% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@INPROCEEDINGS{Savli:150643,
      author       = {Savli, Markus and Ding, Yu-Shin and Neumeister, Alexander
                      and Bauer, Andreas and Häusler, Daniela and Wadsak,
                      Wolfgang and Mitterhauser, Markus and Lanzenberger, Rupert},
      title        = {{H}ierarchical organization of the serotonergic system: {A}
                      multi-tracer {PET} study on healthy subjects},
      reportid     = {FZJ-2014-00690},
      year         = {2013},
      abstract     = {Introduction The serotonergic system is a highly diverse
                      composition of various pre- and postsynaptic receptor
                      subtypes and the serotonin transporter. Previous in vivo and
                      postmortem studies revealed a rather distinct distribution
                      pattern of these proteins throughout the human brain [1-2].
                      The cerebral cortex has often been subdivided into numerous
                      areas characterized by structural, functional and
                      cytoarchitectonic features [3] while protein-based
                      organizations schemes are lacking. 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. 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. After
                      motion correction and spatial normalization in SPM8 dynamic
                      PET scans were quantified from radioactivity concentrations
                      by a multi-linear reference tissue model (MRTM2; 5HT1A,
                      5-HT1B, SERT; BPND) and a bolus/infusion approach (5HT2A;
                      BPP) in PMOD 3.3. A standard template in MNI stereotactic
                      space served for ROI delineation. The ROI template based on
                      the macro-anatomical criteria according to AAL (automated
                      anatomical labeling) including 52 regions [4]. 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 R2.15.0. All values were z-transformed across
                      areas prior to analysis in order to establish equal weight
                      between the protein bindings. Results Receptor densities as
                      represented by binding potentials were computed for all
                      ROIs. Hierarchical cluster analysis of group-average BP
                      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. Of note is the strikingly
                      pronounced dissimilarity between these two clusters given by
                      the high distance. In the cortical cluster occipital,
                      parietal and frontal ROIs displayed closer similarities than
                      temporal ROIs. Basal ganglia ROIs showed shorter Euclidean
                      distance than raphe nuclei in the subcortical cluster. XIth
                      International Conference on Quantification of Brain Function
                      with PET, May 20-23, 2013, Shanghai, China Discussion We
                      quantified in vivo PET data of 4 key proteins of the
                      serotonergic system and subsequently used a data-driven
                      approach to identify 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.
                      Furthermore, temporal ROIs but also some frontal ROIs (ACC,
                      Insula) exert a similar role as opposed to the remaining
                      lobes. This result reflects an explicit hierarchical
                      organization of the serotonergic system and emphasizes
                      functions and interactions of the binding proteins beyond
                      topologies.},
      month         = {May},
      date          = {2013-05-20},
      organization  = {XIth International Conference on
                       Quantification of Brain Function with
                       PET, Shanghai (China), 20 May 2013 - 23
                       May 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/150643},
}