Biomedical subjects

Katrin Amunts

Publications and source records attributed to Katrin Amunts.

At least 19 recordsLinked to original sources

PubMed2021

1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans.

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.

Brain↗

PubMed2007

Observer-independent analysis of high-resolution MR images of the human cerebral cortex: in vivo delineation of cortical areas.

Using high-resolution MRI, it is now possible to examine the living human cortex down to a resolution of less than 300 mum. Thus, in vivo imaging is now approaching the resolution that has been successfully used in histological analysis of the cerebral cortex for many years, e.g., low-magnification light microscopy. This allows unprecedented views of cortical microstructure that reflect defined histological features, specifically, individual cortical layers. As in histological brain mapping, it is possible to use the changes in the cortical lamination patterns to define individual cortical areas. This allows in vivo neuroanatomical maps to be generated for individual subjects and precise correlation of the results from functional imaging studies in these subjects with their own microanatomical information. To this end, we adapted the well-established observer-independent cytoarchitectonic mapping techniques for defining cortical borders based on changes in cortical lamination for in vivo parcellation of high-resolution structural MR images.

Brain Mapping↗

PubMed2006

A new toolbox for combining magnetoencephalographic source analysis and cytoarchitectonic probabilistic data for anatomical classification of dynamic brain activity.

Size and location of activated cortical areas are often identified in relation to their surrounding macro-anatomical landmarks such as gyri and sulci. The sulcal pattern, however, is highly variable. In addition, many cortical areas are not linked to well defined landmarks, which in turn do not have a fixed relationship to functional and cytoarchitectonic boundaries. Therefore, it is difficult to unambiguously attribute localized neuronal activity to the corresponding cortical areas in the living human brain. Here we present new methods that are implemented in a toolbox for the objective anatomical identification of neuromagnetic activity with respect to cortical areas. The toolbox enables the platform independent integration of many types of source analysis obtained from magnetoencephalography (MEG) together with probabilistic cytoarchitectonic maps obtained in postmortem brains. The probability maps provide information about the relative frequency of a given cortical area being located at a given position in the brain. In the new software, the neuromagnetic data are analyzed with respect to cytoarchitectonic maps that have been transformed to the individual subject brain space. A number of measures define the degree of overlap between and distance from the activated areas and the corresponding cytoarchitectonic maps. The implemented algorithms enable the investigator to quantify how much of the reconstructed current density can be attributed to distinct cortical areas. Dynamic correspondence patterns between the millisecond-resolved MEG data and the static cytoarchitectonic maps are obtained. We show examples for auditory and visual activation patterns. However, size and location of the postmortem brain areas as well as the inverse method applied to the neuromagnetic data bias the anatomical classification. Therefore, the adaptation to the respective application and a combination of the objective quantities are discussed.

Acoustic Stimulation↗

PubMed2006

Amygdala control of emotion-induced forgetting and remembering: evidence from Urbach-Wiethe disease.

When presented in a neutral context, emotional items interfere with episodic encoding of temporally contiguous non-emotional items, resulting in dissociable valence-dependent retrograde and arousal-dependent anterograde modulatory effects. By studying two rare patients with congenital lipoid proteinosis (Urbach-Wiethe) and a focal disease emphasis on the basolateral amygdala (BLA), we demonstrate that this bidirectional modification of episodic encoding by emotion depends on the integrity of the amygdala, as both retrograde and anterograde modulatory effects are absent. Our findings implicate the amygdala in a neural circuitry that orchestrates rapid retrograde and anterograde regulation of episodic memory access upon criteria of behavioral significance.

Adaptation, Psychological↗

PubMed2006

Genetic contributions to human brain morphology and intelligence.

