑区激活计数结果差异均有统计学意义（均P〈0．05）。（3）fMRI结果显示，ADHD患儿双侧前额叶、右额中回以及左额下回部位功能低下。结论ADHD患儿在选择性注意及执行功能方面存在缺陷，fMRI对检测正常儿童及ADHD患儿大脑皮质激活情况均具有重要意义。     

基于静息和任务状态下的精神分裂症患者丘脑及其相关网络连接的功能磁共振成像

目的：探讨精神分裂症患者丘脑及其相关网络连接是否存在异常及脑功能连接对执行表现的影响。方法采用血氧水平依赖性功能磁共振成像方法,在静息和2-back任务状态下检测14例偏执型精神分裂症患者和16名正常志愿者的脑功能连接,将前额叶内侧皮层（ MPFC,BA10）作为种子点,应用SPM2、AFNI及Matlab软件进行图像数据处理,分别对患者组和正常对照组的2-back任务和静息状态行组内和组间两个水平的统计分析,统计阈值概率设定为P＝0.005（未校正）。结果正常对照组在静息状态时,与MPFC正相关的功能连接脑区主要分布在左侧丘脑前核、双额上回内侧（ BA6）、右胼胝体下部（伏隔核）（ BA34）及小脑蚓部等,患者组主要分布在双前额叶内侧回（BA9/10）;正常对照组在2-back任务时,与MPFC负相关的功能连接脑区主要分布在左侧丘脑背侧、双侧运动前区外侧（ BA6）、左顶下小叶/楔前叶（ BA7）、右侧小脑半球,患者组主要分布在右侧小脑半球、左顶上小叶/楔前叶（ BA7）、左额上回（ BA6）。正常对照组的反应正确率高于患者组[（89.89±8.05）％vs．（78.30±8.76）％,P＝0.01],其执行正确率与左侧丘脑背侧的相关性有统计学意义（ r＝-0.52,P＝0.04）。结论丘脑前核和背侧部在功能上分属不同系统。精神分裂症患者在静息状态时左侧丘脑前核-右侧伏隔核功能连接减低,2-back任务时左侧丘脑背侧部与前额叶、顶叶-小脑的功能连接减低,可能是精神分裂症患者执行能力低下的原因之一。     

偏执型精神分裂症Stroop实验的fMRI研究

目的研究偏执型精神分裂症完成注意力Stroop实验时的fMRI特点,探讨其脑功能机制。方法偏执型精神分裂症14例,正常对照组16例,按年龄、性别、文化层次进行配对。刺激采用Stroop任务,运用刺激-休息-刺激的模式。分别将两组数据标准化、合并和平均,对两组平均后的脑激活图像的激活区域及激活数目进行比较。结果①偏执型精神分裂症完成有色字和无色字干扰的Stroop实验反应时间长于对照组(P<0.05);完成有色字干扰Stroop实验错误率显著高于对照组(P<0.05);②偏执型精神分裂症在有色字干扰Stroop实验下左侧额中回、右侧前扣带皮质脑区激活计数小于对照组(P<0.05),颞叶、右侧额上回脑区激活计数高于对照组(P<0.05);③偏执型精神分裂症在两种Stroop实验时脑区激活计数无显著性差异(P>0.05),对照组在有色字干扰Stroop实验时右侧额下回、左侧额中回脑区激活计数显著多于无色字干扰的脑区激活计数(P<0.05)。结论Stroop实验激活了左右两侧额中回、额下回以及前扣带皮质;偏执型精神分裂症存在选择性注意障碍,这些障碍可能与左侧额中回、右侧前扣带回皮质以及颞叶脑区功能障碍有关。     

Working memory dysfunction in schizophrenia compared to healthy controls and patients with depression: evidence from event-related fMRI

