Aversive and compensatory classical conditioning with diazepam as conditional stimulus

The purpose of the first experiment was to investigate whether diazepam could acquire anxiogenic properties by signalling an aversive event. Rats were trained in an operant chamber in the pentylenetetrazol (PTZ) model of anxiety. Thereafter the animals were divided into groups that received classical diazepam conditioning (Group 1), and conditioning of diazepam + tone (Group 2). In the test phase diazepam was injected prior to placement in the operant chamber. Group 2 selected the PTZ-appropriate lever more often than the other groups, indicating that the tone induced anxiety, and diazepam did not. Tones and shock may therefore be more easily associated than diazepam and shock. The second experiment investigated this. Rats were trained the same way as in the first experiment. Thereafter the experimental group received injections of a small dose of diazepam prior to a second injection of a large dose of diazepam. The hypothesis was that a compensatory anxiogenic conditional response to diazepam's anxiolytic effect should be elicited by the small dose. There were no differences between the groups in lever selection, indicating that a compensatory anxiogenic response was not elicited.     

Anticipation of interoceptive threat in highly anxiety sensitive persons

Anticipatory anxiety plays a major role in the etiology of panic disorder. Although anticipatory anxiety elicited by expectation of interoceptive cues is specifically relevant for panic patients, it has rarely been studied. Using a population analogue in high fear of such interoceptive arousal sensations (highly anxiety sensitive persons) we evaluated a new experimental paradigm to assess anticipatory anxiety during anticipation of interoceptive (somatic sensations evoked by hyperventilation) and exteroceptive (electric shock) threat. Symptom reports, autonomic arousal, and defensive response mobilization (startle eyeblink response) were monitored during threat and matched safe conditions in 26 highly anxiety sensitive persons and 22 controls. The anticipation of exteroceptive threat led to a defensive and autonomic mobilization as indexed by a potentiation of the startle response and an increase in skin conductance level in both experimental groups. During interoceptive threat, however, only highly anxiety sensitive persons but not the controls exhibited a startle response potentiation as well as autonomic activation. The anticipation of a hyperventilation procedure thus seems a valid paradigm to investigate anticipatory anxiety elicited by interoceptive cues in the clinical context.     

Acoustic startle reflexes in the rat during consummatory behavior.

Auditory startle reflexes were elicited in thirsty rats when they were drinking water or were between drinking boutsmthe reaction was greater during drinking, this enhancement developing over the first few seconds after drinking onset. The startle reaction was lowest immediately after the termination of drinking. Reflex enhancement was reduced when thirsty rats drank milk rather than the more preferred water. The reflex was smaller with increased water deprivation, but enhancement produced by drinking was apparent at all levels of deprivation studied, satiety to 4-days deprivation. The inhibitory effect of a preliminary stimulus was not affected by consummatory behavior. Attention is drawn to suggestive parallels between these behavioral effects and other consequences of consummatory activity, primarily having to do with electrophysiological events and arousal processes     

Strategic and automatic threat processing in chronic musculoskeletal pain: a startle probe investigation

Attentional bias research with chronic pain samples has yielded conflicting results. In the present investigation the startle paradigm was used to test the postulate that fear-based mechanisms play an important role in attentional biases for pain-related threat in chronic pain. Participants, including 31 individuals with chronic musculoskeletal pain and 20 healthy controls, completed a startle task designed to measure attention to different types of words (neutral vs sensory pain vs affective pain vs health catastrophe) presented at different levels of cognitive processing (strategic vs automatic). Measures of fear-based individual difference variables, including anxiety sensitivity and fear of pain, were also completed. Startle amplitudes and latencies to acoustic startle probes that followed word presentations were recorded. Data were analyzed with repeated measures ANOVAs and correlational analysis. Significant between-group differences were found indicating that, relative to chronic pain participants, healthy controls had higher startle amplitude index scores for health catastrophe words. There was also a trend among patients with chronic pain for greater startle amplitude index scores for strategic presentations of sensory pain words. In the automatic condition, all participants demonstrated a lower startle latency index for sensory words relative to both affect and health catastrophe words, suggesting participants had more difficulty disengaging from affect and health catastrophe words or were more avoidant of sensory words. Correlational analyses indicated that startle response indices for words related to health catastrophe became more pronounced for chronic pain patients as anxiety sensitivity and fear of pain increased. Implications and directions for future research are discussed.     

