Publications

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    ABSTRACT: The last two decades have seen an unprecedented development of human brain mapping approaches at various spatial and temporal scales. Together, these have provided a large fundus of information on many different aspects of the human brain including the micro- and macrostructural segregation, regional specialization of function, connectivity, and temporal dynamics. Atlases are central in order to integrate such diverse information in a topographically meaningful way. It is noteworthy, that the brain mapping field has been developed along several major lines such as structure vs. function, postmortem vs. in vivo, individual features of the brain vs. population-based aspects, or slow vs. fast dynamics. In order to understand human brain organization, however, it seems inevitable that these different lines are integrated and combined into a multimodal human brain model. To this aim, we held a workshop to determine the constraints of a multi-modal human brain model that are needed to enable (i) an integration of different spatial and temporal scales and data modalities into a common reference system, and (ii) efficient data exchange and analysis. As detailed in this report, to arrive at fully interoperable atlases of the human brain will still require much work at the frontiers of data acquisition, analysis, and representation. Among them, the latter may provide the most challenging task, in particular when it comes to representing features of vastly different scales of space, time and abstraction. The potential benefits of such endeavor, however, clearly outweigh the problems, as only such kind of multi-modal human brain atlas may provide a starting point from which the complex relationships between structure, function, and connectivity may be explored.
    NeuroImage 06/2014; · 6.25 Impact Factor
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    ABSTRACT: Healthy aging has been found associated with less efficient response conflict solution, but the cognitive and neural mechanisms have remained elusive. In a two-experiment study, we first examined the behavioural consequences of this putative age-related decline for conflicts induced by spatial stimulus-response incompatibility. We then used resting-state functional magnetic resonance imaging data from a large, independent sample of adults (n = 399; 18-85 years) to investigate age differences in functional connectivity between the nodes of a network previously found associated with incompatibility-induced response conflicts in the very same paradigm. As expected, overcoming interference from conflicting response tendencies took longer in older adults, even after accounting for potential mediator variables (general response speed and accuracy, motor speed, visuomotor coordination ability, and cognitive flexibility). Experiment 2 revealed selective age-related decreases in functional connectivity between bilateral anterior insula, pre-supplementary motor area, and right dorsolateral prefrontal cortex. Importantly, these age effects persisted after controlling for regional grey-matter atrophy assessed by voxel-based morphometry. Meta-analytic functional profiling using the BrainMap database showed these age-sensitive nodes to be more strongly linked to highly abstract cognition, as compared with the remaining network nodes, which were more strongly linked to action-related processing. These findings indicate changes in interregional coupling with age among task-relevant network nodes that are not specifically associated with conflict resolution per se. Rather, our behavioural and neural data jointly suggest that healthy aging is associated with difficulties in properly activating non-dominant but relevant task schemata necessary to exert efficient cognitive control over action.
    Brain Structure and Function 04/2014; · 7.84 Impact Factor
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    ABSTRACT: The visualization of the progression of brain tissue loss in neurodegenerative diseases like corticobasal syndrome (CBS) can provide not only information about the localization and distribution of the volume loss, but also helps to understand the course and the causes of this neurodegenerative disorder. The visualization of such medical imaging data is often based on 2D sections, because they show both internal and external structures in one image. Spatial information, however, is lost. 3D visualization of imaging data is capable to solve this problem, but it faces the difficulty that more internally located structures may be occluded by structures near the surface. Here, we present an application with two designs for the 3D visualization of the human brain to address these challenges. In the first design, brain anatomy is displayed semi-transparently; it is supplemented by an anatomical section and cortical areas for spatial orientation, and the volumetric data of volume loss. The second design is guided by the principle of importance-driven volume rendering: A direct line-of-sight to the relevant structures in the deeper parts of the brain is provided by cutting out a frustum-like piece of brain tissue. The application was developed to run in both, standard desktop environments and in immersive virtual reality environments with stereoscopic viewing for improving the depth perception. We conclude, that the presented application facilitates the perception of the extent of brain degeneration with respect to its localization and affected regions.
