Discriminative Stimulus Research Articles

The use of a picture activity schedule for vocal stereotypy reduction in a child with autism

Children with ASD exhibit auto-stimulatory behaviour of different types, with the most common behavioural problem being auto-stimulatory stereotyped behaviour. It is believed that vocal auto-stimulatory behaviour occurs because the individuals with ASD do not receive sufficient stimulation from their environment and therefore have the need to stimulate themselves by emitting vocal stereotypy of different form and magnitude. The participant is a 10-year-old boy diagnosed with ASD. The intervention used was a picture activity schedule. Results showed an immediate decrease in self-stimulatory behaviour upon implementation of the intervention, with a 100% success rate. There is insufficient research on the implementation of picture activity schedules in order to reduce self-stimulatory behaviour in children with ASD. The present study shows that picture activity schedules can be used in certain situations where it is inappropriate to exhibit self-stimulating behaviour. It is not certain if the picture activity schedule functioned as a prompt for the participant to actively engage in his spare time, or if it functioned as a discriminative stimulus for situations when the problem behaviour is inappropriate. The social validity of the intervention was discussed, as well as suggestions for future research implementation.

Knowledge of Threat Biases Perceptual Decision Making in Anxiety: Evidence From Signal Detection Theory and Drift Diffusion Modeling

BackgroundThreat biases are considered key factors in the development and maintenance of anxiety. However, these biases are poorly operationalized and remain unquantified. Furthermore, it is unclear whether and how prior knowledge of threat and its uncertainty induce these biases and how they manifest in anxiety. MethodParticipants (n = 55) used prestimulus cues to decide whether the subsequently presented stimuli were threatening or neutral. The cues either provided no information about the probability (high uncertainty) or indicated high probability (low uncertainty) of encountering threatening or neutral targets. We used signal detection theory and hierarchical drift diffusion modeling to quantify bias. ResultsHigh-uncertainty threat cues improved discrimination of subsequent threatening and neutral stimuli more than neutral cues. However, anxiety was associated with worse discrimination of threatening versus neutral stimuli following high-uncertainty threat cues. Using hierarchical drift diffusion modeling, we found that threat cues biased decision making not only by shifting the starting point of evidence accumulation toward the threat decision but also by increasing the efficiency with which sensory evidence was accumulated for both threat-related and neutral decisions. However, higher anxiety was associated with a greater shift of starting point toward the threat decision but not with the efficiency of evidence accumulation. ConclusionsUsing computational modeling, these results highlight the biases by which knowledge regarding uncertain threat improves perceptual decision making but impairs it in case of anxiety.

Partial reinforcement extinction and omission effects in the elimination and recovery of discriminated operant behavior.

Three experiments explored how training reinforcement schedules and context influence the elimination and recovery of human operant behavior. In Experiment 1, participants learned a discriminated operant response in Context A before the response was eliminated with extinction in Context B. They then received a final test in each context. Groups were trained with a discriminative stimulus that predicted a reinforced response on either every trial (continuous reinforcement [CRF]) or some of the trials (partial reinforcement [PRF]). Extinction was slower following PRF training (a partial reinforcement extinction effect [PREE]) and extinguished responding increased when tested in Context A ("ABA" renewal). Experiment 2 further confirmed the PREE was obtained equally whether extinction occurred in the training context (Context A) or a new context (Context B) which is consistent with trial-based accounts of the PREE. Experiment 3 used the same design as Experiment 1 to evaluate the influence of training reinforcement on response elimination with an omission contingency. Across the omission training phase in Context B, the decrease in responding occurred more slowly in the PRF-trained group in comparison to the CRF-trained group, perhaps the first demonstration of what might be termed a PRF omission effect. Again, ABA renewal was observed in Context A. Training reinforcement schedule therefore had a similar influence on response elimination with extinction and omission. Elimination and recovery of human instrumental behavior, with extinction or omission, are influenced by training reinforcement schedule and context. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Telepractice in speech-language pathology: Assessing remote speech discrimination

