Aversive conditioning, anxiety, and the strategic control of attention.

What we pay attention to is influenced by both reward learning and aversive conditioning. Although early attention tends to be biased toward aversively conditioned stimuli, sustained ignoring of such stimuli is also possible. How aversive conditioning influences how a person chooses to search, or the strategic control of attention, has not been explored. In the present study, participants learned an association between a colour and an aversive outcome during a training phase, and in a subsequent test phase searched for one of two targets presented on each trial; one target was rendered in the aversively conditioned colour (CS+) and the other in a neutral colour (CS-). Given the distribution of colour stimuli in the search array, it was more optimal to search for and report a target in one of the two colours on some trials. Our results demonstrate that participants were biased away from the CS+ target, which resulted in non-optimal search on some trials. Surprisingly, rather than accentuate this bias, greater state anxiety was associated with a stronger tendency to find and report the CS+ target. Our findings have implications for our understanding of the learning-dependent control of attention and abnormal attentional biases observed in high-anxious individuals.

Observational learning of threat-related attentional bias.

Attentional bias to threat has been almost exclusively examined after participants experienced repeated pairings between a conditioned stimulus (CS) and an aversive unconditioned stimulus (US). This study aimed to determine whether threat-related attentional capture can result from observational learning, when participants acquire knowledge of the aversive qualities of a stimulus without themselves experiencing aversive outcomes. Non-clinical young-adult participants (N = 38) first watched a video of an individual (the demonstrator) performing a Pavlovian conditioning task in which one colour was paired with shock (CS+) and another colour was neutral (CS-). They then carried out visual search for a shape-defined target. Oculomotor measures evidenced an attentional bias toward the CS+ colour, suggesting that threat-related attentional capture can ensue from observational learning. Exploratory analyses also revealed that this effect was positively correlated with empathy for the demonstrator. Our findings extend empirical and theoretical knowledge about threat-driven attention and provide valuable insights to better understand the formation of anxiety disorders.

Value-Biased Competition in the Auditory System of the Brain.

Attentional capture by previously reward-associated stimuli has predominantly been measured in the visual domain. Recently, behavioral studies of value-driven attention have demonstrated involuntary attentional capture by previously reward-associated sounds, emulating behavioral findings within the visual domain and suggesting a common mechanism of attentional capture by value across sensory modalities. However, the neural correlates of the modulatory role of learned value on the processing of auditory information has not been examined. Here, we conducted a neuroimaging study on human participants using a previously established behavioral paradigm that measures value-driven attention in an auditory target identification task. We replicate behavioral findings of both voluntary prioritization and involuntary attentional capture by previously reward-associated sounds. When task-relevant, the selective processing of high-value sounds is supported by reduced activation in the dorsal attention network of the visual system (FEF, intraparietal sulcus, right middle frontal gyrus), implicating cross-modal processes of biased competition. When task-irrelevant, in contrast, high-value sounds evoke elevated activation in posterior parietal cortex and are represented with greater fidelity in the auditory cortex. Our findings reveal two distinct mechanisms of prioritizing reward-related auditory signals, with voluntary and involuntary modes of orienting that are differently manifested in biased competition.

Alteration of early attentional processing after analogue trauma exposure: evidence from event-related potentials.

The present study aimed to determine whether exposure to an analogue traumatic event affects attentional processing of emotional information. Two groups of non-clinical participants matched on anxiety level, depression symptoms and stressful life events viewed either a trauma or a neutral film. They then performed an emotional Stroop task during which both continuous electroencephalographic activity was recorded and intrusive memories were measured. Results revealed that the valence effect (measured by the difference between emotional and neutral conditions) for the P1 amplitude was significantly greater in participants who viewed the trauma film than in participants who viewed the neutral film. This interaction was specific to words semantically related to the analogue trauma event and did not extend to all negative words. Further analyses revealed a relationship between intrusions frequency, P1 amplitude and emotional Stroop interference, indicating a link between attention and intrusive memories. Our findings suggest that exposure to potentially traumatic events has an important impact on neurocognitive function, even in the absence of psychopathology, and that this impact occurs at an early, possibly automatic stage of processing.

