Respiratory sinus arrhythmia as an index of parasympathetic cardiac control during the cardiac defense response

Biological Psychology 35 (1993) 17-35 0 1993 Elsevier Science Publishers B.V. All rights reserved

17 0301.0511/93/$06.00

Respiratory sinus arrhythmia as an index of parasympathetic cardiac control during the cardiac defense response Gustav0

A. Reyes de1 Paso, Juan Godoy

and Jaime

Vila

Departamento de Personalidad, Evaluacibn y Tratamiento Psicol6gico, Facultad de Filosofk y Letras (Edificio B), University of Granada, 18011 Granada, Spain

The respiratory sinus arrhythmia (RSA) is being used by psychophysiologists as an index of parasympathetic cardiac control mainly in tasks within a tonic response paradigm. In procedures which engender phasic responses the belief exists that the RSA could be contaminated by slower nonrhythmic trends in the data. In the present paper two experiments are reported. The first experiment valuates, through beta-adrenergic blocking, the validity of the RSA as an index of phasic changes in parasympathetic cardiac control during phasic changes in sympathetic activation: the cardiac defense response (CDR) to intense auditory stimulation. The second experiment examines the RSA response pattern associated with the CDR. The results of the first experiment, that the RSA response pattern is not significantly influenced by the beta-adrenergic block, suggest that RSA may index phasic changes in parasympathetic cardiac control during phasic response procedures such as those which elicit the CDR. The results of the second study indicate that the CDR is associated with a pattern of changes in RSA made up of four components -reduction, increase, reduction and increasewhich run parallel, but in opposite direction, to the heart rate changes. The results of both studies are consistent with a parasympathetic mediation of the first two components of the CDR and a sympathetic-parasympathetic interactive mediation of the last two components. Keywords: Respiratory pathetic.

sinus arrhythmia,

defense

response,

heart

rate, beta-blockade,

parasym-

1. Introduction Respiratory sinus arrhythmia (RSA) is a phenomenon which consists of the occurrence of cyclical fluctuations in the heart rate in close correspondence with the respiratory phase: increases in heart rate during inspiration and decreases during expiration, although the exact phase may depend upon Correspondence to: Gustav0 A. Reyes de1 Paso, Departamento de Personalidad, Tratamiento Psicologico, Facultad de Filosofia y Letras (Edificio B), Universidad 18011 Granada, Spain.

Evaluation y de Granada,

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the respiratory rate. These fluctuations depend on specific respiratory patterns. Patterns characterized by low breathing rates and high amplitudes result in maximum RSA changes, while patterns characterized by high rates and low amplitudes reduce it drastically (Eckberg, 1983). Several different physiological mechanisms are implicated in RSA. However, the final efferent pathway is due to the inhibition of the vagus during inspiration (Katona, Poitras, Barnett & Terry, 1970). Given this vagal modulation of the RSA, its amplitude -the difference in. milliseconds between the minimum heart period found during inspiration (when vagal activity is inhibited) and the maximum heart period found during expiration (period in which vagal activity is present)has been proposed as a non-invasive index of the parasympathetic cardiac control (Fouad, Tarazi, Ferrario, Fighaly & Alicandro, 1984; Katona & Jih, 1975; Lipson & Katona, 1979; McCabe, Yongue, Ackles & Porges, 198.5; McCabe, Yongue, Porges & Ackles, 1984; Yongue, McCabe, Kelley, Rivera & Porges, 1981; Yongue et al., 1982). RSA amplitude has been used, almost exclusively, as a measure of parasympathetic cardiac control in mental stress tasks where interest has been focused on tonic responses, using both time domain techniques -the peak-to-trough method(Grossman, Stemmler & Meinhardt, 1990; Grossman & Svebak, 1987) and frequence domain techniques -spectral analysis (Mulder, 1988). With respect to phasic response procedures, the idea exists that the peak-to-trough method -spectral analysis cannot be used because of violation of the assumption of stationaritycould be contaminated by slower, nonrhythmic trends in the data. This interference could distort the RSA amplitude values obtained, either in the direction of an overestimation or an underestimation. However, there are no strong theoretical or empirical grounds to support such an assumption under all phasic response conditions. For example, let us assume a phasic response in which first a sympathetic activation is produced followed by a sympathetic inhibition. In the first case, using the peak-to-trough method, the minimum heart period obtained during inspiration (vagal inhibition) would be contaminated by the concurrent sympathetic activation. With respect to obtaining the maximum heart period during expiration (vagal activation), this would be similarly contaminated by the sympathetic activation, since a sympathetic activation component would exist in addition to the vagal activation component. However, on making the subtraction between both heart periods the sympathetic components would cancel each other out, leaving uncontaminated the components that relate to parasympathetic activation. In the case of sympathetic inhibition the same would occur. The RSA would fluctuate over the nonrhythmic trend produced by the sympathetic inhibition. The only conditions that could generate contamination in the RSA amplitude would be changes in sympathetic activation sufficiently rapid to affect each respiratory phase differentially. However, given the slowness of

