FSP 3 - Karl Zilles - BMFZ - Biologisch-Medizinisches Forschungszentrum
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The relation of structure and function within the human cerebral cortex and its association with neuropathology as revealed in combination with animal models.

 Karl Zilles, C. und O. Vogt-Institut für Hirnforschung

1. Abstract

A. According to our project description we maintained our line of investigation of the human cerebral cortex focussing on association areas of the parietal lobe and the extrastriatal areas of the visual system. The results have been published. These studies will be continued.

B. In collaboration with the Center for Epilepsy Bethel and the Institute for Neurophysiology University of Münster we continued our studies on heat shock protein expression in patients with epilepsy and in an animal model for tonic clonic seizures (PTZ model). For the latter we were able to show that astrocytes, which express the oxidative stress marker HSP-27 during the course of seizure episodes, become affected by a region-specific nitration and partial inhibition of glutamine synthase. These functional changes occur independently of quantitative changes in the amount of glutamine synthase. Therefore, future studies shall address the hypothesis, whether the observed seizure-induced nitration of the enzyme is part of an initially protective cerebral pathway in order to cope with seizure related phenomena of hyperexcitation. In addition, we started to address seizure and ischemia related changes of oligodendrocytes using oligodendrocyte specific stress markers.

C. We continued our studies on the receptors for nitric oxide, the soluble guanylyl cyclases (sGC) in the cerebral cortex of primates. In addition, we use now recently developed antibodies, which are specific for various regions within the sGC molecule to analyse the functional changes and role of sGC in development and neuropathology.

D. In vitro studies in combination with animal models for certain conditions known from hepatic encephalopathy. We analysed the mechanisms of ammonia induced NADH-oxidases and RNA oxidation in collaboration with the Clinic for Gastroenterology, Hepatology and Infectiology, SFB 575. This study will be continued.

E. In collaboration with the Institute of Anatomy of the University of Leipzig and the Max Planck Institute for Evolutionary Anthropology, Leipzig we studied the changes of the auditory nuclei within the brain stem (SOC) during the phylogeny of non-human primates in comparison to humans.


2. Publications:

Book Chapters:

Amunts, K., Zilles, K.: Hirnatlas. In: Funktionelle MRT in Psychiatrie und Neurologie (Hrsg. F. Schneider, G.R. Fink), pp. 632-655. Springer, Heidelberg (2007)

Amunts, K., Zilles, K.: Funktionelle Neuroanatomie. In: Funktionelle MRT in Psychiatrie und Neurologie (Hrsg. F. Schneider, G.R. Fink), pp.9-59. Springer, Heidelberg (2007)

Palomero-Gallagher N, Zilles K. Transmitter Receptor Systems in Cingulate Regions and Areas. In: Vogt BA, editor. Cingulate Neurobiology & Disease, volume 1: Infrastructure, Diagnosis, Treatment. Oxford University Press. Chapter 2, in press (2008)



Malikovic, A., Amunts, K., Schleicher, A., Mohlberg, H., Eickhoff, S.B., Wilms, M., Palomero-Gallagher, N., Armstrong, E., Zilles, K.: Cytoarchitectonic analysis of the human extrastriate cortex in the region of V5/MT+: A probabilistic, stereotaxic map of area hOc5. Cerebral Cortex 2007;17(3):562-74

Topic, B., Willuhn, I., Palomero-Gallagher, N., Zilles, K., Huston, J.P., Hasenöhrl, R.U.: Impaired maze performance in aged rats is accompanied by increased density of NMDA, 5-HT1A and α-adrenoceptor binding in hippocampus. Hippocampus 2007;17(1): 68-77

Amunts, K., Armstrong, E., Malikovic, A., Hömke, L., Mohlberg, H., Schleicher, A., Zilles, K.: Gender-specific left-right asymmetries in human visual cortex. J. Neurosci.2007;27:1356-64

Elmenhorst, D., Meyer, P.T., Winz, O.H., Matusch, A., Ermert, J., Coenen, H.H., Basheer, R., Haas, H.L., Zilles, K., Bauer, A.: Sleep deprivation increases A1 adenosine receptor binding in the human brain: a [18F]CPFPX PET study. J. Neurosci. 2007; 27(9): 2410-15.

Eickhoff, S.B., Schleicher, A., Scheperjans, F., Palomero-Gallagher, N., Zilles, K.: Analysis of neurotransmitter receptor distribution patterns in the cerebral cortex. NeuroImage 2007;34(4): 1317-30

Hilbig, H., Nowack, S., Boeckler, K., Bidmon, H.-J., Zilles, K.: Characterisation of neuronal subsets surrounded by perineuronal nets in the rhesus auditory brain stem. J. Anat.2007;210(5): 507-17.

Eickhoff, S.B., Paus, T., Caspers, S., Grosbras, M.-H., Evans, A.C., Zilles, K., Amunts, K.: Assignment of functional activations to probabilistic cytoarchitectonic areas revisited. NeuroImage 2007;36(3):511-21

Walters, N.B., Eickhoff, S.B., Schleicher, A., Zilles, K., Amunts, K., Egan, G.F., Watson, J.D.: Observer-independent analysis of high-resolution MR images of the human cerebral cortex: In vivo delineation of cortical areas. Hum. Brain Mapp. 2007;28(1):1-8.

