Biomedical subjects

K Zilles

Publications and source records attributed to K Zilles.

At least 37 records · Page 2Linked to original sources

PubMed2003

Localized morphological brain differences between English-speaking Caucasians and Chinese-speaking Asians: new evidence of anatomical plasticity.

Deformation field morphometry was applied to magnetic resonance images to detect differences in brain shape between English-speaking Caucasians and Chinese-speaking Asians. Anatomical differences between these two groups were limited to gyri in the frontal, temporal and parietal lobes, which are known (through functional imaging studies) to differentiate Chinese speakers from English speakers. We interpret these anatomical differences as evidence of neural plasticity shaped by the process of language acquisition during childhood. While anatomical plasticity due to manual skill acquisition (e.g. in musicians) has been established, to our knowledge this is the first report of a brain anatomical difference attributable to a learned cognitive strategy.

Adult↗

PubMed2003

Synchronization tomography: a method for three-dimensional localization of phase synchronized neuronal populations in the human brain using magnetoencephalography.

We present a noninvasive technique which allows the anatomical localization of phase synchronized neuronal populations in the human brain with magnetoencephalography. We study phase synchronization between the reconstructed current source density (CSD) of different brain areas as well as between the CSD and muscular activity. We asked four subjects to tap their fingers in synchrony with a rhythmic tone, and to continue tapping at the same rate after the tone was switched off. The phase synchronization behavior of brain areas relevant for movement coordination, inner voice, and time estimation changes drastically when the transition to internal pacing occurs, while their averaged amplitudes remain unchanged. Information of this kind cannot be derived with standard neuroimaging techniques like functional magnetic resonance imaging or positron emission tomography.

Brain↗

PubMed2003

Developmental hemispheric asymmetry of interregional metabolic correlation of the auditory cortex in deaf subjects.

The functional connectivity of the auditory cortex might be altered in deaf subjects due to the loss of auditory input. We studied the developmental changes of functional connectivity of the primary auditory cortex (A1) in deaf children, deaf adults, and normal hearing adults by examining interregional metabolic correlation with (18)F-FDG PET. The mean activity of FDG uptake in the cytoarchitectonically defined A1 region served as a covariate in the interregional and interhemispheric correlation analysis. A1 metabolic rate was correlated with that of the ipsilateral superior temporal lobe in both normal and deaf subjects. This correlated area was larger in deaf children than in deaf or normal hearing adults. Concerning the functional connectivity of A1, a hemispheric asymmetry was found in that the extent of interregional correlation was clearly larger in the right than in the left hemisphere. This asymmetry was particularly pronounced in the younger deaf children. Both extent and asymmetry of the functional connectivity of A1 subsided with age. Contrary to this, a correlation between the left and the right primary auditory cortices was absent in younger deaf children but became apparent as they grew older.

Adolescent↗

PubMed2002

Stereotaxic localization, intersubject variability, and interhemispheric differences of the human auditory thalamocortical system.

Population (probability) maps of cytoarchitectonically defined cortical maps and myeloarchitectonically defined subcortical fiber tracts of the human brain became recently available. These maps can be used for the precise anatomical localization of activated foci as found in functional imaging studies. The aim of this study is to evaluate population maps of the human acoustic radiation (AR) for the purpose of brain mapping studies. Thus, a stereotaxic 3-D representation of the human AR was computed which includes myeloarchitectonic probabilistic maps of AR and its thalamic origin, i.e. the cytoarchitectonically defined medial geniculate nucleus (MGN). These maps were compared with earlier, mostly schematic drawings of AR and MGN. To generate these maps, the degree of intersubject variability of AR and MGN in each stereotaxic position was quantified for the standard axes (x, y, and z) of the reference space in a series of 10 adult human postmortem brains. The results show that the location and volumes of AR and MGN vary considerably between individuals and hemispheres. It is demonstrated that this striking degree of spatial variations may lead to structural-functional mismatch in brain mapping studies based on the Talairach atlas (discrepancy maps). Furthermore, the volumetric measures showed no hemispheric asymmetry for AR and MGN. In contrast to earlier maps, our approach provides microanatomically defined data as a probabilistic reference system for research in auditory structure-function relationships.

Adult↗

PubMed2002

Task instructions influence the cognitive strategies involved in line bisection judgements: evidence from modulated neural mechanisms revealed by fMRI.

