未服药的强迫障碍患者脑灰质体积异常的MRI研究

目的:应用脑磁共振成像(MRI)基于体素的形态测量学(VBM)比较未服药的强迫障碍患者脑灰质体积与正常人群间的差异,并探讨强迫障碍患者脑灰质体积的改变与临床现象之间的相关性。方法:纳入符合美国精神障碍诊断与统计手册第4版(DSM-Ⅳ)诊断标准的20例未服药的强迫障碍门诊患者,以及20名性别、年龄和受教育程度相匹配的健康对照。所有被试均接受头部磁共振扫描。采用VBM的分析方法,比较强迫障碍患者与健康对照之间脑灰质体积的差异。采用耶鲁-布郎强迫量表(Y-BOCS)、汉密顿抑郁量表(HAM D)、汉密顿焦虑量表(HAM A)评估临床症状。在控制焦虑、抑郁症状的前提下,分析强迫障碍患者异常的脑灰质体积与临床现象之间的关系。结果:与对照组相比,强迫障碍组的眶额回、颞上回、颞下回、小脑、楔前叶、辅助运动区及中央后回的灰质体积减少(P0.05,Al-phaSim校正);眶额回灰质体积的减少与Y-BOCS量表总分呈负相关(r=-0.49,P0.05)。结论:本研究结果提示眶额-纹状体-丘脑环路中的眶额回在强迫障碍的发生中起重要的作用,其他脑区如颞叶和小脑灰质体积减少,可能也参与了强迫障碍的发生。     

基于VBM-DARTEL的局灶性皮质发育不良脑灰质体积异常检测方法

目的:局灶性皮质发育不良(Focal Cortical Dysplasia,FCD)是导致药物难治性癫痫的重要病因之一。如何应用磁共振影像探究FCD全脑解剖结构的异常变化部位和定位,对临床诊断和治疗具有重要意义。方法:本文建立一种基于VBM-DARTEL的FCD脑灰质异常检测方法。该方法包括对磁共振结构像进行图像分割、DARTEL模板制作、图像标准化等,最后使用双样本独立t检验统计分析患者组和对照组全脑灰质体积的差异,从而得到FCD脑灰质的病变特征。结果:与正常对照组相比,FCD患者组双侧大脑半球存在广泛脑区的灰质体积异常;FCD患者的脑灰质存在萎缩,并伴有灰质体积异常增大的脑区,且多集中在额叶和颞叶等区域。结论:基于DARTEL的VBM方法可以有效地检测FCD患者脑灰质体积的异常变化,且能准确定位FCD病灶。     

强迫症患者大脑皮层形态与前瞻记忆的关系

目的:分析强迫症(obsessive-compulsive disorder, OCD)患者是否存大脑皮层形态异常,及其与前瞻记忆的关系。方法:36名强迫症患者和26名对照组被试分别完成了大脑结构磁共振扫描及评估前瞻记忆等变量的系列评估量表。比较强迫症组和对照组皮层厚度与灰质体积差异,并分别计算两组大脑皮层形态与前瞻记忆的相关。结果:OCD组左脑楔前叶等脑区皮层厚度及右脑扣带回后部等脑区灰质体积显著低于对照组。对照组前瞻记忆分量表得分与右脑中颞叶等脑区灰质体积和左脑扣带回后部等脑区皮层厚度呈显著负相关。OCD组前瞻记忆分量表得分与上额叶等脑区灰质体积呈显著正相关。结论:与对照组相比,OCD组大部分皮质表现出衰退。正常人群某些脑区皮质衰退与较差的前瞻记忆有关,而OCD组不同脑区的皮层形态与前瞻记忆的关系异于对照组。     

丁丙诺啡舌下片合并东莨菪碱、异丙嗪药物依赖者脑灰质密度的研究

目的:观察盐酸丁丙诺啡舌下片(sublingual buprenorphine)合并东莨菪碱(scopolamine)、异丙嗪(promet鄄hazine)药物依赖者(简称BSP依赖者)脑灰质密度的变化,并比较其与海洛因依赖者脑结构损害的异同。方法:采用基于像素的形态学测量(voxel-based morphometry,VBM)方法对16例BSP依赖者、20例海洛因依赖者停药第3天、第2个月的脑灰质密度进行了组间以及组内自身前后对比研究,并设立18例正常对照者。结果:与正常对照组相比,BSP滥用可导致成瘾者大脑广泛性脑结构损害,表现为灰质密度下降,涉及额叶、顶叶、颞叶、枕叶、岛叶、纹状体等脑区;与海洛因依赖组相比,停药3天BSP依赖组脑区灰质受损程度重于海洛因依赖组,且随着停药时间的延长,BSP依赖者灰质恢复进程慢于海洛因依赖者。结论:BSP滥用可造成依赖者广泛性、严重的脑皮质结构异常,主要集中在额叶等与成瘾关系密切的脑区。BSP滥用较海洛因更易损伤大脑皮质神经元,且大脑灰质恢复进程慢于海洛因依赖组,这提示BSP滥用对大脑皮质神经元的损害在短时间难以恢复。     