PurposeTo evaluate adult remote performance in speech discrimination on the Temple Assessment of Language and Short-term Memory in Aphasia (TALSA), and to compare to remote performance in NU-6 word repetition and participant ratings of self-perceived hearing ability obtained via remote session. MethodSixty older adults completed TALSA speech discrimination of concrete, low frequency words and of non-words via telephone. Remote repetition of words controlled for sound frequency was assessed using the Northwestern University (NU-6) word lists administered in live voice and recorded voice conditions. Forty-six of the participants completed questionnaires about their hearing via Zoom videoconference. ResultsMean performance in TALSA speech discrimination for words was similar to performance in NU-6 word repetition. Word repetition of NU-6 lists did not differ significantly for live voice versus recorded voice conditions. TALSA non-word speech discrimination was significantly worse than TALSA speech discrimination for words and was associated with age and self-reported hearing ability. ConclusionsTALSA speech discrimination can be administered remotely to evaluate potential perceptual influences on auditory comprehension. In remote assessment, participants demonstrated the expected pattern of more accurate speech discrimination for word stimuli than for non-words. The non-word TALSA condition may be particularly useful for detecting speech perception impairment, both in face-to-face and telepractice sessions. Similar performance of participants in both live voice and recorded conditions of the NU-6 word lists suggests that recordings used in SLP receptive language or memory assessment, including the TALSA, need not be abandoned in favor of live voice to support audition during telepractice.

Comparing the Effect of Echoic and Listener Responding in the Development of Complex Intraverbals.

This study aimed to compare the effects of echoic and listener responding in the emergence of complex intraverbal behavior in four children with autism spectrum disorder (ASD). Each participant was taught to provide an echoic response or a listener response for different discriminative stimuli for each condition. We used a nonconcurrent multiple probe design across participants and adapted an alternating treatment design to compare the effects between the two conditions. Pre- and posttests were used to evaluate the effects of the two different prompt types in the emergence of complex intraverbals. The results indicate that the echoic response was more effective than the listener response at increasing the emergence of complex intraverbal responses in three out of four participants.

Ventral Pallidal GABAergic Neuron Calcium Activity Encodes Cue-Driven Reward Seeking and Persists in the Absence of Reward Delivery.

Reward-seeking behavior is often initiated by environmental cues that signal reward availability. This is a necessary behavioral response; however, cue reactivity and reward-seeking behavior can become maladaptive. To better understand how cue-elicited reward seeking becomes maladaptive, it is important to understand the neural circuits involved in assigning appetitive value to rewarding cues and actions. Ventral pallidum (VP) neurons are known to contribute to cue-elicited reward-seeking behavior and have heterogeneous responses in a discriminative stimulus (DS) task. The VP neuronal subtypes and output pathways that encode distinct aspects of the DS task remain unknown. Here, we used an intersectional viral approach with fiber photometry to record bulk calcium activity in VP GABAergic (VP GABA) neurons in male and female rats as they learned and performed the DS task. We found that VP GABA neurons are excited by reward-predictive cues but not neutral cues and that this response develops over time. We also found that this cue-evoked response predicts reward-seeking behavior and that inhibiting this VP GABA activity during cue presentation decreases reward-seeking behavior. Additionally, we found increased VP GABA calcium activity at the time of expected reward delivery, which occurred even on trials when reward was omitted. Together, these findings suggest that VP GABA neurons encode reward expectation, and calcium activity in these neurons encodes the vigor of cue-elicited reward seeking.SIGNIFICANCE STATEMENT VP circuitry is a major driver of cue-evoked behaviors. Previous work has found that VP neurons have heterogenous responses and contributions to reward-seeking behavior. This functional heterogeneity is because of differences of neurochemical subtypes and projections of VP neurons. Understanding the heterogenous responses among and within VP neuronal cell types is a necessary step in further understanding how cue-evoked behavior becomes maladaptive. Our work explores the canonical GABAergic VP neuron and how the calcium activity of these cells encodes components of cue-evoked reward seeking, including the vigor and persistence of reward seeking.

The relationship between central and mid-peripheral motion perception and the hazard perception test in younger and older adults.

