Dataset Information

Impaired reward-related learning signals in remitted unmedicated patients with recurrent depression.

ABSTRACT: One of the core symptoms of major depressive disorder is anhedonia, an inability to experience pleasure. In patients with major depressive disorder, a dysfunctional reward-system may exist, with blunted temporal difference reward-related learning signals in the ventral striatum and increased temporal difference-related (dopaminergic) activation in the ventral tegmental area. Anhedonia often remains as residual symptom during remission; however, it remains largely unknown whether the abovementioned reward systems are still dysfunctional when patients are in remission. We used a Pavlovian classical conditioning functional MRI task to explore the relationship between anhedonia and the temporal difference-related response of the ventral tegmental area and ventral striatum in medication-free remitted recurrent depression patients (n = 36) versus healthy control subjects (n = 27). Computational modelling was used to obtain the expected temporal difference errors during this task. Patients, compared to healthy controls, showed significantly increased temporal difference reward learning activation in the ventral tegmental area (PFWE,SVC = 0.028). No differences were observed between groups for ventral striatum activity. A group × anhedonia interaction [t(57) = -2.29, P = 0.026] indicated that in patients, higher anhedonia was associated with lower temporal difference activation in the ventral tegmental area, while in healthy controls higher anhedonia was associated with higher ventral tegmental area activation. These findings suggest impaired reward-related learning signals in the ventral tegmental area during remission in patients with depression. This merits further investigation to identify impaired reward-related learning as an endophenotype for recurrent depression. Moreover, the inverse association between reinforcement learning and anhedonia in patients implies an additional disturbing influence of anhedonia on reward-related learning or vice versa, suggesting that the level of anhedonia should be considered in behavioural treatments.

SUBMITTER: Geugies H

PROVIDER: S-EPMC6734943 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Impaired reward-related learning signals in remitted unmedicated patients with recurrent depression.

Geugies Hanneke H Mocking Roel J T RJT Figueroa Caroline A CA Groot Paul F C PFC Marsman Jan-Bernard C JC Servaas Michelle N MN Steele J Douglas JD Schene Aart H AH Ruhé Henricus G HG

Brain : a journal of neurology 20190801 8

One of the core symptoms of major depressive disorder is anhedonia, an inability to experience pleasure. In patients with major depressive disorder, a dysfunctional reward-system may exist, with blunted temporal difference reward-related learning signals in the ventral striatum and increased temporal difference-related (dopaminergic) activation in the ventral tegmental area. Anhedonia often remains as residual symptom during remission; however, it remains largely unknown whether the abovemention ...[more]

PMID: 31280309

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Project description:The authors assessed the functioning of mesolimbic and striatal areas involved in reward-based spatial learning in unmedicated adults with obsessive-compulsive disorder (OCD).Functional MRI blood-oxygen-level-dependent response was compared in 33 unmedicated adults with OCD and 33 healthy, age-matched comparison subjects during a reward-based learning task that required learning to use extramaze cues to navigate a virtual eight-arm radial maze to find hidden rewards. The groups were compared in their patterns of brain activation associated with reward-based spatial learning versus a control condition in which rewards were unexpected because they were allotted pseudorandomly to experimentally prevent learning.Both groups learned to navigate the maze to find hidden rewards, but group differences in neural activity during navigation and reward processing were detected in mesolimbic and striatal areas. During navigation, the OCD group, unlike the healthy comparison group, exhibited activation in the left posterior hippocampus. Unlike healthy subjects, participants in the OCD group did not show activation in the left ventral putamen and amygdala when anticipating rewards or in the left hippocampus, amygdala, and ventral putamen when receiving unexpected rewards (control condition). Signal in these regions decreased relative to baseline during unexpected reward receipt among those in the OCD group, and the degree of activation was inversely associated with doubt/checking symptoms.Participants in the OCD group displayed abnormal recruitment of mesolimbic and ventral striatal circuitry during reward-based spatial learning. Whereas healthy comparison subjects exhibited activation in this circuitry in response to the violation of reward expectations, unmedicated OCD participants did not and instead over-relied on the posterior hippocampus during learning. Thus, dopaminergic innervation of reward circuitry may be altered, and future study of anterior/posterior hippocampal dysfunction in OCD is warranted.

Project description:IMPORTANCE—Suicide can be viewed as an escape from unendurable punishment at the cost of any future rewards. Could faulty estimation of these outcomes predispose to suicidal behavior? In behavioral studies, many of those who have attempted suicide misestimate expected rewards on gambling and probabilistic learning tasks.OBJECTIVES—To describe the neural circuit abnormalities that underlie disadvantageous choices in people at risk for suicide and to relate these abnormalities to impulsivity, which is one of the components of vulnerability to suicide.DESIGN—Case-control functional magnetic resonance imaging study of reward learning using are inforcement learning model.SETTING—University hospital and outpatient clinic.PATIENTS—Fifty-three participants 60 years or older, including 15 depressed patients who had attempted suicide, 18 depressed patients who had never attempted suicide (depressed control subjects), and 20 psychiatrically healthy controls.MAIN OUTCOMES AND MEASURES—Components of the cortical blood oxygenation level–dependent response tracking expected and unpredicted rewards.RESULTS—Depressed elderly participants displayed 2 distinct disruptions of control over reward-guided behavior. First, impulsivity and a history of suicide attempts (particularly poorly planned ones) were associated with a weakened expected reward signal in the paralimbic cortex,which in turn predicted the behavioral insensitivity to contingency change. Second, depression was associated with disrupted corticostriatothalamic encoding of unpredicted rewards, which in turn predicted the behavioral over sensitivity to punishment. These results were robust to the effects of possible brain damage from suicide attempts, depressive severity, co-occurring substance use and anxiety disorders, antidepressant and anticholinergic exposure, lifetime exposure to electroconvulsive therapy, vascular illness, and incipient dementia.CONCLUSIONS AND RELEVANCE—Altered paralimbic reward signals and impulsivity and/or carelessness may facilitate unplanned suicidal acts. This pattern, also seen in gambling and cocaine use, may reflect a primary deficit in the paralimbic cortex or in its mesolimbic input. The over reactivity to punishment in depression may be caused in part by a disruption of appetitive learning in the corticostriatothalamic circuits.

Dataset Information

Impaired reward-related learning signals in remitted unmedicated patients with recurrent depression.

Publications

Impaired reward-related learning signals in remitted unmedicated patients with recurrent depression.

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