Chapter Contents:
a. Definition
b. What aspect of allostasis does modes of cardiac control potentially measure?
c. How are modes measured?
d. Is the mode of cardiac control related to chronic stress?
e. Does modes of cardiac control vary with psychosocial factors?
f. References

Definition

Heart rate reactivity refers to the mean increase in heart rate observed in response to a task or stressor. The conditions under which reactivity scores should be based on simple change scores (i.e., HR_{stressor period} -HR_{prestressor period}) versus residualized change scores are now established, and over the past decade attention has turned to the use of heart rate reactivity as an index of individual differences in arousability, stress reactivity, or proclivity for disease. An individual's classification as high or low in HR reactivity in a given situation ignores possible differences in the autonomic origins of this reactivity, however. An individual's classification as high in HR reactivity in a given situation could originate in elevated sympathetic reactivity, vagal withdrawal, or reciprocal activation of the sympathetic and vagal outflows to the heart. Research on cardiac reactivity has generally emphasized variations in HR reactivity rather than variations in the autonomic origins of HR reactivity. This classification of individuals in terms of HR reactivity relegates variations in the autonomic origins of HR reactivity to the error term, a practice that may obscure the relationship between autonomic responses to stressors and behavioral, humoral, or clinical outcomes. This practice also ignores the manner in which HR reactivity is orchestrated by the brain - that is, the "mode of autonomic control."

Quantifying differences in the autonomic determinants of HR reactivity across situations or individuals requires replacing the conceptualization of HR reactivity as a unidimensional (e.g., sympathetic activation) vector with a two-dimensional autonomic plane. Berntson, Cacioppo, and Quigley (1991) outlined such an autonomic model and reviewed the evidence for the hypothesis that HR reactivity can derive from multiple modes of autonomic control (Berntson, Cacioppo, & Quigley, 1993; Cacioppo, 1994). According to this conceptualization, reliable differences exist not only in HR reactivity to psychological stressors, but also in sympathetic cardiac reactivity and in vagal cardiac reactivity. Nine possible modes of control are possible: 1) reciprocal sympathetic activation, in which sympathetic activity increases and parasympathetic activity decreases; 2) reciprocal parasympathetic activation, in which parasympathetic activity increases and sympathetic activity decreases; 3) uncoupled sympathetic activation, in which sympathetic activity increases and parasympathetic activity remains unchanged; 4) uncoupled sympathetic inhibition, in which sympathetic activity decreases and parasympathetic activity remains unchanged; 5) uncoupled parasympathetic activation, in which parasympathetic activity increases and sympathetic activity remains unchanged; 6) uncoupled parasympathetic inhibition, in which parasympathetic activity decreases and sympathetic activity remains unchanged; 7) coactivation, in which activity in both branches increases; 8) coinhibition, in which both branches decreases; and 9) nonresponse, in which activity in both branches is unchanged from basal levels. These distinct modes of autonomic control have different response properties that reflect the orchestration of two antagonistic systems. Reciprocal modes of autonomic activation, for instance, are characterized by the largest dynamic ranges, directional stability, and response lability, whereas coactivation/coinhibition modes of autonomic activation are characterized by the smallest dynamic ranges, directional stability, and response lability. (The response properties of uncoupled modes of autonomic control fall between these extremes.) Thus, reciprocal modes are effective control mechanisms for changing autonomic state quickly (as in baroreceptor-medidated cardiovascular responses to hypotensive states) but the responses tend to be stereotyped and may take a toll across time on visceral systems. Coactivational states, in contrast, can result in substantial neural activation of the heart but little if any appreciable cardiovascular response because of the antagonistic chronotropic effects of sympathetic and vagal activation of the heart. Such coactivational states, which have been observed in response to conditioned stimuli in aversive classical conditioning studies, appear to foster visceral flexibility in conditions in which the most appropriate behavioral responses are uncertain.

What Aspect of Allostasis Does Modes of Cardiac Control Potentially Measure?

