Classical Aversive Conditioning Research Articles

Context-induced renewal of passive but not active coping behaviours in the shock-probe defensive burying task.

Renewal is the return of extinguished responding after removal from the extinction context. Renewal has been extensively studied using classical aversive conditioning procedures that measure a passive freezing response to an aversive conditioned stimulus. However, coping responses to aversive stimuli are complex and can be reflected in passive and active behaviours. Using the shock-probe defensive burying task, we investigated whether different coping responses are susceptible to renewal. During conditioning, male, Long-Evans rats were placed into a specific context (Context A) where an electrified shock-probe delivered a 3 mA shock upon contact. During extinction, the shock-probe was unarmed in either the same (Context A) or a different context (Context B). Renewal of conditioned responses was assessed in the conditioning context (ABA) or in a novel context (ABC or AAB). Renewal of passive coping responses, indicated by an increased latency and a decreased duration of shock-probe contacts, was observed in all groups. However, renewal of passive coping, measured by increased time spent on the side of the chamber opposite the shock-probe, was only found in the ABA group. Renewal of active coping responses linked to defensive burying was not observed in any group. The present findings highlight the presence of multiple psychological processes underlying even basic forms of aversive conditioning and demonstrate the importance of assessing a broader set of behaviours to tease apart these different underlying mechanisms. The current findings suggest that passive coping responses may be more reliable indicators for assessing renewal than active coping behaviours associated with defensive burying.

Human threat circuits: Threats of pain, aggressive conspecific, and predator elicit distinct BOLD activations in the amygdala and hypothalamus.

Threat processing, enabled by threat circuits, is supported by a remarkably conserved neural architecture across mammals. Threatening stimuli relevant for most species include the threat of being attacked by a predator or an aggressive conspecific and the threat of pain. Extensive studies in rodents have associated the threats of pain, predator attack and aggressive conspecific attack with distinct neural circuits in subregions of the amygdala, the hypothalamus and the periaqueductal gray. Bearing in mind the considerable conservation of both the anatomy of these regions and defensive behaviors across mammalian species, we hypothesized that distinct brain activity corresponding to the threats of pain, predator attack and aggressive conspecific attack would also exist in human subcortical brain regions. Forty healthy female subjects underwent fMRI scanning during aversive classical conditioning. In close analogy to rodent studies, threat stimuli consisted of painful electric shocks, a short video clip of an attacking bear and a short video clip of an attacking man. Threat processing was conceptualized as the expectation of the aversive stimulus during the presentation of the conditioned stimulus. Our results demonstrate differential brain activations in the left and right amygdala as well as in the left hypothalamus for the threats of pain, predator attack and aggressive conspecific attack, for the first time showing distinct threat-related brain activity within the human subcortical brain. Specifically, the threat of pain showed an increase of activity in the left and right amygdala and the left hypothalamus compared to the threat of conspecific attack (pain > conspecific), and increased activity in the left amygdala compared to the threat of predator attack (pain > predator). Threat of conspecific attack revealed heightened activity in the right amygdala, both in comparison to threat of pain (conspecific > pain) and threat of predator attack (conspecific > predator). Finally, for the condition threat of predator attack we found increased activity in the bilateral amygdala and the hypothalamus when compared to threat of conspecific attack (predator > conspecific). No significant clusters were found for the contrast predator attack > pain. Results suggest that threat type-specific circuits identified in rodents might be conserved in the human brain.

