Pavlovian Research Articles

Multimodal assessment of the role of intolerance of uncertainty in fear acquisition and extinction

Personality traits linked to internalizing disorders influence the way we develop fears, but also how we regain a sense of safety. In the present study, we investigated the effect of intolerance of uncertainty (IU) on defensive responses using a differential fear conditioning protocol with an extinction phase. The conditioned stimulus was associated with an aversive sound (90 dB) in 75 % of the presentations during acquisition. A final sample of 176 participants completed the experiment. We measured self-reports of associative (expectancy of the unconditioned stimulus in acquisition) and evaluative learning (arousal and valence), and both physiological (skin conductance response) and electrocortical responses (steady-state visually evoked potentials, ssVEPs; late positive potentials, LPP) to the conditioned stimuli. Our results show that IU's impact is limited, with no effect in both acquisition and extinction. These findings emphasize the necessity of large samples in research on inter-individual differences and contribute to our understanding of how IU may or may not be involved in fear and safety learning processes considering multiple aspects of fear responding.

Charged wormhole solutions in 4D Einstein-Gauss-Bonnet gravity

In the present work, we construct models of static wormholes in 4-dimensional Einstein-Gauss-Bonnet (4D EGB) gravity with an (an)isotropic energy momentum tensor (EMT) and a Maxwell field as supporting matters for the wormhole geometry assuming a constant redshift function. We obtain exact spherically symmetric wormhole solutions in 4D EGB gravity for isotropic and anisotropic matter sources under the effect of electric charge. The solutions are more generalized in the sense of incorporating the charge contributions. Furthermore, we examine the null, weak and strong energy conditions at the wormhole throat of radius r=r0. We demonstrate that at the wormhole throat, the classical energy conditions are violated by arbitrary small amount. Additionally, we analyze the wormhole geometry incorporating semiclassical corrections through embedding diagrams. We discover that the wormhole solutions are in equilibrium as the anisotropic and hydrostatic forces cancel each other.

Understanding the shift to compulsion in addiction: insights from personality traits, social factors, and neurobiology.

Compulsion stands as a central symptom of drug addiction; however, only a small fraction of individuals who use drugs exhibit compulsive characteristics. Differences observed in Sign-trackers (ST) and Goal-trackers (GT) during Pavlovian conditioning may shed light on individual variances in drug addiction. Here, we focus on the behavioral attributes, formation processes, and neural mechanisms underlying ST and how they drive addiction toward compulsivity in humans. We will explore addiction from three interconnected levels: individual personality traits, social factors, and neurobiology. Furthermore, we distinguish between the processes of sensitization and habituation within ST. These nuanced distinctions across various aspects of addiction will contribute to our understanding of the addiction development process and the formulation of targeted preventive strategies.

Chronic social defeat stress gives rise to social avoidance through fear learning

Chronic social defeat stress (CSDS), a widely used rodent model of stress, reliably leads to decreased social interaction in stress susceptible animals. Here, we investigate a role for fear learning in this response using male 129 Sv/Ev mice, a strain that is more vulnerable to CSDS than the commonly used C57BL/6 strain. We first demonstrate that defeated 129 Sv/Ev mice avoid a CD-1 mouse, but not a conspecific, indicating that motivation to socialize is intact in this strain. CD-1 avoidance is characterized by approach behavior that results in running in the opposite direction, activity that is consistent with a threat response. We next test whether CD-1 avoidance is subject to the same behavioral changes found in traditional models of Pavlovian fear conditioning. We find that associative learning occurs across 10 days CSDS, with defeated mice learning to associate the color of the CD-1 coat with threat. This leads to the gradual acquisition of avoidance behavior, a conditioned response that can be extinguished with 7 days of repeated social interaction testing (5 tests/day). Pairing a CD-1 with a tone leads to second-order conditioning, resulting in avoidance of an enclosure without a social target. Finally, we show that social interaction with a conspecific is a highly variable response in defeated mice that may reflect individual differences in generalization of fear to other social targets. Our data indicate that fear conditioning to a social target is a key component of CSDS, implicating the involvement of fear circuits in social avoidance.

