Fronto-parietal hypo-activation during working memory independent of structural abnormalities: conjoint fMRI and sMRI analyses in adolescent offspring of schizophrenia patients

Adolescent offspring of schizophrenia patients (HR-S) are an important group in whom to study impaired brain function and structure, particularly of the frontal cortices. Studies of working memory have suggested behavioral deficits and fMRI-measured hypoactivity in fronto-parietal regions in these subjects. Independent structural MRI (sMRI) studies have suggested exaggerated frontal gray matter decline. Therefore the emergent view is that fronto-parietal deficits in function and structure characterize HR-S. However, it is unknown if fronto-parietal sub-regions in which fMRI-measured hypo-activity might be observed are precisely those regions of the cortex in which gray matter deficits are also observed. To investigate this question we conducted conjoint analyses of fronto-parietal function and structure in HR-S (n=19) and controls (n=24) with no family history of psychoses using fMRI data during a continuous working memory task (2 back), and sMRI collected in the same session. HR-S demonstrated significantly reduced BOLD activation in left dorso-lateral prefrontal cortex (BA 9/46) and bilateral parietal cortex (BA 7/40). Sub-regions of interest were created from the significant fronto-parietal functional clusters. Analyses of gray matter volume from volume-modulated gray matter segments in these clusters did not reveal significant gray matter differences between groups. The results suggest that functional impairments in adolescent HR-S can be independent of impairments in structure, suggesting that the relationship between impaired function and structure is complex. Further studies will be needed to more closely assess whether impairments in function and structure provide independent or interacting pathways of vulnerability in this population.     

Functional brain maps of Tower of London performance: a positron emission tomography and functional magnetic resonance imaging study

Regional cerebral blood flow (rCBF) and blood oxygenation level-dependent (BOLD) contrasts represent different physiological measures of brain activation. The present study aimed to compare two functional brain imaging techniques (functional magnetic resonance imaging versus [(15)O] positron emission tomography) when using Tower of London (TOL) problems as the activation task. A categorical analysis (task versus baseline) revealed a significant BOLD increase bilaterally for the dorsolateral prefrontal and inferior parietal cortex and for the cerebellum. A parametric haemodynamic response model (or regression analysis) confirmed a task-difficulty-dependent increase of BOLD and rCBF for the cerebellum and the left dorsolateral prefrontal cortex. In line with previous studies, a task-difficulty-dependent increase of left-hemispheric rCBF was also detected for the premotor cortex, cingulate, precuneus, and globus pallidus. These results imply consistency across the two neuroimaging modalities, particularly for the assessment of prefrontal brain function when using a parametric TOL adaptation.     

The effect of gender on planning: An fMRI study using the Tower of London task

Since the introduction of brain mapping, evidences of functional gender differences have been corroborating previous behavioral and neuropsychological results showing a sex-specific brain organization. We investigated gender differences in brain activation during the performance of the Tower of London (TOL) task which is a standardized test to assess executive functions. Eighteen healthy subjects (9 females and 9 males) underwent fMRI scanning while solving a series of TOL problems with different levels of difficulty. Data were analyzed by modeling both genders and difficulty task load. Task-elicited brain activations comprised a bilateral fronto-parietal network, common to both genders; within this network, females activated more than males in dorsolateral prefrontal cortex (DLPFC) and right parietal cortex, whereas males showed higher activity in precuneus. A prominent parietal activity was found at low level of difficulty while, with heavier task demand, several frontal regions and subcortical structures were recruited. Our results suggest peculiar gender strategies, with males relying more on visuospatial abilities and females on executive processing.     

基于自动脑分割技术分析中国正常中老年人群脑结构体积

目的 采用自动脑分割技术分析中国正常中老年人群脑结构体积的差异。方法 对96名正常中老年志愿者采集MRI，以自动脑分割技术获得脑内各结构体积，观察脑内各结构体积在不同性别、年龄及左右侧之间的差异，分析年龄对脑内结构体积的影响。结果 不同性别之间，颅脑总体积绝对值，右侧壳核、左、右侧尾状核、右侧苍白球、右侧额叶灰质及左侧顶叶灰质标准体积值差异均有统计学意义（P均<0.05）。左右侧之间，丘脑、壳核、尾狀核、额叶、顶叶、枕叶、颞叶、扣带回灰质、岛叶及侧脑室标准体积值差异均有统计学意义（P均<0.05）。脑脊液、右侧脑室及第三脑室体积与年龄呈正相关（r=0.60、0.51、0.57，P均<0.05），双侧额叶和左侧岛叶，皮层灰质、顶叶灰质、颞叶灰质及左侧枕叶灰质体积与年龄均呈负相关（P均<0.05）。结论 自动脑分割技术能直观快速显示正常中老年人脑结构体积。不同性别健康中老年人脑内结构体积存在差异，随年龄增加，脑脊液、侧脑室及第三脑室体积增大，皮层灰质、额叶灰白质、顶枕颞叶灰质及岛叶体积缩小。     

