Conditioned Aversion Paradigm Research Articles

Reversal of Conditioned Food Aversion Using a Cognitive Intervention: A Sham-Controlled, Randomized, Parallel Study

Background: Aversive conditioning weakens the gratifying value of a comfort meal. The aim was to determine the effect of a cognitive intervention to reverse aversive conditioning and restore hedonic postprandial response. Methods: This was a randomized, sham-controlled, single-blind, parallel study that was conducted on 12 healthy women (n = 6 in each group). The reward value of a comfort meal was measured on different days: at initial exposure, after aversive conditioning (administration of the same meal with a masked fat overload on the previous day) and after a cognitive intervention (disclosing the aversive conditioning paradigm in the test group vs. no explanation in the control group). The primary outcome, digestive wellbeing, was determined using graded scales at regular intervals before and after ingestion. Results: At initial exposure, the comfort meal produced a rewarding experience that was impaired using aversive conditioning; upon re-exposure to the original meal, the cognitive intervention increased meal wanting and liking; improved digestive wellbeing and mood; tended to reduce postprandial satiety, bloating/fullness; and abolished discomfort/pain, thereby restoring the hedonic value of the comfort meal. By contrast, sham intervention had no effects, and the postprandial sensations remained like the responses to the offending meal. Conclusion: In this proof-of-concept study, we demonstrate that in healthy women, a mild, short-term acquired aversion to a comfort meal can be reversed using a cognitive intervention. ClinicalTrials.gov ID: NCT05897411.

Evaluation of taste aversion learning procedure for the generalization of aversion using palatable foods

An experiment to evaluate the effectiveness of the taste aversion conditioning paradigm in the generalization of aversion with palatable foods was performed. Ten experimentally naive females Wistar rats and three types of foods were used: a) standard purina rodent chow, b) vanilla flavor cookies and c) chocolate-flavored cookies. Subjects were divided into two groups. Using the taste aversion conditioning paradigm protocol, subjects were exposed to the types of food keeping an intake record. The experiment demonstrated that rats can acquire an aversion to palatable foods accompanied by a tendency to generalize, when using elements that share characteristics such as nutritional content and texture. In addition, the intake of a food that does not share the characteristics of texture, taste, smell and energy content with the one used for conditioning was not been affected. These findings indicate that the aversion generalization seems to depend on the properties of the food used.

Honey bees can store and retrieve independent memory traces after complex experiences that combine appetitive and aversive associations.

Real-world experiences often mix appetitive and aversive events. Understanding the ability of animals to extract, store and use this information is an important issue in neurobiology. We used honey bees as model organism to study learning and memory after a differential conditioning paradigm that combines appetitive and aversive training trials. First, we used an aversive conditioning paradigm that constitutes a clear opposite of the well-known appetitive olfactory conditioning of the proboscis extension response. A neutral odour is presented paired with the bitter substance quinine. Aversive memory is evidenced later as an odour-specific impairment in appetitive conditioning. Then, we tested the effect of mixing appetitive and aversive conditioning trials distributed along the same training session. Differential conditioning protocols like this were used previously to study the ability to discriminate odours; however, they were not focused on whether appetitive and aversive memories are formed. We found that after differential conditioning, honey bees establish independent appetitive and aversive memories that do not interfere with each other during acquisition or storage. Finally, we moved the question forward to retrieval and memory expression to evaluate what happens when appetitive and the aversive learned odours are mixed during a test. Interestingly, opposite memories compete in such a way that they do not cancel each other out. Honey bees showed the ability to switch from expressing appetitive to aversive memory depending on their satiation level.

Alpha-band EEG suppression as a neural marker of sustained attentional engagement to conditioned threat stimuli.

