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October 2004 - January 2013
January 2013 - present
Publications
Publications (613)
Three-Dimensional Polarized Light Imaging (3D-PLI) and Computational Scattered Light Imaging (ComSLI) map dense nerve fibers in brain sections with micrometer resolution using visible light. 3D-PLI reconstructs single fiber orientations, while ComSLI captures multiple directions per pixel, offering deep insights into brain tissue structure. Here, w...
Three-Dimensional Polarized Light Imaging (3D-PLI) and Computational Scattered Light Imaging (ComSLI) map dense nerve fibers in brain sections with micrometer resolution using visible light. 3D-PLI reconstructs single fiber orientations, while ComSLI captures multiple directions per pixel, offering deep insights into brain tissue structure. Here, w...
A comprehensive understanding of the organizational principles in the human brain requires, among other factors, well-quantifiable descriptors of nerve fiber architecture. Three-dimensional polarized light imaging (3D-PLI) is a microscopic imaging technique that enables insights into the fine-grained organization of myelinated nerve fibers with hig...
A previously published genome-wide association study (GWAS) meta-analysis across eight neuropsychiatric disorders identified antagonistic single-nucleotide polymorphisms (SNPs) at eleven genomic loci where the same allele was protective against one neuropsychiatric disorder and increased the risk for another. Until now, these antagonistic SNPs have...
Background
Neuropathologic studies of brains from autopsy series show tau inclusions (pretangles, neuropils threads, neurofibrillary tangles) are detectable more than a decade before amyloid-β (Aβ) deposition in Alzheimer’s disease (AD) and develop in a characteristic manner that forms the basis for AD staging. An alternative position views patholo...
While the analysis of gait and balance can be an important indicator of age- or disease-related changes, it remains unclear if repeated performance of gait and balance tests in healthy adults leads to habituation effects, if short-term gait and balance training can improve gait and balance performance, and whether the placement of wearable sensors...
Background
Niemann-Pick disease type C1 (NPC1, MIM 257220) is a heritable lysosomal storage disease characterized by a progressive neurological degeneration that causes disability and premature death. A murine model of Npc1−/− displays a rapidly progressing form of Npc1 disease, which is characterized by weight loss, ataxia, and increased cholester...
Neurotransmitter receptor densities are relevant for understanding the molecular architecture of brain regions. Quantitative in vitro receptor autoradiography, has been introduced to map neurotransmitter receptor distributions of brain areas. However, it is very time and cost-intensive, which makes it challenging to obtain whole-brain distributions...
The Evolutionary Roots of Human Brain Diseases takes an innovative approach and assembles recent findings ranging from evolutionary biology and anthropology to clinical neurosciences, all showing the price on health of human brain evolution. Written by experts in their field, the chapters explore the tenet that extensive human brain development dur...
The Evolutionary Roots of Human Brain Diseases takes an innovative approach and assembles recent findings ranging from evolutionary biology and anthropology to clinical neurosciences, all showing the price on health of human brain evolution. Written by experts in their field, the chapters explore the tenet that extensive human brain development dur...
The Evolutionary Roots of Human Brain Diseases takes an innovative approach and assembles recent findings ranging from evolutionary biology and anthropology to clinical neurosciences, all showing the price on health of human brain evolution. Written by experts in their field, the chapters explore the tenet that extensive human brain development dur...
The Evolutionary Roots of Human Brain Diseases takes an innovative approach and assembles recent findings ranging from evolutionary biology and anthropology to clinical neurosciences, all showing the price on health of human brain evolution. Written by experts in their field, the chapters explore the tenet that extensive human brain development dur...
The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread...
The mesial piriform region plays a central role in olfaction. Its small size and complex geometry, however, make it a difficult target in functional neuroimaging studies, while histological maps often represent schematic drawings, which are not compatible with requirements for modern imaging. To bridge this gap, cytoarchitectonic analysis and mappi...
