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Biomedical subjects

Marko Wilke

Publications and source records attributed to Marko Wilke.

At least 19 recordsLinked to original sources

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.

Adolescent↗

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.

Brain↗

Language lateralization in magnetoencephalography: two tasks to investigate hemispheric dominance.

Hemispheric specialization for language has been the focus of many studies, mainly using functional magnetic resonance imaging. Here, we used magnetoencephalography to investigate hemispheric dominance and time-dependent aspects of cortical language processing. We implemented a verb generation task and a newly designed vowel identification task. Eleven healthy adults were investigated. By using oscillatory magnetoencephalography spectral analysis, significant hemispheric differences were found for both tasks in cerebral language areas. Robust left-lateralization in frontal brain regions was observed with the verb generation task, confirming previous functional magnetic resonance imaging and magnetoencephalography studies. Our new vowel identification task yields significant left-lateralization in posterior language regions, making this silent and child-friendly task a valuable alternative for non-invasive language assessment in difficult populations.

Brain↗

Lesion-induced right-hemispheric language and organization of nonverbal functions.

Early left-hemispheric brain lesions may lead to a reorganization of language into the right hemisphere. Language functions are consecutively spared, but visuospatial functions show slight deficits. Cortical 'crowding' of the right hemisphere has been suggested as an explanation for this effect, but no direct evidence has as yet been put forward. We examined six patients with early left-hemispheric brain lesions and subsequent right-hemispheric language organization with functional magnetic resonance imaging and compared their activation patterns in a verbal and two nonverbal tasks with the patterns of six controls. In the patient group, nonverbal functions were reorganized neither interhemispherically nor intrahemispherically. Instead, verbal and nonverbal functions were mediated by a common right-hemispheric network. This argues in favour of the 'crowding hypothesis'.

Adolescent↗

An fMRI task battery for assessing hemispheric language dominance in children.

Hemispheric dominance for language is an important issue in functional neuroimaging, particularly driven by efforts to overcome the need for the invasive Wada test, which is all the more pressing in children. Here, we aimed at developing new paradigms for functional magnetic resonance imaging (fMRI) for assessment of language dominance that can be used in younger children and allow for performance monitoring. Two new tasks (letter and animal task) were developed and compared to two reference tasks (synonyms and verb generation task) from the literature. Overall, 23 healthy children participated (13 boys, 10 girls, 10.2 +/- 2.5 years, range 6.1-15.3 years). Analysis was done using statistical nonparametrical mapping (SnPM2) on SPM2. Both reference tasks show activation in a number of left-frontal brain regions. The letter task induced a very localized activation in the left hemisphere's Broca's region, while not activating other frontal brain regions. Lateralization (as assessed in different anatomically and functionally defined regions) was consistent and strong. The animal task failed to activate frontal brain regions and was not suitable for assessing language dominance in children in this form. We conclude that while both reference tasks are useful for determining language dominance, they coactivate a number of task-related frontal areas not directly involved in language processing. Additionally, one task is not applicable in young children while the other does not allow performance monitoring. The letter task allows to selectively activate language areas in the dominant hemisphere and is applicable even in the very lowest age group amenable to fMRI investigations while still allowing performance monitoring. It may thus be a useful tool in assessing normal and pathological language organization.

Animals↗

Visuospatial deficits in patients with early left-hemispheric lesions and functional reorganization of language: consequence of lesion or reorganization?

INTRODUCTION: Patients with early left-hemispheric lesions have repeatedly been reported to show spared language functions (which are then mediated by the right hemisphere), but exhibit deficits in visuospatial functions. The "crowding hypothesis" explains these deficits by a neuronal scarcity in the right hemisphere for the original right hemispheric functions. An alternative hypothesis suggests direct lesion effects as the sole reason for the visuospatial impairments. The scope of this study was to examine the relations between visuospatial skills and hemispheric preference for language, and between visuospatial skills and cerebral lesion size. METHODS: In a sample of young adults with pre- or perinatally acquired focal lesions of the left hemisphere and unilateral spastic cerebral palsy on the right side, we assessed intelligence and neuropsychological functions in the verbal and visuospatial domains. The behavioural data was correlated with structural MRI information and language preference as assessed using fMRI. RESULTS: Patients with right hemispheric language production were impaired in visuospatial functions, compared not only to normal controls, but also to patients without right hemispheric language preference. Additionally, the degree of right hemispheric language correlated negatively with performance in visuospatial tasks. Lesion size correlated negatively only with performance IQ, which again correlated negatively with motor impairment of the patients and thus does not seem to reflect true cognitive deficits. CONCLUSION: Visuospatial deficits in patients with early left-hemispheric lesions are a consequence of lesion-induced right hemispheric language organization, thus lending further support to the "crowding hypothesis".

