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Morphometry of otoliths in chicken macula lagena.

The macula lagena located at the apical end of the cochlea in birds is characterized by the presence of numerous otoliths with unclear sensory functions. These otoliths are reported to be similar to those in the vestibular system but their detailed features in morphology are unknown. In the present study, we examined the number, size and shape of otoliths from the macula lagena in Chinese domestic chickens (Gallus Ling Nan) with a scanning electron microscope for morphometry. For chickens aged 10-15 post-hatch days, the otoliths in each macula lagena were counted to be 16,055 +/- 4038 (mean +/- S.D., n = 4). The average length and width were 12.98 +/- 3.70 microm and 5.10 +/- 1.48 microm (n = 526 otoliths), respectively. The ratio of length to width for the otolith was 2.58 +/- 0.39 (n = 526 otoliths) and remained relatively constant despite their variations in physical size. Almost all the otoliths were in regular shape and appeared like isolated cylinders with smooth facets at each end, but a few of them (0.025% of 64,221 otoliths screened) were found to be in odd shapes, such as T-shape and cross-shape. The results suggest that otoliths in the macula lagena and those in the vestibular system of bird's inner ear have similar physical properties and may play a similar role in sensing gravitational and acceleration signals.

Acoustic Maculae↗

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.

Adolescent↗

Dissociation of grey and white matter reduction in spinocerebellar ataxia type 3 and 6: a voxel-based morphometry study.

The aim of this study was to examine the different patterns of cerebellar and/or brainstem atrophy in spinocerebellar ataxia (SCA) type 3 and 6. Eighteen patients (SCA3 n=9, SCA6 n=9) and 15 healthy volunteers were studied. Voxel-based morphometry (VBM) was applied to segmented grey matter (GM) and white matter (WM) of high-resolution T1-weighted brain volumes of each group. We found reduction of grey matter in the pons as well as in the vermis in SCA3 as compared to control subjects. In SCA6 significant grey matter loss was found in hemispheric lobules bilaterally as well as in the vermis. White matter analysis revealed significant changes in SCA3, especially in the pons, in the white matter surrounding the dentate nucleus (DN) and in the cerebellar peduncles, whereas no significant white matter reduction was found in SCA6 patients. Our results demonstrate different patterns of grey and white matter affection detected by magnetic resonance imaging (MRI) in SCA3 and SCA6 patients, confirming the pathological concept of cortical cerebellar atrophy in SCA6. In contrast, SCA3 represents a form of ponto-cerebellar atrophy with predominant affection of pontine nuclei and fibre tracts.

Aged↗

Voxel-based morphometry of human brain with age and cerebrovascular risk factors.

The objectives of this study were to evaluate the correlations of the volumes of the gray matter and white matter with age, and the correlations of the tissue probabilities of the gray matter and white matter with age and several cerebrovascular risk factors. We obtained magnetic resonance (MR) images of the brain and clinical information from 769 normal Japanese subjects. We processed the MR images automatically by correcting for inter-individual differences in brain size and shape, and by segmenting the MR images into the gray matter and white matter. Volumetry of the brain revealed a significant negative correlation between the gray matter volume and age, which was not observed between white matter volume and age. Voxel-based morphometry showed that age, systolic blood pressure, and alcohol drinking correlated with the regional tissue probabilities of the gray matter and white matter.

Adolescent↗

Voxel-based morphometry in autopsy proven PSP and CBD.

The aim of this study was to compare the patterns of grey and white matter atrophy on MRI in autopsy confirmed progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), and to determine whether the patterns vary depending on the clinical syndrome. Voxel-based morphometry was used to compare patterns of atrophy in 13 PSP and 11 CBD subjects and 24 controls. PSP and CBD subjects were also subdivided into those with a dominant dementia or extrapyramidal syndrome. PSP subjects showed brainstem atrophy with involvement of the cortex and underlying white matter. Frontoparietal grey and subcortical grey matter atrophy occurred in CBD. When subdivided, PSP subjects with an extrapyramidal syndrome had more brainstem atrophy and less cortical atrophy than CBD subjects with an extrapyramidal syndrome. PSP subjects with a dementia syndrome had more subcortical white matter atrophy than CBD subjects with a dementia syndrome. These results show regional differences between PSP and CBD that are useful in predicting the underlying pathology, and help to shed light on the in vivo distribution of regional atrophy in PSP and CBD.