Attention helps us to be aware of the external world, and this may be especially important when a threat stimulus predicts an aversive outcome. Electroencephalogram (EEG) alpha-band suppression has long been considered as a neural signature of attentional engagement. The present study was designed to test whether attentional engagement, as indexed by alpha-band suppression, is increased in a sustained manner following a conditioned stimulus (CS) that is paired with an aversive (CS+) vs neutral (CS-) outcome. We tested 70 healthy young adults in aversive conditioning and extinction paradigms. One of three colored circles served as the CS+, which was paired in 50% of the trials with a noise burst (unconditioned stimulus, US). The other colored circles (CS-) were never paired with the US. For conditioning, we found greater alpha-band suppression for the CS+ compared to the CS-; this suppression was sustained through the time of the predicted US. This effect was significantly reduced for extinction. These results indicate that conditioned threat stimuli trigger an increase in attentional engagement as subjects monitor the environment for the predicted aversive stimulus. Moreover, this alpha-band suppression effect may be valuable for future studies examining normal or pathological increases in attentional monitoring following threat stimuli.

Parallel mechanisms of visual memory formation across distinct regions of the honey bee brain.

Visual learning is vital to the behavioral ecology of the Western honey bee (Apis mellifera). Honey bee workers forage for floral resources, a behavior that requires the learning and long-term memory of visual landmarks, but how these memories are mapped to the brain remains poorly understood. To address this gap in our understanding, we collected bees that successfully learned visual associations in a conditioned aversion paradigm and compared gene expression correlates of memory formation in the mushroom bodies, a higher-order sensory integration center classically thought to contribute to learning, as well as the optic lobes, the primary visual neuropil responsible for sensory transduction of visual information. We quantified expression of CREB and CaMKII, two classical genetic markers of learning, and fen-1, a gene specifically associated with punishment learning in vertebrates. As expected, we found substantial involvement of the mushroom bodies for all three markers but additionally report the involvement of the optic lobes across a similar time course. Our findings imply the molecular involvement of a sensory neuropil during visual associative learning parallel to a higher-order brain region, furthering our understanding of how a tiny brain processes environmental signals.

Learning biases to angry and happy faces during Pavlovian aversive conditioning.

Learning biases in Pavlovian aversive conditioning have been found in response to specific categories of threat-relevant stimuli, such as snakes or angry faces. This has been suggested to reflect a selective predisposition to preferentially learn to associate stimuli that provided threats to survival across evolution with aversive outcomes. Here, we contrast with this perspective by highlighting that both threatening (angry faces) and rewarding (happy faces) social stimuli can produce learning biases during Pavlovian aversive conditioning. Using a differential aversive conditioning paradigm, the present study (N = 107) showed that the conditioned response to angry and happy faces was more readily acquired and more resistant to extinction than the conditioned response to neutral faces. Strikingly, whereas the effects for angry faces were of moderate size, the conditioned response persistence to happy faces was of relatively small size and influenced by interindividual differences in their affective evaluation, as indexed by a Go/No-Go Association Task. Computational reinforcement learning analyses further suggested that angry faces were associated with a lower inhibitory learning rate than happy faces, thereby inducing a greater decrease in the impact of negative prediction error signals that contributed to weakening extinction learning. Altogether, these findings provide further evidence that the occurrence of learning biases in Pavlovian aversive conditioning is not specific to threat-related stimuli and depends on the stimulus' affective relevance to the organism. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Conspecific and interspecific stimuli reduce initial performance in an aversive learning task in honey bees (Apis mellifera).

The purpose of this experiment was to investigate whether honey bees (Apis mellifera) are able to use social discriminative stimuli in a spatial aversive conditioning paradigm. We tested bees' ability to avoid shock in a shuttle box apparatus across multiple groups when either shock, or the absence of shock, was associated with a live hive mate, a dead hive mate, a live Polistes exclamans wasp or a dead wasp. Additionally, we used several control groups common to bee shuttle box research where shock was only associated with spatial cues, or where shock was associated with a blue or yellow color. While bees were able to learn the aversive task in a simple spatial discrimination, the presence of any other stimuli (color, another bee, or a wasp) reduced initial performance. While the color biases we discovered are in line with other experiments, the finding that the presence of another animal reduces performance is novel. Generally, it appears that the use of bees or wasps as stimuli initially causes an increase in overall activity that interferes with early performance in the spatial task. During the course of the experiment, the bees habituate to the insect stimuli (bee or wasp), and begin learning the aversive task. Additionally, we found that experimental subject bees did not discriminate between bees or wasps used as stimulus animals, nor did they discriminate between live or dead stimulus animals. This may occur, in part, due to the specialized nature of the worker honey bee. Results are discussed with implications for continual research on honey bees as models of aversive learning, as well as research on insect social learning in general.