Vision standards for driving are typically based on visual acuity, despite evidence that it is a poor predictor of driving safety and performance. However, visual motion perception is potentially relevant for driving, as the vehicle and surroundings are in motion. This study explored whether tests of central and mid-peripheral motion perception better predict performance on a hazard perception test (HPT), which is related to driving performance and crash risk, than visual acuity. Additionally, we explored whether age influences these associations, as healthy ageing impairs performance on some motion sensitivity tests. Sixty-five visually healthy drivers (35 younger, mean age: 25.5; SD 4.3 years; 30 older adults, mean age: 71.0; SD 5.4 years) underwent a computer-based HPT, plus four different motion sensitivity tests both centrally and at 15° eccentricity. Motion tests included minimum displacement to identify motion direction (Dmin ), contrast detection threshold for a drifting Gabor (motion contrast), coherence threshold for a translational global motion stimulus and direction discrimination for a biological motion stimulus in the presence of noise. Overall, HPT reaction times were not significantly different between age groups (p = 0.40) nor were maximum HPT reaction times (p = 0.34). HPT response time was associated with motion contrast and Dmin centrally (r = 0.30, p = 0.02 and r = 0.28, p = 0.02, respectively) and with Dmin peripherally (r = 0.34, p = 0.005); these associations were not affected by age group. There was no significant association between binocular visual acuity and HPT response times (r = 0.02, p = 0.29). Some measures of motion sensitivity in central and mid-peripheral vision were associated with HPT response times, whereas binocular visual acuity was not. Peripheral testing did not show an advantage over central testing for visually healthy older drivers. Our findings add to the growing body of evidence that the ability to detect small motion changes may have potential to identify unsafe road users.

Response-specific effects of punishment of a discriminated operant response

To determine whether the punishment of a discriminated operant behavior has effects that are specific to the punished response, rats were reinforced for performing two different instrumental responses (lever pressing and chain pulling) in the presence of a single discriminative stimulus (S). They were then either punished with mild footshock for performing one of the responses (R1) in S, or they received the same shocks in a noncontingent manner while performing R1 in S (i.e., a yoked control). In final tests of both R1 and R2 in S, the punished rats were more suppressed to R1 than R2, but the yoked rats were not. The results extend previous results with extinction rather than punishment learning (Bouton, Trask, & Carranza-Jasso, 2016) and support a larger parallel between extinction and punishment of both free-operant and discriminated-operant responding. Punishment is like extinction in creating a response-specific inhibition of either free or discriminated operant behavior.

Characterizing neural coding performance for populations of sensory neurons: comparing a weighted spike distance metrics to other analytical methods.

The identity of sensory stimuli is encoded in the spatio-temporal patterns of responses of the encoding neural population. For stimuli to be discriminated reliably, differences in population responses must be accurately decoded by downstream networks. Several methods to compare patterns of responses have been used by neurophysiologists to characterize the accuracy of the sensory responses studied. Among the most widely used analyses, we note methods based on Euclidean distances or on spike metric distances. Methods based on artificial neural networks and machine learning that recognize and/or classify specific input patterns have also gained popularity. Here, we first compare these three strategies using datasets from three different model systems: the moth olfactory system, the electrosensory system of gymnotids, and leaky-integrate-and-fire (LIF) model responses. We show that the input-weighting procedure inherent to artificial neural networks allows the efficient extraction of information relevant to stimulus discrimination. To combine the convenience of methods such as spike metric distances but leverage the advantages of weighting the inputs, we propose a measure based on geometric distances where each dimension is weighted proportionally to how informative it is. We show that the result of this Weighted Euclidian Distance (WED) analysis performs as well or better than the artificial neural network we tested and outperforms the more traditional spike distance metrics. We applied information theoretic analysis to LIF responses and compared their encoding accuracy with the discrimination accuracy quantified through this WED analysis. We show a high degree of correlation between discrimination accuracy and information content, and that our weighting procedure allowed the efficient use of information present to perform the discrimination task. We argue that our proposed measure provides the flexibility and ease of use sought by neurophysiologists while providing a more powerful way to extract relevant information than more traditional methods.

Metacontingency Terminology, Philosophical Assumptions, and the Scientific Dialogue: A Response to Ardila-Sánchez and Hayes (2023).