    Frontiers in Neuroinformatics 01/2014; 8:42.
  • Movement Disorders 12/2013; · 4.56 Impact Factor
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    ABSTRACT: Biotin-responsive basal ganglia disease (BBGD) is an autosomal recessive disorder, which is caused by mutations in the SLC19A3 gene. BBGD typically causes (sub)acute episodes with encephalopathy and subsequent neurological deterioration. If untreated, the clinical course may be fatal. Our report on a 6-year-old child with BBGD highlights that the disease is a crucial differential diagnosis of Leigh syndrome. Therefore, biotin and thiamine treatment is recommended for any patient with symmetrical basal ganglia lesions and neurological symptoms until BBGD is excluded. In addition, we exemplify that deformation-field-based morphometry of brain magnetic resonance images constitutes a novel quantitative tool, which might be very useful to monitor disease course and therapeutic effects in neurometabolic disorders.
    JIMD reports. 10/2013;
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    ABSTRACT: Recently, two extrastriate visual areas on the posterior fusiform gyrus, areas FG1 and FG2, were identified based on cytoarchitectonical criteria (Caspers et al. in Brain Struct Funct 218:511-526, 2013a). They are located within the object-related ventral visual stream at the transition between early and higher-order (category-specific) visual areas. FG2 has a topographical position which is best comparable to the face or visual word-form recognition area. However, the precise function of FG2 is presently unknown. Since transmitter receptors are key molecules of neurotransmission, we analysed the regional and laminar distribution of 15 different receptor binding sites by means of quantitative in vitro receptor autoradiography. Significant differences between receptor densities of both areas were found for NMDA, GABAB, M3, nicotinic α4/β2 and 5-HT1A receptors as well as for GABAA associated benzodiazepine binding sites. These results support the cytoarchitectonic segregation of FG1 and FG2 into two distinct cortical areas. In addition, principal component and hierarchical cluster analyses of the multireceptor data of both fusiform areas and 24 visual, auditory, somatosensory and multimodal association areas not only revealed the typical receptor architectonic characteristics of visual areas for FG1 and FG2, but also suggest their putative function as object recognition regions due to the similarity of their receptor fingerprints with those of areas of the ventral visual stream. Furthermore, FG1 and FG2 build a cluster with the multimodal association areas of the inferior parietal lobule. This underlines their hierarchically high position in the visual system of the human cerebral cortex.
    Brain Structure and Function 10/2013; · 7.84 Impact Factor
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    ABSTRACT: The ventral stream of the human extrastriate visual cortex shows a considerable functional heterogeneity from early visual processing (posterior) to higher, domain-specific processing (anterior). The fusiform gyrus hosts several of those "high-level" functional areas. We recently found a subdivision of the posterior fusiform gyrus on the microstructural level, that is, two distinct cytoarchitectonic areas, FG1 and FG2 (Caspers et al., Brain Structure & Function, 2013). To gain a first insight in the function of these two areas, here we studied their behavioral involvement and coactivation patterns by means of meta-analytic connectivity modeling based on the BrainMap database (www.brainmap.org), using probabilistic maps of these areas as seed regions. The coactivation patterns of the areas support the concept of a common involvement in a core network subserving different cognitive tasks, that is, object recognition, visual language perception, or visual attention. In addition, the analysis supports the previous cytoarchitectonic parcellation, indicating that FG1 appears as a transitional area between early and higher visual cortex and FG2 as a higher-order one. The latter area is furthermore lateralized, as it shows strong relations to the visual language processing system in the left hemisphere, while its right side is stronger associated with face selective regions. These findings indicate that functional lateralization of area FG2 relies on a different pattern of connectivity rather than side-specific cytoarchitectonic features. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.
