K Zilles

RWTH Aachen University, Aachen, North Rhine-Westphalia, Germany

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Publications (294)943.05 Total impact

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    ABSTRACT: Parkinson's disease (PD) is a well-characterized neurological disorder with regard to its neuropathological and symptomatic appearance. At the genetic level, mutations of particular genes, e.g. Parkin and DJ-1, were found in human hereditary PD with early onset. Neurotransmitter receptors constitute decisive elements in neural signal transduction. Furthermore, since they are often altered in neurological and psychiatric diseases, receptors have been successful targets for pharmacological agents. However, the consequences of PD-associated gene mutations on the expression of transmitter receptors are largely unknown. Therefore, we studied the expression of 16 different receptor binding sites of the neurotransmitters glutamate, GABA, acetylcholine, adrenaline, serotonin, dopamine and adenosine by means of quantitative receptor autoradiography in Parkin and DJ-1 knockout mice. These knockout mice exhibit electrophysiological and behavioral deficits, but do not show the typical dopaminergic cell loss. We demonstrated differential changes of binding site densities in eleven brain regions. Most prominently, we found an up-regulation of GABAB and kainate receptor densities in numerous cortical areas of Parkin and DJ-1 knockout mice, as well as increased NMDA but decreased AMPA receptor densities in different brain regions of the Parkin knockout mice. The alterations of three different glutamate receptor types may indicate the potential relevance of the glutamatergic system in the pathogenesis of PD. Furthermore, the cholinergic M1, M2 and nicotinic receptors as well as the adrenergic α2 and the adenosine A2A receptors showed differentially increased densities in Parkin and DJ-1 knockout mice. Taken together, knockout of the PD-associated genes Parkin or DJ-1 results in differential changes of neurotransmitter receptor densities, highlighting a possible role of altered non-dopaminergic, and in particular of glutamatergic neurotransmission in PD pathogenesis.
    Neuroscience 11/2015; DOI:10.1016/j.neuroscience.2015.10.054 · 3.36 Impact Factor
  • J. Caspers · S B Eickhoff · K. Amunts · G. Antoch · K. Zilles ·
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    ABSTRACT: Purpose: To investigate the distribution of co-activation patterns of the recently identified ventral visual areas FG1 and FG2 of the posterior fusiform gyrus using the novel meta-analytic approach PaMiNI (Pattern Mining in NeuroImaging). Materials and Methods: All neuroimaging experiments reporting activation foci within FG1 or FG2 were retrieved from the BrainMap database. The stereotaxic activation foci in standard reference space were analyzed with PaMiNI. Here, Gaussian mixture modeling was applied to the stereotaxic coordinates of all foci to identify the underlying brain regions of each dataset. Then, association analysis was performed to reveal frequent co-activations across the modeled brain regions. Results: Co-activation patterns of FG1 were mainly found within the visual system, i.e. in early visual areas, and were symmetrically distributed across both hemispheres. FG2 features several extra-visual co-activations, mainly to inferior frontal, premotor and parietal regions. Furthermore, the co-activations of FG2 showed clear lateralization to the left FG2. Conclusion: FG1 shows characteristics of an intermediate visual area between the early ventral visual cortex and the category-specific higher-order areas. Co-activation patterns of FG2 indicate that FG2 is a higher-order visual area that probably corresponds to the posterior fusiform face area and partly the visual word-form area.
    RöFo - Fortschritte auf dem Gebiet der R 09/2015; 187(10):892-898. DOI:10.1055/s-0041-105062 · 1.40 Impact Factor
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    Brain Stimulation 04/2015; 8(4). DOI:10.1016/j.brs.2015.04.002 · 4.40 Impact Factor
  • K. Zilles · N. Palomero-Gallagher · K. Amunts ·

    Brain Mapping, 01/2015: pages 137-156; , ISBN: 9780123973160
  • N. Palomero-Gallagher · K. Amunts · K. Zilles ·

