Regional binding potential (<i>BP</i>) values for 5-HT_2A and D₂ receptors in cerebral cortical regions.

<p>Mean <i>BP</i> values for [¹⁸F]altanserin for 5-HT_2A receptors (blue) and [¹¹C]FLB 457 for D₂ receptors (red) were plotted for 76 cerebral regions. The numbers represent regions defined in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0189318#pone.0189318.t001" target="_blank">Table 1</a>. Raw data of <i>BP</i> values is available as supporting information (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0189318#pone.0189318.s001" target="_blank">S1 File</a>).</p

A diagram of procedures of correlation and clustering analyses.

<p>A) Individual binding potential (<i>BP)</i> values of [¹⁸F]altanserin and [¹¹C]FLB 457 were extracted for 76 regions in seven subjects. B) A correlation matrix of correlation coefficients was calculated between <i>BP</i> values of [¹⁸F]altanserin and [¹¹C]FLB 457 for the 76 regions. An example of a scatter diagram (top) shows the correlation between <i>BP</i> values of [¹¹C]FLB 457 in the left superior parietal gyrus (region #53) and the <i>BP</i> values of [¹⁸F]altanserin in the left fusiform gyrus (region #49). C) Biclustering was performed on the matrix using an iterative signature algorithm (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0189318#sec005" target="_blank">Methods</a>). R⁽ⁿ⁾ and C⁽ⁿ⁾: sets of rows and columns at the n^th iteration, Score_row and Score_column: the evaluation scores for the rows and columns, Thr.row and Thr.column: thresholds for the rows and columns. D) Two clusters of regions were identified (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0189318#sec014" target="_blank">Results</a>).</p

Correlation matrix of regions extracted as clusters using the biclustering analysis and their adjacent regions (outside of the yellow boxes).

<p>(A) The first cluster consisted of correlations between 5-HT_2A receptor binding potentials (<i>BP</i>) for the frontal and parietal cortices and D₂ receptor <i>BP</i> for broad cortical regions (71 regions). Regions in the first cluster (inside the yellow boxes): supplementary motor area (19, 20), superior parietal gyrus (53, 54), paracentral lobule (63, 64); regions adjacent to the first cluster (outside of the yellow boxes): inferior parietal gyrus (55, 56), postcentral gyrus (51, 52), precuneus (61, 62), and superior frontal gyrus (3, 4). (B) The second cluster consisted of correlations between 5-HT_2A receptor <i>BP</i> for the bilateral hippocampi and D₂ receptor <i>BP</i> for broad regions (73 regions) in the cerebral cortex. Regions in the second cluster (inside the yellow boxes): hippocampus (33, 34), regions adjacent to the second cluster (outside of the yellow boxes): parahippocampus (35, 36) and fusiform (49, 50).</p

Brain regions used for the correlation matrix analysis.

<p>Brain regions used for the correlation matrix analysis.</p

Correlation matrix of regions containing 5-HT_2A and D₂ receptors.

<p>A correlation matrix was generated based on Spearman’s correlation coefficients (<i>r</i> values) between individual binding potential values of [¹⁸F]altanserin for 5-HT_2A receptors (columns) and [¹¹C]FLB457 for D₂ receptors (rows) in 76 regions. The numbers represent regions defined in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0189318#pone.0189318.t001" target="_blank">Table 1</a>. Raw data of the matrix is available as supporting information (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0189318#pone.0189318.s002" target="_blank">S2 File</a>).</p

Each atlas shows regional pairs extracted as clusters using the bicluster analysis.

<p><b>(A)</b> Regions for 5-HT_2A receptors and those for D₂ receptors in the first cluster. <b>(B)</b> Regions for 5-HT_2A receptors and those for D₂ receptors in the second cluster.</p

Anatomical relationships between serotonin 5-HT_2A and dopamine D₂ receptors in living human brain

<div><p>Serotonin 2A (5-HT_2A) receptors and dopamine D₂ receptors are intimately related to the physiology and pathophysiology of neuropsychiatric disorders. A large number of studies have reported the effectiveness of psychotropic agents targeting 5-HT_2A and D₂ receptors in these disorders. In addition to the individual functions of these receptors, the interaction between the two neurotransmitter systems has been studied in the living brain. However, little is known about their regional relationship in individual human brains. We investigated regional relationships between 5-HT_2A and D₂ receptors using positron emission tomography (PET) and a bicluster analysis of the correlation matrix of individual variation in the two receptor densities to identify groups of distinctive regional correlations between the two receptors.</p><p>Methods</p><p>Seven healthy volunteers underwent PET scans with [¹⁸F]altanserin and [¹¹C]FLB 457 for 5-HT_2A and D₂ receptors, respectively. As a measure of receptor density, a binding potential (<i>BP</i>) was calculated from PET data for 76 cerebral cortical regions. A correlation matrix was calculated between the binding potentials of [¹⁸F]altanserin and [¹¹C]FLB 457 for those regions. The regional relationships were investigated using a bicluster analysis of the correlation matrix with an iterative signature algorithm.</p><p>Results</p><p>We identified two clusters of regions. The first cluster identified a distinct profile of correlation coefficients between 5-HT_2A and D₂ receptors, with the former in regions related to sensorimotor integration (supplementary motor area, superior parietal gyrus, and paracentral lobule) and the latter in most cortical regions. The second cluster identified another distinct profile of correlation coefficients between 5-HT_2A receptors in the bilateral hippocampi and D₂ receptors in most cortical regions.</p><p>Conclusions</p><p>The observation of two distinct clusters in the correlation matrix suggests regional interactions between 5-HT_2A and D₂ receptors in sensorimotor integration and hippocampal function. A bicluster analysis of the correlation matrix of these neuroreceptors may be beneficial in understanding molecular networks in the human brain.</p></div

Brain regions used for the correlation matrix analysis.

<p>Brain regions used for the correlation matrix analysis.</p