Vagal modulation of responses to mental challenge in posttraumatic stress disorder

Abstract

Background: Studies of the autonomic nervous system in posttraumatic stress syndrome (PTSD) have focused on the sympathetic modulation of arousal and have neglected the parasympathetic contribution. This study addresses the parasympathetic control of heart rate in individuals who have survived traumatic events.

Methods: Twenty-nine survivors, 14 with current PTSD and 15 without, participated in the study. The groups were comparable with regard to age, type of trauma, time since the latest traumatic event, and lifetime exposure to traumatic events. Electrocardiograms were recorded during rest and an arithmetic task. Heart period, respiratory sinus arrhythmia (RSA), and the amplitude of the Traube–Hering-Mayer wave were quantified.

Results: The groups did not differ on resting measures. During the arithmetic task, the past trauma group showed a significant increase in RSA (p < .007), whereas the PTSD group did not. In the past trauma group only, RSA and heart period were highly correlated (r = .75), thereby suggesting that the response to challenge was under vagal control.

Conclusions: Trauma survivors who develop PTSD differ from those who do not in the extent to which their heart rate response to challenge is controlled by vagal activity. Responses to challenge in PTSD may be mediated by nonvagal, possibly sympathetic mechanisms.

Introduction

Psychophysiologic research of posttraumatic stress disorder (PTSD) is expanding rapidly (for a review, see Orr 1997). Due to the prominence of hyperarousal symptoms in PTSD, research has focused primarily on the sympathetic branch of the autonomic nervous system. Previous studies have consistently shown an elevated phasic activation of the sympathetic nervous system in PTSD in response to trauma-related cues (Murburg et al 1995), to chemical challenges such as yohimbine (Southwick et al 1997), and to anxious expectation (e.g., McFall et al 1992). Elevated heart rate levels upon admission to an emergency room, following trauma, have been reported in individuals who later developed PTSD (Shalev et al 1998). However, baseline sympathetic activity is not believed to be higher in PTSD McFall and Murburg 1994, Murburg et al 1995.

Overlooked in the psychophysiologic investigation of PTSD is the parasympathetic nervous system. The parasympathetic nervous system, and especially the vagal regulation of heart rate, is involved in stress reactions and the long-term consequences of stress (e.g., Porges 1992). The vagus nerve, the 10th cranial nerve, serves as a conduit from the brain stem to several visceral organs. The myelinated cardioinhibitory vagal fibers, which originate in the nucleus ambiguus and terminate on the cardiac sinoatrial node, contribute to the regulation of the heart rate response to and the recovery from stress. These vagal fibers functionally slow heart rate and actively inhibit the sympathetic influences to the heart (Vanhoutte and Levy 1979). The parasympathetic control of the heart is often synergistic and reciprocal with the energetic function of the sympathetic nervous system. For example, to support the metabolic demands associated with body movement, withdrawal of the “vagal brake” potentiates the expression of the sympathetic influences on the heart.

The vagal control of heart rate via the myelinated vagal fibers varies with respiration (Richter and Spyer 1990). Thus, the vagal influence to the heart may be evaluated by quantifying the amplitude of rhythmic fluctuations in heart rate that are associated with breathing frequencies (respiratory sinus arrhythmia [RSA]).

Methods for measuring vagal activity by quantifying RSA in humans have been validated and refined during the past decade Berntson et al 1991, Berntson et al 1993, Berntson et al 1994a, Porges and Bohrer 1990, Porges and Byrne 1992. Time series analyses provide widely accepted methods to compute RSA (e.g., Berntson et al 1997, Porges and Bohrer 1990). In this study, RSA was defined as the heart rate variability in the frequency band between 0.12 and 0.40 Hz. This frequency band selectively reflects the activity of the vagal efferent fibers originating in the nucleus ambiguus and is characterized by a respiratory rhythm Porges 1995, Porges 1997. The respiratory rhythm, although influenced by peripheral feedback, reflects a central respiratory rhythm emerging from the interneuronal communication between the nucleus ambiguus and the nucleus of the solitary tract (Richter and Spyer 1990).

Another measure of heart rate variability may be derived from quantifying the amplitude of an oscillation known as the Traube-Hering-Mayer (THM) wave (e.g., Hatch et al 1986) or 0.1 Hz wave (for overview, see Byrne and Porges 1992). The THM wave is characterized by a slower heart rate rhythm, usually observed between the frequencies of 0.06 and 0.1 Hz. The neurophysiologic mechanisms mediating the THM wave, although less understood, are assumed to be related to the regulation of blood pressure, since similar oscillations are observed in blood pressure. Since research has demonstrated that the two components of heart rate variability may respond differentially (e.g., Byrne and Porges 1992, Hatch et al 1986) and the cardiac contribution to blood pressure involves sympathetic influences, several researchers have assumed that the amplitude of the THM wave reflects sympathetic as well as vagal mechanisms (e.g., Akelrod et al 1981). However, since blocking the vagal influence on the heart with atropine removes both RSA and THM wave (e.g., Goddard et al 1995), the amplitude of the THM wave may reflect the joint effect of both vagal pathways originating from both vagal source nuclei in the medulla, the nucleus ambiguus, and the dorsal motor nucleus (Porges 1995).

Vagal influences to the heart serve to dampen the sympathetic reactions to stress and to promote calm behavioral states and self-regulation (Porges 1995). Consistent with this protective function of vagal tone, low-amplitude RSA has been associated with vulnerability to the effect of stress. Low-amplitude RSA has been associated with medically and psychologically stressed populations such as premature neonates Fox and Porges 1985, Porges 1992, infants Izrad et al 1991, Porges et al 1994, school-age children (Suess et al 1994), and neurosurgical patients (Donchin et al 1992). An increase in tonic levels of RSA has been observed in patients with major depressive disorder following successful treatment (Balogh et al 1993). Moreover, general anxiety disorder patients who exhibited less reduction in RSA following imipramine also exhibited greater symptom reduction (McLeod et al 1992).

In addition to the research on tonic levels of RSA, RSA is responsive to psychologic and behavioral demands. A marked reduction in RSA amplitude has been observed during procedures that produce panic symptoms (George et al 1989) as well as during tasks requiring sustained attention or increased motor activity (e.g., Hatfield et al 1998). Neurophysiologically, the amygdala may play a role in translating the psychologic experiences associated with fear and trauma into the vagal responses. The amygdala, a limbic structure that has been postulated to play a role in fear conditioning and in PTSD (e.g., Davis et al 1997), projects to the nuclei of the vagus in the brain stem (Schwaber et al 1980), and may effect the vagal response to fear.

Despite its hypothetical relevance to PTSD, there are only two published reports of parasympathetic activity in PTSD Cohen et al 1997, Cohen et al 1998. Cohen and colleagues reported significantly lower resting RSA in PTSD, and absence of autonomic response to the recounting of the triggering stressful event. Our study was conducted to ask several questions relating vagal regulation of the heart in PTSD. First, the study evaluated whether base levels and reactivity of the amplitude of RSA were different in PTSD than they were in participants who had experienced trauma without developing PTSD. Second, the study evaluated the vagal contribution to the heart rate responses observed during the mental arithmetic challenge. It was hypothesized that the vulnerability to stress, characteristic of PTSD, would be paralleled by both low-amplitude RSA and a reliance on neural mechanisms, other than vagal, to mediate heart rate responses to stress.