In recent years, brain research has indisputably entered a new epoch, driven by substantial methodological advances and digitally enabled data integration and modelling at multiple scales—from molecules to the whole brain. Major advances are emerging at the intersection of neuroscience with technology and computing. This new science of the brain co...
Microstructural tissue organization underlies the complex connectivity of the brain and controls properties of connective, muscle, and epithelial tissue. However, discerning microstructural architecture with high resolution for large fields of view remains prohibitive. We address this challenge with computational scattered light imaging (ComSLI), w...
Introduction: The red nucleus is part of the motor system controlling limb movements. While this seems to be a function common in many vertebrates, its organization and circuitry have undergone massive changes during evolution. In primates, it is subdivided into the magnocellular and parvocellular parts that give rise to rubrospinal and rubro-oliva...
Specialization of brain areas and subregions, as well as their integration into large-scale networks are key principles in neuroscience. Consolidating both local and global cortical organization, however, remains challenging. Our study developed a new approach to map global, cortex-wise similarities of microstructure, structural connectivity, and f...
The hippocampus has a unique microarchitecture, is situated at the nexus of multiple macroscale functional networks, contributes to numerous cognitive as well as affective processes, and is highly susceptible to brain pathology across common disorders. These features make the hippocampus a model to understand how brain structure covaries with funct...
The medial temporal lobe (MTL) cortex, located adjacent to the hippocampus, is crucial for memory and prone to the accumulation of certain neuropathologies such as Alzheimer's disease neurofibrillary tau tangles. The MTL cortex is composed of several subregions which differ in their functional and cytoarchitectonic features. As neuroanatomical scho...
The hippocampus has a unique microarchitecture, is situated at the nexus of multiple macroscale functional networks, contributes to numerous cognitive as well as affective processes, and is highly susceptible to brain pathology across common disorders. These features make the hippocampus a model to understand how brain structure covaries with funct...
Areas of the dorsolateral prefrontal cortex (DLPFC) are part of the frontoparietal control, default mode, salience, and ventral attention networks. The DLPFC is involved in executive functions, like working memory, value encoding, attention, decision-making, and behavioral control. This functional heterogeneity is not reflected in existing neuroana...
The segregation of the cortical mantle into cytoarchitectonic areas provides a structural basis for the specialization of different brain regions. In vivo neuroimaging experiments can be linked to this postmortem cytoarchitectonic parcellation via Julich-Brain. This atlas embeds probabilistic maps that account for inter-individual variability in th...
Background
The medial temporal lobe (MTL) cortex, located adjacent to the hippocampus, is crucial for memory and a hotspot of neurodegenerative processes (e.g., accumulation of tau tangles or TDP‐43). Importantly, the MTL cortex comprises several subregions with distinct functional, cytoarchitectonic, and macro‐anatomical features (Fig. 1). In vivo...
Background
The medial temporal lobe (MTL) cortex, located adjacent to the hippocampus, is crucial for memory and a hotspot of neurodegenerative processes (e.g., accumulation of tau tangles or TDP‐43). Importantly, the MTL cortex comprises several subregions with distinct functional, cytoarchitectonic, and macro‐anatomical features (Fig. 1). In vivo...
The hippocampus is an archicortical structure, consisting of subfields with unique circuits. Understanding its microstructure, as proxied by these subfields, can improve our mechanistic understanding of learning and memory and has clinical potential for several neurological disorders. One prominent issue is how to parcellate, register, or retrieve...
The hippocampus is an archicortical structure, consisting of subfields with unique circuits. Understanding its microstructure, as proxied by these subfields, can improve our mechanistic understanding of learning and memory and has clinical potential for several neurological disorders. One prominent issue is how to parcellate, register, or retrieve...
The hippocampus is an archicortical structure, consisting of subfields with unique circuits. Understanding its microstructure, as proxied by these subfields, can improve our mechanistic understanding of learning and memory and has clinical potential for several neurological disorders. One prominent issue is how to parcellate, register, or retrieve...