Reduced safety processing during aversive social conditioning in psychosis and clinical risk.

Social impairment occurs across the psychosis spectrum, but its pathophysiology remains poorly understood. Here we tested the hypothesis that reduced differential responses (aversive vs. neutral) in neural circuitry underpinning aversive conditioning of social stimuli characterizes the psychosis spectrum. Participants age 10-30 included a healthy control group (HC, analyzed n = 36) and a psychosis spectrum group (PSY, n = 71), including 49 at clinical risk for psychosis and 22 with a frank psychotic disorder. 3T fMRI utilized a passive aversive conditioning paradigm, with neutral faces as conditioned stimuli (CS) and a scream as the unconditioned stimulus. fMRI conditioning was indexed as the activation difference between aversive and neutral trials. Analysis focused on amygdala, ventromedial prefrontal cortex, and anterior insula, regions previously implicated in aversive and social-emotional processing. Ventromedial prefrontal cortex activated more to neutral than aversive CS; this "safety effect" was driven by HC and reduced in PSY, and correlated with subjective emotional ratings following conditioning. Insula showed the expected aversive conditioning effect, and although no group differences were found, its activation in PSY correlated with anxiety severity. Unexpectedly, amygdala did not show aversive conditioning; its activation trended greater for neutral than aversive CS, and did not differ significantly based on group or symptom severity. We conclude that abnormalities in social aversive conditioning are present across the psychosis spectrum including clinical risk, linked to a failure of safety processing. Aversive and safety learning provide translational paradigms yielding insight into pathophysiology of psychosis risk, and providing potential targets for therapeutic and preventative interventions.

Functional Source Separation for EEG-fMRI Fusion: Application to Steady-State Visual Evoked Potentials.

Neurorobotics is one of the most ambitious fields in robotics, driving integration of interdisciplinary data and knowledge. One of the most productive areas of interdisciplinary research in this area has been the implementation of biologically-inspired mechanisms in the development of autonomous systems. Specifically, enabling such systems to display adaptive behavior such as learning from good and bad outcomes, has been achieved by quantifying and understanding the neural mechanisms of the brain networks mediating adaptive behaviors in humans and animals. For example, associative learning from aversive or dangerous outcomes is crucial for an autonomous system, to avoid dangerous situations in the future. A body of neuroscience research has suggested that the neurocomputations in the human brain during associative learning involve re-shaping of sensory responses. The nature of these adaptive changes in sensory processing during learning however are not yet well enough understood to be readily implemented into on-board algorithms for robotics application. Toward this overall goal, we record the simultaneous electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI), characterizing one candidate mechanism, i.e., large-scale brain oscillations. The present report examines the use of Functional Source Separation (FSS) as an optimization step in EEG-fMRI fusion that harnesses timing information to constrain the solutions that satisfy physiological assumptions. We applied this approach to the voxel-wise correlation of steady-state visual evoked potential (ssVEP) amplitude and blood oxygen level-dependent imaging (BOLD), across both time series. The results showed the benefit of FSS for the extraction of robust ssVEP signals during simultaneous EEG-fMRI recordings. Applied to data from a 3-phase aversive conditioning paradigm, the correlation maps across the three phases (habituation, acquisition, extinction) show converging results, notably major overlapping areas in both primary and extended visual cortical regions, including calcarine sulcus, lingual cortex, and cuneus. In addition, during the acquisition phase when aversive learning occurs, we observed additional correlations between ssVEP and BOLD in the anterior cingulate cortex (ACC) as well as the precuneus and superior temporal gyrus.