Bidirectional operant conditioning of heart rate in rats with sucrose reward

Sucrose was used to reinforce heart rate (HR) increases in one group of unrestrained rats and to reinforce decreases in another. A third group received noncontingent sucrose presentations, and a fourth was presented with an empty dipper. After 10 conditioning sessions HR, as measured by changes in tonic levels, was significantly greater in the Fast group than in the Noncontingent group, which in turn maintained significantly higher levels than the Slow group. There was no difference between the Noncontingent and No-sucrose groups. Behavioral observations indicated that the Fast animals increased the percentage of time spent in such high-HR categories as rearing and walking; however, there were no corresponding systematic decreases in the Slow animals. Moreover, the Fast and Slow groups differed significantly with regard to the HRs associated with five behavioral categories. The overall pattern of results suggests that some degree of cardiospecific effect may have been exerted by the operant contingencies.     

Strategic and Automatic Threat Processing in Chronic Musculoskeletal Pain: A Startle Probe Investigation

Attentional bias research with chronic pain samples has yielded conflicting results. In the present investigation the startle paradigm was used to test the postulate that fear‐based mechanisms play an important role in attentional biases for pain‐related threat in chronic pain. Participants, including 31 individuals with chronic musculoskeletal pain and 20 healthy controls, completed a startle task designed to measure attention to different types of words (neutral vs sensory pain vs affective pain vs health catastrophe) presented at different levels of cognitive processing (strategic vs automatic). Measures of fear‐based individual difference variables, including anxiety sensitivity and fear of pain, were also completed. Startle amplitudes and latencies to acoustic startle probes that followed word presentations were recorded. Data were analyzed with repeated measures ANOVAs and correlational analysis. Significant between‐group differences were found indicating that, relative to chronic pain participants, healthy controls had higher startle amplitude index scores for health catastrophe words. There was also a trend among patients with chronic pain for greater startle amplitude index scores for strategic presentations of sensory pain words. In the automatic condition, all participants demonstrated a lower startle latency index for sensory words relative to both affect and health catastrophe words, suggesting participants had more difficulty disengaging from affect and health catastrophe words or were more avoidant of sensory words. Correlational analyses indicated that startle response indices for words related to health catastrophe became more pronounced for chronic pain patients as anxiety sensitivity and fear of pain increased. Implications and directions for future research are discussed.     

Air-puff-elicited startle: Habituation over trials and measurement of a hypothetical emotional response

In the first of two experiments, it was demonstrated that an air puff elicited a reliable startle reflex in rats which showed no habituation over 50 trials. In the second study an attempt was made to measure an emotional response by recording startle reactions to the air puff during presentation of a presumed fear-eliciting CS. It was concluded that the air-puff-elicited startle reflex can be employed as an indirect measure of a hypothetical emotional response.     

Ontogenetic dissociation of two classes of habituation.

The rates of decrement of two classes of response (an elicited startle reflex and emitted exploratory behavior) were determined in rats of two different ages (15 and 36 days). The rate of decrement in the startle reflex was not clearly differentiated as a function of age. In contrast, there was no evidence of habituation of exploration in the younger animals, whereas the older rats uniformly showed profound response decrements. This ontogenetic dissociation of the two instances of response decrement indicates that accounts of both instances in terms of a common process called habituation may be unwarranted. In addition, these data, in conjunction with earlier findings, indirectly support the possibility that reflex decrements may be relatively more dependent on brain serotonin whereas decrements in exploration may be more dependent on normal cholinergic activity in brain.     

Startle responding and context conditioning

The possibility that acoustic startle stimuli could support a conditional response (freezing) to contextual stimuli was investigated. Rats were exposed to three acoustic startle stimuli on the first day, and one on the second day. On day 1, 20 rats received naloxone pretreatment and another 20 received saline (placebo) pretreatment. Half of each group received a high-intensity acoustic stimulus, the other half a low-intensity acoustic stimulus. Both the higher stimulus intensity and the naloxone pretreatment led to greater freezing behavior during the 3-minute test period before the single startle stimulus on day 2. These findings support the notion that increased actual or perceived intensity of the acoustic startle stimulus increases conditioning to contextual stimuli as indexed by freezing behavior.     