Studies on working memory (WM) dysfunction in schizophrenia have reported several functionally aberrant brain areas including the lateral prefrontal cortex, superior temporal areas and the striatum. However, less is known about the relationship of WM-dysfunction, cerebral activation, task-accuracy and diagnostic specificity. Using a novel WM-task and event-related functional magnetic resonance imaging (fMRI), we studied healthy control subjects (n=17) and partially remitted, medicated inpatients meeting DSM-IV criteria for schizophrenia (n=19) and major depressive disorder (n=12). Due to the event-related technique, we excluded incorrectly performed trials, thus controlling for accuracy-related activation confounds. Compared with controls, patients with schizophrenia showed less activation in frontoparietal and subcortical regions at high cognitive load levels. Compared with patients with depression, schizophrenic patients showed less prefrontal activation in left inferior frontal cortex and right cerebellum. In patients with schizophrenia, a lack of deactivation of the superior temporal cortex was found compared to both healthy controls and patients with depression. Thus, we could not confirm previous findings of impaired lateral prefrontal activation during WM performance in schizophrenic patients after the exclusion of incorrectly performed or omitted trials in our functional analysis. However, superior temporal cortex dysfunction in patients with schizophrenia may be regarded as schizophrenia-specific finding in terms of psychiatric diagnosis specificity.     

Discriminating schizophrenia and bipolar disorder by fusing fMRI and DTI in a multimodal CCA+ joint ICA model

Diverse structural and functional brain alterations have been identified in both schizophrenia and bipolar disorder, but with variable replicability, significant overlap and often in limited number of subjects. In this paper, we aimed to clarify differences between bipolar disorder and schizophrenia by combining fMRI (collected during an auditory oddball task) and diffusion tensor imaging (DTI) data. We proposed a fusion method, "multimodal CCA+ joint ICA", which increases flexibility in statistical assumptions beyond existing approaches and can achieve higher estimation accuracy. The data collected from 164 participants (62 healthy controls, 54 schizophrenia and 48 bipolar) were extracted into "features" (contrast maps for fMRI and fractional anisotropy (FA) for DTI) and analyzed in multiple facets to investigate the group differences for each pair-wised groups and each modality. Specifically, both patient groups shared significant dysfunction in dorsolateral prefrontal cortex and thalamus, as well as reduced white matter (WM) integrity in anterior thalamic radiation and uncinate fasciculus. Schizophrenia and bipolar subjects were separated by functional differences in medial frontal and visual cortex, as well as WM tracts associated with occipital and frontal lobes. Both patients and controls showed similar spatial distributions in motor and parietal regions, but exhibited significant variations in temporal lobe. Furthermore, there were different group trends for age effects on loading parameters in motor cortex and multiple WM regions, suggesting that brain dysfunction and WM disruptions occurred in identified regions for both disorders. Most importantly, we can visualize an underlying function-structure network by evaluating the joint components with strong links between DTI and fMRI. Our findings suggest that although the two patient groups showed several distinct brain patterns from each other and healthy controls, they also shared common abnormalities in prefrontal thalamic WM integrity and in frontal brain mechanisms.     

Convergent evidence of the contribution of TP53 genetic variation (Pro72Arg) to metabolic activity and white matter volume in the frontal lobe in schizophrenia patients

Abnormalities in white matter (WM) volumes and integrity in schizophrenia, together with post-mortem studies showing reduced expression of oligodendrocyte/myelination genes and apoptotic processes taking place in oligodendrocytes, suggest the interest of major regulators of apoptosis as candidate genes for some features related to myelin integrity in schizophrenia. Protein p53, encoded by TP53 gene, has a central role in the control of apoptosis and is involved in oligodendrocyte development. TP53 gene polymorphisms may account for variability in WM features, metabolic activity and biochemical markers of neuronal integrity and membrane turnover. Pro72Arg and Ins16bp polymorphisms at TP53 gene were analyzed in 20 DSM-IV schizophrenia patients. T1/T2-weighted sequences of these patients were acquired using a 1.5T Philips Gyroscan system. Scans were transformed into Talairach space and segmented into gray matter (GM), WM and cerebrospinal fluid (CSF) using Statistical Parametric Mapping under a ROI approach. Likewise dorsolateral prefrontal cortex (DLPFC) metabolic activity was measured using a procedure based on MRI/PET image fusion. In 13 of these patients proton magnetic resonance spectroscopy was used to examine N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) levels in dorsolateral-medial prefrontal cortex (DLMPFC). MRI data were adjusted for age and brain volume using regression parameters from a healthy control group (n=45). Patients Pro/Arg heterozygous (Pro72Arg polymorphism) showed a generalized deficit in whole-brain WM that was especially prominent in frontal lobe and a lower metabolic activity in the DLPFC as compared to Pro/Pro homozygous. Pro/Arg subjects also showed decreased NAA/Cho and increased Cho/Cr ratios in right DLMPFC. TP53 genetic variability influences WM volumes in frontal lobes and it seems to modulate the metabolic activity in this region. Our results suggest that TP53 might influence aspects of myelin and white matter integrity which may account for some of the frontal dysfunction features commonly described in these patients.     

