Nonreinforced Conditioned Stimulus Research Articles

HIV Interacts with Posttraumatic Stress Disorder to Impact Fear Psychophysiology in Trauma-Exposed Black Women.

The prevalence of posttraumatic stress disorder (PTSD) among people living with HIV (PLWH) is higher than in the general population and can impact health behaviors. The influence of HIV on PTSD psychophysiology requires further investigation due to implications for the treatment of PTSD in PLWH. Utilizing fear-potentiated startle (FPS), we aimed to interrogate the influence of PTSD and HIV on fear responses. Women (18-65 years of age) recruited from the Women's Interagency HIV Study in Atlanta, GA (n = 70, 26 without HIV and 44 with HIV), provided informed consent and completed a semistructured interview to assess trauma exposure and PTSD symptom severity. Participants also underwent an FPS paradigm to assess fear acquisition and extinction: Psychophysiological indices that measure how individuals learn new fear and then subsequently attempt to suppress this fear. Women with PTSD, who did not have HIV, exhibited a greater startle response compared to women without PTSD or HIV during late acquisition to both the danger cue, reinforced conditioned stimulus (CS+, p = 0.013)), and the safety cue, non-reinforced conditioned stimulus (CS-, p = 0.046)), whereas women living with HIV (WLH) and PTSD demonstrated blunted fear responses compared to women with PTSD only. During extinction, WLH comorbid with PTSD exhibited an increased fear response during the extinction period in comparison to all other groups (p = 0.023). Women without PTSD demonstrated a reduction in the fear response during extinction regardless of HIV status. Our findings indicate that HIV further modifies fear psychophysiology in WLH with comorbid PTSD, highlighting the importance of considering HIV status in conjunction with PTSD treatment.

Endocannabinoid and neuroendocrine contributions to fear learning in humans

Fear learning is an important process that is essential for our survival. Impairments in this implicit form of emotion regulation is associated with several stress-related psychiatric disorders. Here, our goal was to determine the contributions of canonical stress systems, i.e., neuroendocrine and endocannabinoid systems, to fear learning in a population with histories of chronic stress exposure. In a 2×2 factorial design, adult participants (n=100) with or without histories of childhood trauma or substance use disorders completed a laboratory session to assess fear conditioning and extinction. Blood samples were collected to quantify peripheral levels of endocannabinoids and cortisol. Overall, 2-arachidonoyl glycerol (2AG), an endocannabinoid important for the termination of the stress response, was significantly negatively associated with self-reported anxiety and difficulties in emotion regulation, indicating that individuals with lower 2AG levels tend to be more anxious and have greater impairments in emotion regulation. Although there were no main effects of group on different aspects of fear learning, baseline levels of cortisol and endocannabinoids influenced fear learning in the sample overall. Specifically, higher baseline cortisol levels were associated with better acquisition of conditioned fear. Furthermore, baseline 2AG levels were related to the early extinction of conditioned fear such that higher levels of 2AG were coupled with greater distinction between the reinforced conditioned stimulus (CS+) and the non-reinforced conditioned stimulus (CS-). While additional analyses are ongoing, these results provide valuable insight into the neurobiology of fear learning and highlight potential molecular targets that could have therapeutic potential.

An analysis of fear inhibition and fear extinction in a sample of veterans with obstructive sleep apnea (OSA): Implications for co-morbidity with post-traumatic stress disorder (PTSD)

Obstructive sleep apnea (OSA) is a respiratory condition characterized by interrupted sleep due to repeated, temporary collapse of the soft tissue of the upper airway that can lead to a cascade of physiological and psychological adverse health outcomes. The most common therapeutic interventions for OSA patients include the application of continuous positive airway pressure (CPAP) which acts to keep the airway open and, as such, provides less interrupted and more restorative sleep. Improved sleep has been linked to more efficacious treatments for psychiatric conditions most notably those that include cognitive-behavioral elements, new learning, and memory consolidation. In the current study, we investigated the acquisition, inhibition, and extinction of conditioned fear in OSA patients, before and after CPAP therapy, using an established fear-potentiated startle paradigm. Patients with OSA displayed an intact ability to acquire, inhibit, and extinguish fear prior to CPAP treatment and this ability was significantly enhanced following CPAP usage. In addition, those patients with more severe OSA, as measured by apnea-hypopnea index (AHI), were more likely to show improved fear inhibition and extinction. Lastly, we observed impairments in discrimination between reinforced and nonreinforced conditioned stimuli, in the inhibition of fear, and in fear extinction in a subset of patients with OSA and co-morbid posttraumatic stress disorder (PTSD). These data suggest that evolving treatment algorithms for PTSD should address disrupted sleep problems prior to initiation of inhibition/extinction-based exposure therapies.