Achievement motivation modulates Pavlovian aversive conditioning to goal-relevant stimuli

Pavlovian aversive conditioning is a fundamental form of learning helping organisms survive in their environment. Previous research has suggested that organisms are prepared to preferentially learn to fear stimuli that have posed threats to survival across evolution. Here, we examined whether enhanced Pavlovian aversive conditioning can occur to stimuli that are relevant to the organism’s concerns beyond biological and evolutionary considerations, and whether such preferential learning is modulated by inter-individual differences in affect and motivation. Seventy-two human participants performed a spatial cueing task where the goal-relevance of initially neutral stimuli was experimentally manipulated. They subsequently underwent a differential Pavlovian aversive conditioning paradigm, in which the goal-relevant and goal-irrelevant stimuli served as conditioned stimuli. Skin conductance response was recorded as an index of the conditioned response and participants’ achievement motivation was measured to examine its impact thereon. Results show that achievement motivation modulated Pavlovian aversive learning to goal-relevant vs. goal-irrelevant stimuli. Participants with high achievement motivation more readily acquired a conditioned response to goal-relevant compared with goal-irrelevant stimuli than did participants with lower achievement motivation. However, no difference was found between goal-relevant and goal-irrelevant stimuli during extinction. These findings suggest that stimuli that are detected as relevant to the organism can induce facilitated Pavlovian aversive conditioning even though they hold no inherent threat value and no biological evolutionary significance, and that the occurrence of such learning bias is critically dependent on inter-individual differences in the organism’s concerns, such as achievement motivation.

Aversive learning-induced plasticity throughout the adult mammalian olfactory system: insights across development.

Experiences, such as sensory learning, are known to induce plasticity in mammalian sensory systems. In recent years aversive olfactory learning-induced plasticity has been identified at all stages of the adult olfactory pathway; however, the underlying mechanisms have yet to be identified. Much of the work regarding mechanisms of olfactory associative learning comes from neonates, a time point before which the brain or olfactory system is fully developed. In addition, pups and adults often express different behavioral outcomes when subjected to the same olfactory aversive conditioning paradigm, making it difficult to directly attribute pup mechanisms of plasticity to adults. Despite the differences, there is evidence of similarities between pups and adults in terms of learning-induced changes in the olfactory system, suggesting at least some conserved mechanisms. Identifying these conserved mechanisms of plasticity would dramatically increase our understanding of how the brain is able to alter encoding and consolidation of salient olfactory information even at the earliest stages following aversive learning. The focus of this review is to systematically examine literature regarding olfactory associative learning across developmental stages and search for similarities in order to build testable hypotheses that will inform future studies of aversive learning-induced sensory plasticity in adults.

Event-related potential components as measures of aversive conditioning in humans.

For more than 60 years, the gold standard for assessing aversive conditioning in humans has been the skin conductance response (SCR), which arises from the activation of the peripheral nervous system. Although the SCR has been proven useful, it has some properties that impact the kinds of questions it can be used to answer. In particular, the SCR is slow, reaching a peak 4-5 s after stimulus onset, and it decreases in amplitude after a few trials (habituation). The present study asked whether the late positive potential (LPP) of the ERP waveform could be a useful complementary method for assessing aversive conditioning in humans. The SCR and LPP were measured in an aversive conditioning paradigm consisting of three blocks in which one color was paired with a loud noise (CS+) and other colors were not paired with the noise (CS-). Participants also reported the perceived likelihood of being exposed to the noise for each color. Both SCR and LPP were significantly larger on CS+ trials than on CS- trials. However, SCR decreased steeply after the first conditioning block, whereas LPP and self-reports were stable over blocks. These results indicate that the LPP can be used to assess aversive conditioning and has several useful properties: (a) it is a direct response of the central nervous system, (b) it is fast, with an onset latency of 300 ms, (c) it does not habituate over time.