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the cardiovascular changes mediated by the sympathetic nervous system with respect to parasympathetic responsiveness (Davis, McCloskey & Potter, 1977; Koepchen, Kliissendorf & Sommer, 1981; Eckberg, Nerhed & Wallin, 1985) distorting conditions would rarely occur and the contamination produced would be small. Data from Grossman and Wientjes (1986) seem to agree with this view. These authors analyzed a period of cardiac activity of duration 1 min in order to obtain the average amplitude of the RSA, firstly, using the raw data with a complex and sizeable non-respiratory trend in the data and, secondly, with the trend filtered out. In spite of the short period used and the great non-respiratory fluctuation, the difference between the filtered and the unfiltered RSA amplitude estimates was only 2.7 ms. On the other hand, data from our laboratory (Reyes de1 Paso, 1992) show that the correlations between RSA amplitude and a set of cardio-respiratory variables (respiratory rate, respiratory periods, respiratory amplitude, heart period, heart rate, heart period variability and heart rate variability) are similar during rest (tonic paradigm) and intense auditory stimulation (phasic paradigm). In the present paper two studies are reported. The first aimed to evaluate the validity of the peak-to-trough method for RSA amplitude measurement as an index of phasic changes in parasympathetic cardiac control during responses which present phasic changes in sympathetic activity. For this the cardiac defense response (CDR) to intense auditory stimulation was selected, the RSA amplitude being analyzed both under normal conditions and under beta-adrenergic blockade. The second study was intended to examine the changes in the RSA amplitude associated with each accelerative and decelerative component of the CDR in order to evaluate its autonomic mediation. The CDR constitutes a particular type of phasic heart rate response to discrete intense or aversive stimuli. It has been traditionally considered as indicative of basic psychological processes, either cognitive (attention, perception, memory and so on) or motivational (drive, arousal, stress and so on) in nature, as well as of physiopathological processes presumably involved in the development of various cardiovascular and emotional disorders (coronary heart disease, hypertension, anxiety problems and so on). From a descriptive point of view, the CDR is characterized by a complex response pattern with four components, two accelerative and two decelerative in alternating order occurring within the 80 s post-stimulus (Fernandez, 1986; Vila & Fernandez, 1989). The amplitudes of the two accelerative components are greater than those of the two decelerative ones, the maximum amplitude of each component being reached approximately at 3, 15, 35 and 65 s respectively (latency), and the duration of each new component increasing progressively with respect to the previous one (Fernandez, 1986; Vila & Fernandez, 1989). Research into the physiological significance of this response pattern has focused on indirect measures of sympathetic activation such as the T-wave

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amplitude of the ECG, first differential of the carotid pulse (dP/dT) and pulse transit time (Turpin & Siddle, 1978, 1981; Fernandez & Vila, 1989a, 1989b). The results consistently suggest a clear sympathetic mediation of the second acceleration and second deceleration and a probable parasympathetic mediation of the first acceleration and first deceleration. This description and interpretation of the CDR, as a pattern of heart rate changes with both accelerative and decelerative components and both vagal and sympathetic mediation, is contrary to the traditional view on the defense reaction which assumes the unidirectionality (acceleration) of the heart rate changes and its exclusive sympathetic mediation (Bard, 1960; Cannon, 1929; Graham, 1979; Lisander, 1970), an assumption which rules out vagal influences and, in particular, the baroreceptor reflex in the mediation of the defense response. Although such an assumption has been questioned from several points of view -the involvement of the parasympathetic nervous system in stress and emotions has been clearly demonstrated by numerous authors (Adams, Baccelli, Mancia, & Zanchetti, 1971; Bond, 1943; Grossman and Svebak, 1987; Vingerhoets, 1985>- no research has been reported so far on measures of parasympathetic activation during the evocation of the CDR. The present paper is an attempt to provide data on this direction.