Menthol blunts the interoceptive discriminative stimulus effects of nicotine in female but not male rats.

Menthol is a widely used tobacco constituent that has shown to enhance nicotine's reinforcing effects. To determine whether injected menthol also alters nicotine's stimulus effects, we used a drug discrimination task. A total of 57 adult Sprague-Dawley rats (28M, 29F) received 20 positive and 20 negative days (intermixed) of discrimination training. On positive days, rats received a group-specific menthol and nicotine injection (VEH + 0.1 NIC, 1 M + 0.1 NIC, 5 M + 0.1 NIC, VEH + 0.4 NIC, 1 M + 0.4 NIC, 5 M + 0.4 NIC; mg/kg) before eight 15-s cue light presentations (conditioned stimulus (CS)), each followed by 4-s sucrose access. On negative days, all rats were injected with vehicle and saline before eight non-reinforced CS presentations. Next, rats underwent generalization testing with 30 dose combinations of menthol and nicotine. The change in drug-mediated anticipatory goal tracking during the CS was calculated as a difference score (CS minus pre-CS responding). All groups readily acquired drug discrimination. However, difference scores for the 5M + 0.1 NIC group were lower for females. Additionally, females had lower scores for 0.05, 0.1, and 0.4 mg/kg nicotine generalization tests. The lowest nicotine dose discriminable from saline was 0.05 mg/kg for females but 0.025 mg/kg for males. Co-administration with 5 or 10 mg/kg menthol weakened discrimination performance between 0.1 and 0.4 mg/kg and between 0.1 and 0.05 mg/kg nicotine for 0.1 mg/kg nicotine training groups. Female rats that were trained with 0.1 mg/kg nicotine were more sensitive to menthol's modulatory effects on nicotine's stimulus effects. This highlights the importance of taking sex and training dose into account when evaluating the interoceptive stimulus effects of nicotine and menthol.

Primary auditory cortex representation of fear-conditioned musical sounds.

Auditory cortex is required for discriminative fear conditioning beyond the classical amygdala microcircuit, but its precise role is unknown. It has previously been suggested that Heschl's gyrus, which includes primary auditory cortex (A1), but also other auditory areas, encodes threat predictions during presentation of conditioned stimuli (CS) consisting of monophones, or frequency sweeps. The latter resemble natural prosody and contain discriminative spectro‐temporal information. Here, we use functional magnetic resonance imaging (fMRI) in humans to address CS encoding in A1 for stimuli that contain only spectral but no temporal discriminative information. Two musical chords (complex) or two monophone tones (simple) were presented in a signaled reinforcement context (reinforced CS+ and nonreinforced CS−), or in a different context without reinforcement (neutral sounds, NS1 and NS2), with an incidental sound detection task. CS/US association encoding was quantified by the increased discriminability of BOLD patterns evoked by CS+/CS−, compared to NS pairs with similar physical stimulus differences and task demands. A1 was defined on a single‐participant level and based on individual anatomy. We find that in A1, discriminability of CS+/CS− was higher than for NS1/NS2. This representation of unconditioned stimulus (US) prediction was of comparable magnitude for both types of sounds. We did not observe such encoding outside A1. Different from frequency sweeps investigated previously, musical chords did not share representations of US prediction with monophone sounds. To summarize, our findings suggest decodable representation of US predictions in A1, for various types of CS, including musical chords that contain no temporal discriminative information.

Delay of reinforcement versus rate of reinforcement in Pavlovian conditioning.

