Pavlovian Responses Research Articles

Highly Promising 2D/1D BP-C/CNT Bionic Opto-Olfactory Co-Sensory Artificial Synapses for Multisensory Integration.

The development of high-performance artificial synaptic neuromorphic devices poses a significant challenge in the creation of biomimetic sensing neural systems that seamlessly integrate both sensory and computational functionalities. In pursuit of this objective, promising bionic opto-olfactory co-sensory artificial synapse devices are constructed utilizing the BP-C/CNT (2D/1D) hybrid filter membrane as the resistive layer. Experimental results demonstrated that the devices seamlessly integrated the light modulation, gas detection, and biological synaptic functions into a single device while addressing the challenge with separating artificial synaptic devices from sensors. These devices offered the following advantages: 1) Simulating visual synapses, they can effectively replicate fundamental synaptic functions under both electrical and optical stimulation. 2) By emulating olfactory synapse responses to specific gases, they can achieve ultra-low detection limits and rapid identification of ethanol and acetone gases. 3) They enable photo-olfactory co-sensing simulations that mimic synaptic function under light-modulated pulse conditions in distinct gas environments, facilitating the study of synaptic learning rules and Pavlovian responses. This work provides a pioneering approach for exploring highly stable 2D BP-based optoelectronics and advancing the development of biomimetic neural systems.

Sex-biased effects of outcome devaluation by sensory-specific satiety on Pavlovian-conditioned behavior.

Goal-directed behavior relies on accurate mental representations of the value of expected outcomes. Disruptions to this process are a central feature of several neuropsychiatric disorders, including addiction. Goal-directed behavior is most frequently studied using instrumental paradigms paired with outcome devaluation, but cue-evoked behaviors in Pavlovian settings can also be goal-directed and therefore sensitive to changes in outcome value. Emerging literature suggests that male and female rats may differ in the degree to which their Pavlovian-conditioned responses are goal-directed, but interpretation of these findings is complicated by the tendency of female and male rats to engage in distinct types of Pavlovian responses when trained with localizable cues. Here, we used outcome devaluation via sensory-specific satiety to assess the behavioral responses in male and female Long Evans rats trained to respond to an auditory CS (conditioned stimulus) in a Pavlovian-conditioning paradigm. We found that satiety-induced devaluation led to a decrease in behavioral responding to the reward-predictive CS, with males showing an effect on both port entry latency and probability and females showing an effect only on port entry probability. Overall, our results suggest that outcome devaluation affects Pavlovian-conditioned responses in both male and female rats, but that females may be less sensitive to outcome devaluation.

A new circuit underlying the renewal of appetitive Pavlovian responses: Commentary on Brown and Chaudhri (2022).

A new circuit underlying the renewal of appetitive Pavlovian responses: Commentary on Brown and Chaudhri (2022).

Reinstatement of Pavlovian responses to alcohol cues by stress.

Stress may contribute to relapse to alcohol use in part by enhancing reactivity to cues previously paired with alcohol. Yet, standard models of stress-induced reinstatement generally use contingent presentations of alcohol-paired cues to reinforce instrumental behaviors, making it difficult to isolate the ability of cues to invigorate alcohol-seeking. Here we sought to test the impact of stress on behavioral responses to alcohol-paired cues, using a model of stress-induced reinstatement of Pavlovian conditioned approach, inspired by Nadia Chaudhri's work on context-induced reinstatement. Long Evans rats were trained to associate one auditory cue with delivery of alcohol or sucrose and an alternative auditory cue with no reward. Following extinction training, rats were exposed to a stressor prior to being re-exposed to the cues under extinction conditions. We assessed the effects of yohimbine, intermittent footshock and olfactory cues paired with social defeat on responses to alcohol-paired cues and the effects of yohimbine on responses to sucrose-paired cues. The pharmacological stressor, yohimbine, enhanced alcohol seeking in a Pavlovian setting, but not in a cue-selective manner. Intermittent footshock and social defeat cues did not enhance alcohol seeking in this paradigm. While yohimbine elicited reinstatement of reward-seeking in a Pavlovian setting, these effects may be unrelated to activation of stress systems or to interactions with specific cues.

Split-Second Unlearning: Developing a Theory of Psychophysiological Dis-ease.