Manual line bisection and a perceptual variant thereof (the Landmark test) are widely used to assess visuospatial neglect in neurological patients, but little is known about the cognitive strategies involved. In the Landmark test, one could explicitly compare the lengths of the left and right line segments; alternatively, one could compute the centre of mass of the display. We here investigate with functional MRI if these cognitive strategies modulate the neural mechanisms underlying judgements whether pre-transected horizontal lines are correctly bisected (the Landmark test) in normal volunteers. Functional neuroimaging (fMRI) was carried out in 12 healthy volunteers who judged: (a) whether the line segments on either side of the transection mark were of equal length, and (b) whether the transection mark was in the centre of the line. Line centre judgements were made significantly faster than line length comparisons. Increased neural activity common to both strategies was observed in inferior parietal lobes bilaterally and right temporooccipital cortex. Further activations, most likely reflecting general task demands like response selection and motor control, were found in the precentral gyrus bilaterally, supplementary motor area bilaterally, right anterior cingulate, right dorsolateral prefrontal cortex, cerebellar vermis, and right thalamus and right putamen. Explicit length comparisons (relative to line centre judgements) differentially activated left superior posterior parietal cortex, with a tendency toward activation of the equivalent area on the right, while the reverse comparison revealed differential activation in the lingual gyrus bilaterally and anterior cingulate cortex. The activations observed in inferior parietal cortex during task performance using either strategy are consistent with the results of lesion studies. The differential activation of superior posterior parietal cortex following length instructions suggests that explicit comparisons of spatial extent were implicated. The differential activation of bilateral occipital cortex following centre judgements suggests that the centre of a line is extracted at an early stage of visual processing.

Adult↗

PubMed2002

Excitatory and inhibitory neurons express c-Fos in barrel-related columns after exploration of a novel environment.

Recent work has shown that behaviorally meaningful sensory information processing is accompanied by the induction of several transcription factors in the barrel cortex of rodents. It is now generally accepted that stimulus-transcription coupling is an important step in the sequence of events leading to long-term plastic changes in neuronal structure and function. Nevertheless, so far few data are available as to what types of neurons are involved in such a genomic response. Here, we determined the morphological and neurochemical identity of neurons in rat barrel cortex showing a c-Fos-immunoreactive nucleus after exploration of an enriched environment. Double stainings of c-Fos and glial fibrillary acidic protein excluded astrocytes as a possible cell type expressing this transcription factor. By morphological phenotyping with intracellular Lucifer Yellow injections, it was found that a large majority were probably excitatory pyramidal cells, but inhibitory interneurons were also found to contain c-Fos-immunoreactive nuclei. By neurochemical phenotyping of GABAergic interneurons with specific antibodies, a significant induction was found, in a layer-dependent manner, for the populations of glutamic acid decarboxylase-, parvalbumin-, calbindin- and vasoactive intestinal polypeptide-immunoreactive neurons but not for calretinin-immunoreactive cells in experimental compared to control columns. From these data we conclude that thalamic afferents effectively drive cortical excitatory as well as inhibitory intracortical circuits. Thus, the adaptations of receptive field properties of cortical neurons after different manipulations of the sensory periphery are likely to be caused by plastic changes in excitatory and inhibitory networks.

Afferent Pathways↗

PubMed2002

The importance of seeing it coming: a functional magnetic resonance imaging study of motion-in-depth towards the human observer.

Despite their crucial biological relevance, the neural structures differentially activated by the detection of optic flow towards the observer remain to be elucidated. Here, we deploy functional magnetic resonance imaging with normal volunteers to locate the areas differentially activated when motion towards the observer is detected. Motion towards the observer, compared with motion away, showed significant activations (P<0.05, corrected for multiple comparisons), as assessed using statistical parametric mapping, in the lateral inferior occipital cortex bilaterally and in right lateral superior occipital cortex. The areas implicated do not extend into area V5 or subdivisions thereof.Our data suggest that the representations of motion towards the observer implicate perceptual and attentional mechanisms acting at early stages of visual processing in extrastriate cortex. From the standpoint of efficient biological engineering, it makes sense that such crucially important functions as object motion towards the observer would be computed in early visual processing areas. Further studies will be required to determine the extent to which the effects we observed in lateral occipital cortex reflect differential attention to different types of motion, as contrasted with the derivation of explicit representations of motion towards the observer.