Perceptual processing of stimuli related to an analogue traumatic event: An ERP study.

Previous research has suggested that exposure to potentially traumatic events can lead to increased perceptual processing specific to trauma-related stimuli. Moreover, conceptual processing strategies during encoding may reduce the effect of trauma exposure on perceptual processing. The current study investigated the effect of a trauma film on perceptual processing with visual evoked potentials. Participants were primed with perceptual or conceptual processing strategies, then viewed a trauma film and a control film. Participants then looked at emotionally negative and neutral images that were related or unrelated to the films. The amplitude of the P1 evoked potential was measured during image presentation. P1 amplitude was more positive specifically for negative film-related stimuli. Moreover, this effect was stronger in participants primed with perceptual processing. These results suggest that potentially traumatic events increase perceptual processing specifically for trauma-related stimuli, and that conceptual encoding strategies attenuate the effect of exposure to potentially traumatic events on perception.

Fear of the known: semantic generalisation of fear conditioning across languages in bilinguals.

While modern theories of emotion emphasize the role of higher-order cognitive processes such as semantics in human emotion, much research into emotional learning has ignored the potential contributions of such processes. This study aimed to determine whether emotional learning affects semantic representations of words independent of perceptual features by assessing whether fear conditioning to a neutral word generalises across languages in bilingual participants. Two sessions differing according to the reinforced language were performed by English-Spanish bilinguals. In each session, a neutral word was reinforced by an electrical shock whereas its equivalent in the other language was never paired with shock. Across two sessions within our sample, we found replicable evidence that fear conditioning consistently transferred to the non-reinforced language as measured by both self-reported fear and electrodermal activity, irrespective of the conditioned language. Our findings extend knowledge about the role of semantic similarity in fear generalisation and highlight the importance of higher-order cognitive processes in human emotions.

Semantic generalization of value-based attentional priority.

This study aimed to determine whether attentional prioritization of stimuli associated with reward transfers across conceptual knowledge independently of physical features. Participants successively performed two color-word Stroop tasks. In the learning phase, neutral words were associated with high, low, or no monetary reward. In the generalization phase (in which no reward was delivered), synonyms of words previously paired with reward served as Stroop stimuli. Results are consistent with semantic generalization of stimulus-reward associations, with synonyms of high-value words impairing color-naming performance, although this effect was particular to participants who were unaware of the reward contingencies.

An mGlu4-Positive Allosteric Modulator Alleviates Parkinsonism in Primates.

BACKGROUND: Levodopa remains the gold-standard treatment for PD. However, it becomes less effective as the disease progresses and produces debilitating side effects, such as motor fluctuations and l-dopa-induced dyskinesia. Modulation of metabotropic glutamate receptor 4 represents a promising antiparkinsonian approach in combination with l-dopa, but it has not been demonstrated in primates. OBJECTIVE: We studied whether a novel positive allosteric modulator of the metabotropic glutamate receptor 4, PXT002331 (foliglurax), could reduce parkinsonism in primate models. METHODS: We assessed the therapeutic potential of PXT002331 in three models of MPTP-induced parkinsonism in macaques. These models represent three different stages of disease evolution: early stage and advanced stage with and without l-dopa-induced dyskinesia. RESULTS: As an adjunct to l-dopa, PXT002331 induced a robust and dose-dependent reversal of parkinsonian motor symptoms in macaques, including bradykinesia, tremor, posture, and mobility. Moreover, PXT002331 strongly decreased dyskinesia severity, thus having therapeutic efficacy on both parkinsonian motor impairment and l-dopa-induced dyskinesia. PXT002331 brain penetration was also assessed using PET imaging in macaques, and pharmacodynamic analyses support target engagement in the therapeutic effects of PXT002331. CONCLUSIONS: This work provides a demonstration that a positive allosteric modulator of metabotropic glutamate receptor 4 can alleviate the motor symptoms of PD and the motor complications induced by l-dopa in primates. PXT002331 is the first compound of its class to enter phase IIa clinical trials. © 2018 International Parkinson and Movement Disorder Society.

Dissociating conscious expectancies from automatic-link formation in an electrodermal conditioning paradigm.

