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.     

Signature tau neuropathology in gray and white matter of corticobasal degeneration

Corticobasal degeneration (CBD) is an adult-onset progressive neurodegenerative disorder characterized by L-dopa-resistant rigidity, focal cortical deficits, and variable dementia. The neuropathological hallmark of CBD is the deposition of filamentous inclusions in neurons and glia composed of hyperphosphorylated tau with only four microtubule-binding repeats (4R-tau). To characterize the regional burden of tau pathology in CBD, we studied 12 brains with the neuropathological diagnosis of CBD using biochemical and histochemical techniques. Eleven brain regions were evaluated including gray and white matter from frontal, parietal, temporal, and occipital lobes and cerebellum as well as basal ganglia. Although the distribution of tau pathology was variable, neuropathological and biochemical data showed a similar burden of tau abnormalities in frontal, temporal, and parietal lobes and basal ganglia of both hemispheres. This included abundant, sarkosyl-insoluble 4R-tau in both gray and white matter of two or more of these cortical regions and basal ganglia, and to a lesser extent, cerebellar white matter. The insoluble tau pathology in gray and white matter showed overlapping but distinct phosphorylated epitopes suggesting cell-type and subcellular localization (ie, cell bodies versus cell processes)-specific differences in tau phosphorylation. In contrast, soluble tau was composed of normal 4R/3R-tau ratios indicating no gross abnormality in tau splicing. Thus, although clinically heterogeneous, CBD is a distinct lobar and basal ganglionic tauopathy with selective aggregation of 4R-tau.     

The COMT val158met polymorphism and brain morphometry in healthy young adults

Catechol-O-methyltransferase (COMT) is the most important mechanism for dopamine degradation in the prefrontal cortex and contains a functional polymorphism (val(158)met) influencing enzyme activity. The low-activity met allele has been associated with better performance on cognitive tasks relying on the prefrontal cortex. Whether COMT also affects brain structure, is still unclear. This study investigated the relationship between the COMT val(158)met polymorphism and brain anatomy in healthy young adults. In a cross-sectional study, structural MRI data and DNA for COMT genotyping were obtained from 154 healthy young adults. Statistical Parametric Mapping software (SPM2) and optimized voxel-based morphometry were used to determine total and regional gray and white matter density differences between genotype groups, as well as age-related gray and white matter density differences within the genotype groups. We found a significant effect of COMT genotype on age-related differences in gray and white matter density in females but not in males. In female val carriers increased gray matter in the temporal and parietal lobe and the cerebellum and increased white matter in the frontal lobes were positively correlated with age; in female met homozygotes decreased gray matter density in the parietal lobe and decreased white matter density in the frontal lobes, the parahippocampal gyrus and the corpus callosum were positively correlated with age. These results suggest that the COMT val(158)met polymorphism may affect age-related differences in gray and white matter density in females.     

A brain MRI study in subjects with borderline personality disorder

Background: There have been only a few brain computed tomography imaging studies, with mostly negative findings, in subjects with borderline personality disorder (BPD). This is the first MRI study which evaluated the structural abnormalities of the brain in subjects with the sole diagnosis of BPD. Methods: Twenty-five subjects with BPD were compared with age-, gender-matched healthy comparison subjects (n=25) on volumes of the frontal lobes, the temporal lobes, the lateral ventricles, and the cerebral hemispheres in brain magnetic resonance imaging. Results: Subjects with BPD had a significantly smaller frontal lobe compared to comparison subjects (multivariate regression analysis, t=2.225, df=46, P=0.031). There were no significant differences in volumes of the temporal lobes, the lateral ventricles, and the cerebral hemispheres between subjects with and without BPD. Limitations: Strict inclusion and exclusion criteria employed in the present study may make it difficult to generalize our findings. The gray matter and white matter of the brain were not measured separately. Differences in head tilt during image acquisition were not corrected. Conclusions: The current study reports a smaller frontal lobe volume on brain MRI in subjects with BPD compared with healthy comparison subjects. This finding may serve as a potentially useful biological variable that may allow for subtyping BPD.     

