Computational Mechanisms Underlying Multi-Step Planning Deficits in Methamphetamine Use Disorder.

Current theories suggest individuals with methamphetamine use disorder (iMUDs) have difficulty considering long-term outcomes in decision-making, which could contribute to risk of relapse. Aversive interoceptive states (e.g., stress, withdrawal) are also known to increase this risk. The present study analyzed computational mechanisms of planning in iMUDs, and examined the potential impact of an aversive interoceptive state induction. A group of 40 iMUDs and 49 healthy participants completed two runs of a multi-step planning task, with and without an anxiogenic breathing resistance manipulation. Computational modeling revealed that iMUDs had selective difficulty identifying the best overall plan when this required enduring negative short-term outcomes - a mechanism referred to as aversive pruning. Increases in reported craving before and after the induction also predicted greater aversive pruning in iMUDs. These results highlight a novel mechanism that could promote poor choice in recovering iMUDs and create vulnerability to relapse.

Heuristics in risky decision-making relate to preferential representation of information.

When making choices, individuals differ from one another, as well as from normativity, in how they weigh different types of information. One explanation for this relates to idiosyncratic preferences in what information individuals represent when evaluating choice options. Here, we test this explanation with a simple risky-decision making task, combined with magnetoencephalography (MEG). We examine the relationship between individual differences in behavioral markers of information weighting and neural representation of stimuli pertinent to incorporating that information. We find that the extent to which individuals (N = 19) behaviorally weight probability versus reward information is related to how preferentially they neurally represent stimuli most informative for making probability and reward comparisons. These results are further validated in an additional behavioral experiment (N = 88) that measures stimulus representation as the latency of perceptual detection following priming. Overall, the results suggest that differences in the information individuals consider during choice relate to their risk-taking tendencies.

Emotion-Induced Frontal Alpha Asymmetry as a Candidate Predictor of Relapse After Discontinuation of Antidepressant Medication.

BACKGROUND: One in 3 patients relapse after antidepressant discontinuation. Thus, the prevention of relapse after achieving remission is an important component in the long-term management of major depressive disorder. However, no clinical or other predictors are established. Frontal reactivity to sad mood as measured by functional magnetic resonance imaging has been reported to relate to relapse independently of antidepressant discontinuation and is an interesting candidate predictor. METHODS: Patients (n = 56) who had remitted from a depressive episode while taking antidepressants underwent electroencephalography (EEG) recording during a sad mood induction procedure prior to gradually discontinuing their medication. Relapse was assessed over a 6-month follow-up period. Thirty five healthy control participants were also tested. Current source density of the EEG power in the alpha band (8-13 Hz) was extracted and alpha asymmetry was computed by comparing the power across 2 hemispheres at frontal electrodes (F5 and F6). RESULTS: Sad mood induction was robust across all groups. Reactivity of alpha asymmetry to sad mood did not distinguish healthy control participants from patients with remitted major depressive disorder on medication. However, the 14 (25%) patients who relapsed during the follow-up period after discontinuing medication showed significantly reduced reactivity in alpha asymmetry compared with patients who remained well. This EEG signal provided predictive power (69% out-of-sample balanced accuracy and a positive predictive value of 0.75). CONCLUSIONS: A simple EEG-based measure of emotional reactivity may have potential to contribute to clinical prediction models of antidepressant discontinuation. Given the very small sample size, this finding must be interpreted with caution and requires replication in a larger study.

The selective serotonin reuptake inhibitor sertraline alters learning from aversive reinforcements in patients with depression: evidence from a randomized controlled trial.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for depression and anxiety. However, little is known about how pharmacological action is related to cognitive and affective processes. Here, we examine whether specific reinforcement learning processes mediate the treatment effects of SSRIs. METHODS: The PANDA trial was a multicentre, double-blind, randomized clinical trial in UK primary care comparing the SSRI sertraline with placebo for depression and anxiety. Participants (N = 655) performed an affective Go/NoGo task three times during the trial and computational models were used to infer reinforcement learning processes. RESULTS: There was poor task performance: only 54% of the task runs were informative, with more informative task runs in the placebo than in the active group. There was no evidence for the preregistered hypothesis that Pavlovian inhibition was affected by sertraline. Exploratory analyses revealed that in the sertraline group, early increases in Pavlovian inhibition were associated with improvements in depression after 12 weeks. Furthermore, sertraline increased how fast participants learned from losses and faster learning from losses was associated with more severe generalized anxiety symptoms. CONCLUSIONS: The study findings indicate a relationship between aversive reinforcement learning mechanisms and aspects of depression, anxiety, and SSRI treatment, but these relationships did not align with the initial hypotheses. Poor task performance limits the interpretability and likely generalizability of the findings, and highlights the critical importance of developing acceptable and reliable tasks for use in clinical studies. FUNDING: This article presents research supported by NIHR Program Grants for Applied Research (RP-PG-0610-10048), the NIHR BRC, and UCL, with additional support from IMPRS COMP2PSYCH (JM, QH) and a Wellcome Trust grant (QH).

Different components of cognitive-behavioral therapy affect specific cognitive mechanisms.