2. Experiment

1

To evaluate the validity of the peak-to-trough method as a measure of RSA amplitude during the CDR, the response pattern of the RSA amplitude was analyzed before and after the blockade of the sympathetic beta-adrenergic activity. If the response pattern is substantially similar it can be deduced that the said index is not significantly affected by the parallel changes in sympathetic activity. As a measure of sympathetic beta-adrenergic activity during the CDR, the stroke volume obtained through impedance cardiography was also recorded and analyzed (Sherwood et al., 1990). 2.1. Method 2.1.1. Subjects The subjects were six male medical students aged between 23 and 25. Each student received an amount of money for his participation. None of the subjects was receiving psychiatric or pharmacological treatment, none of them had histories of cardiovascular disorders, and physical examination revealed no ECG abnormalities. 2.1.2. Apparatus Respiratory activity was measured using a Respitrace (R) belt around half of the chest. The heart period was continuously recorded from lead II of the

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ECG by a Gould (R) amplifier. The stroke volume was obtained through an IFM/ Impedance Cardiograph (Model 400) device. A Letica LE-150 auditory stimulator and SUN-SE 20 headphones were used to present the auditory stimulus, which consisted of a distorted sound of frequency 400 Hz, intensity 109 dB, duration 0.5 s and a virtually instantaneous rise. 2.1.3. Procedure One hour prior to the registration of physiological measures subjects were provided with a peripheral intravenous line. Once in the laboratory, the subject sat in a comfortable armchair naked from the waist upwards. Then the experimenter placed, in this order, the metallic tapes for the registration of the impedance cardiography, the ECG electrodes, the transducer for the registration of the respiration and, lastly, the headphones. Then the experimenter left the subject’s room and turned down the lighting to a pre-established subdued level. The physiological reaction test consisted of 10 min of rest period and one trial of intense auditory stimulation. Once this first phase was over the drug was administered intravenously. Metoprolol, a specific beta-adrenergic (pl) block was chosen, so as not to influence the vasomotor activity, and administered in doses of lo-15 mg until an increase in the heart period of at least 25% was produced. The physiological reaction test was then repeated. 2.1.4. Data reduction and analysis Analysis of RSA amplitude and stroke volume was carried out using previously developed computer programs. The RSA amplitudes were obtained using the peak-to-trough method, as explained in the introduction, with the temporal phase relation between respiratory and cardiac activity adjusted in accordance with the results of Eckberg (1983). When the minimum heart period during inspiration is longer than the maximum heart period during expiration an RSA amplitude of zero is assigned to that respiratory cycle (Reyes de1 Paso, 1992). The stroke volume as an index of the sympathetic beta-adrenergic influences on the myocardium was recorded using the impedance cardiography method (Sherwood et al., 1990). Finally, in order to analyze the form of the RSA and the stroke volume responses to the auditory stimulus during the 80 s after stimulus onset, the same methodology used in the analysis of the form of CDR was applied (Vila and Fernandez, 1989). The RSA amplitude and stroke volume were obtained for the medians of ten successively longer intervals: two intervals of 3 s, two intervals of 5 s, three intervals of 7 s and three intervals of 13 s. Analysis of the results was undertaken by means of both visual and statistical scrutiny of the response pattern of RSA and stroke volume. Statistical analysis was by means of analysis of variance with within-group (repeated observations) factors. These factors were Form with 10 levels (the 10 medians) and Drug with 2 levels

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62k

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27

34

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) and after (- --) beta-adrenergic blockade. Fig. 1. RSA response pattern before ((Numbers on the horizontal axis represent the midpoints of the ten selected intervals.)

(present or absent). Because of the problem of violations of the homogeneity of covariance assumption in repeated measures designs, the GreenhouseGeisser epsilon correction was applied for the adjustment of the degrees of freedom. Results are reported with the original degrees of freedom and the corrected p-values. 2.2. Results After the administration of metroprolol the heart period increased by 29% (888 ms vs. 1146 ms), the effect of the drug being highly significant in the comparison of the rest periods (F(1,5) = 305.33, p < 0.00001). Figure 1 graphically illustrates the response pattern of the RSA amplitude before and after administration of the beta-adrenergic block. The (10 X 2) ANOVA showed a significant main effect of Form (F(9,45) = 3.46, p < 0.05). The Drug factor does not show any main or interaction effect. As can be seen in Fig. 1 the form of the response of the RSA amplitude is substantially similar before and after the administration of metroprolol. As regards stroke volume, Figure 2 graphically illustrates the response pattern before and after the administration of the beta-adrenergic block. The (10 X 2) ANOVA showed a significant main effect of Form (F(9,45) = 3.67, p < 0.05) and Drug (F(1,5) = 12.32, p < 0.05) and a significant Form X Drug interaction (F(9,45) = 3.23, p < 0.05). Before drug administration the Form factor was significant (F(9;45) = 3.95, p < 0.01). After metroprolol administration it did not pro-

