Positional and surface area asymmetry of the human cerebral cortex

Previous studies of cortical asymmetry have relied mainly on voxel-based morphometry (VBM), or manual segmentation of regions of interest. This study uses fully automated, surface-based techniques to analyse position and surface area asymmetry for the mid-surfaces of 112 right-handed subjects' cortical hemispheres from a cohort of young adults. Native space measurements of local surface area asymmetry and vertex position asymmetry were calculated from surfaces registered to a previously validated hemisphere-unbiased surface-based template. Our analysis confirms previously identified hemispheric asymmetries (Yakovlevian torque, frontal and occipital petalia) in enhanced detail. It does not support previous findings of gender/asymmetry interactions or rightward planum parietale areal increase. It reveals several new findings, including a striking leftward increase in surface area of the supramarginal gyrus (peak effect 18%), compared with a smaller areal increase in the left Heschl's gyrus and planum temporale region (peak effect 8%). A second finding was rightward increase in surface area (peak effect 10%) in a band around the medial junction between the occipital lobe, and parietal and temporal lobes. By clearly separating out the effects of structural translocation and surface area change from those of thickness and curvature, this study resolves the confound of these variables inherent in VBM studies.     

Cerebral asymmetry and the effects of sex and handedness on brain structure: a voxel-based morphometric analysis of 465 normal adult human brains

We used voxel-based morphometry (VBM) to examine human brain asymmetry and the effects of sex and handedness on brain structure in 465 normal adults. We observed significant asymmetry of cerebral grey and white matter in the occipital, frontal, and temporal lobes (petalia), including Heschl's gyrus, planum temporale (PT) and the hippocampal formation. Males demonstrated increased leftward asymmetry within Heschl's gyrus and PT compared to females. There was no significant interaction between asymmetry and handedness and no main effect of handedness. There was a significant main effect of sex on brain morphology, even after accounting for the larger global volumes of grey and white matter in males. Females had increased grey matter volume adjacent to the depths of both central sulci and the left superior temporal sulcus, in right Heschl's gyrus and PT, in right inferior frontal and frontomarginal gyri and in the cingulate gyrus. Females had significantly increased grey matter concentration extensively and relatively symmetrically in the cortical mantle, parahippocampal gyri, and in the banks of the cingulate and calcarine sulci. Males had increased grey matter volume bilaterally in the mesial temporal lobes, entorhinal and perirhinal cortex, and in the anterior lobes of the cerebellum, but no regions of increased grey matter concentration.     

Hippocampal gray matter reduction associates with memory deficits in adolescents with history of prematurity

Using optimized voxel-based morphometry (VBM), we compared the relationship between hippocampal and thalamic gray matter loss and memory impairment in 22 adolescents with history of prematurity (HP) and 22 normal controls. We observed significant differences between groups in verbal learning and verbal recognition, but not in visual memory. VBM analysis showed significant left hippocampal and bilateral thalamic reductions in HP subjects. Using stereological methods, we also observed a reduction in hippocampal volume, with left posterior predominance. We found correlations between left hippocampal gray matter reductions (assessed by VBM) and verbal memory (learning and percentage of memory loss) in the premature group. The stereological analysis showed a correlation between verbal learning and the left posterior hippocampus. Our results suggest that left hippocampal tissue loss may be responsible for memory impairment and is probably related to the learning disabilities that HP subjects present during schooling.     

Handedness and cerebral anatomical asymmetries in young adult males

Using voxel-based morphometry, we measured the cerebral anatomical asymmetries in a sample of 56 young right-handed males and then compared voxelwise asymmetry indices of these subjects to those of 56 young left-handed males. In the right-handed, the clusters of grey matter asymmetry corresponding to the leftward occipital petalia and planum temporale asymmetries were retrieved. Strong rightward temporo-parietal asymmetries were also observed, but the rightward grey matter asymmetry in the frontal lobe was less massive than previously described. Group comparisons of left- and right-handed subjects' asymmetry maps, performed at a statistical threshold not corrected for multiple comparisons, revealed significant effects of handedness on this pattern of anatomical asymmetry in frontal regions, notably in the lower central and precentral sulci, and also in the planum temporale, with right-handed subjects being more leftward asymmetric. Concerning white matter, although almost no focal differences between left- and right-handed subjects were detected, volumetric analyses at the hemispheric level revealed a leftward asymmetry, which happened to be significantly less marked in the left-handed. This latter result, together with the pattern of leftward white matter asymmetries, suggested that anatomical correlates of the left hemispheric specialization for language would exist in white matter. In the population we studied, differences in anatomical asymmetry between left- and right-handed subjects provided structural arguments for a greater functional ambilaterality in left-handed subjects.     