Impulse Buying Behaviour in Live Streaming Commerce: The Influence of Celebrity-Owned Brands

Celebrity-owned brands have quickly become popular. Live streaming commerce has become one of the new business models adopted by celebrities to promote their products online in this era since traditional marketing methods are no longer able to meet all the consumer’s shopping needs and styles. We proposed a research model based on the Stimulus Response theory (SR Theory) to explore the reaction and behaviour of consumers after a certain stimuli factor. A total of 100 valid sample questionnaires with their experience in live streaming shopping were taken. This research adopted PLS-SEM statistical analysis as an empirical evaluation. Subsequently after the empirical investigation, it was found that attractiveness of the live streamer affects consumer’s impulse buying of celebrity-owned brands. Similarly, expertise of the live streamer also affects consumer’s online impulse buying of celebrity owned brands. However, the trustworthiness of the live streamer on live streaming commerce does not affect the online impulse buying of celebrity owned brands. In this paper, we build a framework for impulse buying in live streaming commerce. We verify this framework under Malaysian context. The findings of this paper provide concrete suggestions to business owners and celebrities for their marketing strategies.

Independent operations of appetitive and aversive conditioning systems lead to simultaneous production of conflicting memories in an insect.

Pavlovian conditioning is a ubiquitous form of associative learning that enables animals to remember appetitive and aversive experiences. Animals possess appetitive and aversive conditioning systems that memorize and retrieve appetitive and aversive experiences. Here, we addressed a question of whether integration of competing appetitive and aversive information takes place during the encoding of the experience or during memory retrieval. We developed novel experimental procedures to address this question using crickets (Gryllus bimaculatus), which allowed selective blockade of the expression of appetitive and aversive memories by injecting octopamine and dopamine receptor antagonists. We conditioned an odour (conditioned stimulus 1, CS1) with water and then with sodium chloride solution. At 24 h after conditioning, crickets retained both appetitive and aversive memories, and the memories were integrated to produce a conditioned response (CR). Importantly, when a visual pattern (CS2) was conditioned with CS1, appetitive and aversive memories formed simultaneously. This indicates that appetitive and aversive second-order conditionings are achieved at the same time. The memories were integrated for producing a conditioned response. We conclude that appetitive and aversive conditioning systems operate independently to form parallel appetitive and aversive memories, which compete to produce learned behaviour in crickets.

Sex and the facilitation of cued fear by prior contextual fear conditioning in rats.

Previous studies have shown that the formation of new memories can be influenced by prior experience. This includes work using Pavlovian fear conditioning in rodents that has shown that an initial fear conditioning experience can become associated with and facilitate the acquisition of new fear memories, especially when they occur close together in time. However, most of the prior studies used only males as subjects, resulting in questions about the generalizability of the findings from this work. Here we tested whether prior contextual fear conditioning would facilitate later learning of cued fear conditioning in both male and female rats, and if there were differences based on the interval between the two conditioning episodes. Our results showed that levels of cued fear were not influenced by prior contextual fear conditioning or by the interval between training; however, females showed lower levels of cued fear. Freezing behavior in the initial training context differed by sex, with females showing lower levels of contextual fear, and by the type of initial training, with rats given delayed shock showing higher levels of fear than rats given immediate shock during contextual fear conditioning. These results indicate that contextual fear conditioning does not prime subsequent cued fear conditioning and that female rats express lower levels of cued and contextual fear conditioning than males.

Defensive behaviors and c-fos expression in the midbrain.

Pavlovian fear conditioning serves as a valuable method for investigating species-specific defensive reactions (SSDRs) such as freezing and flight responses. The present study examines the role of white noise under different experimental conditions. Given that white noise has been shown to elicit both conditional (associative) and unconditional (nonassociative) defensive responses, we compared the response to noise following three separate training conditions: shock-only, white noise paired with shock, and context-only. Results showed that baseline freezing level significantly changed across groups: Both the shock-only group and the white noise paired with shock group froze more than the context-only group on the test day. White noise evoked differential freezing between groups on day 2: The shock-only group froze more than the context-only group although both groups were never exposed to white noise during training. Further, an activity burst triggered by white noise was similar for the shock-only and white noise paired with shock groups during testing, although shock-only group was never exposed to white noise stimuli during training. This aligned with c-fos data, indicating similar c-fos activity levels across different periaqueductal gray (PAG) regions for both shock-only and white noise paired with shock groups. However, the driving force behind c-fos activation-whether freezing, activity burst, or a combination of both-remains uncertain, warranting further analysis to explore specific correlations between SSDRs and c-fos activity within the PAG and related brain areas.

