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28th CiNet Monthly Seminar : Karl Zilles “Multimodal and Multiscale Mapping of Cortical Organization”


CiNet Monthly Seminar

November 30, 2018
16:00 ~ 17:00
CiNet 1F Conference Room

“Multimodal and Multiscale Mapping of Cortical Organization”

Karl Zilles
Senior Professor
Institute of Neuroscience and Medicine, Research Centre Jülich
Host : Hiromasa Takemura ( Kida Group)

Understanding of the anatomical organization of the cerebral cortex requires multimodal and multiscale approaches and the visualization of the different data in a common reference space or brain [1,2,10]. To reach this goal, we develop methods for the analysis of basic aspects of the cortex which enable multiscale imaging from the micron- to the entire brain-dimension, and multimodal imaging by integrating quantitative, observer-independent cytoarchitecture [1,4,7,11], multi-receptor analysis [6,7], and connectivity analysis [3].

1. Quantitative, observer-independent cytoarchitectonic analysis

The cerebral cortex is not homogeneous, but can be subdivided into areas with distinct characteristics in cell distribution and composition of the layers [14]. These cytoarchitectonic features provide the microstructural basis for a reliably parcellation of the cortex [1], and – beyond macroanatomical landmarks [12] – for a profound understanding of neuroimaging data.

Examples illustrating the method, the detection of the degree of interindividual variability (probability maps)[14], and novel maps of the human and monkey cortex will be shown.

2. Multi-receptor fingerprints and their impact on functional networks

Resting-state analyses have become increasingly popular in recent years, providing exciting new insight into the functional network organization of the brain. Functional networks need to have a molecular underpinning, which can be found in the endowment of brain areas with neurotransmitter receptors, i.e. key molecules of signal processing. Their distinct regional and laminar distribution patterns provide the basis for the functional properties of different brain areas [6,7,8,13]. This not only applies to individual areas, but also to brain networks. Assessing the organization of receptor distribution patterns mutually complements the cyto- and fiber architecture on a functional level.

Examples of the regional and laminar distribution of 15 different receptor types in entire brains, particularly in the visual, somatosensory and limbic structures of human [5,6,8,13], monkey [16] and rat [16] brains will be shown. The application of receptor fingerprints will be demonstrated, which enable a characterization of the molecular organization of cortical areas [6,8] and layers [13]. Finally, the impact of fingerprints on the identification of functional networks will be demonstrated.

3. Connectivity: The anatomical ground-truth

The birefringence of neuronal tissue, particularly of myelinated fibers enables the visualization of single nerve fibers and entire fiber tracts in post mortem brains using the technique of Polarized Light Imaging (PLI)[3]. The spatial orientation of fibres can be revealed at an in-plane resolution of 1.3 micrometer. We have used this technique in human, monkey, rat and mouse brains to demonstrate the course of fibre tracts in the white matter [3,9] and the myeloarchitecture of the cerebral cortex [15].

Examples of the spatial orientation of fibres will be demonstrated in serial sections through the visual cortex and the hippocampus [9]. PLI can also serve as an independent method for validation of data based on diffusion weighted imaging. In conclusion, PLI provides an unprecedented spatial resolution of the anatomical ground truth of fibre tracts and reveals a hitherto unknown complexity of structural connectivity.


