Interoceptive fear conditioning and panic disorder: the role of conditioned stimulus-unconditioned stimulus predictability

Interoceptive fear conditioning is at the core of contemporary behavioral accounts of panic disorder. Yet, to date only one study has attempted to evaluate interoceptive fear conditioning in humans (see Acheson, Forsyth, Prenoveau, & Bouton, 2007). That study used brief (physiologically inert) and longer-duration (panicogenic) inhalations of 20% CO(2)-enriched air as an interoceptive conditioned (CS) and unconditioned (US) stimulus and evaluated fear learning in three conditions: CS only, CS-US paired, and CS-US unpaired. Results showed fear conditioning in the paired condition, and fearful responding and resistance to extinction in an unpaired condition. The authors speculated that such effects may be due to difficulty discriminating between the CS and the US. The aims of the present study are to (a) replicate and expand this line of work using an improved methodology, and (b) clarify the role of CS-US discrimination difficulties in either potentiating or depotentiating fear learning. Healthy participants (N=104) were randomly assigned to one of four conditions: (a) CS only, (b) contingent CS-US pairings, (c) unpaired CS and US presentations, or (d) an unpaired "discrimination" contingency, which included an exteroceptive discrimination cue concurrently with CS onset. Electrodermal and self-report ratings served as indices of conditioned responding. Consistent with expectation, the paired contingency and unpaired contingencies yielded elevated fearful responding to the CS alone. Moreover, adding a discrimination cue to the unpaired contingency effectively attenuated fearful responding. Overall, findings are consistent with modern learning theory accounts of panic and highlight the role of interoceptive conditioning and unpredictability in the etiology of panic disorder.     

Loss of associability by a conditioned inhibitor

In each of three experiments two groups of rats received inhibitory conditioning to one stimulus. Prior to a test phase of excitatory conditioning to this stimulus, one group was repeatedly exposed to the inhibitory stimulus by itself while the other group received no such exposure. Excitatory conditioning occurred most slowly in the group which received the exposure training. The first experiment indicated that this difference was not due to the exposure treatment enhancing the inhibitory properties of the stimulus. The results of Experiment III confirmed this conclusion and also indicated that the differences between the two groups during testing were due to differences in the associability of the inhibitory stimulus.     

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.     

Differential effects of forward or simultaneous conditioned stimulus-unconditioned stimulus intervals on the defensive behavior system of the Norway rat (Rattus norvegicus)

To test several predictions derived from a behavior-systems approach, the authors assessed Pavlovian fear conditioning in rats after 30 trials of forward, simultaneous, or unpaired training. Direct evidence of conditioned fear was collected through observation of flight and freezing reactions during presentations of the conditioned stimulus (CS) alone. The authors also tested the CS's potential to reinforce an instrumental escape response in an escape-from-fear paradigm. On the one hand, rats that received forward training showed conditioned freezing, but no conditioned flight was observed. On the other hand, rats that received simultaneous training showed conditioned flight, but no conditioned freezing was observed. Rats that received either forward or simultaneous pairings showed instrumental learning of the escape-from-fear response. Implications for several theories of Pavlovian conditioning are discussed.     

Conditioned acceleration and conditioned suppression in pigeons

Two experiments were performed to investigate the effects on pigeons' keypecking behavior of stimuli that signal different kinds of aversive events: time-out from positive reinforcement, electric shock, loud noise, and loud tone. Behavior maintained by a variable-interval schedule of reinforcement was suppressed by a stimulus before shock, was accelerated by a stimulus before time-out from positive reinforcement, and was unchanged by a stimulus before loud noise or a stimulus before loud tone. Conditioned acceleration with time-out from positive reinforcement and conditioned suppression with shock were obtained regardless of whether a response contingent or response-independent procedure was employed.     

Loss of associability by a compound stimulus comprising excitatory and inhibitory elements

In each of two experiments rats learned a discrimination between a stimulus (A) that signaled shock and a compound stimulus (AB) that signaled no shock. In Experiment 1 it was found that the AB compound acquired excitatory strength only slowly when, in a second phase of training, it was made to signal the occurrence of shock. In Experiment 2 the acquisition of inhibitory strength by the compound was similarly found to be retarded. This second experiment also replicated the results of Experiment 1. The relevance of these results to current theories of latent inhibition and attention is discussed.     

Conditioned suppression with extinction as the signalled stimulus

The key pecking of pigeons that was maintained by a 60-sec random-interval schedule of food reinforcement was suppressed during a variable-duration warning stimulus that signalled a 5-min extinction period. The onset of the extinction period immediately followed the termination of the warning signal and was independent of the subject's responses. All subjects eventually showed nearly complete suppression of responding during the warning stimulus.     

Conditioned reinforcement as a function of duration of stimulus

Pigeons were provided with three keys. Pecking the center key produced grain on a schedule that alternated at unpredictable times between a variable-interval component and extinction. On concurrent variable-interval schedules, pecking either side key produced a stimulus associated with the variable-interval component on the center key provided that said schedule was currently in effect. The independent variable was the length of time this stimulus remained on the keys. Pecking one side key produced the stimulus for 27 seconds, whereas the duration produced by pecking the other key varied for successive blocks of sessions. For the first four birds, the values tested were 3, 9, 27, and 81 seconds. For the second group, numbering three birds, the values tested were 1, 3, 9, and 27 seconds. The dependent variable was the proportion of total side key pecks that occurred on the variable key. For all birds, the function was positive in slope and negative in acceleration. This finding supports a formulation that ascribes the maintenance of observing responses in a normal setting to the fact that the subject exposes itself to the positive discriminative stimulus for a longer mean duration than it does to the negative stimulus.     