Functional neuroanatomy of auditory working memory in schizophrenia: relation to positive and negative symptoms

Functional brain imaging studies of working memory (WM) in schizophrenia have yielded inconsistent results regarding deficits in the dorsolateral prefrontal (DLPFC) and parietal cortices. In spite of its potential importance in schizophrenia, there have been few investigations of WM deficits using auditory stimuli and no functional imaging studies have attempted to relate brain activation during auditory WM to positive and negative symptoms of schizophrenia. We used a two-back auditory WM paradigm in a functional MRI study of men with schizophrenia (N = 11) and controls (N = 13). Region of interest analysis was used to investigate group differences in activation as well as correlations with symptom scores from the Brief Psychiatric Rating Scale. Patients with schizophrenia performed significantly worse and were slower than control subjects in the WM task. Patients also showed decreased lateralization of activation and significant WM related activation deficits in the left and right DLPFC, frontal operculum, inferior parietal, and superior parietal cortex but not in the anterior cingulate or superior temporal gyrus. These results indicate that in addition to the prefrontal cortex, parietal cortex function is also disrupted during WM in schizophrenia. Withdrawal-retardation symptom scores were inversely correlated with frontal operculum activation. Thinking disturbance symptom scores were inversely correlated with right DLPFC activation. Our findings suggest an association between thinking disturbance symptoms, particularly unusual thought content, and disrupted WM processing in schizophrenia.     

An MRI study of spatial probability brain map differences between first-episode schizophrenia and normal controls

We created a spatial probability atlas of schizophrenia to provide information about the neuroanatomic variability of brain regions of patients with the disorder. Probability maps of 16 regions of interest (ROIs) were constructed by taking manually parcellated ROIs from subjects' magnetic resonance images (MRIs) and linearly transforming them into Talairach space using the Montreal Neurological Institute (MNI) template. ROIs included temporal, parietal, and prefrontal cortex subregions, with a principal focus on temporal lobe structures. Subject Ns ranged from 11 to 28 for the different ROIs. Our global measure of the spatial distribution of the transformed ROI was the sum of voxels with 50% overlap among subjects. The superior temporal gyrus (STG) and fusiform gyrus (FG) had lower values for schizophrenic subjects than for normal controls, suggestive of greater spatial variability for these ROIs in schizophrenic subjects. For the computation of statistical significance of group differences in portions of the ROI, we used voxel-wise comparisons and Fisher's exact test. First-episode schizophrenic patients compared with controls showed lower probability (P < 0.05) at dorso-posterior areas of planum temporale and Heschl's gyrus, lateral and anterior regions in the left hippocampus (HIPP), and dorsolateral regions of fusiform gyrus. Importantly, most ROIs of schizophrenic subjects showed a significantly lower spatial overlap than controls, even after nonlinear spatial normalization, suggesting a greater heterogeneity in the spatial distribution of ROIs. There is consequently a need for caution in neuroimaging studies where data from schizophrenic subjects are normalized to a particular stereotaxic coordinate system based on healthy controls. Apparent group differences in activation may simply reflect a greater heterogeneity of spatial distribution in schizophrenia.     

