General and anxiety-linked influences of acute serotonin reuptake inhibition on neural responses associated with attended visceral sensation.

Ordinary sensations from inside the body are important causes and consequences of our affective states and behaviour, yet the roles of neurotransmitters in interoceptive processing have been unclear. With a within-subjects design, this experiment tested the impacts of acute increases of endogenous extracellular serotonin on the neural processing of attended internal sensations and the links of these effects to anxiety using a selective serotonin reuptake inhibitor (SSRI) (20 mg CITALOPRAM) and a PLACEBO. Twenty-one healthy volunteers (fourteen female, mean age 23.9) completed the Visceral Interoceptive Attention (VIA) task while undergoing functional magnetic resonance imaging (fMRI) with each treatment. The VIA task required focused attention on the heart, stomach, or visual sensation. The relative neural interoceptive responses to heart sensation [heart minus visual attention] (heart-IR) and stomach sensation [stomach minus visual attention] (stomach-IR) were compared between treatments. Visual attention subtraction controlled for the general effects of CITALOPRAM on sensory processing. CITALOPRAM was associated with lower interoceptive processing in viscerosensory (the stomach-IR of bilateral posterior insular cortex) and integrative/affective (the stomach-IR and heart-IR of bilateral amygdala) components of interoceptive neural pathways. In anterior insular cortex, CITALOPRAM reductions of heart-IR depended on anxiety levels, removing a previously known association between anxiety and the region's response to attended heart sensation observed with PLACEBO. Preliminary post hoc analysis indicated that CITALOPRAM effects on the stomach-IR of the amygdalae corresponded to acute anxiety changes. This direct evidence of general and anxiety-linked serotonergic influence on neural interoceptive processes advances our understanding of interoception, its regulation, and anxiety.

Feasibility of unconscious instrumental conditioning: A registered replication.

The extent to which high-level, complex functions can proceed unconsciously has been a topic of considerable debate. While unconscious processing has been demonstrated for a range of low-level processes, from feature integration to simple forms of conditioning and learning, theoretical contributions suggest that increasing complexity requires conscious access. Here, we focus our attention on instrumental conditioning, which has been previously shown to proceed without stimulus awareness. Yet, instrumental conditioning also involves integrating information over a large temporal scale and distinct modalities in order to deploy selective action, constituting a process of substantial complexity. With this in mind, we revisit the question of feasibility of instrumental conditioning in the unconscious domain. Firstly, we address the theoretical and practical considerations relevant to unconscious learning in general. Secondly, we aim to replicate the first study to show instrumental conditioning in the absence of stimulus awareness (Pessiglione et al., 2008), following the original design and supplementing the original crucial analyses with a Bayesian approach (Experiment 1). We found that apparent unconscious learning took place when replicating the original methods directly and according to the tests of awareness used. However, we could not establish that the full sample was unaware in a separate awareness check. We therefore attempted to replicate the effect yet again with improved methods to address the issues related to sensitivity and immediacy (Experiment 2), including an individual threshold-setting task and a trial-by-trial awareness check permitting exclusion of individual aware trials. Here, we found evidence for absence of unconscious learning. This result provides evidence that instrumental conditioning did not occur without stimulus awareness in this paradigm, supporting the view that complex forms of learning may rely on conscious access. Our results provides support for the proposal that perceptual consciousness may be necessary for complex, flexible processes, especially where selective action and behavioural adaptation are required.

Awareness is required for autonomic performance monitoring in instrumental learning: Evidence from cardiac activity.

Performance monitoring is a vital aspect of successful learning and decision-making. Performance errors are reflected in the autonomic nervous system, indicating the need for behavioral adjustment. As part of this response, errors cause a pronounced deceleration in heart rate, compared to correct decisions, and precede explicit awareness of stimulus-response outcome contingencies. However, it is unknown whether those signals are present and able to inform instrumental learning without stimulus awareness, where explicit performance monitoring is disabled. With mixed evidence for unconscious instrumental learning, determining the presence or absence of autonomic signatures of performance monitoring can shed light on its feasibility. Here, we employed an unconscious instrumental conditioning task, where successful learning is evidenced by increased approach responses to visually masked rewarding stimuli, and avoidance of punishing stimuli. An electrocardiogram (ECG) assessed cardiac activity throughout the learning process. Natural fluctuations of awareness under masking permitted us to contrast learning and cardiac deceleration for trials with, versus without, conscious stimulus awareness. Our results demonstrate that on trials where participants did not consciously perceive the stimulus, there was no differentiation in cardiac response between rewarding and punishing feedback, indicating an absence of performance monitoring. In contrast, consciously perceived stimuli elicited the expected error-related deceleration. This result suggests that, in unconscious instrumental learning, the brain might be unable to acquire knowledge of stimulus values to guide correct instrumental choices. This evidence provides support for the notion that consciousness might be required for flexible adaptive behavior, and that this may be mediated through bodily signals.

A single oral dose of citalopram increases interoceptive insight in healthy volunteers.

RATIONALE: Interoception is the signalling, perception, and interpretation of internal physiological states. Many mental disorders associated with changes of interoception, including depressive and anxiety disorders, are treated with selective serotonin reuptake inhibitors (SSRIs). However, the causative link between SSRIs and interoception is not yet clear. OBJECTIVES: To ascertain the causal effect of acute changes of serotonin levels on cardiac interoception. METHODS: Using a within-participant placebo-controlled design, forty-seven healthy human volunteers (31 female, 16 male) were tested on and off a 20 mg oral dose of the commonly prescribed SSRI, citalopram. Participants made judgements on the synchrony between their heartbeat and auditory tones and then expressed confidence in each judgement. We measured three types of interoceptive cognition. RESULTS: Citalopram increased cardiac interoceptive insight, measured as correspondence of self-reported confidence to the likelihood that interoceptive judgements were actually correct. This effect was driven by enhanced confidence for correct interoceptive judgements and was independent of measured cardiac and reported subjective effects of the drug. CONCLUSIONS: An acute change of serotonin levels can increase insight into the reliability of inferences made from cardiac interoceptive sensations.

Approach-Avoidance Decisions Under Threat: The Role of Autonomic Psychophysiological States.

Acutely challenging or threatening situations frequently require approach-avoidance decisions. Acute threat triggers fast autonomic changes that prepare the body to freeze, fight or flee. However, such autonomic changes may also influence subsequent instrumental approach-avoidance decisions. Since defensive bodily states are often not considered in value-based decision-making models, it remains unclear how they influence the decision-making process. Here, we aim to bridge this gap by discussing the existing literature on the potential role of threat-induced bodily states on decision making and provide a new neurocomputational framework explaining how these effects can facilitate or bias approach-avoid decisions under threat. Theoretical accounts have stated that threat-induced parasympathetic activity is involved in information gathering and decision making. Parasympathetic dominance over sympathetic activity is particularly seen during threat-anticipatory freezing, an evolutionarily conserved response to threat demonstrated across species and characterized by immobility and bradycardia. Although this state of freezing has been linked to altered information processing and action preparation, a full theoretical treatment of the interactions with value-based decision making has not yet been achieved. Our neural framework, which we term the Threat State/Value Integration (TSI) Model, will illustrate how threat-induced bodily states may impact valuation of competing incentives at three stages of the decision-making process, namely at threat evaluation, integration of rewards and threats, and action initiation. Additionally, because altered parasympathetic activity and decision biases have been shown in anxious populations, we will end with discussing how biases in this system can lead to characteristic patterns of avoidance seen in anxiety-related disorders, motivating future pre-clinical and clinical research.