Psychophysiological “stress” underpins many conditions including anxiety, depression, phobias, chronic fatigue syndrome and non-specific musculoskeletal pain such as fibromyalgia. In this article we develop an understanding of chronic psychophysiological stress from a psychological educational perspective, by drawing on supporting evidence that significant emotional events in early life (traumatic and benign) can influence health and well-being later in life. We suggest that traumatic events instigate psychophysiological “stress” responses and the formation of emotional memory images (EMIs) within very short time frames, i.e., “split-second learning.” Once formed these emotional memories are triggered in daily living “re-playing” psychophysiological stress responses, resulting in chronic psychophysiological “dis-ease.” We describe a novel therapeutic approach to scan clients for mannerisms signifying a subconscious “freeze-like” stress response that involves the client as a curious observer within their own experience, feeding back the non-verbal cues as they arrive in the moment. By breaking down the observable fragments of their split-second Pavlovian response to the trigger, clients can detach their EMI from the psychophysiology stress response, i.e., “split-second unlearning.” Our split-second unlearning model recognizes the EMI as a barrier to moving forward and needs to be unlearned before the client can become naturally adaptive again. We argue that this approach places the client at the center of the work without the need of getting bogged down in a life-long narrative.

Metabotropic group II glutamate receptors in the basolateral amygdala mediate cue-triggered increases in incentive motivation.

Reward-associated cues can trigger incentive motivation for reward and invigorate reward-seeking behaviour via Pavlovian-to-instrumental transfer (PIT). Glutamate signaling within the basolateral amygdala (BLA) modulates cue-triggered increases in incentive motivation. However, the role of BLA metabotropic group II glutamate (mGlu2/3) receptors is largely unknown. In Experiment 1, we characterized cue-triggered increases in incentive motivation for water reward using the PIT paradigm. In Experiment 2, we assessed the influence of intra-BLA microinjections of the mGlu2/3 receptor agonist LY379268 on this effect. Water-restricted male Sprague-Dawley rats learned to press a lever for water. Separately, they learned to associate one of two auditory cues with free water. On test days, rats could lever press under extinction conditions (no water), with intermittent, non-contingent CS+ and CS- presentations. In Experiment 1, rats were tested under baseline conditions. In Experiment 2, rats received intra-BLA microinjections of LY379268 (0, 3 and 6 [Formula: see text]g/hemisphere) before testing. Across experiments, CS+, but not CS-, presentations increased water-associated lever pressing during testing, even though responding was reinforced neither by water nor the CS+. Intra-BLA LY379268 abolished both CS+ potentiated pressing on the water-associated lever and CS+ evoked conditioned approach to the site of water delivery. LY379268 did not influence locomotion or instrumental and Pavlovian response rates during intervals between CS presentations or during the CS-, indicating no motor effects. mGlu2/3 receptor activity in the BLA mediates cue-triggered potentiation of incentive motivation for reward, suppressing both cue-induced increases in instrumental pursuit of the reward and anticipatory approach behaviour.

Dopamine D2R upregulation in ventral striatopallidal neurons does not affect Pavlovian or go/no-go learning.

Ventral striatal dopamine is thought to be important for associative learning. Dopamine exerts its role via activation of dopamine D1 and D2 receptors in the ventral striatum. Upregulation of dopamine D2R in ventral striatopallidal neurons impairs incentive motivation via inhibiting synaptic transmission to the ventral pallidum. Here, we determined whether upregulation of D2Rs and the resulting impairment in ventral striatopallidal pathway function modulates associative learning in an auditory Pavlovian reward learning task as well as Go/No-Go learning in an operant based reward driven Go/No-Go task. We found that upregulation of D2Rs did not affect Pavlovian learning or the extinction of Pavlovian responses, and neither did it alter No-Go learning. We however observed a delay in the Go component of the task which may indicate a deficit in learning though it could also be attributed to the established locomotor hyperactivity of the mice. In combination with previously published findings, our data suggest that D2Rs in ventral striatopallidal neurons play a specific role in regulating motivation by balancing cost/benefit computations but do not necessarily affect associative learning. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Mobile and non-mobile Internet Use Disorder: Specific risks and possible shared Pavlovian conditioning processes. •.

