Beyond negative valence: 2-week administration of a serotonergic antidepressant enhances both reward and effort learning signals.
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ABSTRACT:
SUBMITTER: Scholl J
PROVIDER: S-EPMC5331946 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Optimal decision making mandates organisms learn the relevant features of choice options. Likewise, knowing how much effort we should expend can assume paramount importance. A mesolimbic network supports reward learning, but it is unclear whether other choice features, such as effort learning, rely on this same network. Using computational fMRI, we show parallel encoding of effort and reward prediction errors (PEs) within distinct brain regions, with effort PEs expressed in dorsomedial prefrontal cortex and reward PEs in ventral striatum. We show a common mesencephalic origin for these signals evident in overlapping, but spatially dissociable, dopaminergic midbrain regions expressing both types of PE. During action anticipation, reward and effort expectations were integrated in ventral striatum, consistent with a computation of an overall net benefit of a stimulus. Thus, we show that motivationally relevant stimulus features are learned in parallel dopaminergic pathways, with formation of an integrated utility signal at choice.
| S-EPMC5584432 | biostudies-literature
Project description:ImportanceNearly 1 in 3 patients with major depressive disorder who respond to antidepressants relapse within 6 months of treatment discontinuation. No predictors of relapse exist to guide clinical decision-making in this scenario.ObjectivesTo establish whether the decision to invest effort for rewards represents a persistent depression process after remission, predicts relapse after remission, and is affected by antidepressant discontinuation.Design, setting, and participantsThis longitudinal randomized observational prognostic study in a Swiss and German university setting collected data from July 1, 2015, to January 31, 2019, from 66 healthy controls and 123 patients in remission from major depressive disorder in response to antidepressants prior to and after discontinuation. Study recruitment took place until January 2018.ExposureDiscontinuation of antidepressants.Main outcomes and measuresRelapse during the 6 months after discontinuation. Choice and decision times on a task requiring participants to choose how much effort to exert for various amounts of reward and the mechanisms identified through parameters of a computational model.ResultsA total of 123 patients (mean [SD] age, 34.5 [11.2] years; 94 women [76%]) and 66 healthy controls (mean [SD] age, 34.6 [11.0] years; 49 women [74%]) were recruited. In the main subsample, mean (SD) decision times were slower for patients (n?=?74) compared with controls (n?=?34) (1.77 [0.38] seconds vs 1.61 [0.37] seconds; Cohen d?=?0.52; P?=?.02), particularly for those who later relapsed after discontinuation of antidepressants (n?=?21) compared with those who did not relapse (n?=?39) (1.95 [0.40] seconds vs 1.67 [0.34] seconds; Cohen d?=?0.77; P?<?.001). This slower decision time predicted relapse (accuracy?=?0.66; P?=?.007). Patients invested less effort than healthy controls for rewards (F1,98?=?33.970; P?<?.001). Computational modeling identified a mean (SD) deviation from standard drift-diffusion models that was more prominent for patients than controls (patients, 0.67 [1.56]; controls, -0.71 [1.93]; Cohen d?=?0.82; P?<?.001). Patients also showed higher mean (SD) effort sensitivity than controls (patients, 0.31 [0.92]; controls, -0.08 [1.03]; Cohen d?=?0.51; P?=?.05). Relapsers differed from nonrelapsers in terms of the evidence required to make a decision for the low-effort choice (mean [SD]: relapsers, 1.36 [0.35]; nonrelapsers, 1.17 [0.26]; Cohen d?=?0.65; P?=?.02). Group differences generally did not reach significance in the smaller replication sample (27 patients and 21 controls), but decision time prediction models from the main sample generalized to the replication sample (validation accuracy?=?0.71; P?=?.03).Conclusions and relevanceThis study found that the decision to invest effort was associated with prospective relapse risk after antidepressant discontinuation and may represent a persistent disease process in asymptomatic remitted major depressive disorder. Markers based on effort-related decision-making could potentially inform clinical decisions associated with antidepressant discontinuation.