Ardila-Sánchez and Hayes (2023, this issue) discuss how differing philosophical assumptions might reflect on differing metacontingency terminology and debate some of the arguments presented by Sampaio and Haydu (2023). We respond by restating the urgent need to clarify the definition of cultural milieu, which is illustrated by an argument about discriminative stimuli as components of the cultural milieu. We clarify that the differences in metacontingency terminology that we did not emphasize were related to interlocking behavioral contingencies (IBCs) and cultural consequences, and not to cultural milieu and group-rule generation. We question any rigid separations of "Skinnerian" and "Kantorian views" of cultural phenomena, insisting that we focus on a unified culturo-behavior science. We elucidate that verbal responses and stimuli may participate in IBCs, cultural antecendents, or selecting environment variables; answer some questions about the latter two concepts; and clarify that the we presented a COVID-19 psychological support project not to empirically validate the concept, but to illustrate and test the conceptual coherence of the terms and theory.

Neurophysiological correlates of tactile width discrimination in humans.

Tactile information processing requires the integration of sensory, motor, and cognitive information. Width discrimination has been extensively studied in rodents, but not in humans. Here, we describe Electroencephalography (EEG) signals in humans performing a tactile width discrimination task. The first goal of this study was to describe changes in neural activity occurring during the discrimination and the response periods. The second goal was to relate specific changes in neural activity to the performance in the task. Comparison of changes in power between two different periods of the task, corresponding to the discrimination of the tactile stimulus and the motor response, revealed the engagement of an asymmetrical network associated with fronto-temporo-parieto-occipital electrodes and across multiple frequency bands. Analysis of ratios of higher [Ratio 1: (0.5-20 Hz)/(0.5-45 Hz)] or lower frequencies [Ratio 2: (0.5-4.5 Hz)/(0.5-9 Hz)], during the discrimination period revealed that activity recorded from frontal-parietal electrodes was correlated to tactile width discrimination performance between-subjects, independently of task difficulty. Meanwhile, the dynamics in parieto-occipital electrodes were correlated to the changes in performance within-subjects (i.e., between the first and the second blocks) independently of task difficulty. In addition, analysis of information transfer, using Granger causality, further demonstrated that improvements in performance between blocks were characterized by an overall reduction in information transfer to the ipsilateral parietal electrode (P4) and an increase in information transfer to the contralateral parietal electrode (P3). The main finding of this study is that fronto-parietal electrodes encoded between-subjects' performances while parieto-occipital electrodes encoded within-subjects' performances, supporting the notion that tactile width discrimination processing is associated with a complex asymmetrical network involving fronto-parieto-occipital electrodes.

Psychological and physiological correlates of stimulus discrimination in adults.

The discrimination of cues in the environment that signal danger ("fear cue") is important for survival but depends critically on the discernment of such cues from ones that pose no threat ("safety cues"). In rodents, we previously demonstrated the underlying neurobiological mechanisms that support fear versus safety discrimination and documented that these mechanisms extend to the discrimination of reward as well. While learning about reward is equally important for survival, it remains an under-studied area of research, particularly in human studies of conditional discrimination. In the present study, we translated our rodent task of fear reward and neutral discrimination (fear, reward, and neutral discrimination [FRND]) for use in humans. Undergraduate students (N = 53) completed the FRND while electrodermal activity was recorded. Skin conductance response (SCR) amplitude, a marker of arousal response, was derived for fear, reward, and neutral cues that signaled no outcome; critical trials assessed conditional discrimination using combined fear + neutral and reward + neutral cues. Participants provided likeability ratings for each cue type. Results demonstrated that participants rated reward cues the best, fear cues the worst, and neutral cues in between, while SCR amplitude was largest for fear and reward cues and lowest for neutral cues. SCR amplitudes were reduced for fear + neutral (compared to fear) and reward + neutral cues (compared to reward). Results demonstrate that the FRND is a useful paradigm for the assessment of psychological and physiological discrimination of fear and reward. Implications and directions for future work are discussed.

SΔp: The Missing Discriminative Stimulus for Non-Punishment.

As the natural science of behavior evolves, the use of precise terminology is critical to maintain its conceptual and terminological integrity. The current state of terminology in stimulus control is well developed with respect to reinforcement and incomplete with respect to punishment. In this paper, we aim to make the case that the current conceptualization for discriminative stimulus control in relation to punishment would be enhanced by modifying the definition of the discriminative stimulus for punishment (SDp) and by adding a new term to the current taxonomy that denotes when a punishment contingency is inactive.