Adolescent↗

Comprehensive language mapping in children, using functional magnetic resonance imaging: what's missing counts.

Noninvasive language mapping is a frequently used application of functional magnetic resonance imaging. The examination of children, however, poses both practical and technical challenges. To this effect, we have developed two new paradigms mainly requiring passive listening to stories from which several key words were removed. Results were compared with a standard active verb-generation task, particularly with regard to hemispheric dominance in frontal brain areas. Fifteen healthy children (seven boys, eight girls, 6-14 years) were scanned. Distinct frontal activation was seen in our new tasks, which was stronger when the tasks were analyzed specifically with regard to the missing words. This confirms the hypothesis that the removal of these words is the key in inducing frontal activation. Frontal lateralization was consistent and strong in all three paradigms. Additionally, receptive language areas are also mapped by our new tasks. We conclude that our two new, child-friendly functional magnetic resonance imaging paradigms are useful in determining hemispheric dominance for language in children too young or too impaired to execute an active task. They also allow robust mapping of receptive language areas.

Adolescent↗

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.

Adolescent↗

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.

Brain↗

BOLD fMRI signal increases with age in selected brain regions in children.

To determine whether the BOLD signal used in fMRI is age dependent in childhood, 332 healthy children (age 4.9-18.9 years) performed tasks in a periodic block design during 3 T fMRI: (1) a verb generation task interleaved with a finger tapping task; (2) a word-picture matching task interleaved with an image discrimination task. Significant correlations between percent signal change in BOLD effect and age occurred in left Broca's, middle frontal, Wernicke's, and inferior parietal regions, and anterior cingulate during the verb generation task; in precentral, postcentral, middle frontal, supplementary motor, and precuneus regions during the finger tapping task; and in bilateral lingula gyri during the word-picture matching task. Thus, BOLD effect increases with age in children during sensorimotor and language tasks.

Adolescent↗

Voxel-based morphometry in adolescents with bipolar disorder: first results.

Bipolar disorder is an increasingly recognized cause of significant morbidity in the pediatric age group. However, there is still a large degree of uncertainty regarding the underlying neurobiological deficits. In this preliminary study, we performed automated volumetric studies and whole-brain voxel-based morphometry (VBM) on gray matter. Imaging data from 10 adolescents with bipolar disorder were compared with data from 52 age- and gender-matched healthy controls. Previously defined brain parcellations and optimized VBM protocols were used, based on custom-made pediatric reference data. An additional, exploratory whole-brain comparison was also implemented. The volumetric region-of-interest study revealed significantly greater gray matter volume in central gray matter structures bilaterally (including the basal ganglia and the thalamus) and the left temporal lobe in the bipolar group. VBM confirmed bilaterally larger basal ganglia. Localized gray matter deficits in bipolar subjects were found in the medial temporal lobe, orbito-frontal cortex, and the anterior cingulate, confirming and extending earlier studies.

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↗

Abnormal frontal white matter tracts in bipolar disorder: a diffusion tensor imaging study.

