Fear-conditioned respiration and its association to cardiac reactivity
Introduction
Both clinical phenomenology and theory highlight the centrality of respiratory behavior and respiratory distress in states of fear (e.g., Ley, 1985, Gorman et al., 2000, Sinha et al., 2000, Wilhelm et al., 2001). Despite this, ventilatory correlates of conditioned fear responses in humans are not well documented, perhaps because, compared to other psychophysiological measures of learning (e.g., heart rate), changes in the mechanics of respiration are slower and more variable. A more tractable respiratory parameter, however, may be carbon dioxide pressure, since, in many circumstances, healthy subjects are able to regulate arterial carbon dioxide pressure, maintaining it within relatively narrow limits. As a consequence, normal breathing is characterized by little variability in carbon dioxide pressure (Shea, 1997), compared to the variability in respiratory timing and volume parameters (Bruce and Daubenspeck, 1995). In the current study, we assessed end-tidal carbon dioxide pressure (PetCO2, a valid approximation of arterial CO2 pressure; Gardner, 1996, Pahn et al., 1987) during affective conditioning. PetCO2 is thought to be less variable than timing and volume parameters of breathing. Moreover, it is the only relevant outcome measure in the context of hyperventilation, which reflects a breathing pattern in excess of metabolic needs that occurs during emotional arousal, particularly fear (Van Diest et al., 2001a, Van Diest et al., 2001b, Van Diest et al., 2005).
The control of breathing is a complex interplay that relies on many factors, including the bulbopontine respiratory network, central and peripheral chemoreceptor control, modulation of respiratory muscles by mechanoreceptors, and numerous suprapontine networks located in the limbic, cerebellar, and cortical areas (Gallego et al., 2001, Shea, 1996). It is not currently known how these different networks interact during an emotional event and in which measures they are reflected. Addressing this concern, Boiten, 1993, Boiten, 1998 suggested that, in addition to assessing traditional respiratory parameters of depth (tidal volume) and rate (total cycle time, inspiratory time, expiratory time and post-expiratory pause) of breathing, compound measures should also be pursued. One such parameter is the ratio of inspiratory time to the total breathing cycle time (inspiratory duty cycle), which reflects the cyclical on/off switching of the central inspiratory drive mechanism (Gautier, 1980). Several authors suggest that, in contrast to volume parameters, this timing parameter is weakly controlled by the chemical drive to breathe, allowing for its modulation by non-metabolic factors (Gallego et al., 1996, Rafferty and Gardner, 1996).
Thus, to the extent that respiratory changes in anticipation of an aversive event are not driven by changes in metabolism, one would expect to see effects of affective learning on timing, compared to volume parameters. This is exactly what has been observed in studies of humans using a standard aversive conditioning paradigm (e.g., tone CS and shock US; Ley, 1999). Obrist (1968) described important interindividual differences in the direction of the conditioned breathing responses: whereas most participants showed a slightly increased breathing frequency following conditioning, a subgroup of participants showed a marked decrease in respiratory activity in response to the CS. The latter also showed a more sustained conditioned cardiac deceleration.
Similar to respiration, fear-conditioned heart rate responses also show different patterns among individuals (Hamm and Vaitl, 1996, Hodes et al., 1985, Moratti and Keil, 2005). Heart rate decreases or increases have been interpreted as distinguishing between defensive attention and fear in the context of the defense cascade model (Lang et al., 1997). This model describes an aversive motivational circuit that, with increasing arousal, triggers reactions ranging from orienting to fight/flight. The associated autonomic and somatic responses can be functionally organized into two broad output classes of defensive immobility and attention (i.e., freezing and hypervigilance in which the organism is passive, but primed to respond) and defensive action (contextual variations in fight/flight that are more or less direct responses to nociception or imminent attack).
