Biomedical subjects

Karl Zilles

Publications and source records attributed to Karl Zilles.

At least 91 records · Page 5Linked to original sources

PubMed2004

Outstanding language competence and cytoarchitecture in Broca's speech region.

Studies on brains of individuals with an exceptional mental capacity are of widespread interest. Here, we analyze the cytoarchitecture of areas 44 and 45 (anatomical correlates of Broca's speech region) of a person with a documented extraordinary competence in language performance (Emil Krebs, E.K.), and compared it with 11 control brains. Morphometry and multivariate statistical analysis revealed significant cytoarchitectonic differences between E.K. and the controls in left and right areas 44, in right 45, and in interhemispheric asymmetries. We conclude, that the exceptional language competence of E.K. may be related to distinct cytoarchitectonic features in Broca's region.

Adult↗

PubMed2004

Quantification of cerebral A1 adenosine receptors in humans using [18F]CPFPX and PET.

Adenosine is an important neuromodulator. Basic cerebral effects of adenosine are exerted by the A1 adenosine receptor (A1AR), which is accessible in vivo by the novel ligand [F]8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine ([F]CPFPX) and positron emission tomography (PET). The present study investigates the applicability of kinetic models to describe the cerebral kinetics of [F]CPFPX in order to quantify A1AR density in vivo. Six healthy volunteers underwent dynamic PET scanning and arterial blood sampling after bolus injection of [F]CPFPX. For quantitative analysis, a standard two-tissue compartment model (2TCM) was compared with a one-tissue compartment model (1TCM) and Logan's graphical analysis (GA). The 2TCM described the cerebral kinetics of [F]CPFPX significantly better than the 1TCM (in all regions and subjects examined). The estimated values of the regional total distribution volumes (DVt) correlated strongly between the 2TCM and GA (linear regression r = 0.99, slope: 1.007). The DVt correlation between the 2TCM and the 1TCM was comparably high, but there was a significant bias towards lower DVt estimates given by the 1TCM (r: 0.99, slope: 0.929). It is concluded that a 2TCM satisfactorily accounts for the cerebral kinetics of [F]CPFPX. GA represents an attractive alternative method of analysis.

Adenosine A1 Receptor Antagonists↗

PubMed2004

Heat shock protein-27 is upregulated in the temporal cortex of patients with epilepsy.

PURPOSE: Heat shock protein-27 (HSP-27) belongs to the group of small heat shock proteins that become induced in response to various pathologic conditions. HSP-27 has been shown to protect cells and subcellular structures, particularly mitochondria, and serves as a carrier for estradiol. It is a reliable marker for tissues affected by oxidative stress. Oxidative stress and related cellular defence mechanisms are currently thought to play a major role during experimentally induced epileptic neuropathology. We addressed the question whether HSP-27 becomes induced in the neocortex resected from patients with pharmacoresistant epilepsy. METHODS: Human epileptic temporal neocortex was obtained during neurosurgery, and control tissue was obtained at autopsy from subjects without known neurologic diseases. The tissues were either frozen for Western blot analysis or fixed in Zamboni's fixative for the topographic detection of HSP-27 at the cellular level by means of immunohistochemistry. RESULTS: HSP-27 was highly expressed in all epilepsy specimens and in the cortex of a patient who died in the final stage of multiple sclerosis (positive control), whereas only low amounts of HSP-27 were detectable in control brains. In epilepsy patients, HSP-27 was present in astrocytes and in the walls of blood vessels. The intracortical distribution patterns varied strongly among the epilepsy specimens. CONCLUSIONS: These results demonstrate that HSP-27 becomes induced in response to epileptic pathology. Although the functional aspects of HSP-27 induction during human epilepsy have yet to be elucidated, it can be concluded that HSP-27 is a marker for cortical regions in which a stress response has been caused by seizures.

Adolescent↗

PubMed2004

Transmitter receptors and functional anatomy of the cerebral cortex.