Getting away from the cutoff in regression discontinuity designs

Regression discontinuity (RD) designs are highly popular in economic research because of their strong internal validity and straightforward intuition. While RD estimates are local in nature, several recent articles propose methods that generalize RD estimates to units outside a small neighborhood of the cutoff. In this article, I introduce the getaway package, which implements the method proposed by Angrist and Rokkanen (2015, Journal of the American Statistical Association 110: 1331-1344) to extrapolate treatment-effect estimates “away from the cutoff”, relying on a classical unconfoundedness condition. Additionally, the package features a data-driven algorithm designed to identify a set of covariates that fulfills the unconfoundedness assumption. It also incorporates a toolkit intended for testing and visualization purposes.

Retina-Inspired Large-Area Solution-Processed flexible Multi-Band organic neuromorphic synaptic transistor arrays

The proliferation of high-efficacy, pliable organic neuromorphic synaptic transistors is quintessential for the integration into wearable artificial intelligence ecosystems. Nevertheless, their development is hindered by substantial energy demands and suboptimal charge carrier mobility. To surmount these obstacles, we exploit solution-processed poly(amic acid) (PAA) dielectrics and organic semiconductors to engineer pliable arrays of organic neuromorphic synaptic transistors atop a polyethylene terephthalate (PET) matrix. The polar group and nanogroove structure of PAA obtain excellent semiconductor crystal structure, and the excellent dielectric properties enable these engineered arrays to show a charge carrier mobility peak of 29.83 cm2 V−1 s−1 an aggregate mean mobility of 15.87 cm2 V−1 s−1 (standard deviation is 6.71) at a voltage of −3 V and the energy expenditure per synaptic transaction was only 0.26 fJ. Additionally, the transistors possess the aptitude for photodetection across ultraviolet–visible to near-infrared spectral bands. The successful execution of flexible imaging, Pavlovian classical conditioning reflex associative learning, coupled with a 93.9 % accuracy in handwritten numeral recognition, corroborates the viability of these high-mobility, low-power organic neuromorphic synaptic transistor arrays.

The interplay of multiple unconditioned stimuli in evaluative conditioning: A weighted averaging framework for attitude formation via stimulus co-occurrences.

Evaluative conditioning (EC) is a key effect in attitude formation, leading to changes in the liking of neutral attitude objects due to their pairing with positive or negative stimuli. Despite EC's significance, current theories and most empirical findings are limited to stimulus pairings with a single affective stimulus at a time. In contrast, social environments often involve more complex combinations of affective stimuli. In this article, we introduce a novel framework grounded in information integration research to understand how conditioned attitudes develop in the presence of multiple affective stimuli. Through 10 experiments with different designs, measures, materials, and pairing procedures, we find that individuals' conditioned attitudes follow the average valence of all affective stimuli present with a stronger weighting of negative stimuli. This weighted averaging rule bears two implications for EC in more complex stimulus combinations. First, EC effects are nonmonotonous, such that additional stimuli of the same valence do not produce incremental EC effects. Second, EC effects are interdependent, such that the impact of one stimulus is weakest when accompanied by another negative stimulus and strongest when no other affective stimulus is present. We examine different cognitive processes underlying this weighted averaging rule, including potential differences in pairing memory or changes in the affective stimuli's valence when other stimuli are present. Our findings present a novel theoretical perspective on EC and offer valuable insights into attitude change from stimulus co-occurrences in stimulus-rich environments. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Eye tracking is more sensitive than skin conductance response in detecting mild environmental stimuli.

