Meike Pappens

Learning to fear suffocation: A new paradigm for interoceptive fear conditioning

The present study aimed to establish a new interoceptive fear conditioning paradigm. The conditioned stimulus (CS) was a flow resistor that slightly obstructs breathing; the unconditional stimulus (US) was a breathing occlusion. The paired group (N = 21) received 6 acquisition trials with paired CS-US presentations. The unpaired group (N = 19) received 6 trials of unpaired CS-US presentations. In the extinction phase, both groups were administered 6 CS-only trials. Measurements included startle eyeblink response, electrodermal responses, and self-reported US expectancy. In the paired group, startle blink responses were larger during CS compared to intertrial interval during acquisition and extinction. Electrodermal and US expectancies were larger for the paired than for the unpaired group during acquisition, but not during extinction. The present paradigm successfully established interoceptive fear conditioning with panic-relevant stimuli.

Learning to fear obstructed breathing: Comparing interoceptive and exteroceptive cues

The present study investigated interoceptive fear conditioning (IFC) to an interoceptive and exteroceptive conditional stimulus (CS) with a severe respiratory load applied for 30s as the unconditional stimulus (US). CSs were another, weak respiratory load in the intero-IFC study (N=74), and a neutral picture in the extero-IFC study (N=42). CSs preceded the US in the paired groups, whereas the unpaired groups received the same number of unpaired CSs and USs. We measured startle blink EMG, self-reported fear and respiration. In the intero-IFC study, the CS-load was associated with larger startle blinks and a smaller decrease in respiratory rate and tidal volume in the paired compared to the unpaired group. In the extero-IFC study, the CS-picture evoked an increase in tidal volume and self-reported fear only in the paired group. In addition, startle potentiation during the CS-picture was greater for the paired than for the unpaired group.

Psychophysiological responses to CO2 inhalation

Inhalation of CO(2)-enriched air has been used as a laboratory model for a number of anxiety disorders, such as general anxiety disorder and panic disorder. Because studies describing psychophysiological responses to this challenge are scarce, the present studies investigated skin conductance level, eyeblink startle, self-reported anxiety and fractional end-tidal carbon dioxide during inhalation of CO(2)-enriched air. In study 1, thirty-five healthy volunteers inhaled 7.5% CO(2) for 2min. In study 2, twenty healthy volunteers inhaled 20% CO(2) for 30s. Control groups (N=20 in each study) inhaled room air during the same time periods. Compared to room air breathing, both CO(2)-mixtures were associated with increases in skin conductance levels, self-reported anxiety and fractional end-tidal CO(2.) Eyeblink startles were inhibited during CO(2) compared to room air breathing in both experiments. Our findings suggest that inhalation of CO(2)-enriched air is associated with a circa-strike defensive response pattern, corroborating its application as an interoceptive, panic-relevant stimulus in fear research.

Psychophysiological responses to inspiratory resistive loads.

Fear of interoceptive sensations is relevant for a number of psychiatric and somatic disorders. Pappens et al. (2010, Biol. Psychol. 84, 98-103) reported elevated skin conductance responses (SCR), subjective fear, and a paradoxical lack of startle potentiation during aversive respiratory stimulation with an inspiratory resistive load (IRL). This study aimed to replicate these findings and to explore whether the lack of startle potentiation during an aversive IRL is related to attentional allocation to the IRL. Reaction times to the acoustic startle probe served as an indirect index of attentional focus on the respiratory stimulus. The earlier findings on SCR and subjective fear were replicated. However, startle potentiation occurred for the aversive IRL with a 1500 ms lead interval, and reaction times to the acoustic probe were not slower for the aversive IRL compared to other types of lead stimuli. This suggests that startle potentiation during aversive respiratory stimulation with IRLs only occurs when an exteroceptive task limits attentional allocation to the interoceptive experience.