GA

1

0 2

1

,

5

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Reyes de1 Paso et al. / RSA as index of cardiac control

I

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Fig. 2. Stroke volume response pattern before () and after (- --) beta-adrenergic blockade. (Numbers on the horizontal axis represent the midpoints of the ten selected intervals.)

duce significant effects. The response pattern obtained shows an increase from the third median (second 91, up to the ninth median (second 64) after stimulus presentation. 2.3. Discussion The response pattern of the RSA amplitude is substantially similar before and after the beta-adrenergic block as suggested by the lack of significant effect of the Drug factor or its interaction with Form. On the other hand, the results obtained with respect to stroke volume, before drug administration, suggest a clear sympathetic activation in association with the second accelerative component of the CDR, a result which is similar to those reported in previous studies using other indexes of sympathetic activation (Turpin & Siddle, 1978, 1981; FemLndez & Vila, 1989a). The results obtained in this experiment are consistent with those obtained by Grossman and Wientjes (1986) with respect to the non-alteration of the RSA amplitude values by complex trends present in the data and by Reyes de1 Paso (1992) with respect to the non-alteration of the correlations between the RSA amplitude and various cardio-respiratory variables during the evocation of the CDR in relation to the rest period. However, in the present study, owing to methodological difficulties with the time effect of the drug, no counterbalancing was employed to control the order effect of the pharmacological blockade. This may impose limitations upon the final interpretation of results, since the second test might be affected, in addition to the drug, by an order effect. Nevertheless, such an effect would probably run in the same direction as the

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expected effect of the drug -reduction of sympathetic influencesproducing no strong contamination of the results concerning our basic prediction: similarity of the RSA response pattern with (first part) and without (second part) phasic changes in sympathetic activation. If this is the case, the present results would seem to validate the use of RSA amplitude as an index of phasic changes in parasympathetic cardiac control during tasks with phasic response paradigm.

3. Experiment

2

The aim of this experiment was to examine the relationships between the RSA amplitude and the CDR pattern. This general aim was divided into two specific objectives: firstly, to examine the effect of intense auditory stimulation typically used in the study of the CDR (see Turpin, 1986; Fernindez & Vila, 1989b) on the RSA amplitude and, secondly, to analyze the relationships between the RSA amplitude changes and the evocation of the CDR. For this purpose both the heart rate and the RSA amplitude values are reported in the present paper. The data concerning respiratory activity, which were also analyzed in relation to these two objectives, will be reported in a separate paper (Reyes de1 Paso and Vila, 1992). However, a brief description of the main results concerning respiration will also be presented here in order to facilitate the final discussion of the RSA results. 3.1. Method 3.1.1. Subjects The subjects were 42 volunteer psychology students 20 men and 22 women, aged between 18 and 23. Each student received a course credit for his/her participation. None of the subjects was receiving psychiatric or pharmacological treatment or had any cardio-respiratory or auditory deficiency. 3.1.2. Apparatus A Grass 7 polygraph was used for the physiological recording. The respiratory activity was recorded using a 7Pl preamplifier and a Grass PRT pneumatic transducer placed half way up the thorax. Heart rate (HR) was recorded using a 7P4 cardiotachometer and ECG electrodes in the lead II configuration. A Letica LE-150 auditory stimulator and SUN-SE 20 headphones were used to present the auditory stimulus, which consisted of a distorted sound of frequency 400 Hz, intensity 100 dB, duration 0.5 s and a virtually instantaneous rise time. The physiological data acquisition, as well as stimulus control, was carried out by using a computerized system with a