Aged↗

Deformation tensor morphometry of semantic dementia with quantitative validation.

High-resolution structural MRI scans of 20 subjects diagnosed with semantic dementia were compared against scans of 20 cognitively normal control subjects using whole brain deformation tensor morphometry to study spatially consistent differences in local anatomical size. A fine lattice free-form volume registration algorithm was used to estimate a continuous mapping from a reference MRI to each individual subject MRI. The Jacobian of these transformations at each voxel were used to quantitatively map relative anatomical size in each individual brain. Intensity consistent filtering was applied to the determinant of these Jacobians. A careful validation using manually traced gyral anatomy was carried out and used to select an optimal deformation tensor filter scale at which to examine the anatomical size maps. General linear modeling at each voxel was used to decompose the influence of age and head size from the primary diagnosis. Maps of the T statistic of the diagnosis across the 40 subjects highlighted significant (P < 0.01 Bonferroni corrected) focal tissue contraction effects related to dementia diagnosis in the left temporal pole extending into the hippocampus, occipitotemporal gyrus and parahippocampal gyrus. Some evidence of greater focal contraction in gray over white matter was also apparent. Contraction effects were also seen, but with reduced significance in the right temporal anatomy, focused toward the temporal pole and hippocampal regions. Additional lower significance findings (P < 0.05 permutation corrected) were detected in the left superior frontal gyrus, left orbital gyrus and left parietal lobe.

Aged↗

Voxel-based morphometry of comorbid schizophrenia and learning disability: analyses in normalized and native spaces using parametric and nonparametric statistical methods.

We employed voxel-based morphometry (VBM) to compare the distributions of grey matter found in structural magnetic resonance imaging (MRI) brain scans of patients with comorbid learning disability with schizophrenia, schizophrenia alone, learning disability alone, and normal controls. Our primary aim was to replicate a previous region of interest (ROI) finding that comorbids and schizophrenics belong to the same population. Nonparametric analysis in normalized space showed no significant differences in grey matter distribution between the comorbid and schizophrenia groups. Furthermore, this analysis showed significant grey matter reductions in the comorbid and schizophrenia groups when compared to the learning-disabled or the normal controls. Parametric analysis localized the significant grey matter reductions between the normal controls and the comorbid and schizophrenia groups to the prefrontal and temporal lobes. It also identified an area of increased grey matter, on the inferior aspect of the postcentral gyrus, in the learning-disabled alone compared to the other groups. Native space parametric and nonparametric analyses, based on modulation of the normalized scans, confirmed the similarity in grey matter distribution of the comorbid and schizophrenia groups. Results confirm the ROI finding that in native space the learning-disabled group possesses the least and normal controls the most grey matter for the cohort. An increase in the basal ganglia of patients with schizophrenia vs. the learning-disabled, probably attributable to antipsychotic medication, was identified in the native space analysis. The native space results did not however register statistically significant temporal lobe reductions found under normalized analysis between schizophrenics and normal controls. This may be attributable to minor physical anomalies (MPA) in the schizophrenic cranium. Overall, these VBM results replicate previous ROI findings and are compatible with the view that comorbid learning disability with schizophrenia is a severe form of schizophrenia, rather than a consequence of learning disability. VBM has the facility to compare grey matter distributions in this structurally diverse cohort.

Adult↗

Less white matter concentration in autism: 2D voxel-based morphometry.

Autism is a neurodevelopmental disorder affecting behavioral and social cognition, but there is little understanding about the link between the functional deficit and its underlying neuroanatomy. We applied a 2D version of voxel-based morphometry (VBM) in differentiating the white matter concentration of the corpus callosum for the group of 16 high functioning autistic and 12 normal subjects. Using the white matter density as an index for neural connectivity, autism is shown to exhibit less white matter concentration in the region of the genu, rostrum, and splenium removing the effect of age based on the general linear model (GLM) framework. Further, it is shown that the less white matter concentration in the corpus callosum in autism is due to hypoplasia rather than atrophy.

Adolescent↗

Voxel-based morphometry detects patterns of atrophy that help differentiate progressive supranuclear palsy and Parkinson's disease.