Whereas defensive attention is associated with cardiac deceleration, cardiac acceleration prepares the organism to actively escape from an imminent threat, and previous studies have found that different individuals show different cardiac reactions following aversive conditioning (Hamm and Vaitl, 1996, Hodes et al., 1985). For instance, when a picture was paired with a loud noise, participants could be clustered based on their conditioned heart rate responses, which consisted of acceleration or deceleration (Hodes et al., 1985). Compared to individuals showing cardiac deceleration, individuals showing a conditioned cardiac acceleration to the CS+, also reported greater fear to the CS+ than the CS− (Hodes et al., 1985), showed more resistance to extinction in electrodermal responses (Hodes et al., 1985) and displayed potentiated startle responses to the CS+ (Hamm and Vaitl, 1996). This pattern of results is interpreted as indicating that, whereas all participants learned an anticipatory orienting response (late interval heart rate deceleration), only accelerators showed a conditioned preparation for defensive action.
Several findings from other studies suggest that respiration also distinguishes between defensive attention and action. Decreases in breathing frequency and/or a tendency towards expiration (i.e., decreased inspiratory duty cycle time) have been reported as part of the orienting response and during sustained attention in humans (Barry, 1982, Boiten et al., 1994, Denot-Ledunois et al., 1998, Obrist et al., 1969, Stekelenburg and Van Boxtel, 2001). This may either be a direct consequence of a decreased somatic activity during defensive immobility (Obrist et al., 1969), or, it may be functional to inhibit breathing under threat for two reasons: (1) prompting an increase in blood flow to the brain, due to the cerebrovascular dilating effect of CO2 (Giardino et al., 2007, Kastrup et al., 1998), or (2) suppressing the noise associated with breathing in the presence of a predator (Fokkema, 1999). Defensive action, on the other hand, seems to prompt an increased cardio-respiratory activation, as well as a tendency towards hyperventilation (decreased PetCO2; Van Diest et al., 2001a, Van Diest et al., 2001b).
The present study aimed to investigate fear conditioning of breathing behavior. To this end, respiratory and PetCO2, as well as heart rate responses, were studied during a prototypical affective learning paradigm. Pictures of human faces served as the conditioned stimulus (CS), a loud human scream as the unconditioned stimulus (US). We expected that differential conditioning of respiratory timing parameters, PetCO2 and heart rate would be established during acquisition and dissipate during a subsequent extinction phase. In addition, we expected that heart rate responses would closely follow respiratory timing and PetCO2 responses.
Section snippets
Participants
Forty-two students aged 18–31 years old (mean age 20 years; 24 women) from the University of Florida volunteered to participate in return for course credit in their General Psychology class.
Design and materials
A differential delay-conditioning paradigm was used. Coloured pictures of neutral or angry male faces (“Karolinska Directed Emotional Faces”; Lundqvist et al., 1998) presented for 8 s served as conditioned stimuli. A 95-dB human scream (6 s duration) presented at picture offset was the unconditioned stimulus.
Respiration
During acquisition, participants breathed faster (had a shorter total respiratory cycle time) in response to the CS+ compared to the CS−, F(1, 36) = 6.66, p < .01, ; see Table 1.
A significant conditioning effect was also found for inspiratory duty cycle time: the relative inspiratory time increased more in response to the CS+ than to the CS−, F(1, 33) = 4.77, p < .05, , see Table 1. No significant-conditioning effects were found for the subcomponents of the respiratory cycle time
Discussion
The present study documents aversive conditioning of respiratory and subjective responses in a human fear conditioning paradigm using human faces as the CS and a loud human scream as the US. Following the experiment, participants rated the CS+, but not the CS− higher in arousal and in unpleasantness as compared to prior to the conditioning procedure. The primary finding, however, was that participants learned to breathe faster with a higher inspiratory duty time in response to the CS+ compared
Acknowledgements
This research was supported in part by grants from the National Institute of Dental Research (DE 13956) to Margaret M. Bradley and the National Institute of Mental Health (P50 MH 72850) to Peter J. Lang. The research was conducted while Ilse Van Diest was at the NIMH Center for the Study of Emotion and Attention at the University of Florida, funded as a post-doctoral research associate by the Fund of Scientific Research – Flanders.
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