Effects of processing speed on cerebral asymmetry for left- and right-oriented faces

A free-vision chimeric facial emotion judgment task and a tachistoscopic face-recognition reaction time task were administered to 20 male right-handed subjects. The tachistoscopic task involved judgments of whether a poser in the centrally presented full-face photograph was the same or different poser than in a profile photograph presented in the left or right visual field (LVF, RVF). The free-vision task was that used by J. Levy, W. Heller, M. Banich, and L. Burton (1983, Brain and Cognition, 2, 404-419) and involved judging which of two chimeric faces appeared happier, in which the two chimeras were mirror images of each other and each chimera consisted of a smiling half-face joined at the midline to a neutral half-face of the same poser. For the tachistoscopic task, subjects were divided into groups of Fast and Slow responders by a median split of the mean reaction times. For the Fast subjects, judgments were faster in the LVF than in the RVF, and there was a significant interaction between visual field and profile direction, such that responses were faster for medially oriented profiles; i.e., LVF responses were faster for right-facing than for left-facing profiles, with the reverse relationship in the RVF. The Slow responders did not show these effects. Only the Fast group showed the bias for choosing the chimera with the smile on the left as happier, and mean response speed and the LVF advantage on the tachistoscopic test correlated with the leftward bias on the free-vision task for all subjects combined. It was suggested that overall response speed on the face-matching task reflected the extent to which specialized and more efficient right hemisphere functions were activated.     

Negative self-focused cognitions mediate the effect of trait social anxiety on state anxiety

The cognitive model of social anxiety predicts that negative self-focused cognitions increase anxiety when anticipating social threat. To test this prediction, 36 individuals were asked to anticipate and perform a public-speaking task. During anticipation, negative self-focused cognitions or relaxation were experimentally induced while self-reported anxiety, autonomic arousal (heart rate, heart rate variability, skin conductance level), and acoustic eye-blink startle response were assessed. As predicted, negative self-focused cognitions mediated the effects of trait social anxiety on self-reported anxiety and heart rate variability during negative anticipation. Furthermore, trait social anxiety predicted increased startle amplitudes. These findings support a central assumption of the cognitive model of social anxiety.     

Greater sustained anxiety but not phasic fear in women compared to men

Startle reflex studies in rodents indicate that female are more reactive than rats in experimental models of sustained anxiety but not in models of phasic fear (Toufexis, 2007). This study examined evidence for a similar effect in humans. Participants were exposed to three conditions, (1) predictable aversive shocks signaled by a cue, (2) unpredictable shocks, and (3) no shocks. Acoustic startle stimuli were delivered regularly across conditions. Phasic startle potential to the threat cue in the predictable condition was not affected by sex. In contrast, and consistent with basic research, the sustained increase in startle in the predictable and unpredictable conditions was greater in women compared to men. Animal studies suggest that such an effect may be mediated by the effects of sexual dimorphism in limbic structures, including the bed nucleus of the stria terminalis. However, psychosocial factors may also contribute to this effect.     

Is Acoustic Startle a Viable Exposure Protocol for Posttraumatic Stress Disorder? A Clinical Case Study

Exaggerated startle is a common symptom (based on Diagnostic and Statistical Manual of Mental Disorders [fourth edition] Criterion D) for many patients with posttraumatic stress disorder (PTSD). Findings from previous studies suggest that exaggerated startle may be due to trauma exposure or pretrauma vulnerability factors for PTSD development. The present clinical case study reports on a patient with PTSD characterized by a very prominent startle response and preference against standard trauma-related exposure strategies. On the basis of recent findings that interoceptive exposure exercises (e.g. shaking head side to side, hyperventilation) elicit trauma-related memories (Wald & Taylor, 2008), the authors sought to determine whether repeated application of an acoustic startle stimulus would serve to diminish the prominent startle response and facilitate exposure and overall symptom reduction by eliciting trauma-related memories. The protocol was successful in eliciting vivid and distressing trauma-related memories. Over the course of seven exposure trials, the patient demonstrated a decrease in distress elicited during the protocol, improved mood, and reduced general anxiety and trauma-related distress. He also reported significantly decreased startle response to loud noises encountered during activities of daily living. Although preliminary, these finding suggest that the acoustic startle protocol may be a viable (interoceptive) exposure strategy for individuals with PTSD, particularly those with exaggerated startle responses and those who are not amenable to standard trauma-related exposure strategies.     