| S-EPMC7042923 | biostudies-literature
Project description:OBJECTIVE:To determine whether infants exposed in utero to serotonin reuptake inhibitor (SRI) antidepressants or a DSM-IV-TR-defined mood disorder have significantly more neonatal discontinuation signs compared to an unexposed group of infants at 2-4 weeks after birth. METHODS:This secondary analysis was derived from 2 observational studies with enrollment from July 2000 to December 2011 in Cleveland, Ohio, and Pittsburgh, Pennsylvania. Mothers (n = 214) belonged to one of 3 groups based on exposure status during pregnancy: (1) Comparison-women who did not take psychotropics during pregnancy and had no major mood disorder; (2) SRI-exposed-women with a mood disorder who were taking an SRI but no benzodiazepines; and (3) Mood Disorder-women with depression or bipolar disorder who did not take psychotropic medications. The infants were examined for signs according to the Finnegan Scale by evaluators blind to maternal exposure status. RESULTS:The rates of sign presence (defined as a score ? 2 on the Finnegan Scale) in the SRI, Mood Disorder, and Comparison groups were similar at 34.1%, 35.1%, and 30.4%, respectively. Women in the SRI group had a significantly higher preterm birth rate (24.4%) compared to the other 2 groups (7.4% and 8.9% in the Mood Disorder and Comparison groups, respectively; P = .012). Preterm newborns had a significantly higher sign rate compared to full-term newborns (54% vs 31%, P = .020). We observed a significant relationship between Finnegan signs and preterm birth. CONCLUSIONS:The presence of neonatal signs at 2-4 weeks was more closely associated with prematurity than with in utero SRI or mood disorder exposure. TRIAL REGISTRATION:ClinicalTrials.gov identifiers: NCT00279370 and NCT00585702.
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Project description:In the present study, we investigated the regulatory mechanisms underlying sperm hyperactivation enhanced by 5-hydroxytryptamine (5-HT) in hamsters. First, we examined the types of 5-HT receptors that regulate hyperactivation. Hyperactivation was significantly enhanced by 5-HT2A and 5-HT4 receptor agonists. Moreover, the results of the motility assay revealed that 5-HT2A, 5-HT3, and 5-HT4 receptor agonists significantly decreased the velocity and/or amplitude of sperm. Under 5-HT2 receptor stimulation, hyperactivation was associated with phospholipase C (PLC), inositol 1,4,5-trisphosphate (IP3) receptor, soluble adenylate cyclase (sAC), and protein kinase A (PKA). In contrast, under 5-HT4 receptor stimulation, hyperactivation was associated with transmembrane adenylate cyclase (tmAC), sAC, PKA, and CatSper channels. Accordingly, under the condition that sperm are hyperactivated, 5-HT likely stimulates PLC/IP3 receptor signals via the 5-HT2A receptor and tmAC/PKA/CatSper channel signals via the 5-HT4 receptor. After sAC and PKA are activated by these stimulations, sperm hyperactivation is enhanced.
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Project description:Antidepressant usage in prodromal Huntington Disease (HD) remains uncharacterized, despite its relevance in designing experiments, studying outcomes of HD, and evaluating the efficacy of therapeutic interventions. We searched baseline medication logs of 787 prodromal HD and 215 healthy comparison (HC) participants for antidepressant use. Descriptive and mixed-effects logistic regression modeling characterized usage across participants. At baseline, approximately one in five prodromal HD participants took antidepressants. Of those, the vast majority took serotonergic antidepressants (selective serotonin reuptake inhibitor (SSRI) or serotonin/norepinephrine reuptake inhibitor (SNRI)). Significantly more prodromal HD participants used serotonergic antidepressants than their HC counterparts. Because of the prevalence of these medications, further analyses focused on this group alone. Mixed-effects logistic regression modeling revealed significant relationships of both closer proximity to diagnosis and female sex with greater likelihood to be prescribed a serotonergic antidepressant. More prodromal HD participants took antidepressants in general and specifically the subclass of serotonergic antidepressants than their at-risk counterparts, particularly when they were closer to predicted time of conversion to manifest HD. These propensities must be considered in studies of prodromal HD participants.