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MED ANL-947 12 bit analog-digital converter which collected 25 samples per second from each recording channel and a digital “input-output” Data Translation card (model DT-2817). 3.1.3. Procedure On arrival at the laboratory, the subject was given general information about the session and completed a personal questionnaire with information relevant to the selection criteria. Then the subject went into the experimental room, sat down in an armchair and the instructions for the physiological reaction test were read to him/her. These described the test as a routine procedure to examine the effect of sound on relaxation and requested the subject to remain still throughout the test and to try and breathe as normally and evenly as possible. After reading the instructions, the experimenter placed on the subject, in this order, the pneumatic transducer, the ECG electrodes and the headphones. Then the experimenter left the subject’s room and turned down the lighting to a pre-established subdued level. The physiological reaction test lasted 20 min, and was structured according to the following sequence: 10 min of rest period and tree trials of duration 150 s with presentation of the auditory stimulus. The intertrial interval lasted 85 s. 3.1.4. Data reduction and analysis 3.1.4.1. CDR. Following the procedure described in previous studies (Vila & Fernandez, 1989), the CDR was defined as the second-by-second heart rate during the 80 s after stimulus onset expressed in terms of differential scores with respect to the average heart rate during the 15 s prior to stimulus onset (baseline). To analyze the form of the response, the 80 heart rate values were reduced to 10 corresponding to the medians of 10 progressively longer intervals: two intervals of 3 s, two intervals of 5 s, three intervals of 7 s and three intervals of 13 s. The CDR parameters included measures of amplitude, latency and duration of each accelerative and decelerative component together with a global parameter which defines the presence or absence of the CDR pattern. These parameters are based on the determination of four sequential points, which mark the beginning of each accelerative and decelerative period, defined as the first of three (for first acceleration and deceleration) or four (for second acceleration and deceleration) consecutive heart rate values above or below baseline within specific periods after stimulus onset: 10 s for first acceleration, 25 s for first deceleration, 60 s for second acceleration and 80 s for second deceleration. If the criterion of three or four consecutive heart rate values is not achieved within each period, the criterion is successively reduced to three, two, one or the highest/lowest heart rate value within the period. Once the four points are determined, the maximum amplitude, its latency, and the duration of each component are easily

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obtained. Finally, the global parameter takes into account the average of the three highest consecutive heart rate values within seconds l-10 (first acceleration), the three lowest consecutive heart rate values within seconds 5-25 (first deceleration) and the six highest consecutive heart rate values within seconds 15-60 (second acceleration), according to the following formula: global parameter = first acceleration minus first deceleration plus double the second acceleration. Based on this parameter and a similar one for baseline variability (taking into account the three highest consecutive and the three lowest consecutive heart rate values), subjects are categorized as showing the CDR pattern if global parameter & 35 and global parameter minus baseline variability 2 5. 3.1.4.2. RSA. RSA amplitude was obtained as the average (sum of the individual RSA amplitudes divided by the number of respiratory cycles) for the 15 s before and the 80 s after stimulus onset and for the individual respiratory cycle in which the stimulus was presented and the cycle immediately following. The maximum individual RSA amplitude during the first accelerative and first decelerative component of the CDR were also obtained. The analysis times (15 s pre and 80 s post) were chosen because they are the times used in the analysis of the CDR. However, in order to obtain complete respiratory cycles, the analysis times were slightly extended in both extremes. Finally, to analyze the form of the RSA amplitude along the 80 s after stimulus, the same methodology used in the previous experiment and in the analysis of the CDR (reduction to ten medians) was applied. 3.1.4.3. Statistical analysis. The statistical analysis involved analysis of variance with within-group (repeated observations) factors. These factors were Medians (or Comparison Conditions) and Trials. The Greenhouse-Geisser epsilon correction was applied for the adjustment of the degrees of freedom. Results are reported with the original degrees of freedom and the corrected probability values. 3.2. Results 3.2.1. Effect of the auditory stimulus on the RSA amplitude This effect was analyzed comparing, firstly, the form of the response along the 80 s post-stimulus period and, secondly, the respiratory cycle in which the stimulus is presented and the immediately following cycle with the average of the 80 s post-stimulus period. 3.2.1.1. Form of the response (medians). The statistical analysis of the Form of the response was carried out using a (10 x 3) ANOVA (Keppel, 1982), with the two factors within-group (Form and Trials). The analysis showed a

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--I o-----o2 t.-.-.-_

3

Fig. 3. RSA response pattern to the three presentations of the auditory stimulus. (Numbers on the horizontal axis represent the midpoints of the ten selected intervals.)