The skin conductance (SC) and eye tracking data are two potential arousal-related psychophysiological signals that can serve as the interoceptive unconditioned response to aversive stimuli (e.g. electric shocks). The current research investigates the sensitivity of these signals in detecting mild electric shock by decoding the hidden arousal and interoceptive awareness (IA) states. While well-established frameworks exist to decode the arousal state from the SC signal, there is a lack of a systematic approach that decodes the IA state from pupillometry and eye gaze measurements. We extract the physiological-based features from eye tracking data to recover the IA-related neural activity. Employing a Bayesian filtering framework, we decode the IA state in fear conditioning and extinction experiments where mild electric shock is used. We independently decode the underlying arousal state using binary and marked point process (MPP) observations derived from concurrently collected SC data. Eight of 11 subjects present a significantly (P-value ) higher IA state in trials that were always accompanied by electric shock ( ) compared to trials that were never accompanied by electric shock ( ). According to the decoded SC-based arousal state, only five (binary observation) and four (MPP observation) subjects present a significantly higher arousal state in trials than trials. In conclusion, the decoded hidden brain state from eye tracking data better agrees with the presented mild stimuli. Tracking IA state from eye tracking data can lead to the development of contactless monitors for neuropsychiatric and neurodegenerative disorders.

Modulation of cortical representations of sensory and contextual information underlies aversive associative learning

Cortical neurons encode both sensory and contextual information, yet it remains unclear how experiences modulate these cortical representations. Here, we demonstrate that trace eyeblink conditioning (TEC), an aversive associative-learning paradigm linking conditioned (CS) with unconditioned stimuli (US), finely tunes cortical coding at both population and single-neuron levels. Initially, we show that the primary somatosensory cortex (S1) is necessary for TEC acquisition, as evidenced by local muscimol administration. At the population level, TEC enhances activity in a small subset (∼20%) of CS- or US-responsive primary neurons (rPNs) while diminishing activity in non-rPNs, including locomotion-tuned or unresponsive PNs. Crucially, TEC learning modulates the encoding of sensory versus contextual information in single rPNs: CS-responsive neurons become less responsive, while US-responsive neurons gain responses to CS. Moreover, we find that the cholinergic pathway, via nicotinic receptors, underlies TEC-induced modulations. These findings suggest that experiences dynamically tune cortical representations through cholinergic pathways.

Signalling unpaired unconditional stimuli during extinction does not impair their effect to reduce renewal of conditional fear

Presenting unpaired unconditional stimuli (US) during extinction training reduces the renewal of conditional fear due to context change and slows re-acquisition. The present study investigated whether this reduced return of fear is mediated by Pavlovian inhibitory conditioning to the conditional stimulus paired with the US during acquisition (CS+) that is acquired when this stimulus is presented without the US in an excitatory extinction context. Using an ABA renewal paradigm that trained extinction in a context different from acquisition and renewal test, participants either received no USs (Standard), five unsignalled US presentations (Unsignalled) or five presentations of the US preceded by a novel, third CS (Signalled) during extinction training. Extinction was followed by tests for renewal and re-acquisition. Replicating previous results, renewal of electrodermal conditional responses was observed in group Standard, but not in group Unsignalled. Signalling the additional USs, and thus reducing context conditioning and the potential for inhibitory conditioning, did not reduce their effect in that renewal was absent in group Signalled. These results are inconsistent with an inhibitory conditioning account of the effects of unpaired US presentations during extinction. A trial sequence learning account or an arousal account may explain the effects of unpaired presentations of the US during extinction.