Voxel-based morphometric comparison of hippocampal and extrahippocampal abnormalities in patients with left and right hippocampal atrophy

We used voxel-based morphometry (VBM), an automatic whole-brain MR image analysis technique, to investigate gray matter abnormalities in patients with temporal lobe epilepsy (TLE), in whom hippocampal atrophy (HA) was demonstrated by application of the Cavalieri method of modern design stereology. VBM results (P < 0.05, corrected) indicated preferential gray matter concentration (GMC) reduction in anterior hippocampus in patients with left HA and posterior hippocampus in patients with right HA. GMC reduction was also found in right dorsal prefrontal cortex in left and right HA patients. Prefrontal atrophy may be due to epileptiform excitotoxic discharges from the reciprocally connected pathological hippocampus, and may be the underlying biological cause for executive dysfunction in patients with TLE. GMC excess in ipsilateral parahippocampal, cerebellar, and pericallosal regions was common to both left and right HA groups relative to controls, and is hypothesized to reflect diminished gray-white matter demarcation, underlying white matter atrophy, or structural displacement due to cerebrospinal fluid expansion. However, bilateral temporal lobe GMC excess was observed in left HA patients, while ipsilateral temporal lobe GMC excess was observed in right HA patients. This work demonstrates methodological consistency between automated VBM and manual stereological analysis of the hippocampus in group comparisons, indicates widespread extrahippocampal gray matter abnormalities in unilateral HA, and suggests that there may be inherent differences in the effect of TLE on temporal lobe structures depending on the side of HA.     

A voxel-based approach to gray matter asymmetries

Voxel-based morphometry (VBM) was used to analyze gray matter (GM) asymmetries in a large sample (n = 60) of male and female professional musicians with and without absolute pitch (AP). We chose to examine these particular groups because previous studies using traditional region-of-interest (ROI) analyses have shown differences in hemispheric asymmetry related to AP and gender. Voxel-based methods may have advantages over traditional ROI-based methods since the analysis can be performed across the whole brain with minimal user bias. After determining that the VBM method was sufficiently sensitive for the detection of differences in GM asymmetries between groups, we found that male AP musicians were more leftward lateralized in the anterior region of the planum temporale (PT) than male non-AP musicians. This confirmed the results of previous studies using ROI-based methods that showed an association between PT asymmetry and the AP phenotype. We further observed that male non-AP musicians revealed an increased leftward GM asymmetry in the postcentral gyrus compared to female non-AP musicians, again corroborating results of a previously published study using ROI-based methods. By analyzing hemispheric GM differences across our entire sample, we were able to partially confirm findings of previous studies using traditional morphometric techniques, as well as more recent, voxel-based analyses. In addition, we found some unusually pronounced GM asymmetries in our musician sample not previously detected in subjects unselected for musical training. Since we were able to validate gender- and AP-related brain asymmetries previously described using traditional ROI-based morphometric techniques, the results of our analyses support the use of VBM for examinations of GM asymmetries.     

Abnormal association between reduced magnetic mismatch field to speech sounds and smaller left planum temporale volume in schizophrenia

Schizophrenia is associated with language-related dysfunction. A previous study [Schizophr. Res. 59 (2003c) 159] has shown that this abnormality is present at the level of automatic discrimination of change in speech sounds, as revealed by magnetoencephalographic recording of auditory mismatch field in response to across-category change in vowels. Here, we investigated the neuroanatomical substrate for this physiological abnormality. Thirteen patients with schizophrenia and 19 matched control subjects were examined using magnetoencephalography (MEG) and high-resolution magnetic resonance imaging (MRI) to evaluate both mismatch field strengths in response to change between vowel /a/ and /o/, and gray matter volumes of Heschl's gyrus (HG) and planum temporale (PT). The magnetic global field power of mismatch response to change in phonemes showed a bilateral reduction in patients with schizophrenia. The gray matter volume of left planum temporale, but not right planum temporale or bilateral Heschl's gyrus, was significantly smaller in patients with schizophrenia compared with that in control subjects. Furthermore, the phonetic mismatch strength in the left hemisphere was significantly correlated with left planum temporale gray matter volume in patients with schizophrenia only. These results suggest that structural abnormalities of the planum temporale may underlie the functional abnormalities of fundamental language-related processing in schizophrenia.     

