Versatility of Fear-Potentiated Startle Paradigms for Assessing Human Conditioned Fear Extinction and Return of Fear

Abstract

Fear conditioning methodologies have often been employed as testable models for assessing learned fear responses in individuals with anxiety disorders such as post-traumatic stress disorder (PTSD) and specific phobia. One frequently used paradigm is measurement of the acoustic startle reflex under conditions that mimic anxiogenic and fear-related conditions. For example, fear-potentiated startle is the relative increase in the frequency or magnitude of the acoustic startle reflex in the presence of a previously neutral cue (e.g., colored shape; termed the conditioned stimulus or CS+) that has been repeatedly paired with an aversive unconditioned stimulus (e.g., airblast to the larynx). Our group has recently used fear-potentiated startle paradigms to demonstrate impaired fear extinction in civilian and combat populations with PTSD. In the current study, we examined the use of either auditory or visual CSs in a fear extinction protocol that we have validated and applied to human clinical conditions. This represents an important translational bridge in that numerous animal studies of fear extinction, upon which much of the human work is based, have employed the use of auditory CSs as opposed to visual CSs. Participants in both the auditory and visual groups displayed robust fear-potentiated startle to the CS+, clear discrimination between the reinforced CS+ and non-reinforced CS−, significant extinction to the previously reinforced CS+, and marked spontaneous recovery. We discuss the current results as they relate to future investigations of PTSD-related impairments in fear processing in populations with diverse medical and psychiatric histories.

Human fear extinction and return of fear using reconsolidation update mechanisms: The contribution of on-line expectancy ratings

“…Traditionally, these data provide the experimenter with validation that the CS–US association was successfully learned during fear acquisition in that there is often a high correlation between physiological indices of fear (e.g., startle, skin conductance) and US-expectancy responses (e.g., Norrholm, Anderson, et al, 2011; Norrholm, Jovanovic, et al, 2011). As the study of conditioned fear is extended into fear extinction and return of fear paradigms (which often include multiple test sessions with varying temporal and contextual factors), dissociations begins to emerge between physiological measures and US-expectancy responses (see (Kindt & Soeter, 2013; Norrholm et al, 2008; Soeter & Kindt, 2010, 2011b; Weike et al, 2007).…”

“…The eyeblink component of the acoustic startle response was measured according to previously published methods (Norrholm et al, 2006; Norrholm, Anderson, et al, 2011; Norrholm, Jovanovic, et al, 2011). The startle probe was a 108-dB [A], 40 ms burst of white noise with near instantaneous rise time delivered binaurally with headphones.…”

“…Empirical evidence suggests that these symptoms can arise as a result of impaired fear inhibition (Jovanovic, Kazama, Bachevalier, & Davis, 2011; Jovanovic & Norrholm, 2011; Jovanovic et al, 2009, 2010), over-generalization of fear responses (Lissek, 2012), and/or dysregulation of fear extinction learning (Norrholm & Jovanovic, 2011; Norrholm, Anderson, et al, 2011; Norrholm, Jovanovic, et al, 2011) and extinction recall (Milad et al, 2008, 2009). According to the principles of fear conditioning, the traumatic event serves as an unconditioned stimulus (e.g., improvised explosive device detonation; termed the US) and previously neutral ambient cues (e.g., smoke, palm trees) in the trauma environment become associated with this “US” as a result of trauma exposure.…”

Pain-relief learning in flies, rats, and man: basic research and applied perspectives

“…In addition, startle entails postural (see above), autonomic (e.g., Hamm et al 2003a), and electrocortical (e.g., Schupp et al 1997) responses serving to make the subject ready for an imminent fight-or-flight situation, as well as modulations of the postauricular reflex (e.g., Benning et al 2004;Franklin et al 2013a) (note that the latter can reveal positive valence by increased amplitude). In humans, as in rats, the amplitude of the startle response is increased in the presence of a shock-associated or an aversive stimulus (Lang et al 1990;Grillon and Baas 2003;Andreatta et al 2010;Norrholm et al 2011). In turn and important in the current context, numerous studies have revealed that startle is decreased by stimuli associated with reward or pleasure (e.g., Geier et al 2000;Skolnick and Davidson 2002;Conzelmann et al 2009), although there is a lack of pure reward-conditioning studies with the startle response as a dependent measure.…”

Conditioned Fear Associated Phenotypes as Robust, Translational Indices of Trauma-, Stressor-, and Anxiety-Related Behaviors

“…In order to bridge this gap, Norrholm and colleagues examined the use of auditory and visual CSs in fear conditioning of healthy participants (58). Briefly, healthy participants acquired fear to auditory stimuli comparable to the participants who were fear conditioned with visual stimuli.…”