Variation in gray matter (GM) and white matter (WM) volume of the adult human brain is primarily genetically determined. Moreover, total brain volume is positively correlated with general intelligence, and both share a common genetic origin. However, although genetic effects on morphology of specific GM areas in the brain have been studied, the heritability of focal WM is unknown. Similarly, it is unresolved whether there is a common genetic origin of focal GM and WM structures with intelligence. We explored the genetic influence on focal GM and WM densities in magnetic resonance brain images of 54 monozygotic and 58 dizygotic twin pairs and 34 of their siblings. For genetic analyses, we used structural equation modeling and voxel-based morphometry. To explore the common genetic origin of focal GM and WM areas with intelligence, we obtained cross-trait/cross-twin correlations in which the focal GM and WM densities of each twin are correlated with the psychometric intelligence quotient of his/her cotwin. Genes influenced individual differences in left and right superior occipitofrontal fascicle (heritability up to 0.79 and 0.77), corpus callosum (0.82, 0.80), optic radiation (0.69, 0.79), corticospinal tract (0.78, 0.79), medial frontal cortex (0.78, 0.83), superior frontal cortex (0.76, 0.80), superior temporal cortex (0.80, 0.77), left occipital cortex (0.85), left postcentral cortex (0.83), left posterior cingulate cortex (0.83), right parahippocampal cortex (0.69), and amygdala (0.80, 0.55). Intelligence shared a common genetic origin with superior occipitofrontal, callosal, and left optical radiation WM and frontal, occipital, and parahippocampal GM (phenotypic correlations up to 0.35). These findings point to a neural network that shares a common genetic origin with human intelligence.

Adolescent↗

PubMed2006

Interaction of negative olfactory stimulation and working memory in schizophrenia patients: development and evaluation of a behavioral neuroimaging task.

Negative affect plays a crucial role in the psychopathology of schizophrenia. Although it is known that negative emotion has a strong effect on cognitive performance, this interaction has mainly been studied in healthy volunteers. Hence, working memory was assessed in 24 schizophrenia patients and 24 matched comparison subjects with a 0-back/2-back continuous performance test. Simultaneously, negative emotion was induced by olfactory stimulation. Although subjective ratings confirmed that stimulation with a negative odor was associated with a significant increase in negative affect in patients and healthy volunteers, working memory performance was affected differentially in healthy volunteers and schizophrenia patients. Whilst a similar trend of a reduced behavioral performance during negative odor stimulation was observed in patients, only controls demonstrated a significantly higher response time and a reduced number of correct reactions during higher working memory demands (2-back). Patients, on the other hand, revealed an increase in false alarms during both conditions. The present data indicate a differential effect of negative mood induction on working memory performance in schizophrenia patients and healthy subjects.

Adult↗

PubMed2006

The human inferior parietal cortex: cytoarchitectonic parcellation and interindividual variability.

The inferior parietal cortex (IPC) integrates information from different sensory modalities and plays an important role in a variety of higher cognitive functions. Brodmann (Brodmann, K., 1909. Vergleichende Lokalisationslehre der Grosshirnrinde. Barth, Leipzig) proposed a cytoarchitectonic subdivision of the IPC into only two cortical areas, a rostral (BA 40) and a caudal (BA 39) area. Although his scheme was repeatedly challenged by other observers, it is still used for the anatomical localization of functional imaging data. The apparent differences between all these cyto- and myeloarchitectonic maps may be caused partly by the observer-dependent procedure of defining cytoarchitectonic borders by pure visual inspection of histological sections and partly by the interindividual variability of cytoarchitecture. The present observations and the resulting cortical map of the IPC are based on quantitative, observer-independent definitions of cytoarchitectonic borders and take into account each area's topographical variability across brains. Ten human postmortem brains were scanned using an MRI 3-D FLASH sequence prior to histological processing. After embedding in paraffin, serial sections through whole brains were prepared, and the sections were stained for cell bodies. Following high-resolution digitization of sections containing the IPC, we defined the cytoarchitecture and borders of each cortical area of this brain region using a multivariate statistical analysis of laminar cell density profiles. In contrast to previous observations, we found seven cytoarchitectonic areas in the IPC: five in the rostral (covering the region of BA 40) and two in the caudal part (covering the region of BA 39). We observed considerable interindividual variability in the topography of each area. A consistent correspondence between macroanatomical landmarks and cytoarchitectonic borders was not found. This new cytoarchitectonic map of the human IPC demonstrates regional differences in the cortical microstructure that is suggestive of functional differentiation. Furthermore, the map is registered in three dimensions and thereby provides a robust anatomical base for interpreting functional imaging studies.

Adult↗

PubMed2006

Testing anatomically specified hypotheses in functional imaging using cytoarchitectonic maps.