    Human Brain Mapping 09/2013; · 6.88 Impact Factor
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    ABSTRACT: Human ventral temporal cortex (VTC) plays a pivotal role in high-level vision. An under-studied macroanatomical feature of VTC is the mid-fusiform sulcus (MFS), a shallow longitudinal sulcus separating the lateral and medial fusiform gyrus (FG). Here, we quantified the morphological features of the MFS in 69 subjects (ages 7-40), and investigated its relationship to both cytoarchitectonic and functional divisions of VTC with four main findings. First, despite being a minor sulcus, we found that the MFS is a stable macroanatomical structure present in all 138 hemispheres with morphological characteristics developed by age 7. Second, the MFS is the locus of a lateral-medial cytoarchitechtonic transition within the posterior FG serving as the boundary between cytoarchitectonic regions FG1 and FG2. Third, the MFS predicts a lateral-medial functional transition in eccentricity bias representations in children, adolescents, and adults. Fourth, the anterior tip of the MFS predicts the location of a face-selective region, mFus-faces/FFA-2. These findings are the first to illustrate that a macroanatomical landmark identifies both cytoarchitectonic and functional divisions of high-level sensory cortex in humans and have important implications for understanding functional and structural organization in the human brain.
    NeuroImage 09/2013; · 6.25 Impact Factor
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    ABSTRACT: The neuroimaging technique 3D-polarized light imaging (3D-PLI) has opened up new avenues to study the complex nerve fiber architecture of the human brain at sub-millimeter spatial resolution. This polarimetry technique is applicable to histological sections of postmortem brains utilizing the birefringence of nerve fibers caused by the regular arrangement of lipids and proteins in the myelin sheaths surrounding axons. 3D-PLI provides a three-dimensional description of the anatomical wiring scheme defined by the in-section direction angle and the out-of-section inclination angle. To date, 3D-PLI is the only available method that allows bridging the microscopic and the macroscopic description of the fiber architecture of the human brain. Here we introduce a new approach to retrieve the inclination angle of the fibers independently of the properties of the used polarimeters. This is relevant because the image resolution and the signal transmission inuence the measured birefringent signal (retardation) significantly. The image resolution was determined using the USAF- 1951 testchart applying the Rayleigh criterion. The signal transmission was measured by elliptical polarizers applying the Michelson contrast and histological slices of the optic tract of a postmortem brain. Based on these results, a modified retardation-inclination transfer function was proposed to extract the fiber inclination. The comparison of the actual and the inclination angles calculated with the theoretically proposed and the modified transfer function revealed a significant improvement in the extraction of the fiber inclinations.
    Proc SPIE 09/2013;
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    ABSTRACT: Reference brains are indispensable tools in human brain mapping, enabling integration of multimodal data into an anatomically realistic standard space. Available reference brains, however, are restricted to the macroscopic scale and do not provide information on the functionally important microscopic dimension. We created an ultrahigh-resolution three-dimensional (3D) model of a human brain at nearly cellular resolution of 20 micrometers, based on the reconstruction of 7404 histological sections. "BigBrain" is a free, publicly available tool that provides considerable neuroanatomical insight into the human brain, thereby allowing the extraction of microscopic data for modeling and simulation. BigBrain enables testing of hypotheses on optimal path lengths between interconnected cortical regions or on spatial organization of genetic patterning, redefining the traditional neuroanatomy maps such as those of Brodmann and von Economo.
