基于体素的形态测量法分析高功能孤独性障碍患儿的脑组织密度

目的 分析学龄孤独性障碍患儿脑组织密度.方法 对17例智能正常的孤独性障碍患儿(病例组)以及15名年龄、性别、智商与之相匹配的健康儿童(对照组)进行T1加权三维磁共振成像扫描,应用基于体素的形态测量法(VBM)比较两组脑灰质及脑白质密度的差异.结果 与对照组相比,孤独性障碍患儿右侧小脑前叶的脑灰质密度低.右前扣带回、右额中回区域的脑白质密度低,双侧顶下小叶、右缘上回、右中央后回、右颞上回、右小脑后叶、左楔前叶、左楔叶的脑灰质密度高(P<0.001).结论 智力正常的学龄孤独性障碍患儿脑组织密度异常明显,且部位广泛.     

长期海洛因依赖者前额叶功能连接的变化

以前额叶为种子点,利用静息态fMRI进行全脑时域相关的功能连接分析,观察长期海洛因成瘾者前额叶功能连接的变化。结果发现相比于正常对照,以左侧前额叶为种子点进行功能连接分析,海洛因成瘾者左侧前额叶与左侧海马、右侧前扣带回、左侧额中回、右侧额中回、右侧楔前叶功能连接明显降低;以右侧前额叶为种子点进行功能连接分析,海洛因成瘾者右侧前额叶与左侧眶额叶、左侧额中回功能连接明显降低。提示长期海洛因成瘾者前额叶与相关脑区的功能连接减弱,可能与海洛因成瘾的维持与戒断后复吸相关。     

Cue-induced cocaine craving: neuroanatomical specificity for drug users and drug stimuli

OBJECTIVE: Cocaine-related cues have been hypothesized to perpetuate drug abuse by inducing a craving response that prompts drug-seeking behavior. However, the mechanisms, underlying neuroanatomy, and specificity of this neuroanatomy are not yet fully understood. METHOD: To address these issues, experienced cocaine users (N=17) and comparison subjects (N=14) underwent functional magnetic resonance imaging while viewing three separate films that portrayed 1 ) individuals smoking crack cocaine, 2) outdoor nature scenes, and 3) explicit sexual content. Candidate craving sites were identified as those that showed significant activation in the cocaine users when viewing the cocaine film. These sites were then required to show significantly greater activation when contrasted with comparison subjects viewing the cocaine film (population specificity) and cocaine users viewing the nature film (content specificity). RESULTS: Brain regions that satisfied these criteria were largely left lateralized and included the frontal lobe (medial and middle frontal gyri, bilateral inferior frontal gyrus), parietal lobe (bilateral inferior parietal lobule), insula, and limbic lobe (anterior and posterior cingulate gyrus). Of the 13 regions identified as putative craving sites, just three (anterior cingulate, right inferior parietal lobule, and the caudate/lateral dorsal nucleus) showed significantly greater activation during the cocaine film than during the sex film in the cocaine users, which suggests that cocaine cues activated similar neuroanatomical substrates as naturally evocative stimuli in the cocaine users. Finally, contrary to the effects of the cocaine film, cocaine users showed a smaller response than the comparison subjects to the sex film. CONCLUSIONS: These data suggest that cocaine craving is not associated with a dedicated and unique neuroanatomical circuitry; instead, unique to the cocaine user is the ability of learned, drug-related cues to produce brain activation comparable to that seen with nondrug evocative stimuli in healthy comparison subjects.     