This commentary addresses a recent article by Montag et al. (2019) about the relevance of distinguishing between mobile and non-mobile Internet Use Disorder (IUD). In response to the review, we reflect on the clinical relevance of this distinction and, in parallel, we propose some Pavlovian conditioning processes as possible mechanisms underlying different IUDs. We believe that, from a clinical point of view, it is of fundamental importance assessing both specific “forms” of IUDs and the underlying mechanisms that would be shared across different IUDs, like multiple and parallel classes of Pavlovian responses and the influences of Internet cues on Internet-related addictive behaviors that may be influenced by the probability of obtaining Internet rewards.

The Anomaly of Anomaly of Anomaly

The Anomaly of Anomaly of Anomaly

Adolescents exhibit reduced Pavlovian biases on instrumental learning

Multiple learning systems allow individuals to flexibly respond to opportunities and challenges present in the environment. An evolutionarily conserved “Pavlovian” learning mechanism couples valence and action, promoting a tendency to approach cues associated with reward and to inhibit action in the face of anticipated punishment. Although this default response system may be adaptive, these hard-wired reactions can hinder the ability to learn flexible “instrumental” actions in pursuit of a goal. Such constraints on behavioral flexibility have been studied extensively in adults. However, the extent to which these valence-specific response tendencies bias instrumental learning across development remains poorly characterized. Here, we show that while Pavlovian response biases constrain flexible action learning in children and adults, these biases are attenuated in adolescents. This adolescent-specific reduction in Pavlovian bias may promote unbiased exploration of approach and avoidance responses, facilitating the discovery of rewarding behavior in the many novel contexts that adolescents encounter.

Stimulation of the vagus nerve reduces learning in a go/no-go reinforcement learning task

When facing decisions to approach rewards or to avoid punishments, we often figuratively go with our gut, and the impact of metabolic states such as hunger on motivation are well documented. However, whether and how vagal feedback signals from the gut influence instrumental actions is unknown. Here, we investigated the effect of non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) vs. sham (randomized cross-over design) on approach and avoidance behavior using an established go/no-go reinforcement learning paradigm in 39 healthy human participants (23 female) after an overnight fast. First, mixed-effects logistic regression analysis of choice accuracy showed that taVNS acutely impaired decision-making, p = .041. Computational reinforcement learning models identified the cause of this as a reduction in the learning rate through taVNS (∆α = −0.092, pboot = .002), particularly after punishment (∆αPun = −0.081, pboot = .012 vs. ∆αRew =−0.031, pboot = .22). However, taVNS had no effect on go biases, Pavlovian response biases or response time. Hence, taVNS appeared to influence learning rather than action execution. These results highlight a novel role of vagal afferent input in modulating reinforcement learning by tuning the learning rate according to homeostatic needs.

Augmented reality cuisine

Augmented reality cuisine

Opposing roles for amygdala and vmPFC in the return of appetitive conditioned responses in humans

Learning accounts of addiction and obesity emphasize the persistent power of Pavlovian reward cues to trigger craving and increase relapse risk. While extinction can reduce conditioned responding, Pavlovian relapse phenomena—the return of conditioned responding following successful extinction—challenge the long-term success of extinction-based treatments. Translational laboratory models of Pavlovian relapse could therefore represent a valuable tool to investigate the mechanisms mediating relapse, although so far human research has mostly focused on return of fear phenomena. To this end we developed an appetitive conditioning paradigm with liquid food rewards in combination with a 3-day design to investigate the return of appetitive Pavlovian responses and the involved neural structures in healthy subjects. Pavlovian conditioning (day 1) was assessed in 62 participants, and a subsample (n = 33) further completed extinction (day 2) and a reinstatement test (day 3). Conditioned responding was assessed on explicit (pleasantness ratings) and implicit measures (reaction time, skin conductance, heart rate, startle response) and reinstatement effects were further evaluated using fMRI. We observed a return of conditioned responding during the reinstatement test, evident by enhanced skin conductance responses, accompanied by enhanced BOLD responses in the amygdala. On an individual level, psychophysiological reinstatement intensity was significantly anticorrelated with ventromedial prefrontal cortex (vmPFC) activation, and marginally anticorrelated with enhanced amygdala-vmPFC connectivity during late reinstatement. Our results extend evidence from return of fear phenomena to the appetitive domain, and highlight the role of the vmPFC and its functional connection with the amygdala in regulating appetitive Pavlovian relapse.