significant main effect of Form (F(9,369) = 7.57, p < 0.01). The Trials factor and the interaction were not significant. As can be observed in Fig. 3, the response pattern is fundamentally characterized by a great increase in the second median, followed by a decrease with maximum amplitude in the fifth median and a final slight increase in the seventh median that is maintained in the three remaining ones. This response pattern does not show habituation along the three trials. 3.2.1.2. Respiratory cycle in which the stimulus is presented and the cycle immediately after. The statistical analysis was carried out using a (2 X 3) ANOVA, the two factors within-group (Comparison Condition and Trials). Respiratory cycle in which the stimulus is presented. The analysis only showed a significant main effect of the Comparison factor (F(1,41) = 5.77, p < 0.05). RSA amplitude decreases (- 19.6 ms as average in the three trials) in the respiratory cycle in which the stimulus is presented. Respiratory cycle immediately after the stimulus. The analysis only showed a significant main effect of the Comparison factor (F&41) = 53,43, p < 0.01). RSA amplitude increases (50.6 ms as average in the three trials) in the respiratory cycle immediately following the respiratory cycle in which the stimulus is presented. 3.2.2. The CDR 3.2.2.1.

Form of the response. Analysis was carried out using a (10 X 3) ANOVA with the two factors within-group (Form and Trials). Results showed a significant main effect of Form (F(9,369) = 11.39, p < 0.01) and a

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G.A. Reyes de1 Paso et al. / RSA as index of cardiac control

I,,, I 1 1 I I I I 44 57 70 02 5 9 14 20 27 34 Fig. 4. CDR pattern to the three presentations of the auditory stimulus. (Number of the horizontal axis represent the midpoints of the ten selected intervals.)

significant interaction of Form x Trials @(l&738) = 3.32, p < 0.01). As can be observed in Fig. 4, the response pattern reproduces the two accelerative and two decelerative components described in previous studies. This response pattern shows habituation in some components, specifically the last three ones, as reflected by the significant Form x Trials interaction. 3.2.2.2. CDR parameters and evocation. This analysis was restricted to the first trial, since the magnitude of the CDR components is greatest. The first acceleration has, on average, a maximum amplitude of 13.2 bpm, reaches this value at second 5.02 and has a total duration of 7.15 s:The first deceleration has a maximum amplitude of -9.78 bpm, reaches this value at second 14.2 and has a total duration of 14.08 s. The second acceleration has a maximum amplitude of 13.45 bpm, reaches this value at second 31.28 and has a total duration of 22.05 s. Finally, the second deceleration has a maximum amplitude of - 10.92 bpm, reaching this value at second 60.03. The duration of the second deceleration is not obtained because it is not fully represented within the 80 s post-stimulus onset. As regards the frequency of subjects showing the CDR pattern, 6 out of 20 male and 10 out of 22 female subjects showed the typical response pattern (presence of second acceleration) according to the criterion described above. These results are very similar to those previously reported (FernPndez & Vila, 1989b), except that the amplitude of the accelerative components and the number of subjects showing the CDR are slightly reduced. 3.2.3. RSA amplitude and the CDR Analysis of the relationships between the respiratory activity and the CDR was carried out, firstly, re-examining the previously described RSA amplitude

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I

I1

025

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) and did not evoke (- - -1 the Fig. 5. RSA response pattern for the groups who evoked (CDR pattern. (Numbers on the horizontal axis represent the midpoints of the ten selected intervals.)

effects in terms of the evocation or not of the CDR and, secondly, through Pearson’s Product Moment correlations between the RSA amplitude and the CDR parameters. 3.2.3.1. Differential analysis in terms of CDR evocation. Statistical analysis involved the same ANOVAS as in Section 3.2.1, except that a between-group factor was added (CDR evocation at two levels) and a within-group factor (Trials) was dropped. In reporting the results, only’the data showing significant effects of the CDR factor will be presented. Form of the response (Medians). The 2( X 101 ANOVA showed a significant interaction of CDR x Form (F(9,360) = 4.04, p < 0.01). The analysis of this interaction shows that the Form factor is significant both if the CDR is not elicited (F(9,215) = 4.08, p < 0.01) and if it is (F(9,125) = 3.57, p < 0.01). However, both groups differ in the pattern of response. When the CDR is not elicited the significant trends were linear and quadratic (Flinear = lO,lO, P < O*O1;Fquadratic = 6.09, p < 0.05), while when the CDR is elicited only the quartic trend was significant (F = 21.85, p < 0.01). As can be observed in Fig. 5, the elicitation of the CDR was associated with a response pattern consisting of four components: decrease, increase, decrease and increase, while when the CDR was not elicited the response pattern consists only of an increase followed by a return to baseline after the second median without substantial changes in the remaining ones.