A comparison between voxel-based cortical thickness and voxel-based morphometry in normal aging

The morphology of cortical grey matter is commonly assessed using T1-weighted MRI together with automated computerised methods such as voxel-based morphometry (VBM) and cortical thickness measures. In the presented study we investigate how grey matter changes identified using voxel-based cortical thickness (VBCT) measures compare with local grey matter volume changes identified using VBM. We use data from a healthy aging population to perform the comparison, focusing on brain regions where age-related changes have been observed in previous studies. Our results show that overall, in healthy aging, VBCT and VBM yield very consistent results but VBCT provides a more sensitive measure of age-associated decline in grey matter compared with VBM. Our findings suggest that while VBCT selectively investigates cortical thickness, VBM provides a mixed measure of grey matter including cortical surface area or cortical folding, as well as cortical thickness. We therefore propose that used together, these techniques can separate the underlying grey matter changes, highlighting the utility of combining these complementary methods.     

β-Amyloid affects frontal and posterior brain networks in normal aging

Although deposition of β-amyloid (Aβ), a pathological hallmark of Alzheimer's disease (AD), has also been reported in cognitively intact older people, its influence on brain structure and cognition during normal aging remains controversial. Using PET imaging with the radiotracer Pittsburgh compound B (PIB), structural MRI, and cognitive measures, we examined the relationships between Aβ deposition, gray matter volume, and cognition in older people without AD. Fifty-two healthy older participants underwent PIB-PET and structural MRI scanning and detailed neuropsychological tests. Results from the whole-brain voxel-based morphometry (VBM) analysis revealed that gray matter volume in the left inferior frontal cortex was negatively associated with amyloid deposition across all participants whereas reduced gray matter volume was shown in the posterior cingulate among older people with high amyloid deposition. When gray matter density measures extracted from these two regions were related to other brain regions by applying a structural covariance analysis, distinctive frontal and posterior brain networks were seen. Gray matter volume in these networks in relation to cognition, however, differed such that reduced frontal network gray matter volume was associated with poorer working memory performance while no relationship was found for the posterior network. The present findings highlight structural and cognitive changes in association with the level of Aβ deposition in cognitively intact normal elderly and suggest a differential role of Aβ-dependent gray matter loss in the frontal and posterior networks in cognition during normal aging.     

正常婴儿与隐源性婴儿痉挛症患儿大脑皮层灰质的MR形态学定量分析

目的通过对脑灰质结构进行定量分析,寻找隐源性婴儿痉挛可能的发病部位、探讨发病机制。方法对16例平均年龄6.4个月的隐源性婴儿痉挛患儿和年龄、性别匹配的16例正常婴儿进行脑部高分辨磁共振解剖成像,借助SPM脑成像处理软件对磁共振图像进行解剖分割,用基于体素的形态学对比方法定量检测患儿组和对照组全脑灰质的体积,比较两组间的差异。结果隐源性婴儿痉挛组在左额下回(47区)、右颞上回(22区)、左中央后回(1～2区)、右额中回(9/10区)、右中央前回(6区)、右扣带回(31区),左颞中回(21区)和颞上回(38区)等灰质体积明显减少,与正常婴儿组比较,差异有显著性(P<0.001)。结论隐源性婴儿痉挛患儿额叶和颞叶的灰质体积明显减少,以额叶和颞叶为主的皮层结构异常可能是本组患儿的发病原因。     

Parieto-occipital grey matter abnormalities in children with Williams syndrome

Williams syndrome (WS) is a neurodevelopmental disorder resulting from a hemizygous deletion of chromosome 7q11.23. The phenotype of WS consists of typical dysmorphic features, supravalvular aortic stenosis, infantile hypercalcemia and growth retardation. While language and facial recognition seem to be relatively spared, visuospatial constructive disabilities are a hallmark of the neurobehavioral profile of WS. In order to search for actual structural abnormalities underlying this precisely defined neurodevelopmental disorder, we performed anatomical magnetic resonance imaging (MRI) in 9 WS children (11.6 +/- 3.1 years; age range: 5.5-15 years) and 11 normal age-matched control children (11.8 +/- 2.2 years; age range: 8-15 years) using voxel-based morphometry (VBM). VBM is a fully automated whole-brain technique that delivers a voxel-wise assessment of regional grey and white matter concentration. A significant decrease in grey matter concentration was detected in the left parieto-occipital region of WS children (P < 0.05 corrected height threshold). The location of this abnormality in WS children coincides with the location of the structural abnormality previously described using the same method in 13 WS adults. These parieto-occipital abnormalities are consistent with the cognitive profile of WS which includes severe visuospatial construction and numerical cognition deficits. The demonstration of identical structural abnormalities in both adults and children argues for their early origin. Additionally, our study provides support for the use of advanced structural imaging techniques in children, in order to improve our understanding of neurobehavioral phenotypes associated with well-defined genetic disorders.     