A comprehensive assessment of gray and white matter volumes and their relationship to outcome and severity in schizophrenia

Preliminary data suggest an association of posterior cortical gray matter reduction with poor outcome in schizophrenia. We made a systematic MRI assessment of regional gray and white matter volumes, parcellated into 40 Brodmann's areas, in 104 patients with schizophrenia (51 with good outcomes, 53 with poor outcomes) and 41 normal comparison subjects, and investigated correlations of regional morphometry with outcome and severity of the illness. Schizophrenia patients displayed differential reductions in frontal and to a lesser degree temporal gray matter volumes in both hemispheres, most pronounced in the frontal pole and lateral temporal cortex. White matter volumes in schizophrenia patients were bilaterally increased, primarily in the frontal, parietal, and isolated temporal regions, with volume reductions confined to anterior cingulate gyrus. In patients with schizophrenia as a group, higher illness severity was associated with reduced temporal gray matter volumes and expanded frontal white matter volumes in both hemispheres. In comparison to good-outcome group, patients with poor outcomes had lower temporal, occipital, and to a lesser degree parietal gray matter volumes in both hemispheres and temporal, parietal, occipital, and posterior cingulate white matter volumes in the right hemisphere. While gray matter deficits in the granular cortex were observed in all schizophrenia patients, agranular cortical deficits in the left hemisphere were peculiar to patients with poor outcomes. These results provide support for frontotemporal gray matter reduction and frontoparietal white matter expansion in schizophrenia. Poor outcome is associated with more posterior distribution (posteriorization) of both gray and white matter changes, and with preferential impairment in the unimodal visual and paralimbic cortical regions.     

Increased glial metabolites predict increased working memory network activation in HIV brain injury

Deficits in attention and working memory are common in human immuno deficiency virus type 1 (HIV-1)-infected patients, but the pathophysiology of these deficits is poorly understood. Modern neuroimaging techniques, such as proton magnetic resonance spectroscopy ((1)H MRS) and functional MRI (fMRI), can assess some of the processes underlying HIV brain injury. To evaluate the model that attentional deficits in early HIV brain disease are related to brain inflammation, (1)H MRS and fMRI were performed in 14 HIV-positive subjects [acquired immunodeficiency syndrome (AIDS) dementia complex stage 1 or less]. Increasing attentional load on three working memory tasks was assessed with fMRI, and the concentrations of brain metabolites were measured with (1)H MRS in the frontal gray and white matter, and basal ganglia. Metabolite concentrations were correlated with fMRI blood oxygenation level-dependent (BOLD) signals, using a random-effects linear regression model in SPM99. Several positive correlations were observed between the BOLD signal strength in the working memory network (posterior parietal cortex and lateral prefrontal cortex) and the concentrations of frontal white matter and basal ganglia metabolites that are predominant in glial cells (choline-containing compounds, myo-inositol, and total creatine). In contrast, BOLD signals in the working memory network were not correlated with the concentration of N-acetyl compounds, which are markers of neuronal viability, or with metabolite concentrations in the frontal gray matter. These findings are consistent with previous results that mild HIV brain injury is associated with increased glial activation without major involvement of neuronal abnormalities. We propose that the inflammatory glial abnormalities reduce the efficiency of neural processing, and necessitate compensatory increases in attention in patients, and associated BOLD signals, to perform a given task. The same mechanism may also contribute to cognitive dysfunction in other brain diseases that involve inflammation.     

Frontostriatal system in planning complexity: a parametric functional magnetic resonance version of Tower of London task

In the present study, we sought to investigate which brain structures are recruited in planning tasks of increasing complexity. For this purpose, a parametric self-paced pseudo-randomized event-related functional MRI version of the Tower of London task was designed. We tested 22 healthy subjects, enabling assessment of imaging results at a second (random effects) level of analysis. Compared with baseline, planning activity was correlated with increased blood oxygenation level-dependent (BOLD) signal in the dorsolateral prefrontal cortex, striatum, premotor cortex, supplementary motor area, and visuospatial system (precuneus and inferior parietal cortex). Task load was associated with increased activity in these same regions. In addition, increasing task complexity was correlated with activity in the left anterior prefrontal cortex, a region supposed to be specifically involved in third-order higher cognitive functioning.     