单、双相抑郁障碍患者大脑灰质体积比较

目的:检测单、双相抑郁组、健康对照组的脑灰质体积差异,为鉴别单、双相抑郁障碍提供参考。方法:入组单相抑郁患者17例、双相抑郁患者19例及健康对照28例,以基于体素形态学分析对脑结构磁共振图像进行预处理。结果:与健康对照比较,单、双相抑郁障碍显示了右小脑前叶灰质体积显著减少;与另两组被试比较,单相抑郁障碍显示右颞上回灰质体积显著减少;相关分析显示双相抑郁障碍右小脑前叶灰质体积与抑郁量表得分呈负相关。结论:单、双相抑郁障碍以右小脑前叶灰质体积下降为共同特征,而右颞上回灰质体积差异显示了两种疾病神经解剖结构差异。     

正常人和精神分裂症患者脑灰质体积分析的性别效应

目的:通过比较男性和女性正常人、男性和女性精神分裂症患者之间的脑灰质体积差异,探讨脑结构分析中的性别效应。方法:采集60例正常人(30例男性)和96例精神分裂症患者(48例男性)的高分辨率三维脑结构磁共振图像,运用基于体素的形态测量法(VBM)进行分析,获得每一个体的脑灰质体积图像。采用两样本t检验分别比较男性和女性正常人,男性和女性精神分裂症患者之间的脑灰质体积差异。结果:与女性正常人相比,男性正常人左侧的颞中回和额中回、右侧的边缘叶和颞中回的灰质体积较大(P<0.001),而左侧尾状核和右侧海马的灰质体积较小(P<0.001)。与女性精神分裂症患者相比,男性患者双侧的颞下回和海马、左侧的颞上回和颞中回的灰质体积较大(P<0.001),而未发现灰质体积较小的脑区。结论:性别效应是影响正常人或精神分裂症患者脑结构分析的重要因素。     

精神分裂症患者额叶、颞叶和边缘脑区的灰质体积下降

目的:探讨精神分裂症患者全脑灰质体积变化及其特点.方法:对85例精神分裂症患者和85例健康对照进行脑结构磁共振成像,以最近更新的基于体素的形态测量法检测两组的脑灰质体积差异.结果:精神分裂症患者存在脑灰质体积下降,主要位于双侧颞上回、岛叶和额下回,左侧海马和右侧颢下回.结论:额叶、颞叶和边缘脑区的异常可能是精神分裂症的关键的病理基础.     

脑结构形态学改变是精神分裂症的遗传内表型

目的 通过对首发精神分裂症患者及其未患病同胞的磁共振成像脑结构分析,探讨遗传因素对脑结构改变的影响程度,为发现精神分裂症的遗传内表型提供实验依据.方法 采用优化的基于体素的形态学研究方法对15例首发精神分裂症患者、19名首发精神分裂症患者未患病同胞及38名正常对照的大脑磁共振图像进行处理,采用一般线性模型进行统计分析.结果 与正常对照组相比,患者组在双侧颢叶、双侧枕叶、左侧岛叶、左侧额叶额上回及右豆状核苍白球灰质有明显减少;在双侧顶叶及双侧边缘叶扣带回灰质增加;未患病同胞组在右侧颞叶、双侧枕叶、左侧岛叶及左侧额叶中央前回等区域灰质明显减少;在左侧顶叶及双侧小脑后叶灰质增加.患者较同胞左侧顶叶楔前叶灰质有增加,未发现两者其他区域存在明显差异.结论 精神分裂症患者及其同胞存在相似的脑结构异常,遗传因素可能是导致精神分裂症脑结构异常的重要因素,提示脑结构形态学改变是精神分裂症的遗传内表型.     