The currently available architectonic maps of the human cerebral cortex do not match the high degree of cortical segregation as shown by functional imaging. Such functional imaging studies have demonstrated a considerable number of functionally specialized areas not displayed in the architectonic maps. We therefore analysed the regional and laminar distribution of various transmitter receptors in the human cerebral cortex, because these signalling molecules play a crucial role in cortical functions. They may provide a novel and functionally more relevant insight into the regional organization of the cortex, which cannot be achieved by architectonic observations in cell body- or myelin-stained sections. Serial cryostat sections through whole human hemispheres were used for quantitative receptor autoradiography. The regional and laminar densities of numerous receptors of classic transmitter systems were analysed. Alternating sections were stained for comparisons based on cyto- or myeloarchitectonic criteria. Our results demonstrate that the regional distribution of transmitter receptors reflects well-established cyto- and myeloarchitectonically defined borders of cortical areas, but in addition enables the identification of more cortical areas than previously demonstrated. Moreover, the laminar distribution patterns of a given receptor type in different cortical areas as well as those of different receptor types in the same cortical area reveal novel and functionally relevant data concerning the intracortical organization in the human cerebral cortex.

Aged↗

PubMed2004

Genetic load on amygdala hypofunction during sadness in nonaffected brothers of schizophrenia patients.

OBJECTIVE: In a previous study, the authors reported that patients with schizophrenia show subcortical-limbic hypoactivity during sadness. In this study, they capitalized on those findings in order to assess the genetic influence of negative mood experience in schizophrenia patients. Brain activity was measured during mood induction in patients with schizophrenia and their first-degree nonaffected relatives. METHOD: Functional magnetic resonance imaging was used to investigate 13 male patients with schizophrenia, their nonaffected brothers (N=13), and a group of 26 individually matched healthy subjects unrelated to the siblings during induction of sad and happy moods as well as during a cognitive control task. A regional analysis was applied to investigate a possible subcortical-limbic dysfunction in relatives. RESULTS: Mood induction was successful in all groups according to subjective ratings. During sadness induction, the patients and their nonaffected siblings demonstrated less activity in the amygdala compared with the healthy group of nonrelatives. Other regions of interest, such as the left orbitofrontal cortex, the left superior temporal cortex, and the left precuneus/posterior cingulate revealed significant group differences only between patients and nonrelated healthy subjects. During positive mood induction, no group differences could be found in the amygdala. CONCLUSIONS: Following induction of sad mood, both patients with schizophrenia and their nonaffected brothers displayed reduced brain activity in the amygdala. Such hypoactivity is likely to represent a genetic influence and indicates that efficient compensatory mechanisms capable of preventing the onset of the illness must exist in nonaffected relatives.

Adult↗

PubMed2003

Cortical orofacial motor representation in Old World monkeys, great apes, and humans. I. Quantitative analysis of cytoarchitecture.

Social life in anthropoid primates is mediated by interindividual communication, involving movements of the orofacial muscles for the production of vocalization and gestural expression. Although phylogenetic diversity has been reported in the auditory and visual communication systems of primates, little is known about the comparative neuroanatomy that subserves orofacial movement. The current study reports results from quantitative image analysis of the region corresponding to orofacial representation of primary motor cortex (Brodmann's area 4) in several catarrhine primate species (Macaca fascicularis, Papio anubis, Pongo pygmaeus, Gorilla gorilla, Pan troglodytes, and Homo sapiens) using the Grey Level Index method. This cortical region has been implicated in the execution of skilled motor activities such as voluntary facial expression and human speech. Density profiles of the laminar distribution of Nissl-stained neuronal somata were acquired from high-resolution images to quantify cytoarchitectural patterns. Despite general similarity in these profiles across catarrhines, multivariate analysis showed that cytoarchitectural patterns of individuals were more similar within-species versus between-species. Compared to Old World monkeys, the orofacial representation of area 4 in great apes and humans was characterized by an increased relative thickness of layer III and overall lower cell volume densities, providing more neuropil space for interconnections. These phylogenetic differences in microstructure might provide an anatomical substrate for the evolution of greater volitional fine motor control of facial expressions in great apes and humans.

Aged↗

PubMed2003

Anxiety-related behavior and densities of glutamate, GABAA, acetylcholine and serotonin receptors in the amygdala of seven inbred mouse strains.

