Cue Conditions Research Articles

Nicotine Motivated Behavior in C. elegans.

To maximize the advantages offered by Caenorhabditis elegans as a high-throughput (HTP) model for nicotine dependence studies, utilizing its well-defined neuroconnectome as a robust platform, and to unravel the genetic basis of nicotine-motivated behaviors, we established the nicotine conditioned cue preference (CCP) paradigm. Nicotine CCP enables the assessment of nicotine preference and seeking, revealing a parallel to fundamental aspects of nicotine-dependent behaviors observed in mammals. We demonstrated that nicotine-elicited cue preference in worms is mediated by nicotinic acetylcholine receptors and requires dopamine for CCP development. Subsequently, we pinpointed nAChR subunits associated with nicotine preference and validated human GWAS candidates linked to nicotine dependence involved in nAChRs. Functional validation involves assessing the loss-of-function strain of the CACNA2D3 ortholog and the knock-out (KO) strain of the CACNA2D2 ortholog, closely related to CACNA2D3 and sharing human smoking phenotypes. Our orthogonal approach substantiates the functional conservation of the α2δ subunit of the calcium channel in nicotine-motivated behavior. Nicotine CCP in C. elegans serves as a potent affirmation of the cross-species functional relevance of GWAS candidate genes involved in nicotine seeking associated with tobacco abuse, providing a streamlined yet comprehensive system for investigating intricate behavioral paradigms within a simplified and reliable framework.

Exploring retro-cue effects on visual working memory: insights from double-cue paradigm.

In the realm of visual working memory research, the retro-cue paradigm helps us study retro-cue effects such as retro-cue benefit (RCB) and retro-cue cost (RCC). RCB reflects better performance with cued items, while RCC indicates poorer performance with uncued items. Despite consistent evidence for RCB, it's still uncertain whether it remains when previously uncued items are cued afterward. Additionally, research findings have been inconsistent. This study combines prior experiments by controlling the proportion of cue types and the number of memory items. Besides, using a CDA index to assess the status of items after the cue appeared. Results showed better performance under the double-cue condition (involving two cues pointing inconsistently with only the second cue being valid) compared to the neutral-cue condition, and better performance under the single-cue condition compared to double-cue. EEG data revealed that after the appearance of the second cue in the double-cue condition, there was a significant increase in CDA wave amplitude compared to the single-cue condition. Behavior results suggests that RCB occurs under double-cue but to a lesser extent than the single-cue. And EEG outcomes indicates that individuals did not remove the uncued item from their visual working memory after the first cue. Instead, they kept it in a passive state and then shifted it to an active state after the appearance of the second cue.

Recognizing facial expressions of emotion amid noise: A dynamic advantage.

Humans communicate internal states through complex facial movements shaped by biological and evolutionary constraints. Although real-life social interactions are flooded with dynamic signals, current knowledge on facial expression recognition mainly arises from studies using static face images. This experimental bias might stem from previous studies consistently reporting that young adults minimally benefit from the richer dynamic over static information, whereas children, the elderly, and clinical populations very strongly do (Richoz, Jack, Garrod, Schyns, & Caldara, 2015, Richoz, Jack, Garrod, Schyns, & Caldara, 2018b). These observations point to a near-optimal facial expression decoding system in young adults, almost insensitive to the advantage of dynamic over static cues. Surprisingly, no study has yet tested the idea that such evidence might be rooted in a ceiling effect. To this aim, we asked 70 healthy young adults to perform static and dynamic facial expression recognition of the six basic expressions while parametrically and randomly varying the low-level normalized phase and contrast signal (0%-100%) of the faces. As predicted, when 100% face signals were presented, static and dynamic expressions were recognized with equal efficiency with the exception of those with the most informative dynamics (i.e., happiness and surprise). However, when less signal was available, dynamic expressions were all better recognized than their static counterpart (peaking at ∼20%). Our data show that facial movements increase our ability to efficiently identify emotional states of others under the suboptimal visual conditions that can occur in everyday life. Dynamic signals are more effective and sensitive than static ones for decoding all facial expressions of emotion for all human observers.

