title: Corticostriatothalamic reward prediction error signals and executive control in late-life depression.
abstract: BACKGROUND
  Altered corticostriatothalamic encoding of reinforcement is a core feature of depression. Here we examine reinforcement learning in late-life depression in the theoretical framework of the vascular depression hypothesis. This hypothesis attributes the co-occurrence of late-life depression and poor executive control to prefrontal/cingulate disconnection by vascular lesions.
  
  
  METHODS
  Our fMRI study compared 31 patients aged ⩾60 years with major depression to 16 controls. Using a computational model, we estimated neural and behavioral responses to reinforcement in an uncertain, changing environment (probabilistic reversal learning).
  
  
  RESULTS
  Poor executive control and depression each explained distinct variance in corticostriatothalamic response to unexpected rewards. Depression, but not poor executive control, predicted disrupted functional connectivity between the striatum and prefrontal cortex. White-matter hyperintensities predicted diminished corticostriatothalamic responses to reinforcement, but did not mediate effects of depression or executive control. In two independent samples, poor executive control predicted a failure to persist with rewarded actions, an effect distinct from depressive oversensitivity to punishment. The findings were unchanged in a subsample of participants with vascular disease. Results were robust to effects of confounders including psychiatric comorbidities, physical illness, depressive severity, and psychotropic exposure.
  
  
  CONCLUSIONS
  Contrary to the predictions of the vascular depression hypothesis, altered encoding of rewards in late-life depression is dissociable from impaired contingency learning associated with poor executive control. Functional connectivity and behavioral analyses point to a disruption of ascending mesostriatocortical reward signals in late-life depression and a failure of cortical contingency encoding in elderly with poor executive control.
authors.affiliation: Department of Psychiatry,University of Pittsburgh,Pittsburgh, PA,USA.
authors.forename: A Y
authors.initials: AY
authors.lastname: Dombrovski
authors.affiliation: Department of Psychiatry,University of Pittsburgh,Pittsburgh, PA,USA.
authors.forename: K
authors.initials: K
authors.lastname: Szanto
authors.affiliation: University of British Columbia,Vancouver,Canada.
authors.forename: L
authors.initials: L
authors.lastname: Clark
authors.affiliation: Department of Psychiatry,University of Pittsburgh,Pittsburgh, PA,USA.
authors.forename: H J
authors.initials: HJ
authors.lastname: Aizenstein
authors.affiliation: Department of Psychiatry,University of Pittsburgh,Pittsburgh, PA,USA.
authors.forename: H W
authors.initials: HW
authors.lastname: Chase
authors.affiliation: Department of Psychiatry,University of Pittsburgh,Pittsburgh, PA,USA.
authors.forename: C F
authors.initials: CF
authors.lastname: Reynolds
authors.affiliation: Department of Psychiatry,University of Pittsburgh,Pittsburgh, PA,USA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Siegle
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002540:Cerebral Cortex / Q000503:physiopathology*; D003865:Major Depressive Disorder / Q000503:physiopathology*; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017072:Neostriatum / Q000503:physiopathology*; D012054:Reinforcement, Psychology; D012201:Reward; D013788:Thalamus / Q000503:physiopathology*
keywords: reward