title: Ventro-lateral prefrontal activity during working memory is modulated by MAO A genetic variation.
abstract: Several lines of evidence have highlighted the role of the serotonergic system in working memory (WM) processes. The X-linked Mono-Amine Oxidase A (MAO A) gene, coding for an enzyme especially involved in the serotonin (5-HT) catabolism, presents a well-characterized functional polymorphism consisting in a variable number of tandem repeats (VNTR) in the promoter region with high activity and low activity variants. The high activity allele carriers have been associated with higher enzyme expression, lower amine concentration and altered prefrontal cortex (PFC) function during motor inhibition, but a direct effect of MAO A genotype on WM-related brain activity has not been demonstrated. We have studied the relationship of this polymorphism to brain activity elicited by a spatial working memory task (n-back) using blood oxygenation level-dependent functional magnetic resonance imaging in 30 healthy male individuals matched for a series of demographic and genetic variables (COMT Val108/158Met). We show that the high activity allele was significantly (p-level<0,001) associated with increased activity of the right ventro-lateral PFC (VLPFC, BA 47) during the high load condition of the n-back task. Our data reveal pronounced genotype-related functional changes in specific prefrontal region (VLPFC) subserving spatial working memory. Moreover, given the well-known role of this area in inhibitory control, our finding also provides new evidence for the involvement of 5-HT in PFC-mediated WM function.
authors.affiliation: Institute of Neurological Sciences, National Research Council, Piano Lago di Mangone, Cosenza, Italy. a.cerasa@isn.cnr.it
authors.forename: Antonio
authors.initials: A
authors.lastname: Cerasa
authors.forename: Maria C
authors.initials: MC
authors.lastname: Gioia
authors.forename: Francesco
authors.initials: F
authors.lastname: Fera
authors.forename: Luca
authors.initials: L
authors.lastname: Passamonti
authors.forename: Maria
authors.initials: M
authors.lastname: Liguori
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Lanza
authors.forename: Maria
authors.initials: M
authors.lastname: Muglia
authors.forename: Angela
authors.initials: A
authors.lastname: Magariello
authors.forename: Aldo
authors.initials: A
authors.lastname: Quattrone
mesh_terms: D000293:Adolescent; D000328:Adult; D001923:Brain Chemistry / Q000235:genetics; D001931:Brain Mapping; D004252:DNA Mutational Analysis; D004789:Enzyme Activation / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D005787:Gene Frequency; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D008995:Monoamine Oxidase / Q000235:genetics*; D009433:Neural Inhibition / Q000235:genetics; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic / Q000235:genetics*; D017397:Prefrontal Cortex / Q000033:anatomy & histology / Q000201:enzymology*; D012701:Serotonin / Q000378:metabolism*; D013028:Space Perception / Q000502:physiology; D015854:Up-Regulation / Q000235:genetics
chemical_list: D007527:Isoenzymes; D012701:Serotonin; D008995:Monoamine Oxidase