The amygdala is a brain region involved in the regulation of anxiety-related behavior. The purpose of this study was to correlate anxiety-related behavior of inbred mouse strains (BA//c, BALB/cJ, C3H/HeJ, C57BL/6J, CPB-K, DBA/2J, NMRI) to receptor binding in the amygdala. Binding site densities of receptors (NMDA, AMPA, kainate, GABA(A), serotonin, muscarinergic M(1)-M(2)) were measured with quantitative receptor autoradiography using tritiated ligands. Measurements of fear-sensitized acoustic startle response (ASR; induced by footshocks), elevated plus maze (EPM) behavior and receptor binding studies showed differences between the strains except for AMPA and muscarinergic M(2) receptors. Factor analysis revealed a Startle Factor with positive loadings of the density of serotonin and kainate receptors, and the amplitudes of the baseline and fear-sensitized ASRs. A second Anxiety-related Factor only correlated with the fear-sensitized ASR and anxiety parameters on the EPM but not receptor densities. There were also two General Activity Factors defined by (negative) correlations with entries to closed arms of the EPM. Because the density of NMDA and muscarinergic M(1) receptors also correlated negatively with the two factors, these receptors had a positive effect on general activity. In contrast, correlations of GABA(A), serotonin, and kainate receptors had the opposite sign as compared to closed arm entries. It is concluded that hereditary variations in the amygdala, particularly in kainate and serotonin receptors, play a role for the baseline and fear-sensitized ASR, whereas the general activity is influenced by many neurotransmitter receptor systems.

Acoustic Stimulation↗

PubMed2003

Broca's region: cytoarchitectonic asymmetry and developmental changes.

Functional imaging and clinical studies in children and adults have provided evidence of developmental changes in the hemispheric specialization for language. Whereas cytoarchitectonic asymmetry has been demonstrated in Broca's region of adults, the anatomical correlates of developmental changes in language dominance are largely unknown. In the present postmortem study of 34 human brains (ages ranging from 3.5 months to 85 years), the cytoarchitecture of areas 44 and 45 as the putative anatomical correlates of Broca's region, their developmental changes, and interhemispheric asymmetry were analyzed. Asymmetry as estimated by Euclidean distances between feature vectors of cytoarchitectonic profiles of left and right areas 44 and 45 was already found in 1-year-old infants. Asymmetry tended to increase with age, which was significant in area 45, but not in area 44. An adult-like, left-larger-than-right asymmetry in the volume fraction of cell bodies [gray level index (GLI)] was reached at approximately 5 years in area 45 and 11 years in area 44. These time points indicate a delayed development of the cytoarchitectonic asymmetry in Broca's region in comparison with that of the primary motor cortex. It may be hypothesized that the delayed maturation is the microstructural basis of the development of language abilities and the influence of language practice on cytoarchitecture during childhood. Interhemispheric asymmetry in the cytoarchitecture of areas 44 and 45 continues to change throughout life. We conclude that the cytoarchitectonic asymmetry of areas 44 and 45 is a result of microstructural plasticity that endures throughout almost the whole lifespan.

Adult↗

PubMed2003

Lateralized cognitive processes and lateralized task control in the human brain.

The principles underlying human hemispheric specialization are poorly understood. We used functional magnetic resonance imaging of letter and visuospatial decision tasks with identical word stimuli to address two unresolved problems. First, hemispheric specialization depended on the nature of the task rather than on the nature of the stimulus. Second, analysis of frontal candidate regions for cognitive control showed increased coupling between left anterior cingulate cortex (ACC) and left inferior frontal gyrus during letter decisions, whereas right ACC showed enhanced coupling with right parietal areas during visuospatial decisions. Cognitive control is thus localized in the same hemisphere as task execution.

Adult↗

PubMed2003

Automated image analysis of disturbed cytoarchitecture in Brodmann area 10 in schizophrenia.

To detect cytoarchitectonic abnormalities in the Brodmann area 10 (BA10) of schizophrenic patients, we applied a newly modified variant of the gray-level index (GLI) method as fully automated image analysis method providing cytoarchitectonic profiles of the whole cortex as a scanning tool. Microscopic images of silver-stained sections of 20 schizophrenic brains compared to 20 control brains were automatically scanned and binarized at an adaptive threshold. In 30 measuring fields through the whole cortical depth, the dependent measure of gray-level index (GLI) as the area-percentage covered by perikarya in a measuring field was obtained providing a cytoarchitectonic profile. GLI is an estimate of the volume density of perikarya. A statistical analysis of mean GLI values was performed for six compartments, separately, approximately corresponding to cortical layers. Results revealed significant GLI reductions in schizophrenic brains in all six compartments suggesting either a decreased perikarya fraction or an increased neuropil fraction. The described automated image analysis method providing cytoarchitectonic profiles can be applied as a fast and observer-independent scanning tool to detect cytoarchitectonic abnormalities in multiple brain regions.