Low-Cost Virtual Reality to Support Imaginal Exposure Within PTSD Treatment: A Case Report Study Within a Community Mental Healthcare Setting

Revisiting what happened during (or after) a traumatic event is an important part of the treatment process in trauma-focused cognitive therapy (TF-CT). However, clinicians may have difficulty helping patients to intentionally retrieve these memories in order to engage with their content. As such, clinical tools to support the access and delivery of imaginal exposure content within treatment may prove to be particularly useful for therapists. This case report introduces work undertaken with Mr. A, a 38-year-old male, who 2 years prior had experienced a city centre assault. Initial assessment revealed a PCL-5 score of 64 and he met DSM-5 criteria for posttraumatic stress disorder (PTSD). Mr. A received 10 sessions of TF-CT wherein the traditional imaginal exposure components were implemented via a newly developed virtual reality (VR) development workflow called “VR Photoscan.” After 10 sessions, results showed PCL-5 scores decreased from 64 to 19 and Mr. A no longer met DSM-5 PTSD criteria. VR Photoscan was used during 4/10 sessions and included (1) reliving, (2) memory updating, and (3) stimulus discrimination activities. Mr. A also reported VR Photoscan as helpful regarding preparation for site visits. In conclusion, VR Photoscan technology provided a more visceral exposure experience which supported Mr. A to revisit the trauma memory. He reported high levels of satisfaction with the quality of the virtual environment and no issues using the VR technology. Produced with lower costs and shorter development times than typical computer-generated environments, VR Photoscan may be more easily implemented within routine care, although further research is required.

Aging effect of cross-modal interactions during audiovisual detection and discrimination by behavior and ERPs.

Numerous studies have shown that aging greatly affects audiovisual integration; however, it is still unclear when the aging effect occurs, and its neural mechanism has yet to be fully elucidated. We assessed the audiovisual integration (AVI) of older (n = 40) and younger (n = 45) adults using simple meaningless stimulus detection and discrimination tasks. The results showed that the response was significantly faster and more accurate for younger adults than for older adults in both the detection and discrimination tasks. The AVI was comparable for older and younger adults during stimulus detection (9.37% vs. 9.43%); however, the AVI was lower for older than for younger adults during stimulus discrimination (9.48% vs. 13.08%) behaviorally. The electroencephalography (EEG) analysis showed that comparable AVI amplitude was found at 220-240 ms for both groups during stimulus detection and discrimination, but there was no significant difference between brain regions for older adults but a higher AVI amplitude in the right posterior for younger adults. Additionally, a significant AVI was found for younger adults in 290-310 ms but was absent for older adults during stimulus discrimination. Furthermore, significant AVI was found in the left anterior and right anterior at 290-310 ms for older adults but in the central, right posterior and left posterior for younger adults. These results suggested that the aging effect of AVI occurred in multiple stages, but the attenuated AVI mainly occurred in the later discriminating stage attributed to attention deficit.

Pharmacokinetic and Pharmacodynamic Consequences of Cytochrome P450 3A Inhibition on Mitragynine Metabolism in Rats.