Normal neuroanatomical variation due to age: the major lobes and a parcellation of the temporal region

We used high-resolution MRI to investigate gray and white matter aging in the major lobes of the cerebrum (frontal, parietal, temporal, occipital) and the major sectors of the temporal lobe (temporal pole, superior temporal gyrus, infero-temporal region, parahippocampal gyrus, amygdala, hippocampus). Subjects included 87 adults between the ages of 22 and 88 years. Regions of interest were hand-traced on contiguous 1.5mm coronal slices. For the cerebrum in general, gray matter decreased linearly with age, resulting in a decline of about 9.1-9.8% between the ages of 30 and 70 years, and a decline of 11.3-12.3% by the age of 80. In contrast, white matter volume increased until the mid-50s, after which it declined at an accelerated rate. At 70 years, white matter volume was only 5.6-6.4% less than at 30 years, but by age 80, a cubic regression model predicted that the decrease would be 21.6-25.0%. Multivariate analyses indicate that the frontal gray matter was most strongly associated with age, while occipital gray and white matter were least associated. Reduction in volume in the hippocampus was best modeled by a cubic regression model rather than a linear model. No sex differences in aging were found for any regions of interest.     

Quantification of gray matter changes in the cerebral cortex after isolated cerebellar damage: a voxel-based morphometry study

There is growing evidence based on behavioral and functional imaging studies about the cerebellar involvement in the modulation of cognitive functions. However, it still remains to be clarified how the cerebellum interacts with brain regions sub-serving different cognitive domains. In this study we used magnetic resonance imaging (MRI) and voxel based morphometry (VBM) to investigate changes of cerebral gray matter (GM) density in 15 patients with a focal cerebellar damage (CD) compared to 15 healthy controls. T2-weighted scans and T1-weighted volumes were collected from each subject. With the exception of the cerebellar lesion, none of the patients showed any additional brain MRI abnormality. T1-volumes were analyzed by voxel-based morphometry. Consistent with their neuropsychological abnormalities, patients with right-CD compared to controls showed a reduction of GM density mainly involving the left frontal, parietal and temporal lobes. Conversely, patients with left-CD did not show any significant neuropsychological or cerebral GM abnormality. The present study indicates that specific GM changes may be detected in patients with isolated CD and cognitive dysfunction. We discuss the findings in terms of cerebellar influence on the neuronal networks involved in higher level functions of the association cortex.     

Global and local development of gray and white matter volume in normal children and adolescents

Over the last decade, non-invasive, high-resolution magnetic resonance imaging has allowed investigating normal brain development. However, much is still not known in this context, especially with regard to regional differences in brain morphology between genders. We conducted a large-scale study utilizing fully automated analysis-approaches, using high-resolution MR-imaging data from 200 normal children and aimed at providing reference data for future neuroimaging studies. Global and local aspects of normal development of gray and white matter volume were investigated as a function of age and gender while covarying for known nuisance variables. Global developmental patterns were apparent in both gray and white matter, with gray matter decreasing and white matter increasing significantly with age. Gray matter loss was most pronounced in the parietal lobes and least in the cingulate and in posterior temporal regions. White matter volume gains with age were almost uniform, with an accentuation of the pyramidal tract. Gender influences were detectable for both gray and white matter. Voxel-based analyses confirmed significant differences in brain morphology between genders, like a larger amygdala in boys or a larger caudate in girls. We could demonstrate profound influences of both age and gender on normal brain morphology, confirming and extending earlier studies. The knowledge of such influence allows for the consideration of age- and gender-effects in future pediatric neuroimaging studies and advances our understanding of normal and abnormal brain development.     

Effects of age on tissues and regions of the cerebrum and cerebellum.

Normal volunteers, aged 30 to 99 years, were studied with MRI. Age was related to estimated volumes of: gray matter, white matter, and CSF of the cerebrum and cerebellum; gray matter, white matter, white matter abnormality, and CSF within each cerebral lobe; and gray matter of eight subcortical structures. The results were: 1) Age-related losses in the hippocampus were significantly accelerated relative to gray matter losses elsewhere in the brain. 2) Among the cerebral lobes, the frontal lobes were disproportionately affected by cortical volume loss and increased white matter abnormality. 3) Loss of cerebral and cerebellar white matter occurred later than, but was ultimately greater than, loss of gray matter. It is estimated that between the ages of 30 and 90 volume loss averages 14% in the cerebral cortex, 35% in the hippocampus, and 26% in the cerebral white matter. Separate analyses were conducted in which genetic risk associated with the Apolipoprotein E epsilon4 allele was either overrepresented or underrepresented among elderly participants. Accelerated loss of hippocampal volume was observed with both analyses and thus does not appear to be due to the presence of at-risk subjects. MR signal alterations in the tissues of older individuals pose challenges to the validity of current methods of tissue segmentation, and should be considered in the interpretation of the results.     