    Science 06/2013; 340(6139):1472-1475. · 31.20 Impact Factor
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    ABSTRACT: Primary progressive aphasia (PPA) is a rare clinical dementia syndrome with predominant, progressive language impairment. Clinical symptoms, linguistic impairment and the course of the disease may vary considerably between patients. In order to capture these aspects, longitudinal assessments of neurofunctional changes in PPA including their relationship to behaviour and clinical symptoms are mandatory, ideally at intervals shorter than 1year. Here, we report a longitudinal fMRI study investigating the development of lexical processing and their neural basis in PPA patients over 1year. Four logopenic PPA patients and four matched controls were scanned 3 times (T1, T2, T3, at 6months intervals) while performing a visual lexical decision task on German words and pseudowords. Group differences for the lexicality effect (pseudowords>words) were assessed at time point T1 and its longitudinal changes in the BOLD signal associated with the lexicality effect were analysed. Brain atrophy was assessed with a high-resolution MPRAGE sequence and analysed using deformation based morphometry (DBM). From the very beginning of the study, PPA patients showed reduced left-hemispheric and increased right-hemispheric activations compared to controls. During the progression of the disease, activation increased predominantly in left posterior middle temporal gyrus (pMTG) and inferior frontal junction area, whereas the same regions decreased in activity in control brains. Interestingly, DBM data showed that this increase in activation in PPA patients was accompanied by progressing atrophy in the same regions. At a behavioural level, the accuracy in the lexical decision task was comparably high for both groups during the whole period of examination, despite some large variability between patients. To conclude, the dissociation between (i) maintained high performance, (ii) increased activity in regions involved in lexical access such as pMTG, and (iii) progressive atrophy of the very same regions supports the notion of a compensatory mechanism in brains of PPA patients for maintaining language while brain atrophy is progressing. The activity increase within a left-lateralised fronto-temporal network seems vital for high-level performance, whereas initial right-hemispheric recruitment of homologue language regions, which is reminiscent of that in vascular aphasics, has no continuous impact on lexical performance.
    Brain and Language 06/2013; · 3.39 Impact Factor
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    ABSTRACT: Cytoarchitectonic area 44 of Broca's region in the left inferior frontal gyrus is known to be involved in several functional domains including language, action and music processing. We investigated whether this functional heterogeneity is reflected in distinct modules within cytoarchitectonically defined left area 44 using meta-analytic connectivity-based parcellation (CBP). This method relies on identifying the whole-brain co-activation pattern for each area 44 voxel across a wide range of functional neuroimaging experiments and subsequently grouping the voxels into distinct clusters based on the similarity of their co-activation patterns. This CBP-analysis revealed that five separate cluster exist within left area 44. A post-hoc functional characterization and functional connectivity analysis of these five clusters was then performed. The two posterior clusters were primarily associated with action processes, in particular with phonology and overt speech (posterior-dorsal cluster) and with rhythmic sequencing (posterior-ventral cluster). The three anterior clusters were primarily associated with language and cognition, in particular with working-memory (anterior-dorsal cluster), with detection of meaning (anterior-ventral cluster) and with task switching/ cognitive control (inferior frontal junction cluster). These five clusters furthermore showed specific and distinct connectivity patterns. The results demonstrate that left area 44 is heterogeneous, thus supporting anatomical data on the molecular architecture of this region, and provide a basis for more specific interpretations of activations localized in area 44.
    NeuroImage 06/2013; · 6.25 Impact Factor
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    ABSTRACT: BACKGROUND: Although it is well established that there is cognitive dysfunction in spinocerebellar ataxia type 3 (SCA3), it is unknown whether cognition deteriorates with disease progression. We therefore prospectively studied cognitive function in patients with SCA3. METHODS: Eleven patients with SCA3 were assessed using an extensive neuropsychological test battery and retested after 3.5 ± 0.4 years. RESULTS: In addition to ataxia and motor control, verbal learning and verbal and figural memory deteriorated significantly during the follow-up period. An increase in depressive symptoms was not observed. CONCLUSIONS: The observation that memory and learning abilities deteriorated with disease progression suggests that cognitive dysfunction is an integral part of SCA3. Because the applied tests for memory function did not require motor responses, cognitive decline cannot be attributed to progressive cerebellar ataxia. The deterioration of verbal and figural memory can be explained either by extracerebellar pathology or by disruption of cerebellar-cerebral circuitries. © 2013 Movement Disorder Society.