M74. fMRI of Social Aversion in Early Psychosis and Psychosis Risk

Abstract Background: Social impairment is prevalent and disabling in established psychosis as well as during the psychosis prodrome. Neuroimaging studies in healthy people have identified a set of interconnected regions involved in social cognition, aversive processing, and emotion regulation, including the amygdala, ventromedial prefrontal cortex (vmPFC), and anterior insular cortex (AIC). We hypothesize that across the psychosis spectrum from risk to frank schizophrenia, dysfunction in these regions and associated circuitry is associated with aberrant aversive learning and with negative symptoms that cause social impairment. Here we report results of a 3T fMRI study testing this hypothesis using a social aversive conditioning paradigm. Methods: fMRI participants (n = 81) were youth and young adults (age 10–30) in 3 demographically-matched groups: frank psychosis (PSY, n = 22), clinical risk (CR, n = 27) and healthy control (HC, n = 32). During fMRI, participants performed the aversive conditioning paradigm we report here, as well as a reversal paradigm and resting-state imaging. Male faces with neutral expressions served as conditioned stimuli (CS), and a loud scream was the aversive unconditioned stimulus (US), co-terminating with 50% contingency. fMRI analysis focused on the difference in regional activation between aversive (CS+, trials without a US) and neutral (CS−) conditions. We examined categorical group differences as well as dimensional relationships to negative, positive, and anxiety symptoms. Results: Subjective ratings of the faces as well as autonomic measures (pupil dilation) confirmed conditioning effects in HC, with reduced CS+ vs CS− discrimination in both PSY and CR groups. Across all subjects, AIC showed CS+ > CS− activation, while vmPFC activated to CS− but deactivated to CS+ (CS+ CS− response, with transient activation at stimulus onset and again at the time when US might appear. Relative to HC, both CR and PSY showed decreased differentiation of CS+ < CS− in the vmPFC. Across CR and PSY, amygdala conditioning was positively correlated with negative symptom severity. Conclusion: These results demonstrate similar social aversive conditioning abnormalities in both established psychosis and those at clinical risk, providing further support for the spectrum conceptualization of psychosis. On average, psychosis spectrum individuals exhibit a failure to engage ventromedial prefrontal cortex during aversive conditioning. This prefrontal region is critical for emotional regulation including modulating threat responses, and may underpin impaired behavioral discrimination. Negative symptom severity is associated with exaggerated amygdala conditioning, suggesting that negative symptoms may be related to heightened aversive learning rather than a failure of discrimination.

An animal model of compulsive sexual behavior induced by morphine

It is well recognized that psychoactive drugs impact sexual function, performance, and arousal. Chronic use of drugs in general leads to compulsive sexual behavior (CSB) in substance abusers and causes high rates of sexually transmitted diseases, including HIV, although different drugs are associated with variable degrees of sexual risk behavior. Existing research has consistently demonstrated high rates of cooccurrence between CSBs and substance use disorders, with comorbidity rates ranging from 40% to 60%. Morphine is one of the most abusive illicit drugs in the world. Similar to effects of psychostimulants, morphine abuse is commonly associated with loss of sexual inhibition and subsequent compulsive sexual behavior, including heightened sexual desire, numerous sexual partners, and lack of protection. Previous research has focused almost exclusively on the effects of drugs of abuse on sexual motivation and performance. Although such effects are indeed reported in humans as well, the human studies have indicated that one of the largest and most problematic effects of drugs on sex behavior is the increase in risk-taking behaviors related to sexual activity. Yet, few animal studies have attempted to investigate this phenomenon, in part probably due to a lack of an established paradigm to study CSB in rodents. This study aims to develop an animal model of CSB in morphine pretreated (total 330 mg/kg; i.p. 5 d) male rats by a sexual aversion conditioning paradigm, in which increasing intensity foot-shock is paired with sexual contact to assess the compultive motivation. Following 7 d morphine withdrawal, a sexually receptive female rat is placed in the stimuluscage, the male rat can contact with the female rat by going through an electric rods. The current value of the electric rods was increased after each trial according to the following: 0.2, 0.3, 0.4, 0.6, 0.8, 1, 1.4, 1.8 mA. To avoid foot damage, the cut-off of 2 mA was introduced. The results show that morphine pretreated group expresses a persistent preference toward the sexually receptive female despite the foot-shock, as indicated by a significant increase in the current value compared to saline pretreated group. Moreover, the compulsive motivation to approach a sexually receptive female rat is no difference betweent saline pretreated rats and morphine pretreated but sexually naive rats, thereby suggesting that sexual experience in male rats is a critical influence factor for CSB. We think the model has a higher face and predictive validity compared to previous models and the model will help further examine the neurobiological underpinnings of CSB as well as providing a tool to study the influence factors on CSB in detail.

