Perceptual sensitivity to sensory and affective aspects of dyspnea: Test-retest reliability and effects of fear of suffocation.

Perceptual sensitivity for dyspnea (i.e. breathlessness) is often quantified using the slope of magnitude estimations plotted against the physical stimulus intensities of respiratory loads. This study investigated whether this slope and its stability varies as a function of (1) affective versus sensory aspects of dyspnea, and (2) interindividual differences in Fear of Suffocation. Eighty-three healthy women performed a load magnitude estimation task twice one week apart. Resistive loads of increasing magnitude (0-2.4-5-7.4-12.4-20 cmH20/l/s) were repeatedly presented for a single flow-targeted inspiration. One group rated the intensity of loads, another their unpleasantness. Neither slopes nor intercepts differed between sensory versus affective aspects of dyspnea. Intercepts were lower in the second compared to the first session. Fear of Suffocation was associated with flatter slopes. Test-retest reliabilities were low to moderate suggesting that perceptual sensitivity to dyspnea is less stable than commonly assumed.

Modeling the development of panic disorder with interoceptive conditioning.

Panic disorder is characterized by the paroxysmal occurrence and fear of bodily symptoms. In recent years it has been proposed that patients "learn" to fear cardiorespiratory sensations through interoceptive conditioning. This study sought to model the initial stage of this process in healthy volunteers (N=44) using mild cardiac sensations. An additional aim was to explore whether anxiety sensitivity - a known risk factor for panic disorder - modulates such interoceptive learning. Infusions of pentagastrin and saline were used to manipulate the presence versus absence of cardiac sensations, respectively, and served as conditioned stimuli in a differential interoceptive conditioning paradigm. Inhalation of 35% CO2-enriched air served as the panicogenic, unconditioned stimulus (UCS). In half of the participants ("prepared" condition), cardiac sensations caused by pentagastrin were followed by inhalation of CO2-enriched air (penta CS+), whereas the absence of such sensations (saline) was followed by room air (saline CS-). The reversed combination ("unprepared" condition) was used in the other half of the participants. Conditioning effects showed up for self-reported UCS-expectancy, but not for skin conductance and anxiety ratings. Only participants from the prepared group learned to expect the UCS, and differential learning was impaired with higher scores on anxiety sensitivity. Expectancy learning was more easily established towards the presence compared to the absence of cardiac sensations, whereas the reverse effect was observed for safety learning. Modeling impaired discriminatory learning and the moderating effect of anxiety sensitivity provides new insight in the development of panic disorder.

Defensive activation to (un)predictable interoceptive threat: The NPU respiratory threat test (NPUr).

Potentially life-threatening interoceptive sensations easily engage the behavioral defensive system. Resulting fear and anxiety toward interoceptive threat are functionally distinct states that are hypothesized to play a prominent role in the etiology of panic disorder. The present study aimed to investigate whether fear- and anxiety-potentiated startle responses occur to predictable and unpredictable interoceptive threat, respectively. Therefore, we modified the NPU threat test (Schmitz & Grillon, ) and replaced the aversive electrocutaneous stimulus with an aversive interoceptive stimulus (a breathing occlusion, making it briefly impossible to breathe). Healthy participants (N = 48) underwent three instructed conditions. A visual cue signaled the occlusion in the predictable condition (P), whereas another cue was unrelated to the occurrence of the occlusion in the unpredictable condition (U). The safe condition (N) also had a visual cue, but no occlusion. Both fear- and anxiety-potentiated startle blink responses were observed in response to predictable and unpredictable respiratory threat, respectively. The current study presents and validates the NPU respiratory threat test (NPUr) as an ecologically valid paradigm to study both anxiety and fear in response to a panic-relevant interoceptive threat. The paradigm allows future testing of contextual generalization, investigation of different clinical groups, and more explicit comparisons of defensive responding to interoceptive versus exteroceptive threats.

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.

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.

Resting heart rate variability predicts safety learning and fear extinction in an interoceptive fear conditioning paradigm.

This study aimed to investigate whether interindividual differences in autonomic inhibitory control predict safety learning and fear extinction in an interoceptive fear conditioning paradigm. Data from a previously reported study (N = 40) were extended (N = 17) and re-analyzed to test whether healthy participants' resting heart rate variability (HRV) - a proxy of cardiac vagal tone - predicts learning performance. The conditioned stimulus (CS) was a slight sensation of breathlessness induced by a flow resistor, the unconditioned stimulus (US) was an aversive short-lasting suffocation experience induced by a complete occlusion of the breathing circuitry. During acquisition, the paired group received 6 paired CS-US presentations; the control group received 6 explicitly unpaired CS-US presentations. In the extinction phase, both groups were exposed to 6 CS-only presentations. Measures included startle blink EMG, skin conductance responses (SCR) and US-expectancy ratings. Resting HRV significantly predicted the startle blink EMG learning curves both during acquisition and extinction. In the unpaired group, higher levels of HRV at rest predicted safety learning to the CS during acquisition. In the paired group, higher levels of HRV were associated with better extinction. Our findings suggest that the strength or integrity of prefrontal inhibitory mechanisms involved in safety- and extinction learning can be indexed by HRV at rest.

Categorical interoception: perceptual organization of sensations from inside.

Adequate perception of bodily sensations is essential to protect health. However, misinterpretation of signals from within the body is common and can be fatal, for example, in asthma or cardiovascular disease. We suggest that placing interoceptive stimuli into interoceptive categories (e.g., the category of symptoms vs. the category of benign sensations) leads to perceptual generalization effects that may underlie misinterpretation. In two studies, we presented stimuli inducing respiratory effort (respiratory loads) either organized into categories or located on a continuous dimension. We found pervasive effects of categorization on magnitude estimations, affective stimulus evaluations, stimulus recognition, and breathing behavior. These findings indicate the need for broadening perspectives on interoception to include basal processes of stimulus organization, in order for interoceptive bias to be understood. The results are relevant to a wide range of interoception-related phenomena, from emotion to symptom perception.

Breath holding duration as a measure of distress tolerance: examining its relation to measures of executive control.

Recent research considers distress (in)tolerance as an essential component in the development of various forms of psychopathology. A behavioral task frequently used to assess distress tolerance is the breath holding task. Although breath holding time (BHT) has been associated with behavioral outcomes related to inhibitory control (e.g., smoking cessation), the relationship among breath holding and direct measures of executive control has not yet been thoroughly examined. The present study aims to assess (a) the BHT-task's test-retest reliability in a 1-year follow-up and (b) the relationship between a series of executive function tasks and breath holding duration. One hundred and thirteen students completed an initial BHT assessment, 58 of which also completed a series of executive function tasks [the Wisconsin Card Sorting Test (WCST), the Parametric Go/No-Go task and the N-back memory updating task]. A subsample of these students (N = 34) repeated the breath holding task in a second session 1 year later. Test-retest reliability of the BHT-task over a 1-year period was high (r = 0.67, p < 0.001), but none of the executive function tasks was significantly associated with BHT. The rather moderate levels of unpleasantness induced by breath holding in our sample may suggest that other processes (physiological, motivational) besides distress tolerance influence BHT. Overall, the current findings do not support the assumption of active inhibitory control in the BHT-task in a healthy sample. Our findings suggest that individual differences (e.g., in interoceptive or anxiety sensitivity) should be taken into account when examining the validity of BHT as a measure of distress tolerance.