The power of swearing: What we know and what we don’t

Swearing produces effects that are not observed with other forms of language use. Thus, swearing is powerful. It generates a range of distinctive outcomes: physiological, cognitive, emotional, pain-relieving, interactional and rhetorical. However, we know that the power of swearing is not intrinsic to the words themselves. Hence, our starting question is: How does swearing get its power? In this Overview Paper, our aim is threefold. (1) We present an interdisciplinary analysis of the power of swearing (‘what we know’), drawing on insights from cognitive studies, pragmatics, communication, neuropsychology, and biophysiology. We identify specific effects of swearing, including, inter alia: emotional force and arousal; increased attention and memory; heightened autonomic activity, such as heart rate and skin conductance; hypoalgesia (pain relief); increased strength and stamina; and a range of distinctive interpersonal, relational and rhetorical outcomes. (2) We explore existing (possible) explanations for the power of swearing, including, in particular, the hypothesis that aversive classical conditioning takes place via childhood punishments for swearing. (3) We identify and explore a series of questions and issues that remain unanswered by current research/theorising (‘what we don’t know’), including the lack of direct empirical evidence for aversive classical conditioning; and we offer directions for future research.

Conditional Regulation of Blood Pressure in Response to Emotional Stimuli by the Central Nucleus of the Amygdala in Rats.

Humans and animals can determine whether a situation is favorable to them and act accordingly. For this, the autonomic tuning of the cardiovascular system to supply energy to active skeletal muscles through the circulatory system is as important as motor control. However, how the autonomic cardiovascular responses are regulated in dynamically changing environments and the neuronal mechanisms underlying these responses remain unclear. To resolve these issues, we recorded the blood pressure and heart rate of head-restrained rats during dynamically changing appetitive and aversive classical conditioning tasks. The rats displayed various associations between conditioned stimuli and unconditioned stimuli in appetitive (sucrose water), neutral (no outcome), and aversive (air puff) blocks. The blood pressure and heart rate in the appetitive block gradually increased in response to the reward-predicting cue and the response to the actual reward vigorously increased. The reward-predictive response was significantly higher than the responses obtained in the neutral and aversive condition blocks. To investigate whether the reward-predictive pressor response was caused by orofacial movements such as anticipatory licking behavior, we separately analyzed high- and low-licking trials. The conditioned pressor response was observed even in trials with low-licking behaviors. Blood pressure and heart rate responses to the air puff-predicting cue in the aversive block were not significantly different from the responses in the neutral block. The conditioned blood pressure response rapidly changed with condition block switching. Furthermore, to examine the contribution of the amygdala as an emotion center to these conditioned responses, we bilaterally microinjected a GABAA receptor agonist, muscimol, into the central nucleus of the amygdala. Pharmacological inactivation of the central nucleus of the amygdala significantly decreased the reward-predictive pressor responses. These results suggest that the blood pressure is adaptively and rapidly regulated by emotional conditioned stimuli and that the central nucleus of the amygdala participates in regulating the pressor response in dynamically changing situations.

Aversive Conditioning of Spatial Position Sharpens Neural Population-Level Tuning in Visual Cortex and Selectively Alters Alpha-Band Activity.

Processing capabilities for many low-level visual features are experientially malleable, aiding sighted organisms in adapting to dynamic environments. Explicit instructions to attend a specific visual field location influence retinotopic visuocortical activity, amplifying responses to stimuli appearing at cued spatial positions. It remains undetermined both how such prioritization affects surrounding nonprioritized locations, and if a given retinotopic spatial position can attain enhanced cortical representation through experience rather than instruction. The current report examined visuocortical response changes as human observers (N = 51, 19 male) learned, through differential classical conditioning, to associate specific screen locations with aversive outcomes. Using dense-array EEG and pupillometry, we tested the preregistered hypotheses of either sharpening or generalization around an aversively associated location following a single conditioning session. Competing hypotheses tested whether mean response changes would take the form of a Gaussian (generalization) or difference-of-Gaussian (sharpening) distribution over spatial positions, peaking at the viewing location paired with a noxious noise. Occipital 15 Hz steady-state visual evoked potential responses were selectively heightened when viewing aversively paired locations and displayed a nonlinear, difference-of-Gaussian profile across neighboring locations, consistent with suppressive surround modulation of nonprioritized positions. Measures of alpha-band (8-12 Hz) activity were differentially altered in anterior versus posterior locations, while pupil diameter exhibited selectively heightened responses to noise-paired locations but did not evince differences across the nonpaired locations. These results indicate that visuocortical spatial representations are sharpened in response to location-specific aversive conditioning, while top-down influences indexed by alpha-power reduction exhibit posterior generalization and anterior sharpening.SIGNIFICANCE STATEMENT It is increasingly recognized that early visual cortex is not a static processor of physical features, but is instead constantly shaped by perceptual experience. It remains unclear, however, to what extent the cortical representation of many fundamental features, including visual field location, is malleable by experience. Using EEG and an aversive classical conditioning paradigm, we observed sharpening of visuocortical responses to stimuli appearing at aversively associated locations along with location-selective facilitation of response systems indexed by pupil diameter and EEG alpha power. These findings highlight the experience-dependent flexibility of retinotopic spatial representations in visual cortex, opening avenues toward novel treatment targets in disorders of attention and spatial cognition.