Progressive supranuclear palsy (PSP) and Parkinson's disease (PD) are neurodegenerative diseases with distinctive pathological appearances. Early clinical diagnosis can be difficult. MRI may help differentiate PSP from PD, but the differences are often only obvious with advanced disease. It would be useful to have an unbiased assessment of difference to guide visual assessment of MRI as an aid to clinical diagnosis. Voxel-based morphometry (VBM) offers nonbiased, observer-independent morphometric MRI analysis. Our objectives were to assess structural differences between PSP, PD, and normal controls and test the clinical utility of the results. T1-weighted MR images in 12 patients with clinically diagnosed PSP, 12 with PD, and 12 age- and sex-matched controls were normalized to a common stereotaxic space and segmented into gray matter (GM) and white matter (WM) then analyzed using VBM. MRI scans were reviewed by a neuroradiologist blinded to the clinical diagnosis and assigned to the "non-PSP" or "PSP" group based on regional differences highlighted using VBM. VBM revealed significant group differences between PSP and PD as well as PSP and controls, with tissue reduction demonstrated in the region of the cerebral peduncles and midbrain. With these regional differences as a guide, neuroradiological diagnosis achieved a sensitivity of 83% and a specificity of 79%. VBM did not detect dramatic changes in frontal regions despite significant frontal cognitive decline in the PSP group. Pathology in the basal ganglia rather than tissue loss in the frontal lobes could be responsible for this. This information may help in the differentiation of PSP in clinical practice.

Aged↗

Superior temporal sulcus anatomical abnormalities in childhood autism: a voxel-based morphometry MRI study.

The underlying neurobiology of autism, a severe pervasive developmental disorder, remains unknown. Few neocortical brain MRI abnormalities have been reported. Using rest functional brain imaging, two independent studies have described localized bilateral temporal hypoperfusion in children with primary autism. In order to search for convergent evidence of anatomical abnormalities in autistic children, we performed an anatomical MRI study using optimized whole-brain voxel-based morphometry (VBM). High-resolution 3-D T1-weighted MRI data sets were acquired in 21 children with primary autism (mean age 9.3 +/- 2.2 years) and 12 healthy control children (mean age 10.8 +/- 2.7 years). By comparing autistic children to normal children, we found bilaterally significant decreases of grey matter concentration located in superior temporal sulcus (STS) (P < 0.05 corrected, after small volume correction; SVC). Children with autism were also found to have a decrease of white matter concentration located in the right temporal pole and in cerebellum (P < 0.05, corrected) compared to normal children. These results suggest that autism is associated with bilateral anatomical abnormalities localized in the STS and are remarkably consistent with functional hypoperfusion previously reported in children with autism. The multimodal STS areas are involved in highest level of cortical integration of both sensory and limbic information. Moreover, the STS is now recognized as a key cortical area of the "social brain" and is implicated in social perceptual skills that are characteristically impaired in autism. Therefore, the convergent anatomical and functional temporal abnormalities observed in autism may be important in the understanding of brain behavior relationships in this severe developmental disorder.

Adolescent↗

Comparison of standard and optimized voxel-based morphometry for analysis of brain changes associated with temporal lobe epilepsy.

We compared statistical parametric maps (SPMs) of group-wise regional gray matter differences between temporal lobe epilepsy (TLE) patients with unilateral hippocampal atrophy (HA) determined by manual volumetric analysis relative to a healthy control population using standard and optimized voxel-based morphometry (VBM). We also investigated the impact of customized neuroanatomical templates on SPMs. Standard and optimized VBM analyses of gray matter concentration (GMC) and gray matter volume (GMV) correctly identified HA, regardless of the template used for normalization. The distribution of hippocampal and extrahippocampal abnormalities differed according to the technique (standard v optimized; GMC v GMV), but was not dependent on template type (default v customized) within each technique. In particular, hippocampal GMC reduction was confined to subregions of hippocampus, whereas GMV reduction was observed in the hippocampal head, body, and tail. Unlike standard and optimized GMC reduction, symmetrical GMV reduction was observed in bilateral thalamus, lenticular nuclei, cerebellum, and ipsilateral entorhinal cortex, perirhinal cortex, and fusiform gyrus in both left and right HA patients. These results show that group-wise SPMs of GMC (i.e., regional distribution of gray matter) and GMV (i.e., volume per se) reduction can identify focal atrophy that has been quantified with manual region of interest techniques, although effects are attenuated in analyses of GMC. Unlike SPMs of GMC, analyses of GMV revealed similar extrahippocampal abnormalities as previous region-of-interest volumetric and histopathological studies of intractable TLE. We suggest that in studies of neurological disorders, optimized VBM analyses of GMV may reveal subtle neuroanatomical changes that are not identified in analyses of GMC.