Risky decision making and the anterior cingulate cortex in abstinent drug abusers and nonusers

Risky decision making is a hallmark behavioral phenotype of drug abuse; thus, an understanding of its biological bases may inform efforts to develop therapies for addictive disorders. A neurocognitive task that measures this function (Rogers Decision-Making Task; RDMT) was paired with measures of regional cerebral perfusion to identify brain regions that may underlie deficits in risky decision making in drug abusers. Subjects were abstinent drug abusers (> or =3 months) and healthy controls who underwent positron emission tomography scans with H(2)(15)O. Drug abusers showed greater risk taking and heightened sensitivity to rewards than control subjects. Both drug abusers and controls exhibited significant activations in a widespread network of brain regions, primarily in the frontal cortex, previously implicated in decision-making tasks. The only significant group difference in brain activation, however, was found in the left pregenual anterior cingulate cortex, with drug abusers exhibiting less task-related activation than control subjects. There were no significant correlations between neural activity and task performance within the control group. In the drug abuse group, on the other hand, increased risky choices on the RDMT negatively correlated with activation in the right hippocampus, left anterior cingulate gyrus, left medial orbitofrontal cortex, and left parietal lobule, and positively correlated with activation in the right insula. Drug abuse severity was related positively to right medial orbitofrontal activity. Attenuated activation of the pregenual ACC in the drug abusers relative to the controls during performance on the RDMT may underlie the abusers' tendency to choose risky outcomes.     

反社会人格障碍男性青年大脑白质异常改变： 证据来自于基于体素脑形态测量学的DARTEL分析

SPM8 DARTEL工具包对3D脑结构成像数据对男性青年反社会人格障碍者和正常组的大脑白质结构进行基于体素的形态学分析（VBM）。结果显示,与正常对照者比较,反社会人格障碍者主要表现为双侧前额叶、右岛叶、中央前回,左右颞上回、右中央后回、右侧顶下小叶、右侧楔前叶、右枕中叶、右海马旁回及双侧扣带回等多个脑区白质体积密度增加,左颞中叶、右小脑的白质体积密度减小。相关分析显示,额内侧回的白质体积密度增加与反社会行为的评分(PDQ)有正相关。提示反社会人格障碍者存在多个脑区的白质形态学明显异常,这些异常可能与其反社会行为有关。     

White matter integrity of the whole brain is disrupted in first-episode schizophrenia

Diffusion tensor imaging studies in schizophrenia have demonstrated lower diffusion anisotropy within white matter that provides information about brain white matter integrity. We have examined whether white matter is abnormal in first-episode schizophrenia by using diffusion tensor imaging. Twenty-one schizophrenic patients and healthy controls underwent diffusion tensor imaging scans that analyzed by using a rigorous voxel-based approach. We found that fractional anisotropy in white matter of the patients was lower than that in controls at the cerebral peduncle, frontal regions, inferior temporal gyrus, medial parietal lobes, hippocampal gyrus, insula, right anterior cingulum bundle and right corona radiata. These results suggested that white matter integrity of the whole brain was disrupted in early illness onset of schizophrenia.     

Are structural brain abnormalities associated with suicidal behavior in patients with psychotic disorders?

Suicide represents a major health problem world-wide. Nevertheless, the understanding of the neurobiological underpinnings of suicidal behavior remains far from complete. We compared suicide attempters to non-attempters, and high vs. low lethality attempters, to identify brain regions associated with suicidal behavior in patients with psychotic disorders. 489 individuals with schizophrenia, schizoaffective disorder, or psychotic bipolar disorder I and 262 healthy controls enrolled in the B-SNIP study were studied. Groups were compared by attempt history and the highest medical lethality of previous suicide attempts. 97 patients had a history of a high lethality attempt, 51 of a low lethality attempt and 341 had no attempt history. Gray matter volumes were obtained from 3T structural MRI scans using FreeSurfer. ANCOVAs were used to examine differences between groups, followed by Hochberg multiple comparison correction. Compared to non-attempters, attempters had significantly less gray matter volume in bilateral inferior temporal and superior temporal cortices, left superior parietal, thalamus and supramarginal regions, right insula, superior frontal and rostral middle frontal regions. Among attempters, a history of high lethality attempts was associated with significantly smaller volumes in the left lingual gyrus and right cuneus. Compared to non-attempters, low lethality attempters had significant decreases in the left supramarginal gyrus, thalamus and the right insula. Structural brain abnormalities may distinguish suicide attempters from non-attempters and high from low lethality attempters among individuals with psychotic disorders. Regions in which differences were observed are part of neural circuitries that mediate inhibition, impulsivity and emotion, visceral, visual and auditory perception.     