Complexity and plasticity in honey bee phototactic behaviour

The ability to move towards or away from a light source, namely phototaxis, is essential for a number of species to find the right environmental niche and may have driven the appearance of simple visual systems. In this study we ask if the later evolution of more complex visual systems was accompanied by a sophistication of phototactic behaviour. The honey bee is an ideal model organism to tackle this question, as it has an elaborate visual system, demonstrates exquisite abilities for visual learning and performs phototaxis. Our data suggest that in this insect, phototaxis has wavelength specific properties and is a highly dynamical response including multiple decision steps. In addition, we show that previous experience with a light (through exposure or classical aversive conditioning) modulates the phototactic response. This plasticity is dependent on the wavelength used, with blue being more labile than green or ultraviolet. Wavelength, intensity and past experience are integrated into an overall valence for each light that determines phototactic behaviour in honey bees. Thus, our results support the idea that complex visual systems allow sophisticated phototaxis. Future studies could take advantage of these findings to better understand the neuronal circuits underlying this processing of the visual information.

Monoamines, Insulin and the Roles They Play in Associative Learning in Pond Snails.

Molluscan gastropods have long been used for studying the cellular and molecular mechanisms underlying learning and memory. One such gastropod, the pond snail Lymnaea stagnalis, exhibits long-term memory (LTM) following both classical and operant conditioning. Using Lymnaea, we have successfully elucidated cellular mechanisms of learning and memory utilizing an aversive classical conditioning procedure, conditioned taste aversion (CTA). Here, we present the behavioral changes following CTA training and show that the memory score depends on the duration of food deprivation. Then, we describe the relationship between the memory scores and the monoamine contents of the central nervous system (CNS). A comparison of learning capability in two different strains of Lymnaea, as well as the filial 1 (F1) cross from the two strains, presents how the memory scores are correlated in these populations with monoamine contents. Overall, when the memory scores are better, the monoamine contents of the CNS are lower. We also found that as the insulin content of the CNS decreases so does the monoamine contents which are correlated with higher memory scores. The present review deepens the relationship between monoamine and insulin contents with the memory score.

Attention to a threat-related feature does not interfere with concurrent attentive feature selection.

Visual features associated with a task and those that predict noxious events both prompt selectively heightened visuocortical responses. Conflicting views exist regarding how the competition between a task-related and a threat-related feature is resolved when they co-occur in time and space. Utilizing aversive classical Pavlovian conditioning, we investigated the visuocortical representation of two simultaneously presented, fully overlapping visual stimuli. Isoluminant red and green random dot kinematogram (RDK) stimuli were flickered at distinct tagging frequencies (8.57Hz, 12Hz) to elicit distinguishable steady-state visual evoked potentials (ssVEPs). Occasional coherent motion events prompted a motor response (task) or predicted a noxious noise (threat). These events occurred either in the green (task cue), the red (threat cue), or in both RDKs simultaneously. In the initial habituation phase, participants responded to coherent motion of the green RDK with a key press, but no loud noise was presented at any time. Here, selective amplification was seen for the task-relevant (green) RDK, and interference was observed when both RDKs simultaneously showed coherent motion. Upon pairing the threat cue with the noxious noise in the subsequent acquisition phase, the threat cue-evoked ssVEP (red RDK) was also amplified, but this amplification did not interact with amplification of the task cue or alter the behavioral or visuocortical interference effect observed during simultaneous coherent motion. Although competing feature conjunctions resulted in interference in the visual cortex, the acquisition of a bias toward an individual threat-related feature did not result in additional cost effects.

