Marko Wilke

Cognitive functions correlate with white matter architecture in a normal pediatric population : A diffusion tensor MRI study

A possible relationship between cognitive abilities and white matter structure as assessed by magnetic resonance diffusion tensor imaging (DTI) was investigated in the pediatric population. DTI was performed on 47 normal children ages 5–18. Using a voxelwise analysis technique, the fractional anisotropy (FA) and mean diffusivity (MD) were tested for significant correlations with Wechsler full‐scale IQ scores, with subject age and gender used as covariates. Regions displaying significant positive correlations of IQ scores with FA were found bilaterally in white matter association areas, including frontal and occipito‐parietal areas. No regions were found exhibiting correlations of IQ with MD except for one frontal area significantly overlapping a region containing a significant correlation with FA. The positive direction of the correlation with FA is the same as that found previously with age, and indicates a positive relationship between fiber organization and/or density with cognitive function. The results are consistent with the hypothesis that regionally specific increased fiber organization is a mechanism responsible for the normal development of white matter tracts. Hum Brain Mapp, 2005.

LI-tool: A new toolbox to assess lateralization in functional MR-data

A lateralization index (LI) is commonly computed to describe the asymmetry of activation as detectable by various functional imaging techniques, particularly functional magnetic resonance imaging (fMRI). In this article, we examine and compare different approaches that have been used in the past. For illustration purposes, 100 synthetic datasets and real fMRI-data from 12 subjects were evaluated. As shown before, the calculation of a lateralization index suffers from a number of drawbacks, namely vulnerability to statistical outliers, data sparsity, thresholding effects and lack of taking into account regional variability of activation. Optional processing steps investigated here seem to increase reliability of the such-calculated indices. To allow a more standardized, reproducible and accessible evaluation of laterality effects, current and new approaches have been implemented in a versatile toolbox running within the spm2 or spm5 software environment.

Template-O-Matic: a toolbox for creating customized pediatric templates.

Processing pediatric neuroimaging data is a challenge due to pervasive morphological changes that occur in the human brain during normal development. This is of special relevance when reference data is used as part of the processing approach, as in spatial normalization and tissue segmentation. Current approaches construct reference data (templates) by averaging brain images from a control group of subjects, or by creating custom templates from the group under study. In this technical note, we describe a new, and generalized method of constructing such appropriate reference data by statistically analyzing a large sample (n=404) of healthy children, as acquired during the NIH MRI study of normal brain development. After eliminating non-contributing demographic variables, we modeled the effects of age (first, second, and third-order terms) and gender, for each voxel in gray matter and white matter. By appropriate weighting with the parameter estimates from these analyses, complete tissue maps can be generated automatically from this database to match a pediatric population selected for study. The algorithm is implemented in the form of a toolbox for the SPM5 image data processing suite, which we term Template-O-Matic. We compare the performance of this approach with the current method of template generation and discuss the implications of our approach.

Size matters: Increased grey matter in boys with conduct problems and callous–unemotional traits

Brain imaging studies of adults with psychopathy have identified structural and functional abnormalities in limbic and prefrontal regions that are involved in emotion recognition, decision-making, morality and empathy. Among children with conduct problems, a small subgroup presents callous-unemotional traits thought to be antecedents of psychopathy. No structural brain imaging study has examined this subgroup of children. The present study used voxel-based morphometry to compare whole brain grey matter volumes and concentrations of boys with elevated levels of callous-unemotional conduct problems and typically developing boys and explored four a priori regions of interest. sMRI scans were collected from 23 boys with elevated levels of callous-unemotional conduct problems (mean age = 11 years 8 months) and 25 typically developing boys (mean age = 11 years 6 months) selected from a community sample of children. Data were analysed using optimized voxel-based morphometry. Study-specific probability maps were created and four a priori regions of interest identified (orbitofrontal, anterior cingulate and anterior insular cortices and amygdala). Both grey matter volume and concentration were examined controlling for cognitive ability and hyperactivity-inattention symptoms. Boys with callous-unemotional conduct problems, as compared with typically developing boys, presented increased grey matter concentration in the medial orbitofrontal and anterior cingulate cortices, as well as increased grey matter volume and concentration in the temporal lobes bilaterally. These findings may indicate a delay in cortical maturation in several brain areas implicated in decision making, morality and empathy in boys with callous-unemotional conduct problems.