Mitragynine, an opioidergic alkaloid present in Mitragyna speciosa (kratom), is metabolized by cytochrome P450 3A (CYP3A) to 7-hydroxymitragynine, a more potent opioid receptor agonist. The extent to which conversion to 7-hydroxymitragynine mediates the in vivo effects of mitragynine is unclear. The current study examined how CYP3A inhibition (ketoconazole) modifies the pharmacokinetics of mitragynine in rat liver microsomes in vitro. The study further examined how ketoconazole modifies the discriminative stimulus and antinociceptive effects of mitragynine in rats. Ketoconazole [30 mg/kg, oral gavage (o.g.)] increased systemic exposure to mitragynine (13.3 mg/kg, o.g.) by 120% and 7-hydroxymitragynine exposure by 130%. The unexpected increase in exposure to 7-hydroxymitragynine suggested that ketoconazole inhibits metabolism of both mitragynine and 7-hydroxymitragynine, a finding confirmed in rat liver microsomes. In rats discriminating 3.2 mg/kg morphine from vehicle under a fixed-ratio schedule of food delivery, ketoconazole pretreatment increased the potency of both mitragynine (4.7-fold) and 7-hydroxymitragynine (9.7-fold). Ketoconazole did not affect morphine's potency. Ketoconazole increased the antinociceptive potency of 7-hydroxymitragynine by 4.1-fold. Mitragynine (up to 56 mg/kg, i.p.) lacked antinociceptive effects both in the presence and absence of ketoconazole. These results suggest that both mitragynine and 7-hydroxymitragynine are cleared via CYP3A and that 7-hydroxymitragynine is formed as a metabolite of mitragynine by other routes. These results have implications for kratom use in combination with numerous medications and citrus juices that inhibit CYP3A. SIGNIFICANCE STATEMENT: Mitragynine is an abundant kratom alkaloid that exhibits low efficacy at the μ-opioid receptor (MOR). Its metabolite, 7-hydroxymitragynine, is also an MOR agonist but with higher affinity and efficacy than mitragynine. Our results in rats demonstrate that cytochrome P450 3A (CYP3A) inhibition can increase the systematic exposure of both mitragynine and 7-hydroxymitragynine and their potency to produce MOR-mediated behavioral effects. These data highlight potential interactions between kratom and CYP3A inhibitors, which include numerous medications and citrus juices.

Cortical visual impairment at birth can be improved rapidly by vision training in adulthood: A case study.

Cortical visual impairment (CVI) is a severe loss of visual function caused by damage to the visual cortex or its afferents, often as a consequence of hypoxic insults during birth. It is one of the leading causes of vision loss in children, and it is most often permanent. Several studies have demonstrated limited vision restoration in adults who trained on well-controlled psychophysical tasks, after acquiring CVI late in life. Other studies have shown improvements in children who underwent vision training. However, little is known about the prospects for the large number of patients who acquired CVI at birth but received no formal therapy as children. We, therefore, conducted a proof-of-principle study in one CVI patient long after the onset of cortical damage (age 18), to test the training speed, efficacy and generalizability of vision rehabilitation using protocols that had previously proven successful in adults. The patient trained at home and in the laboratory, on a psychophysical task that required discrimination of complex motion stimuli presented in the blind field. Visual function was assessed before and after training, using perimetric measures, as well as a battery of psychophysical tests. The patient showed remarkably rapid improvements on the training task, with performance going from chance to 80% correct over the span of 11 sessions. With further training, improved vision was found for untrained stimuli and for perimetric measures of visual sensitivity. Some, but not all, of these performance gains were retained upon retesting after one year. These results suggest that existing vision rehabilitation programs can be highly effective in adult patients who acquired CVI at a young age. Validation with a large sample size is critical, and future work should also focus on improving the usability and accessibility of these programs for younger patients.

Auditory and Somatosensory Development for Speech in Later Childhood.

This study collected measures of auditory-perceptual and oral somatosensory acuity in typically developing children and adolescents aged 9-15 years. We aimed to establish reference data that can be used as a point of comparison for individuals with residual speech sound disorder (RSSD), especially for RSSD affecting American English rhotics. We examined concurrent validity between tasks and hypothesized that performance on at least some tasks would show a significant association with age, reflecting ongoing refinement of sensory function in later childhood. We also tested for an inverse relationship between performance on auditory and somatosensory tasks, which would support the hypothesis of a trade-off between sensory domains. Ninety-eight children completed three auditory-perceptual tasks (identification and discrimination of stimuli from a "rake"-"wake" continuum and category goodness judgment for naturally produced words containing rhotics) and three oral somatosensory tasks (bite block with auditory masking, oral stereognosis, and articulatory awareness, which involved explicit judgments of relative tongue position for different speech sounds). Pairwise associations were examined between tasks within each domain and between task performance and age. Composite measures of auditory-perceptual and somatosensory functions were used to investigate the possibility of a sensory trade-off. Statistically significant associations were observed between the identification and discrimination tasks and the bite block and articulatory awareness tasks. In addition, significant associations with age were found for the category goodness and bite block tasks. There was no statistically significant evidence of a trade-off between auditory-perceptual and somatosensory domains. This study provided a multidimensional characterization of speech-related sensory function in older children/adolescents. Complete materials to administer all experimental tasks have been shared, along with measures of central tendency and dispersion for scores in two subgroups of age. Ultimately, we hope to apply this information to make customized treatment recommendations for children with RSSD based on sensory profiles.