Generalization of Fear to Respiratory Sensations

Interoceptive fear conditioning (IFC), fear generalization and a lack of safety learning have all been hypothesized to play a role in the pathogenesis of panic disorder, but have never been examined in a single paradigm. The present study aims to investigate whether healthy participants (N=43) can learn both fear and safety to an interoceptive sensation, and whether such learning generalizes to other, similar sensations. Two intensities of inspiratory breathing impairment (induced by two pressure threshold loads of 6 and 25 cm H2O) served as interoceptive conditional stimuli (CSs) in a differential conditioning paradigm. An inspiratory occlusion was used as the unconditioned stimulus (US). Generalization was tested 24h after conditioning, using four generalization stimuli with intensities in-between CS+ and CS- (GSs: 8-10.5-14-18.5 cm H2O). Measures included US-expectancy, startle blink EMG responses, electrodermal activity and respiration. Perceptual discrimination of interoceptive CSs and GSs was explored with a discrimination task prior to acquisition and after generalization. Results indicate that differential fear learning was established for US-expectancy ratings. The group with a low intensity CS+ and a high intensity CS- showed the typical pattern of differential fear responding and a similarity-based generalization gradient. In contrast, the high intensity CS+ and low intensity CS- group showed impaired differential learning and complete generalization of fear. Our findings suggest that interoceptive fear learning and generalization are modulated by stimulus intensity and that the occurrence of discriminatory learning is closely related to fear generalization.

Interoceptive fear learning to mild breathlessness as a laboratory model for unexpected panic attacks

Fear learning is thought to play an important role in panic disorder. Benign interoceptive sensations can become predictors (conditioned stimuli – CSs) of massive fear when experienced in the context of an initial panic attack (unconditioned stimulus – US). The mere encounter of these CSs on a later moment can induce anxiety and fear, and precipitate a new panic attack. It has been suggested that fear learning to interoceptive cues would result in unpredictable panic. The present study aimed to investigate whether fear learning to an interoceptive CS is possible without declarative knowledge of the CS–US contingency. The CS consisted of mild breathlessness (or: dyspnea), the US was a suffocation experience. During acquisition, the experimental group received six presentations of mild breathlessness immediately followed by suffocation; for the control group both experiences were always separated by an intertrial interval. In the subsequent extinction phase, participants received six unreinforced presentations of the CS. Expectancy of the US was rated continuously and startle eyeblink electromyographic, skin conductance, and respiration were measured. Declarative knowledge of the CS–US relationship was also assessed with a post-experimental questionnaire. At the end of acquisition, both groups displayed the same levels of US expectancy and skin conductance in response to the CS, but the experimental group showed a fear potentiated startle eyeblink and a different respiratory response to the CS compared to the control group. Further analyses on a subgroup of CS–US unaware participants confirmed the presence of startle eyeblink conditioning in the experimental group but not in the control group. Our findings suggest that interoceptive fear learning is not dependent on declarative knowledge of the CS–US relationship. The present interoceptive fear conditioning paradigm may serve as an ecologically valid laboratory model for unexpected panic attacks.

Retention of perceptual generalization of fear extinction

Fear reduction obtained during a fear extinction procedure can generalize from the extinction stimulus to other perceptually similar stimuli. Perceptual generalization of fear extinction typically follows a perceptual gradient, with increasing levels of fear reduction the more a stimulus resembles the extinction stimulus. The current study aimed to investigate whether perceptual generalization of fear extinction can be observed also after a retention interval of 24h. Fear was acquired to three geometrical figures of different sizes (CS(+), CS1(+) and CS2(+)) by consistently pairing them with a short-lasting suffocation experience (US). Three other geometrical figures that were never followed by the US served as control stimuli (CS(-), CS1(-), CS2(-)). Next, only the CS(+) was extinguished by presenting it in the absence of the US. One day later, fear responses to all stimuli were assessed without any US-presentation. Outcome measures included startle blink EMG, skin conductance, US expectancy, respiratory rate and tidal volume. On day 2 spontaneous recovery of fear was observed in US expectancy and tidal volume, but not in the other outcomes. Evidence for the retention of fear extinction generalization was present in US expectancy and skin conductance, but a perceptual gradient in the retention of generalized fear extinction could not be observed.