Age-related networks of regional covariance in MRI gray matter: Reproducible multivariate patterns in healthy aging

Healthy aging is associated with brain volume reductions that involve the frontal cortex, but also affect other brain regions. We sought to identify an age-related network pattern of MRI gray matter using a multivariate statistical model of regional covariance, the Scaled Subprofile Model (SSM) with voxel based morphometry (VBM) in 29 healthy adults, 23-84 years of age (Group 1). In addition, we evaluated the reproducibility of the age-related gray matter pattern derived from a prior SSM VBM study of 26 healthy adults, 22-77 years of age (Group 2; Alexander et al., 2006) in relation to the current sample and tested the ability of the network analysis to extract an age-related pattern from both cohorts combined. The SSM VBM analysis of Group 1 identified a regional pattern of gray matter atrophy associated with healthy aging (R² = 0.64, p < 0.000001) that included extensive reductions in bilateral dorsolateral and medial frontal, anterior cingulate, insula/perisylvian, precuneus, parietotemporal, and caudate regions with areas of relative preservation in bilateral cerebellum, thalamus, putamen, mid cingulate, and temporal pole regions. The age-related SSM VBM gray matter pattern, previously reported for Group 2, was highly expressed in Group 1 (R² = 0.52, p < 0.00002). SSM analysis of the combined cohorts extracted a common age-related pattern of gray matter showing reductions involving bilateral medial frontal, insula/perisylvian, anterior cingulate and, to a lesser extent, bilateral dorsolateral prefrontal, lateral temporal, parietal, and caudate brain regions with relative preservation in bilateral cerebellum, temporal pole, and right thalamic regions. The results suggest that healthy aging is associated with a regionally distributed pattern of gray matter atrophy that has reproducible regional features. Whereas the network patterns of atrophy included parietal, temporal, and subcortical regions, involvement of the frontal brain regions showed the most consistently extensive and reliable reductions across samples. Network analysis with SSM VBM can help detect reproducible age-related MRI patterns, assisting efforts in the study of healthy and pathological aging.     

精神分裂症患者大脑灰质结构异常的VBM初步分析

目的评价基于体素的形态学分析法(VBM)分析精神分裂症大脑灰质结构的价值。方法采用GE Signa Twin Speed1.5T超导型MRI成像系统,对9例精神分裂症患者和9例年龄、性别与之相匹配的正常人行全脑扫描,获取16～18层脑结构MRT1图像。数据分析采用以SPM2软件包为基础的全自动VBM技术进行处理。结果与正常对照组比较,精神分裂症患者灰质明显减少区域在双侧前扣带回、前额叶、右侧颞上回(P<0.005),且大脑灰质减少具有不对称性,前额区偏侧化系数(AIs)为 0.19,颞区为-0.50。灰质明显增多的区域在右前额叶与右枕区、左顶下小叶(P<0.005),也具有不对称性,前额区AIs为-0.77,顶叶 1.00,枕区为-0.73。结论精神分裂症患者大脑灰质结构异常。VBM法具有简便、自动化的特点,在精神分裂症脑形态结构研究方面前景广阔。     

慢性梗阻性肺部病变患者脑皮质MRI形态学初步研究

目的研究应用基于体素的形态学分析(VBM)方法,观察慢性梗阻性肺部病变(COPD)患者的大脑皮质变化。材料与方法搜集在住院中的COPD患者(患者组)25例和年龄、性别、文化背景等相似的志愿者(对照组)25例进行肺功能、精神状态检查及血气分析。二组均行3D T1WI检查,采用VBM、FSL分析软件(簇体积减少70体素)。应用一般线性模型进行统计学分析,计算两组的全脑灰质总体积,基于体素比较两组全脑灰质各个体素体积的差异。结果COPD患者日常生活活动性、简易精神状态测试、视觉重建及数字记忆测试预测值明显低于正常人。患者额叶的双侧眶回、双侧额下回三角区(Broca区),以及双额内側回、右侧前岛回及深部核团等局部灰质体积较正常对照组减少(P值均0.01)。以统计学t值最大的体素在MNI中的坐标值分析,萎缩最明显的Brodmann脑区主要有47脑区(额上叶皮层)、双侧的13脑区(岛叶皮层)、22脑区(颞上回),及双侧的32脑区(前上扣带回皮层)、24脑区(前下扣带回皮质)。结论COPD患者的多个脑区可出现皮层体积的减少。损伤区域主要涉及前额叶皮质,以及双额内側回、右侧前岛回。与阻塞性睡眠呼吸暂停、先天性中枢呼气不足综合征以及高海拔居民的脑损伤部位相一致。     

