Overnight fasting affects avoidance learning and relief.

Objectives: prolonged fasting influences threat and reward processing, two fundamental systems underpinning adaptive behaviors. In animals, overnight fasting sensitizes the mesolimbic-dopaminergic activity governing avoidance, reward, and fearextinction learning. Despite evidence that overnight fasting may also affect reward and fear learning in humans, effects on human avoidance learning have not been studied yet. Here, we examined the effects of 16 h-overnight fasting on instrumental avoidance and relief from threat omission.Methods: to this end, 50 healthy women were randomly assigned to a Fasting (N = 25) or a Re-feeding group (N = 25) and performed an Avoidance-Relief Task.Results: we found that fasting decreases unnecessary avoidance during signaled safety; this effect was mediated via a reduction in relief pleasantness during signaled absence of threat. A fasting-induced reduction in relief was also found during fear extinction learning.Discussion: we conclude that fasting optimizes avoidance and safety learning. Future studies should test whether these effects also hold for anxious individuals.

Experimental models in psychopathology research: The relation between Research Domain Criteria and Experimental Psychopathology.

Experimental Psychopathology (EPP) and the Research Domain Criteria (RDoC) are research approaches that have developed in parallel, providing inter-related yet different scientific frameworks to investigate psychopathology at the intersection of fundamental and applied research. Here we address the overlap and differences between RDoC and EPP, and the challenges that both approaches face. Although overlap between EPP and RDoC can be clearly observed, each approach has its own unique strengths and weaknesses. These aspects will be illustrated by examples with respect to fear conditioning, an experimental procedure that has played a central role in both EPP and RDoC. We see much potential in boosting psychopathology research by combining the strengths of these two approaches.

Probiotics-induced changes in gut microbial composition and its effects on cognitive performance after stress: exploratory analyses.

Stress negatively affects cognitive performance. Probiotics remediate somatic and behavioral stress responses, hypothetically by acting on the gut microbiota. Here, in exploratory analyses, we assessed gut microbial alterations after 28-days supplementation of multi-strain probiotics (EcologicBarrier consisting of Lactobacilli, Lactococci, and Bifidobacteria in healthy, female subjects (probiotics group n = 27, placebo group n = 29). In an identical pre-session and post-session, subjects performed a working memory task before and after an acute stress intervention. Global gut microbial beta diversity changed over time, but we were not able to detect differences between intervention groups. At the taxonomic level, Time by Intervention interactions were not significant after multiple comparison correction; the relative abundance of eight genera in the probiotics group was higher (uncorrected) relative to the placebo group: Butyricimonas, Parabacteroides, Alistipes, Christensenellaceae_R-7_group, Family_XIII_AD3011_group, Ruminococcaceae_UCG-003, Ruminococcaceae_UCG-005, and Ruminococcaceae_UCG-010. In a second analysis step, association analyses were done only within this selection of microbial genera, revealing the probiotics-induced change in genus Ruminococcaceae_UCG-003 was significantly associated with probiotics' effect on stress-induced working memory changes (rspearman(27) = 0.565; pFDR = 0.014) in the probiotics group only and independent of potential confounders (i.e., age, BMI, and baseline dietary fiber intake). That is subjects with a higher increase in Ruminococcaceae_UCG-003 abundance after probiotics were also more protected from negative effects of stress on working memory after probiotic supplementation. The bacterial taxa showing an increase in relative abundance in the probiotics group are plant fiber degrading bacteria and produce short-chain fatty acids that are known for their beneficial effect on gut and brain health, e.g., maintaining intestinal-barrier and blood-brain-barrier integrity. This study shows that gut microbial alterations, modulated through probiotics use, are related to improved cognitive performance in acute stress circumstances.

Dopamine: from prediction error to psychotherapy.

Dopamine, one of the main neurotransmitters in the mammalian brain, has been implicated in the coding of prediction errors that govern reward learning as well as fear extinction learning. Psychotherapy too can be viewed as a form of error-based learning, because it challenges erroneous beliefs and behavioral patterns in order to induce long-term changes in emotions, cognitions, and behaviors. Exposure therapy, for example, relies in part on fear extinction principles to violate erroneous expectancies of danger and induce novel safety learning that inhibits and therefore reduces fear in the long term. As most forms of psychotherapy, however, exposure therapy suffers from non-response, dropout, and relapse. This narrative review focuses on the role of midbrain and prefrontal dopamine in novel safety learning and investigates possible pathways through which dopamine-based interventions could be used as an adjunct to improve both the response and the long-term effects of the therapy. Convincing evidence exists for an involvement of the midbrain dopamine system in the acquisition of new, safe memories. Additionally, prefrontal dopamine is emerging as a key ingredient for the consolidation of fear extinction. We propose that applying a dopamine prediction error perspective to psychotherapy can inspire both pharmacological and non-pharmacological studies aimed at discovering innovative ways to enhance the acquisition of safety memories. Additionally, we call for further empirical investigations on dopamine-oriented drugs that might be able to maximize consolidation of successful fear extinction and its long-term retention after therapy, and we propose to also include investigations on non-pharmacological interventions with putative prefrontal dopaminergic effects, like working memory training.