Conditioned stimulus (CS) duration is a determinant of conditioned responding, with increases in duration leading to reductions in response rates. The CS duration effect has been proposed to reflect sensitivity to the reinforcement rate across cumulative exposure to the CS, suggesting that the delay of reinforcement from the onset of the cue is not crucial. Here, we compared the effects of delay and rate of reinforcement on Pavlovian appetitive conditioning in mice. In Experiment 1, the influence of reinforcement delay on the timing of responding was removed by making the duration of cues variable across trials. Mice trained with variable duration cues were sensitive to differences in the rate of reinforcement to a similar extent as mice trained with fixed duration cues. Experiments 2 and 3 tested the independent effects of delay and reinforcement rate. In Experiment 2, food was presented at either the termination of the CS or during the CS. In Experiment 3, food occurred during the CS for all cues. The latter experiment demonstrated an effect of delay, but not reinforcement rate. Experiment 4 ruled out the possibility that the lack of effect of reinforcement rate in Experiment 3 was due to mice failing to learn about the nonreinforced CS exposure after the presentation of food within a trial. These results demonstrate that although the CS duration effect is not simply a consequence of timing of conditioned responses, it is dependent on the delay of reinforcement. The results provide a challenge to current associative and nonassociative, time-accumulation models of learning.

Fear-Potentiated Startle and Fear Extinction in a Sample of Undergraduate Women Exposed to a Campus Mass Shooting.

Posttraumatic stress disorder (PTSD) is a common psychological disorder that affects a substantial minority of individuals. Previous research has suggested that PTSD can be partially explained as a disorder of impaired fear inhibition. The current study utilized a previously validated fear acquisition and extinction paradigm in a sample of 75 undergraduate women who were exposed to a campus mass shooting that occurred in 2008. We used a protocol in which conditioned fear was first acquired through the presentation of one colored shape (reinforced conditioned stimulus, CS+) that was paired with an aversive airblast to the larynx (unconditioned stimulus, US) and a different colored shape that was not paired with the airblast (non-reinforced conditioned stimulus, CS-). Fear was extinguished 10 min later through repeated presentations of the CSs without reinforcement. Number of clinically significant posttraumatic stress symptoms (PTSS) immediately following the mass shooting were positively associated with fear-potentiated startle (FPS) to the CS+ and CS- during late periods of acquisition. During early periods of fear extinction, PTSS was positively associated with FPS to the CS+. Results from the current study suggest that PTSS is related to altered fear inhibition and extinction during an FPS paradigm. In line with similar research, women with greater PTSS demonstrated a greater “fear load,” suggesting that these women experienced elevated fear to the CS+ during extinction after conditioned fear was acquired.

Rescaling of temporal expectations during extinction.

Previous research suggests that extinction learning is temporally specific. Changing the conditioned stimulus (CS) duration between training and extinction can facilitate the loss of the conditioned response (CR) within the extinction session but impairs long-term retention of extinction. In 2 experiments using conditioned magazine approach with rats, we examined the relation between temporal specificity of extinction and CR timing. In Experiment 1, rats were trained on a 12-s, fixed CS-unconditional stimulus interval and then extinguished with CS presentations that were 6, 12, or 24 s in duration. The design of Experiment 2 was the same except rats were trained using partial rather than continuous reinforcement. In both experiments, extending the CS duration in extinction facilitated the diminution of CRs during the extinction session, but shortening the CS duration failed to slow extinction. In addition, extending (but not shortening) the CS duration caused temporal rescaling of the CR, in that the peak CR rate migrated later into the trial over the course of extinction training. This migration partially accounted for the faster loss of the CR when the CS duration was extended. Results are incompatible with the hypothesis that extinction is driven by cumulative CS exposure and suggest that temporally extended nonreinforced CS exposure reduces conditioned responding via temporal displacement rather than through extinction per se. (PsycINFO Database Record

Neural Substrates of Overgeneralized Conditioned Fear in PTSD.