OBJECTIVES: Prefrontal white matter has been hypothesized to be integral to the pathophysiology of bipolar disorder. Recent morphometric studies however, have not observed changes in white matter in bipolar patients. We hypothesized that changes in prefrontal function in bipolar disorder, widely reported in the literature, may be related to a loss of white matter tract integrity with a resultant dysconnectivity syndrome. In this study we utilized diffusion tensor imaging (DTI) to examine prefrontal white matter in patients with bipolar disorder. METHODS: Nine patients with bipolar disorder and nine healthy controls were recruited. DTI and localizing anatomic data were acquired, and regions of interest (ROIs) identified in the prefrontal white matter at 15, 20, 25, and 30 mm superior to the anterior commissure (AC). Fractional anisotropy (FA) and trace apparent diffusion coefficient (TADC) were compared by ROI between study groups. RESULTS: The FA of ROIs 25 and 30 mm above the AC was significantly reduced in patients with bipolar disorder; FA of all ROIs showed high-medium to large effect sizes. No significant group differences were identified in TADC. CONCLUSIONS: Our findings suggest that a loss of bundle coherence is present in prefrontal white matter. This loss of coherence may contribute to prefrontal cortical pathology in patients with bipolar disorder.

Adult↗

Variability of gray and white matter during normal development: a voxel-based MRI analysis.

This study was aimed at investigating regional and local variability of brain tissue during normal human brain development. We investigated high-resolution MR-imaging data using SPM99 (Wellcome Department, University College London, UK). A pixel-wise variation coefficient of gray and white matter was calculated to visualize local variability. Data from 200 normal children (5-18 years) were analyzed. We found a profound interaction between variability of brain structures and normal development in both gray and white matter. Variability in gray and white matter shows regionally specific, age-related variations, possibly offering a new tool for the assessment of subtle brain abnormalities. Our results emphasize the necessity to take this variability into account when planning pediatric neuroimaging studies.

Adolescent↗

Bright spots: correlations of gray matter volume with IQ in a normal pediatric population.

The localization of brain areas related to cognitive functions has yet to be thoroughly explored in children. We therefore set out to apply volumetric, voxel-based, and structural connectivity analyses to magnetic resonance images from a large sample of healthy children. We could confirm a strong correlation of whole-brain gray matter volume and the individual intelligence quotient; however, this correlation only developed with age in our sample, in that it was not present in the younger children. With the application of an optimized protocol for voxel-based morphometry, the anterior cingulate was shown to be directly correlated with a measure of human intelligence. Furthermore, an analysis of structural connectivity identified gray matter volume in several distinct brain areas to be related to cognitive functions. The implications of our findings for normal development, pathological processes, and our understanding of cognition are discussed and related to previous findings.

Aging↗

Language processing during natural sleep in a 6-year-old boy, as assessed with functional MR imaging.

Functional MR imaging for language lateralization was performed in a 6-year-old child before neurosurgical intervention. A passive story-listening task was used; this revealed a bilateral language network. The task was repeated during the same session when the child had fallen asleep and surprisingly yielded strong activation in similar language areas. Our findings suggest that language processing does occur during natural sleep, even in young children. This potentially allows for an assessment of language functions, even in sleeping children.

Brain Mapping↗

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.

Adult↗

Assessment of spatial normalization of whole-brain magnetic resonance images in children.

Commonly used frameworks for spatial normalization of brain imaging data (e.g., Talairach-space) are based on one or more adult brains. As pediatric brains are different in size and shape from adult brains and continue to develop through childhood, we aimed to assess the influence of age on various spatial normalization parameters. One hundred forty-eight healthy children aged 5-18 years were included in this study. The linear scaling parameters and the deformations from the non-linear spatial normalization to both a standard adult and a custom pediatric template were analyzed within SPM99. The effect of using a brain mask on the linear and of using different levels of constraint on the non-linear spatial normalization was assessed. Of the linear scaling factors, only the X-dimension (left-right) showed a significant age-correlation when based on brain tissue, whereas the overall scaling was not correlated with age. When based on the whole head, a very strong age-effect can be found in all dimensions. Non-linear deformations also show localized correlations with age, most pronounced in parietal and frontal areas. The total amount of volume change is significantly lower when using a pediatric template. It is also substantially influenced by the degree of regularization that is exerted on the spatial normalization parameters. Our results suggest that in the cortical areas showing a strong correlation of deformation with age, caution should be used in assigning imaging results in children to a specific morphological structure. Also, to minimize the amount of deformation during non-linear spatial normalization, a pediatric template should be used. Further implications of our findings on developmental neuroimaging studies are discussed.

Adolescent↗