Adult↗

PubMed2002

Architectonics of the human cerebral cortex and transmitter receptor fingerprints: reconciling functional neuroanatomy and neurochemistry.

The density of transmitter receptors varies between different locations in the human cerebral cortex. We hypothesized that this variation may reflect the cyto- and myeloarchitectonical as well as the functional organisation of the cortex. We compared data from different imaging modalities (postmortem studies: cyto- and myeloarchitecture, quantitative in vitro receptor autoradiography; in vivo studies: PET receptor neuroimaging) in order to test our hypothesis. The regional and laminar distribution of the densities of numerous receptor types representing all classical transmitter systems as well as the adenosine system are visualized and measured in different cortical areas. The receptor distribution patterns segregate motor, primary sensory, unimodal sensory, multimodal association and other functionally identified cortical areas from each other. Areas of similar function show similar receptor fingerprints and differ from those with other properties. Thus, receptor distribution patterns reflect an organisational structure strictly correlated with the architectonics and functions of the human cerebral cortex.

Aged↗

PubMed2002

Neural activity in human primary motor cortex areas 4a and 4p is modulated differentially by attention to action.

The mechanisms underlying attention to action are poorly understood. Although distracted by something else, we often maintain the accuracy of a movement, which suggests that differential neural mechanisms for the control of attended and nonattended action exist. Using functional magnetic resonance imaging (fMRI) in normal volunteers and probabilistic cytoarchitectonic maps, we observed that neural activity in subarea 4p (posterior) within the primary motor cortex was modulated by attention to action, while neural activity in subarea 4a (anterior) was not. The data provide the direct evidence for differential neural mechanisms during attended and unattended action in human primary motor cortex.

Adult↗

PubMed2002

The influence of explicit instructions and stimulus material on lateral frontal responses to an encoding task.

In this functional magnetic resonance imaging study, we explored the effects of both stimulus material and encoding task demands on activation in lateral prefrontal cortex (PFC). Two factors were manipulated: material type and task instructions. Subjects encoded words or abstract figures (factor 1: stimulus type) and were required to make either a meaning-based or a form-based (letter or shape) decision about each stimulus (factor 2: task instructions). Abstract figures engendered significantly higher levels of right PFC activity than did words. This effect was seen for meaning-based and form-based processing tasks and was significantly greater for the former. We did not observe a differential response of left lateral PFC to verbal and pictorial material. A double dissociation, however, was found within left PFC. A ventrolateral region (within left inferior frontal gyrus) showed the highest levels of activity when words were processed according to their meaning whereas activity in a more dorsolateral region (within left middle frontal gyrus) was greatest when words were processed according to their form (constituent letters). We have therefore observed a main effect of material type in producing lateralized activation of frontal lobes, although the strength of this effect is sensitive to the nature of the task that subjects are asked to perform. Left-side lateral PFC activity is also sensitive to task instructions but this effect was specific to verbal material. The complex patterns of frontal effect counsel against any simple dichotomy of frontal function at the level of either material or task type.

Adult↗

PubMed2001

A probabilistic atlas and reference system for the human brain: International Consortium for Brain Mapping (ICBM).

Motivated by the vast amount of information that is rapidly accumulating about the human brain in digital form, we embarked upon a program in 1992 to develop a four-dimensional probabilistic atlas and reference system for the human brain. Through an International Consortium for Brain Mapping (ICBM) a dataset is being collected that includes 7000 subjects between the ages of eighteen and ninety years and including 342 mono- and dizygotic twins. Data on each subject includes detailed demographic, clinical, behavioural and imaging information. DNA has been collected for genotyping from 5800 subjects. A component of the programme uses post-mortem tissue to determine the probabilistic distribution of microscopic cyto- and chemoarchitectural regions in the human brain. This, combined with macroscopic information about structure and function derived from subjects in vivo, provides the first large scale opportunity to gain meaningful insights into the concordance or discordance in micro- and macroscopic structure and function. The philosophy, strategy, algorithm development, data acquisition techniques and validation methods are described in this report along with database structures. Examples of results are described for the normal adult human brain as well as examples in patients with Alzheimer's disease and multiple sclerosis. The ability to quantify the variance of the human brain as a function of age in a large population of subjects for whom data is also available about their genetic composition and behaviour will allow for the first assessment of cerebral genotype-phenotype-behavioural correlations in humans to take place in a population this large. This approach and its application should provide new insights and opportunities for investigators interested in basic neuroscience, clinical diagnostics and the evaluation of neuropsychiatric disorders in patients.

