Região de Broca: novos princípios organizacionais e mapeamento de receptor múltiplo

quinta-feira, setembro 23, 2010

Broca's Region: Novel Organizational Principles and Multiple Receptor Mapping

Katrin Amunts1,2#*, Marianne Lenzen1,2,3#, Angela D. Friederici3, Axel Schleicher4, Patricia Morosan1, Nicola Palomero-Gallagher1, Karl Zilles1,4

1 Research Centre Jülich, Institute for Neuroscience and Medicine (INM-1, INM-2), Jülich, Germany, 2 Jülich-Aachen Research Alliance (JARA), RWTH Aachen University, Department of Psychiatry and Psychotherapy, Aachen, Germany, 3 Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, 4 C. u. O. Vogt-Institute for Brain Research, University of Duesseldorf, Duesseldorf, Germany

Abstract

There is a considerable contrast between the various functions assigned to Broca's region and its relatively simple subdivision into two cytoarchitectonic areas (44 and 45). Since the regional distribution of transmitter receptors in the cerebral cortex has been proven a powerful indicator of functional diversity, the subdivision of Broca's region was analyzed here using a multireceptor approach. The distribution patterns of six receptor types using in vitro receptor autoradiography revealed previously unknown areas: a ventral precentral transitional cortex 6r1, dorsal and ventral areas 44d and 44v, anterior and posterior areas 45aand 45p, and areas op8 and op9 in the frontal operculum. A significant lateralization of receptors was demonstrated with respect to the cholinergic M2 receptor, particularly in area 44v+d. We propose a new concept of the anterior language region, which elucidates the relation between premotor cortex, prefrontal cortex, and Broca's region. It offers human brain homologues to the recently described subdivision of area 45, and the segregation of the ventral premotor cortex in macaque brains. The results provide a novel structural basis of the organization of language regions in the brain.

Author Summary

Broca's region is involved in many aspects of language processing in the brain. Such detailed functional diversity, however, is in contrast to its classical anatomical subdivision into only two cortical areas. Since the regional distribution of neurotransmitter receptors has been proven to be a powerful indicator of functional segregation, we revised the subdivision of Broca's region by analyzing the distribution of six different receptor types in the human brain. On the basis of these results, we propose a novel map of Broca's and neighboring regions with several, previously unknown areas. Moreover, a significant left-sided interhemispheric asymmetry of receptors was found, mainly for the cholinergic muscarinic M2 type. This asymmetry correlates with the well-known left-sided dominance for language. Finally, we present a model of the molecular organization of the anterior human language region and neighboring prefrontal and motor areas on the basis of similarities in their receptor patterns. This model contributes to our understanding of the relation between motor areas and classical Broca region. Our results are important for future studies of the functional segregation and the role of mirror neurons in the human brain, and are relevant for revealing homologies between human and macaque brains.

Citation: Amunts K, Lenzen M, Friederici AD, Schleicher A, Morosan P, et al. (2010) Broca's Region: Novel Organizational Principles and Multiple Receptor Mapping. PLoS Biol 8(9): e1000489. doi:10.1371/journal.pbio.1000489

Academic Editor: David Poeppel, New York University, United States of America

Received: March 15, 2010; Accepted: August 10, 2010; Published: September 21, 2010

Copyright: © 2010 Amunts et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This work was supported by the Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany (AF), the Bundesministerium für Bildung und Forschung (01GW0771, 01GW0623; KA), and the Deutsche Forschungsgemeinschaft (AM 118/1–2). The study was partially supported by the Initiative and Networking Fund of the Helmholtz Association within the Helmholtz Alliance on Systems Biology (KZ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Abbreviations: 6r1, ventral precentral transitional area located between area 6 and area 44 of Brodmann;6v1, 6v2, ventrally located areas within a region defined as area 6 by Brodmann; GLI, grey level index; op 5–7, opercular areas, located caudally and ventrally to the region of interest; op 8 and op 9, opercular areas 8 and 9; ROI, region of interest

* E-mail: k.amunts@fz-juelich.de

# These authors contributed equally to this work.

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