Pharmacological diacylglycerol lipase inhibition impairs contextual fear extinction in mice.

Acquisition and extinction of associative fear memories are critical for guiding adaptive behavioral responses to environmental threats, and dysregulation of these processes is thought to represent important neurobehavioral substrates of trauma and stress-related disorders including posttraumatic stress disorder (PTSD). Endogenous cannabinoid (eCB) signaling has been heavily implicated in the extinction of aversive fear memories and we have recently shown that pharmacological inhibition of 2-arachidonoylglycerol (2-AG) synthesis, a major eCB regulating synaptic suppression, impairs fear extinction in an auditory cue conditioning paradigm. Despite these data, the role of 2-AG signaling in contextual fear conditioning is not well understood. Here, we show that systemic pharmacological blockade of diacylglycerol lipase, the rate-limiting enzyme catalyzing in the synthesis of 2-AG, enhances contextual fear learning and impairs within-session extinction. In sham-conditioned mice, 2-AG synthesis inhibition causes a small increase in unconditioned freezing behavior. No effects of 2-AG synthesis inhibition were noted in the Elevated Plus Maze in micetested after fear extinction. These data provide support for 2-AG signaling in the suppression of contextual fear learning and the expression of within-session extinction of contextual fear memories.

Higher sensory processing sensitivity: increased cautiousness in attentional processing in conflict contexts

ABSTRACT While interest grows in investigating sensory processing sensitivity (SPS), few studies have employed objective behavioural measures to directly explore the underlying attentional processing. The present study utilised two modified versions of the Emotional Attention Networks Test Integration (E-ANTI) to investigate whether and how emotion interacts with three attentional networks associated with SPS when emotion information was target-irrelevant (Experiment 1) and target-relevant (Experiment 2), respectively. Both experiments involved four manipulated within-subject factors: Signal (tone vs. no-tone), Cue Validity (valid vs. invalid), Flanker Congruency (congruent vs. incongruent), and Emotion (fearful vs. happy). Linear mixed models were employed, and three attentional networks were successfully captured in both experiments. In Experiment 1, we observed that as SPS increased, the difference in reaction time between valid and invalid cue conditions decreased, especially in incongruent trials. Participants rated fearful faces as more arousing than happy faces as SPS increased. In Experiment 2, we found that slow responding to fearful faces reduced as SPS increased, particularly in incongruent trials. The observed effects related to SPS in both experiments were particularly pronounced in incongruent conditions, suggesting that SPS may modulate attentional processes in high-conflict situations. Overall, higher SPS may be associated with increased cautiousness in conflict contexts.

The frequency and cueing mechanisms of involuntary autobiographical memories while driving

ABSTRACT Involuntary autobiographical memories (IAMs) have been typically studied with paper diaries, kept for a week or longer. However, such studies are unable to capture the true frequency of IAMs, nor the level of detail that would give new insights into the mechanisms of IAMs. To address this gap, a new audio-recording method was developed and tested on the first author who recorded 674 IAMs while driving a car on a 30–40-minute-long habitual route on 20 occasions. Results revealed very high frequency of IAMs (almost 34 per journey) that were reported more often in response to dynamic (one-off) than static cues. Moreover, a substantial number of memory chains and long-term priming of IAMs by previously encountered incidental stimuli were also recorded. Based on these results, a new theoretical model is proposed in which the occurrence of IAMs is determined by an interplay of factors at the time of the IAM, such as the type of ongoing activity and internal or external triggers, as well as different types of long-term priming. The results also have practical implications for studying mind-wandering and safety issues in driving and aircraft-flying, where periods of concentration are followed by monotony and less demanding tasks.

A study on the effect of different channel cues on learning in immersive 360° videos.