Based on quantitative cyto- and receptor architectonic analyses, we identified 35 prefrontal areas, including novel subdivisions of Walker's areas 10, 9, 8B, and 46. Statistical analysis of receptor densities revealed regional differences in lateral and ventrolateral prefrontal cortex. Indeed, structural and functional organization of subdivisions...
Based on quantitative cyto- and receptor architectonic analyses, we identified 35 prefrontal areas, including novel subdivisions of Walker’s areas 10, 9, 8B, and 46. Statistical analysis of receptor densities revealed regional differences in lateral and ventrolateral prefrontal cortex. Indeed, structural and functional organization of subdivisions...
Based on quantitative cyto- and receptor architectonic analyses, we identified 35 prefrontal areas, including novel subdivisions of Walker’s areas 10, 9, 8B, and 46. Statistical analysis of receptor densities revealed regional differences in lateral and ventrolateral prefrontal cortex. Indeed, structural and functional organization of subdivisions...
Based on quantitative cyto- and receptor architectonic analyses, we identified 35 prefrontal areas, including novel subdivisions of Walker’s areas 10, 9, 8B, and 46. Statistical analysis of receptor densities revealed regional differences in lateral and ventrolateral prefrontal cortex. Indeed, structural and functional organization of subdivisions...
The hippocampus is an archicortical structure, consisting of subfields with unique circuits. Understanding its microstructure, as proxied by these subfields, can improve our mechanistic understanding of learning and memory and has clinical potential for several neurological disorders. One prominent issue is how to parcellate, register, or retrieve...
The hippocampus is an archicortical structure, consisting of subfields with unique circuits. Understanding its microstructure, as proxied by these subfields, can improve our mechanistic understanding of learning and memory and has clinical potential for several neurological disorders. One prominent issue is how to parcellate, register, or retrieve...
The human frontal operculum (FOp) is a brain region that covers parts of the ventral frontal cortex next to the insula. Functional imaging studies showed activations in this region in tasks related to language, somatosensory, and cognitive functions. While the precise cytoarchitectonic areas that correlate to these processes have not yet been revea...
The medial temporal lobe (MTL) cortex, located adjacent to the hippocampus, is crucial for memory and prone to the accumulation of certain neuropathologies such as Alzheimer’s disease neurofibrillary tau tangles. The MTL cortex is composed of several subregions which differ in their functional and cytoarchitectonic features. As neuroanatomical scho...
Neurotransmitter receptors are key molecules in signal transmission, their alterations are associated with brain dysfunction. Relationships between receptors and their corresponding genes are poorly understood, especially in humans. We combined in vitro receptor autoradiography and RNA sequencing to quantify, in the same tissue samples (7 subjects)...
The hippocampus is an archicortical structure, consisting of subfields with unique circuits. Understanding its microstructure, as proxied by these subfields, can improve our mechanistic understanding of learning and memory and has clinical potential for several neurological disorders. One prominent issue is how to parcellate, register, or retrieve...
Brain research has in recent years indisputably entered a new epoch, driven by substantial methodological advances and digitally enabled data integration and modeling at multiple scales – from molecules to the whole system. Major advances are emerging at the intersection of neuroscience with technology and computing. This new science of the brain i...
Model-based data analysis of whole-brain dynamics links the observed data to model parameters in a network of neural masses. Recently, studies focused on the role of regional variance of model parameters. Such analyses however necessarily depend on the properties of preselected neural mass model. We introduce a method to infer from the functional d...
We improve the determination of nerve fiber orientations in brain tissue sections that have been measured with Computational Scattered Light Imaging by close examination of low intensity signals with iterative thresholding.
We present a method for direct imaging of nerve fiber orientations in cell-body stained histological brain sections, which was not yet possible for paraffin-treated tissue.