Eickhoff, S. B., Grefkes, C., Zilles, K., Fink, G.R.: The somatotopic organization of cytoarchitectonic areas on the human parietal operculum. Cerebral Cortex 2007;17(7): 1800-11.

Amunts, K., Schleicher, A., Zilles, K.: Cytoarchitecture of the cerebral cortex - more than localization. NeuroImage 2007;37(4): 1061-1065.

Eickhoff, S.B., Rottschy, C., Zilles, K.: Laminar distribution and co-distribution of neurotransmitter receptors in human early visual cortex. Brain Structure Function 2007; 212(3-4):255-67.

Meyer, P.T., Elmenhorst, D., Boy, C., Winz, O., Matusch, A., Zilles, K., Bauer, A.: Effect of aging on cerebral A1 adenosine receptors: a [18F]CPFPX PET study in humans. Neurobiol. Aging 2007;28(12):1914-24.

Elmenhorst, D., Meyer, P.T., Matusch, A., Winz, O., Zilles, K., Bauer, A.: Test-Retest stability of cerebral A1 adenosine receptor quantification using [18F]CPFPX and PET. Europ. J. Nucl. Med. Mol. Imaging. 2007;34(7):1061-70.

Matusch, A., Hurlemann, R., Kops, E. R., Winz, O., Elmenhorst, D., Herzog, H., Zilles, K., Bauer, A.: Acute S-ketamine application does not alter cerebral [18F]altanserin binding: a pilot PET Study in humans. J. Neural Transmission 2007;114(11):1433-42.
Reinehr R, Görg B, Becker S, Qvartskhava N, Bidmon HJ, Selbach O, Haas HL, Schliess F, Häussinger D. Hypoosmotic swelling and ammonia increase oxidative stress by NADPH oxidase in cultured astrocytes and vital brain slices. Glia. 2007;55(7):758-71.

Rottschy, C., Eickhoff, S., Schleicher, A., Mohlberg, H., Kujovic, M., Zilles, K., Amunts, K.: The ventral visual cortex in humans: Cytoarchitectonic mapping of two extrastriate areas. Human Brain Mapping 2007;28(10):1045-59.

Naito, E., Scheperjans, F., Eickhoff, S.B., Amunts, K., Roland, P., Zilles, K., Ehrsson, H.H.: Cytoarchitectonic areas in human superior parietal lobule are functionally implicated by an illusion of bimanual interaction with an external object J. Neurophysiol. 2008;99(2): 695-703.

Pieperhoff , P., Hömke, L., Schneider, F., U. Habel, U., N.J. Shah, N.J., K. Zilles, K., Amunts, K.: Deformation field morphometry reveals age-related structural differences between the brains of adults up to 51 years. J. Neurosci. 2008;28(4): 828-842.

Hurlemann, R., Matusch, A., Kuhn, K.-U., Berning, J., Elmenhorst, S., Winz, O., Kolsch, H., Zilles, K., Wagner, M., Maier, W., Bauer, A.: 5-HT2A receptor density is decreased in at-risk mental state. Psychopharmacology 2008;195(4):579-90.

Boy, C., Meyer, P.T., Kircheis, G., Holschbach, M.H., Herzog, H., Elmenhorst, D., Kaiser, H.J., Coenen, H.H., Häussinger, D., Zilles, K., Bauer, A.: Cerebral adenosine A1 receptors (A1AR) in liver cirrhosis. Eur. J. Nucl. Med. Mol. Imaging 2008;35(3):589-97.
Schenker NM, Buxhoeveden DP, Blackmon WL, Amunts K, Zilles K, Semendeferi K. A comparative quantitative analysis of cytoarchitecture and minicolumnar organization in Broca's area in humans and great apes. J Comp Neurol. 2008;510(1):117-28.

Palomero-Gallagher, N., Schleicher, A., Lindemann, S., Lessenich, A., Zilles, K., Löscher, W.: Receptor fingerprinting the circling ci2 rat mutant: insights into brain asymmetry and motor control. Exp. Neurol.2008;210(2): 624-37.

Palomero-Gallagher, N., Mohlberg, H., Zilles, K., Vogt, B.: Cytology and receptor architecture of human anterior cingulate cortex. J. Comp. Neurol. 2008;508(6):906-26.

Eickhoff, S.B., Dafotakis, M., Grefkes, C., Shah, N.J., Zilles, K., Piza-Katzer, H.: Central adaptation following heterotopic hand replantation probed by fMRI and effective connectivity analysis. Exp. Neurol. 2008;212(1):132 - 144.

Scheperjans, F., Hermann, K., Eickhoff, S.B., Amunts, K., Schleicher, A., Zilles, K.: Observer-independent cytoarchitectonic mapping of the human superior parietal cortex. Cerebral Cortex 2008;18(9):846-67.