Psychological therapies are among the most effective treatments for common mental health problems-however, we still know relatively little about how exactly they improve symptoms. Here, we demonstrate the power of combining theory with computational methods to parse effects of different components of cognitive-behavioral therapies onto underlying mechanisms. Specifically, we present data from a series of randomized-controlled experiments testing the effects of brief components of behavioral and cognitive therapies on different cognitive processes, using well-validated behavioral measures and associated computational models. A goal setting intervention, based on behavioral activation therapy activities, reliably and selectively reduced sensitivity to effort when deciding how to act to gain reward. By contrast, a cognitive restructuring intervention, based on cognitive therapy materials, reliably and selectively reduced the tendency to attribute negative everyday events to self-related causes. The effects of each intervention were specific to these respective measures. Our approach provides a basis for beginning to understand how different elements of common psychotherapy programs may work.

The computational structure of consummatory anhedonia.

Anhedonia is a reduction in enjoyment, motivation, or interest. It is common across mental health disorders and a harbinger of poor treatment outcomes. The enjoyment aspect, termed 'consummatory anhedonia', in particular poses fundamental questions about how the brain constructs rewards: what processes determine how intensely a reward is experienced? Here, we outline limitations of existing computational conceptualisations of consummatory anhedonia. We then suggest a richer reinforcement learning (RL) account of consummatory anhedonia with a reconceptualisation of subjective hedonic experience in terms of goal progress. This accounts qualitatively for the impact of stress, dysfunctional cognitions, and maladaptive beliefs on hedonic experience. The model also offers new views on the treatments for anhedonia.

The Association of Non-Drug-Related Pavlovian-to-Instrumental Transfer Effect in Nucleus Accumbens With Relapse in Alcohol Dependence: A Replication.

BACKGROUND: The Pavlovian-to-instrumental transfer (PIT) paradigm measures the effects of Pavlovian conditioned cues on instrumental behavior in the laboratory. A previous study conducted by our research group observed activity in the left nucleus accumbens (NAcc) elicited by a non-drug-related PIT task across patients with alcohol dependence (AD) and healthy control subjects, and the left NAcc PIT effect differentiated patients who subsequently relapsed from those who remained abstinent. In this study, we aimed to examine whether such effects were present in a larger sample collected at a later date. METHODS: A total of 129 recently detoxified patients with AD (21 females) and 74 healthy, age- and gender-matched control subjects (12 females) performing a PIT task during functional magnetic resonance imaging were examined. After task assessments, patients were followed for 6 months. Forty-seven patients relapsed and 37 remained abstinent. RESULTS: We found a significant behavioral non-drug-related PIT effect and PIT-related activity in the NAcc across all participants. Moreover, subsequent relapsers showed stronger behavioral and left NAcc PIT effects than abstainers. These findings are consistent with our previous findings. CONCLUSIONS: Behavioral non-drug-related PIT and neural PIT correlates are associated with prospective relapse risk in AD. This study replicated previous findings and provides evidence for the clinical relevance of PIT mechanisms to treatment outcome in AD. The observed difference between prospective relapsers and abstainers in the NAcc PIT effect in our study is small overall. Future studies are needed to further elucidate the mechanisms and the possible modulators of neural PIT in relapse in AD.

Components of Behavioral Activation Therapy for Depression Engage Specific Reinforcement Learning Mechanisms in a Pilot Study.

Background: Behavioral activation is an evidence-based treatment for depression. Theoretical considerations suggest that treatment response depends on reinforcement learning mechanisms. However, which reinforcement learning mechanisms are engaged by and mediate the therapeutic effect of behavioral activation remains only partially understood, and there are no procedures to measure such mechanisms. Objective: To perform a pilot study to examine whether reinforcement learning processes measured through tasks or self-report are related to treatment response to behavioral activation. Method: The pilot study enrolled 13 outpatients (12 completers) with major depressive disorder, from July of 2018 through February of 2019, into a nine-week trial with BA. Psychiatric evaluations, decision-making tests and self-reported reward experience and anticipations were acquired before, during and after the treatment. Task and self-report data were analysed by using reinforcement-learning models. Inferred parameters were related to measures of depression severity through linear mixed effects models. Results: Treatment effects during different phases of the therapy were captured by specific decision-making processes in the task. During the weeks focusing on the active pursuit of reward, treatment effects were more pronounced amongst those individuals who showed an increase in Pavlovian appetitive influence. During the weeks focusing on the avoidance of punishments, treatment responses were more pronounced in those individuals who showed an increase in Pavlovian avoidance. Self-reported anticipation of reinforcement changed according to formal RL rules. Individual differences in the extent to which learning followed RL rules related to changes in anhedonia. Conclusions: In this pilot study both task- and self-report-derived measures of reinforcement learning captured individual differences in treatment response to behavioral activation. Appetitive and aversive Pavlovian reflexive processes appeared to be modulated by separate psychotherapeutic interventions, and the modulation strength covaried with response to specific interventions. Self-reported changes in reinforcement expectations are also related to treatment response. Trial Registry Name: Set Your Goal: Engaging in GO/No-Go Active Learning, #NCT03538535, http://www.clinicaltrials.gov.