Immersive 360° videos are of interest to educators because of their ability to provide immersive sensory experience and other features. This study examined the effects of four cue conditions on 360° video learning performance, attention, cognitive load, and mood using eye-tracking devices, brainwave meters, and subjective questionnaires. The randomly assigned participants (n = 62) did go to the experimental group (visual cues only, auditory cues only, and audiovisual cues) or the control group (no cues). The results showed that visual and audiovisual cues effectively guide learners' attention to the related learning content, reduce cognitive load during learning, and improve retention performance but have no significant effect on knowledge transfer or long-term memory. Auditory cues increase the number of times learners look at the related learning content but do not affect gaze duration and distract their attention, hindering the acquisition of relevant learning content. The study also found that visual cues effectively increase the number of times learners looked at the content. However, they do not affect gaze duration. The study also revealed that visual cues effectively increase learners' relaxation when viewing 360° videos. The study's findings can provide a reference for the instructional processing of information related to 360° video design and its practical application in teaching.

The Merits of Bilateral Application of Middle Ear Implants in Patients With Bilateral Conductive and/or Mixed Hearing Loss.

This study investigated sound localization abilities in patients with bilateral conductive and/or mixed hearing loss (BCHL) when listening with either one or two middle ear implants (MEIs). Sound localization was measured by asking patients to point as quickly and accurately as possible with a head-mounted LED in the perceived sound direction. Loudspeakers, positioned around the listener within a range of +73°/-73° in the horizontal plane, were not visible to the patients. Broadband (500 Hz-20 kHz) noise bursts (150 ms), roved over a 20-dB range in 10 dB steps was presented. MEIs stimulate the ipsilateral cochlea only and therefore the localization response was not affected by crosstalk. Sound localization was better with bilateral MEIs compared with the unilateral left and unilateral right conditions. Good sound localization performance was found in the bilaterally aided hearing condition in four patients. In two patients, localization abilities equaled normal hearing performance. Interestingly, in the unaided condition, when both devices were turned off, subjects could still localize the stimuli presented at the highest sound level. Comparison with data of patients implanted bilaterally with bone-conduction devices, demonstrated that localization abilities with MEIs were superior. The measurements demonstrate that patients with BCHL, using remnant binaural cues in the unaided condition, are able to process binaural cues when listening with bilateral MEIs. We conclude that implantation with two MEIs, each stimulating only the ipsilateral cochlea, without crosstalk to the contralateral cochlea, can result in good sound localization abilities, and that this topic needs further investigation.

Navigational Competency is Mediated by Foraging Experience and Light Conditions in the Nocturnal Bull Ant Myrmecia midas

The nocturnal bull ants of the genus Myrmecia, Myrmecia midas travel in both bright and dim settings on the ground and also vertically up on trees navigating towards targets. It is known that foragers retain multiple panoramic memories of terrestrial landmarks as well as celestial cues along their foraging route. It is likely that they can compare these stored views with their current visual input to return to their nest. Here we examined whether nocturnal M. midas foragers’ navigational efficiency and success at view-based navigation suffer at low light levels (night time) compared with daylight levels of brightness. When exposed to panoramic cues in dim conditions, which had dimmer light levels than their peak foraging period, they were less well oriented and less likely to find the nest, with the catchment area smaller at night than during the day. At different displacement distances from the nest, initial navigational behaviours differed. Foragers displayed more scanning near the starting point at shorter distances, while with increasing distance they switched more to loops of systematic searching or heading off in some direction without scans. In the dim conditions, landmark guidance became less effective, perhaps explaining why foragers limit their navigational activities mostly to the twilight hours, when light levels are still adequate, and mostly forage in a tree through the night.

Impaired orienting function detected through eye movements in patients with temporal lobe epilepsy.