Fischl, B., Rajendran, N., Busa, E., Augustinack, J., Hinds, O., Mohlberg, H., Amunts, K., Zilles, K.: Cortical folding patterns and predicting cytoarchitecture. Cerebral Cortex 2008;18(8):1973-80.

Caspers, S., Eickhoff, S.B., Geyer, S., Scheperjans, F., Mohlberg, H., Zilles, K., Amunts, K.: The human inferior parietal lobule in stereotaxic space. Brain Structure and Function 2008;212(6):481-95.

Zaborszky, L., Hoemke, L., Mohlberg, H., Schleicher, A., Amunts, K., Zilles, K.: Stereotaxic probabilistic maps of the magnocellular cell groups in human basal forebrain. NeuroImage 2008;42(3):1127-41.

Oishi, K., Zilles, K., Amunts, K., Faria, A., Jiang, H., Xin Li, X., Akhter, K., Hua, K., Woods, R., Toga, A.W., Pike, G.B., Rosa-Neto, P., Evans, A., Zhang, J., Huang, H., Miller, M.I., van Zijl, P.C.M., Mazziotta, J., Mori, S.: Human brain white matter atlas: Identification and assignment of common anatomical structures in superficial white matter. NeuroImage 2008;43(3):447-57.

Eickhoff, S.B., Rottschy, C., Kujovic, M., Palomero-Gallagher, N., Schleicher, A., Zilles, K.: Organizational principles of human visual cortex revealed by receptor mapping. Cerebral Cortex 2008;18(11):2637-45.

Pieperhoff, P., Südmeyer, M., Hömke, L., Zilles, K., Schnitzler, A., Amunts, K.: Detection of structural changes of the human brain in longitudinally acquired MR images by deformation field morphometry: Methodological analysis, validation and application. NeuroImage 2008;43(2):269-87.

Görg B, Qvartskhava N, Keitel V, Bidmon HJ, Selbach O, Schliess F, Häussinger D. Ammonia induces RNA oxidation in cultured astrocytes and brain in vivo. Hepatology. 2008;48(2):567-79.

Eickhoff, S.B., Grefkes, C., Fink, G.R., Zilles, K.: Functional lateralisation of face, hand and trunk representation in anatomically defined human somatosensory areas. Cerebral Cortex 2008;18(12):2820-30.

Bidmon, H.J., Görg, B., Palomero-Gallagher, N., Schleicher, A., Häussinger, D., Speckmann, E.J., Zilles, K.: Glutamine synthetase becomes nitrated and its activity is reduced during repeated seizure activity in the pentylentetrazole model of epilepsy. Epilepsia 2008;49(10):1733-48.

Eickhoff, S.B., Laird, A.R., Grefkes, C., Wang, L.E., Zilles, K., Fox, P.T.: Coordinate-based ALE meta-analysis of neuroimaging data: A random-effects approach based on empirical estimates of spatial uncertainty. Human Brain Mapping (in press)

Hömke, L., Amunts, K., Bönig, L., Fretz, C., Binkofski, F., Zilles, K., Weder, B.: Analysis of lesions in patients with unilateral tactile agnosia using cytoarchitectonic probabilistic maps. Human Brain Mapping (in press)

Scheperjans, F., Eickhoff, S.B., Hömke, L., Mohlberg, H., Hermann, K., Amunts, K., Zilles, K.:Probabilistic maps, morphometry, and variability of cytoarchitectonic areas in human superior parietal cortex. Cerebral Cortex (in press)

Eickhoff, S.B., Heim, S., Zilles, K., Amunts, K.: A systems perspective on the effective connectivity of overt speech production. Phil. Trans. Royal Soc. London (in press)

Palomero-Gallagher, N., Vogt, B.A., Schleicher, A., Mayberg, H.S., Zilles, K.: Receptor architecture of human cingulate cortex: Evaluation of the four-region neurobiological model. Human Brain Mapping (in press)

Hurlemann, R., Schlaepfer, T., Matusch, A., Reich, H., Shah, N.J., Zilles, K., Maier, W., Bauer, A.: Reduced 5-HT(2A) receptor signaling following selective bilateral amygdala damage. Social Cognitive and Affective Neuroscience (in press)
Hilbig H, Beil B, Hilbig H, Call J, Bidmon HJ. Superior olivary complex organization and cytoarchitecture may be correlated with function and catarrhine primate phylogeny. Brain Struct. Funct. (in press).

3. Collabor

The above listed projects are done in collaboration with

Institut for Medicine (INB-3) Research Center Jülich; Prof. Dr. D. Häussinger, Clinic for Gastroenterology, Hepatology and Infectiology, University Düsseldorf; Prof. Dr. O.W. Witte. Neurological Clinic, University, Jena; Prof. Dr. E.-J. Speckmann, Institute for Neurophysiology University Münster; Dr. H. Pannek, Center for Epilepsy, Bethel, Bielefeld; Prof. S. Behrends, Institute for Pharmakology and Toxikology, TU Braunschweig; Prof. H. Hilbig, Department of Anatomy, Universität Leipzig and Dr. J. Call, Max Planck Institute for Evolutionary Anthropology, Leipzig.


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