A Pavlovian account for paradoxical effects of motivation on controlling response vigour

In high stakes situations, people sometimes choke under pressure, performing below their abilities. Here, we suggest a novel mechanism to account for this paradoxical effect of motivation: the automatic adjustment of action vigour to potential reward. Although adaptive on average, this mechanism may impede fine motor control. Such detrimental effect was observed in three studies (n = 74 in total), using behavioural tasks where payoff depended on the precision of handgrip squeezing or golf putting. Participants produced more force for higher incentives, which aggravated their systematic overshooting of low-force targets. This reward bias was specific to action vigour, as reward did not alter action timing, direction or variability across trials. Although participants could report their reward bias, they somehow failed to limit their produced force. Such an automatic link between incentive and force level might correspond to a Pavlovian response that is counterproductive when action vigour is not instrumental for maximizing reward.

Individual differences in blink rate modulate the effect of instrumental control on subsequent Pavlovian responding

RationalePavlovian conditioned responses to cues that signal threat are rapidly acquired and tend to persist over time. However, recent research suggests that the ability to actively avoid or exert control over an anticipated threat can diminish the subsequent expression of Pavlovian responses. Studies in animal models suggest that active avoidance behavior and its consequences may be mediated by dopaminergic function. In the present study, we sought to replicate the finding that active control over threat can attenuate subsequent Pavlovian responding in humans and conducted exploratory analyses testing whether individual differences in blink rate, a putative index of dopaminergic function, might modulate this effect.MethodsParticipants underwent Pavlovian aversive conditioning, followed immediately by one of two conditions. In the active avoidance condition, participants had the opportunity to actively prevent the occurrence of an anticipated shock, whereas in a yoked extinction condition, participants passively observed the cessation of shocks, but with no ability to influence their occurrence. The following day, the conditioned stimuli were presented without shock, but both groups of participants had no opportunity to employ active instrumental responses. Blink rate was measured throughout the task, and skin conductance responses served as our index of Pavlovian conditioned responding.ResultsConsistent with our previous findings, we observed that the group that could actively avoid the shock on day 1 exhibited attenuated recovery of Pavlovian conditioned responses. Further, we found that individuals in the active avoidance group with higher blink rates exhibited a more robust attenuation of spontaneous recovery.ConclusionThis finding suggests that individual variation in dopaminergic function may modulate the efficacy with which active avoidance strategies can attenuate reactive Pavlovian responses.

Frontal network dynamics reflect neurocomputational mechanisms for reducing maladaptive biases in motivated action.

Motivation exerts control over behavior by eliciting Pavlovian responses, which can either match or conflict with instrumental action. We can overcome maladaptive motivational influences putatively through frontal cognitive control. However, the neurocomputational mechanisms subserving this control are unclear; does control entail up-regulating instrumental systems, down-regulating Pavlovian systems, or both? We combined electroencephalography (EEG) recordings with a motivational Go/NoGo learning task (N = 34), in which multiple Go options enabled us to disentangle selective action learning from nonselective Pavlovian responses. Midfrontal theta-band (4 Hz–8 Hz) activity covaried with the level of Pavlovian conflict and was associated with reduced Pavlovian biases rather than reduced instrumental learning biases. Motor and lateral prefrontal regions synchronized to the midfrontal cortex, and these network dynamics predicted the reduction of Pavlovian biases over and above local, midfrontal theta activity. This work links midfrontal processing to detecting Pavlovian conflict and highlights the importance of network processing in reducing the impact of maladaptive, Pavlovian biases.

Dorsal hippocampal neural immune signaling regulates heroin-conditioned immunomodulation but not heroin-conditioned place preference