Modes of cardiac control appear to reflect dynamic and cumulative allostatic load. Nomethetic analyses have revealed that brief psychological stressors (e.g., mental arithmetic, public speaking) produce reciprocal sympathetic activation of the heart - that is, increased sympathetic activation in conjunction with vagal withdrawal. Importantly, individual differences in modes of cardiac control studies are also evident in studies of psychological stressors, with individuals who show greater sympathetic activation also showing poorer immunosurveillance. The possibility that modes of cardiac control reflect cumulative allostatic load is supported by recent research in which modes of control in response to brief stressors was examined in caregivers and age-matched controls. Results revealed that more caregivers were characterized by reciprocal sympathetic activation than controls.

How Are Modes Measured?

To measure modes of cardiac control requires a means of measuring the separable autonomic origins of HR reactivity. Autonomic blockade and noninvasive measures of respiratory sinus arrhythmia (RSA) and cardiac preejection period (PEP) have been used for this purpose. Although there are important limitations to the use of PEP and RSA measures, both psychometric studies (Cacioppo, Uchino, & Berntson, 1994) and autonomic blockade research (e.g., Berntson et al., 1994; Cacioppo, Berntson, et al., 1994) have shown that these measures can serve as noninvasive indices of the autonomic control of the heart in some stress-reactivity protocols.

In autonomic blockade research, RSA was found to be the best noninvasive marker of vagal control of the heart whereas PEP was found to be the best noninvasive marker of sympathetic control of the heart (Berntson et al., 1994; Cacioppo et al., 1994). In an illustrative psychometric study, the interrelationships among HR, RSA, and PEP reactivity measures were found to be consistent with the use of RSA and PEP reactivity as noninvasive indices of the vagal and sympathetic determinants, respectively, of stress-induced HR reactivity (Cacioppo, Uchino, et al., 1994). Basal HR, task HR, and HR reactivity (calculated as a simple change score and as a residualized change score) during sitting were correlated with the corresponding index during standing, and we performed comparable analyses for the indices based on RSA and on PEP to determine test-retest reliabilities at two different basal levels of autonomic control. Results revealed that test-retest correlations ranged from .53 to .82 (ps < .01). The finding that HR, RSA, and PEP reactivity indices during sitting were highly predictive of the corresponding reactivity measures during standing provided support for the use of PEP and RSA as indices of the autonomic substrates of cardiac reactivity in psychological stress-reactivity paradigms. Subsequent analyses (whether we used simple change scores or residualized change scores) provided additional evidence:

1. The correlations between stressed-induced changes in RSA and in HR were all negative, reflecting the negative chronotropic effects of vagal input to the heart. That is, individuals who displayed stress-induced increases in RSA also were likely to show small increases in HR, whereas individuals who showed stressed-induced decreases in RSA (reflecting vagal withdrawal) also displayed large increases in HR. Furthermore, the median correlation among these measures was statistically significant (median r = -.53, p < .01).
2. The correlations among stressed-induced changes in PEP and in HR were uniformly large and negative, consistent with the notion that stress-induced sympathetic cardiac activation shortens PEP and elevates HR. The median correlation among these measures was also statistically significant (median r = -.54, p < .01).
3. The correlations between the RSA and PEP reactivity measures revealed that these indices did not consistently covary across individuals, and the median correlation among these measures was not significant (median r =.29, n.s.). These results are consistent with the notion that stress-induced changes in RSA and in PEP can vary independently and that each predicts unique autonomic determinants of HR reactivity.

Is the Mode of Cardiac Control Related to Chronic Stress?

Although research addressing whether modes of cardiac control are related to chronic stress and health is still largely lacking, we were able to address this question in a recent study investigating the autonomic and endocrine responses to short- and long-term psychological stress in 27 women caring for a spouse with a progressive dementia (high chronic stress) and 37 controls who were category matched for age and family income (low chronic stress). Measures were taken before (low acute stress) and immediately following (high acute stress) exposure to the laboratory stressors. Affective measures confirmed that acute and chronic stressors were associated with dysphoria. Chronic stress was associated with enhanced cardiac sympathetic activation (as indexed by PEP), elevated blood pressure, and heightened plasma levels of ACTH, whereas acute stress produced elevated heart rate, cardiac sympathetic activation, increased systolic blood pressure, and higher plasma concentrations of ACTH, cortisol, and epinephrine. No significant differences between caregivers and controls were found in the levels of any individual psychological, autonomic, or neuroendocrine response to the laboratory stressors. Caregivers, however, were significantly more likely than control participants to demonstrate a reciprocally activated sympathetically dominant mode of autonomic response to the brief stressors.