Quantitative maps of neurotransmitter receptor densities are important tools for characterising the molecular organisation of the brain and key for understanding normal and pathologic brain function and behaviour. We describe a novel method for reconstructing 3-dimensional cortical maps for data sets consisting of multiple different types of 2-dime...
A comprehensive description of how neurons and entire brain regions are interconnected is fundamental for a mechanistic understanding of brain function and dysfunction. Neuroimaging has shaped the way to approaching the human brain’s connectivity on the basis of diffusion magnetic resonance imaging and tractography. At the same time, polarization,...
This review focuses on cyto- and receptor architectonics as biological correlates of function and connectivity. It introduces the three-dimensional cytoarchitectonic probabilistic maps of cortical areas and nuclei of Julich-Brain Atlas, available at EBRAINS, to study structure-functions relationships. The maps are linked to the BigBrain as microana...
In recent years, the microscopy technology referred to as Polarized Light Imaging (3D-PLI) has successfully been established to study the brain’s nerve fiber architecture at the micrometer scale. The myelinated axons of the nervous tissue introduce optical birefringence that can be used to contrast nerve fibers and their tracts from each other. Bey...
The dorsolateral prefrontal cortex (DLPFC) plays a key role in cognitive control and executive functions, including working memory, attention, value encoding, decision making, monitoring, and controlling behavioral strategies. However, the relationships between this variety of functions and the underlying cortical areas, which specifically contribu...
In the avian brain, adult neurogenesis has been reported in the telencephalon of several species, but the functional significance of this trait is still ambiguous. Homing pigeons (Columba livia f.d.) are well-known for their navigational skills. Their brains are functionally adapted to homing with, e.g., larger hippocampi. So far, no comprehensive...
The human insular cortex supports multifunctional integration including interoceptive, sensorimotor, cognitive and social-emotional processing. Different concepts of the underlying microstructure have been proposed over more than a century. However, a 3D map of the cytoarchitectonic segregation of the insula in standard reference space, that could...
Cognitive neuroscience aims to provide biologically relevant accounts of cognition. Contemporary research linking spatial patterns of neural activity to psychological constructs describes 'where' hypothesised functions occur, but not 'how' these regions contribute to cognition. Technological, empirical, and conceptual advances allow this mechanisti...
There are currently no standard methods for evaluating gait and balance performance at home. Smartphones include acceleration sensors and may represent a promising and easily accessible tool for this purpose. We performed an interventional feasibility study and compared a smartphone-based approach with two standard gait analysis systems (force plat...
Based on quantitative cyto- and receptor architectonic analyses, we identified 35 prefrontal areas and introduced a novel subdivision of Walker’s areas 10, 9, 8B and 46. Statistical analysis of receptor densities revealed regional differences in lateral and ventrolateral prefrontal cortex. Since structural and functional organization of subdivision...
Learning and memory are linked to dynamic changes at the level of synapses in brain areas that are involved in cognitive tasks. For example, changes in neurotransmitter receptors are prerequisite for tuning signals along local circuits and long-range networks. However, it is still unclear how a series of learning events promotes plasticity within t...
Brain areas at the parahippocampal gyrus of the temporal–occipital transition region are involved in different functions including processing visual–spatial information and episodic memory. Results of neuroimaging experiments have revealed a differentiated functional parcellation of this region, but its microstructural correlates are less well unde...
The sagittal stratum is a prominent and macroscopically clearly visible white-matter structure within occipital and parietal lobes with a highly organized structure of parallel fibers running in rostro-caudal direction. Apart from the major tract running through, i.e., the optic radiation, the source and arrangement of other fibers within the sagit...
Brain areas show specific cellular, molecular, and gene expression patterns that are linked to function, but their precise relationships are largely unknown. To unravel these structure-function relationships, a combined analysis of 53 neurotransmitter receptor genes, receptor densities of six transmitter systems and cytoarchitectonic data of the au...