Brain structural changes in schizophrenia patients with persistent hallucinations

Schizophrenia is characterised by the presence of a heterogeneous range of symptoms. Although there is a consensus regarding ventricular enlargement and regional grey matter deficits, the brain structural correlates of specific symptoms, such as auditory hallucinations, are not clearly defined. We used an automated voxel-wise analysis of dual-echo spin-echo MRI data from 28 patients with schizophrenia characterised by persistent hallucinations and 32 healthy controls. Patients demonstrated grey matter (GM) volume decrements in the insula bilaterally, and in the right superior temporal and fusiform gyri, and left inferior temporal gyrus. With the exception of the insula, these GM volume losses were correlated with severity of auditory hallucinations. GM excesses were observed in the right caudate nucleus and middle temporal gyrus. White matter deficits were observed adjacent to the left superior temporal gyrus, in the right internal capsule and inferior longitudinal fasciculus. These findings support the proposition that there are structural changes in the neural circuits underlying broader processing of affect-laden information in patients with schizophrenia prone to experiencing auditory hallucinations. Such deficits may obscure important cues for recognition of internal speech, contributing to failures of self-monitoring.     

PET imaging of dopamine D2 receptors in monkey models of cocaine abuse: genetic predisposition versus environmental modulation

OBJECTIVE: Animals self-administer many of the drugs that humans abuse, including cocaine. This article describes studies using preclinical animal models to differentiate the influences of neurobiological predisposition from environmental modulation of cocaine addiction, including studies from the authors' laboratory using nonhuman primates. METHOD: Addiction is described in terms of vulnerability, maintenance, and abstinence. This review focuses on dopamine receptor function, in particular that of the D2-like receptors, as measured by the noninvasive imaging procedure positron emission tomography. Findings from human studies of addiction and animal models are reviewed. RESULTS: There appears to be an inverse relationship between D2 receptor availability and vulnerability to the reinforcing effects of cocaine. Environmental variables can increase or decrease D2 receptor binding in an orderly fashion, and the resulting changes in D2 function influence the vulnerability to abuse cocaine. In maintenance, chronic cocaine exposure produces decreases in D2 receptor binding, which may be a mechanism that contributes to continued drug use. Finally, during abstinence there are individual differences in rates of recovery of D2 receptor availability. CONCLUSIONS: The goal of the preclinical research described in this review is to achieve a better understanding of individual differences in susceptibility and vulnerability to the reinforcing effects of cocaine. It is clear that the development of novel animal models will extend our understanding of the neurobiological basis of drug addiction to include a greater appreciation of the role of environmental factors in affecting predisposition, mediating continued drug use, and triggering relapse.     

Correlation between white matter damage and gray matter lesions in multiple sclerosis patients

We observed the characteristics of white matter fibers and gray matter in multiple sclerosis patients, to identify changes in diffusion tensor imaging fractional anisotropy values following white matter fiber injury. We analyzed the correlation between fractional anisotropy values and changes in whole-brain gray matter volume. The participants included 20 patients with relapsing-remitting multiple sclerosis and 20 healthy volunteers as controls. All subjects underwent head magnetic resonance imaging and diffusion tensor imaging. Our results revealed that fractional anisotropy values decreased and gray matter volumes were reduced in the genu and splenium of corpus callosum, left anterior thalamic radiation, hippocampus, uncinate fasciculus, right corticospinal tract, bilateral cingulate gyri, and inferior longitudinal fasciculus in multiple sclerosis patients. Gray matter volumes were significantly different between the two groups in the right frontal lobe(superior frontal, middle frontal, precentral, and orbital gyri), right parietal lobe(postcentral and inferior parietal gyri), right temporal lobe(caudate nucleus), right occipital lobe(middle occipital gyrus), right insula, right parahippocampal gyrus, and left cingulate gyrus. The voxel sizes of atrophic gray matter positively correlated with fractional anisotropy values in white matter association fibers in the patient group. These findings suggest that white matter fiber bundles are extensively injured in multiple sclerosis patients. The main areas of gray matter atrophy in multiple sclerosis are the frontal lobe, parietal lobe, caudate nucleus, parahippocampal gyrus, and cingulate gyrus. Gray matter atrophy is strongly associated with white matter injury in multiple sclerosis patients, particularly with injury to association fibers.     