Patients with temporal lobe epilepsy (TLE) often exhibit attention function impairment. The orienting network is the subsystem of the attention network that has not been fully studied. In this study, we used eye-tracking technology with an attention network test (ANT)-based task to assess the orienting function of TLE patients, aiming to characterize their eye movement patterns. A total of 37 TLE patients and 29 healthy controls (HCs) completed the ANT task based on eye-tracking technology. Orienting function damage was mainly assessed by the ANT orienting effect. Eye movement metrics, such as mean first goal-directed saccade latency (MGSL), total saccades, and saccade amplitudes, were compared between groups. The TLE patients had a significantly lower ANT orienting effect (HC, 54.05 ± 34.05; TLE, 32.29 ± 39.54) and lower eye-tracking orienting effect (HC, 116.98 ± 56.59; TLE, 86.72 ± 59.10) than those of the HCs. The larger orienting effects indicate that orienting responses are faster when receiving a spatial cue compared with a center cue. In the spatial cue condition, compared with HCs, the TLE group showed a longer first goal-directed saccade latency (HC, 76.77 ± 58.87 ms; TLE, 115.14 ± 59.15 ms), more total saccades (HC, 28.46 ± 12.30; TLE, 36.69 ± 15.13), and larger saccade amplitudes (HC, 0.75° ± 0.60°; TLE, 1.36° ± 0.89°). Furthermore, there was a positive correlation of the orienting-effect score between the ANT task and eye-tracking metrics (r = 0.58, p < 0.05). We innovatively developed a new detection method using eye-tracking technology in combination with an ANT-based task to detect the orienting function in TLE patients. The current research demonstrated that TLE patients had a significant orienting dysfunction with a specific saccade pattern characterized by a longer first goal-directed saccade latency, more total saccades, and larger saccade amplitudes. These oculomotor metrics are likely to be a better indicator of orienting function and may potentially be used for behavioral-based interventions and long-term cognition monitoring in TLE patients.

Emotional event perception is related to lexical complexity and emotion knowledge

Inferring emotion is a critical skill that supports social functioning. Emotion inferences are typically studied in simplistic paradigms by asking people to categorize isolated and static cues like frowning faces. Yet emotions are complex events that unfold over time. Here, across three samples (Study 1 N = 222; Study 2 N = 261; Study 3 N = 101), we present the Emotion Segmentation Paradigm to examine inferences about complex emotional events by extending cognitive paradigms examining event perception. Participants were asked to indicate when there were changes in the emotions of target individuals within continuous streams of activity in narrative film (Study 1) and documentary clips (Study 2, preregistered, and Study 3 test-retest sample). This Emotion Segmentation Paradigm revealed robust and reliable individual differences across multiple metrics. We also tested the constructionist prediction that emotion labels constrain emotion inference, which is traditionally studied by introducing emotion labels. We demonstrate that individual differences in active emotion vocabulary (i.e., readily accessible emotion words) correlate with emotion segmentation performance.

Manipulation of phasic arousal by auditory cues is associated with subsequent changes in visual orienting to faces in infancy

This eye-tracking study investigated the effect of sound-induced arousal on social orienting under different auditory cue conditions in 5-month-old (n = 25; n = 13 males) and 10-month-old infants (n = 21; n = 14 males) participating in a spontaneous visual search task. Results showed: (1) larger pupil dilation discriminating between high and low volume (b = 0.02, p = 0.007), but not between social and non-social sounds (b = 0.004, p = 0.64); (2) faster visual orienting (b = − 0.09, p < 0.001) and better social orienting at older age (b = 0.94, p < 0.001); (3) a fast habituation effect on social orienting after high-volume sounds (χ2(2) = 7.39, p = 0.025); (4) a quadratic association between baseline pupil size and target selection (b = − 1.0, SE = 0.5, χ2(1) = 4.04, p = 0.045); (5) a positive linear association between pupil dilation and social orienting (b = 0.09, p = 0.039). Findings support adaptive gain theories of arousal, extending the link between phasic pupil dilation and task performance to spontaneous social orienting in infancy.

