title: Altered brain activation in a reversal learning task unmasks adaptive changes in cognitive control in writer's cramp.
abstract: Previous receptor binding studies suggest dopamine function is altered in the basal ganglia circuitry in task-specific dystonia, a condition characterized by contraction of agonist and antagonist muscles while performing specific tasks. Dopamine plays a role in reward-based learning. Using fMRI, this study compared 31 right-handed writer's cramp patients to 35 controls in reward-based learning of a probabilistic reversal-learning task. All subjects chose between two stimuli and indicated their response with their left or right index finger. One stimulus response was rewarded 80%, the other 20%. After contingencies reversal, the second stimulus response was rewarded in 80%. We further linked the DRD2/ANKK1-TaqIa polymorphism, which is associated with 30% reduction of the striatal dopamine receptor density with reward-based learning and assumed impaired reversal learning in A + subjects. Feedback learning in patients was normal. Blood-oxygen level dependent (BOLD) signal in controls increased with negative feedback in the insula, rostral cingulate cortex, middle frontal gyrus and parietal cortex (pFWE < 0.05). In comparison to controls, patients showed greater increase in BOLD activity following negative feedback in the dorsal anterior cingulate cortex (BA32). The genetic status was not correlated with the BOLD activity. The Brodmann area 32 (BA32) is part of the dorsal anterior cingulate cortex (dACC) that plays an important role in coordinating and integrating information to guide behavior and in reward-based learning. The dACC is connected with the basal ganglia-thalamo-loop modulated by dopaminergic signaling. This finding suggests disturbed integration of reinforcement history in decision making and implicate that the reward system might contribute to the pathogenesis in writer's cramp.
authors.affiliation: Department of Neurology, Kiel University, Germany.
authors.forename: Kirsten E
authors.initials: KE
authors.lastname: Zeuner
authors.affiliation: Department of Neurology, Kiel University, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Knutzen
authors.affiliation: Department of Neurology, Kiel University, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Granert
authors.affiliation: Department of Neurology, Kiel University, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Sablowsky
authors.affiliation: Department of Neurology, Kiel University, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Götz
authors.affiliation: Department of Radiology and Neuroradiology, Kiel University, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Wolff
authors.affiliation: Department of Radiology and Neuroradiology, Kiel University, Germany.
authors.forename: Olav
authors.initials: O
authors.lastname: Jansen
authors.affiliation: Movement Disorders Section, Department of Neurology, Hannover Medical School, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Dressler
authors.affiliation: Department of Neurology, Kiel University, Germany.
authors.forename: Susanne A
authors.initials: SA
authors.lastname: Schneider
authors.affiliation: Institute of Neurogenetics, University of Lübeck, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Klein
authors.affiliation: Department of Neurology, Kiel University, Germany.
authors.forename: Günther
authors.initials: G
authors.lastname: Deuschl
authors.affiliation: Department of Neurology, Kiel University, Germany.
authors.forename: Thilo
authors.initials: T
authors.lastname: van Eimeren
authors.affiliation: Department of Neurology, Kiel University, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Witt
mesh_terms: D000222:Adaptation, Physiological; D000328:Adult; D000368:Aged; D001479:Basal Ganglia / Q000503:physiopathology; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D003071:Cognition / Q000502:physiology*; D020821:Dystonic Disorders / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D000068156:Formative Feedback; D005838:Genotype; D006179:Gyrus Cinguli / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics; D012193:Reversal Learning / Q000502:physiology*; D055815:Young Adult
chemical_list: C581293:DRD2 protein, human; D017448:Receptors, Dopamine D2; C489948:ANKK1 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: Basal ganglia; DRD2/ANKK1-TaqIa polymorphism; Functional magnetic resonance imaging; Probabilistic response; Reversal learning; Reward; Striatum; Task specific dystonia; Writer's cramp