Mismatch Negativity in Rat Auditory Cortex Represents the Empirical Salience of Sounds.

Mismatch negativity (MMN) is an N-methyl-D-aspartic acid-mediated component and thus has been widely considered a major candidate biomarker of schizophrenia. However, at present, no direct evidence has linked the MMN response and aberrant salience processing reported in schizophrenia patients, i.e., whether MMN represents empirical salience of the deviant stimulus. To test the eligibility of the MMN response as a biomarker of schizophrenia, we hypothesized and verified that the MMN in the rat auditory cortex encodes empirical salience, which depends on both empirical rarity of sound and association of sound with salient events through classical conditioning. We exposed rats to sound or appetitive or aversive classical conditioning and extinction training of aversive conditioning, then recorded MMN from the auditory cortex. We focused on the frequency-dependent asymmetry of the MMN amplitude; increment frequency changes elicit asymmetrically larger MMN amplitudes than do decremental frequency changes. We found that sound exposure reversed this asymmetry in rats, indicating that MMN encodes the empirical rarity of deviant sounds. The MMN amplitude was larger in the appetitive or aversive classical conditioning groups, and smaller after extinction training following aversive conditioning. These results indicate that the MMN response reflects the empirical salience of sound. The present work first linked MMN with empirical salience processing and expands the possibilities of MMN as a strong clinical biomarker of schizophrenia.

Fan-Shaped Body Neurons in the Drosophila Brain Regulate Both Innate and Conditioned Nociceptive Avoidance

Multiple brain regions respond to harmful nociceptive stimuli. However, it remains unclear as to whether behavioral avoidance of such stimuli can be modulated within the same or distinct brain networks. Here, we found subgroups of neurons localized within a well-defined brain region capable of mediating both innate and conditioned nociceptive avoidance in Drosophila. Neurons in the ventral, but not the dorsal, of the multiple-layer organized fan-shaped body (FB) are responsive to electric shock (ES). Silencing ES-responsive neurons, but not non-responsive neurons, leads to reduced avoidance of harmful stimuli, including ES and heat shock. Activating these neurons consistently triggers avoidance and can serve as an unconditional stimulus in an aversive classical conditioning task. Among the three groups of responsive neurons identified, two also have reduced activity in ES-conditioned odor avoidance. These results demonstrate that both innate and conditioned nociceptive avoidance might be represented within neurons confined to a single brainregion.

Polymorphisms that affect GABA neurotransmission predict processing of aversive prediction errors in humans

Learning is one of our most adaptive abilities, allowing us to adjust our expectations about future events. Aberrant learning processes may underlie disorders such as anxiety, motivating the search for the neural mechanisms that underpin learning. Animal studies have shown that the neurotransmitter GABA is required for the computation of prediction errors, the mismatches between anticipated and experienced outcomes, which drive new learning. Given that evidence from human studies is lacking, we sought to determine whether these findings extend to humans. Here, in two samples of Caucasian individuals, we investigated whether genetically determined individual differences in GABA neurotransmission predict the P3 event-related potential, an EEG component known to reflect prediction error processing. Consistent with the results of animal studies, we show that a weighted genetic risk score computed from the number of GABRB2 rs1816072 A alleles (associated with increased expression of the GABAA receptor β2 subunit gene) and the number of ErbB4 rs7598440 T alleles (associated with increased GABA concentration) predicts optimal prediction error processing during aversive classical conditioning with both visual (Experiment 1, N = 90; p = .010) and auditory (Experiment 2; N = 92; p = .031) unconditioned stimuli. Our finding that optimal processing of aversive prediction errors is reduced in individuals genetically predisposed towards decreased GABA neurotransmission suggests a potential mechanism linking GABA and anxiety. Specifically, reduced GABA signalling via GABAA receptors could result in aberrant learning from aversive experiences and vulnerability to anxiety disorders.