Scattered Light Imaging (SLI) is a novel approach for microscopically revealing the fibre architecture of unstained brain sections. The measurements are obtained by illuminating brain sections from different angles and measuring the transmitted (scattered) light under normal incidence. The evaluation of scattering profiles commonly relies on a peak...
Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association...
The inferior frontal sulcus is conceptualized as the landmark delineating ventro-from dorsolateral prefrontal cortex. Functional imaging studies report activations within the sulcus during tasks addressing cognitive control and verbal working memory, while their microstructural correlates are not well defined. Existing microstructural maps, e.g., B...
This poster documented research about the cytoarchitectural variation in the temporal lobe of 10 primate species.
Cytoarchitecture is a basic principle of brain microstructure used to define parcellations. To account for variations of the cytoarchitectonic parcellation between individual brains, a three-dimensional probabilistic atlas called the Jülich-Brain has been built from 23 postmortem brains [Amunts2020]. For this purpose, all the brains were aligned us...
The method 3D polarised light imaging (3D-PLI) measures the birefringence of histological brain sections to determine the spatial course of nerve fibres (myelinated axons). While the in-plane fibre directions can be determined with high accuracy, the computation of the out-of-plane fibre inclinations is more challenging because they are derived fro...
The human metathalamus plays an important role in processing visual and auditory information. Understanding its layers and subdivisions is important to gain insights in its function as a subcortical relay station and involvement in various pathologies. Yet, detailed histological references of the microanatomy in 3D space are still missing. We there...
Emotions are valenced mental responses and associated physiological reactions that occur spontaneously and automatically in response to internal or external stimuli, and can influence our behavior, and can themselves be modulated to a certain degree voluntarily or by external stimuli. They are subserved by large-scale integrated neuronal networks w...
The cover image is based on the Research Article A comparative study of pre‐alpha islands in the entorhinal cortex from selected primates and in lissencephaly by Michael Schön et al., https://doi.org/10.1002/cne.25233.
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Idiopathic Parkinson’s disease (PD) is a neurodegenerative disorder with a broad spectrum of motor and non-motor symptoms. The neuropathological characteristics of idiopathic PD are the degeneration of dopaminergic neurons in the striatum, and the propagation of aggregates of misfolded α-synuclein in the brain following a specific patte...
Understanding the human brain is a "Grand Challenge" for 21st century research. Computational approaches enable large and complex datasets to be addressed efficiently, supported by artificial neural networks, modeling and simulation. Dynamic generative multiscale models, which enable the investigation of causation across scales and are guided by pr...
The Virtual Brain (TVB) is now available as open-source services on the cloud research platform EBRAINS. It offers software for constructing, simulating and analysing brain network models including the TVB simulator; magnetic resonance imaging (MRI) processing pipelines to extract structural and functional brain networks; combined simulation of lar...
We present a conceptually simple framework for object instance segmentation, called Contour Proposal Network (CPN), which detects possibly overlapping objects in an image while simultaneously fitting closed object contours using a fixed-size representation based on Fourier Descriptors. The CPN can incorporate state-of-the-art object detection archi...
The Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has...
The temporal cortex encompasses a large number of different areas ranging from the six-layered isocortex to the allocortex. The areas support auditory, visual, and language processing, as well as emotions and memory. The primary auditory cortex is found at the Heschl gyri, which develop early in ontogeny with the Sylvian fissure, a deep and charact...
Existing cytoarchitectonic maps of the human and macaque posterior occipital cortex differ in the number of areas they display, thus hampering identification of homolog structures. We applied quantitative in vitro receptor autoradiography to characterize the receptor architecture of the primary visual and early extrastriate cortex in macaque and hu...
The correct reconstruction of individual (crossing) nerve fibers is a prerequisite when constructing a detailed network model of the brain. The recently developed technique Scattered Light Imaging (SLI) allows the reconstruction of crossing nerve fiber pathways in whole brain tissue samples with micrometer resolution: the individual fiber orientati...
