Bayesian Learning Models of Pain: A Call to Action

Learning is fundamentally about action, enabling the successful navigation of a changing and uncertain environment. The experience of pain is central to this process, indicating the need for a change in action so as to mitigate potential threat to bodily integrity. This review considers the application of Bayesian models of learning in pain that inherently accommodate uncertainty and action, which, we shall propose are essential in understanding learning in both acute and persistent cases of pain

Neural Circuitry of Novelty Salience Processing in Psychosis Risk: Association With Clinical Outcome

Psychosis has been proposed to develop from dysfunction in a hippocampal-striatal-midbrain circuit, leading to aberrant salience processing. Here, we used functional magnetic resonance imaging (fMRI) during novelty salience processing to investigate this model in people at clinical high risk (CHR) for psychosis according to their subsequent clinical outcomes. Seventy-six CHR participants as defined using the Comprehensive Assessment of At-Risk Mental States (CAARMS) and 31 healthy controls (HC) were studied while performing a novelty salience fMRI task that engaged an a priori hippocampal-striatal-midbrain circuit of interest. The CHR sample was then followed clinically for a mean of 59.7 months (~5 y), when clinical outcomes were assessed in terms of transition (CHR-T) or non-transition (CHR-NT) to psychosis (CAARMS criteria): during this period, 13 individuals (17%) developed a psychotic disorder (CHR-T) and 63 did not. Functional activation and effective connectivity within a hippocampal-striatal-midbrain circuit were compared between groups. In CHR individuals compared to HC, hippocampal response to novel stimuli was significantly attenuated (P = .041 family-wise error corrected). Dynamic Causal Modelling revealed that stimulus novelty modulated effective connectivity from the hippocampus to the striatum, and from the midbrain to the hippocampus, significantly more in CHR participants than in HC. Conversely, stimulus novelty modulated connectivity from the midbrain to the striatum significantly less in CHR participants than in HC, and less in CHR participants who subsequently developed psychosis than in CHR individuals who did not become psychotic. Our findings are consistent with preclinical evidence implicating hippocampal-striatal-midbrain circuit dysfunction in altered salience processing and the onset of psychosis

The effect of dopamine agonists on adaptive and aberrant salience in Parkinson's disease

Clinical evidence suggests that after initiation of dopaminergic medications some patients with Parkinson's disease (PD) develop psychotic symptoms, such as hallucinations and delusions. Here, we tested the hypothesis that the neurocognitive basis of this phenomenon can be defined as the formation of arbitrary and illusory associations between conditioned stimuli and reward signals, called aberrant salience. Young, never-medicated PD patients and matched controls were assessed on a speeded reaction time task in which the probe stimulus was preceded by conditioned stimuli that could signal monetary reward by color or shape. The patients and controls were re-evaluated after 12 weeks during which the patients received a dopamine agonist (pramipexole or ropinirole). Results indicated that dopamine agonists increased both adaptive and aberrant salience in PD patients, that is, formation of real and illusory associations between conditioned stimuli and reward, respectively. This effect was present when associations were assessed by means of faster responding after conditioned stimuli signaling reward (implicit salience) and overt rating of stimulus-reward links (explicit salience). However, unusual feelings and experiences, which are subclinical manifestations of psychotic-like symptoms, were specifically related to irrelevant and illusory stimulus-reward associations (aberrant salience) in PD patients receiving dopamine agonists. The learning of relevant and real stimulus-reward associations (adaptive salience) was not related to unusual experiences. These results suggest that dopamine agonists may increase psychotic-like experiences in young patients with PD, possibly by facilitating dopaminergic transmission in the ventral striatum, which results in aberrant associations between conditioned stimuli and reward

(Mis)computation in Computational Psychiatry

An adequate explication of miscomputation should do justice to relevant practices in the computational sciences. While philosophers of computation have neglected scientific practices outside computer science, here I focus on computational psychiatry. I argue that computational psychiatrists use a concept of miscomputation in their explanations, and that this concept should be explicated as interest-relative and perspectival, alt-hough non-arbitrary, relatively clear-cut, experimentally evaluable, and instrumentally useful. To the extent my argument is convincing, we should reconsider the general adequacy of the mechanistic view of computation for illuminating relevant methodological and explanatory practices in the computational sciences

(Mis)computation in Computational Psychiatry

An adequate explication of miscomputation should do justice to relevant practices in the computational sciences. While philosophers of computation have neglected scientific practices outside computer science, here I focus on computational psychiatry. I argue that computational psychiatrists use a concept of miscomputation in their explanations, and that this concept should be explicated as interest-relative and perspectival, alt-hough non-arbitrary, relatively clear-cut, experimentally evaluable, and instrumentally useful. To the extent my argument is convincing, we should reconsider the general adequacy of the mechanistic view of computation for illuminating relevant methodological and explanatory practices in the computational sciences