Relative durations of conditioned stimulus and intertrial interval in conditioned suppression.

The effects of the relative durations of the conditional stimulus and the intertrial interval on bar pressing during a conditioned-suppression procedure were examined as a function of two additional variables--type of operant baseline schedule and rate of shock presentation. In Experiment 1, response suppression was compared across components of a multiple fixed-ratio, random-ratio, fixed-interval, random-interval schedule, at relative conditioned-stimulus/intertrial-interval durations of 1/1, 1/4, and 1/9. In Experiment 2, relative conditioned-stimulus/intertrial-interval duration (1/5, 3/3, or 5/1) was manipulated across groups, while shock frequency (2, 6, or 10 shocks/hr) was manipulated within groups. In both experiments, suppression during the signal was virtually complete at all relative durations. Responding was also suppressed during the intertrial interval, but that suppression varied as a function of experimental manipulations. In Experiment 1, intertrial-interval response rates were higher when relative signal duration was 1/9 than when it was 1/1, although both relative signal duration and shock frequency, which covaried, could have contributed to the difference. In Experiment 2, the patterning of response rates between successive shocks was affected by relative duration, absolute rates during the intertrial interval varied as a function of shock frequency, and differences between suppression during the signal and suppression during the intertrial interval were affected by both relative duration and shock frequency. The data support an analysis based upon relationships between shock-correlated and intertrial-interval stimuli and, as assessed by the relative-delay-to-reinforcement metric, are comparable to results that have been reported from experiments using similar manipulations under the autoshaping paradigm.     

Memory for associative history of a conditioned stimulus

The common assumption that the current, but not the past, associative status of a conditioned stimulus (CS) is represented in memory is examined with respect to various behavioral phenomena within the existing literature and is found to be inadequate. This assumption is frequently expressed as associative path independence, which posits that the memorial effects of stimulus events occurring during a conditioning trial depend only on the associative strength of the CS at the initiation of that trial. Twelve laboratory phenomena are reviewed in which behavior is readily interpretated in terms of subjects remembering past as well as present associations. The possibility that behavior is influenced by past associative states as well as current associative strength is contrasted with several alternative explanations, including the suggestion that the current associative state of a CS is defined by variables in addition to associative strength. However, these alternatives are only partially successful without additional assumptions that increase their complexity. Contrary to many prevailing models, we conclude that subjects appear to retain the associative history of a CS.     

Conditioned nausea in rats: Assessment by conditioned disgust reactions, rather than conditioned taste avoidance

The terms conditioned taste avoidance and conditioned taste aversion are often used interchangeably in the literature; however, considerable evidence indicates that they may represent different processes. Conditioned taste avoidance is measured by the amount that a rat drinks in a consumption test that includes both appetitive phases and consummatory phases of responding. However, conditioned taste aversion is more directly assessed using the taste reactivity (TR) test that includes only the consummatory phase of responding. Rats display a conditioned taste aversion as conditioned disgust reactions (gapes, chin rubs, and paw treads) during an intraoral infusion of a nausea-paired flavored solution. Only treatments that produce nausea produce conditioned disgust reactions, but even rewarding drugs produce conditioned taste avoidance. Furthermore, treatments that alleviate nausea prevent the establishment and the expression of conditioned disgust reactions, but they do not necessarily modify conditioned taste avoidance. Considerable evidence exists indicating that these two measures can be independent of one another. The potential of a compound to produce conditioned disgust reactions is a reflection of its nausea-inducing properties. Taste avoidance may be motivated by conditioned fear rather than conditioned nausea, but conditioned disgust is motivated by conditioned nausea. (PsycINFO Database Record (c) 2008 APA, all rights reserved).     

Modulation of a discrete Pavlovian conditioned reflex by a putative emotive Pavlovian conditioned stimulus

Three experiments showed the modulation of a rabbit eyeblink conditioned response (CR) to a Pavlovian conditioned stimulus (CS) by 30-s stimuli (A & B) that had been differentially paired with paraorbital shock. The CS (Y) was a 1,050-ms cue that had been paired with paraorbital shock outside A or B. In testing, the amplitude of CRs was greater when Y was presented within A than within B. Differential modulation occurred whether shock in A had been preceded by another 1,050-ms cue, X(AX+,BX-;Experiment 1) or not (A+B-;Experiment 2). Experiment 3 compared the technique of Experiment 1 (AX+) with that of Experiment 2 (A+) and found the latter to be advantageous for facilitation of CRs to Y by A. These data are consistent with the predictions of a model of Pavlovian conditioning (AESOP, Wagner & Brandon, 1989) that distinguishes between emotive and sensory conditioning as did Konorski (1967).     

Reinstatement of fear to an extinguished conditioned stimulus.

Four experiments are reported which demonstrate the ability of an unconditioned stimulus (UCS) presentation following extinction to partially reinstate the conditioned response. These experiments are interpreted in terms of the strengthening of an extinction-reduced UCS representation. The first two experiments address alternative interpretations in terms of sensitization, reinstating the stimulus conditions of acquisition, conditioning of background cues, and stimulus generalization. Experiment 3 suggests that reinstatement is possible with a UCS qualitatively different from that used in conditioning. Experiment 4 explores an alternative extinction procedure which especially preserves the conditioned stimulus-unconditioned stimulus association while encouraging modification of the UCS representation. The results are discussed both in terms of related empirical phenomena, such as spontaneous recovery and sensory preconditioning, and in relation to the general role of the UCS representation in conditioning.