Big data obtained from unraveling human brain structure raise processing demands.
The method 3D polarised light imaging (3D-PLI) measures the birefringence of histological brain sections to determine the spatial course of nerve fibres (myelinated axons). While the in-plane fibre directions can be determined with high accuracy, the computation of the out-of-plane fibre inclinations is more challenging because they are derived fro...
The internal organization of hippocampal formation has been studied for more than a century. Although early accounts emphasized its subfields along the medial–lateral axis, findings in recent decades have highlighted also the anterior-to-posterior (i.e., longitudinal) axis as a key contributor to this brain region’s functional organization. Hence,...
Cytoarchitecture describes the spatial organization of neuronal cells in the brain, including their arrangement into layers and columns with respect to cell density, orientation, or presence of certain cell types. It allows to segregate the brain into cortical areas and subcortical nuclei, links structure with connectivity and function, and provide...
Impaired phonological processing is a leading symptom of multifactorial language and learning disorders suggesting a common biological basis. Here we evaluated studies of dyslexia, dyscalculia, specific language impairment (SLI), and the logopenic variant of primary progressive aphasia (lvPPA) seeking for shared risk genes in Broca’s and Wernicke’s...
The correct reconstruction of individual (crossing) nerve fibers is a prerequisite when constructing a detailed network model of the brain. The recently developed technique Scattered Light Imaging (SLI) allows the reconstruction of crossing nerve fiber pathways in whole brain tissue samples with micrometer resolution: The individual fiber orientati...
Neuroimaging stands to benefit from emerging ultrahigh-resolution 3D histological atlases of the human brain; the first of which is 'BigBrain'. Here, we review recent methodological advances for the integration of BigBrain with multi-modal neuroimaging and introduce a toolbox, 'BigBrainWarp', that combines these developments. The aim of BigBrainWar...
Machine-learning can reliably predict individual age from MRI data, revealing that patients with neurodegenerative disorders show an elevated biological age. A surprising gap in the literature, however, pertains to Parkinson’s disease. Here we evaluate brain age in two cohorts of Parkinson’s patients and investigated the relationship between indivi...
The entorhinal cortex (EC) is the main interface between the sensory association areas of the neocortex and the hippocampus. It is crucial for the evaluation and processing of sensory data for long-term memory consolidation, and shows damage in many brain diseases, e.g., neurodegenerative diseases, such as Alzheimer's disease and developmental diso...
Population neuroimaging allows for extracting general principles of brain-phenotype relationships. Capturing individual brain-behavior profiles in groups with pronounced inter-individual variability, like the older adult population, however, remains challenging. Therefore, deep characterization is required to link multilevel brain, cognitive and li...
Human brain atlases provide spatial reference systems for data characterizing brain organization at different levels, coming from different brains. Cytoarchitecture is a basic principle of the microstructural organization of the brain, as regional differences in the arrangement and composition of neuronal cells are indicators of changes in connecti...
The human lateral geniculate body (LGB) with its six sickle shaped layers (lam) represents the principal thalamic relay nucleus for the visual system. Cytoarchitectonic analysis serves as the groundtruth for multimodal approaches and studies exploring its function. This technique, however, requires experienced knowledge about human neuroanatomy and...
The ‘BigBrain’ is a high-resolution data set of the human brain that enables three-dimensional (3D) analyses with a 20 µm spatial resolution at nearly cellular level. We use this data set to explore pre-α (cell) islands of layer 2 in the entorhinal cortex (EC), which are early affected in Alzheimer’s disease and have therefore been the focus of res...
A bstract
Neuroimaging stands to benefit from emerging ultrahigh-resolution histological atlases of the human brain; the first of which is “BigBrain”. Ongoing research aims to characterise regional differentiation of cytoarchitecture with BigBrain and to optimise registration of BigBrain with standard neuroimaging templates. Together, this work pav...