The statistical inference on functional imaging data is severely complicated by the embedded multiple testing problem. Defining a region of interest (ROI) where the activation is hypothesized a priori helps to circumvent this problem, since in this case the inference is restricted to fewer simultaneous tests, rendering it more sensitive. Cytoarchitectonic maps obtained from postmortem brains provide objective, a priori ROIs that can be used to test anatomically specified hypotheses about the localization of functional activations. We here analyzed three methods for the definition of ROIs based on probabilistic cytoarchitectonic maps. (1) ROIs defined by the volume assigned to a cytoarchitectonic area in the summary map of all areas (maximum probability map, MPM), (2) ROIs based on thresholding the individual probabilistic maps and (3) spherical ROIs build around the cytoarchitectonic center of gravity. The quality with which the thus defined ROIs represented the respective cytoarchitectonic areas as well as their sensitivity for detecting functional activations was subsequently statistically evaluated. Our data showed that the MPM method yields ROIs, which reflect most adequately the underlying anatomical hypotheses. These maps also show a high degree of sensitivity in the statistical analysis. We thus propose the use of MPMs for the definition of ROIs. In combination with thresholding based on the Gaussian random field theory, these ROIs can then be applied to test anatomically specified hypotheses in functional neuroimaging studies.

Artifacts↗

PubMed2006

Head motion during overt language production in functional magnetic resonance imaging.

Head motion parameters (translation, rotation) during an event-related functional magnetic resonance imaging experiment of overt picture naming were investigated for two fixation conditions. We compared normal fixation with cushions and belts with the additional use of a bite-bar. Neither mean nor maximum values differed between the two conditions for any of the parameters. By applying the head motion parameters to the cytoarchitectonically defined volume of the left Brodmann area 44, we demonstrated volume overlap of 95% (normal fixation) to 100% (bite-bar) that did not differ significantly between fixation conditions. The data encourage further use of overt language production in functional magnetic resonance imaging with careful head fixation but no bite-bar.

Adult↗

PubMed2006

Cytoarchitectonic analysis of the human extrastriate cortex in the region of V5/MT+: a probabilistic, stereotaxic map of area hOc5.

Functional imaging studies identified a motion-sensitive area (V5/MT+) in the vicinity of the posterior branch of the inferior temporal sulcus that has no correlate in any classical cytoarchitectonic map. The aim of the present study was to identify a cytoarchitectonic correlate of this region in 10 human postmortem brains and to provide a probability map of this area. Observer-independent mapping revealed an area, hOc5 (h for human, Oc for occipital lobe), that has a broad layer III, a high cell density in layer II/III, and a low one in layer V. Most of area hOc5 is found in the depths of the anterior occipital sulcus and the anterior parts of either the inferior lateral occipital or the inferior occipital sulcus. After 3-dimensional reconstruction and registration to a standard reference space, a probability map of the area measured the individual variability of its size and location. The mean spatial locations of area hOc5 are -43, -73, 10 (left) and 49, -70, 11 (right). The locations and their relationships to sulci strongly suggest that hOc5 is the cytoarchitectonic correlate of human V5/MT+. This hypothesis was supported by comparing the cytoarchitectonic probabilistic map with results from a functional imaging study.

Adult↗

PubMed2006

Segregation of visceral and somatosensory afferents: an fMRI and cytoarchitectonic mapping study.

Ano-rectal stimulation provides an important model for the processing of somatosensory and visceral sensations in the human nervous system. In spite of their anatomical proximity, the anal canal is innervated by somatosensory afferents whereas the rectum is innervated by the visceral nervous system. In a functional magnetic resonance (fMRI) experiment, we examined the cerebral responses to pneumatic balloon distension of these two structures to test whether somatosensory and visceral stimulation elicited distinct brain activations in spite of their spinal convergence. The specificity of the identified activations was analyzed by Bayesian mixed effects modeling. Activations in the parietal operculum were also compared to the location of cytoarchitectonically defined areas OP 1-4, which are part of the secondary somatosensory cortex (SII), to analyze whether the SII region was activated by anal and/or rectal stimulation. The lowest segregation between visceral and somatosensory stimuli was in the insular cortex, which supports the interpretation of the insula as an integrative region, receiving input from different sensory modalities. The most distinct segregation was found in the fronto-parietal operculum. Here the activations following anal and rectal stimulation were not only functionally but also anatomically distinct. Anal sensations were processed similar to other somatosensory stimuli in the SII cortex (area OP 4). Rectal afferents on the other hand were not processed in SII. Rather, they evoked activation at a more anterior location on the precentral operculum. These results demonstrate a functionally and anatomically distinct processing of somatosensory and visceral afferents in the human cerebral cortex.

Adult↗

PubMed2006

Cytoarchitectonic identification and probabilistic mapping of two distinct areas within the anterior ventral bank of the human intraparietal sulcus.