强迫症患者大脑灰质体积变化——基于体素的形态学分析

目的探讨强迫症(OCD)患者大脑灰质体积的变化,并分析其在发病过程中可能存在的相关机制。方法选择31例年龄17～47岁重度强迫症患者和31例正常对照被试者,获取脑结构磁共振T1图像,使用基于体素的形态学测量(VBM)方法,比较强迫症组和对照组大脑灰质体积的差异,并将患者灰质体积差异区与其临床评分进行相关分析。结果与对照组相比,OCD患者在左侧壳核、岛叶、运动前区、顶上小叶以及右侧角回处体积显著减小。左侧壳核和岛叶的体积与患者贝克焦虑量表(BAI)评分成显著负相关。结论左侧壳核、岛叶、运动前区、顶上小叶以及右侧角回的灰质体积变化影响了该脑区功能,从而导致了OCD患者的部分症状。其中左侧壳核以及岛叶的损伤与患者焦虑情绪的异常密切相关。     

基于体素的形态学分析唇腭裂患儿脑结构特征

目的 采用基于体素的形态学分析(VBM)方法探讨唇腭裂患儿脑结构特征.方法 在1.5 T磁共振扫描仪上采集数据,运用优化VBM方法比较10例唇腭裂患儿及10例正常对照婴幼儿的脑结构.对2组婴幼儿的灰白质密度和体积进行基于体素的双样本t检验,对比结果采用国际通用的统计参数图(SPM)表示,分析唇腭裂患儿大脑灰质密度及体积异常区域分布特征及其临床意义.结果 唇腭裂组的灰质体积在属于额上回的双侧前额叶内侧显著低于正常对照组(差异团簇体积体素个数:5220、4871,团簇水平校正后P值均小于0.05),灰质密度在左侧颞上回显著高于正常对照组(体素水平校正后P值小于0.05),脑白质密度和体积均无显著性的差异.结论 唇腭裂患儿与听觉及认知有关的皮层可能异于正常婴幼儿,应对此类患儿进行中枢听觉处理功能及认知功能的早期检查和早期干预.     

Gray matter reduction associated with psychopathology and cognitive dysfunction in unipolar depression: a voxel-based morphometry study

BACKGROUND: Functional neuroimaging studies on both cognitive processing and psychopathology in patients with major depression have reported several functionally aberrant brain areas within limbic-cortical circuits. However, less is known about the relationship between psychopathology, cognitive deficits and regional volume alterations in this patient population. METHODS: By means of voxel-based morphometry (VBM) and a standardized neuropsychological test battery, we examined 15 patients meeting DSM-IV criteria for major depression disorder and 14 healthy controls in order to investigate the relationship between affective symptoms, cognitive deficits and structural abnormalities. RESULTS: Patients with depression showed reduced gray matter concentration (GMC) in the left inferior temporal cortex (BA 20), the right orbitofrontal (BA 11) and the dorsolateral prefrontal cortex (BA 46). Reduced gray matter volume (GMV) was found in the left hippocampal gyrus, the cingulate gyrus (BA 24/32) and the thalamus. Structure-cognition correlation analyses revealed that decreased GMC of the right medial and inferior frontal gyrus was associated with both depressive psychopathology and worse executive performance as measured by the Wisconsin Card Sorting Test (WCST). Furthermore, depressive psychopathology and worse performance during the WCST were associated with decreased GMV of the hippocampus. Decreased GMV of the cingulate cortex was associated with worse executive performance. LIMITATIONS: Moderate illness severity, medication effects, and the relatively small patient sample size should be taken into consideration when reviewing the implications of these results. CONCLUSIONS: The volumetric results indicate that regional abnormalities in gray matter volume and concentration may be associated with both psychopathological changes and cognitive deficits in depression.     