[1] Amunts, K., Zilles, K.: Architectonic mapping of the human brain beyond Brodmann. Neuron 88: 1086-1107 (2015)
[2] Amunts, K., Lepage, C., Borgeat, L., Mohlberg, H., Dickscheid, T., Rousseau, M.-E., Bludau, S., Lewis, L., Oros-Peusquens, A.-M., Bazin, P.-L., Shah, N.J., Lippert, T., Zilles, K., Evans, A.: The BigBrain – an ultra-high resolution 3D human brain model. Science 340: 1472-1475 (2013)
[3] Axer, M., Amunts, K., Graessel, D., Palm, C., Dammers, J., Axer, H., Pietrzyk, U., Zilles, K.: A novel approach to the human connectome: Ultra-high resolution mapping of fiber tracts in the brain. Neuroimage 54:1091-1101 (2011)
[4] Gomez, J., Barnett, M.A., Natu, V.S., Mezer, A., Palomero-Gallagher, N., Weiner, K.S., Amunts, K., Zilles, K., Grill-Spector, K. (2016). Growth of tissue in human cortex is coupled with the development of face processing. Science 355: 68-71 (2017)
[5] Kedo, O., Zilles, K., Palomero-Gallagher, N., Schleicher, A., Mohlberg, H., Bludau, S., Amunts, K.: Receptor-driven, multimodal mapping of the human amygdala. Brain Struct. Funct. 223:1637-1666 (2017)
[6] Palomero-Gallagher, N., Zilles, K.: Cortical layers: Cyto-, myelo-, receptor- and synaptic architecture in human cortical areas. Neuroimage DOI:10.1016/j.neuroimage.2017.08.035 (2017)
[7] Palomero-Gallagher, N., Zilles, K.: Cyto- and Receptorarchitectonic Mapping of the Human Brain, pp. 355-388. In: Huitinga, I. and Webster, M.J. (eds.) Brain Banking. Elsevier, San Diego (2018)
[8] Palomero-Gallagher, N., Amunts, K., Zilles, K.: Transmitter receptor distribution in the human brain. In: Brain Mapping: An Encyclopedic Reference (Ed. Toga, A.W.). Section Anatomy & Physiology (Eds. Zilles, K., Amunts, K.), Chapter 221: 261-275 Elsevier Academic Press, San Diego (2015)
[9] Zeineh, M.M., Palomero-Gallagher, N., Axer, M., Graessel, D., Goubran, M., Wree, A., Woods, R., Amunts, K., Zilles, K.: Direct visualization and mapping of the spatial course of fiber tracts at microscopic resolution in the human hippocampus. Cerebral Cortex 27(3):1779-1794 (2017)
[10] Zilles, K., Amunts, K.: Centenary of Brodmann’s map conception and fate. Nature Rev. Neurosci. 11: 139-145 (2010)
[11] Zilles, K., Amunts, K.: Segregation and wiring in the brain. Science 335: 1582-1584 (2012)
[12] Zilles, K., Amunts, K.: Anatomical basis for functional specialization. In: fMRI: From Nuclear Spins to Brain Function. Uludag, K., Ugurbil, K., Berliner, L. (Eds.), pp. 27-66. Springer, New York (2015)
[13] Zilles, K., Palomero-Gallagher, N.: Multiple transmitter receptors in regions and layers of the human cerebral cortex. Front. Neuroanat. 11:78. doi: 10.3389/fnana.2017.00078 (2017)
[14] Zilles, K., Palomero-Gallagher, N., Bludau, S., Mohlberg, H., Amunts, K.: Cytoarchitecture and maps of the human cerebral cortex. In: Brain Mapping: An Encyclopedic Reference (Ed. Toga, A.W.). Section Anatomy & Physiology (Eds. Zilles, K., Amunts, K.), Chapter 207: 115-135, Elsevier Academic Press, San Diego (2015)
[15] Zilles, K., Palomero-Gallagher, N., Graessel, D., Schloemer, P., Cremer, M., Woods, R., Amunts, K., Axer, M.: High-resolution fiber and fiber tract imaging using polarized light microscopy in the human, monkey, rat and mouse brain. In: Rockland K.S. (Ed.), Axons and Brain Architecture, pp. 369-389. Elsevier Academic Press, San Diego (2016)
[16] Zilles, K., Palomero-Gallagher, N.: Comparative analysis of receptor subtypes that identify primary cortical sensory areas. In (Kaas, J., Striedter, G., Krubitzer, L., Herculano-Houzel, S., Preuss, T., eds.) Evolution of the Nervous Systems. Second Edition, Vol. 2 The Nervous Systems of Early Mammals and their Evolution, pp. 225-245. Elsevier, Oxford (2017)