Anatomical studies in the macaque cortex and functional imaging studies in humans have demonstrated the existence of different cortical areas within the intraparietal sulcus (IPS). Such functional segregation, however, does not correlate with presently available architectonic maps of the human brain. This is particularly true for the classical Brodmann map, which is still widely used as an anatomical reference in functional imaging studies. The aim of this cytoarchitectonic mapping study was to use previously defined algorithms to determine whether consistent regions and borders can be found within the cortex of the anterior IPS in a population of 10 post-mortem human brains. Two areas, the human intraparietal area 1 (hIP1) and the human intraparietal area 2 (hIP2), were delineated in serial histological sections of the anterior, lateral bank of the human IPS. The region hIP1 is located posterior and medial to hIP2, and the former is always within the depths of the IPS. The latter, on the other hand, sometimes reaches the free surface of the superior parietal lobule. The delineations were registered to standard reference space, and probabilistic maps were calculated, thereby quantifying the intersubject variability in location and extent of both areas. In the future, they can be a tool for analyzing structure-function relationships and a basis for determining degrees of homology in the IPS among anthropoid primates. We conclude that the human IPS has a more finely grained parcellation than shown in Brodmann's map.

Adult↗

PubMed2006

Pattern reversal visual evoked responses of V1/V2 and V5/MT as revealed by MEG combined with probabilistic cytoarchitectonic maps.

Pattern reversal stimulation provides an established tool for assessing the integrity of the visual pathway and for studying early visual processing. Numerous magnetoencephalographic (MEG) and electroencephalographic (EEG) studies have revealed a three-phasic waveform of the averaged pattern reversal visual evoked potential/magnetic field, with components N75(m), P100(m), and N145(m). However, the anatomical assignment of these components to distinct cortical generators is still a matter of debate, which has inter alia connected with considerable interindividual variations of the human striate and extrastriate cortex. The anatomical variability can be compensated for by means of probabilistic cytoarchitectonic maps, which are three-dimensional maps obtained by an observer-independent statistical mapping in a sample of ten postmortem brains. Transformed onto a subject's brain under consideration, these maps provide the probability with which a given voxel of the subject's brain belongs to a particular cytoarchitectonic area. We optimize the spatial selectivity of the probability maps for V1 and V2 with a probability threshold which optimizes the self- vs. cross-overlap in the population of postmortem brains used for deriving the probabilistic cytoarchitectonic maps. For the first time, we use probabilistic cytoarchitectonic maps of visual cortical areas in order to anatomically identify active cortical generators underlying pattern reversal visual evoked magnetic fields as revealed by MEG. The generators are determined with magnetic field tomography (MFT), which reconstructs the current source density in each voxel. In all seven subjects, our approach reveals generators in V1/V2 (with a greater overlap with V1) and in V5 unilaterally (right V5 in three subjects, left V5 in four subjects) and consistent time courses of their stimulus-locked activations, with three peak activations in V1/V2 (contributing to C1m/N75m, P100m, and N145m) and two peak activations in V5 (contributing to P100m and N145m). The reverberating V1/V2 and V5 activations demonstrate the effect of recurrent activation mechanisms including V1 and extrastriate areas and/or corticofugal feedback loops. Our results demonstrate that the combined investigation of MEG signals with MFT and probabilistic cytoarchitectonic maps significantly improves the anatomical identification of active brain areas.

Adult↗

PubMed2006

Identifying human parieto-insular vestibular cortex using fMRI and cytoarchitectonic mapping.

The parieto-insular vestibular cortex (PIVC) plays a central role in the cortical vestibular network. Although this region was first defined and subsequently extensively studied in nonhuman primates, there is also ample evidence for a human analogue in the posterior parietal operculum. In this study, we functionally and anatomically characterize the putative human equivalent to macaque area PIVC by combining functional magnetic resonance imaging (fMRI) of the cortical response to galvanic vestibular stimulation (GVS) with probabilistic cytoarchitectonic maps of the human parietal operculum. Our fMRI data revealed a bilateral cortical response to GVS in posterior parieto-insular cortex. Based on the topographic similarity of these activations to primate area PIVC, we suggest that they constitute the functionally defined human equivalent to macaque area PIVC. The locations of these activations were then compared to the probabilistic cytoarchitectonic maps of the parietal operculum (Eickhoff et al. [2005a]: Cereb Cortex, in press; Eickhoff et al. [2005c]: Cereb Cortex, in press), whereby the functionally defined PIVC matched most closely the cytoarchitectonically defined area OP 2. This activation of OP 2 by vestibular stimulation and its cytoarchitectonic features, which are similar to other primary sensory areas, suggest that area OP 2 constitutes the human equivalent of macaque area PIVC.