Adult↗

PubMed2003

AMPA, kainate, and NMDA receptor densities in the hippocampus of untreated male rats and females in estrus and diestrus.

Steroid hormones systematically affect numerous neuronal targets, thus influencing, in a permanent or a transitory manner, the way the brain reacts to external and internal stimuli. The hippocampus is an important brain region for learning and memory and the glutamatergic intrahippocampal pathway plays a major role in performing such functions. We applied quantitative in vitro receptor autoradiography to examine how the in vivo hormone milieu affects the densities of AMPA, kainate, and NMDA receptors in the hippocampus of adult male rats and females in estrus and diestrus. All three examined receptor types presented significant gender-specific differences in their densities. The hippocampus of male rats contains significantly more AMPA, kainate, and NMDA receptors than that of female rats. Female rats in diestrus have significantly higher AMPA receptor densities than female rats in estrus. AMPA changes occurred to the same extent in CA1-3 and in the dentate gyrus. Significant differences in the densities of NMDA receptors were observed in the CA1-3 regions, whereas kainate receptor differences were restricted to the CA1 region. These results further support that steroid hormones, through their modulation of AMPA and NMDA receptors, may be involved in the control of synaptic efficacy and, therefore, influence learning and memory.

Animals↗

PubMed2003

Cell type-specific circuits of cortical layer IV spiny neurons.

Sensory signal processing in cortical layer IV involves two major morphological classes of excitatory neurons: spiny stellate and pyramidal cells. It is essentially unknown how these two cell types are integrated into intracortical networks and whether they play different roles in cortical signal processing. We mapped their cell-specific intracortical afferents in rat somatosensory cortex through a combination of whole-cell patch-clamp recordings and caged glutamate photolysis. Spiny stellate cells received monosynaptic excitation and inhibition originating almost exclusively from neurons located within the same barrel. Pyramidal cells, by contrast, displayed additional excitatory inputs from nongranular layers and from neighboring barrels. Their inhibitory inputs originated, as for spiny stellate cells, mainly from neurons located in the same barrel. These results indicate that spiny stellate cells act predominantly as local signal processors within a single barrel, whereas pyramidal cells globally integrate horizontal and top-down information within a functional column and between neighboring barrels.

Afferent Pathways↗

PubMed2003

Behavioral deficits and recovery following transient focal cerebral ischemia in rats: glutamatergic and GABAergic receptor densities.

The neurobiologic mechanisms underlying the recovery process following stroke are poorly understood. The present study investigated glutamatergic and gamma-amino butyric acid (GABA)-ergic receptor densities following experimental stroke in rats exposed to different environmental housing or pharmacologic interventions. About 2 days after transient (120 min) middle cerebral artery (MCA) occlusion, the rats were singly housed in standard cages or were moved to an enriched environment and treated for 10 days with either 0.9% NaCl or with the alpha(2)-adrenoceptor antagonist, atipamezole (1.0 mg/kg, s.c.). The limb-placing, foot-slip, and water-maze tests were used to assess behavioral deficits and recovery following ischemia. The rats were decapitated on day 25 after the operation and their brains were processed for [3H]MK-801, [3H]D,L,-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), [3H]kainate, and [3H]muscimol autoradiography. Receptor binding site densities were different between sham-operated rats and ischemic rats only in the lesion core and lateral ventroposterior thalamic nucleus. Ischemic rats housed in an enriched environment and treated with atipamezole had better performance in the limb-placing test. The deficit in the water-maze test was most pronounced in ischemic rats housed in standard cages. There were a number of correlations between the behavioral data and receptor binding densities in ischemic rats. For example, recovery in the limb-placing test correlated with [3H]AMPA receptor binding sites in the contralateral frontal cortex (r=0.616, P<0.05), hindlimb cortex (r=0.649, P<0.05), and parietal cortex (r=0.674, P<0.05) in ischemic rats housed in an enriched environment. There were similar correlations between limb-placing recovery and [3H]kainate binding sites in the contralateral cortices in ischemic rats housed in standard cages. In addition, there were particularly strong clustered correlations between swimming speed in the water-maze test and [3H]AMPA receptor binding sites in the hippocampal subregions in the ischemic rats housed in an enriched environment. The present results suggest that transient focal cerebral ischemia does not induce significant long-term changes in glutamatergic and GABAergic receptors in areas remote from the infarct area. The correlational data, however, suggest an important role for the contralateral cortex in the behavioral outcome and maintenance of the recovered state of ischemic rats, depending on housing conditions. In addition, attenuation of spatial learning deficits observed in ischemic rats housed in an enriched environment might be due to an increase in the swimming speed through hippocampal AMPA receptor-mediated mechanisms.

