Investigation of reward learning and feedback sensitivity in non-clinical participants with a history of early life stress

Early life stress (ELS) is an important risk factor for the development of depression. Impairments in reward learning and feedback sensitivity are suggested to be an intermediate phenotype in depression aetiology therefore we hypothesised that healthy adults with a history of ELS would exhibit reward processing deficits independent of any current depressive symptoms. We recruited 64 adults with high levels of ELS and no diagnosis of a current mental health disorder and 65 controls. Participants completed the probabilistic reversal learning task and probabilistic reward task followed by depression, anhedonia, social status, and stress scales. Participants with high levels of ELS showed decreased positive feedback sensitivity in the probabilistic reversal learning task compared to controls. High ELS participants also trended towards possessing a decreased model-free learning rate. This was coupled with a decreased learning ability in the acquisition phase of block 1 following the practice session. Neither group showed a reward induced response bias in the probabilistic reward task however high ELS participants exhibited decreased stimuli discrimination. Overall, these data suggest that healthy participants without a current mental health diagnosis but with high levels of ELS show deficits in positive feedback sensitivity and reward learning in the probabilistic reversal learning task that are distinct from depressed patients. These deficits may be relevant to increased depression vulnerability.

CRF-R1 Antagonist Treatment Exacerbates Circadian Corticosterone Secretion under Chronic Stress, but Preserves HPA Feedback Sensitivity

Despite promising initial reports, corticotropin-releasing factor receptor type-1 (CRF-R1) antagonists have mostly failed to display efficacy in clinical trials for anxiety or depression. Rather than broad-spectrum antidepressant/anxiolytic-like drugs, they may represent an ‘antistress’ solution for single stressful situations or for patients with chronic stress conditions. However, the impact of prolonged CRF-R1 antagonist treatments on the hypothalamic–pituitary–adrenal (HPA) axis under chronic stress conditions remained to be characterized. Hence, our study investigated whether a chronic CRF-R1 antagonist (crinecerfont, formerly known as SSR125543, 20 mg·kg−1·day−1 ip, 5 weeks) would alter HPA axis basal circadian activity and negative feedback sensitivity in mice exposed to either control or chronic stress conditions (unpredictable chronic mild stress, UCMS, 7 weeks), through measures of fecal corticosterone metabolites, plasma corticosterone, and dexamethasone suppression test. Despite preserving HPA axis parameters in control non-stressed mice, the 5-week crinercerfont treatment improved the negative feedback sensitivity in chronically stressed mice, but paradoxically exacerbated their basal corticosterone secretion nearly all along the circadian cycle. The capacity of chronic CRF-R1 antagonists to improve the HPA negative feedback in UCMS argues in favor of a potential therapeutic benefit against stress-related conditions. However, the treatment-related overactivation of HPA circadian activity in UCMS raise questions about possible physiological outcomes with long-standing treatments under ongoing chronic stress.

Neural signature of error processing in major depression

The clinical presentation of major depression (MD) is heterogenous and comprises various affective and cognitive symptoms including an increased sensitivity to errors. Various electrophysiological but only few functional magnetic resonance imaging (fMRI) studies investigated neural error processing in MD with inconsistent findings. Thus, reliable evidence regarding neural signatures of error processing in patients with current MD is limited despite its potential relevance as viable neurobiological marker of psychopathology. We therefore investigated a sample of 16 young adult female patients with current MD and 17 healthy controls (HC). During fMRI, we used an established Erikson-flanker Go/NoGo-paradigm and focused on neural alterations during errors of commission. In the absence of significant differences in rates of errors of commission in MD compared to HC, we observed significantly (p < 0.05, FWE-corrected on cluster level) enhanced neural activations of the dorsal anterior cingulate cortex (dACC) and the pre-supplementary motor area (pre-SMA) in MD relative to HC and thus, in brain regions consistently associated to neural error processing and corresponding behavioral adjustments. Considering comparable task performance, in particular similar commission error rates in MD and HC, our results support the evidence regarding an enhanced responsivity of neural error detection mechanisms in MD as a potential neural signature of increased negative feedback sensitivity as one of the core psychopathological features of this disorder.

Study of motor load regulation training with visual feedback in patients with diabetic polyneuropathy

BACKGRAUND: Violation of gait and body balance in patients with diabetic polyneuropathy actualizes the development of new effective measures of motor rehabilitation. In this regard, an observation was carried out in which biofeedback training was used for the reference reaction in the conditions of variable feedback parameters.AIMS: To investigate the effect of a stepwise change in the depth of feedback (sensitivity) in a motor-cognitive task with visual feedback on the reference response to the result of its execution.METHODS: Single-sample observational observation with controlled conditions. 27 patients with diabetic polyneuropathy. All patients were treated according to modern standards. The observation was performed in one series at the beginning of the course of inpatient treatment. Estimation of body balance on a power platform — stabiloplatform) — stabilometry. The procedure included 5 stages of management, in which the patient followed the instructions (training) in which there was a stepwise increase in the depth of feedback («sensitivity») at each stage from 10 to 50% of the conditional «normal», with a step of 10%. A quantitative assessment of the external result (execution of instructions) and parameters of regulation of the vertical posture was carried out.RESULTS: All patients included in the follow-up showed that the implementation of instructions with increasing depth of feedback decreased sharply when the conditionally «normal» value was exceeded by 30–35%. At the same time, the initial parameters of vertical posture control in the sample patients did not affect the dynamics of results when performing the task with visual feedback. Factor analysis indicates the presence of the only significant factor associated with the effectiveness of performing a motor-cognitive task here — changes in the depth of feedback. The accepted significance level α = 0.05.CONCLUSIONS: The depth of feedback in motor-cognitive tasks with visual feedback is a key characteristic that affects performance. The ability to increase the depth of feedback in the range of about 35; from conditionally «normal», can be useful for ensuring differentiation of loads during motor rehabilitation of patients in order to increase the effectiveness of training. In addition, in theoretical terms, the proposed model of the motor-cognitive problem can be relevant in the study of «dual» problems, where the relationship of motor and cognitive components is studied.