Association of Unc-51-like Kinase 4 (ULK4) with the reactivity of the extended reward system in response to conditioned stimuli

Objectives ULK4 is an established candidate gene for mental disorders and antipsychotic treatment response. We investigated the association of functional genetic variation at the ULK4 locus with the human extended dopaminergic reward system using fMRI during the performance of a well-established reward paradigm. Methods Two hundred and thirty-four patients were included in this study. Association of genetic variation in the ULK4 gene with reward system functioning were determined using the Desire-Reason-Dilemma (DRD) paradigm which allows to assess brain activation in response to conditioned reward stimuli. Results Variant prioritisation revealed the strongest functional signatures for the ULK4 variant rs17215589, coding for amino acid exchange Ala715Thr. For rs17215589 minor allele carriers, we detected increased activation responses to conditioned reward stimuli in the ventral tegmental area, nucleus accumbens and several cortical brain regions of the extended reward system. Conclusions Our findings provide further evidence in humans that genetic variation in ULK4 may increase the vulnerability to mental disorders, by modulating the extended reward system function. Future studies are needed to confirm the modulation of the extended reward system by ULK4 and to specify the role of this mechanism in the pathogenesis of psychiatric disorders.

The unique face of comorbid anxiety and depression: Increased frontal, insula and cingulate cortex response during Pavlovian fear-conditioning

BackgroundDysregulation of fear processing through altered sensitivity to threat is thought to contribute to the development of anxiety disorders and major depressive disorder (MDD). However, fewer studies have examined fear processing in MDD than in anxiety disorders. The current study used propensity matching to examine the hypothesis that comorbid MDD and anxiety (AnxMDD) shows greater neural correlates of fear processing than MDD, suggesting that the co-occurrence of AnxMDD is exemplified by exaggerated defense related processes. Methods195 individuals with MDD (N = 65) or AnxMDD (N = 130) were recruited from the community and completed multi-level assessments, including a Pavlovian fear learning task during functional imaging. Visual images paired with threat (conditioned stimuli: CS+) were compared to stimuli not paired with threat (CS-). ResultsMDD and AnxMDD showed significantly different patterns of activation for CS+ vs CS- in the dorsal anterior insula/inferior frontal gyrus (partial eta squared; ηp2 = 0.02), dorsolateral prefrontal cortex (ηp2 = 0.01) and dorsal anterior/mid cingulate cortex (ηp2 = 0.01). These differences were driven by greater activation to the CS+ in AnxMDD versus MDD. LimitationsLimitations include the cross-sectional design, a scream US rather than shock and half the number of MDD as AnxMDD participants. ConclusionsAnxMDD showed a pattern of increased activation in regions identified with fear processing. Effects were consistently driven by threat, further suggesting fear signaling as the emergent target process. Differences emerged in regions associated with salience processing, attentional orienting/conflict, self-relevant processing and executive functioning in comorbid anxiety and depression, thereby highlighting potential treatment targets for this prevalent and treatment resistant group.

Effects of social dominance and acute social stress on morphology of microglia and structural integrity of the medial prefrontal cortex

Chronic stress increases activity of the brain’s innate immune system and impairs function of the medial prefrontal cortex (mPFC). However, whether acute stress triggers similar neuroimmune mechanisms is poorly understood. Across four studies, we used a Syrian hamster model to investigate whether acute stress drives changes in mPFC microglia in a time-, subregion-, and social status-dependent manner. We found that acute social defeat increased expression of ionized calcium binding adapter molecule 1 (Iba1) in the infralimbic (IL) and prelimbic (PL) and altered the morphology Iba1+ cells 1, 2, and 7 days after social defeat. We also investigated whether acute defeat induced tissue degeneration and reductions of synaptic plasticity 2 days post-defeat. We found that while social defeat increased deposition of cellular debris and reduced synaptophysin immunoreactivity in the PL and IL, treatment with minocycline protected against these cellular changes. Finally, we tested whether a reduced conditioned defeat response in dominant compared to subordinate hamsters was associated with changes in microglia reactivity in the IL and PL. We found that while subordinate hamsters and those without an established dominance relationships showed defeat-induced changes in morphology of Iba1+ cells and cellular degeneration, dominant hamsters showed resistance to these effects of social defeat. Taken together, these findings indicate that acute social defeat alters microglial morphology, increases markers of tissue degradation, and impairs structural integrity in the IL and PL, and that experience winning competitive interactions can specifically protect the IL and reduce stress vulnerability.