The key point of a paradigm initially proposed by Perruchet (Pavlov J Biol Sci 20:163-170, 1985) to dissociate conscious expectancies from automatic-link formation in classical conditioning settings is the use of a partial reinforcement schedule, in which the unconditioned stimulus (US) follows the conditioned stimulus (CS) only half of the time on average. Given (pseudo) randomization, the whole sequence comprises runs of CS alone and runs of CS-US pairs of various lengths. When the preceding run goes from a long sequence of CS alone to a long sequence of CS-US pairs (via shorter sequences), associative strength should grow up, whereas conscious expectancy should decrease. Earlier studies have shown that, in most cases, conditioned performance parallels associative strength. As an exception, however, a few reports suggest that conditioned electrodermal responses (EDRs) would follow predicted changes in US expectancies. This paper presents an experiment that replicates this outcome. However, when the performances from a control group were taken as a baseline to control for response habituation, corrected conditioned EDRs were shown to follow associative strength. This suggests that the atypical pattern of conditioned EDRs in the Perruchet paradigm would be due to the fact that EDRs are more sensitive to habituation than responses involved in other associative learning settings. These results further challenge the recent "propositional" view of conditioning, which stipulates that conditioned responses in humans are the consequence of participants' conscious inferences about the relationships between the CS and the US, which would lead the CS to generate conscious expectancy for the US.

Instructional learning of threat-related attentional capture is modulated by state anxiety.

The present study aimed to determine whether persistent threat-related attentional capture can result from instructional learning, when participants acquire knowledge of the aversive qualities of a stimulus through verbal instruction. Fifty-four nonclinical adults first performed a visual search task in which a green or red circle was presented as a target. They were instructed that one of these two colors might be paired with an electric shock if they responded slowly or inaccurately, whereas the other color was never associated with shock. However, no shocks were actually delivered. In a subsequent test phase, in which participants were explicitly informed that shocks were no longer possible, former-target-color stimuli were presented as distractors in a visual search task for a shape-defined target. In both tasks, although participants were never exposed to the electric shock, we observed a significant correlation between threat-related attentional priority and state anxiety. Our results demonstrate that exposure to a stimulus with the belief that it could be threatening is sufficient to generate a persistent attentional bias toward that stimulus, but this effect is modulated by state anxiety. Attentional biases for fear-relevant stimuli have been implicated in anxiety disorders, and our findings demonstrate that for anxious participants, attentional biases can be entirely the product of erroneous beliefs concerning the linking between stimuli and possible outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Reliably Measuring Learning-Dependent Distractor Suppression with Eye Tracking.

In the field of psychological science, behavioral performance in computer-based cognitive tasks often exhibits poor reliability. The absence of reliable measures of cognitive processes contributes to non-reproducibility in the field and impedes investigation of individual differences. Specifically in visual search paradigms, response time-based measures have shown poor test-retest reliability and internal consistency across attention capture and distractor suppression, but one study has demonstrated the potential for oculomotor measures to exhibit superior reliability. Therefore, in this study, we investigated three datasets to compare the reliability of learning-dependent distractor suppression measured via distractor fixations (oculomotor capture) and latency to fixate the target (fixation times). Our findings reveal superior split-half reliability of oculomotor capture compared to that of fixation times regardless of the critical distractor comparison, with the reliability of oculomotor capture in most cases falling within the range that is acceptable for the investigation of individual differences. We additionally find that older adults have superior oculomotor reliability compared with young adults, potentially addressing a significant limitation in the aging literature of high variability in response time measures due to slower responses. Our findings highlight the utility of measuring eye movements in the pursuit of reliable indicators of distractor processing and the need to further test and develop additional measures in other sensory domains to maximize statistical power, reliability, and reproducibility.

Protocol to evaluate the effectiveness of a virtual-reality-based behavioral intervention in enhancing sensory responses to real-world warning.

Habituation to signals that warn of a potential danger in high-risk work environments is a critical causal factor of workplace accidents. Such habituation is hard to measure in a real-world setting, and no existing intervention can effectively curb it. Here, we present a protocol to enhance workers' sensory responses to frequently encountered warnings at workplaces using a virtual-reality-based behavioral intervention. We describe steps for performing a virtual reality experiment and an electroencephalography (EEG) experiment with human participants. For complete details on the use and execution of this protocol, please refer to Kim et al.1.