Reduced amygdala responsivity during conditioning to trauma-related stimuli in posttraumatic stress disorder.

Exaggerated conditioned fear responses and impaired extinction along with amygdala overactivation have been observed in posttraumatic stress disorder (PTSD). These fear responses might be triggered by cues related to the trauma through higher-order conditioning, where reminders of the trauma may serve as unconditioned stimuli (US) and could maintain the fear response. We compared arousal, valence, and US expectancy ratings and BOLD brain responses using fMRI in 14 traumatized persons with PTSD and 14 without PTSD (NPTSD) and 13 matched healthy controls (HC) in a differential aversive conditioning paradigm. The US were trauma-specific pictures for the PTSD and NPTSD group and equally aversive and arousing for the HC; the conditioned stimuli (CS) were graphic displays. During conditioning, the PTSD patients compared to the NPTSD and HC indicated higher arousal to the conditioned stimulus that was paired with the trauma picture (CS+) compared to the unpaired (CS-), increased dissociation during acquisition and extinction, and failure to extinguish the CS/US-association compared to NPTSD. During early and late acquisition, the PTSD patients showed a significantly lower amygdala activation to CS+ versus CS- and a negative interaction between activation in the amygdala and dorsolateral prefrontal cortex (PFC), while NPTSD and HC displayed a negative interaction between amygdala and medial PFC. These findings suggest maladaptive anticipatory coping with trauma-related stimuli in patients with PTSD, indicated by enhanced conditioning, with related abnormal amygdala reactivity and connectivity, and delayed extinction.

Dissociable Learning Processes Underlie Human Pain Conditioning

SummaryPavlovian conditioning underlies many aspects of pain behavior, including fear and threat detection [1], escape and avoidance learning [2], and endogenous analgesia [3]. Although a central role for the amygdala is well established [4], both human and animal studies implicate other brain regions in learning, notably ventral striatum and cerebellum [5]. It remains unclear whether these regions make different contributions to a single aversive learning process or represent independent learning mechanisms that interact to generate the expression of pain-related behavior. We designed a human parallel aversive conditioning paradigm in which different Pavlovian visual cues probabilistically predicted thermal pain primarily to either the left or right arm and studied the acquisition of conditioned Pavlovian responses using combined physiological recordings and fMRI. Using computational modeling based on reinforcement learning theory, we found that conditioning involves two distinct types of learning process. First, a non-specific “preparatory” system learns aversive facial expressions and autonomic responses such as skin conductance. The associated learning signals—the learned associability and prediction error—were correlated with fMRI brain responses in amygdala-striatal regions, corresponding to the classic aversive (fear) learning circuit. Second, a specific lateralized system learns “consummatory” limb-withdrawal responses, detectable with electromyography of the arm to which pain is predicted. Its related learned associability was correlated with responses in ipsilateral cerebellar cortex, suggesting a novel computational role for the cerebellum in pain. In conclusion, our results show that the overall phenotype of conditioned pain behavior depends on two dissociable reinforcement learning circuits.

Development of a Protocol for Studying Premature Onset of Fear as a Feature of Pathological Fear: The Effects of Conditional Stimulus Duration and Counting Behavior

We propose that the premature onset of fear responding is a potentially important feature of pathological fear. A behavioral protocol to study the temporal regulation of fear in humans is, however, lacking. The present study aims at developing such a protocol for healthy individuals. To this end, we investigated the effect of conditional stimulus duration (50 seconds or 90 seconds) and the effect of verbal counting during presentation of the conditional stimulus (counting or no counting) in an aversive conditioning paradigm. Results favored training conditions in which participants were asked to count for the duration of the conditional stimulus, regardless of conditional stimulus duration. Under these training conditions, we observed optimal temporal control over the onset of fear. Furthermore, it was shown that intervals followed by an aversive stimulus were retrospectively estimated to have lasted longer than those that were not followed by an aversive stimulus. We argue that the developed protocol may serve as a powerful method to study premature onset of fear responding in future studies.

Classical conditioning in borderline personality disorder: an fMRI study.