Adolescent↗

Voxel-based analysis of multiple-system atrophy of cerebellar type: complementary results by combining voxel-based morphometry and voxel-based relaxometry.

Voxel-based relaxometry (VBR) is a novel morphometric method that analyses the relaxation rate R2 derived from multi-echo T2-weighted images on a voxel-by-voxel basis. We used VBR to study the brain morphology of 14 patients suffering from multiple-system atrophy of cerebellar type (MSA-C) and compared the results with those obtained by voxel-based morphometry (VBM) of T1-weighted images. VBR analysis revealed reduction of relaxation rate R2 in the cerebellum and brainstem reflecting infratentorial brain atrophy. The affected regions largely corresponded to those regions in which VBM showed reductions of grey and white matter. In addition, R2 was increased in the putamen, a region in which VBM did not show abnormalities. Our data show that the combination of VBR and VBM provided convergent and complimentary information about the brain morphology of MSA-C.

Atrophy↗

Voxel-based morphometry of the thalamus in patients with refractory medial temporal lobe epilepsy.

Previous research has suggested that patients with refractory medial temporal lobe epilepsy (MTLE) show gray matter atrophy both within the temporal lobes as well as in the thalamus. However, these studies have not distinguished between different nuclei within the thalamus. We examined whether thalamic atrophy correlates with the nuclei's connections to other regions in the limbic system. T1-weighted MRI scans were obtained from 49 neurologically healthy control subjects and 43 patients diagnosed with chronic refractory MTLE that was unilateral in origin (as measured by ictal EEG and hippocampal atrophy observed on MRI). Measurements of gray matter concentration (GMC) were made using automated segmentation algorithms. GMC was analyzed both voxel-by-voxel (preserving spatial precision) as well as using predefined regions of interest. Voxel-based morphometry revealed intense GMC reduction in the anterior portion relative to posterior thalami. Furthermore, thalamic atrophy was greater ipsilateral to the MTLE origin than on the contralateral side. Here we demonstrate that the thalamic atrophy is most intense in the thalamic nuclei that have strong connections with the limbic hippocampus. This finding suggests that thalamic atrophy reflects this region's anatomical and functional association with the limbic system rather than a general vulnerability to damage.

Adolescent↗

Voxel-based morphometry and stereology provide convergent evidence of the importance of medial prefrontal cortex for fluid intelligence in healthy adults.

We investigated whether a relationship exists between frontal lobe volume and fluid intelligence as measured by both Cattell's Culture Fair test and the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Performance scale, but not with crystallized intelligence as measured by the WAIS-R Verbal scale, in healthy adults, using two well-established image analysis techniques applied to high-resolution MR brain images. Firstly, using voxel-based morphometry (VBM), we investigated whether a significant relationship exists between gray matter concentration and fluid intelligence on a voxel-by-voxel basis. Secondly, we applied the Cavalieri method of modern design stereology in combination with point counting to investigate possible relationships between macroscopic volumes of relevant brain regions defined as dorsolateral, dorsomedial, orbitolateral, and orbitomedial prefrontal cortex on the basis of neuroanatomical landmarks, and fluid intelligence. We also examined the effect on these relationships of normalizing regional brain volumes to intracranial volume. VBM analysis revealed a positive correlation between gray matter concentration in the medial region of prefrontal cortex and Culture Fair scores (corrected for multiple comparisons), and also WAIS-R Performance Intelligence sum of scaled scores (SSS) (uncorrected for multiple comparisons before controlling for age, and this converges with the stereological finding of the positive correlation between volume of dorsomedial prefrontal cortex normalized to intracranial volume and Culture Fair scores after controlling for age. WAIS-R Verbal Intelligence SSS showed no correlations. We interpret our findings, from independent analyses of both VBM and stereology, as evidence of the importance of medial prefrontal cortex in supporting fluid intelligence.