腺苷负荷脑血流灌注显像的可行性研究

目的 数为参照,分别计算两侧大脑额叶、颞叶、顶叶、枕叶ROI放射性计数与其比值,比较同一组ROI在腺苷负荷状态下与静息状态下放射性计数比值.对视为异常部位的大脑ROI按其对腺苷负荷后脑血流灌注变化的反应进行分类.结果 所有患者进行腺苷负荷显像,没有因出现严重不良反应而终止,部分患者出现轻微不良反应并在腺苷注射结束后迅速消失.共获得视为正常的174组大脑ROI,静息显像的比值与负荷显像的比值比较显示,额叶、颞叶、顶叶差异有统计学意义(0.901±0.100比0.956±0.149,0.923±0.070比0.981±0.090,0.840±0.126比0.887±0.091,均P＜0.05),枕叶差异无统计学意义(1.102±0.146比1.010±0.124,P＞0.05).获得视为异常的49处ROI,其中静息状态局部脑血流量正常,腺苷负荷后局部脑血流量减低的有10处;静息状态局部脑血流量减低,腺苷负荷后局部脑血流量减低更加明显的有9处;静息状态局部脑血流量减低,腺苷负荷后局部脑血流量减低改善的有27处;静息状态局部脑血流量减低,腺苷负荷后局部脑血流量减低区无明显变化的有3处.结论 腺苷能用于负荷脑血流灌注显像,且不良反应少.     

Relative contributions of the cerebellar vermis and prefrontal lobe volumes on cognitive function across the adult lifespan

Recent research has revealed significant relationships between the vermian regions of the cerebellum and cognitive functions typically associated with prefrontal lobe function. These relationships are believed to be supported by anatomical connections between the distant brain regions. Recent evidence also suggests that age-related reductions in the posterior vermis are associated with age-related decline in frontal lobe cognitive functions, but these studies did not consider concomitant age-related atrophy of the prefrontal lobes. In the present study we addressed this issue by examining cognitive and structural MRI data obtained from 251 adults ranging in age from 18 to 79. Cognition was examined with a computerized cognitive battery and volumes of the cerebellar vermian regions and the prefrontal lobes were determined using quantitative morphometry. Results of the study revealed that both prefrontal and vermian volumes were smaller in older adults compared to younger adults, and both volumes correlated with cognitive performances in the older individuals. However, after controlling for prefrontal volume, the relationships between cognitive function and vermian volumes were eliminated, whereas prefrontal lobe volume remained significantly related to cognitive function after controlling for vermian volumes. These results suggest that while a reduction in cerebellar vermian volume does not significantly relate to normal age-related cognitive decline, prefrontal volume is significantly related to cognitive aging. Our results are consistent with the frontal aging hypothesis.     

Klinefelter's syndrome (XXY) as a genetic model for psychotic disorders.

Males with an extra-X chromosome (Klinefelter's syndrome) frequently, although not always, have an increased prevalence of psychiatric disturbances that range from attention deficit disorder in childhood to schizophrenia or severe affective disorders during adulthood. In addition, they frequently have characteristic verbal deficits. Thus, examining brain magnetic resonance imaging (MRI) scans of these individuals may yield clues to the influence of X chromosome genes on brain structural variation corresponding to psychiatric and cognitive disorders. Eleven adult XXY and 11 age matched XY male controls were examined with a structured psychiatric interview, battery of cognitive tests, and an MRI scan. Ten of eleven of the XXY men had some form of psychiatric disturbance, four of whom had auditory hallucinations compared with none of the XY controls. Significantly smaller frontal lobe, temporal lobe, and superior temporal gyrus (STG) cortical volumes were observed bilaterally in the XXY men. In addition, diffusion tensor imaging (DTI) of white matter integrity resulted in four regions of reduced fractional anisotropy (FA) in XXY men compared with controls, three in the left hemisphere, and one on the right. These correspond to the left posterior limb of the internal capsule, bilateral anterior cingulate, and left arcuate bundle. Specific cognitive deficits in executive functioning attributable to frontal lobe integrity and verbal comprehension were noted. Thus, excess expression of one or more X chromosome genes influences both gray and white matter development in frontal and temporal lobes, as well as white matter tracts leading to them, and may in this way contribute to the executive and language deficits observed in these adults. Future prospective studies are needed to determine which gene or genes are involved and whether their expression could be modified with appropriate treatments early in life. Brain expressed genes that are known to escape inactivation on extra-X chromosomes would be prime candidates.     