Acute stress impairs reward learning in men

Acute stress is ubiquitous in everyday life, but the extent to which acute stress affects how people learn from the outcomes of their choices is still poorly understood. Here, we investigate how acute stress impacts reward and punishment learning in men using a reinforcement-learning task. Sixty-two male participants performed the task whilst under stress and control conditions. We observed that acute stress impaired participants' choice performance towards monetary gains, but not losses. To unravel the mechanism(s) underlying such impairment, we fitted a reinforcement-learning model to participants' trial-by-trial choices. Computational modeling indicated that under acute stress participants learned more slowly from positive prediction errors - when the outcomes were better than expected - consistent with stress-induced dopamine disruptions. Such mechanistic understanding of how acute stress impairs reward learning is particularly important given the pervasiveness of stress in our daily life and the impact that stress can have on our wellbeing and mental health.ortuguese Foundation for Science and Technology (FCT) to A. Seara-Cardoso [PTDC/MHC-PCN/2296/2014, co-financed by FEDER through COMPETE2020 under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-016747)] and to A. Mesquita (IF/00750/2015). J. Carvalheiro was supported by a FCT PhD fellowship (PD/BD/128467/2017). This study was conducted at the Psychology Research Centre (PSI/01662), School of Psychology, University of Minho, supported by FCT and the Portuguese Ministry of Science, Technology and Higher Education (UID/PSI/01662/2019), through national funds (PIDDAC

Longitudinal alterations in motivational salience processing in ultra-high-risk subjects for psychosis

Impairments in the attribution of salience are thought to be fundamental to the development of psychotic symptoms and the onset of psychotic disorders. The aim of the present study was to explore longitudinal alterations in salience processing in ultra-high-risk subjects for psychosis.; A total of 23 ultra-high-risk subjects and 13 healthy controls underwent functional magnetic resonance imaging at two time points (mean interval of 17 months) while performing the Salience Attribution Test to assess neural responses to task-relevant (adaptive salience) and task-irrelevant (aberrant salience) stimulus features.; At presentation, high-risk subjects were less likely than controls to attribute salience to relevant features, and more likely to attribute salience to irrelevant stimulus features. These behavioural differences were no longer evident at follow-up. When attributing salience to relevant cue features, ultra-high-risk subjects showed less activation than controls in the ventral striatum at both baseline and follow-up. Within the high-risk sample, amelioration of abnormal beliefs over the follow-up period was correlated with an increase in right ventral striatum activation during the attribution of salience to relevant cue features.; These findings confirm that salience processing is perturbed in ultra-high-risk subjects for psychosis, that this is linked to alterations in ventral striatum function, and that clinical outcomes are related to longitudinal changes in ventral striatum function during salience processing

Dopaminergic basis for signalling belief updates, but not surprise, and the link to paranoia

Distinguishing between meaningful and meaningless sensory information is fundamental to forming accurate representations of the world. Dopamine is thought to play a central role in processing the meaningful information content of observations, which motivates an agent to update their beliefs about the environment. However, direct evidence for dopamine’s role in human belief updating is lacking. We addressed this question in healthy volunteers who performed a model-based functional magnetic resonance imaging (fMRI) task designed to separate the neural processing of meaningful and meaningless sensory information. We modelled participant behaviour using a normative Bayesian observer model, and used the magnitude of the model-derived belief update following an observation to quantify its meaningful information content. We also acquired positron emission tomography (PET) imaging measures of dopamine function in the same subjects. We show that the magnitude of belief updates about task structure (meaningful information), but not pure sensory surprise (meaningless information), are encoded in midbrain and ventral striatum activity. Using PET we show that the neural encoding of meaningful information is negatively related to dopamine-2/3 receptor availability in the midbrain and dexamphetamine-induced dopamine release capacity in the striatum. Trial-by-trial analysis of task performance indicated that subclinical paranoid ideation is negatively related to behavioural sensitivity to observations carrying meaningful information about the task structure. The findings provide direct evidence implicating dopamine in model-based belief updating in humans, and have implications for understating the pathophysiology of psychotic disorders where dopamine function is disrupted

The neurobiology of interoception in health and disease

Interoception is the sensing of internal bodily sensations. Interoception is an umbrella term that encompasses (1) the afferent (body‐to‐brain) signaling through distinct neural and humoral (including immune and endocrine) channels; (2) the neural encoding, representation, and integration of this information concerning internal bodily state; (3) the influence of such information on other perceptions, cognitions, and behaviors; (4) and the psychological expression of these representations as consciously accessible physical sensations and feelings. Interoceptive mechanisms ensure physiological health through the cerebral coordination of homeostatic reflexes and allostatic responses that include motivational behaviors and associated affective and emotional feelings. Furthermore, the conscious, unitary sense of self in time and space may be grounded in the primacy and lifelong continuity of interoception. Body‐to‐brain interactions influence physical and mental well‐being. Consequently, we show that systematic investigation of how individual differences, and within‐individual changes, in interoceptive processing can contribute to the mechanistic understanding of physical and psychological disorders. We present a neurobiological overview of interoception and describe how interoceptive impairments at different levels relate to specific physical and mental health conditions, including sickness behaviors and fatigue, depression, eating disorders, autism, and anxiety. We frame these findings in an interoceptive predictive processing framework and highlight potential new avenues for treatments