Heightened generalization of fear from an aversively reinforced conditioned stimulus (CS+, a conditioned danger cue) to resembling stimuli is widely accepted as a pathogenic marker of posttraumatic stress disorder (PTSD). Indeed, a distress response to benign stimuli that "resemble" aspects of the trauma is a central feature of the disorder. To date, the link between overgeneralization of conditioned fear and PTSD derives largely from clinical observations, with limited empirical work on the subject. This represents the first effort to examine behavioral and brain indices of generalized conditioned fear in PTSD using systematic methods developed in animals known as generalization gradients: the gradual decline in conditioned responding as the presented stimulus gradually differentiates from CS+. Gradients of conditioned fear generalization were assessed using functional MRI and behavioral measures in U.S. combat veterans who served in Iraq or Afghanistan and had PTSD (N=26), subthreshold PTSD (N=19), or no PTSD (referred to as trauma control subjects) (N=17). Presented stimuli included rings of graded size, with extreme sizes serving as CS+ (paired with shock) and as a nonreinforced conditioned stimulus (CS-, a conditioned safety cue), and with intermediate sizes forming a continuum of similarity between CS+ and CS-. Generalization gradients were assessed as response slopes from CS+, through intermediate ring sizes, to CS-, with less steep slopes indicative of stronger generalization. Relative to trauma control subjects, PTSD patients showed stronger conditioned generalization, as evidenced by less steep generalization gradients in both behavioral risk ratings and brain responses in the left and right anterior insula, left ventral hippocampus, dorsolateral and dorsomedial prefrontal cortex, and caudate nucleus. Severity of PTSD symptoms across the three study groups was positively correlated with levels of generalization at two such loci: the right anterior insula and left ventral hippocampus. The results point to evidence of brain-based markers of overgeneralized fear conditioning related to PTSD. These findings provide further understanding of a central yet understudied symptom of trauma-related psychopathology.

Pain-avoidance versus reward-seeking: an experimental investigation.

According to fear-avoidance models, a catastrophic interpretation of a painful experience may give rise to pain-related fear and avoidance, leading to the development and maintenance of chronic pain problems in the long term. However, little is known about how exactly motivation and goal prioritization play a role in the development of pain-related fear. This study investigates these processes in healthy volunteers using an experimental context with multiple, competing goals. In a differential human fear-conditioning paradigm, 57 participants performed joystick movements. In the control condition, one movement (conditioned stimulus; CS) was followed by a painful electrocutaneous unconditioned stimulus (pain-US) in 50% of the trials, whereas another movement (nonreinforced conditioned stimulus; CS) was not. In the experimental condition, a reward in the form of lottery tickets (reward-US) accompanied the presentation of the pain-US. Participants were classified into 3 groups, as a function of the goal, they reported to be the most important: (1) pain-avoidance, (2) reward-seeking, and (3) both goals being equally important. Results indicated that neither the reward co-occurring with pain nor the prioritized goal modulated pain-related fear. However, during subsequent choice trials, participants selected the painful movement more often when the reward was presented compared with the context in which the reward was absent. The latter effect was dependent on goal prioritization, with more frequent selections in the reward-seeking group, and the least selections in the pain-avoidance group. Taken together, these results underscore the importance of competing goals and goal prioritization in the attenuation of avoidance behavior.

Medial prefrontal pathways for the contextual regulation of extinguished fear in humans

The maintenance of anxiety disorders is thought to depend, in part, on deficits in extinction memory, possibly due to reduced contextual control of extinction that leads to fear renewal. Animal studies suggest that the neural circuitry responsible fear renewal includes the hippocampus, amygdala, and dorsomedial (dmPFC) and ventromedial (vmPFC) prefrontal cortex. However, the neural mechanisms of context-dependent fear renewal in humans remain poorly understood. We used functional magnetic resonance imaging (fMRI), combined with psychophysiology and immersive virtual reality, to elucidate how the hippocampus, amygdala, and dmPFC and vmPFC interact to drive the context-dependent renewal of extinguished fear. Healthy human participants encountered dynamic fear-relevant conditioned stimuli (CSs) while navigating through 3-D virtual reality environments in the MRI scanner. Conditioning and extinction were performed in two different virtual contexts. Twenty-four hours later, participants were exposed to the CSs without reinforcement while navigating through both contexts in the MRI scanner. Participants showed enhanced skin conductance responses (SCRs) to the previously-reinforced CS+ in the acquisition context on Day 2, consistent with fear renewal, and sustained responses in the dmPFC. In contrast, participants showed low SCRs to the CSs in the extinction context on Day 2, consistent with extinction recall, and enhanced vmPFC activation to the non-reinforced CS−. Structural equation modeling revealed that the dmPFC fully mediated the effect of the hippocampus on right amygdala activity during fear renewal, whereas the vmPFC partially mediated the effect of the hippocampus on right amygdala activity during extinction recall. These results indicate dissociable contextual influences of the hippocampus on prefrontal pathways, which, in turn, determine the level of reactivation of fear associations.