Mapping motor inhibition: conjunctive brain activations across different versions of go/no-go and stop tasks

Conjunction analysis methods were used in functional magnetic resonance imaging to investigate brain regions commonly activated in subjects performing different versions of go/no-go and stop tasks, differing in probability of inhibitory signals and/or contrast conditions. Generic brain activation maps highlighted brain regions commonly activated in (a) two different go/no-go task versions, (b) three different stop task versions, and (c) all 5 inhibition task versions. Comparison between the generic activation maps of stop and go/no-go task versions revealed inhibitory mechanisms specific to go/no-go or stop task performance in 15 healthy, right-handed, male adults. In the go/no-go task a motor response had to be selectively executed or inhibited in either 50% or 30% of trials. In the stop task, the motor response to a go-stimulus had to be retracted on either 50 or 30% of trials, indicated by a stop signal, shortly (250 ms) following the go-stimulus. The shared "inhibitory" neurocognitive network by all inhibition tasks comprised mesial, medial, and inferior frontal and parietal cortices. Generic activation of the go/no-go task versions identified bilateral, but more predominantly left hemispheric mesial, medial, and inferior frontal and parietal cortices. Common activation to all stop task versions was in predominantly right hemispheric anterior cingulate, supplementary motor area, inferior prefrontal, and parietal cortices. On direct comparison between generic stop and go/no-go activation maps increased BOLD signal was observed in left hemispheric dorsolateral prefrontal, medial, and parietal cortices during the go/no-go task, presumably reflecting a left frontoparietal specialization for response selection.     

Voxel-based morphometric analysis of gray matter in first episode schizophrenia

Voxel-based morphometry (VBM) may afford a more rapid and extensive survey of gray matter abnormalities in schizophrenia than manually drawn region of interest (ROI) analysis, the current gold standard in structural MRI. Unfortunately, VBM has not been validated by comparison with ROI analyses, nor used in first-episode patients with schizophrenia or affective psychosis, who lack structural changes associated with chronicity. An SPM99-based implementation of VBM was used to compare a group of 16 patients with first-episode schizophrenia and a group of 18 normal controls and, as a further comparison, 16 first-episode patients with affective psychosis. All groups were matched for age and handedness. High spatial resolution structural images were normalized to the SPM99 template and then segmented, smoothed, and subjected to an ANCOVA. Schizophrenia vs control group comparisons: Voxel-by-voxel comparison of gray matter densities showed that only the left STG region was significantly different when corrected for multiple comparisons (P <.05), consistent with our previously reported manual ROI results. Analysis of the extent of voxel clusters, replicated with permutation analyses, revealed group differences in bilateral anterior cingulate gyri and insula (not previously examined by us with manually drawn ROI) and unilateral parietal lobe, but not in medial temporal lobe (where our ROI analysis had shown differences). However, use of a smaller smoothing kernel and a small volume correction revealed left-sided hippocampal group differences. Affective psychosis comparisons: When the same statistical thresholding criteria were used, no significant differences between affective psychosis patients and controls were noted. Since a major interest was whether patients with affective psychosis shared some anatomical abnormalities with schizophrenia, we applied a small volume correction and searched within the regions that were significantly less dense in schizophrenia compared to control subjects. With this statistical correction, the insula showed, bilaterally, the same pattern of differences in affective disorder subjects as that in schizophrenic subjects, whereas both left STG and left hippocampus showed statistical differences between affectives and schizophrenics, indicating the abnormalities specific to first-episode schizophrenia. These findings suggest both the promise and utility of VBM in evaluating gray matter abnormalities. They further suggest the importance of comparing VBM findings with more traditional ROI analyses until the reasons for the differences between methods are determined.     

