title: Asymmetric dopamine loss differentially affects effort to maximize gain or minimize loss.
abstract: BACKGROUND
  Dopamine (DA) plays an important role in regulating effort expenditure for reward, but whether it is also involved in modulating effort to avoid punishment is not clear. Preference for approach towards rewarding stimuli or away from aversive stimuli is associated with asymmetric activation in anterior brain regions. Asymmetric DA signaling in subcortical-frontal circuits may therefore contribute to differentially energizing behavior towards approach or avoidance behavior. We tested this hypothesis in patients with Parkinson's disease (PD), characterized by asymmetric DA loss.
  
  
  METHODS
  Patients with greater DA deficit in the left (n = 20) or right (n = 19) hemisphere, performed a task that measures separately effort to approach (maximize gains) versus effort to avoid (minimize loss), on and off DA replacement therapy.
  
  
  RESULTS
  When tested off medication, patients with relatively greater DA deficit in the left hemisphere showed greater approach deficit (less effort to increase gain than to avoid loss) whereas the opposite pattern of effort expenditure was demonstrated by patients with greater DA deficit in the right hemisphere. Performing the same task when medicated revealed increased willingness to expend effort, such that increased effort to maximize gain was associated left hemisphere improved DA function (reflected by reduced symptoms), while increased effort to avoid loss was related to right hemisphere improvement.
  
  
  CONCLUSIONS
  These results suggest that asymmetry of DA levels modulates the differential exertion of effort toward attaining rewards versus avoiding aversive consequences, providing new insights into understanding the underlying pathophysiology of behavioral syndromes such as apathy and impulsive-compulsive disorders.
authors.affiliation: Department of Psychology, University of Haifa, Haifa, Israel.
authors.forename: Omer
authors.initials: O
authors.lastname: Porat
authors.affiliation: The Parkinson Disease and Movement Disorders Clinic, The Sagol Neuroscience Center and Department of Neurology, Chaim Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.
authors.forename: Sharon
authors.initials: S
authors.lastname: Hassin-Baer
authors.affiliation: The Parkinson Disease and Movement Disorders Clinic, The Sagol Neuroscience Center and Department of Neurology, Chaim Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.
authors.forename: Oren S
authors.initials: OS
authors.lastname: Cohen
authors.affiliation: Department of Psychology, University of Haifa, Haifa, Israel.
authors.forename: Andrey
authors.initials: A
authors.lastname: Markus
authors.affiliation: Department of Psychology, University of Haifa, Haifa, Israel. Electronic address: rtomer@psy.haifa.ac.il.
authors.forename: Rachel
authors.initials: R
authors.lastname: Tomer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004298:Dopamine / Q000172:deficiency*; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009042:Motivation / Q000502:physiology*; D010300:Parkinson Disease / Q000503:physiopathology*; D012201:Reward; D013647:Task Performance and Analysis
chemical_list: D004298:Dopamine
keywords: Asymmetry; Dopamine; Effort; Motivation; Parkinson's disease