Assessment of Abuse-Related Discriminative Stimulus Effects of Nicotine Aerosol in Rodents.

The rapid increase in e-cigarette use highlights the importance of developing relevant, predictive animal models exploring their potential health implications. The goal of the present study was to examine the abuse-related effects of brief, repeated e-cigarette aerosol exposures in rodents modeling human e-cigarette user behavior. We evaluated the discriminative stimulus effects of brief, repeated puffs of inhaled nicotine in rats that had been trained to discriminate injected nicotine from saline. Locomotor activity measurement following exposure to injected and aerosolized nicotine was also assessed as an additional behavioral outcome. We hypothesized that the stimulus effects of nicotine aerosol were central nervous system (CNS)-mediated and comparable to that produced by an injected nicotine training stimulus. We further hypothesized that number of aerosol puffs and the e-liquid nicotine concentration which was aerosolized would impact the substitution of nicotine aerosol for injected nicotine. Both nicotine injections and exposures to nicotine aerosol produced a dose-dependent effect on locomotor activity. Nicotine aerosol under our puffing conditions produced e-liquid nicotine concentration-dependent and puff-number-dependent complete substitution for the injected nicotine training condition. The nicotinic antagonist, mecamylamine, completely blocked nicotine-appropriate responding produce by the training dose of 0.3 mg/kg injected nicotine as well as that resulting from exposure to aerosol puffs generated by e-liquid containing 3 mg/ml nicotine, demonstrating that the stimulus of inhaled nicotine was most likely CNS-mediated and not due to olfactory stimulus properties. Overall, the results support the hypothesis that an aerosol exposure drug discrimination model in rodents has applicability to studying the abuse-related effects of e-cigarettes. SIGNIFICANCE STATEMENT: Animal models of nicotine aerosol exposure using testing conditions resembling human e-cigarette use are lacking. In this study, we test a novel preclinical model of nicotine vaping in rodents which allows for the exploration of the abuse-related effects of e-cigarettes. This model has the potential to contribute both to our understanding of the abuse-related pharmacological effects of e-cigarettes as well as aid in the development of rationale, evidence-based e-cigarette regulatory policies.

Effects of phase synchronization and frequency specificity in the encoding of conditioned fear-a web-based fear conditioning study.

Oscillatory synchronization in the theta-frequency band was found to play a causal role in binding information of different modalities in declarative memory. Moreover, there is first evidence from a laboratory study that theta-synchronized (vs. asynchronized) multimodal input in a classical fear conditioning paradigm resulted in better discrimination of a threat-associated stimulus when compared to perceptually similar stimuli never associated with the aversive unconditioned stimulus (US). Effects manifested in affective ratings and ratings of contingency knowledge. However, theta-specificity was not addressed so far. Thus, in the present pre-registered web-based fear conditioning study, we compared synchronized (vs. asynchronized) input in a theta-frequency band vs. the same synchronization manipulation in a delta frequency. Based on our previous laboratory design, five visual gratings of different orientations (25°, 35°, 45°, 55°, 65°) served as conditioned stimuli (CS) with only one (CS+) paired with the auditory aversive US. Both CS and US were luminance or amplitude modulated, respectively, in a theta (4 Hz) or delta (1.7 Hz) frequency. In both frequencies, CS-US pairings were presented either in-phase (0° phase lag) or out-of-phase (90°, 180°, 270°), resulting in four independent groups (each group N = 40). Phase synchronization augmented the discrimination of CSs in CS-US contingency knowledge but did not affect valence and arousal ratings. Interestingly, this effect occurred independent of frequency. In sum, the current study proves the ability to successfully conduct complex generalization fear conditioning in an online setting. Based on this prerequisite, our data supports a causal role of phase synchronization in the declarative CS-US associations for low frequencies rather than in the specific theta-frequency band.