Cortical intercorrelations of frontal area volumes in schizophrenia

BACKGROUND: Abnormal regional volume intercorrelations between selected cortical areas in schizophrenia patients were previously reported in several MRI studies. METHODS: A detailed analysis of frontal gray and white matter volume correlations with Brodmann's area volumes in the rest of the cortex was undertaken in normal subjects (n = 42) and patients with schizophrenia (n = 106), divided into good-outcome (n = 52) and poor-outcome (Kraepelinian; n = 54) subtypes. RESULTS: Frontal gray matter volumes were correlated with temporal lobe volumes in schizophrenics but not in normal subjects. Some frontal-parietal and frontal-occipital correlations showed a similar pattern. In comparison to normal subjects, schizophrenia patients showed weaker or absent intercorrelations intrafrontally, specifically between left motor-premotor and eye-movement areas (4, 6, 8) and dorsolateral area 44, as well as between left areas 9 and 46 vs. area 24 (cingulate gyrus). Poor outcome among patients with schizophrenia was associated with weaker correlations between left frontal area 9 and both medial and lateral temporal cortices, as compared to normal subjects or good-outcome patients. CONCLUSIONS: There appears to be a structural component in the task or symptom-related dysfunctional interactions between the frontal and more posterior cortical regions with preferential pathological involvement of frontotemporal and more limited involvement of frontoparietal and fronto-occipital systems in schizophrenia. Impaired regional associations within the frontal lobe, between left motor-premotor and Broca's areas, may play a role in language processing deficits in schizophrenia, while frontocingulate disconnection may result in working memory disturbances. Poor outcome may be associated with more widespread disconnections between prefrontal vs. cingulate and temporal regions in the left hemisphere, consistent with a disruption along the course of the left cingulum or uncinate bundles.     

The effect of appraisal level on processing of emotional prosody in meaningless speech

In visual perception of emotional stimuli, low- and high-level appraisal processes have been found to engage different neural structures. Beyond emotional facial expression, emotional prosody is an important auditory cue for social interaction. Neuroimaging studies have proposed a network for emotional prosody processing that involves a right temporal input region and explicit evaluation in bilateral prefrontal areas. However, the comparison of different appraisal levels has so far relied upon using linguistic instructions during low-level processing, which might confound effects of processing level and linguistic task. In order to circumvent this problem, we examined processing of emotional prosody in meaningless speech during gender labelling (implicit, low-level appraisal) and emotion labelling (explicit, high-level appraisal). While bilateral amygdala, left superior temporal sulcus and right parietal areas showed stronger blood oxygen level-dependent (BOLD) responses during implicit processing, areas with stronger BOLD responses during explicit processing included the left inferior frontal gyrus, bilateral parietal, anterior cingulate and supplemental motor cortex. Emotional versus neutral prosody evoked BOLD responses in right superior temporal gyrus, bilateral anterior cingulate, left inferior frontal gyrus, insula and bilateral putamen. Basal ganglia and right anterior cingulate responses to emotional versus neutral prosody were particularly pronounced during explicit processing. These results are in line with an amygdala-prefrontal-cingulate network controlling different appraisal levels, and suggest a specific role of the left inferior frontal gyrus in explicit evaluation of emotional prosody. In addition to brain areas commonly related to prosody processing, our results suggest specific functions of anterior cingulate and basal ganglia in detecting emotional prosody, particularly when explicit identification is necessary.     

Task switching: a high-density electrical mapping study

Flexibly switching between tasks is one of the paradigmatic functions of so-called "executive control" processes. Neuroimaging studies have implicated both prefrontal and parietal cortical regions in the processing necessary to effectively switch task. Beyond their general involvement in this critical function, however, little is known about the dynamics of processing across frontal and parietal regions. For instance, it remains to be determined to what extent these areas play a role in preparing to switch task before arrival of the stimulus to be acted upon and to what extent they play a role in any switching processes that occur after the stimulus is presented. Here, we used the excellent temporal resolution afforded by high-density mapping of brain potentials to explore the time course of the processes underlying (1) the performance of and (2) the preparation for a switch of task. We detail the contributions of both frontal and parietal processes to these two aspects of the task-switching process. Our data revealed a complex pattern of effects. Most striking was a period of sustained activity over bilateral parietal regions preceding the switch trial. Over frontal regions, activity actually decreased during this same period. Strongest sustained frontal activity was in fact seen for trials on which no switch was required. Further, we find that the first differential activity associated with switching task was over posterior parietal areas (220 ms), whereas over frontal scalp, the first differential activity is found more than 200 ms later. These and other effects are interpreted in terms of a "competition" model in which preparing to switch task is understood as the beginning of a competition between the potentially relevant tasks that is resolved during the switch trial. Our findings are difficult to account for with models that posit a strong role for frontal cortical regions in "reconfiguring" the system during switches of task.     

