title: Lateralization of the serotonin-1A receptor distribution in language areas revealed by PET.
abstract: Lateralization is a well described aspect of the human brain. A plethora of morphological, cytological and functional studies describes hemispheric asymmetry in auditory and language areas. However, no study has reported cortical lateralization in the healthy human brain in vivo on the level of neurotransmitter receptors and in relation to functional organization so far. In this study, we assessed the distribution of the main inhibitory serotonergic receptor (the 5-HT1A receptor) and analyzed its regional binding with regard to hemisphere, sex and plasma levels of sex steroid hormones (testosterone, estradiol, progesterone). We quantified the 5-HT1A receptor binding potential by positron emission tomography (PET) using the highly selective and specific radioligand [carbonyl-11C]WAY-100635 and measured hormone levels in thirty-four (16 females, 18 males) healthy right-handed subjects. The obtained data were analyzed in an automated region of interest (ROI) based approach investigating 14 auditory, language and limbic areas. We found significantly higher 5-HT1A receptor binding in the superior and middle frontal gyri of the right hemisphere, the triangular and orbital parts of the inferior frontal gyrus, the supramarginal gyrus, the superior gyrus of the temporal pole and the middle temporal gyrus. Regions of the primary and secondary auditory cortex (Heschl's gyrus and superior temporal gyrus) and the Rolandic operculum displayed significantly higher receptor binding in the left hemisphere. 5-HT1A receptor binding was 1.8-2.9% higher in right frontal ROIs and 2-3.6% higher in left primary and secondary auditory regions. There was no hemispheric difference in 5-HT(1A) receptor binding in the hippocampus, amygdala, and insula. Post-hoc testing suggested that lateralization of 5-HT1A receptor binding differed between the sexes in the triangular part of the inferior frontal gyrus. For the first time, this PET study shows lateralization of the main inhibitory receptor of the serotonergic system in functionally asymmetric organized regions of the healthy human brain in vivo.
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Fink
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wadsak
authors.forename: Markus
authors.initials: M
authors.lastname: Savli
authors.forename: Patrycja
authors.initials: P
authors.lastname: Stein
authors.forename: Ulrike
authors.initials: U
authors.lastname: Moser
authors.forename: Andreas
authors.initials: A
authors.lastname: Hahn
authors.forename: Leonhard-Key
authors.initials: LK
authors.lastname: Mien
authors.forename: Kurt
authors.initials: K
authors.lastname: Kletter
authors.forename: Markus
authors.initials: M
authors.lastname: Mitterhauser
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kasper
authors.forename: Rupert
authors.initials: R
authors.lastname: Lanzenberger
mesh_terms: D000328:Adult; D001307:Auditory Perception / Q000502:physiology*; D001921:Brain / Q000000981:diagnostic imaging / Q000502:physiology*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D005260:Female; D007839:Functional Laterality / Q000502:physiology*; D006801:Humans; D007802:Language; D008297:Male; D010879:Piperazines / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods*; D011725:Pyridines / Q000493:pharmacokinetics*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D002250:Carbon Radioisotopes; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide