Inrernationol Journal of Psychophysiology, 11 !1991) 125-129

0 1991 Elsevier Science Publishers B.V. 0167-8760/91/$03.50

PSYCHO 00348

125

Empirical evidence against the ‘cycle time dependency’ assumption

Ursula Zimmermann, Manfred Velden and Christoph W6lk Department of Psychology. Unioermty of Osnabriick, Osnnbriick (F.R.G.)

(Accepted 12 November 1990)

Key words: Vagal effect; Time-dependency; Cycle time effect

The interpretation of the ‘cardiac cycle time effect’, also named ‘time-dependent primary bradycardia’ by the Laceys, who first

observed it, has been controversial in psychophysiology. Unconfounded evidence for the dependence of a vagal effect of

psychological stimuli on time of stimulation within the cardiac cycle has been missing to date. An experiment in which the subjects

could not anticipate the occurrence of the stimuli (short tones of a specific frequency that had to be counted) was performed. The

data reduction procedure secured unambiguous interpretation of the data with respect to time-dependency or no time-dependency,

No indication of any kind of cycle time dependency of the vagal effect was found.

INTRODUCTION

The idea of cycle time dependency as it has evolved in the last 15 years in psychophysiology refers to the observation, first published by the Laceys (Lacey and Lacey, 1973), that the lengthening of a cardiac cycle (and the subsequent cycle), induced by a short, psychologically signifi- cant stimulus, depends on exactly where in the cycle the stimulus is given. The Laceys found that the earlier the stimulation occurs in the cycle, the longer this cycle and the shorter the subsequent cycle. The effect has been well documented by several research groups (e.g., Jennings, Van der Molen and Terezis, 1987; Velden, Barry and Walk, 1987) but its psychophysiological meaning is still being debated (Barry, 1987a,b; Jennings, Van der Molen and Somsen, 1987; Van der Molen, Jen- nings, Somsen and Ridderinkhof, 1987; Somsen,

Correspondence: M. Velden, Department of Psychology, Uni- versity of Osnabriick, P.G.B. 4469. D-4500 Osnabrtick, F.R.G.

Molenaar, Van der Molen and Jennings, 1987; Velden, Barry and Wijlk, 1987; Velden and Wiilk, 1987a,b). It has been argued that the effect is a simple time effect in the sense that the earlier in the cycle the stimulus occurs, the more time there is for the vagal effect to affect the length of this cycle (Velden, Karemaker, Wijlk and Schneider, 1988). Velden, Barry and Wiilk (1987) were able to show experimentally that the effect as presented by the Laceys may (but need not) be explained in that manner. From a theoretical view, it may also be argued that a dependency of the strength of a vagal effect on the heart on the time of stimula- tion within the cardiac cycle would require that: (1) the vagal impulses resulting from the stimulus be so short as to be assigned to a specific time within the cardiac cycle; and that (2) the latencies of these impulses only vary to a very small degree. Only if these conditions are met, will experimental control of the cardiac cycle time of the sensory stimulus imply control of cardiac cycle time of the vagal impulses. These conditions, satisfied in ex- periments with direct, electrical stimulation of the vagus nerve disconnected from the brain (e.g.,

126

Karemaker, 1985), will most probably not be

satisfied in case of psychological stimuli, which

must be processed by the cortex. As has been

pointed out by Velden, Karemaker, Walk and

Schneider (1990) unconfounded experimental evi-

dence with respect to the dependency of a vagal

effect of psychological stimuli on time of stimula-

tion within the cardiac cycle is still missing. Such

evidence requires that: (1) the subjects may not

anticipate the time of occurrence of the stimulus:

and (2) that the effect be depicted in such a way

that the simple time effect can be excluded as an

explanation for the results. We therefore per-

formed the following experiment.

METHOD

Sul2jrct.r

37 male and 55 female university students,

ranging in age from 78 to 38 years. served as

subjects.

Apparutus

The ECG was triggered by a Gould ECG

amplifier and was fed into a microcomputer (Eltec

Eurocom 11). A second microcomputer (Eltec

Eurocom II) controlled delivery of the stimuli.

The stimuli were amplified by a stereo hifi-ampli-

fier (Mitsubishi DA-U310) and delivered via two

three-channel boxes (Koch and Overbeck)

mounted (at a distance of about 1.5 m) in front of

the subjects.

Procedure und design

For eliciting heart rate responses to relevant

stimuli, a modification of the ‘oddball paradigm’

(Lacey and Lacey, 1980; Velden, Barry and Walk,

1987) was used. Two kinds of acoustic stimuli

with equal mean rate of occurrence were given in

random order (with the restriction that the same

kind of stimulus did not occur more than four

times in sequence) and the subject had to count

how often one of them was presented. The stimuli

were spaced irregularly over the experimental

phase to prevent the occurrence of anticipatory

reactions. Subjects were seated in a sound at-

tenuated room (Industrial Acoustics Company,

Model 204). In the test period the instructions

were given and then the stimuli were presented

several times for demonstration purposes. The tone

detection experiment was started as soon as the

subject was able to discriminate perfectly between

them.

The two acoustic stimuli that had to be dis-

criminated were white noise and white noise mixed

with a 1000 Hz sine wave tone, both lasting 20 ms

(including 5 ms rise and 5 ms fall time) at a

volume of 67 dB (A). During the experimental

phase each of these two stimuli were delivered 48

times. They appeared in random order. The inter-

trial interval varied in steps of full seconds be-

tween 21 and 36 s, each of the 16 interval lengths

appearing equally often and in random order.

Half of the subjects were instructed to count the

times the white noise was delivered, the other half

to count the white noise mixed with the sine wave

tone.

The 96 trials were grouped into three blocks of

32 trials each, with each block lasting about 15

min. At the end of each block the experimenter

entered the cabin and asked the subject about the

counted number. Immediate feedback about the

correctness of the response was given. The first

block contained the white noise mixed with the

sine wave tones 17 times, the second 15. and the

third 16 times. The whole experiment, including

instructions and stimulus demonstrations, lasted

about 1 h.

Data rrductron

Data analysis was done for the trials with the

significant stimuli only. For depicting the vagal

effect of the stimulation, the procedure proposed

by Graham (1978) and Velden and Wiilk (1987c,

see also Velden and Graham, 1988) for plotting

cardiac activity over real time was employed. The

procedure implies that the heart rate values for

time intervals (half seconds in the present case) be

weighted averages in the sense that the heart rate

values of the cycles participating in a time interval

be weighted by the amount of time the cycles

extend within the time interval.

The time of stimulus presentation within the

cardiac cycle was not measured in proportions of

the cardiac cycle (for example quintiles or deciles)

127

as done by the Laceys, but in real time intervals of 150 ms length after the R-wave. The rationale for proceeding in this way is given in Fig. 1. The drawn line shows the course of the depolarization at the pacemaker cells of the heart. The broken line shows the effect of some vagal stimulus (arrow) on the course of the depolarization. The two scales in the lower part of the figure show a partitioning of the cycle into quintiles for an unaffected cycle (upper scale) and the one lengthened by the stimulus. It can be seen that the stimulus falls into different quintiles in the two cycles. Keeping in mind that the physiological basis of cycle time dependency can only be a different state of de- polarization of the pacemaker cells at the time of stimulation, partitioning of the cycle into propor- tional units may thus lead to different cycle times (like quintile three and quintile two in the above case) when the state of depolarization is actually identical. So if one wants to test the dependence of a vagal effect on the state of depolarization at the time of stimulation, time of stimulation should be given in real time units. Even if one thinks of other possible sources for cycle time dependency, such effects should only show up by dividing the cardiac cycle into real time rather than cardiac

“1

\

Fig. 1. Partitioning of an unaffected cycle (__ ) and one affected by the stimulus (arrow, ) into quintiles. Stimulus falls into different quintiles under the two conditions.

J 4 J

0 5 10 15

SECONDS Fig. 2. Stimulus induced changes of heart rate. Mean values for

significant stimuli (48 trials for each of 92 subjects).

time units. Such a source may, for example, be changes in the central nervous effectiveness of the stimulus caused by the baroreceptor afferent burst during the systolic upstroke. Such changes in per- ceptual performance over the cardiac cycle, time locked to the pulse wave, have been shown by Velden and Juris (1975) and Wiilk and Velden (1987).

RESULTS

Fig. 2 shows mean heart rate at half second intervals commencing 5 s before and ending 10 s after the stimulus, averaged over 48 trials and 92 subjects. Obviously the use of long and varying interstimulus intervals prevented the occurrence of an anticipatory response. With respect to the dif- ference between the last and the first value it should be kept in mind that the average time between them was 12.5 s (mean IS1 = 27.5 s).

Fig. 3 shows the course of the vagal effect as a function of time of stimulation within the cardiac cycle. The four curves show the vagal effect for stimulation in four time intervals of 150 ms length after the R-wave. Mean numbers of stimuli per subject in each interval were: 8.62 (O-149), 8.80 (150-299) 9.45 (300-449), and 7.63 (450-599). Time intervals later than 600 ms after the R-wave

I

L

0 1 2 3

TIME FROM STIMULATION (SEC)

Fig. 3. Course of vagal effect if stimulus falls into different real

time segments of 150 ms length.

were not included because heart rate was not low

enough for each trial and each subject to yield a

comparable number of stimulations in such inter-

vals as compared to the earlier intervals. The vagal

effect is shown from the time of stimulation to

half a second after it ended and turned into a

sympathetically dominated one. In order to allow

a better comparison of the effects of the four

stimulation conditions, they are expressed as

changes in heart rate with respect to the last

cardiac cycle before stimulation. There is no indi-

cation of cycle time specificity of the vagal effect,

which is also reflected in an insignificant cycle

time (four intervals of 150 ms) X time (six half

second periods) interaction ( F,5,,3hS = 1.68, P =

0.14).

If one wants to draw information from the

differences between the curves (in spite of the

insignificant F-value), it should be noted that for

the first half second after the stimulus, where the

differences are maximal, they may not be interpre-

ted in terms of cycle time dependency because of

the neural latencies involved (there is, for exam-

ple, a larger deceleration for the 450-599 ms inter-

val than for the 150-299 ms interval).

For the sake of comparability with the Laceys’

subsequent 7

\

same cycle

I I t I I 1 I I

0 150 300 450

TIME FROM R-WAVE (MSEC)

Fig. 4. Effect of sensory stimulus on same and subsequent cardiac cycle when stimulating at different real time intervals

within the cycle.

/

subsequent /

1 2 3 4 5

OUINTILE

Fig. 5. Effect of sensory stimulus on bame and subsequent

cardiac cycle when stimulating at different quintiles within the

cycle.

129

data, the effect of the stimulation on the same and the subsequent cycle was measured, cycle time being measured both in real time (Fig. 4) and quintiles (Fig. 5). Similar to the Laceys’ results the effect for the same and the subsequent cycle is in opposite directions, reflected statistically in both a cycle x real time and a cycle x quintile interaction

(F3.273 = 6.22, P < 0.01, and F4.364 = 8.65, P < 0.01). For the same cycle there is a lengthening effect only if stimulation occurs within the first 150 ms of the cycle or in the first quintile. With anticipatory responses excluded by the experimen- tal design (see Fig. 2) this is in accordance with the latencies to be expected due to the physiologi- cal processes involved (see Karemaker, 1985). With essentially no cycle time effect (Fig. 3), this dif- ferential effect on the lengths of the same and the subsequent cycle must be a simple time effect as described by Velden, Karemaker, WBlk and Schneider (1988) and assumed by Velden, Barry and Walk (1987) with respect to the Laceys’ data.

DISCUSSION

Seeing this empirical evidence in combination with theoretical considerations, which make a cycle time effect with psychological stimuli highly un- likely (the vagal activity resulting from a stimulus which has to be analyzed and assessed by the cortex will probably be too long and too variable in latency as to be assigned to a specific phase of the cardiac cycle), we may conclude that there is no ‘time-dependent primary bradycardia’ in the Laceys’ sense. After 15 years of research about cycle time dependency, this may serve as a warn- ing not to prematurely draw analogies from physi- ological to psychophysiological processes, in the present case from vagal effects on the heart of short electrical stimulations of the vagus nerve, disconnected from the brain, to vagal effects on the heart of short, significant, sensory stimuli.

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