Generalisation of value-based attentional priority is category-specific.

A large body of research suggests that previously reward-associated stimuli can capture attention. Recent evidence also suggests that value-driven attentional biases can occur for a particular category of objects. However, it is unclear how broadly these category-level attentional biases can generalise. In the present study, we examined whether value-driven attentional biases can generalise to new exemplars of a category or semantically related categories using a modified version of the value-driven attentional capture paradigm. In an initial training phase, participants searched for two categories of objects and were rewarded for correctly fixating members of one target category. In a subsequent test phase, participants searched for two new categories of objects. A new exemplar of one of the previous target categories or a member of a semantically related category could appear as a critical distractor in this phase. Participants were more likely to initially fixate the critical distractor and fixated the distractor longer when it was a new exemplar of the previously rewarded category. However, similar findings were not observed for members of semantically related categories. Together, these findings suggest that the generalisation of value-based attentional priority is category-specific.

Conscious expectancy rather than associative strength elicits brain activity during single-cue fear conditioning.

The neurocognitive processes underlying Pavlovian conditioning in humans are still largely debated. The conventional view is that conditioned responses (CRs) emerge automatically as a function of the contingencies between a conditioned stimulus (CS) and an unconditioned stimulus (US). As such, the associative strength model asserts that the frequency or amplitude of CRs reflects the strength of the CS-US associations. Alternatively, the expectation model asserts that the presentation of the CS triggers conscious expectancy of the US, which is responsible for the production of CRs. The present study tested the hypothesis that there are dissociable brain networks related to the expectancy and associative strength theories using a single-cue fear conditioning paradigm with a pseudo-random intermittent reinforcement schedule during functional magnetic resonance imaging. Participants' (n = 21) trial-by-trial expectations of receiving shock displayed a significant linear effect consistent with the expectation model. We also found a positive linear relationship between the expectancy model and activity in frontoparietal brain areas including the dorsolateral prefrontal cortex (PFC) and dorsomedial PFC. While an exploratory analysis found a linear relationship consistent with the associated strength model in the insula and early visual cortex, our primary results are consistent with the view that conscious expectancy contributes to CRs.

Virtual accident curb risk habituation in workers by restoring sensory responses to real-world warning.

In high-risk work environments, workers become habituated to hazards they frequently encounter, subsequently underestimating risk and engaging in unsafe behaviors. This phenomenon has been termed "risk habituation" and identified as a vital root cause of fatalities and injuries at workplaces. Providing an effective intervention that curbs workers' risk habituation is critical in preventing occupational injuries and fatalities. However, there exists no empirically supported intervention for curbing risk habituation. To this end, here we investigated how experiencing an accident in a virtual reality (VR) environment affects workers' risk habituation toward repeatedly exposed workplace hazards. We examined an underlying mechanism of risk habituation at the sensory level and evaluated the effect of the accident intervention through electroencephalography (EEG). The results of pre- and posttreatment analyses indicate experiencing the virtual accident effectively curbs risk habituation at both the behavioral and sensory level. The findings open new vistas for occupational safety training.

Cross-modal generalization of value-based attentional priority.

This study aimed to determine whether value-based attentional biases learned in the auditory domain can correspondingly shape visual attention. A learning phase established associations between auditory words and monetary rewards via a modified version of the dichotic listening task. In a subsequent test phase, participants performed a Stroop task including written representations of auditory words previously paired with reward and semantic associates of formerly rewarded words. Results support a semantic generalization of value-driven attention from the auditory to the visual domain. The findings provide valuable insight into a critical aspect of adaptation and the understanding of maladaptive behaviors (e.g., addiction).

Pavlovian learning in the selection history-dependent control of overt spatial attention.

Learning from rewarding and aversive outcomes shapes how sensory signals are processed by the attention system, reflecting a consequence of selection history. Substantial evidence points to Pavlovian associative learning as the mechanism by which previously reward-associated and aversively conditioned stimulus features gain attentional priority. On the basis of differences between reward-dependent feature-based and space-based attentional biases, it has been suggested that reinforcement learning underlies the influence of selection history on spatial attention. By pairing the orienting of overt spatial attention with aversive electric shock, we provide direct evidence that Pavlovian learning between locations and outcomes can shape spatial attention. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Motivated suppression of value- and threat-modulated attentional capture.