Repeated pairings of heroin and a context results in Pavlovian associations which manifest as heroin-conditioned appetitive responses and peripheral immunomodulation upon re-exposure to heroin-paired conditioned stimuli (CS). The dorsal hippocampus (DH) plays a key role in the neurocircuitry governing these context-heroin associations. Within the DH, expression of the pro-inflammatory cytokine interleukin-1β (IL-1β) is required for heroin-conditioned peripheral immunomodulation to occur. However, the role of signaling via IL-1 receptor type 1 (IL-1R1) has not been examined. Furthermore, it has not been evaluated whether the involvement of IL-1 in associative learning extends to classically conditioned appetitive behaviors, such as conditioned place preference (CPP). The first set of experiments investigated whether DH IL-1R1 signaling during CS re-exposure modulates heroin-conditioned immunomodulation and heroin-CPP. The second set of experiments employed chemogenetic techniques to examine whether DH astroglial signaling during CS re-exposure alters the same Pavlovian responses. This line of investigation is based on previous research indicating that astrocytes support hippocampal-dependent learning and memory through the expression of IL-1β protein and IL-1R1. Interestingly, IL-1R1 antagonism disrupted heroin-conditioned suppression of peripheral immune parameters but failed to alter heroin-CPP. Similarly, chemogenetic stimulation of Gi-signaling in DH astrocytes attenuated heroin-conditioned peripheral immunomodulation but failed to alter heroin-CPP. Collectively our data show that both IL-1R1 stimulation and astrocyte signaling in the DH are critically involved in the expression of heroin-conditioned immunomodulation but not heroin-CPP. As such these findings strongly suggest hippocampal neuroimmune signaling differentially regulates Pavlovian immunomodulatory and appetitive behaviors.

Ventral pallidal encoding of reward-seeking behavior depends on the underlying associative structure.

Despite its being historically conceptualized as a motor expression site, emerging evidence suggests the ventral pallidum (VP) plays a more active role in integrating information to generate motivation. Here, we investigated whether rat VP cue responses would encode and contribute similarly to the vigor of reward-seeking behaviors trained under Pavlovian versus instrumental contingencies, when these behavioral responses consist of superficially similar locomotor response patterns but may reflect distinct underlying decision-making processes. We find that cue-elicited activity in many VP neurons predicts the latency of instrumental reward seeking, but not of Pavlovian response latency. Further, disruption of VP signaling increases the latency of instrumental but not Pavlovian reward seeking. This suggests that VP encoding of and contributions to response vigor are specific to the ability of incentive cues to invigorate reward-seeking behaviors upon which reward delivery is contingent.

Pavlovian Control of Escape and Avoidance.

To survive in complex environments, animals need to have mechanisms to select effective actions quickly, with minimal computational costs. As perhaps the computationally most parsimonious of these systems, Pavlovian control accomplishes this by hardwiring specific stereotyped responses to certain classes of stimuli. It is well documented that appetitive cues initiate a Pavlovian bias toward vigorous approach; however, Pavlovian responses to aversive stimuli are less well understood. Gaining a deeper understanding of aversive Pavlovian responses, such as active avoidance, is important given the critical role these behaviors play in several psychiatric conditions. The goal of the current study was to establish a behavioral and computational framework to examine aversive Pavlovian responses (activation vs. inhibition) depending on the proximity of an aversive state (escape vs. avoidance). We introduce a novel task in which participants are exposed to primary aversive (noise) stimuli and characterized behavior using a novel generative computational model. This model combines reinforcement learning and drift-diffusion models so as to capture effects of invigoration/inhibition in both explicit choice behavior as well as changes in RT. Choice and RT results both suggest that escape is associated with a bias for vigorous action, whereas avoidance is associated with behavioral inhibition. These results lay a foundation for future work seeking insights into typical and atypical aversive Pavlovian responses involved in psychiatric disorders, allowing us to quantify both implicit and explicit indices of vigorous choice behavior in the context of aversion.

Dissociation of place preference and tolerance responses to sucrose using a dopamine antagonist in the planarian

In rodents, sucrose has been found to elicit addictive-like behaviours like the development of tolerance and the association with cues present at the time of consumption. Furthermore, the neurochemical response to sucrose binges is equivalent to the one observed in response to the abuse of addictive substances like cocaine. The experiments reported here address the effects of sucrose on an invertebrate model, the Platyhelminth brown planarian. The animals exposed to a 10% sucrose solution in one context developed a conditioned place preference (CPP) which was subsequently extinguished in the absence of the rewarding agent. However, one exposure to sucrose per se sufficed to reinstate the CPP response, suggesting sucrose-induced CPP can be characterised as a standard Pavlovian response. The same training procedure led to the development of context-specific tolerance to the effects of sucrose. However, comparing animals treated with dopamine D1 antagonist (SCH-23390) with control animals showed that the establishment of CPP, but not the development of tolerance, is mediated by the dopamine reward system.