Adult↗

Comparison of different methodological implementations of voxel-based morphometry in neurodegenerative disease.

Voxel-based morphometry (VBM) is a popular method for probing inter-group differences in brain morphology. Variation in the detailed implementation of the algorithm, however, will affect the apparent results of VBM analyses and in turn the inferences drawn about the anatomic expression of specific disease states. We qualitatively assessed group comparisons of 43 normal elderly control subjects and 51 patients with probable Alzheimer's disease, using five different VBM variations. Based on the known pathologic expression of the disease, we evaluated the biological plausibility of each. The use of a custom template and custom tissue class prior probability images (priors) produced inter-group comparison maps with greater biological plausibility than the use of the Montreal Neurological Institute (MNI) template and priors. We present a method for initializing the normalization to a custom template, and conclude that, when incorporated into the VBM processing chain, it yields the most biologically plausible inter-group differences of the five methods presented.

Aged↗

Using voxel-based morphometry to map the structural changes associated with rapid conversion in MCI: a longitudinal MRI study.

Capturing the dynamics of gray matter (GM) atrophy in relation to the conversion from mild cognitive impairment (MCI) to clinically probable Alzheimer's disease (AD) would be of considerable interest. In this prospective study we have used a novel longitudinal voxel-based method to map the progression of GM loss in MCI patients over time and compared converters to non-converters. Eighteen amnestic MCI patients were followed-up for a predefined fixed period of 18 months and conversion was judged according to NINCDS-ADRDA criteria for probable AD. Each patient underwent a high-resolution T1-weighted volume MRI scan both at entry in the study and 18 months later. We used an optimal VBM protocol to compare baseline imaging data of converters to those of non-converters. Moreover, to map GM loss from baseline to follow-up assessment, we used a modified voxel-based morphometry (VBM) procedure specially designed for longitudinal studies. At the end of the follow-up period, seven patients had converted to probable AD. Areas of lower baseline GM value in converters mainly included the hippocampus, parahippocampal cortex, and lingual and fusiform gyri. Regions of significant GM loss over the 18-month follow-up period common to both converters and non-converters included the temporal neocortex, parahippocampal cortex, orbitofrontal and inferior parietal areas, and the left thalamus. However, there was significantly greater GM loss in converters relative to non-converters in the hippocampal area, inferior and middle temporal gyrus, posterior cingulate, and precuneus. This accelerated atrophy may result from both neurofibrillary tangles accumulation and parallel pathological processes such as functional alteration in the posterior cingulate. The ability to longitudinally assess GM changes in MCI offers new perspectives to better understand the pathological processes underlying AD and to monitor the effects of treatment on brain structure.

Aged↗

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.

Aging↗

Grey matter loss in relapsing-remitting multiple sclerosis: a voxel-based morphometry study.

Global grey matter (GM) loss has been reported in multiple sclerosis (MS). We addressed the question of if and where GM loss is localized by means of optimized voxel-based morphometry, applied to MRI studies of 51 patients with clinically defined relapsing-remitting MS and 34 age-matched normal subjects, segmented into normal and abnormal brain tissues using a multiparametric approach. Segmented GM volumes were subsequently compared on a voxel-by-voxel basis to highlight regions of relative GM loss (P < 0.05, corrected for multiple comparisons at AnCova). Additionally, localized differences in brain asymmetry between the MS and the control groups were assessed by comparing on a voxel-by-voxel basis maps of GM differences between the two hemispheres (P < 0.05 corrected for multiple comparisons). In MS patients, GM volume was significantly decreased at the level of the left fronto-temporal cortex and precuneus, as well as of anterior cingulate gyrus and of caudate nuclei bilaterally. The only cortical region of significant GM loss in the right hemisphere was located in the postcentral area. Furthermore, GM loss regions were colocalized with increased GM asymmetries (Left < Right) in MS, confirming a preferential left-sided GM loss. Caudate atrophy correlated with lesion load, while no correlation between cortical regional GM loss and disease duration, clinical status or lesion load emerged. Our findings suggest that in RR-MS cortical GM reduction preferentially involves left fronto-temporal structures and deep GM, the latter correlating preferentially to global lesion load.

Adult↗