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Project description:Research in motivation and emotion has been increasingly influenced by the perspective that processes underpinning the motivated approach of rewarding goals are distinct from those underpinning enjoyment during reward consummation. This distinction recently inspired the construction of the Temporal Experience of Pleasure Scale (TEPS), a self-report measure that distinguishes trait anticipatory pleasure (pre-reward feelings of desire) from consummatory pleasure (feelings of enjoyment and gratification upon reward attainment). In a university community sample (N = 97), we examined the TEPS subscales as predictors of (1) the willingness to expend effort for monetary rewards, and (2) affective responses to a pleasant mood induction procedure. Results showed that both anticipatory pleasure and a well-known trait measure of reward motivation predicted effort-expenditure for rewards when the probability of being rewarded was relatively low. Against expectations, consummatory pleasure was unrelated to induced pleasant affect. Taken together, our findings provide support for the validity of the TEPS anticipatory pleasure scale, but not the consummatory pleasure scale.
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Project description:Ascribing affective valence to stimuli or mental states is a fundamental property of human experiences. Recent neuroimaging meta-analyses favor the workspace hypothesis for the neural underpinning of valence, in which both positive and negative values are encoded by overlapping networks but are associated with different patterns of activity. In the present study, we further explored this framework using functional near-infrared spectroscopy (fNIRS) in conjunction with multivariate analyses. We monitored the fronto-temporal and occipital hemodynamic activity of 49 participants during the viewing of affective images (passive condition) and during the imagination of affectively loaded states (active condition). Multivariate decoding techniques were applied to determine whether affective valence is encoded in the cortical areas assessed. Prediction accuracies of 89.90?±?13.84% and 85.41?±?14.43% were observed for positive versus neutral comparisons, and of 91.53?±?13.04% and 81.54?±?16.05% for negative versus neutral comparisons (passive/active conditions, respectively). Our results are consistent with previous studies using other neuroimaging modalities that support the affective workspace hypothesis and the notion that valence is instantiated by the same network, regardless of whether the affective experience is passively or actively elicited.
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Project description:Apathy is a common but poorly understood condition with a wide societal impact observed in several brain disorders as well as, to some extent, in the normal population. Hence the need for better characterization of the underlying mechanisms. The processes by which individuals decide to attribute physical effort to obtain rewards might be particularly relevant to relate to apathy traits. Here, we designed two paradigms to assess individual differences in physical effort production and effort-based decision-making and their relation to apathy in healthy people. Apathy scores were measured using a modified version of the Lille Apathy Rating Scale, suitable for use in a non-clinical population. In the first study, apathy scores were correlated with the degree to which stake (reward on offer) and difficulty level impacts on physical effort production. Individuals with relatively high apathy traits showed an increased modulation of effort while more motivated individuals generally exerted greater force across different levels of stake. To clarify the underlying mechanisms for this behavior, we designed a second task that allows independent titration of stake and effort levels for which subjects are willing to engage in an effortful response to obtain a reward. Our results suggest that apathy traits in the normal population are related to the way reward subjectively affects the estimation of effort costs, and more particularly manifest as decreased willingness to exert effort when rewards are small, or below threshold. The tasks we introduce here may provide useful tools to further investigate apathy in clinical populations.
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Project description:Effort and reward jointly shape many human decisions. Errors in predicting the required effort needed for a task can lead to suboptimal behavior. Here, we show that effort estimations can be biased when retrospectively reestimated following receipt of a rewarding outcome. These biases depend on the contingency between reward and task difficulty and are stronger for highly contingent rewards. Strikingly, the observed pattern accords with predictions from Bayesian cue integration, indicating humans deploy an adaptive and rational strategy to deal with inconsistencies between the efforts they expend and the ensuing rewards.
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Project description:We report bulk RNAseq data obtained from the Anterior Cingulate Cortex (ACC) microdissected from Untrained (n=5) and Trained (n=6) wild-type mice for an instrumental task, the lever-press task for food reward.
2021-03-24 | GSE169392 | GEO