Adult↗

PubMed2006

The anatomical segregation of the frontal cortex: what does it mean for function?

The frontal cortex consists of numerous areas, each with a special architecture (cyto-, myelo-, receptorarchitecture, etc.), connectivity and function. Quantitative tools of the analysis may assist in defining these cortical areas, and their position in a hierarchy of cortical regions and subregions. They enable a reliable definition of areal borders, and the consideration of intersubject variability. In our particular case, fMRI studies investigating certain aspects of cognitive control indicated to a rather circumscribed area in the posterior frontolateral cortex--the so-called IFJ area--which seems to correspond anatomically to a previously uncharted cortical area dorsally to area 44 as detected in histological sections of post mortem brains.

Animals↗

PubMed2006

Left-right asymmetry in volume and number of neurons in adult Broca's area.

Total neuron number in, and volume of, Brodmann areas (BA) 44 and 45 (Broca's area) were studied in Nissl-stained sections from the left and right hemispheres of five adult men and five adult women. The volume of BA 44 was greater in the left hemisphere than in the right in all ten cases, although asymmetry was only significant for the subgroup of male subjects. For six of the ten subjects (including all females), the volume of BA 45 was greater in the left hemisphere than the right. This asymmetry was significant only for the women. A significant left-over-right asymmetry has been found in total neuron number in male BA 44. Although the total number of neurons in left BA 45 was larger in all five female subjects, this asymmetry did not reach significant difference. In the male subjects no significant asymmetry difference in total neuron number was found in BA 45 either. There was no significant hemispheric asymmetry or gender interaction for neuronal number density, either in BA 44 or 45. This study is the first quantitative study of total number of neurons in BA 44 and 45 in adult subjects, and demonstrates that both the volume and the total neuron number of BA 44 and 45 on the left are generally greater than that of the right hemisphere, with the possible exception of the male BA 45. In addition, it shows that the inter-individual variability was also very large (more than twofold) in the numerical values of all variables.

Adult↗

PubMed2006

Towards multimodal atlases of the human brain.

Atlases of the human brain have an important impact on neuroscience. The emergence of ever more sophisticated imaging techniques, brain mapping methods and analytical strategies has the potential to revolutionize the concept of the brain atlas. Atlases can now combine data describing multiple aspects of brain structure or function at different scales from different subjects, yielding a truly integrative and comprehensive description of this organ. These integrative approaches have provided significant impetus for the human brain mapping initiatives, and have important applications in health and disease.

Anatomy, Artistic↗

PubMed2006

Impairment in the specificity of emotion processing in schizophrenia.

OBJECTIVE: Deficits in emotion processing are a hallmark of schizophrenia, with consequences for social functioning and subjective well-being. However, their specificity and characteristics have not been ascertained psychometrically. The authors' purpose was to examine a differential deficit for processing emotional facets of the face compared to judgment of nonemotional features (age) and facial memory. The authors also sought to establish whether the deficit affects sensitivity or specificity of performance. METHOD: Participants were 20 patients with schizophrenia and 20 healthy subjects matched for age, gender, and parental education. The authors examined emotional discrimination abilities compared to age discrimination and recognition memory for faces with standardized faces displaying the universal emotions of happiness, sadness, anger, and fear. Percent correct in each condition and for each emotion were assessed as well as sensitivity (correct identification of a target emotion) and specificity (correct rejection of a nontarget emotion) for emotion recognition. RESULTS: Patients with schizophrenia were differentially impaired in the discrimination of emotional aspects of facial expressions compared to nonemotional aspects and memory. Within the emotional task, patients showed differential impairment in specificity and insensitivity to the emotion displayed. CONCLUSIONS: When identical stimuli were used across tasks, differential impairment was seen in patients with schizophrenia for processing emotional faces, although the nonemotional task proved harder for both groups. Impairment in the specificity of emotion identification may lead to misunderstanding of social communication and may underlie difficulties in social adjustment experienced by people with schizophrenia. Emotion discrimination tests could augment the neurobehavioral evaluation of patients.

Adult↗