Generalization of Fear Effects in Reinstatement to a Discrete Stimulus

The purpose of this study was to investigate generalization of reinstated fear effects to a discrete stimulus. McAllister and McAllister (2006) reported that reinstated fear could generalize over time to similar contexts. The present study aimed to determine if reinstated fear could generalize to similar or different stimuli than conditioning after a long delay between reinstatement and testing. Rat subjects were randomly assigned to six groups (n = 10) which received conditioning and extinction to a 3000 Hz tone. Reinstatement conditioning was then conducted with either the same, similar, or different CS as used in conditioning. Testing for reinstated fear with the original CS was conducted after either a short or long delay following reinstatement. Reinstated fear was measured by freezing responses during the target stimulus. The results indicated support for an increase in generalization of reinstated CS fear, as well as evidence for an incubation effect for fear reinstated to the same CS. The clinical applications of these results are discussed. RUNNING HEAD: GENERALIZATION OF FEAR 3 Generalization of Fear Effects in Reinstatement to a Discrete Stimulus Anxiety disorders are one of the most common mental disorders in America, affecting 18.1% of the adult population and 25.1% of 13 to 18 year olds (Kessler, Chiu, Demler, & Walters, 2005; Merikangas et al., 2010). Exposure therapy, which involves exposing individuals to an object or situation that they fear until the object no longer elicits a fear response (i.e., extinction treatment), has become the first line of treatment for such disorders (Hermans et al., 2005). It was originally believed that extinction treatment could erase fear to a CS (Rescorla & Wagner, 1972), making exposure therapy an effective long term treatment. However, recovery of fear following extinction has been observed both in human and animal models (Laborda, McConnell, & Miller, 2011). Researchers have reported that 33% to 62% of phobic individuals show a return of fear as soon as a month after treatment (Rachman & Lopatka, 1988). The return of fear can be partial or full compared to the fear level that was present before exposure therapy. For example, Rose and McGlynn (1997) administered exposure therapy to 20 participants diagnosed with a phobia of snakes. The exposures involved presenting the participant with a snake inside of a Plexiglas container. Each exposure lasted for 5 minutes, with a 2 minute break before the snake was presented again. The participant received at least 6 exposures, and with each one the snake was progressively moved closer until it was within 6 feet. The exposures were administered until the participants’ originally reported 100-point Subjective Units of Discomfort scale (SUDs) rating decreased by half. To determine if the participants experienced a return of fear, SUDs ratings were recorded at follow-up after 1-week and again 4-weeks post treatment. It was found that 25% of participants experienced a return of fear, even though all participants received the same amount of exposure. Additionally, the participants’ original SUDs score and heart rate during exposure RUNNING HEAD: GENERALIZATION OF FEAR 4 failed to predict which participants would experience a return of fear. These results demonstrate the challenge of predicting the return of fear following exposure therapy, and thus the difficulty of determining long term effectiveness of treatment, leading researchers to analyze the return of fear following traditional extinction treatments (McAllister & McAllister, 2006). Research has demonstrated that extinction cannot erase fear (McAllister & McAllister, 1994). As time passes following extinction trials, spontaneous recovery of fear can occur. A change in an individual’s environment can also result in recovered fear, such as confronting a phobic stimulus outside of the exposure treatment context (renewal). Rapid reconditioning is further support that extinction cannot erase fear, as learning a fear response occurs more quickly after it has been extinguished. Additionally, fear can return with exposure to an aversive stimulus after extinction, a process known as reinstatement (e.g. McConnell & Miller, 2013). The following literature review presents these phenomena, with a focus on reinstatement and its application in the clinical setting. Classical Conditioning of Fear and Extinction The foundation for studying the development and treatment of anxiety disorders begins with an understanding of the fundamentals of classical conditioning (e.g. Pavlov, 1927). Classical (or Pavlovian) conditioning is a form of learning in which a neutral stimulus (conditioned stimulus, CS) is repeatedly paired with an excitatory stimulus (unconditioned stimulus, US) until the CS is able to elicit a new, learned response (conditioned response, CR), without the presence of the US. Animal models, utilizing these conditioning processes, have