Evidence for premotor cortex activity during dynamic visuospatial imagery from single-trial functional magnetic resonance imaging and event-related slow cortical potentials

A strong correspondence has been repeatedly observed between actually performed and mentally imagined object rotation. This suggests an overlap in the brain regions involved in these processes. Functional neuroimaging studies have consistently revealed parietal and occipital cortex activity during dynamic visuospatial imagery. However, results concerning the involvement of higher-order cortical motor areas have been less consistent. We investigated if and when premotor structures are active during processing of a three-dimensional cube comparison task that requires dynamic visuospatial imagery. In order to achieve a good temporal and spatial resolution, single-trial functional magnetic resonance imaging (fMRI) and scalp-recorded event-related slow cortical potentials (SCPs) were recorded from the same subjects in two separate measurement sessions. In order to reduce inter-subject variability in brain activity due to individual differences, only male subjects (n = 13) with high task-specific ability were investigated. Functional MRI revealed consistent bilateral activity in the occipital (Brodmann area BA18/19) and parietal cortex (BA7), in lateral and medial premotor areas (BA6), the dorsolateral prefrontal cortex (BA9), and the anterior insular cortex. The time-course of SCPs indicated that task-related activity in these areas commenced approximately 550-650 ms after stimulus presentation and persisted until task completion. These results provide strong and consistent evidence that the human premotor cortex is involved in dynamic visuospatial imagery.     

Human frontal cortex: an MRI-based parcellation method.

The frontal lobe is not a single anatomical and functional brain region. Several lines of research have demonstrated that particular subregions within the frontal lobe are associated with specific motor and cognitive functions in the human being. Our main purpose is to develop a magnetic resonance image (MRI)-based parcellation method of the frontal lobe that permits us to explore plausible abnormalities in functionally relevant frontal subregions in brain illnesses. We describe a procedure using MRI for subdividing the entire frontal cortex into 11 subregions: supplementary motor area (SMA), rostral anterior cingulate gyrus (r-ACiG), caudal anterior cingulate gyrus (c-ACiG), superior cingulate gyrus (SCiG), medial frontal cortex (MFC), straight gyrus (SG), orbitofrontal cortex (OFC), precentral gyrus (PCG), superior frontal gyrus (SFG), inferior frontal gyrus (IFG), and middle frontal gyrus (MFG). Our method posits to conserve the topographic uniqueness of individual brains and is based on our ability to visualize both the three-dimensional (3D) rendered brain and the three orthogonal planes simultaneously. The reliability study for gray matter volume and surface area of each subregion was performed on a set of 10 MR scans by two raters. The intraclass R coefficients for gray matter volume of each subregion ranged between 0.86 and 0.99. We describe here a reproducible and reliable topography-based parcellation method of the frontal lobe that will allow us to use new approaches to understand the role of particular frontal cortical subregions in schizophrenia and other brain illnesses.     

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。     

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.     

Optimized voxel-based morphometry in children with developmental dyscalculia

Developmental dyscalculia (DD) is a specific learning disability affecting the normal acquisition of arithmetic skills. Current studies estimate that 3-6% of the school population is affected by DD. Genetic, neurobiological, and epidemiologic evidence indicates that dyscalculia is a brain-based disorder. Imaging studies suggest the involvement of parietal and prefrontal cortices in arithmetic tasks. The aim of the present study was to analyze if children with DD show structural differences in parietal, frontal, and cingulate areas compared to typically achieving children. Magnetic resonance imaging was obtained from 12 children with DD aged 9.3+/-0.2 years and 12 age-matched control children without any learning disabilities on a 1.5 T whole-body scanner. Voxel-based morphometry analysis with an optimization of spatial segmentation and normalization procedures was applied to compare the two groups in order to find differences in cerebral gray and white matter. Compared to controls, children with DD show significantly reduced gray matter volume in the right intraparietal sulcus (IPS), the anterior cingulum, the left inferior frontal gyrus, and the bilateral middle frontal gyri. White matter comparison demonstrates clusters with significantly less volume in the left frontal lobe and in the right parahippocampal gyrus in dyscalculic children. The decreased gray and white matter volumes in the frontoparietal network might be the neurological substrate of impaired arithmetic processing skills. The white matter volume decrease in parahippocampal areas may have influence on fact retrieval and spatial memory processing.