Effect of transcranial direct current stimulation on semantic discrimination eyeblink conditioning

BackgroundTranscranial direct current stimulation (tDCS) is a neuromodulation method that has been used to modulate learning. We tested whether anodal tDCS targeted at the left DLPFC could enhance learning in a semantic variant of discrimination eyeblink conditioning, i.e., whether the stimulation would have a specific effect on the discrimination ability, rate of acquisition, amplitude of the conditioned response (CR), or all of these. MethodsImmediately prior to the eyeblink conditioning, the participants received either active stimulation of 1mA for 10min or sham stimulation. The anode was placed over F3 and the cathode over the right supraorbital area. The conditioned stimuli (CSs) were common Finnish male and female names that were presented as text. Male names were reinforced with an unconditioned stimulus. ResultsStimulation had no effect on the learning rate or discrimination ratio, but the stimulated participants showed steeper CR acquisition in the initial phase of the experiment. Nevertheless, the participants in the stimulation group showed greater eyeblink CRs to the non-reinforced CS. DiscussionContrary to our initial hypothesis, the magnitude and rate of CRs to non-reinforced CS was higher in the active stimulation group than in the sham stimulation group, which may suggest deterioration of discrimination and contingency awareness in the used task. Our observations may suggest a lack of effect on the participants’ ability to discriminate between two different types of CS. Furthermore, cathodal modulation of the right prefrontal cortex may explain the change in magnitude and rate of CRs to non-reinforced CS.

Changes in the distribution of response rates across the CS-US interval: Evidence that responding switches between two distinct states.

Two experiments used the peak procedure to examine timing of conditioned responses in a magazine approach paradigm with rats. A conditioned stimulus (CS) was reinforced with food on 50% of trials. Food was delivered at a fixed time, 20 s, 30 s, or 40 s into the CS presentation. Response rates were recorded during nonreinforced CS presentations that extended well beyond the scheduled time of food delivery. The mean response rate (averaged over many trials) increased during the CS, peaking at the expected time of reinforcement, and decreased again. Detailed analyses of the frequency distribution of response rates showed that responding was described by 2 distinct distributions, consistent with the rat being in a low response state on some trials and in a high response state on others. Modeling of frequency distributions showed that the systematic rise and fall in response rate across a trial was primarily explained by a change in the proportion of time that the rat spent in the low versus high response state. However, the change in responding was also explained in part by a continuous shift in the high response state, such that responding in that state increased and then decreased gradually across the trial. These results support accounts describing response timing as an abrupt change from low to high responding during the CS, but also provide evidence for a continuous change in conditioning strength across the duration of the CS. The implications of these findings for timing and associative theories of conditioning are discussed. (PsycINFO Database Record

Competing Goals Attenuate Avoidance Behavior in the Context of Pain

Current fear-avoidance models consider pain-related fear as a crucial factor in the development of chronic pain. However, pain-related fear often occurs in a context of multiple, competing goals. This study investigated whether pain-related fear and avoidance behavior are attenuated when individuals are faced with a pain avoidance goal and another valued but competing goal, operationalized as obtaining a monetary reward. Fifty-five healthy participants moved a joystick toward different targets. In the experimental condition, a movement to one target (conditioned stimulus [CS+]) was followed by a painful unconditioned stimulus (pain-US) and a rewarding unconditioned stimulus (reward-US) on 50% of the trials, whereas the other movement (nonreinforced conditioned stimulus [CS−]) movement was not. In the control condition, the CS+ movement was followed by the pain-US only. Results showed that pain-related fear was elevated in response to the CS+ compared to the CS− movement, but that it was not influenced by the reward-US. Interestingly, participants initiated a CS+ movement slower than a CS− movement in the control condition but not in the experimental condition. Also, in choice trials, participants performed the CS+ movement more frequently in the experimental than in the control condition. These results suggest that the presence of a valued competing goal can attenuate avoidance behavior. PerspectiveThe current study provides experimental evidence that both pain and competing goals impact on behavioral decision making and avoidance behavior. These results provide experimental support for treatments of chronic pain that include an individual's pursuit of valuable daily life goals, rather than limiting focus to pain reduction only.

