title: Different Roles of COMT and HTR2A Genotypes in Working Memory Subprocesses.
abstract: Working memory is linked to the functions of the frontal areas, in which neural activity is mediated by dopaminergic and serotonergic tones. However, there is no consensus regarding how the dopaminergic and serotonergic systems influence working memory subprocesses. The present study used an imaging genetics approach to examine the interaction between neurochemical functions and working memory performance. We focused on functional polymorphisms of the catechol-O-methyltransferase (COMT) Val(158)Met and serotonin 2A receptor (HTR2A) -1438G/A genes, and devised a delayed recognition task to isolate the encoding, retention, and retrieval processes for visual information. The COMT genotypes affected recognition accuracy, whereas the HTR2A genotypes were associated with recognition response times. Activations specifically related to working memory were found in the right frontal and parietal areas, such as the middle frontal gyrus (MFG), inferior frontal gyrus (IFG), anterior cingulate cortex (ACC), and inferior parietal lobule (IPL). MFG and ACC/IPL activations were sensitive to differences between the COMT genotypes and between the HTR2A genotypes, respectively. Structural equation modeling demonstrated that stronger connectivity in the ACC-MFG and ACC-IFG networks is related to better task performance. The behavioral and fMRI results suggest that the dopaminergic and serotonergic systems play different roles in the working memory subprocesses and modulate closer cooperation between lateral and medial frontal activations.
authors.affiliation: Human Information Science Laboratory, NTT Communication Science Laboratories, NTT Corporation, Atsugi, Kanagawa 243-0198, Japan; Department of Child Development, United Graduate School of Child Development, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Hirohito M
authors.initials: HM
authors.lastname: Kondo
authors.affiliation: Division of Cognitive Psychology in Education, Graduate School of Education, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Nomura
authors.affiliation: Human Information Science Laboratory, NTT Communication Science Laboratories, NTT Corporation, Atsugi, Kanagawa 243-0198, Japan; Department of Information Processing, Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology, Yokohama, Kanagawa 226-8503, Japan.
authors.forename: Makio
authors.initials: M
authors.lastname: Kashino
mesh_terms: D000328:Adult; D001931:Brain Mapping; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D005625:Frontal Lobe / Q000502:physiology; D005838:Genotype; D006179:Gyrus Cinguli / Q000502:physiology; D006801:Humans; D008297:Male; D008570:Memory, Short-Term; D009415:Nerve Net / Q000502:physiology; D010296:Parietal Lobe / Q000502:physiology; D011110:Polymorphism, Genetic; D017397:Prefrontal Cortex / Q000502:physiology; D011930:Reaction Time; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D014796:Visual Perception; D055815:Young Adult
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D002394:Catechol O-Methyltransferase