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.     

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.     

Exercise moderates age-related atrophy of the medial temporal lobe

Regional deterioration of brain structure is a typical feature of aging, but emerging evidence suggests that exercise may mitigate the decline. The purpose of the present investigation was to examine the moderating influence of exercise engagement on cross-sectional estimates of age-related brain atrophy at both global and regional levels. Estimates of exercise engagement over the past 10 years and MRI-based measures of global (gray and white) and regional volumes were obtained in a sample of 52 healthy older adults aged 55-79. Volume estimates were obtained in prefrontal, parietal, temporal, occipital, neostriatal, and medial temporal regions. Higher levels of exercise engagement were related to larger superior frontal volumes. Most critically, exercise engagement selectively moderated age-related medial temporal lobe atrophy. Specifically, significant age-related atrophy was observed for older adults who engaged in low levels of exercise, but not for those who engaged in high levels of exercise. This novel finding extends support for the efficacy of exercise to the potential maintenance of medial temporal lobe integrity in older adults.     

Anti-inflammatory drugs reduce age-related decreases in brain volume in cognitively normal older adults

Previous studies have indicated a decreased risk for developing Alzheimer's disease in anti-inflammatory (AI) drug users. Yet few studies have determined whether AI drug use provides a protective effect against normal age-related changes in the brains of older adults. Regional volume changes in gray and white matter were assessed cross-sectionally using optimized voxel-based morphometry in 36 females taking AI drugs as arthritis or pain medication and 36 age- and education-matched female controls. Although mean gray and white matter volume differences between AI drug users and the non-AI group were small, AI drug use interacted with age, such that the non-AI group showed significantly greater age-related volume changes in regions of both gray and white matter compared to the AI drug users. These regions included the superior and medial frontal gyri, middle and inferior temporal gyri, fusiform and parahippocampal gyri, and occipital gray matter as well as temporal, parietal, and midbrain white matter. The results are consistent with the notion that AI drugs provide protection against age-related changes in brain volume. It is possible that inflammation plays a role in volume decreases associated with normal aging, and that suppressing the inflammatory response moderates this decrease.     

Brain anatomy in non-affected parents of autistic probands: a MRI study

BACKGROUND: Autism is a neurodevelopmental disorder with an estimated genetic origin of 90%. Previous studies have reported an increase in brain volume of approximately 5% in autistic subjects, especially in children. If this increase in brain volume is genetically determined, biological parents of autistic probands might be expected to show brain enlargement, or at least intracranial enlargement, as well. Identifying structural brain abnormalities under genetic control is of particular importance as these could represent endophenotypes of autism. METHOD: Using quantitative anatomic brain magnetic resonance imaging, volumes of intracranial, total brain, frontal, parietal, temporal and occipital lobe, cerebral and cortical gray and white matter, cerebellum, lateral ventricle, and third ventricle were measured in biological, non-affected parents of autistic probands (19 couples) and in healthy, closely matched control subjects (20 couples). RESULTS: No significant differences were found between the parents of the autistic probands and healthy control couples in any of the brain volumes. Adding gender as a factor in a second analysis did not reveal a significant interaction effect of gender by group. CONCLUSIONS: The present sample of biological, non-affected parents of autistic probands did not show brain enlargements. As the intracranium is not enlarged, it is unlikely that the brain volumes of the parents of autistic probands have originally been enlarged and have been normalized. Thus, increased brain volume in autism might be caused by the interaction of paternal and maternal genes, possibly with an additional effect of environmental factors, or increased brain volumes might reflect phenotypes of autism.     

Gray matter network associated with risk for Alzheimer's disease in young to middle-aged adults

The apolipoprotein E (APOE) ε4 allele increases the risk for late-onset Alzheimer's disease (AD) and age-related cognitive decline. We investigated whether ε4 carriers show reductions in gray matter volume compared with ε4 non-carriers decades before the potential onset of AD dementia or healthy cognitive aging. Fourteen cognitively normal ε4 carriers, aged 26 to 45 years, were compared with 10 age-matched, ε4 non-carriers using T1-weighted volumetric magnetic resonance imaging (MRI) scans. All had reported first- or second-degree family histories of dementia. Group differences in gray matter were tested using voxel-based morphometry (VBM) and a multivariate model of regional covariance, the Scaled Subprofile Model (SSM). A combination of the first two SSM MRI gray matter patterns distinguished the APOE ε4 carriers from non-carriers. This combined pattern showed gray matter reductions in bilateral dorsolateral and medial frontal, anterior cingulate, parietal, and lateral temporal cortices with covarying relative increases in cerebellum, occipital, fusiform, and hippocampal regions. With these gray matter differences occurring decades before the potential onset of dementia or cognitive aging, the results suggest longstanding, gene-associated differences in brain morphology that may lead to preferential vulnerability for the later effects of late-onset AD or healthy brain aging.     