    Movement Disorders 06/2013; · 4.56 Impact Factor
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    ABSTRACT: The frontal pole has more expanded than any other part in the human brain as compared to our ancestors. It plays an important role for specifically human behavior and cognitive abilities, e.g. action selection (Kovach et al., 2012). Evidence about divergent functions of its medial and lateral part has been provided, both in the healthy brain and in psychiatric disorders. The anatomical correlates of such functional segregation, however, are still unknown due to a lack of stereotaxic, microstructural maps obtained in a representative sample of brains. Here we show that the human frontopolar cortex consists of two cytoarchitectonically and functionally distinct areas: lateral frontopolar area 1 (Fp1) and medial frontopolar area 2 (Fp2). Based on observer-independent mapping in serial, cell-body stained sections of 10 brains, three-dimensional, probabilistic maps of areas Fp1 and Fp2 were created. They show, for each position of the reference space, the probability with which each area was found in a particular voxel. Applying these maps as seed regions for a meta-analysis revealed that Fp1 and Fp2 differentially contribute to functional networks: Fp1 was involved in cognition, working memory and perception, whereas Fp2 was part of brain networks underlying affective processing and social cognition. The present study thus disclosed cortical correlates of a functional segregation of the human frontopolar cortex. The probabilistic maps provide a sound anatomical basis for interpreting neuroimaging data in the living human brain, and open new perspectives for analyzing structure-function relationships in the prefrontal cortex. The new data will also serve as a starting point for further comparative studies between human and non-human primate brains. This allows finding similarities and differences in the organizational principles of the frontal lobe during evolution as neurobiological basis for our behavior and cognitive abilities.
    NeuroImage 05/2013; · 6.25 Impact Factor
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    ABSTRACT: There is extensive evidence for an early vertebrate origin of lateralized motor behavior and of related asymmetries in underlying brain systems. We investigate human lateralized motor functioning in a broad comparative context of evolutionary neural reorganization. We quantify evolutionary trends in the fronto-cerebellar system (involved in motor learning) across 46 million years of divergent primate evolution by comparing rates of evolution of prefrontal cortex, frontal motor cortex, and posterior cerebellar hemispheres along individual branches of the primate tree of life. We provide a detailed evolutionary model of the neuroanatomical changes leading to modern human lateralized motor functioning, demonstrating an increased role for the fronto-cerebellar system in the apes dating to their evolutionary divergence from the monkeys (∼30 million years ago (Mya)), and a subsequent shift toward an increased role for prefrontal cortex over frontal motor cortex in the fronto-cerebellar system in the Homo-Pan ancestral lineage (∼10 Mya) and in the human ancestral lineage (∼6 Mya). We discuss these results in the context of cortico-cerebellar functions and their likely role in the evolution of human tool use and speech.
    Annals of the New York Academy of Sciences 05/2013; · 4.38 Impact Factor
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    ABSTRACT: The human brain connectome is closely linked to the anatomical framework provided by the structural segregation of the cortex into distinct cortical areas. Therefore, a thorough anatomical reference for the analysis and interpretation of connectome data is indispensable to understand the structure and function of different regions of the cortex, the white matter fibre architecture connecting them, and the interplay between these different entities. This article focuses on parcellation schemes of the cerebral grey matter and their relevance for connectome analyses. In particular, benefits and limitations of using different available atlases and parcellation schemes are reviewed. It is furthermore discussed how atlas information is currently used in connectivity analyses with major focus on seed-based and seed-target analyses, connectivity-based parcellation results, and the robust anatomical interpretation of connectivity data. Particularly this last aspect opens the possibility of integrating connectivity information into given anatomical frameworks, paving the way to multi-modal atlases of the human brain for a thorough understanding of structure-function relationships.