Using panicogenic inhalations of carbon dioxide enriched air to induce attentional bias for threat: Implications for the development of anxiety disorders

The tendency for anxious individuals to selectively attend to threatening information is believed to cause and exacerbate anxious emotional responding in a self-perpetuating cycle. The present study sought to examine the relation between differential interoceptive conditioning (IC) using carbon dioxide inhalation as a panicogenic unconditioned stimulus (US) and the development of Stroop colour-naming interference to various non-word conditioned stimuli (CSs). Healthy university students (N = 27) underwent the assessment of colour-naming interference to reinforced CS+ and non-reinforced CS− non-words prior to and following differential fear conditioning. Participants showed greater magnitude electrodermal and verbal-evaluative responses to the CS+ over the CS− non-word following IC, and demonstrated the expected slower colour-naming latencies to the CS+ compared to the CS− non-word from baseline to post-conditioning. We discuss the relation between fear learning and the emergence of attentional bias for threat to further understand the maintenance of anxiety disorders.

Phase-locked hippocampal theta-band responses are related to discriminative eyeblink conditioned responding

Hippocampal electrophysiological oscillatory activity is undoubtedly related to learning and memory. The relative power of spontaneously occurring hippocampal theta (∼4–8Hz) oscillations predicts how fast and how well an animal will learn: more theta predicts faster acquisition of the conditioned response in eyeblink conditioning in both rats and rabbits. Here, our aim was to study how hippocampal theta-band responses to conditioned stimuli elicited during very-long delay discrimination eyeblink conditioning relate to the accompanying conditioned behavior. We trained adult male New Zealand White rabbits using 1500-ms auditory stimuli as conditioned stimuli and a 100-ms airpuff as an unconditioned stimulus. The reinforced conditioned stimulus overlapped and co-terminated with the unconditioned stimulus whereas the non-reinforced conditioned stimulus was always presented alone. Consistent with previous results, hippocampal theta-band responses to the conditioned stimuli diminished in amplitude across training. Interestingly, hippocampal theta-band responses were most consistently time-locked when a well-trained animal failed to suppress behavioral learned responses to the non-reinforced conditioned stimulus. We suggest that phase-locking of hippocampal theta-band oscillations in response to external stimuli reflects retrieval of the dominant memory trace (adaptive or not) along with initiating the most prominent action scheme related to that memory trace.

Temporal properties of fear extinction—Does time matter?

Fear extinction can be defined as the weakening of the expression of a conditioned response (CR) by extended experience of nonreinforcement. Conceptually, two distinct models have been invoked to account for extinction. R. A. Rescorla and A. R. Wagner (1972, A theory of Pavlovian conditioning: Variations in the effectiveness of reinforcement and nonreinforcement, in A. H. B. W. F. Prokasy (Ed.), Classical conditioning: II. Current research and theory, pp. 64-99, New York, NY, Appleton-Century-Crofts) postulated that the number of exposure trials is the primary determinant of CR decrement, whereas C. R. Gallistel and J. Gibbon (2000, Time, rate, and conditioning, Psychological Review, Vol. 107, pp. 289-344) proposed that the decisive event is the cumulated exposure time to the nonreinforced conditioned stimulus (CS) elapsed after the last CS reinforcement. We evaluated these two accounts in a human differential fear conditioning study in which CR was measured with the fear-potentiated startle response. Cumulated duration of nonreinforcement fails to explain our findings, whereas the number of trials appeared critical. In fact, many CS trials with a duration shorter than the acquisition CS duration facilitated within-session extinction, but this effect did not predict the recovery of fear.