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Respiratory cycle in which the stimulus is presented. The 2 X 2 ANOVA showed a significant interaction of CDR X Comparison Condition (F(1,40) = 5.36, p < 0.05). When the CDR is not elicited, the Comparison factor was not significant, while when the CDR is elicited it is (F(1,15) = 10.23, p < 0.01) (69 ms of decrease). 3.2.3.2. Correlations between the RSA amplitude and the CDR parameters. Pearson’s Product Moment correlations between the RSA amplitude and the CDR parameters in the first trial were calculated. Significant positive correlations were observed between RSA amplitude in the 15 s pre- and in the 80 s post-stimulus onset and the amplitudes of the first (0.361 and 0.452) and second accelerative component (0.477 and 0.4051, as well as the global parameter of the CDR (0.408 and 0.346). The maximum RSA amplitude found during the first accelerative component showed a significant positive correlation with the amplitude of this CDR component (0.389). The maximum RSA amplitude found during the first decelerative component showed significant negative correlations with the amplitudes of the two decelerative CDR components (-0.527 and -0.488). Similarly, the RSA amplitude during the 80 s post-stimulus onset demonstrated a negative correlation with the amplitude of the second decelerative CDR component (-0.368). As regards latency parameters, the RSA amplitude in the respiratory cycle in which the stimulus is presented was negatively correlated with the latency of the second accelerative CDR component ( - 0.3371, and the maximum RSA amplitude found during the first accelerative component was negatively correlated with the latency of the first decelerative CDR component (- 0.309). Finally, as far as the duration parameters are concerned, the RSA amplitude in the respiratory cycle in which the stimulus was presented was negatively correlated with the duration of the first accelerative CDR component c-0.315), and the maximum RSA amplitude found during the first decelerative component showed a significant positive correlation with the duration of the first decelerative CDR component (0.362) and a negative one with the duration of the second accelerative CDR component ( - 0.338). 3.2.4. Respiratory actir:ity The effect of the auditory stimulus on various respiratory indices -breathing amplitude, respiratory rate, minute ventilation volume and the inspiratory, expiratory and respiratory periodsas well as the relationship between the respiratory activity and the CDR were analyzed following the same procedure described above for RSA amplitude. A detailed description of these results are reported elsewhere (Reyes de1 Paso & Vila, 1992). Here only a brief description of the effect of the auditory stimulus on the respiratory activity will be reported. In general, the auditory stimulus produced significant effects in breathing amplitude (expressed in terms of

G.A. Reyes de1 Paso et al. / RSA as index of cardiac control

1,,

31

,

d7 0 2 5 8 14 &I Z!7 3’4 64 7b Fig. 6. Respiratory amplitude response pattern to the three presentations of the intense auditory stimulus. (Numbers on the horizontal axis represent the midpoints of the ten selected intervals.)

percentage of change with respect to baseline), no significant changes being observed in the respiratory rate nor in the different respiratory periods. Form of the breathing amplitude response (medians). Following the same procedure used for RSA and CDR, a (10 x 3) ANOVA with two within-group factors (Form and Trials) was performed. The results showed significant main effects of Form (F(9,369) = 13.95, p < 0.01) and Trials (F(2.82) = 3.87, p < 0.05). The interaction was not significant. As can be observed in Fig. 6, the response pattern is fundamentally characterized by a large increase in the first median, followed by a moderate but sustained increase in the remaining ones. On the other hand, a clear habituation is observed in the successive trials which does not alter the form of the response pattern. Breathing amplitude in the respiratory cycle in which’ the stimulus is presented. The breathing amplitude in this cycle was compared with the average breathing amplitude of the 80 s post-stimulus period. The (2 x 3) ANOVA,

with the two factors within-group (Comparison Condition and Trials), showed a significant main effect of the Comparison factor (F(1,41) = 25.28, p < 0.01). The increase in amplitude in the cycle in which the stimulus is presented was 60.2%, 52% and 38% in the first, second and third trial respectively. The Trials factor and the interaction were not significant. 3.3. Discussion

The results obtained in this study suggest that the auditory stimulus produces a clear phasic response on the RSA amplitude. The analysis of the medians show a response pattern made up of three components: an increase component with maximum value in the second median (seconds 4-61, a decrease component with maximum value in the fifth median (seconds 17-23) and a final increase component in the last four medians (seconds