often been used to study conditioned fear. For instance, a rat subject receives paired presentations of a neutral stimulus (CS), such as a tone, followed by an aversive stimulus (US), such as an electric shock. The shock US produces an unlearned reflexive response of pain/fear, called the unconditional response RUNNING HEAD: GENERALIZATION OF FEAR 5 (UR). Eventually these CS-US pairings allow the CS to elicit a new learned response of fear (CR) independent of the US. This is a relatively easy response to condition in animals in controlled laboratory situations (Miller, 1948). If, after acquisition of the CR, the CS is presented repeatedly without the US, a decrease in conditioned responding is observed, a phenomenon called extinction (Pavlov, 1927). Since a common understanding of the mechanisms involved in the development and maintenance of anxiety disorders implicate conditioning procedures (Wolpe, 1958), it should not be surprising that many clinical treatments (i.e. extinction) involve exposure to the feared stimulus until anxiety no longer occurs (Craske, 1999). It would be logical to assume that, eventually, sufficient extinction exposure treatments should return the subject to its preconditioning state. McAllister and McAllister (1994) performed several experiments with rat subjects to test this assumption. Their experiments used an escape-from-fear task, with the speed of hurdle jumping to escape a CS as the measure of fear. Fear was conditioned to the context cues of a start box (CS) and then measured by the subject's speed to escape from those cues to a distinctly different safe box. The first experiment manipulated the duration of context exposure (extinction) after fear conditioning (either 0, 1, 3, or 5 hours of context exposure). The results showed that the groups that received fewer than 5 hours of extinction demonstrated some residual, higher fear levels (faster escape speeds) than the 5-hr exposure group, indicating extinction was not complete after 1 or 3-hr exposure. Using the same measure of fear, the 5-hr exposure group appeared to show performance similar to a non-conditioned control group. However, a second experiment utilizing a different, more sensitive measure of fear (superimposing the CS onto a pre-existing escape response) revealed that remaining fear was present not only after 5 hours of extinction, but even after 30 hours of extinction exposure. RUNNING HEAD: GENERALIZATION OF FEAR 6 Therefore, it is necessary to study the limitations of exposure as a treatment method by researching the impact of extinction on fear. Evidence in support of the notion that extinction does not completely remove fear can be provided by four well-established phenomena: spontaneous recovery, renewal, rapid reconditioning, and reinstatement. Spontaneous recovery Spontaneous recovery is a phenomenon observed after an interval of time is allowed to pass following extinction in which the extinguished response may briefly reappear without further CS-US pairings (Pavlov, 1927). Spontaneous recovery is generally not lasting, in some instances it disappears after a few nonreinforced presentations of the CS, but the phenomenon suggests that some fear may remain after extinction. For example, Wagner, Siegel, Thomas, and Ellison (1964) performed an experiment in which subjects were conditioned to salivate (CR) to the sound of a tone (CS), paired with a food reinforcer. Subsequently, to extinguish the CR, nonreinforced trials of the CS were presented. The subjects were given 10 extinction trials on Day 1, which resulted in the cessation of responding to the CS. At the beginning of Day 2, the subjects displayed a high (spontaneous) recovery of the CR. However, after presenting the CS again without reinforcement, responding ceased. Additionally, the observed spontaneous recovery decreased from day to day as extinction trials continued. This study demonstrated that spontaneous recovery may itself be reduced by multiple extinction treatments, but also is an example that extinction may not completely eliminate conditioned fear. Spontaneous recovery has been observed in human research with subclinical populations as well as individuals diagnosed with anxiety disorders (Laborda et al., 2011). Research manipulations that attenuate spontaneous recovery may lead to methods effective for preventing relapse in anxious individuals after exposure treatment. Several factors have been shown to affect sponRUNNING HEAD: GENERALIZATION OF FEAR 7 taneous recovery, such as extinction-test interval, US strength, extinction cues and acquisitionextinction interval (Larrauri & Schmajuk, 2008; Maren & Chang, 2006; Robbins, 1990). Spontaneous recovery has been shown to increase with time, as longer intervals between extinction and testing result in a larger magnitude of recovery (Robbins, 1990). Rosas and Bouton (1996) reported that conditioning with a weak US did not result in spontaneous recovery after extinction, whereas conditioning with a strong US did. Furthermore, st