Differentiating aversive conditioning in bistable perception: Avoidance of a percept vs. salience of a stimulus.

Alternating conscious visual perception of bistable stimuli is influenced by several factors. In order to understand the effect of negative valence, we tested the effect of two types of aversive conditioning on dominance durations in binocular rivalry. Participants received either aversive classical conditioning of the stimuli shown alone between rivalry blocks, or aversive percept conditioning of one of the two possible perceptual choices during rivalry. Both groups showed successful aversive conditioning according to skin conductance responses and affective valence ratings. However, while classical conditioning led to an immediate but short-lived increase in dominance durations of the conditioned stimulus, percept conditioning yielded no significant immediate effect but tended to decrease durations of the conditioned percept during extinction. These results show dissociable effects of value learning on perceptual inference in situations of perceptual conflict, depending on whether learning relates to the decision between conflicting perceptual choices or the sensory stimuli per se.

Effects of Aversive Classical Conditioning on Sexual Response in Women With Dyspareunia and Sexually Functional Controls

IntroductionIn dyspareunia—a somatically unexplained vulvovaginal pain associated with sexual intercourse—learned pain-related fear and inhibited sexual arousal are supposed to play a pivotal role. Based on research findings indicating that enhanced pain conditioning is involved in the etiology and maintenance of chronic pain, in the present study it was hypothesized that enhanced pain conditioning also might be involved in dyspareunia. AimTo test whether learned associations between pain and sex negatively affect sexual response; whether women with dyspareunia show stronger aversive learning; and whether psychological distress, pain-related anxiety, vigilance, catastrophizing, and sexual excitation and inhibition were associated with conditioning effects. MethodsWomen with dyspareunia (n = 36) and healthy controls (n = 35) completed a differential conditioning experiment, with one erotic picture (the CS+) paired with a painful unconditional stimulus and one erotic picture never paired with pain (the CS−). Main Outcome MeasuresGenital sexual response was measured by vaginal photoplethysmography, and ratings of affective value and sexual arousal in response to the CS+ and CS− were obtained. Psychological distress, pain cognitions, and sexual excitation and inhibition were assessed by validated questionnaires. ResultsThe two groups showed stronger negative affect and weaker subjective sexual arousal to the CS+ during the extinction phase, but, contrary to expectations, women with dyspareunia showed weaker differential responding. Controls showed more prominent lower genital response to the CS+ during acquisition than women with dyspareunia. In addition, women with dyspareunia showed stronger expectancy for the unconditional stimulus in response to the safe CS−. Higher levels of pain-related fear, pain catastrophizing, and sexual inhibition were associated with weaker differential conditioning effects. ConclusionsPairing of sex with pain negatively affects sexual response. The results indicate that a learned association of sex with pain and possibly deficient safety learning play a role in dyspareunia.Both S, Brauer M, Weijenborg P, Laan E. Effects of Aversive Classical Conditioning on Sexual Response in Women With Dyspareunia and Sexually Functional Controls. J Sex Med 2017;14:687–701.