未受教育及受教育儿童语言处理脑区偏侧化的差异:基于体素的MR形态学分析

目的采用基于体素的形态学方法分析未受教育及受教育儿童语言处理相关脑区的偏侧化差异。方法对42名学龄儿童(未受教育组23名,6.0～7.8岁,中位年龄6.5岁;受教育组19名,5.8～7.6岁,中位年龄6.3岁)行高分辨力T1W扫描,采用VBM8软件包进行图像后处理,并采用LI-tools工具软件进行偏侧化分析,比较未受教育组与受教育组的灰质密度(GMD)偏侧化指数情况。结果受教育组的额下回(BA44)以及颞上回(BA22)的GMD偏侧化指数显著高于未受教育组。结论学校教育可能显著促进额下回和颞上回的GMD偏侧化。     

Brain activation mediates the association between structural abnormality and symptom severity in schizophrenia

Thought disorder is a symptom of schizophrenia expressed as disorganized or incoherent speech. Severity of thought disorder correlates with decreased left superior temporal gyrus grey matter volume and cortical activation in posterior temporal regions during the performance of language tasks. The goal of this study was to determine whether language-related activation mediates the association between thought disorder and left superior temporal lobe grey matter volume. 12 patients with schizophrenia were assessed for thought disorder. FMRI images were acquired for each subject while they listened to English speech, along with a high resolution structural image. Thought disorder was used as a covariate in the functional analysis to identify brain regions within which activation correlated with symptom severity. Voxel based morphometry was used to calculate grey matter volume of the planum temporale. A mediation model waste-tested using a four-step multiple regression approach incorporating cortical volume, functional activation and symptom severity. Thought disorder correlated with activation in a single cluster within the left posterior middle temporal gyrus during listening to speech. Grey matter volume within the planum temporale correlated significantly with severity of thought disorder and activation within the functional cluster. Regressing thought disorder on grey matter volume and BOLD response simultaneously led to a significant reduction in the correlation between grey matter volume and thought disorder. These results support the hypothesis that the association between decreased grey matter volume in the left planum temporale and severity of thought disorder is mediated by activation in the posterior temporal lobe during language processing.     

Distribution of grey matter atrophy in Huntington's disease patients: a combined ROI-based and voxel-based morphometric study

The striatum, a subcortical structure, is the principal target of the neurodegenerative process in Huntington's disease (HD). The measurement of striatal atrophy using the bicaudate ratio on CT scanner images has therefore been used for years to assess disease progression, but this measure only takes into account unidimensional changes in the head of the caudate nucleus. Recently, voxel-based morphometry (VBM), which permits automated statistical comparisons of whole-brain MRI images, has been proposed to quantify striatal atrophy. However, VBM was not originally designed to study subcortical structures, and severe deep brain deformations that occur in HD may hamper the automatic processing of VBM. Here, we validate the use of the optimised protocol of VBM to quantify subcortical atrophy in HD by comparing results obtained with this method to those provided by manual segmentation of subcortical structures. We studied 20 patients with early HD and 12 controls matched for age, sex and handedness using an improved T1-weighted sequence that eased grey matter segmentation. Both manual and automated methods evidenced the dorso-ventral gradient of striatal atrophy, a loss of grey matter in the globus pallidus and the thalamus, and similar correlations between clinical scores and subcortical atrophy. Furthermore, we were able to detect with VBM grey matter loss in the substantia nigra, the hypothalamus, the amygdala, the insular cortex and the premotor and sensorimotor cortices. Finally, VBM provided results consistent with previous post mortem results and proved to be a sensitive biomarker capable of correctly managing subcortical distortions throughout HD patients' brains.     