Adult↗

PubMed2001

Hierarchical processing of tactile shape in the human brain.

It is not known exactly which cortical areas compute somatosensory representations of shape. This was investigated using positron emission tomography and cytoarchitectonic mapping. Volunteers discriminated shapes by passive or active touch, brush velocity, edge length, curvature, and roughness. Discrimination of shape by active touch, as opposed to passive touch, activated the right anterior lobe of cerebellum only. Areas 3b and 1 were activated by all stimuli. Area 2 was activated with preference for surface curvature changes and shape stimuli. The anterior part of the supramarginal gyrus (ASM) and the cortex lining the intraparietal sulcus (IPA) were activated by active and passive shape discrimination, but not by other mechanical stimuli. We suggest, based on these findings, that somatosensory representations of shape are computed by areas 3b, 1, 2, IPA, and ASM in this hierarchical fashion.

Adult↗

PubMed2001

Human primary auditory cortex in women and men.

Specific patterns of anatomical symmetry or asymmetry have been associated with sex differences in human brain structure and function. An observer-independent cytoarchitectonic method for the quantification of cell volume densities and areal borders was used to investigate the size and microstructure of primary auditory cortex (Brodmann area 41) in female (n = 14) and male (n = 13) postmortem brains. The total brain volume-adjusted volume of the primary auditory cortex was significantly larger in women than in men bilaterally. Inverse asymmetry towards the right side, as opposed to well-known asymmetries towards the left side, was more frequent in women. Laminar cell volume densities of BA 41 showed no gender effect. The morphometric data confirm (in part) gender differences in the cerebral organization of primary auditory cortex.

Adult↗

PubMed2001

Layer-specific intracolumnar and transcolumnar functional connectivity of layer V pyramidal cells in rat barrel cortex.

Layer V pyramidal cells in rat barrel cortex are considered to play an important role in intracolumnar and transcolumnar signal processing. However, the precise circuitry mediating this processing is still incompletely understood. Here we obtained detailed maps of excitatory and inhibitory synaptic inputs onto the two major layer V pyramidal cell subtypes, intrinsically burst spiking (IB) and regular spiking (RS) cells, using a combination of caged glutamate photolysis, whole-cell patch-clamp recording, and three-dimensional reconstruction of biocytin-labeled cells. To excite presynaptic neurons with laminar specificity, the release of caged glutamate was calibrated and restricted to small areas of 50 x 50 microm in all cortical layers and in at least two neighboring barrel-related columns. IB cells received intracolumnar excitatory input from all layers, with the largest EPSP amplitudes originating from neurons in layers IV and VI. Prominent transcolumnar excitatory inputs were provided by presynaptic neurons also located in layers IV, V, and VI of neighboring columns. Inhibitory inputs were rare. In contrast, RS cells received distinct intracolumnar inhibitory inputs, especially from layers II/III and V. Intracolumnar excitatory inputs to RS cells were prominent from layers II-V, but relatively weak from layer VI. Conspicuous transcolumnar excitatory inputs could be evoked solely in layers IV and V. Our results show that layer V pyramidal cells are synaptically driven by presynaptic neurons located in every layer of the barrel cortex. RS cells seem to be preferentially involved in intracolumnar signal processing, whereas IB cells effectively integrate excitatory inputs across several columns.

Action Potentials↗

PubMed2001

Prefrontal cortex in humans and apes: a comparative study of area 10.

Area 10 is one of the cortical areas of the frontal lobe involved in higher cognitive functions such as the undertaking of initiatives and the planning of future actions. It is known to form the frontal pole of the macaque and human brain, but its presence and organization in the great and lesser apes remain unclear. It is here documented that area 10 also forms the frontal pole of chimpanzee, bonobo, orangutan, and gibbon brains. Imaging techniques and stereological tools are used to characterize this area across species and provide preliminary estimates of its absolute and relative size. Area 10 has similar cytoarchitectonic features in the hominoid brain, but aspects of its organization vary slightly across species, including the relative width of its cortical layers and the space available for connections. The cortex forming the frontal pole of the gorilla appears highly specialized, while area 10 in the gibbon occupies only the orbital sector of the frontal pole. Area 10 in the human brain is larger relative to the rest of the brain than it is in the apes, and its supragranular layers have more space available for connections with other higher-order association areas. This suggests that the neural substrates supporting cognitive functions associated with this part of the cortex enlarged and became specialized during hominid evolution.