Effects of the swimming exercise on the consolidation and persistence of auditory and contextual fear memory

Exposure to negative environmental events triggers defensive behavior and leads to the formation of aversive associative memory. Cellular and molecular changes in the central nervous system underlie this memory formation, as well as the associated behavioral changes. In general, memory process is established in distinct phases such as acquisition, consolidation, evocation, persistence, and extinction of the acquired information. After exposure to a particular event, early changes in involved neural circuits support the memory consolidation, which corresponds to the short-term memory. Re-exposure to previously memorized events evokes the original memory, a process that is considered essential for the reactivation and consequent persistence of memory, ensuring that long-term memory is established. Different environmental stimuli may modulate the memory formation process, as well as their distinct phases. Among the different environmental stimuli able of modulating memory formation is the physical exercise which is a potent modulator of neuronal activity. There are many studies showing that physical exercise modulates learning and memory processes, mainly in the consolidation phase of the explicit memory. However, there are few reports in the literature regarding the role of physical exercise in implicit aversive associative memory, especially at the persistence phase. Thus, the present study aimed to investigate the relationship between swimming exercise and the consolidation and persistence of contextual and auditory-cued fear memory. Male Wistar rats were submitted to sessions of swimming exercise five times a week, over six weeks. After that, the rats were submitted to classical aversive conditioning training by a pairing tone/foot shock paradigm. Finally, rats were evaluated for consolidation and persistence of fear memory to both auditory and contextual cues. Our results demonstrate that classical aversive conditioning with tone/foot shock pairing induced consolidation as well as persistence of conditioned fear memory. In addition, rats submitted to swimming exercise over six weeks showed an improved performance in the test of auditory-cued fear memory persistence, but not in the test of contextual fear memory persistence. Moreover, no significant effect from swimming exercise was observed on consolidation of both contextual and auditory fear memory. So, our study, revealing the effect of the swimming exercise on different stages of implicit memory of tone/foot shock conditioning, contributes to and complements the current knowledge about the environmental modulation of memory process.

PS-05-001 The effects of aversive classical conditioning on sexual response in women with genito-pelvic pain disorder and sexually functional controls

PS-05-001 The effects of aversive classical conditioning on sexual response in women with genito-pelvic pain disorder and sexually functional controls

Aversive learning shapes neuronal orientation tuning in human visual cortex.

The responses of sensory cortical neurons are shaped by experience. As a result perceptual biases evolve, selectively facilitating the detection and identification of sensory events that are relevant for adaptive behaviour. Here we examine the involvement of human visual cortex in the formation of learned perceptual biases. We use classical aversive conditioning to associate one out of a series of oriented gratings with a noxious sound stimulus. After as few as two grating-sound pairings, visual cortical responses to the sound-paired grating show selective amplification. Furthermore, as learning progresses, responses to the orientations with greatest similarity to the sound-paired grating are increasingly suppressed, suggesting inhibitory interactions between orientation-selective neuronal populations. Changes in cortical connectivity between occipital and fronto-temporal regions mirror the changes in visuo-cortical response amplitudes. These findings suggest that short-term behaviourally driven retuning of human visual cortical neurons involves distal top–down projections as well as local inhibitory interactions.

Extinction of aversive classically conditioned human sexual response.

Research has shown that acquired subjective likes and dislikes are quite resistant to extinction. Moreover, studies on female sexual response demonstrated that diminished genital arousal and positive affect toward erotic stimuli due to aversive classical conditioning did not extinguish during an extinction phase. Possible resistance to extinction of aversive conditioned sexual responses may have important clinical implications. However, resistance to extinction of aversive conditioned human sexual response has not been studied using extensive extinction trials. This article aims to study resistance to extinction of aversive conditioned sexual responses in sexually functional men and women. A differential conditioning experiment was conducted, with two erotic pictures as conditioned stimulus (CSs) and a painful stimulus as unconditioned stimuli (USs). Only one CS (the CS+) was followed by the US during the acquisition phase. Conditioned responses were assessed during the extinction phase. Penile circumference and vaginal pulse amplitude were assessed, and ratings of affective value and subjective sexual arousal were obtained. Also, a stimulus response compatibility task was included to assess automatic approach and avoidance tendencies. Men and women rated the CS+ more negative as compared with the CS-. During the first trials of the extinction phase, vaginal pulse amplitude was lower in response to the CS+ than in response to the CS-, and on the first extinction trial women rated the CS+ as less sexually arousing. Intriguingly, men did not demonstrate attenuated genital and subjective sexual response. Aversive conditioning, by means of painful stimuli, only affects sexual responses in women, whereas it does not in men. Although conditioned sexual likes and dislikes are relatively persistent, conditioned affect eventually does extinguish.