Limbic over-activity in depression during preserved performance on the n-back task

The profile of cognitive dysfunction observed in patients with major depressive disorder (MDD) may be partially attributed to a deficit in the central executive component of working memory (WM). This could be the consequence of a functional deficit in regions of cortex that are associated with WM function in healthy adults. In order to investigate this assertion, ten patients with a diagnosis of MDD and ten matched healthy controls undertook a parametric WM task (i.e. the n-back task) during the acquisition of blood oxygen level dependent echo planar magnetic resonance images (BOLD EPI fMRI). There was no significant difference in the behavioral performance of depressed patients and controls. This was true for both accuracy and reaction time on the n-back task. Random effects analysis of the functional imaging data (using SPM99) revealed a significant difference in load-dependent activation in the medial orbitofrontal cortex/rostral anterior cingulate between patients and controls (cluster size (K(E))/volume = 128/1024 mm3, P(corrected) = 0.025). While both participant groups exhibited a significant decrease in activation in this region with increased task difficulty, the magnitude of this decrease was smaller in patients with MDD than in controls. Therefore, this study implies that the performance of WM tasks is associated with a dysfunctional activation of the medial orbitofrontal and rostral anterior cingulate cortex in MDD. The study thus offers a rationale for explaining depressive cognitive impairment by the abnormal fronto-limbic activation found in clinical depression.     

The effects of neuregulin1 on brain function in controls and patients with schizophrenia and bipolar disorder

Recent studies have identified neuregulin1 as a probable susceptibility gene for schizophrenia and bipolar disorder. However, little is known about how this gene may affect brain function to increase vulnerability to these disorders. The present investigation examined the impact of neuregulin1 genotype on brain function in patients with schizophrenia, patients with bipolar I disorder and healthy volunteers. We used functional magnetic resonance imaging to measure brain responses during a verbal fluency task in a total of 115 subjects comprising 41 patients with schizophrenia, 29 patients with bipolar disorder and 45 healthy volunteers. We then used statistical parametric mapping to estimate the main effects of diagnostic group, the main effect of genotype and their interaction. We tested the hypothesis that the high-risk variant of neuregulin1 would be associated with altered prefrontal function. In all three diagnostic groups, the high-risk variant of neuregulin1 was associated with greater deactivation in the left precuneus. In addition, there was an interaction between diagnosis and genotype in two regions of the prefrontal cortex. The right inferior frontal gyrus expressed increased activation in individuals with the high-risk variant, but only in patients with schizophrenia. Conversely, the right posterior orbital gyrus expressed increased activation in individuals with the high-risk variant, but only in patients with bipolar disorder. Our results suggest that genetic variation in neuregulin1 has a measurable impact on brain function and provide preliminary evidence for a disease-specific pattern of gene action in different regions of the prefrontal cortex.     

Evidence for a direct association between cortical atrophy and cognitive impairment in relapsing-remitting MS

Cognitive deficits affecting memory, attention and speed of information processing are common in multiple sclerosis (MS). The mechanisms of cognitive impairment remain unclear. Here, we examined the association between neuropsychological test performance and brain atrophy in a group of mildly disabled patients with relapsing-remitting MS. We applied voxel-based morphometry (SPM2) to investigate the distribution of brain atrophy in relation to cognitive performance. Patients had lower scores than control subjects on tests of memory and executive function, including the PASAT, Digit Span Backward and a test of short-term verbal memory (Memo). Among patients, but not healthy controls, performance on the PASAT, a comprehensive measure of cognitive function and reference task for the cognitive evaluation of MS-patients, correlated with global grey matter volume as well as with grey matter volume in regions associated with working memory and executive function, including bilateral prefrontal cortex, precentral gyrus and superior parietal cortex as well as right cerebellum. Compared to healthy subjects, patients showed a volume reduction in left temporal and prefrontal cortex, recently identified as areas predominantly affected by diffuse brain atrophy in MS. A comparison of low performers in the patient group with their matched control subjects showed more extensive and bilateral temporal and frontal volume reductions as well as bilateral parietal volume loss, compatible with the progression of atrophy found in more advanced MS-patients. These findings indicate that MS-related deficits in cognition are closely associated with cortical atrophy.