Reward anticipation in individuals with subclinical psychotic experiences: A functional MRI approach.

Previous research in patients with psychotic disorder has shown widespread abnormalities in brain activation during reward anticipation. Research at the level of subclinical psychotic experiences in individuals unexposed to antipsychotic medication is limited with inconclusive results. Therefore, brain activation during reward anticipation was examined in a larger sample of individuals with subclinical psychotic experiences (PE). Participants in the PE-group were included based on CAPE scores. A sample of emerging adults aged 16-26 years (n = 47) with PE and healthy controls (HC) (n = 40) underwent fMRI scanning. The Monetary Incentive Delay task was conducted with cues related to win, loss or neutral conditions. fMRI nonparametric tests were used to examine the reward versus neutral cue contrast. A significant main effect of the large win (€3.00) > neutral contrast was found in both groups showing activation in many brain areas, including classic reward regions. Whole brain analysis on the group comparison regarding the large win > neutral contrast showed significantly decreased activation in the right insula, putamen and supramarginal gyrus in the PE-group compared to controls. There was no group difference in the hypothesized reward-related region. Decreased activation in the right insula, putamen and supramarginal gyrus during reward anticipation in individuals with PE may be consistent with altered processing of sensory information, related to decreased emotional valuing and motivational tendencies and/or altered motor-cognitive processes. The absence of group differences in striatal activation suggests that activation here is intact in the earliest stages of psychosis and may exhibit progressive deterioration in as the disease develops.

The predictive value of neural reward processing on exposure therapy outcome: Results from a randomized controlled trial.

BACKGROUND: Exposure is the gold standard treatment for phobic anxiety and is thought to represent the clinical application of extinction learning. Reward sensitivity might however also represent a predictive factor for exposure therapy outcome, as this therapy promotes positive experiences and involves positive comments by the therapist. We hypothesized that high reward sensitivity, as expressed by elevated reward expectancy and reward value, can be associated with better outcome to exposure therapy specifically. METHODS: Forty-four participants with a specific phobia for spiders were included in the current study. Participants were randomly assigned to exposure therapy (n = 25) or progressive muscle relaxation (PMR) (n = 19). Treatment outcome was defined as pre- versus post-therapy phobia symptoms. Before treatment, functional brain responses and behavioral responses (i.e. reaction time and accuracy) during reward anticipation and consumption were assessed with the Monetary Incentive Delay task (MID). Behavioral and neural responses in regions of interest (i.e. nucleus accumbens, ventromedial prefrontal cortex and the ventral tegmental area) as well as across the whole-brain were subsequently regressed on treatment outcomes. RESULTS: Exposure therapy was more effective in reducing phobia symptoms than PMR. Longer reaction times to reward cues and lower activation in the left posterior cingulate cortex during reward consumption were selectively associated with symptoms reductions following exposure therapy but not following PMR. Only within the exposure therapy group, greater symptom reduction was related to increased activation in the ventrolateral prefrontal cortex during reward anticipation, and decreased activation in the medial prefrontal cortex during reward consumption. CONCLUSION: Results indicate that individual differences in reward sensitivity can specifically predict exposure therapy outcome. Although activation in regions of interest were not related to therapy outcome, regions involved in attentional processing of reward cues were predictive of phobic symptom change following exposure therapy but not PMR.

Behavioral pattern separation and its link to the neural mechanisms of fear generalization.

Fear generalization is a prominent feature of anxiety disorders and post-traumatic stress disorder (PTSD). It is defined as enhanced fear responding to a stimulus that bears similarities, but is not identical to a threatening stimulus. Pattern separation, a hippocampal-dependent process, is critical for stimulus discrimination; it transforms similar experiences or events into non-overlapping representations. This study is the first in humans to investigate the extent to which fear generalization relies on behavioral pattern separation abilities. Participants (N = 46) completed a behavioral task taxing pattern separation, and a neuroimaging fear conditioning and generalization paradigm. Results show an association between lower behavioral pattern separation performance and increased generalization in shock expectancy scores, but not in fear ratings. Furthermore, lower behavioral pattern separation was associated with diminished recruitment of the subcallosal cortex during presentation of generalization stimuli. This region showed functional connectivity with the orbitofrontal cortex and ventromedial prefrontal cortex. Together, the data provide novel experimental evidence that pattern separation is related to generalization of threat expectancies, and reduced fear inhibition processes in frontal regions. Deficient pattern separation may be critical in overgeneralization and therefore may contribute to the pathophysiology of anxiety disorders and PTSD.