Prefrontal cortical dysfunction in abstinent cocaine abusers

The anterior cingulate cortex (ACC) and lateral prefrontal (LPFC) cortex are brain regions important to executive cognitive functions (ECF). We determined ACC and LPFC function in 23-day abstinent cocaine abusers using positron emission tomography (PET H(2)(15)O) during performance of a modified version of the Stroop Task. Cocaine abusers showed less activation than non-drug-using comparison subjects in the left ACC and the right LPFC and greater activation in the right ACC. Average amount of cocaine used per week was negatively correlated with activity in the rostral ACC and right LPFC. Disruption of ECF in substance abusers could interfere with attempts to stop drug use and undermine treatment. Since impairment in ECF may be a common feature of various neuropsychiatric disorders, these findings have applicability beyond the neurobiology of addiction.     

Neurological basis of poor insight in psychosis: a voxel-based MRI study

BACKGROUND: As a reflection of poor insight, people with schizophrenia often disagree with carers and clinicians about whether (a) their experiences are abnormal, (b) they are mentally ill, and (c) they need treatment. METHODS: This study used voxel-based morphometry to identify the associations between total and regional grey matter volumes and self-reported and observer-rated insight in 52 patients with schizophrenia or schizoaffective disorder. Thirty healthy participants were also studied. RESULTS: There were positive associations in patients between (i) the ability to recognise experiences as abnormal and the total and right superior temporal gyrus grey matter volumes, (ii), awareness of problems ('something wrong') and the left precuneus grey matter volume and (iii) awareness of symptoms and attributing them to illness and grey matter volumes in the left superior-middle temporal gyrus and the right inferior temporal and lateral parietal gyri. The 'recognition of the need for medication' dimension did not correlate with total or any regional grey matter volumes. Relative to controls, patients had less total and regional grey matter volumes in the thalamus and middle occipital and superior temporal gyri. CONCLUSIONS: Lower grey matter volumes in the temporal and parietal regions that have been implicated in self-monitoring, working memory and access to internal mental states are associated with poor insight on certain dimensions in psychosis.     

应用体素的形态学研究复发缓解型多发性硬化患者的全脑灰质萎缩特点

目的 利用基于体素的形态学研究方法比较复发缓解型多发性硬化(relapsingremitting multiple selerosis,RRMS)患者和健康志愿者局部脑灰质的体积差异,推断灰质体积变化可能的病理生理机制.方法 对32例RRMS患者和32名性别、年龄匹配的健康志愿者进行常规MRI和三维T1WI扫描,采用参数统计软件包SPM5进行图像后处理,对RRMS组及对照组数据进行基于体素的统计学比较.利用相关分析检测患者灰质体积的变化与疾病病程、临床残疾程度及脑内可见病灶体积的相关性.结果 与对照组相比,RRMS患者的灰质萎缩区域分布广泛,在两侧丘脑(左侧2031,右侧1711)、尾状核(左侧815,右侧1031)、海马旁回(左侧313,右侧467)及额、颞、顶、枕叶多个皮质区域,灰质体积差异具有统计学意义(t=8.853～11.163,校正后均P＜0.01).RRMS患者两侧丘脑(左侧r=-0.596,右侧r=-0.694)和右侧尾状核(r=-0.409)的体积与脑内可见病灶的体积呈显著负相关(均P＜0.05).结论 RRMS患者灰质萎缩具有分布广泛的特征,尤其在深部灰质更显著.灰质萎缩的关键机制可能是继发于脑内可见病灶的神经元或轴索变性.