Anatomy, Comparative↗

PubMed2001

Shared k-space echo planar imaging with keyhole.

Time-dependent phenomena are of great interest, and researchers have sought to shed light on these processes with MRI, particularly in vivo. In this work, a new hybrid technique based on EPI and using the concept of keyhole imaging is presented. By sharing peripheral k-space data between images and acquiring the keyhole more frequently, it is shown that the spatial resolution of the reconstructed images can be maintained. The method affords a higher temporal resolution and is more robust against susceptibility and chemical-shift artifacts than single-shot EPI. The method, termed shared k-space echo planar imaging with keyhole (shared EPIK), has been implemented on a standard clinical scanner. Technical details, simulation results, phantom images, in vivo images, and fMRI results are presented. These results indicate that the new method is robust and may be used for dynamic MRI applications. Magn Reson Med 45:109-117, 2001.

Artifacts↗

PubMed2001

Fast T(1) mapping with volume coverage.

Four different sequences which enable high-resolution, multislice T(1) relaxation-time mapping are presented. All these sequences are based on the Look-Locker method with differences arising from the use of either a saturation-recovery or inversion-recovery module prior to data acquisition with a full k-space or banded k-space acquisition scheme. The methods were implemented on a standard clinical scanner and the accuracy of the T(1) results was evaluated against spectroscopic measurements. The accuracy of the T(1) maps validated by phantom imaging measurements is around 1% for species which relax with T(1) times that mimic gray/white matter (T(1) < or = 1000 ms). Additionally, the inherent multislice, multipoint capability of the methods is demonstrated. Finally, in vivo results of the human brain obtained using the faster method are presented. The fastest data acquisition was achieved with a saturation-recovery, banded k-space method where k-space was divided into three segments; an overall acquisition time of around 5 min (for species with T(1) < or = 1 sec) was achieved for a T(1) map which can, in principle, provide whole-brain coverage with a matrix size of 256 x 256 at multiple time-points. Magn Reson Med 46:131-140, 2001.

Brain↗

PubMed2001

Heme oxygenase-1 (HSP-32) and heme oxygenase-2 induction in neurons and glial cells of cerebral regions and its relation to iron accumulation after focal cortical photothrombosis.

Cerebral ischemic injury results in the liberation of heme from degenerating heme-containing proteins. The neurotoxic heme is usually detoxified by the constitutive heme oxygenase-2 (HO-2) and its inducible isoform HO-1(heat shock protein 32) resulting in the formation of biliverdin which becomes reduced to bilirubin, carbon monoxide (CO), and iron. Biliverdin and bilirubin have antioxidative properties whereas CO is discussed as a signaling molecule. Iron if it remains free could catalyze Haber--Weiss and Fenton reactions causing the formation of highly toxic radicals. We have studied the alterations of cerebral HO-2 and HO-1 in relation to iron accumulations after defined cortical photothrombosis within the hindlimb area of the rat. HO-2 immunohistochemistry showed that the number of HO-2-positive neurons in most perilesional regions remained constant. However, much stronger systemic immunoreactivity for HO-2 was observed between days 1 and 7 postlesion. For HO-1 a systemic increase of immunoreactivity occurred also between days 1 and 7. In addition HO-1-positive astrocytes and microglia appeared as early as 4 h postlesion and increased up to day 3 followed by a sharp decline toward day 14 within the injured hemisphere. HO-1-positive astrocytes and microglia occurred in ipsilateral cortex, corpus callosum, hippocampus, striatum, and thalamic nuclei. Additionally an increase of HO-1 in myelin-associated globulin-positive oligodendrocytes was found in ipsilateral and contralateral cortex. Next to the lesion iron accumulation occurred after day 3 and increased strongly toward day 14 at times when HO-1 and -2 had decreased, suggesting that HO activity does not directly contribute to postlesional iron deposition.

Animals↗