Medial temporal lobe abnormalities in pediatric unipolar depression

In vivo anatomical magnetic resonance imaging (MRI) studies in adults with major depressive disorder (MDD) have implicated neurocircuitries involved in mood regulation in the pathophysiology of mood disorders. Specifically, abnormalities in the medial temporal lobe structures have been reported. This study examined a sample of children and adolescents with major depressive disorder to investigate anatomical abnormalities in these key medial temporal brain regions. Nineteen children and adolescents with DSM-IV major depression (mean age +/- S.D.=13.0 +/- 2.4 years; 10 unmedicated) and 24 healthy comparison subjects (mean age +/- S.D.=13.9 +/- 2.9 years) were studied using a 1.5T Philips MRI scanner. We measured hippocampus and amygdala gray matter volumes. MRI structural volumes were compared using analysis of covariance with age and total brain volumes as covariates. Pediatric depressed patients had significantly smaller left hippocampal gray matter volumes compared to healthy controls (1.89 +/- 0.16 cm(3) versus 1.99 +/- 0.18 cm(3), respectively; F=5.0, d.f.=1/39, p=0.03; effect size: eta2(p) =0.11). Unmedicated depressed patients showed a trend towards smaller left hippocampal volumes compared to medicated patients and healthy subjects (F=2.8, d.f.=2/38, p=0.07; effect size: eta2(p) =0.13). There were no statistically significant differences in mean volumes for left or right amygdala. Smaller left hippocampal volumes in children and adolescents with MDD are in agreement with findings from adult studies and suggest that such abnormalities are present early in the course of the illness. Amygdala volumes are not abnormal in this age group. Smaller hippocampal volumes may be related to an abnormal developmental process or HPA axis dysfunction.     

Male elderly subthreshold depression patients have smaller volume of medial part of prefrontal cortex and precentral gyrus compared with age-matched normal subjects: a voxel-based morphometry

BACKGROUND: The brain morphological changes in subthreshold depression (sD) have not been clarified. We examined the structural difference in regional gray matter volume between community-dwelling elderly subjects with sD and age-matched nondepressed normal subjects by voxel-based morphometry (VBM) based on magnetic resonance imaging (MRI). METHODS: Thirty-four community-dwelling elderly subjects with sD and 109 age-matched nondepressed normal subjects were studied by MRI. We defined subjects with sD as those who showed a Geriatric Depression Scale score of 15 or higher and a Mini Mental State Examination score of 22 or higher, and do not fulfill the criteria of major depressive disorder (MDD) in the Diagnostic and Statistical Manual for Mental Disorders IV. We collected brain magnetic resonance images of 34 subjects with sD and 109 age-matched normal subjects, and analyzed the difference in regional gray matter volume between these two groups by VBM. RESULTS: Male subjects with sD had significantly smaller volumes of the medial part of the bilateral frontal lobes and the right precentral gyrus than normal male subjects. LIMITATIONS: We have not clarified the discrepancy in the results of gender difference. CONCLUSIONS: Our study revealed that even community-dwelling elderly male subjects with sD show bilateral prefrontal gray matter volume reduction, which was reported to be observed in elderly patients with MDD, although there is no significant volume reduction in the hippocampus, which was also reported to be observed in MDD. Our study may contribute to clarifying the mechanism underlying brain pathological changes in sD.     

Combined analyses of gray matter voxel-based morphometry and white matter tract-based spatial statistics in pediatric bipolar mania

Background

Ample evidence has suggested the presence of gray matter (GM) and white matter (WM) abnormalities in bipolar disorder (BD) patients, including pediatric bipolar disorder (PBD). However, little research has been done in PBD patients that carefully classify the mood states. The aim of the present study is to investigate the brain structural changes in PBD-mania children and adolescents.

Methods

Eighteen children and adolescents with bipolar mania (male/female, 6/12) aged 10–18 years old and 18 age- and sex-matched healthy controls were included in the present study. The 3D T1-weighted magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) data were obtained on a Siemens 3.0 T scanner. Voxel-based morphometry (VBM) analysis and tract-based spatial statistics (TBSS) analysis were conducted to compare the gray matter volume and white matter fractional anisotropy (FA) value between patients and controls. Correlations of the MRI data of each survived area with clinical characteristics in PBD patients were further analyzed.

Results

As compared with the control group, PBD-mania children showed decreased gray matter volume in the left hippocampus. Meanwhile, significant lower FA value was detected in the right anterior cingulate (AC) in the patient group. No region of increased gray matter volume or FA value was observed in PBD-mania. The hippocampal volume was negatively associated with the Young Mania Rating Scale (YMRS) score when controlling for clinical characteristics in PBD-mania patients, however, there was no significant correlation of FA value of the survived area with illness duration, the onset age, number of episodes, or the YMRS score in PBD-mania patients.

Limitation

The present outcomes require replication in larger samples and verification in medication free subjects.

Conclusions

Our findings highlighted that extensive brain structural lesions (including GM and WM) were existed in PBD-mania. The widespread occurrence of structural abnormalities mainly located in the anterior limbic network (ALN) which suggested that this network might contribute to emotional and cognitive dysregulations in PBD.     