Mapping an intrinsic MR property of gray matter in auditory cortex of living humans: a possible marker for primary cortex and hemispheric differences

Recently, magnetic resonance properties of cerebral gray matter have been spatially mapped--in vivo--over the cortical surface. In one of the first neuroscientific applications of this approach, this study explores what can be learned about auditory cortex in living humans by mapping longitudinal relaxation rate (R1), a property related to myelin content. Gray matter R1 (and thickness) showed repeatable trends, including the following: (1) Regions of high R1 were always found overlapping posteromedial Heschl's gyrus. They also sometimes occurred in planum temporale and never in other parts of the superior temporal lobe. We hypothesize that the high R1 overlapping Heschl's gyrus (which likely indicates dense gray matter myelination) reflects auditory koniocortex (i.e., primary cortex), a heavily myelinated area that shows comparable overlap with the gyrus. High R1 overlapping Heschl's gyrus was identified in every instance suggesting that R1 may ultimately provide a marker for koniocortex in individuals. Such a marker would be significant for auditory neuroimaging, which has no standard means (anatomic or physiologic) for localizing cortical areas in individual subjects. (2) Inter-hemispheric comparisons revealed greater R1 on the left on Heschl's gyrus, planum temporale, superior temporal gyrus and superior temporal sulcus. This asymmetry suggests greater gray matter myelination in left auditory cortex, which may be a substrate for the left hemisphere's specialized processing of speech, language, and rapid acoustic changes. These results indicate that in vivo R1 mapping can provide new insights into the structure of human cortical gray matter and its relation to function.     

Voxel-based morphometry reveals gray matter abnormalities in migraine

BACKGROUND: Migraine is generally considered a functional brain disorder lacking structural abnormalities. Recent magnetic resonance imaging (MRI) studies, however, suggested that migraine may be associated with subtle brain lesions. OBJECTIVE: We evaluated the presence of global or focal gray or white matter alterations in migraine patients using voxel-based morphometry (VBM), a fully automated method of analyzing changes in brain structure. VBM data also were used to evaluate possible differences between episodic and chronic migraine. METHODS: Twenty-seven migraine right-handed patients and 27 healthy controls were selected for the study. Sixteen patients fulfilled the International Headache Society criteria for episodic migraine and 11 for chronic migraine. MRI scans were analyzed with MATLAB 6.5 and SPM2 software, using VBM method. RESULTS: In comparison with controls, migraineurs presented a significant focal gray matter reduction in the Right Superior Temporal Gyrus, Right Inferior Frontal Gyrus, and Left Precentral Gyrus. Chronic migraine patients, compared to episodic, showed a focal gray matter decrease in the bilateral Anterior Cingulate Cortex, Left Amygdala, Left Parietal Operculum, Left Middle and Inferior Frontal Gyrus, Right Inferior Frontal Gyrus, and bilateral Insula. Considering all the migraine patients, a significant correlation between gray matter reduction in anterior cingulate cortex and frequency of migraine attacks was found. CONCLUSIONS: Our study shows that migraine is associated with a significant gray matter reduction in several of the cortical areas involved in pain circuitry. In addition, we found a significant correlation between frequency of migraine attacks and signal alteration in the Anterior Cingulate Cortex. Our data provide new insight into migraine pathophysiology and support the concept that migraine may be a progressive disorder.     

基于自动分割技术联合基于体素的形态学观察帕金森病脑灰质结构

目的 探讨基于自动分割技术联合基于体素的形态学(VBM)观察帕金森病(PD)患者全脑灰质异常区域及分布特征的应用价值。方法 基于自动分割技术,应用FIRST工具对29例PD患者(PD组)及30名健康人(对照组)的T1图像皮层下灰质结构精确分割,对比两组各灰质结构体积。并应用VBM方法对两组脑灰质图像进行比较。结果 两组右侧壳核皮层下灰质体积差异有统计学意义(t=10.201,P<0.05)。与对照组比较,PD组脑灰质体积(右侧初级运动皮层,双侧额叶、边缘叶、部分左侧小脑后叶、右侧小脑前叶、右侧小脑后叶、右侧颞叶、顶叶、壳核及左侧枕叶)广泛减少,部分左侧小脑后叶体积增加,两侧半球脑体积缺失不对称(右侧大于左侧)。结论 通过FIRST工具可精确分割并直接计算皮层下灰质结构体积,应用VBM技术可定量分析脑结构形态学异常;二者结合可较全面地表现PD脑灰质体积广泛减少的形态学特点。     