  • K. Zilles · N. Palomero-Gallagher · K. Amunts ·

  • K. Zilles · N. Palomero-Gallagher ·

  • J N Cremer · K Amunts · J Graw · M Piel · F Rösch · K Zilles ·
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    ABSTRACT: Parkinson's disease (PD) is the second most common neurodegenerative disorder, characterized by alterations of nigrostriatal dopaminergic neurotransmission. Compared to the wealth of data on the impairment of the dopamine system, relatively limited evidence is available concerning the role of major non-dopaminergic neurotransmitter systems in PD. Therefore, we comprehensively investigated the density and distribution of neurotransmitter receptors for glutamate, GABA, acetylcholine, adrenaline, serotonin, dopamine and adenosine in brains of homozygous aphakia mice being characterized by mutations affecting the Pitx3 gene. This genetic model exhibits crucial hallmarks of PD on the neuropathological, symptomatic and pharmacological level. Quantitative receptor autoradiography was used to characterize 19 different receptor binding sites in eleven brain regions in order to understand receptor changes on a systemic level. We demonstrated striking differential changes of neurotransmitter receptor densities for numerous receptor types and brain regions, respectively. Most prominent, a strong up-regulation of GABA receptors and associated benzodiazepine binding sites in different brain regions and concomitant down-regulations of striatal nicotinic acetylcholine and serotonergic receptor densities were found. Furthermore, the densities of glutamatergic kainate, muscarinic acetylcholine, adrenergic α1 and dopaminergic D2/D3 receptors were differentially altered. These results present novel insights into the expression of neurotransmitter receptors in Pitx3(ak) mice supporting findings on PD pathology in patients and indicating on the possible underlying mechanisms. The data suggest Pitx3(ak) mice as an appropriate new model to investigate the role of neurotransmitter receptors in PD. Our study highlights the relevance of non-dopaminergic systems in PD and for the understanding of its molecular pathology. Copyright © 2014. Published by Elsevier Ltd.
    Neuroscience 11/2014; 285. DOI:10.1016/j.neuroscience.2014.10.050 · 3.36 Impact Factor
  • K. Amunts · A. Lindner · K. Zilles ·