Social Orientation in the Luteal Phase: Increased Social Feedback Sensitivity, Inhibitory Response, Interpersonal Anxiety and Cooperation Preference

Cyclical fluctuations of the ovarian hormones estrogen (E2) and progesterone (PROG) have multiple effects on reproduction and development. However, little is known about the roles of E2 and PROG in women’s social behaviors. Here, based on evolutionary theory suggesting social sensitivity and inhibition ability are conductive to maintaining social relationships, we provide evidence for the association between menstrual phases and social orientation. In Study 1, 78 women provided saliva samples and reported their intensity of behavioral activation/inhibition system (BAS/BIS) and interpersonal sensitivity at either of two phases of the menstrual cycle: late follicular phase (FP), and mid-luteal phase (LP). A significant between-subject association emerged, revealing that women with higher PROG levels reported higher levels of social feedback sensitivity, and women with relatively high PROG levels showed a positive association between their E2 levels and inhibitory response. In Study 2, 30 women reported their interpersonal anxiety and finished the social value orientation (SVO) measures at both late FP and mid-LP. A significant within-person effect emerged: women in the mid-LP, which is characterized by higher PROG levels, reported higher levels of interpersonal anxiety and SVO. In sum, these findings revealed that women’s social orientation could fluctuate naturally with ovarian hormones across the menstrual cycle.

Noradrenergic regulation of Win-Stay/Lose-Shift policy and choice determinism in a two-armed bandit task

Recent studies have established that one-trial-back decision policies (Win-Stay/Lose-Shift) and measures of reinforcement learning (RL), e.g. learning rate, can explain how animals perform two-armed bandit tasks. In many published studies, outcomes reverse after one option is selected repeatedly (e.g. 8 selections in a row), and the primary measure of performance is the number of reversals completed. Performance and Win-Stay likelihood are confounded by using recent performance to drive reversals. An alternative design reverses outcomes across options over fixed blocks of trials. We used this blocked design and tested rats in a spatial two-armed bandit task. We analyzed performance using Win-Stay/Lose-Shift (WSLS) metrics and a RL algorithm. We found that WSLS policies remain stable with increasing reward uncertainty, while choice accuracy decreases. Within test sessions, learning rates increased as rats adapted their strategies over the first few reversals but inverse temperature remains stable. We found that muscimol inactivation of medial orbital cortex (mOFC) mediates task performance and negative feedback sensitivity. Finally, we examined the role of the adrenergic system in bandit performance, and found yohimbine (2 mg/kg) dramatically decreased sensitivity to positive feedback, leading to decreases in accuracy and inverse temperature. These effects are partially dependent on a2 adrenergic receptors in OFC. Our findings demonstrate a correspondence between reward schedule, WSLS policies and RL metrics in a task design that is free of the confound between Wins and reversals, and that the noradrenergic influence of mOFC on WSLS policy is dissociable from the regions general role in cognitive flexibility.

Investigation of reward learning and feedback sensitivity in non-clinical participants with a history of early life stress

BackgroundEarly life stress (ELS) is an important risk factor for the development of depression. Impairments in reward learning and feedback sensitivity have been suggested. to be an intermediate phenotype in depression aetiology. We therefore hypothesised that healthy adults with a history of ELS would have impairments in reward learning and feedback sensitivity.MethodsWe recruited 64 adult participants with high levels of ELS and no diagnosis of a current mental health disorder in addition to 65 controls. Participants completed two online reward learning tasks: the probabilistic reversal learning task (PRLT) and probabilistic reward task (PRT). Participants also completed depression, anhedonia, social status and stress scales with PRLT data being additionally analysed utilising a reinforcement learning model.ResultsParticipants with high levels of ELS showed decreased positive feedback sensitivity (PFS) in the PRLT compared to controls. High ELS participants also tended towards possessing a decreased model-free learning rate which strengthened in subsequent analysis. This was coupled with a decreased learning ability in the acquisition phase of block 1 following the practice session. Neither groups of participants showed a reward induced response bias in the PLT however high ELS participants exhibited decreased discrimination ability between stimuli; this was however accounted for by depression symptomology in further analysis.ConclusionsThese data suggest that healthy participants without a mental health diagnosis and high levels of ELS show deficits in PFS and reward learning in the PRLT that are distinct from depressed patients. These deficits may be relevant to an increased vulnerability to depression.