Exposure to the insecticide, imidacloprid, impairs predator-recognition learning in damselfly larvae

Many aquatic organisms use chemosensory information to learn about local predation threats, but contaminants in their environment may impair such cognitive processes. Neonicotinoids are a class of water-soluble systemic insecticides that have become a major concern in aquatic systems. In this study, we explored how a 10-day exposure to various concentrations (0, 0.1, 1.0, or 10.0 μg/L) of the neonicotinoid imidacloprid affects the learned recognition of predator odour by non-target damselfly larvae (Lestes spp). Unexposed larvae and those exposed to the low concentration (0.1 μg/L) demonstrated an appropriate learned response to a novel predator odour following a conditioning with the odour paired with chemical alarm cues. However, such learning failed to occur for larvae that were exposed to imidacloprid concentrations of 1.0 and 10.0 μg/L. Thus, either the cognitive processing of the chemical information was impaired or the chemistry of one or both of the conditioning cues was altered, making them ineffective for learning. In a second experiment, we found evidence for this latter hypothesis. In the absence of background imidacloprid exposure, larvae did not show significant learned responses to the predator odour when the conditioning cues were mixed with imidacloprid (initial pulse solution of 3.0 μg/L) at the start of conditioning (reaching a final concentration of 0.01 μg/L). These findings indicate that even low levels of imidacloprid can have important implications for chemosensory cognition of non-target species in aquatic environments.

Enhancing cognitive function in chronic TBI: The Role of α7 nicotinic acetylcholine receptor modulation

Traumatic brain injury (TBI) results in several pathological changes within the hippocampus that result in adverse effects on learning and memory. Therapeutic strategies to enhance learning and memory after TBI are still in the early stages of clinical development. One strategy is to target the α7 nicotinic acetylcholine receptor (nAChR), which is highly expressed in the hippocampus and contributes to the formation of long-term memory. In our previous study, we found that AVL-3288, a positive allosteric modulator of the α7 nAChR, improved cognitive recovery in rats after moderate fluid-percussion injury (FPI). However, whether AVL-3288 improved cognitive recovery specifically through the α7 nAChR was not definitively determined. In this study we utilized Chrna7 knockout mice and compared their recovery to wild-type mice treated with AVL-3288 after TBI. We hypothesized that AVL-3288 treatment would improve learning and memory in wild-type mice, but not Chrna7−/− mice after TBI. Adult male C57BL/6 wild-type and Chrna7−/− mice received sham surgery or moderate controlled cortical impact (CCI) and recovered for 3 months. Mice were then treated with vehicle or AVL-3288 at 30 min prior to contextual fear conditioning. At 3 months after CCI, expression of α7 nAChR, choline acetyltransferase (ChAT), high-affinity choline transporter (ChT), and vesicular acetylcholine transporter (VAChT) were found to be significantly decreased in the hippocampus. Treatment of wild-type mice at 3 months after CCI with AVL-3288 significantly improved cue and contextual fear conditioning, whereas no beneficial effects were observed in Chrna7−/− mice. Parietal cortex and hippocampal atrophy were not improved with AVL-3288 treatment in either wild-type or Chrna7−/− mice. Our results indicate that AVL-3288 improves cognition during the chronic recovery phase of TBI through modulation of the α7 nAChR.

On the Relevance of Posterior and Midfrontal Theta Activity for Visuospatial Attention.

The aim of this study was to examine whether oscillatory activity in the theta-band is relevant for selective visuospatial attention when there is a strong need for the suppression of interfering and distracting information. A variant of the Eriksen flanker task was employed with bilateral arrays: one array consisting of a target and congruent or incongruent flankers and the second array consisting of neutral distractors. The bilateral arrays were preceded either by a 100% valid spatial cue or by a neutral cue. In the cue-target interval, a major burst in medial frontal theta power was observed, which was largest in the spatial cue condition. In the latter condition, additionally a posterior theta increase was observed that was larger over sites ipsilateral to the forthcoming target array. Functional connectivity analyses revealed that this pretarget posterior theta was related to the midfrontal theta. No such effects were observed in the neutral cue condition. After onset of the bilateral arrays, a major burst in posterior theta activity was observed in both cue conditions, which again was larger above sites ipsilateral to the target array. Furthermore, this posterior theta was in all cases related to the midfrontal theta. Taken together, the findings suggest that a fronto-posterior theta network plays an important role in the suppression of irrelevant and conflicting visual information. The results also suggest that the reciprocal relation between visuospatial attention and executive response control may be closer than commonly thought.

