title: Dopaminergic Modulation of Cognitive Preparation for Overt Reading: Evidence from the Study of Genetic Polymorphisms.
abstract: Choosing and implementing the rules for contextually adequate behavior depends on frontostriatal interactions. Observations in Parkinson's disease and pharmacological manipulations of dopamine transmission suggest that these corticobasal loops are modulated by dopamine. To determine, therefore, the physiological contributions of dopamine to task-rule-related processing, we performed a cue-target fMRI reading paradigm in 71 healthy participants and investigated the effects of COMT Val158Met, DAT1 VNTR 9/10, and DRD2/ANKK1 polymorphisms. The DRD2/ANKK1 polymorphism did not affect results. Intermediate prefrontal dopamine concentrations in COMT Val158Met heterozygotes facilitated preparatory interactions between the mesial prefrontal cortex and the left striatum during preparation for overt reading. To our knowledge, this is the first report of an inverted U-shaped curve modulation of cognition-related brain activity by prefrontal dopamine levels. In contrast, a linear effect of COMT Val158Met and DAT1 VNTR 9/10 polymorphisms on preparatory activity in the left inferior frontal gyrus pointed to a negative interaction between tonic lateral prefrontal and phasic subcortical dopamine. The COMT Val158Met polymorphism affected also feedforward and feedback processing in the sensorimotor speech system. Our results suggest that dopamine modulates corticobasal interactions on both the cortical and subcortical level but differently depending on the specific cognitive subprocesses involved.
authors.affiliation: Cognitive Neuroscience Group, Brain Imaging Center, Institute for Transfusion Medicine and Immunohematology, Goethe University, Frankfurt, Germany.|Department of Neurology, Institute for Transfusion Medicine and Immunohematology, Goethe University, Frankfurt, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Arnold
authors.affiliation: Experimental Neurology, Institute for Transfusion Medicine and Immunohematology, Goethe University, Frankfurt, Germany.
authors.forename: Suzana
authors.initials: S
authors.lastname: Gispert
authors.affiliation: German Red Cross Blood Service Baden-Wuerttemberg-Hessen, Institute for Transfusion Medicine and Immunohematology, Goethe University, Frankfurt, Germany.
authors.forename: Halvard
authors.initials: H
authors.lastname: Bonig
authors.affiliation: Department of Neurology, Institute for Transfusion Medicine and Immunohematology, Goethe University, Frankfurt, Germany.
authors.forename: Frederic
authors.initials: F
authors.lastname: von Wegner
authors.affiliation: Department of Neurology, Institute for Transfusion Medicine and Immunohematology, Goethe University, Frankfurt, Germany.
authors.forename: Sriramya
authors.initials: S
authors.lastname: Somasundaram
authors.affiliation: Cognitive Neuroscience Group, Brain Imaging Center, Institute for Transfusion Medicine and Immunohematology, Goethe University, Frankfurt, Germany.|Department of Neurology, Institute for Transfusion Medicine and Immunohematology, Goethe University, Frankfurt, Germany.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Kell
mesh_terms: D000328:Adult; D000071437:Axon Guidance / Q000235:genetics / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D001931:Brain Mapping; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003071:Cognition / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D018598:Minisatellite Repeats; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011932:Reading; D017448:Receptors, Dopamine D2 / Q000235:genetics; D013060:Speech; D055815:Young Adult
chemical_list: C581293:DRD2 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D017448:Receptors, Dopamine D2; C493214:SLC6A3 protein, human; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; C489948:ANKK1 protein, human; D017346:Protein Serine-Threonine Kinases; D004298:Dopamine
keywords: COMT Val158Met; DAT1 VNTR 9/10; fMRI; inverted U-shaped curved cortical—subcortical interactions; speech production