Effects of hormone therapy on brain morphology of healthy postmenopausal women: a Voxel-based morphometry study

OBJECTIVE: Estrogens are known to be protective in age-associated cognitive changes in humans and in neurodegeneration in animal models. The aim of this study was to evaluate the potential effects of estrogen therapy (ET) on human gray matter volume in vivo. DESIGN: Forty healthy postmenopausal women underwent three-dimensional high-resolution magnetic resonance imaging: 17 were never treated, 16 were currently receiving ET, and 7 had had ET in the past. Voxel-based morphometry (VBM) with SPM2 was used, according to an optimized protocol, to compare women under past and current ET to those never treated. Significance threshold was set at P = 0.01, corrected by false discovery rate. RESULTS: Voxel-based morphometry indicated that estrogen use was associated with greater gray matter volumes in the whole group of treated women, which included the cerebellum (cluster size, Z coordinates: 5,527; 5.15; -14 -54 -10), the amygdaloid-hippocampal complex (left: 19; 3.55; -22 -4 -18; right: 45; 3.61; 16 -6 -16), and extended to the frontal, temporal, parietal, and occipital neocortex. The comparison current ET versus past ET use showed that women who underwent treatment in the past had greater volumes of gray matter compared to women under current treatment. CONCLUSIONS: ET might slow down age-related gray matter loss in postmenopausal women. The structures that exhibited greater volume in association with ET included the cerebellar and cerebral cortices and, typically involved in Alzheimer's disease, the medial temporal structures and the temporoparietal junction.     

Voxel-based assessment of gray and white matter volumes in Alzheimer's disease

Using the study-specific templates and optimized voxel-based morphometry (VBM), this study investigated abnormalities in gray and white matter to provide depiction of the concurrent structural changes in 13 patients with Alzheimer's disease (AD) compared with 14 age- and sex-matched normal controls. Consistent with previous studies, patients with AD exhibited significant gray matter volume reductions mainly in the hippocampus, parahippocampal gyrus, insula, superior/middle temporal gyrus, thalamus, cingulate gyrus, and superior/inferior parietal lobule. In addition, white matter volume reductions were found predominately in the temporal lobe, corpus callosum, and inferior longitudinal fasciculus. Furthermore, a number of additional white matter regions such as precentral gyrus, cingulate fasciculus, superior and inferior frontal gyrus, and sub-gyral in parietal lobe were also affected. The pattern of gray and white matter volume reductions helps us understand the underlying pathologic mechanisms in AD and potentially can be used as an imaging marker for the studies of AD in the future.     

The neuroanatomy of genetic subtype differences in Prader-Willi syndrome

Despite behavioral differences between genetic subtypes of Prader-Willi syndrome (PWS), no studies have been published characterizing brain structure in these subgroups. Our goal was to examine differences in the brain structure phenotype of common subtypes of PWS [chromosome 15q deletions and maternal uniparental disomy 15 (UPD)]. Fifteen individuals with PWS due to a typical deletion [(DEL) type I; n = 5, type II; n = 10], eight with PWS due to UPD, and 25 age-matched healthy-weight individuals (HWC) participated in structural magnetic resonance imaging (MRI) scans. A custom voxel-based morphometry processing stream was used to examine regional differences in gray and white matter volume (WMV) between groups, covarying for age, sex, and body mass index (BMI). Overall, compared to HWC, PWS individuals had lower gray matter volumes (GMV) that encompassed the prefrontal, orbitofrontal and temporal cortices, hippocampus and parahippocampal gyrus, and lower WMVs in the brain stem, cerebellum, medial temporal, and frontal cortex. Compared to UPD, the DEL subtypes had lower GMV primarily in the prefrontal and temporal cortices, and lower white matter in the parietal cortex. The UPD subtype had more extensive lower gray and WMVs in the orbitofrontal and limbic cortices compared to HWC. These preliminary findings are the first structural neuroimaging findings to support potentially separate neural mechanisms mediating the behavioral differences seen in these genetic subtypes.