Is acoustic startle a viable exposure protocol for posttraumatic stress disorder? A clinical case study

Exaggerated startle is a common symptom (based on Diagnostic and Statistical Manual of Mental Disorders [fourth edition] Criterion D) for many patients with posttraumatic stress disorder (PTSD). Findings from previous studies suggest that exaggerated startle may be due to trauma exposure or pretrauma vulnerability factors for PTSD development. The present clinical case study reports on a patient with PTSD characterized by a very prominent startle response and preference against standard trauma-related exposure strategies. On the basis of recent findings that interoceptive exposure exercises (e.g. shaking head side to side, hyperventilation) elicit trauma-related memories (Wald & Taylor, 2008), the authors sought to determine whether repeated application of an acoustic startle stimulus would serve to diminish the prominent startle response and facilitate exposure and overall symptom reduction by eliciting trauma-related memories. The protocol was successful in eliciting vivid and distressing trauma-related memories. Over the course of seven exposure trials, the patient demonstrated a decrease in distress elicited during the protocol, improved mood, and reduced general anxiety and trauma-related distress. He also reported significantly decreased startle response to loud noises encountered during activities of daily living. Although preliminary, these finding suggest that the acoustic startle protocol may be a viable (interoceptive) exposure strategy for individuals with PTSD, particularly those with exaggerated startle responses and those who are not amenable to standard trauma-related exposure strategies.     

Acute episodes of predator exposure in conjunction with chronic social instability as an animal model of post-traumatic stress disorder

People who are exposed to horrific, life-threatening experiences are at risk for developing post-traumatic stress disorder (PTSD). Some of the symptoms of PTSD include persistent anxiety, exaggerated startle, cognitive impairments and increased sensitivity to yohimbine, an alpha(2)-adrenergic receptor antagonist. We have taken into account the conditions known to induce PTSD, as well as factors responsible for long-term maintenance of the disorder, to develop an animal model of PTSD. Adult male Sprague-Dawley rats were administered a total of 31 days of psychosocial stress, composed of acute and chronic components. The acute component was a 1-h stress session (immobilization during cat exposure), which occurred on Days 1 and 11. The chronic component was that on all 31 days the rats were given unstable housing conditions. We found that psychosocially stressed rats had reduced growth rate, reduced thymus weight, increased adrenal gland weight, increased anxiety, an exaggerated startle response, cognitive impairments, greater cardiovascular and corticosterone reactivity to an acute stressor and heightened responsivity to yohimbine. This work demonstrates the effectiveness of acute inescapable episodes of predator exposure administered in conjunction with daily social instability as an animal model of PTSD.     

Affective individual differences and startle reflex modulation

Potentiation of startle has been demonstrated in experimentally produced aversive emotional states, and clinical reports suggest that potentiated startle may be associated with fear or anxiety. To test the generalizability of startle potentiation across a variety of emotional states as well as its sensitivity to individual differences in fearfulness, the acoustic startle response of 17 high- and 15 low-fear adult subjects was assessed during fear, anger, joy, sadness, pleasant relaxation, and neutral imagery. Startle responses were larger in all aversive affective states than during pleasant imagery. This effect was enhanced among high fear subjects, although followup testing indicated that other affective individual differences (depression and anger) may also be related to increased potentiation of startle in negative affect. Startle latency was reduced during high- rather than low-arousal imagery but was unaffected by emotional valence.     