    NeuroImage 04/2013; · 6.25 Impact Factor
  • Karl Zilles, Katrin Amunts
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    ABSTRACT: A recent study demonstrates that intersubject variability in functional connectivity is heterogeneous across the cortex, with significantly higher variability in multimodal association cortex. Rather than being 'noise', intersubject variability is invaluable for understanding principles of brain evolution and ontogenetic development, and for interpreting statistical maps in task-based functional neuroimaging studies.
    Trends in Cognitive Sciences 03/2013; · 16.01 Impact Factor
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    ABSTRACT: The functional specificity of brain areas is diminished with age and accompanied by the recruitment of additional brain regions in healthy older adults. This process has repeatedly been demonstrated within distinct functional domains, in particular the visual system. However, it is yet unclear, whether this phenomenon in healthy aging, i.e., a reduced activation of task-associated areas and increased activation of additional regions, is also present across different functional systems. In the present functional imaging study, comprising 102 healthy subjects, we therefore assessed two distinct tasks engaging the sensory-motor system and the visual attention system, respectively. We found a significant interaction between age and task in the parietal operculum bilaterally. This area as a part of the sensory-motor system showed an age-related decrease in its BOLD-response to the motor task and an age-related increase of neural activity in response to the visual attention task. The opposite response pattern, i.e., reduced visual attention activation and increased response to the motor task, was observed for regions associated with the visual task: the superior parietal area 7A and the dorsal pre-motor cortex. Importantly, task performance was not correlated with age in either task. This age-by-task interaction indicates that a reduction of functional specificity in the aging brain may be counteracted by the increased recruitment of additional regions not only within, but also across functional domains. Our results thus emphasize the need for comparisons across different functional domains to gain a better understanding of age-related effects on the specificity of functional systems.
    Brain Structure and Function 03/2013; · 7.84 Impact Factor
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    ABSTRACT: Cortical folding is a hallmark of many, but not all, mammalian brains. The degree of folding increases with brain size across mammals, but at different scales between orders and families. In this review we summarize recent studies that have shed light on cortical folding and discuss new models that arise from these data. Genetic analyses argue for an independent development of brain volume and gyrification, but more recent data on the cellular development of the cortex and its connectivity highlight the role of these processes in cortical folding (grey matter hypothesis). This, and the widely discussed tension hypothesis, further tested by analyzing the mechanical properties of maturing nerve fibers, synapses, and dendrites, can provide the basis for a future integrative view on cortical folding.
    Trends in Neurosciences 02/2013; · 13.58 Impact Factor
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    ABSTRACT: Phonological and visual dysfunctions may result in reading deficits like those encountered in developmental dyslexia. Here, we use a novel approach to induce similar reading difficulties in normal readers in an event-related fMRI study, thus systematically investigating which brain regions relate to different pathways relating to orthographic-phonological (e.g. grapheme-to-phoneme conversion, GPC) vs. visual processing. Based upon a previous behavioural study (Tholen et al. 2011), the retrieval of phonemes from graphemes was manipulated by lowering the identifiability of letters in familiar vs. unfamiliar shapes. Visual word and letter processing was impeded by presenting the letters of a word in a moving, non-stationary manner. FMRI revealed that the visual condition activated cytoarchitectonically defined area hOC5 in the magnocellular pathway and area 7A in the right mesial parietal cortex. In contrast, the grapheme manipulation revealed different effects localised predominantly in bilateral inferior frontal gyrus (left cytoarchitectonic area 44; right area 45) and inferior parietal lobule (including areas PF/PFm), regions that have been demonstrated to show abnormal activation in dyslexic as compared to normal readers. This pattern of activation bears close resemblance to recent findings in dyslexic samples both behaviourally and with respect to the neurofunctional activation patterns. The novel paradigm may thus prove useful in future studies to understand reading problems related to distinct pathways, potentially providing a link also to the understanding of real reading impairments in dyslexia.
    Brain Structure and Function 02/2013; · 7.84 Impact Factor

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