Decreased cortical gray and cerebral white matter in male patients with familial bipolar I disorder

BACKGROUND: Previous MRI studies of bipolar disorder have failed to consistently demonstrate cortical gray or cerebral white matter tissue loss, as well as sulcal or ventricular enlargement. The inconsistencies are most likely due to the clinical and gender heterogeneity of the study populations as well as the different MRI acquisition and processing techniques. The objective of this study was to determine if there was a cortical gray matter and cerebral white matter deficit as well as sulcal and ventricular enlargement in a homogeneous sample of euthymic male patients with familial bipolar I disorder. METHODS: MRI tissue segmentation was utilized to obtain cortical gray matter, cerebral white matter, ventricular cerebrospinal fluid (CSF), and sulcal CSF volumes in 22 euthymic males with familial bipolar I disorder and 32 healthy male control subjects. RESULTS: Relative to the controls, the familial bipolar I patients demonstrated: (1) significant reductions of both cortical gray matter and cerebral white matter volumes; and (2) significant increases in both sulcal and ventricular CSF volumes. In the bipolar group, there was a significant negative correlation between cortical gray matter volume and sulcal CSF volume. LIMITATIONS: Small sample size, retrospective interviews, possible medication effects. CONCLUSIONS: These results provide evidence for significant cortical gray matter and cerebral white matter deficits and associated sulcal and ventricular enlargement in euthymic males with familial bipolar I disorder.     

Impact of the DISC1 Ser704Cys polymorphism on risk for major depression, brain morphology and ERK signaling

Disrupted-in-schizophrenia 1 (DISC1), identified in a pedigree with a familial psychosis with the chromosome translocation (1:11), is a putative susceptibility gene for psychoses such as schizophrenia and bipolar disorder. Although there are a number of patients with major depressive disorder (MDD) in the family members with the chromosome translocation, the possible association with MDD has not yet been studied. We therefore performed an association study of the DISC1 gene with MDD and schizophrenia. We found that Cys704 allele of the Ser704Cys single-nucleotide polymorphism (SNP) was associated with an increased risk of developing MDD (P=0.005, odds ratio=1.46) and stronger evidence for association in a multi-marker haplotype analysis containing this SNP (P=0.002). We also explored possible impact of Ser704Cys on brain morphology in healthy volunteers using MR imaging. We found a reduction in gray matter volume in cingulate cortex and a decreased fractional anisotropy in prefrontal white matter of individuals carrying the Cys704 allele compared with Ser/Ser704 subjects. In primary neuronal culture, knockdown of endogenous DISC1 protein by small interfering RNA resulted in the suppression of phosphorylation of ERK and Akt, whose signaling pathways are implicated in MDD. When effects of sDISC1 (Ser704) and cDISC1 (Cys704) proteins were examined separately, phosphorylation of ERK was greater in sDISC1 compared with cDISC1. A possible biological mechanism of MDD might be implicated by these convergent data that Cys704 DISC1 is associated with the lower biological activity on ERK signaling, reduced brain gray matter volume and an increased risk for MDD.     

Using the CES-D in a two-phase survey for depressive disorders among nonreferred adolescents in Taipei: a stratum-specific likelihood ratio analysis

BACKGROUND: Efficient screening is important in two-phase surveys. We examined whether the Center for Epidemiologic Studies Depression Scale (CES-D) is an appropriate instrument for screening depressive disorders among adolescents in Taipei, an ethnic group whose depression is little known of. METHODS: Among the 2440 students of a school in Taipei, aged 12 to 16 years who completed the CES-D and eating attitude test (EAT; response rate=98.5%), 178 were randomly selected from four subgroups defined by the 90th percentile of the two screening tools for face-to-face interview, using the Schedule for Affective Disorders and Schizophrenia for Children (K-SADS). Discriminatory validities of instruments for depressive disorders were estimated, and then a stratum-specific likelihood ratio (SSLR) analysis was conducted for instruments with sufficient validity. RESULTS: The prevalence estimates of depressive disorders varied with different levels of impairment, with a value of 2.4% for major depressive disorder and 0.3% for dysthymic disorder if at least two impairment items were endorsed. The areas under the receiver operative characteristic (ROC) curves were consistently high (0.88-0.90) for major depressive disorder with or without impairment requirement, but low (0.49) for dysthymic disorder without impairment requirement. Three strata of CES-D scores (0-28, 29-48, and > or =49) were derived for major depressive disorder with (SSLR=0.63, 3.00, and 11.75) and without (SSLR=0.61, 5.09, and 10.42) impairment requirement. CONCLUSIONS: The CES-D is useful in screening for major depressive disorder among nonreferred adolescents. Three strata are recommended for its practical application.     