Specifically, changes in PEP and RSA, which as expected were uncorrelated (r = .03, n.s.), were used to classify the autonomic responses of caregivers and controls. The results, which are depicted in Figure 1, revealed that caregivers were characterized by a more stereotypic reciprocal sympathetic activation of the heart than were control participants. Of the 31 control participants for whom we had complete data, 11 displayed reciprocal sympathetic activation (35.5%), 1 displayed reciprocal parasympathetic activation (3.2%), 15 were coactivated (48.4%), and 4 were coinhibited (12.9%). In contrast, of the 22 caregivers for whom we had complete data, 15 displayed reciprocal sympathetic activation (68.2%), 1 displayed reciprocal parasympathetic activation (4.5%), 4 were coactivated (18.2%), and 2 were coinhibited (9.1%). Both of these distributions were significantly different from the equal distribution that would be expected by chance, control X² (df = 3) = 15.84, p < .002, caregiver X² (df = 3) = 22.73, p < .001. In order to determine whether the two distributions differed from each other, a chi-square analysis of the caregiver values was carried out, using the frequency distribution of the control group as the expected distribution. The two distributions were significantly different, X² (df = 3) = 11.14, p = .01. Thus, the analysis of the modes of autonomic control of the heart, which is the first of this kind to our knowledge, suggests that caregiving stress affects the manner in which autonomic responses are orchestrated by the brain. Together, these results suggest that the chronic stress of caregiving altered sympathetic and neuroendocrine tonus and led to a shift in the autonomic control of phasic responses to short-term stressors.

Does Modes of Cardiac Control Vary with Psychosocial Factors?

There is a paucity of research addressing the relationship between modes of cardiac control and psychosocial factors. The aforementioned study of caregivers and controls is encouraging in this regard, however. Prior studies have contrasted the psychological and physiological responses of caregivers of relatives with Alzheimer's disease (AD) with age and sociometrically matched controls. Relatives who provide long-term care for a patient with AD report high levels of stress and dysphoria and clinical depression as they attempt to cope with patients' difficult behavior. Caring for a spouse with AD can be stressful for a number of reasons. Seeing the deterioration of a loved one, dealing with the patient's difficult behavior, and struggling with the financial burdens often posed by the patient's treatment may all contribute to the caregiver's perception of stress. Indeed, research has shown how multidimensional the process of caregiving for a loved one with AD can be. For instance, "anticipatory grief" is often present for caregivers, and the caregiving process is described in terms of stages and themes that can include loss of the relationship, expectancy of death, postdeath relief.

The varied stages of caregiving suggest that the stress a caregiver experiences may change over time. For instance, many of the sources of stress are no longer present once the AD patient dies and the caregiver no longer needs to worry about the amount of time that caregiving takes or the patient's difficult behavior and suffering. The absence of these aspects of caregiving could result in fewer difficulties for bereaved caregivers. However, previous research focusing primarily on depression has shown that bereaved caregivers are often no better off than their active counterparts. For instance, bereaved and active caregivers do not differ in terms of syndromal depression or depressive symptoms. Thus, while the extant evidence supports the idea that there are many components that can contribute to the stress caregivers experience, it is not clear that the death of the AD patient has the effect of "lightening the load." It is therefore noteworthy that both active and bereaved caregivers were characterized by the mode of reciprocal sympathetic activation to the brief psychological stressors.

References

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Berntson, G. G., Cacioppo, J. T., & Quigley, K. S. (1991). Autonomic determinism: The modes of autonomic control, the doctrine of autonomic space, and the laws of autonomic constraint. Psychological Review, 98, 459-487.

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