Abstract：

Objective To investigate the feature of regional grey matter volume changes in relapsing-remitting multiple sclerosis (RRMS) patients by voxel-based morphometry ( VBM) and presume the possible pathophysiological basis.Methods Conventional magnetic resonance imaging (MRI) and T1-weighted three-dimensional MRI were obtained from 32 RRMS and 32 sex- and age-matched normal controls.The comparison of grey matter volume between the two groups was analyzed by statistical analysis software SPM5 and VBM.A Pearson correlational analysis was used to assess correlation between gre matter loss and disease duration,expanded disability status scale (EDSS) and visible brain lesion volume.Results Compared with normal controls,RRMS patients had extensive bilateral grey matter atrophy in thalami (left 2031 and right 1711),caudate (left 815 and right 1031) and parahippocampal gyrus (left 313 and right 467),as well as several cortical regions in frontal,temporal,parietal,and occipital lobes (t value were between 8.853 and 11.163,all P ＜ 0.01).Regional grey matter loss in bilateral thalami ( r value were - 0.596 on left and were - 0.694 on right) and right caudate ( r = - 0.409 ) were strongly negatively correlated with visible brain lesion volume in RRMS (all P ＜ 0.05 ).Conclusions By means of VBM,extensive grey matter atrophy are found in RRMS patients,especially in deep grey matter.Axonal degeneration secondary to visible brain lesions may be a key pathogenesis of grey matter atrophy in RRMS.     

Increased cortical recruitment in Huntington's disease using a Simon task

Cognitive deficits in Huntington's disease (HD) have been attributed to neuronal degeneration within the striatum; however, postmortem and structural imaging studies have revealed more widespread morphological changes. To examine the impact of HD-related changes in regions outside the striatum, we used functional magnetic resonance imaging (fMRI) in HD to examine brain activation patterns using a Simon task that required a button press response to either congruent or incongruent arrow stimuli. Twenty mild to moderate stage HD patients and 17 healthy controls were scanned using a 3T GE scanner. Data analysis involved the use of statistical parametric mapping software with a random effects analysis model to investigate group differences brain activation patterns compared to baseline. HD patients recruited frontal and parietal cortical regions to perform the task, and also showed significantly greater activation, compared to controls, in the caudal anterior cingulate, insula, inferior parietal lobules, superior temporal gyrus bilaterally, right inferior frontal gyrus, right precuneus/superior parietal lobule, left precentral gyrus, and left dorsal premotor cortex. The significantly increased activation in anterior cingulate-frontal-motor-parietal cortex in HD may represent a primary dysfunction due to direct cell loss or damage in cortical regions, and/or a secondary compensatory mechanism of increased cortical recruitment due to primary striatal deficits.     

2～3岁广泛性发育障碍儿童脑体积的对照研究

目的:对比分析2～3岁广泛性发育障碍儿童的脑体积异常。方法:对50例广泛性发育障碍儿童(病例组)和36名年龄、性别、智商与之相匹配的发育障碍儿童(对照组)进行T1加权三维磁共振成像扫描,应用基于体素的形态测量法比较两组全脑和脑灰、白质体积的差异。结果:与对照组相比,2～3岁广泛性发育障碍儿童全脑及脑灰、白质体积显著增大(P<0.05);左侧颞中回及颞上回灰质体积显著增大;右侧中央前回、左侧中央后回灰质体积显著减小;额中回、左侧额上回、左侧颞中回、右侧额中回及右侧颞横回处脑白质体积显著增大(P<0.001)。结论:2～3岁广泛性发育障碍儿童可能存在多个脑区体积异常改变。     

Distinct MRI atrophy patterns in autopsy-proven Alzheimer's disease and frontotemporal lobar degeneration

To better define the anatomic distinctions between Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD), we retrospectively applied voxel-based morphometry to the earliest magnetic resonance imaging scans of autopsy-proven AD (N = 11), FTLD (N = 18), and controls (N = 40). Compared with controls, AD patients showed gray matter reductions in posterior temporoparietal and occipital cortex; FTLD patients showed atrophy in medial prefrontal and medial temporal cortex, insula, hippocampus, and amygdala; and patients with both disorders showed atrophy in dorsolateral and orbital prefrontal cortex and lateral temporal cortex (P(FWE-corr) < .05). Compared with FTLD, AD patients had decreased gray matter in posterior parietal and occipital cortex, whereas FTLD patients had selective atrophy in anterior cingulate, frontal insula, subcallosal gyrus, and striatum (P < .001, uncorrected). These findings suggest that AD and FTLD are anatomically distinct, with degeneration of a posterior parietal network in AD and degeneration of a paralimbic fronto-insular-striatal network in FTLD.     