    09/2014; 5(2):43-50. DOI:10.1007/s13295-014-0058-4
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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; 99. DOI:10.1016/j.neuroimage.2014.06.010 · 6.36 Impact Factor
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    ABSTRACT: Cholinergic neurons of the medial forebrain are considered important contributors to brain plasticity and neuromodulation. A reduction of cholinergic innervation can lead to pathophysiological changes of neurotransmission and is observed in Alzheimer's disease. Here we report on six patients with mild to moderate Alzheimer's disease (AD) treated with bilateral low-frequency deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM). During a four-week double-blind sham-controlled phase and a subsequent 11-month follow-up open label period, clinical outcome was assessed by neuropsychological examination using the Alzheimer's Disease Assessment Scale-cognitive subscale as the primary outcome measure. Electroencephalography and [(18)F]-fluoro-desoxyglucose positron emission tomography were, besides others, secondary endpoints. On the basis of stable or improved primary outcome parameters twelve months after surgery, four of the six patients were considered responders. No severe or non-transitional side effects related to the stimulation were observed. Taking into account all limitations of a pilot study, we conclude that DBS of the NBM is both technically feasible and well tolerated.Molecular Psychiatry advance online publication, 6 May 2014; doi:10.1038/mp.2014.32.
    Molecular Psychiatry 05/2014; 20(3). DOI:10.1038/mp.2014.32 · 14.50 Impact Factor
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    ABSTRACT: Healthy aging is accompanied by a decrease in cognitive and motor capacities. In a network associated with movement initiation, we investigated age-related changes of functional connectivity (FC) as well as regional atrophy in a sample of 232 healthy subjects (age range 18-85 years). To this end, voxel-based morphometry and whole-brain resting-state FC were analyzed for the supplementary motor area (SMA), anterior midcingulate cortex (aMCC) and bilateral striatum (Str). To assess the specificity of age-related effects, bilateral primary sensorimotor cortex (S1/M1) closely associated with motor execution was used as control seeds. All regions showed strong reduction of gray matter volume with age. Corrected for this regional atrophy, the FC analysis revealed an age × seed interaction for each of the bilateral Str nodes against S1/M1 with consistent age-related decrease in FC with bilateral caudate nucleus and anterior putamen. Specific age-dependent FC decline of SMA was found in bilateral central insula and the adjacent frontal operculum. aMCC showed exclusive age-related decoupling from the anterior cingulate motor area. The present study demonstrates network as well as node-specific age-dependent FC decline of the SMA and aMCC to highly integrative cortical areas involved in cognitive motor control. FC decrease in addition to gray matter atrophy within the Str may provide a substrate for the declining motor control in elderly. Finally, age-related FC changes in both the network for movement initiation as well as the network for motor execution are not explained by regional atrophy in the healthy aging brain.
    Brain Structure and Function 01/2014; 220(2). DOI:10.1007/s00429-013-0696-2 · 5.62 Impact Factor
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    ABSTRACT: To what extent does musical practice change the structure of the brain? In order to understand how long-lasting musical training changes brain structure, 20 male right-handed, middle-aged professional musicians and 19 matched controls were investigated. Among the musicians, 13 were pianists or organists with intensive practice regimes. The others were either music teachers at schools or string instrumentalists, who had studied the piano at least as a subsidiary subject, and practiced less intensively. The study was based on T1-weighted MR images, which were analyzed using deformation-based morphometry. Cytoarchitectonic probabilistic maps of cortical areas and subcortical nuclei as well as myeloarchitectonic maps of fiber tracts were used as regions of interest to compare volume differences in the brains of musicians and controls. In addition, maps of voxel-wise volume differences were computed and analyzed. Musicians showed a significantly better symmetric motor performance as well as a greater capability of controlling hand independence than controls. Structural MRI-data revealed significant volumetric differences between the brains of keyboard players, who practiced intensively and controls in right sensorimotor areas and the corticospinal tract as well as in the entorhinal cortex and the left superior parietal lobule. Moreover, they showed also larger volumes in a comparable set of regions than the less intensively practicing musicians. The structural changes in the sensory and motor systems correspond well to the behavioral results, and can be interpreted in terms of plasticity as a result of intensive motor training. Areas of the superior parietal lobule and the entorhinal cortex might be enlarged in musicians due to their special skills in sight-playing and memorizing of scores. In conclusion, intensive and specific musical training seems to have an impact on brain structure, not only during the sensitive period of childhood but throughout life.
    Frontiers in Psychology 09/2013; 4:636. DOI:10.3389/fpsyg.2013.00636 · 2.80 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; DOI:10.1016/j.neuroimage.2013.05.052 · 6.36 Impact Factor
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    D Bzdok · A Laird · K Zilles · P Fox · S Eickhoff ·

    Klinische Neurophysiologie 03/2013; 44(01). DOI:10.1055/s-0033-1337198 · 0.12 Impact Factor
  • L Hensel · B Danilo · V Müller · K Zilles · S Eickhoff ·