Latent inhibition in rats neonatally treated chronically with MK-801: Differential effects on conditioned taste aversion and conditioned emotional response

Chronic neonatal blockade of N-methyl-d-aspartate (NMDA) receptors produces various abnormal behaviors in adulthood animals. This study investigated the effects of neonatal treatment chronically with MK-801 in rats on the preexposure-induced retardation of CS-US association, i.e. latent inhibition (LI), of two aversive classical conditioning tasks in adulthood. In conditioned taste aversion (CTA) using sucrose taste and LiCl, neonatal chronic MK-801 (0.4mg/kg twice/day) treatment attenuated the inhibitory effect of sucrose preexposure on the aversive conditioning, although the treatment did not affect CTA conditioning itself. On the other hand, in conditioned emotional response (CER) using tone and electrical foot shock, rats neonatally treated with MK-801 showed the same degree of inhibitory effect of tone preexposure on the aversive conditioning compared with neonatally vehicle-treated rats, and also showed the same level of CER conditioning itself. Thus, the effect of chronic neonatal blockade of NMDA receptors on the LI of classical conditioning in adulthood was differentiated by the task employed. Results suggest that LI of CTA paradigm compared with that of CER is more sensitive to abnormal development after chronic neonatal blockade of NMDA receptors as an index of cognitive/attentional deficits caused by the treatment.

Memory block: A consequence of conflict resolution

Food deprivation for 1 day in the pond snail Lymnaea stagnalis before aversive classical conditioning results in optimal conditioned taste aversion (CTA) and long-term memory (LTM) formation, whereas 5-day food deprivation before training does not. We hypothesize that snails do in fact learn and form LTM when trained after prolonged food deprivation, but that severe food deprivation blocks their ability to express memory. We trained 5-day food-deprived snails under various conditions, and found that memory was indeed formed but is overpowered by severe food deprivation. Moreover, CTA-LTM was context dependent and was observed only when the snails were in a context similar to that in which the training occurred.

The medial orbitofrontal cortex encodes a general unsigned value signal during anticipation of both appetitive and aversive events

The medial orbitofrontal cortex (mOFC)/ventromedial prefrontal cortex (vmPFC) has been proposed to signal the expected value of rewards when learning stimuli-rewards associations. Yet, it is still unclear whether identical or distinct orbitofrontal cortex regions encode expected rewards and punishments at the time of the cue during appetitive and aversive classical conditioning. Moreover, it is unknown whether anticipation of different types of positive and negative reinforcers differentially influence specific orbitofrontal cortex regions. To answer these questions, this study investigated whether the human mOFC/vmPFC region encodes a general unsigned anticipatory value signal for different types of rewards and punishments (responding in a positive fashion in anticipation of both appetitive and aversive events) or a signed expected value signal (responding positively in anticipation of rewards and negatively in anticipation of punishments) when learning cue-outcomes associations. Using a model-based fMRI approach implementing a reinforcement learning model to compute the expected values of two types of rewards (pleasant juice, monetary gain) and two types of punishments (aversive juice, aversive picture), we found that mOFC/vmPFC activity correlated positively with the expected value of the cues, in anticipation of both rewards and punishments. This finding indicates that the mOFC/vmPFC encodes a general unsigned anticipatory value signal, regardless of reinforcers valence (positive/negative) and types (gustatory, visual).