Event-Related Potentials in Cued Go/NoGo Task are Possible Neuromarkers of Monotony

Monotony or mental fatigue occurs during performing low-content and monotonous work, including the work of the operator. It is accompanied by a decrease in the concentration of attention and the speed of its switching, as well as slowing in the processes of perception and motor reactions, which can lead to a loss of vigilance, self-control and the occurrence of drowsiness and, consequently, an increase in the risk of industrial injuries and accidents. In this regard, an urgent task is to develop methods for monitoring the human condition in the process of performing monotonous activities. We investigated the effect of monotony on event-related potentials (ERPs) in the visual cued Go/NoGo test. We analyzed 31-channel EEG data of 25 healthy subjects recorded before and after performing four tests with a total duration of around 1.5 hours, representing the same type of tasks with different instructions and simulating the conditions of monotonous work. After performing four tests, we observe an increase of P2 wave, decrease of the P3 Cue wave and the contingent negative variation (CNV) wave in the Cue condition, as well as the decrease of P300 wave in the NoGo condition. The results obtained in this work are assumed to reflect attenuation in proactive and reactive cognitive control during monotony and allow us to consider the P2, P3 Cue, CNV and P3 NoGo waves as possible candidates for the role of neuromarkers of monotony, which makes it promising to use these indicators in systems for monitoring the human condition during operating work.

Alpha oscillations encode Bayesian belief updating underlying attentional allocation in dynamic environments

In a dynamic environment, expectations of the future constantly change based on updated evidence and affect the dynamic allocation of attention. To further investigate the neural mechanisms underlying attentional expectancies, we employed a modified Central Cue Posner Paradigm in which the probability of cues being valid (that is, accurately indicated the upcoming target location) was manipulated. Attentional deployment to the cued location (α), which was governed by precision of predictions on previous trials, was estimated using a hierarchical Bayesian model and was included as a regressor in the analyses of electrophysiological (EEG) data. Our results revealed that before the target appeared, alpha oscillations (8∼13 Hz) for high-predictability cues (88 % valid) were significantly predicted by precision-dependent attention (α). This relationship was not observed under low-predictability conditions (69 % and 50 % valid cues). After the target appeared, precision-dependent attention (α) correlated with alpha band oscillations only in the valid cue condition and not in the invalid condition. Further analysis under conditions of significant attentional modulation by precision suggested a separate effect of cue orientation. These results provide new insights on how trial-by-trial Bayesian belief updating relates to alpha band encoding of environmentally-sensitive allocation of visual spatial attention.

An explorative single-arm clinical study to assess craving in patients with alcohol use disorder using Virtual Reality exposure (CRAVE)—study protocol

BackgroundAlcohol use disorder (AUD) belongs to the most burdensome clinical disorders worldwide. Current treatment approaches yield unsatisfactory long-term effects with relapse rates up to 85%. Craving for alcohol is a major predictor for relapse and can be intentionally induced via cue exposure in real life as well as in Virtual Reality (VR). The induction and habituation of craving via conditioned cues as well as extinction learning is used in Cue Exposure Therapy (CET), a long-known but rarely used strategy in Cognitive Behavioral Therapy (CBT) of AUD. VR scenarios with alcohol related cues offer several advantages over real life scenarios and are within the focus of current efforts to develop new treatment options. As a first step, we aim to analyze if the VR scenarios elicit a transient change in craving levels and if this is measurable via subjective and psychophysiological parameters.MethodsA single-arm clinical study will be conducted including n = 60 patients with AUD. Data on severity of AUD and craving, comorbidities, demographics, side effects and the feeling of presence in VR will be assessed. Patients will use a head-mounted display (HMD) to immerse themselves into three different scenarios (neutral vs. two target situations: a living room and a bar) while heart rate, heart rate variability, pupillometry and electrodermal activity will be measured continuously. Subjective craving levels will be assessed before, during and after the VR session.DiscussionResults of this study will yield insight into the induction of alcohol craving in VR cue exposure paradigms and its measurement via subjective and psychophysiological parameters. This might be an important step in the development of innovative therapeutic approaches in the treatment of patients with AUD.Trial registrationThis study was approved by the Charité—Universitätsmedizin Berlin Institutional Review Board (EA1/190/22, 23.05.2023). It was registered on ClinicalTrials.gov (NCT05861843).