    Klinische Neurophysiologie 03/2013; 44(01). DOI:10.1055/s-0033-1337260 · 0.12 Impact Factor
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    ABSTRACT: In a previous meta-analysis across almost 200 neuroimaging experiments, working memory for object location showed significantly stronger convergence on the posterior superior frontal gyrus, whereas working memory for identity showed stronger convergence on the posterior inferior frontal gyrus (dorsal to, but overlapping with Brodmann’s area BA 44). As similar locations have been discussed as part of a dorsal frontal—superior parietal reach system and an inferior frontal grasp system, the aim of the present study was to test whether the regions of working-memory related “what” and “where” processing show a similar distinction in parietal connectivity. The regions that were found in the previous meta-analysis were used as seeds for functional connectivity analyses using task-based meta-analytic connectivity modelling and task-independent resting state correlations. While the ventral seed showed significantly stronger connectivity with the bilateral intraparietal sulcus (IPS), the dorsal seed showed stronger connectivity with the bilateral posterior inferior parietal and the medial superior parietal lobule. The observed connections of regions involved in memory for object location and identity thus clearly demonstrate a distinction into separate pathways that resemble the parietal connectivity patterns of the dorsal and ventral premotor cortex in non-human primates and humans. It may hence be speculated that memory for a particular location and reaching towards it as well as object memory and finger positioning for manipulation may rely on shared neural systems. Moreover, the ensuing regions, in turn, featured differential connectivity with the bilateral ventral and dorsal extrastriate cortex, suggesting largely segregated bilateral connectivity pathways from the dorsal visual cortex via the superior and inferior parietal lobules to the dorsal posterior frontal cortex and from the ventral visual cortex via the IPS to the ventral posterior frontal cortex that may underlie action and cognition.
    Brain Structure and Function 11/2012; 218(6). DOI:10.1007/s00429-012-0476-4 · 5.62 Impact Factor
  • C Roski · S Caspers · S Lux · S Eickhoff · K Zilles ·

    Klinische Neurophysiologie 03/2012; 43(01). DOI:10.1055/s-0032-1301592 · 0.12 Impact Factor
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    Klinische Neurophysiologie; 03/2012
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    J. Caspers · K. Zilles · S.B. Eickhoff · C. Beierle ·
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    ABSTRACT: Large-scale neuroimaging databases provide a rich fundus of functional neuroimaging experiments exhibiting maximum activation coordinates for specific task conditions. Aiming to explore major neuronal networks of the human brain, we developed a meta-analytic pattern-mining approach which combines Gaussian mixture modeling with the Apriori algorithm to identify frequent activation patterns within these databases. The approach has been implemented in the PaMiNI (Pattern Mining in NeuroImaging) system, providing manifold facilities for the finding, inspection, and analysis of relevant patterns. After briefly sketching the background of PaMiNI, we give an overview of the system and describe its architecture. Using an example application, a system walkthrough illustrates how PaMiNI can be used for the discovery of networks comprising functionally connected brain regions.
    Computer-Based Medical Systems (CBMS), 2012 25th International Symposium on; 01/2012

Publication Stats

14k Citations
943.05 Total Impact Points


  • 2001-2014
    • RWTH Aachen University
      • • Department of Psychiatry, Psychotherapy and Psychosomatics
      • • Department of Neurology
      Aachen, North Rhine-Westphalia, Germany
  • 1992-2014
    • Heinrich-Heine-Universität Düsseldorf
      • • C.U. O. Vogt-Institute of brain research
      • • Brain Research Institute
      • • Institute of Laser Medicine
      Düsseldorf, North Rhine-Westphalia, Germany
  • 1999-2010
    • Forschungszentrum Jülich
      • Institute of Neurosciences and Medicine (INM)
      Düren, North Rhine-Westphalia, Germany
  • 2006
    • IME Metallurgy
      Aachen, North Rhine-Westphalia, Germany
  • 2002
    • Universitätsklinikum Düsseldorf
      Düsseldorf, North Rhine-Westphalia, Germany
  • 1995
    • University of Applied Science, Budapest
      Budapeŝto, Budapest, Hungary
  • 1983-1991
    • University of Cologne
      • Institute of Anatomy I
      Köln, North Rhine-Westphalia, Germany
  • 1979
    • Christian-Albrechts-Universität zu Kiel
      • Anatomisches Institut
      Kiel, Schleswig-Holstein, Germany
  • 1973
    • Hannover Medical School
      Hanover, Lower Saxony, Germany