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31-76). The more specific analysis carried out on the first two respiratory cycles after stimulus presentation show that, in the respiratory period in which the stimulus is presented, a significant reduction of the amplitude is produced, while in the respiratory period immediately after a very significant increase is observed. As regards the CDR, the results show the typical pattern of heart rate changes described in previous studies with two accelerative and two decelerative components in alternating order. Furthermore, analysis of the amplitude, latency and duration parameters of each component replicates in general those reported previously. The observed differences concerning reduced amplitude of the first and second acceleration and reduced number of subjects showing the CDR can be explained by the difference in intensity of the stimulus used in this study (100 dB) as compared with previous ones (109 dB). Significant relationships between the RSA amplitude response and the CDR were found. When the CDR is evoked the response pattern of the RSA amplitude, as in the CDR, can be described as consisting of four components, two of reduction and two of increase that appear in alternate sequential order: decrease (seconds l-31, increase (seconds 4-111, decrease (seconds 17-301, and increase (seconds 31-63). When the CDR is not elicited the response pattern consists only of an increase followed by a return to baseline after the second median without substantial changes in the remaining ones. This difference in the response pattern is consistent which that found as regards CDR evocation: the RSA amplitude shows mirror image changes to those observed for heart rate. Lastly, relationships between the RSA amplitude and the CDR were also evident in the correlations obtained between both types of parameters. To understand the psychophysiological significance of these results better it is necessary to compare the RSA with the respiratory activity during the CDR evocation. The basic question to answer is whether the RSA response pattern reflects directly the respiratory changes associated with the intense auditory stimulation or reflects something else, for example a centrally mediated response. In our study the auditory stimulus produced a specific response in respiratory amplitude. No significant changes were observed in respiratory rate nor in the different respiratory periods. The form of the respiratory amplitude response (Fig. 6) was characterized by a large increase in the first median, followed by a moderate but sustained increase in the remaining ones. As can be observed by comparing the RSA and the respiratory activity response patterns, the reduction of the RSA amplitude in the first median coincides with a marked increase of the respiratory amplitude, whereas the increase of the RSA amplitude in the subsequent medians coincides with a relative decrease of the respiratory amplitude. The posterior decrease of the RSA amplitude associated with the second accelerative component of the CDR occurs when the respiratory amplitude still shows

GA. Reyes de1 Paso et al. / RSA as index of cardiac control

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increased values with respect to baseline. Finally, the increase of RSA in the last medians occurs in the context of no changes in respiratory amplitude. These results suggest that the RSA response pattern during the CDR is not a direct consequence of the associated respiratory changes. Rather it seems that the RSA is independent of the known respiratory influences on its amplitude. This suggestion is particularly evident in the respiratory cycle in which the stimulus is presented since an RSA decrease coincides with a marked increase of the respiratory amplitude - over 100% from baseline. Consequently, these results seem to support the view that the RSA changes during the CDR reflect a centrally mediated response. The data obtained in this experiment, together with those of Turpin and Siddle (1978, 1981) and Fernandez and Vila (1989a) with respect to indirect measures of sympathetic activation, suggest a parasympathetic mediation during the first acceleration -vagal inhibitionand first deceleration -vagal activationof the CDR and a sympathetic-parasympathetic interaction during the second acceleration and second deceleration. This involvement of the parasympathetic nervous system in the CDR found in the present study is contrary to the traditional view on the defense reaction (Lisander, 1970), which assumes exclusive mediation by the sympathetic nervous system. However, an interpretation of the defense response in terms of both vagal and sympathetic mediation, supported by our present data, is consistent with the results of some studies which investigated the defense response by means of the electrical stimulation of the defense area in cats (Gebber & Snyder, 1970), in which an inhibition of the vagal efferent branch of the baroreceptor reflex was observed. It is also consistent with the results of more behavioral and naturalistic studies on the defense response in animals (Adams et al., 1971; Bond, 1943), as well as on the stress response in humans (Grossman & Svebak, 1987; Vingerhoets, 19851, which did encounter accelerative and decelerative changes in heart rate with both sympathetic and vagal influences.

Acknowledgements Part of this research was supported by a Grant of the Commission of the European Communities Medical and Health Research Program. Concerted Action: Quantification of Parameters for the Study of Breakdown in Human Adaptation. Project Leader Andrew Steptoe.

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