Automatic analysis of cerebral asymmetry: an exploratory study of the relationship between brain torque and planum temporale asymmetry

Leftward occipital and rightward frontal lobe asymmetry (brain torque) and leftward planum temporale asymmetry have been consistently reported in postmortem and in vivo neuroimaging studies of the human brain. Here automatic image analysis techniques are applied to quantify global and local asymmetries, and investigate the relationship between brain torque and planum temporale asymmetries on T1-weighted magnetic resonance (MR) images of 30 right-handed young healthy subjects (15 male, 15 female). Previously described automatic cerebral hemisphere extraction and 3D interhemispheric reflection-based methods for studying brain asymmetry are applied with a new technique, LowD (Low Dimension), which enables automatic quantification of brain torque. LowD integrates extracted left and right cerebral hemispheres in columns orthogonal to the midsagittal plane (2D column maps), and subsequently integrates slices along the brain's anterior-posterior axis (1D slice profiles). A torque index defined as the magnitude of occipital and frontal lobe asymmetry is computed allowing exploratory investigation of relationships between this global asymmetry and local asymmetries found in the planum temporale. LowD detected significant torque in the 30 subjects with occipital and frontal components found to be highly correlated (P<0.02). Significant leftward planum temporale asymmetry was detected (P<0.05), and the torque index correlated with planum temporale asymmetry (P<0.001). However, torque and total brain volume were not correlated. Therefore, although components of cerebral asymmetry may be related, their magnitude is not influenced by total hemisphere volume. LowD provides increased sensitivity for detection and quantification of brain torque on an individual subject basis, and future studies will apply these techniques to investigate the relationship between cerebral asymmetry and functional laterality.     

Structural gray matter differences between first-episode schizophrenics and normal controls using voxel-based morphometry

The aim of this study was to compare the gray matter segments from T1 structural MR images of the brain in first-episode schizophrenic subjects (n = 34) and normal control subjects (n = 36) using automated voxel-based morphometry (VBM). This study is novel in that few studies have examined subjects in their first episode of schizophrenia. The subjects were recruited for the Edinburgh High Risk project and regional brain volumes were previously measured using a semi-automated volumetric region of interest (ROI) method of analysis. The primary interest was to compare the results from the compatible parts of the ROI study and the primary VBM approach. Our secondary interest was to compare the results of a study-specific template that was constructed from the control group to those using the generic T1 template (152 Montreal Neurological Institute brains) supplied with SPM99 (statistical parametric mapping). The images were processed and statistically analyzed using the SPM99 program. VBM analysis identified significant decreases in gray matter in the schizophrenics relative to the normal control group at the corrected voxel level (P < 0.05) in the right anterior cingulate, right medial frontal lobe, left middle temporal gyrus, left postcentral gyrus, and the left limbic lobe. There were no increases in gray matter in the schizophrenics relative to the control group. The construction of a customized template appeared to improve the detection of structural abnormalities. The analyses were subsequently restricted to voxels within the amygdala-hippocampal complex using the SPM small-volume correction. This identified gray matter decreases in the schizophrenics, at the corrected voxel level (P < 0.05), in the left and right uncus and parahippocampal gyri and the right amygdala. These results are compatible with and extend the relevant findings of the previous volumetric ROI analysis, when allowing for the differences between the methods and interpretation of their results.     

Application of an automated voxel-based morphometry technique to assess regional gray and white matter brain atrophy in a canine model of aging

In recent years, voxel-based morphometry (VBM) has emerged as a technique to examine regional brain changes associated with normal and pathological aging. Despite its popularity in studies of human aging, application of VBM to animal models of brain aging is rare. In the present study, VBM techniques were developed to validate earlier region of interest (ROI) measures of brain aging in the dog and to provide a more comprehensive analysis of local changes in a canine model of brain aging. Consistent with previous findings, frontal lobe atrophy increased with age, most notably in aged male dogs. Age-related gray matter reductions were also observed in parietal and temporal lobes, thalamus, cerebellum, and brainstem. Temporal lobe atrophy was particularly prominent in old females. A number of age-related changes in white matter not previously explored in the dog were also identified with VBM. Specifically, aged males exhibited greater decreases in the internal capsula and cranial nerve bundles compared to decreased volumes in the alveus of the hippocampus in old female dogs. Together, the present results indicate that application of VBM techniques in a canine model of aging yields more comprehensive information regarding topographical patterns of brain aging in male and female dogs than previously reported using traditional manual ROI methods.