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@INPROCEEDINGS{Savil:150626,
      author       = {Savil, Markus and Ding, Yu-Shin and Neumeister, Alexander
                      and Bauer, Andreas and Wadsak, Wolfgang and Mitterhauser,
                      Markus and Kasper, Siegfried and Lanzenberger, Rupert},
      title        = {{S}erotonergic organiziation of the human brain: {A}
                      multi-tracer {P}ositron {E}mission {T}omography study of
                      healthy subjects},
      reportid     = {FZJ-2014-00673},
      year         = {2013},
      abstract     = {Introduction The cerebral cortex has often been subdivided
                      into numerous areas characterized by structural, functional
                      and cytoarchitectonic features while protein-based
                      organizations schemes are lacking [1]. In the current study
                      we propose a new organizational model of the brain based on
                      protein distributions of the serotonergic system including
                      the major inhibitory (5-HT1A and 5-HT1B), the major
                      excitatory (5-HT2A) receptors and the transporter (SERT) of
                      healthy subjects measured with positron emission tomography
                      (PET) and dedicated radioligands. Methods Dynamic PET scans
                      were performed in 95 healthy subjects (age=28.0±6.9 years;
                      $59\%$ males) divided into 4 groups using the selective
                      radioligands [carbonyl-11C]WAY100635 for 5-HT1A,
                      [18F]altanserin for 5-HT2A, [11C]P943 for 5-HT1B and
                      [11C]DASB for SERT. Similarities between receptor
                      distribution patterns were analyzed by means of a
                      hierarchical cluster analysis using Euclidean distances in
                      combination with the Ward-linkage method as implemented in
                      R2.15.2. All values were z-transformed across areas prior to
                      analysis in order to establish equal weight between the
                      protein bindings. Results Hierarchical cluster analysis of
                      group-average binding potential values revealed two main
                      protein-distinct clusters. The first exclusively comprised
                      subcortical areas such as the raphe nuclei, thalamus,
                      pallidum, caudate nucleus, putamen, midbrain, and striatum,
                      whereas in the second the remaining cortical areas were
                      aggregated. The two main subclusters from the cortical areas
                      partly follow lobular definitions. The first predominantly
                      comprises frontal, parietal, occipital, and cingulate
                      regions of interest (ROIs) while no marked distinctions are
                      found in further subclusters. The second mainly contains
                      temporal ROIs, but also some frontal ROIs and the
                      hippocampal-amygdala ROIs although with stronger Euclidean
                      distance than cortical ROIs. Discussion Applying a
                      data-driven approach we identified brain regions of similar
                      features within the serotonergic system. Interestingly,
                      spatially distant ROIs such as the subcortical areas were
                      identified with close molecular similarity in contrast to
                      cortical ROIs as given by the large Euclidean distance
                      between these two clusters. The two clusters found were in
                      accordance with the familiar classification of cortical und
                      subcortical ROIs. In the lower clusters stringent lobular
                      definition vanishes. This result reflects an explicit
                      hierarchical organization of the serotonergic system and
                      emphasizes functions and interactions of the binding
                      proteins beyond topologies. Acknowledgements: This research
                      was partly supported by grants from the Austrian National
                      Bank (OeNB 13214 to R.L. and OeNB 13675 to M.M.), the
                      Austrian Science Fund and by an unrestricted
                      investigator-initiated research grant from H. Lundbeck A/S
                      to S.K. References Savli M, Bauer A, Mitterhauser M, Ding
                      YS, Hahn A, Kroll T, Neumeister A, Haeusler D, Ungersboeck
                      J, Henry S, Isfahani SA, Rattay F, Wadsak W, Kasper S,
                      Lanzenberger R: Normative database of the serotonergic
                      system in healthy subjects using multitracer PET.
                      NeuroImage, 2012; 63: 447–459.},
      month         = {Sep},
      date          = {2013-09-16},
      organization  = {13th Annual Meeting of the Austrian
                       Neuroscience Association, Vienna
                       (Austria), 16 Sep 2013 - 19 Sep 2013},
      cin          = {INM-2},
      cid          = {I:(DE-Juel1)INM-2-20090406},
      pnm          = {333 - Pathophysiological Mechanisms of Neurological and
                      Psychiatric Diseases (POF2-333)},
      pid          = {G:(DE-HGF)POF2-333},
      typ          = {PUB:(DE-HGF)1},
      url          = {https://juser.fz-juelich.de/record/150626},
}