Attention prioritizes stimuli previously associated with reward or punishment. The present study examined whether this attentional bias, widely considered to be involuntary and automatic, could be suppressed with sufficient motivation. Participants performed visual search for a shape-defined target. One color-singleton distractor predicted the possibility of receiving a reward and another an electric shock, with each outcome occurring infrequently. Participants were informed that the likelihood to earn a reward or avert punishment depended on fast and accurate performance, thus providing strong motivation to resist distraction by reward- and shock-related stimuli. Results revealed a reduction in the magnitude of attentional capture by reward- and threat-associated distractors, relative to neutral distractors, that persisted into extinction. In a second experiment, we replicated the suppression of value-modulated attentional capture in the absence of the shock condition, thus confirming that the suppression did not result from the presence of threat. Finally, in a third experiment, we replicated the typical pattern of attentional capture by reward cues using a more conventional procedure in which the motivation to suppress valent stimuli was low (the likelihood to be rewarded was high and not contingent on fast performance). This study demonstrates that signals for reward and threat can be actively suppressed with sufficient motivation. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

AV-101, a Pro-Drug Antagonist at the NMDA Receptor Glycine Site, Reduces L-Dopa Induced Dyskinesias in MPTP Monkeys.

N-methyl-D-aspartate (NMDA) receptors have been implicated in L-Dopa-induced dyskinesias (LID) in Parkinson's disease patients, but the use of antagonists that directly inhibit this receptor is associated with severe side effects. L-4-chlorokynurenine (4-Cl-KYN or AV-101) is a pro-drug of 7-chlorokynurenic acid (7-Cl-KYNA), a potent and specific antagonist of the glycine (GlyB) co-agonist site of NMDA receptors. The 7-Cl-KYNA has limited ability to cross the blood-brain barrier, whereas AV-101 readily accesses the brain. We investigated if AV-101 reduces LID in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys while maintaining the antiparkinsonian activity of L-Dopa. A first pilot study using three dyskinetic MPTP monkeys showed that acute AV-101 treatment (250 and 450 mg/kg) reduced LID and maintained the antiparkinsonian activity of L-Dopa. The main study using six additional dyskinetic MPTP monkeys showed that repeated AV-101 treatment (250 mg/kg, b.i.d. for 4 consecutive days) maintained their L-Dopa antiparkinsonian response. We measured significantly less LID when AV-101 was combined with L-Dopa treatment. AV-101 alone or with L-Dopa had no non-motor adverse effects in MPTP monkeys. Our study showed antidyskinetic activity of AV-101 in MPTP monkeys was comparable to amantadine tested previously in our laboratory in this model. We observed no adverse effects with AV-101, which is an improvement over amantadine, with its known side effects.

Mental imagery can generate and regulate acquired differential fear conditioned reactivity.

Mental imagery is an important tool in the cognitive control of emotion. The present study tests the prediction that visual imagery can generate and regulate differential fear conditioning via the activation and prioritization of stimulus representations in early visual cortices. We combined differential fear conditioning with manipulations of viewing and imagining basic visual stimuli in humans. We discovered that mental imagery of a fear-conditioned stimulus compared to imagery of a safe conditioned stimulus generated a significantly greater conditioned response as measured by self-reported fear, the skin conductance response, and right anterior insula activity (experiment 1). Moreover, mental imagery effectively down- and up-regulated the fear conditioned responses (experiment 2). Multivariate classification using the functional magnetic resonance imaging data from retinotopically defined early visual regions revealed significant decoding of the imagined stimuli in V2 and V3 (experiment 1) but significantly reduced decoding in these regions during imagery-based regulation (experiment 2). Together, the present findings indicate that mental imagery can generate and regulate a differential fear conditioned response via mechanisms of the depictive theory of imagery and the biased-competition theory of attention. These findings also highlight the potential importance of mental imagery in the manifestation and treatment of psychological illnesses.