Cardiac modulation of startle: Effects on eye blink and higher cognitive processing

Cardiac cycle time has been shown to affect pre-attentive brainstem startle processes, such as the magnitude of acoustically evoked reflexive startle eye blinks. These effects were attributed to baro-afferent feedback mechanisms. However, it remains unclear whether cardiac cycle time plays a role in higher startle-related cognitive processes, as well. Twenty-five volunteers responded first by ’fast as possible’ button pushes (reaction time, RT), and second, rated perceived intensity of 60 acoustic startle stimuli (85, 95, or 105 dB; 50 ms duration; binaural; instantaneous rise time), which were presented either 230 or 530 ms after the R-wave, and eye blink responses were measured by EMG. RT was divided into evaluation and motor response time according to previous research. Increasing stimulus intensity enhanced startle eye blink, intensity ratings, and RT components. Eye blinks and intensity judgments were lower when startle was elicited at a latency of R + 230 ms, but RT components were differentially affected: the evaluative component was attenuated, and the motor component was accelerated when stimuli were presented 230 ms after the R-wave. We conclude that the cardiac cycle affects the attentive processing of acoustic startle stimuli.     

Startle modulation in non-incarcerated men and women with psychopathic traits

Past research has demonstrated that individuals with psychopathic characteristics are under-responsive to aversive stimuli, however, much of this work has failed to include non-incarcerated samples, or to examine gender differences in this relationship. Additionally, few studies have examined the role of specific personality characteristics, as they relate to both psychopathic behavior and emotional responsiveness. The current study assessed emotional modulation of the startle response in a community sample of 108 men and women (99 with usable startle data) during perception of emotion-laden photographs. Consistent with previous work, men reporting high levels of psychopathy failed to show the typical increase in the startle response when exposed to aversive photographs, but only when responses were elicited relatively early in picture viewing (i.e., 2.0 s as compared to 4.5 s post-photograph onset). Additionally, both genders showed a significant effect of harm avoidance and anxiety on modulation of the startle response, such that individuals reporting low levels of each trait failed to show significant responses to aversive photographs. These results suggest that while deficits in emotional processing extend to non-incarcerated samples, the relationship may be influenced by additional factors including gender, personality, and attributes related to incarceration.     

Temporal specificity of fear conditioning: effects of different conditioned stimulus-unconditioned stimulus intervals on the fear-potentiated startle effect

Separate groups of rats were given 30 pairings of a light (conditioned stimulus, CS) and 500-ms shock (unconditioned stimulus, US) at CS-US intervals of 0, 25, 50, 100, 200, 800, 3,200, 12,800, or 51,200 ms. Other groups had lights and shocks inconsistently paired. The startle reflex was elicited 2-4 days later with a noise burst alone or 25-51,200 ms after light onset. After CS-US pairings over a wide range of intervals (25-51,200 ms), startle was potentiated in testing, sometimes as rapidly as 50 ms after light onset. Magnitude of potentiation and resistance to extinction were generally greater with longer CS-US intervals. In several groups, potentiation was maximal at a test interval that matched the CS-US interval used in training. This temporal specificity sharpened with increasing numbers of training trials but even occurred with a single training trial in which a 51,200-ms CS-US interval was used. The data indicate that even during simple fear conditioning, animals rapidly learn a temporal CS-US relationship. This has important implications for understanding the neural mechanisms of fear conditioning.     

Potentiation of the acoustic startle response by a conditioned stimulus paired with acoustic startle stimulus in rats

The hypothesis that the standard acoustic startle habituation paradigm contains the elements of Pavlovian fear conditioning was tested. In a potentiated startle response paradigm, a startle stimulus and a light conditioned stimulus (CS) were paired. A startle stimulus then was tested alone or following the CS. Freezing behavior was measured to index conditioned fear. The startle response was potentiated on CS trials, and rats froze more in CS than in non-CS periods. In Experiment 1, response to a previously habituated, weak startle stimulus was potentiated. In Experiment 2, response to the same stimulus used as the unconditioned stimulus (US) in training was potentiated. This CS-potentiated response retarded the course of response decrements over training sessions as compared with an explictly unpaired control group. Conditioned fear is a standard feature of this habituation paradigm, serves to potentiate the startle response, and provides an associative dimension lacking in the habituation process per se.