Voxel‐Based Morphometric Analysis in Hypothyroidism Using Diffeomorphic Anatomic Registration via an Exponentiated Lie Algebra Algorithm Approach

The present study aimed to investigate whether brain morphological differences exist between adult hypothyroid subjects and age‐matched controls using voxel‐based morphometry (VBM) with diffeomorphic anatomic registration via an exponentiated lie algebra algorithm (DARTEL) approach. High‐resolution structural magnetic resonance images were taken in ten healthy controls and ten hypothyroid subjects. The analysis was conducted using statistical parametric mapping. The VBM study revealed a reduction in grey matter volume in the left postcentral gyrus and cerebellum of hypothyroid subjects compared to controls. A significant reduction in white matter volume was also found in the cerebellum, right inferior and middle frontal gyrus, right precentral gyrus, right inferior occipital gyrus and right temporal gyrus of hypothyroid patients compared to healthy controls. Moreover, no meaningful cluster for greater grey or white matter volume was obtained in hypothyroid subjects compared to controls. Our study is the first VBM study of hypothyroidism in an adult population and suggests that, compared to controls, this disorder is associated with differences in brain morphology in areas corresponding to known functional deficits in attention, language, motor speed, visuospatial processing and memory in hypothyroidism.     

Reduced cortical thickness in non-medicated patients with obsessive-compulsive disorder

Increasing evidence suggests the presence of grey matter volume abnormalities in patients with obsessive-compulsive disorder (OCD) and the mediation of the expression of different OCD symptoms by discrete neural systems of the brain. However, limited studies have investigated the abnormalities of cortical thickness, and their results are comparatively inconsistent, possibly owing to the inclusion of medicated patients. Therefore, this study investigated cortical thickness abnormalities using surface-based analysis to identify distinct neural correlates of each symptom dimension in non-medicated patients with OCD. Thirty non-medicated patients with OCD and 30 age- and gender-matched healthy controls underwent magnetic resonance imaging. Group comparison of cortical thickness was performed using surface-based analysis. We also conducted correlation analysis between cortical thickness and each symptom dimension score. Compared to the healthy controls, the OCD patients had statistically significant reduction in cortical thickness in the cluster that contained the left superior temporal gyrus and posterior insular cortex (p<.05, corrected); no areas of the brain had significantly greater cortical thickness. Negative correlation was also found between cortical thickness and "cleaning" dimension scores in the left postcentral and right superior parietal gyri. The present results suggest that cortical thinning in the region that contains the left superior temporal gyrus and posterior insula may underlie pathophysiology of OCD and that discrete neural systems may mediate the "cleaning" symptom dimension.     

Depression is associated with increased sensitivity to signals of disgust: A functional magnetic resonance imaging study

Emotions of fear and disgust are related to core symptoms of depression. The neurobiological mechanisms of these associations are poorly understood. This functional magnetic resonance imaging study aimed at examining the Blood oxygenation level dependent (BOLD) response to facial expressions of fear and disgust in patients with major depressive disorder.Nine patients in an episode of major depression and nine healthy controls underwent two functional magnetic resonance imaging experiments where they judged the gender of facial identities displaying different degrees (mild, strong) of fear or disgust, intermixed with non-emotional faces.Compared with healthy controls, patients with depression demonstrated greater activation in left insula, left orbito-frontal gyrus, left middle/inferior temporal gyrus, and right middle/inferior temporal gyrus to expressions of strong disgust. Depressed patients also demonstrated reduced activation in left inferior parietal lobe to mildly fearful faces.Enhanced activation to facial expressions of disgust may reflect an emotion processing bias that suggests high relevance of emotion of disgust to depression.