Adrenergic alpha-Antagonists↗

PubMed2003

Regional cerebral blood flow correlations of somatosensory areas 3a, 3b, 1, and 2 in humans during rest: a PET and cytoarchitectural study.

The concept of functional connectivity relies on the assumption that cortical areas that are directly anatomically connected will show correlations in regional blood flow (rCBF) or regional metabolism. We studied correlations of rCBF of cytoarchitectural areas 3a, 3b, 1, and 2 in the brains of 37 subjects scanned with PET during a rest condition. The cytoarchitectural areas, delineated from 10 postmortem brains with statistical methods, were transformed into the same standard anatomical format as the resting PET images. In areas 3a, 3b, and 1, somatotopically corresponding regions were intercorrelated. Area 2 was correlated with the dorsal pre-motor area. These results were in accordance with the somatosensory connectivity in macaque monkeys. In contrast, we also found correlations between areas 3b and 1 with area 4a, and SMA, and among the left and right hand sector of areas 3a, 3b, and 1. Furthermore, there were no correlations between areas 3b, 1, and 2 with SII or other areas in the parietal operculum, nor of other areas known to be directly connected with areas 3a, 3b, 1, and 2 in macaques. This indicates that rCBF correlations between cortical areas during the rest state only partly reflect their connectivity and that this approach lacks sensitivity and is prone to reveal spurious or indirect connectivity.

Adult↗

PubMed2003

Somatosensory areas engaged during discrimination of steady pressure, spring strength, and kinesthesia.

The aim of this study was to locate neuronal populations in the somatosensory areas engaged during discrimination of differences in: (1) static sustained pressure on the distal phalanx (PRESS); (2) spring strengths (SSTIFF) during active flexion of the right index finger; and (3) the change in position of a limb with contracting muscles, i.e., kinesthesia (KIN), during active flexion of the right index finger. The stimuli used were spring-loaded cylinders. The regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET). The active fields were related to cytoarchitectonic areas of the somatosensory cortex (areas 3a, 3b, 1, and 2) and the primary motor cortex (areas 4a and 4p). We hypothesized that SSTIFF and KIN would activate areas 3a and 2. All three conditions, when contrasted against a rest condition, activated cytoarchitectural areas 3b, 1, and 2, and presumptive somatosensory areas in the left parietal operculum and right supramarginal gyrus in accordance with these areas receiving information from cutaneous mechanoreceptive afferents. Area 3a was only activated in SSTIFF and KIN, consistent with observations in monkeys and cats, showing that afferents from muscle receptors project to area 3a, and indicating that a similar arrangement seems to be apparent in humans. SSTIFF and KIN activated the right anterior lobe of the cerebellum, the left area 4a and left area 2 more than did PRESS, likely due to a combination of active movements and muscle receptor feed-back.

Adult↗

PubMed2003

Performing allocentric visuospatial judgments with induced distortion of the egocentric reference frame: an fMRI study with clinical implications.