Exploring the association between neuroticism and negativity bias in evaluative counterconditioning

People high on neuroticism express a negativity bias in attention, memory, and interpretation, giving primacy to negative rather than positive information. Investigating additional forms of negativity bias in neuroticism could provide further insights into the situations where people who score high on neuroticism tend to remain anchored on negative aspects. We examined whether neuroticism is related to negativity bias in evaluative learning. Instruction-based and experience-based counterconditioning are two evaluative learning procedures in which a conditioned stimulus (CS) is related to a positive or a negative unconditioned stimulus (US) in Phase 1 and with a US of the opposite valence in Phase 2. Using these procedures, we obtained partial support for a negativity bias in counterconditioning among people who scored high on neuroticism. Specifically, participants scoring high on negative emotionality altered the CSs ratings more easily from positive to negative than from negative to positive, a pattern observed in instruction-based counterconditioning (Experiment 1) but not in experience-based counterconditioning (Experiment 2). In line with previous findings, we could conclude that people who score high on neuroticism tend to give primacy to emotionally negative information at the expense of positive information, particularly in ambiguous (learning) contexts.

Immediate Effects of Preconditioning Intermittent Theta Burst Stimulation on Lower Extremity Motor Cortex Excitability in Healthy Participants.

Previous studies have found that inhibitory priming with continuous theta burst stimulation (cTBS) can enhance the effect of subsequent excitatory conditioning stimuli with intermittent theta burst stimulation (iTBS) in the upper limbs. However, whether this combined stimulation approach elicits a comparable compensatory response in the lower extremities remains unclear. This study aimed to investigate how cTBS preconditioning modulated the effect of iTBS on motor cortex excitability related to the lower limb in healthy individuals. Using a randomised cross-over design, a total of 25 healthy participants (19 females, mean age = 24.80 yr) were recruited to undergo three different TBS protocols (cTBS + iTBS, sham cTBS + iTBS, sham cTBS + sham iTBS) in a random order. Each TBS intervention was administered with one-week intervals. cTBS and iTBS were administered at an intensity of 80% active motor threshold (AMT) delivering a total of 600 pulses. Before intervention (T0), immediately following intervention (T1), and 20 min after intervention (T2), the corticomotor excitability was measured for the tibialis anterior muscle of participants' non-dominant leg using a Magneuro100 stimulator and matched double-cone coil. The average amplitude of the motor-evoked potential (MEP) induced by applying 20 consecutive monopulse stimuli at an intensity of 130% resting motor threshold (RMT) was collected and analysed. Compare with T0 time, the MEP amplitude (raw and normalised) at T1 and T2 showed a statistically significant increase following the cTBS + iTBS protocol (p < 0.01), but no significant differences were observed in amplitude changes following other protocols (sham cTBS + iTBS and sham cTBS + sham iTBS) (p > 0.05). Furthermore, no statistically significant difference was found among the three protocols at any given time point (p > 0.05). Preconditioning the lower extremity motor cortex with cTBS prior to iTBS intervention can promptly enhance its excitability in healthy participants. This effect persists for a minimum duration of 20 min. No: ChiCTR2300069315. Registered 13 March, 2023, https://www.chictr.org.cn.

Search for neurophysiological mechanisms of configurational learning

Configural learning is a form of associative learning in which the conditioned stimulus is a holistic set of stimulus elements rather than individual stimuli or their isolated properties. Successfully solving the task of such associative learning requires a holistic analysis of the entire configuration as a whole. The ability to analyze not only individual physical aspects of a stimulus or single objects in a visual scene, but also their holistic combinations, offers significant evolutionary advantages, as configurations often have substantially greater predictive power compared to individual stimulus elements or features. Moreover, the ability to holistically analyze combinations of stimulus field elements or features can be considered an initial, primitive manifestation of consciousness. In the present review, we consider the history of the development of the concept of configural learning, the main methodological avenues of investigation, and currently available neurophysiological data on the putative neural basis of this phenomenon. We find it most interesting to study the processes of configural learning in humans using modern neuroimaging methods, as they provide a glimpse into the holistic brain functioning. Finally, we consider the future tasks aimed to provide a more complete understanding of the neurophysiology of the configural learning phenomenon.