D-cycloserine does not facilitate fear extinction by reducing conditioned stimulus processing or promoting conditioned inhibition to contextual cues

The NMDA receptor partial agonist d-cycloserine (DCS) enhances the extinction of learned fear in rats and exposure therapy in humans with anxiety disorders. Despite these benefits, little is known about the mechanisms by which DCS promotes the loss of fear. The present study examined whether DCS augments extinction retention (1) through reductions in conditioned stimulus (CS) processing or (2) by promoting the development of conditioned inhibition to contextual cues. Rats administered DCS prior to extinction showed enhanced long-term extinction retention (Experiments 3 and 4). The same nonreinforced CS procedure used in extinction also reduced freezing at test when presented as pre-exposure before conditioning, demonstrating latent inhibition (Experiment 1). DCS administered shortly prior to pre-exposure had no effect on latent inhibition using parameters which produced weak (Experiment 2) or strong (Experiment 3) expression of latent inhibition. Therefore, DCS facilitated learning involving CS-alone exposures, but only when these exposures occurred after (extinction) and not before (latent inhibition) conditioning. We also used a retardation test procedure to examine whether the extinction context gained inhibitory properties for rats given DCS prior to extinction. With three different footshock intensities, there was no evidence that DCS promoted accrual of associative inhibition to the extinction context (Experiment 4). The present findings demonstrate that DCS does not facilitate extinction by reducing CS processing or causing the extinction context to become a conditioned inhibitor. Investigations into the mechanisms underlying the augmentation of extinction by DCS are valuable for understanding how fear can be inhibited.

Tools for translational neuroscience: PTSD is associated with heightened fear responses using acoustic startle but not skin conductance measures

Background: Posttraumatic stress disorder (PTSD) patients show heightened fear responses to trauma reminders and an inability to inhibit fear in the presence of safety reminders. Brain imaging studies suggest that this is in part due to amygdala over-reactivity as well as deficient top-down cortical inhibition of the amygdala. Consistent with these findings, previous studies, using fear-potentiated startle (FPS), have shown exaggerated startle and deficits in fear inhibition in PTSD participants. However, many PTSD studies using the skin conductance response (SCR) report no group differences in fear acquisition. Method: The study included 41 participants with PTSD and 70 without PTSD. The fear conditioning session included a reinforced conditioned stimulus (CS+, danger cue) paired with an aversive airblast, and a nonreinforced conditioned stimulus (CS−, safety cue). Acoustic startle responses and SCR were acquired during the presentation of each CS. Results: The results showed that fear conditioned responses were captured in both the FPS and SCR measures. Furthermore, PTSD participants had higher FPS to the danger cue and safety cue compared to trauma controls. However, SCR did not differ between groups. Finally, we found that FPS to the danger cue predicted re-experiencing symptoms, whereas FPS to the safety cue predicted hyper-arousal symptoms. However, SCR did not contribute to PTSD symptom variance. Conclusions: Replicating earlier studies, we showed increased FPS in PTSD participants. However, although SCR was a good measure of differential conditioning, it did not differentiate between PTSD groups. These data suggest that FPS may be a useful tool for translational research. Depression and Anxiety, 2011. © 2011 Wiley Periodicals, Inc.

Fear Extinction in Traumatized Civilians with Posttraumatic Stress Disorder: Relation to Symptom Severity

The symptoms of posttraumatic stress disorder (PTSD) can be explained, at least in part, as an inability to inhibit learned fear during conditions of safety. Our group has shown that fear inhibition is impaired in both combat and civilian PTSD populations. On the basis of our earlier findings, we employed an established fear extinction paradigm to further explore fear dysregulation in a civilian traumatized population. Fear-potentiated startle (FPS) was examined in 127 trauma-exposed individuals with and without PTSD. We used a protocol in which conditioned fear was first acquired through the presentation of one colored shape (reinforced conditioned stimulus, [CS+]) that was paired with an aversive air blast to the larynx (unconditioned stimulus) and a different colored shape that was not paired to the air blast (nonreinforced condition stimulus). Fear was extinguished 10 min later through repeated presentations of the CSs without reinforcement. Both groups demonstrated successful fear conditioning on the basis of startle and unconditioned stimulus-expectancy ratings; however, participants with PTSD displayed greater FPS responses to the CS+ and nonreinforced conditioned stimulus compared with the group without PTSD. During fear extinction, the PTSD group showed elevated FPS responses to the previously reinforced CS+ during the early and middle stages of extinction. During the acquisition and extinction phases, PTSD participants with higher levels of reexperiencing symptoms exhibited greater potentiated startle responses to the CS+ compared with PTSD participants with lower reexperiencing symptoms. These results suggest that PTSD is associated with enhanced fear learning and a greater "fear load" to extinguish after conditioned fear is acquired.