The temporary improvement of visuospatial neglect during galvanic vestibular stimulation (Scand. J. Rehabil. Med. 31 (1999)117) may result from correction of the spatial reference frame distorted by the responsible lesion. Prior to an investigation of the neural basis of this effect in neurological patients, exploration of the neural mechanisms underlying such procedures in normals is required to provide insight into the physiological basis thereof. Despite their clinical impact, the neural mechanisms underlying the interaction of galvanic (and other) vestibular manipulations with visuospatial processing (and indeed the neural bases of how spatial reference frames are computed in man) remain to be clarified. We accordingly used fMRI in normal volunteers to investigate the effect of galvanically induced interference with the egocentric spatial reference frame on the neural processes underlying allocentric visuospatial (line bisection) judgments. A significant specific interaction of galvanic vestibular stimulation with the neural mechanisms underlying allocentric visuospatial judgments was observed in right posterior parietal and ventral premotor cortex only. Activation of these areas previously found to be damaged in visuospatial neglect suggests that these effects reflect the increased processing demands when compensating for the distorted egocentric spatial reference frame while maintaining accurate performance during the allocentric spatial task. These results thus implicate right posterior parietal and right ventral premotor cortex in the computation of spatial reference frames. Furthermore, our data imply a specific physiological basis for the temporary improvement of visuospatial neglect in patients with right hemisphere lesions during galvanic vestibular stimulation and may thus impact upon the rehabilitation of neglect: understanding the interaction of galvanic vestibular stimulation with allocentric visuospatial judgments in healthy volunteers may lead to the more effective deployment of such techniques in neurological patients.

Adult↗

PubMed2003

Neural mechanisms associated with attention to temporal synchrony versus spatial orientation: an fMRI study.

Previous neuropsychological and functional imaging studies have suggested that the right hemisphere is crucially involved in spatial cognition. By contrast, much less is known about the putative left hemisphere specialization for aspects of temporal cognition. Accordingly, we studied with functional magnetic resonance imaging the neural mechanisms underlying attention to stimulus onset synchrony or orientational congruence with identical pairs of geometric figures. In each trial, two rhombuses were presented, each 4 degrees peripheral to a central fixation cross, in the left and right visual hemifields. In half of the trials, subjects were asked to judge and indicate via button presses whether the rhombuses appeared simultaneously. In the other half of the trials, subjects indicated whether the orientation of the rhombuses was the same (Factor 1, task, temporal synchrony, orientation). In half of the trials, subjects responded with their right hand and in the other half with their left hand (Factor 2, hand, right, left). Data were analyzed using SPM99 and a random-effects model. Attention to orientation differentially activated right temporo-occipital cortex. Attention to stimulus onset synchrony activated left anterior superior temporal gyrus, left inferior parietal cortex, left medial frontal gyrus, and right operculum. Activation of right temporo-occipital cortex for attention to stimulus orientation is in good agreement with previous functional neuroimaging studies of stimulus orientation. More importantly, activation of a predominantly left-hemispheric network with attention to stimulus onset synchrony extends the results of previous functional imaging, psychophysical, and neuropsychological studies of temporal processing.

Adult↗

PubMed2003

Left inferior parietal cortex integrates time and space during collision judgments.

Left inferior parietal lobe lesions can cause perturbation of the space-time plans underlying skilled actions. But does the perceptual integration of spatiotemporal information use the same neural substrate or is the role of the left inferior parietal cortex restricted to visuomotor transformations? We use fMRI and a collision judgment paradigm to examine whether the left inferior parietal cortex integrates temporal and spatial variables in situations in which no complex action and no visuomotor transformation is required. We used a perceptual task in which healthy subjects indicated by simple button presses whether two moving objects (of the same or different size) would or would not collide with each other. This task of interest was contrasted with a control task that employed the same stimuli and identical motor responses but in which the size of the two moving objects had to be compared. To assess putative differential eye-movement effects both tasks were performed with and without central fixation. Analysis of the fMRI data (employing a random-effects model and SPM99) showed that collision judgments (relative to size judgments) provoked a significant increase in neural activity in the left inferior parietal cortex (supramarginal gyrus) only. These results show that left inferior parietal cortex is involved in the integration of perceptual spatiotemporal information and thus provide a neural correlate for the use of space-time plans (whose perturbation can lead to apraxia as originally hypothesized by Liepmann). Furthermore, the data suggest that the left supramarginal gyrus combines temporal and spatial variables more widely than previously supposed.

Adolescent↗