Differences in white matter architecture between musicians and non-musicians: a diffusion tensor imaging study.

Previous studies found structural brain differences between musicians and non-musicians. In order to determine possible differences in white matter architecture, diffusion tensor imaging was performed on five adult subjects with musical training since early childhood, and seven adult controls. The musicians displayed significantly greater fractional anisotropy (FA) in the genu of the corpus callosum, while significantly less FA was found in the corona radiata and the internal capsule bilaterally. Further areas also showed significant differences. We hypothesize that these changes are due to the cognitive and motor effects, respectively, of musical training.

A combined bootstrap/histogram analysis approach for computing a lateralization index from neuroimaging data

Cerebral hemispheric specialization has traditionally been described using a lateralization index (LI). Such an index, however, shows a very severe threshold dependency and is prone to be influenced by statistical outliers. Reliability of this index thus has been inherently weak, and the assessment of this reliability is as yet not possible as methods to detect such outliers are not available. Here, we propose a new approach to calculating a lateralization index on functional magnetic resonance imaging data by combining a bootstrap procedure with a histogram analysis approach. Synthetic and real functional magnetic resonance imaging data was used to assess performance of our approach. Using a bootstrap algorithm, 10,000 indices are iteratively calculated at different thresholds, yielding a robust mean, maximum and minimum LI and thus allowing to attach a confidence interval to a given index. Taking thresholds into account, an overall weighted bootstrapped lateralization index is calculated. Additional histogram analyses of these bootstrapped values allow to judge reliability and the influence of outliers within the data. We conclude that the proposed methods yield a robust and specific lateralization index, sensitively detect outliers and allow to assess the underlying data quality.

Normative pediatric brain data for spatial normalization and segmentation differs from standard adult data

Spatial normalization and morphological studies of pediatric brain imaging data based on adult reference data may not be appropriate due to the developmental differences between the two populations. In this study, we set out to create pediatric templates and a priori brain tissue data from a large collection of normal, healthy children to compare it to standard adult data available within a widely used imaging software solution (SPM99, WDOCN, London, UK). Employing four different processing strategies, we found considerable differences between our pediatric data and the adult data. We conclude that caution should be used when analyzing pediatric brain data using adult a priori information. To assess the effects of using pediatric a priori brain information, the data obtained in this study is available to the scientific community from our website (www.irc.cchmc.org). Magn Reson Med 50:749–757, 2003.

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.

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.

Anatomical Signatures of Dyslexia in Children: Unique Information from Manual and Voxel Based Morphometry Brain Measures

Thirteen male control and thirteen male dyslexic children (age, 121-152 months) were studied to determine if voxel based morphometry (VBM) could identify anatomical differences in the right cerebellar anterior lobe, and right and left pars triangularis that were identified with manual measures of the same children. VBM demonstrated significant gray and white matter differences in these three brain regions. In contrast to the manual results, these differences were not significant after controlling for brain volume, suggesting the manual measures captured additional important variance that distinguished the groups. Post-hoc VBM comparisons demonstrated white matter volume differences in a left temporal-parietal region that are consistent in location with results from diffusion tensor imaging studies of dyslexia. The VBM analyses also identified, gray matter volume differences in the left and right lingual gyrus, left inferior parietal lobule and cerebellum, areas that had not been examined with manual methods. We conclude that manual and automated methods provide valuable and complementary approaches to the search for functionally significant neurobiological characteristics of dyslexia.