Previous research suggests disturbed emotional learning and memory in borderline personality disorder (BPD). Studies investigating the neural correlates of aversive differential delay conditioning in BPD are currently lacking. We aimed to investigate acquisition, within-session extinction, between-session extinction recall, and reacquisition. We expected increased activation in the insula, amygdala, and anterior cingulate, and decreased prefrontal activation in BPD patients. During functional magnetic resonance imaging, 27 medication-free female BPD patients and 26 female healthy controls (HC) performed a differential delay aversive conditioning paradigm. An electric shock served as unconditioned stimulus, two neutral pictures as conditioned stimuli (CS+/CS-). Dependent variables were blood-oxygen-level-dependent response, skin conductance response (SCR), and subjective ratings (valence, arousal). No significant between-group differences in brain activation were found [all p(FDR)>0.05]. Within-group comparisons for CS+unpaired>CS- revealed increased insula activity in BPD patients but not in HC during early acquisition; during late acquisition, both groups recruited fronto-parietal areas [p(FDR)<0.05]. During extinction, BPD patients rated both CS+ and CS- as significantly more arousing and aversive than HC and activated the amygdala in response to CS+. In contrast, HC showed increased prefrontal activity in response to CS+>CS during extinction. During extinction recall, there was a trend for stronger SCR to CS+>CS in BPD patients. Amygdala habituation to CS+paired (CS+ in temporal contingency with the aversive event) during acquisition was found in HC but not in patients. Our findings suggest altered temporal response patterns in terms of increased vigilance already during early acquisition and delayed extinction processes in individuals with BPD.

Belief bias and the extinction of induced fear

Some people show slower extinction of UCS expectancies than other people. Little is known about what predicts such delayed extinction. Extinction requires that people deduce the logical implication of corrective experiences challenging the previously learned CS–UCS contingency. “A strong habitual tendency to confirm beliefs” may therefore be a powerful mechanism immunising against refutation of UCS expectancies. This study investigated whether individual differences in such a belief confirming tendency (a process called “belief bias”) may help in explaining individual differences in extinction. We tested whether relatively strong belief bias predicts delayed extinction of experimentally induced UCS expectancies. In a differential aversive conditioning paradigm, we used UCS-irrelevant (Experiment 1) and UCS-relevant (Experiment 2) pictorial stimuli as CS+ and CS−, and electrical stimulation as UCS. Belief bias indeed predicted delayed extinction of UCS expectancies when the CS+ was UCS-relevant (as is typically the case for phobic stimuli, Experiment 2). The study provides preliminary evidence that enhanced belief bias may indeed play a role in the persistence of UCS expectancies, and can thereby contribute to the development and persistence of anxiety disorders. The results also point to the relevance of reasoning tendencies in the search for predictors of delayed extinction of UCS expectancies.

The scent of salience — Is there olfactory-trigeminal conditioning in humans?

Pavlovian fear conditioning has been thoroughly studied in the visual, auditory and somatosensory domain, but evidence is scarce with regard to the chemosensory modality. Under the assumption that Pavlovian conditioning relies on the supra-modal mechanism of salience attribution, the present study was set out to attest the existence of chemosensory aversive conditioning in humans as a specific instance of salience attribution. fMRI was performed in 29 healthy subjects during a differential aversive conditioning paradigm. Two odors (rose, vanillin) served as conditioned stimuli (CS), one of which (CS+) was intermittently coupled with intranasally administered CO2. On the neural level, a robust differential response to the CS+ emerged in frontal, temporal, occipito-parietal and subcortical brain regions, including the amygdala. These changes were paralleled by the development of a CS+-specific connectivity profile of the anterior midcingulate cortex (aMCC), which is a key structure for processing salience information in order to guide adaptive response selection. Increased coupling could be found between key nodes of the salience network (anterior insula, neo-cerebellum) and sensorimotor areas, representing putative input and output structures of the aMCC for exerting adaptive motor control. In contrast, behavioral and skin conductance responses did not show significant effects of conditioning, which has been attributed to contingency unawareness. These findings imply substantial similarities of conditioning involving chemosensory and other sensory modalities, and suggest that salience attribution and adaptive control represent a general, modality-independent principle underlying Pavlovian conditioning.