Anatomical measurements of the orbitofrontal cortex in child and adolescent patients with bipolar disorder

Imaging studies indicate smaller orbitofrontal cortex (OFC) volume in mood disorder patients compared with healthy subjects. We sought to determine whether child and adolescent patients with bipolar disorder have smaller OFC volumes than healthy controls. Fourteen children and adolescents meeting DSM-IV criteria for bipolar disorder (six males and eight females with a mean age+/-S.D.=15.5+/-3.2 years) and 20 healthy controls (11 males and nine females with mean age+/-S.D.=16.9+/-3.8 years) were studied. Orbitofrontal cortex volume was measured using magnetic resonance imaging. Male bipolar patients had smaller gray matter volumes in medial (p=0.044), right medial (0.037) and right (p=0.032) lateral OFC subdivisions compared to male controls. In contrast, female patients had larger gray matter volumes in left (p=0.03), lateral (p=0.012), left lateral (p=0.007), and trends for larger volumes in right lateral and left medial OFC subdivisions compared with female controls. Male patients exhibit smaller gray matter volumes, while female patients exhibit larger volumes in some OFC sub-regions. Gender differences in OFC abnormalities may be involved in illness pathophysiology among young bipolar patients.     

What happens to depressed adolescents? A follow-up study into early adulthood

Background

This study describes the mental illness and psychosocial outcomes of adolescents who experienced a depressive disorder and identifies predictors of full remission and recurrence.

Methods

140 adolescents with major depressive disorder, dysthymic disorder, or depressive disorder NOS were offered psychosocial and/or antidepressant treatment across two clinical trials. Three to nine years later (mean 5.7 years), 111 adolescents and young adults completed self-, parent- and clinician-reported measures of psychopathology and psychosocial functioning in a naturalistic follow-up study. The Structured Clinical Interview for DSM-IV Axis 1 Disorders was used to determine the presence or absence of depressive disorder as well as other Axis 1 Disorders.

Results

By the follow-up assessment, most adolescents made a full remission from their index depressive disorder (92.6%). Recurrence of depressive disorder (52.4%) during the follow-up period was common, as was the experience of other disorders including anxiety, substance abuse and eating disorders. Time to full remission and recurrence did not vary between baseline types of depressive disorder. Self-reported depressive symptoms and anxiety disorder were associated with failure to achieve full remission while socio-economic status, self-reported self-efficacy and depressive symptoms were associated with recurrence of depressive disorder.

Limitations

Due to different treatment starting times, the length of the follow up period varied by up to 5.2 years.

Conclusions

Adolescents who experience depressive disorder are at high risk of ongoing mental illness and psychosocial impairment. Predictors of the course of depressive disorder may be of use in determining which adolescents may require more intensive intervention.     

Associations Between Performance on the Rey-Osterrieth Complex Figure and Regional Brain Volumes in Children with and without Velocardiofacial Syndrome

Ninety-two children with velocardiofacial syndrome (VCFS), a genetic disorder caused by a microdeletion of chromosome 22q11.2 and an age, race, and gender-ratio comparable sample of 59 control participants were included in the project. Participants received an MRI as well as a comprehensive neuropsychological battery; the primary outcome measure in the current report is the Rey-Osterrieth Complex Figure (ROCF). Children with VCFS performed less well on the ROCF and have lower whole brain volume compared to controls. After controlling for whole brain volume differences, children with VCFS have bilaterally less parietal lobe gray and white matter yet more frontal lobe white matter. Brain–behavior relationships include: (a) for both groups, parietal volumes (both gray and white matter) predicted ROCF Copy Organization performance and frontal volumes (both gray and white matter) predicted ROCF Copy Accuracy performance; (b) for controls, frontal white matter also predicted ROCF Copy Organization performance; (c) ROCF Recall Organization performance was best predicted by frontal gray matter volume only in our controls; ROCF Recall Accuracy performance was best predicted by frontal gray matter volume in both groups; and (d) in children with VCFS, performance on the ROCF-Copy Structural Elements Accuracy scale was predicted by right hemisphere white matter volume. Our hypotheses were also retested using IQ-matched and whole brain volume-matched subsamples. Identical results were obtained in these analyses. Assumptions about the organization of and the localization of the brain structures that subserve specific cognitive functions in the typically developing brain may not apply in the abnormally developing brain.