title: BDNF Val66Met polymorphism influence on striatal blood-level-dependent response to monetary feedback depends on valence and agency.
abstract: Animal work implicates the brain-derived neurotrophic factor (BDNF) in function of the ventral striatum (VS), a region known for its role in processing valenced feedback. Recent evidence in humans shows that BDNF Val66Met polymorphism modulates VS activity in anticipation of monetary feedback. However, it remains unclear whether the polymorphism impacts the processing of self-attributed feedback differently from feedback attributed to an external agent. In this study, we emphasize the importance of the feedback attribution because agency is central to computational accounts of the striatum and cognitive accounts of valence processing. We used functional magnetic resonance imaging and a task, in which financial gains/losses are either attributable to performance (self-attributed, SA) or chance (externally-attributed, EA) to ask whether BDNF Val66Met polymorphism predicts VS activity. We found that BDNF Val66Met polymorphism influenced how feedback valence and agency information were combined in the VS and in the right inferior frontal junction (IFJ). Specifically, Met carriers' VS response to valenced feedback depended on agency information, while Val/Val carriers' VS response did not. This context-specific modulation of valence effectively amplified VS responses to SA losses in Met carriers. The IFJ response to SA losses also differentiated Val/Val from Met carriers. These results may point to a reduced allocation of attention and altered motivational salience to SA losses in Val/Val compared to Met carriers. Implications for major depressive disorder are discussed.
authors.affiliation: Laboratory for Social and Neural Systems Research, Department of Economics, University of Zurich, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Chumbley
authors.affiliation: Department of Psychophysiology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Späti
authors.affiliation: Department of Psychology, University of Zurich, Switzerland; Neuroscience Center, University and ETH Zurich, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Dörig
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, Hospital of Psychiatry, University of Zurich, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Brakowski
authors.affiliation: Department of Psychology, University of Zurich, Switzerland; Department of Psychology, University of Bern, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Grosse Holtforth
authors.affiliation: Neuroscience Center, University and ETH Zurich, Switzerland; Department of Psychiatry, Psychotherapy and Psychosomatics, Hospital of Psychiatry, University of Zurich, Switzerland; Zurich Center for Integrative Human Physiology, University of Zurich, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Seifritz
authors.affiliation: Neuroscience Center, University and ETH Zurich, Switzerland; Zurich Center for Integrative Human Physiology, University of Zurich, Switzerland; Preclinical Laboratory for Translational Research into Affective Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Hospital of Psychiatry, University of Zurich, Switzerland. Electronic address: spinellisimona@gmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Spinelli
mesh_terms: D000328:Adult; D001931:Brain Mapping; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002560:Cerebrovascular Circulation / Q000502:physiology; D030141:Feedback, Psychological / Q000502:physiology*; D005260:Female; D005625:Frontal Lobe / Q000098:blood supply / Q000502:physiology; D060005:Genotyping Techniques; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009039:Motion Perception / Q000502:physiology; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D011594:Psychometrics; D012054:Reinforcement, Psychology; D012649:Self Concept; D066328:Ventral Striatum / Q000098:blood supply / Q000502:physiology*; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human
keywords: Brain-derived neurotrophic factor gene; Val66Met; feedback processing; functional magnetic resonance imaging; inferior frontal junction; ventral striatum