Rapid appearance of negative emotion during oral fentanyl self-administration in male and female rats.

Opioid use disorder has become an epidemic in the United States, fuelled by the widespread availability of fentanyl, which produces rapid and intense euphoria followed by severe withdrawal and emotional distress. We developed a new preclinical model of fentanyl seeking in outbred male and female rats using volitional oral self-administration (SA) that can be readily applied in labs without intravascular access. Using a traditional two-lever operant procedure, rats learned to take oral fentanyl vigorously, escalated intake across sessions, and readily reinstated responding to conditioned cues after extinction. Oral SA also revealed individual and sex differences that are essential to studying substance use risk propensity. During a behavioural economics task, rats displayed inelastic demand curves and maintained stable intake across a wide range of fentanyl concentrations. Oral SA was also neatly patterned, with distinct 'loading' and 'maintenance' phases of responding within each session. Using our software DeepSqueak, we analysed ultrasonic vocalizations (USVs), which are innate expressions of current emotional state in rats. Rats produced 50 kHz USVs during loading then shifted quickly to 22 kHz calls despite ongoing maintenance of oral fentanyl taking, reflecting a transition to negative reinforcement. Using fibre photometry, we found that the lateral habenula differentially processed drug cues and drug consumption depending on affective state, with potentiated modulation by drug cues and consumption during the negative affective maintenance phase. Together, these results indicate a rapid progression from positive to negative reinforcement occurs even within an active drug taking session, revealing a within-session opponent process.

Unconditioned response to a naturally aversive stimulus is associated with sensitized defensive responding and self-reported fearful traits in a PTSD sample.

Unconditioned responding (UCR) to a naturally aversive stimulus is associated with defensive responding to a conditioned threat cue (CS+) and a conditioned safety cue (CS-) in trauma-exposed individuals during fear acquisition. However, the relationships of UCR with defensive responses during extinction training, posttraumatic stress disorder (PTSD) symptom severity, and fearful traits in trauma-exposed individuals are not known. In a sample of 100 trauma-exposed adults with a continuum of PTSD severity, we recorded startle responses and skin conductance responses (SCR) during fear acquisition and extinction training using a 140 psi, 250-ms air blast to the larynx as the unconditioned stimulus. We explored dimensional associations of two different measures of UCR (unconditioned startle and unconditioned SCR) with conditioned defensive responding to CS+ and CS-, conditioned fear (CS+ minus CS-), PTSD symptom severity, and a measure of fearful traits (composite of fear survey schedule, anxiety sensitivity index, and Connor-Davidson resilience scale). Unconditioned startle was positively associated with startle potentiation to the threat cue and the safety cue across both learning phases (CS+ Acquisition, CS- Acquisition, CS+ Extinction Training, CS- Extinction Training) and with fearful traits. Unconditioned SCR was positively associated with SCR to the CS+ and CS- and SCR difference score during Acquisition. Neither type of UCR was associated with PTSD symptom severity. Our findings suggest that UCR, particularly unconditioned startle to a naturally aversive stimulus, may inform research on biomarkers and treatment targets for symptoms of pervasive and persistent fear in trauma-exposed individuals.