Biological Psychology 33 (1992) 249-258 0 1992 Elsevier Science Publishers B.V. All rights reserved
249 0301.0511/92/$05.00
Reply
T-wave amplitude: On the meaning of a psychophysiological index Richard Rutgers-The
J. Contrada State Unicersity of New Jersey, New Brunswick, NJ, USA
The preceding article by Furedy, Heslegrave and Scher presents a positive evaluation of T-wave amplitude (TWA) as a psychophysiologic index, and rejects the more cautious and less favorable view contained in a paper by Contrada et al. (1989). In this article I propose that the Furedy et al. perspective rests on: (1) a questionable approach to the logic of causal inference; (2) an unsatisfactory view of measurement validity; (3) the use of imprecise and therefore misleading language; (4) a disregard of valuable observations that can be drawn from the data of individual research subjects; (5) an objection to evaluative conclusions that can provide a useful stimulus to empirical inquiry. Close examination of these issues argues for a skeptical view of the state of knowledge regarding the meaning of TWA alterations. Keywords: T-wave amplitude, psychophysiologic sympathetic activity, parasympathetic
measurement, activity
beta-sympathetic
activity,
alpha-
1. Introduction In the preceding paper, Furedy, Heslegrave and Scher take exception to portions of an article by Contrada, Krantz, Durel, Levy, LaRiccia and Weiss (1989). The underlying question concerns the meaning of alterations in T-wave amplitude (TWA). Furedy and colleagues (e.g. this issue; Furedy & Heslegrave, 1983) have advanced strong claims concerning the validity of TWA as a measure of certain psychological and physiological processes. My colleagues and I have advanced more cautious and less favorable evaluations (e.g. Contrada et al., 1989; Contrada, Dimsdale, Levy & Weiss, 1991; Schwartz & Weiss, 1983; Weiss, Del Bo, Reichek & Engelman, 1980). In this paper I give a critique of five elements of the perspective advanced by Furedy et al.: (1) an approach to causal inference that leads to demonstrably premature conclusions; (2) a view of measurement that artificially compartmentalizes sources of evidence that must be considered jointly in assessCorrespondence to: Richard J. Contrada, Department University New Brunswick, NJ 08903, USA.
of Psychology,
Rutgers-The
State
250
R.J. Contrada / T-wace amplitude
ing validity; (3) a preference for imprecise language that can result in misleading theoretical assertions; (4) a disregard of data from individual subjects that might otherwise usefully inform more systematic investigation; (5) an objection to evaluative conclusions that actually play a constructive role in stimulating empirical research and scientific discourse.
2. Experimentation
and causal inference
2.1. Proximal versus distal causation Experiments document causal relationships between operations designed to influence the organism in some way and measures reflecting that influence. Intervening between operations and dependent measures are events that are not directly manipulated or observed, but that are invoked to provide tentative explanations for observed cause-effect relationships. Thus, in the Contrada et al. study, propranolol, isoproterenol and placebo were administered to subjects, and it appears from the results that “. . . T-wave amplitude is affected by beta-sympathetic activity” (Contrada et al., 1989, p. 491, emphasis added). This conclusion was carefully worded. In the absence of any direct information regarding the causal sequence that was initiated by drug administration, the Contrada et al. (1989) study cannot be taken as support for or against any specific hypothesis regarding the nature of the mechanisms that culminated in changes in TWA. Indeed, use of the term “beta-sympathetic” is inferential, because it is conceivable, albeit unlikely, that drug administration exerted its effects through other pathways. Moreover, Contrada et al. employed only single doses of a beta-adrenergic agonist and a beta-adrenergic antagonist. To have concluded that TWA was not merely affected by beta-sympathetic activity, but faithfully indexed the degree of beta-sympathetic activity, would clearly have been premature. Much more strongly worded conclusions regarding the meaning of TWA changes can be found in the writings of Furedy and colleagues. For example, Furedy and Heslegrave (1983) conclude their evaluation of TWA with the assertion that “. . . laboratories should, at present, consider TWA as an adequate index of SNS activity” (p. 210). To be sure, these authors have elsewhere urged that additional research is needed on this point. But underlying the controversy in this area is not merely disagreement as to whether the preponderance of the evidence points in one direction or another. The problem is in the qualitative distinction between a statistically significant effect (beta-sympathetic activity affects TWA), and so close a coupling between operation and physiologic process that the one is claimed as a measure of the other (TWA indexes SNS activity).
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251
Ironically, an excellent illustration of this point can be found in an article by Heslegrave and Furedy (1980). The diagram in Fig. 1 of that article depicts sympathetic and parasympathetic inputs as distal causes of alterations in carotid dP/dt. These effects depend upon a number of intervening events that are more proximal to carotid dP/dt changes. The illustration makes it clear that there might be a real, but relatively weak, relationship between SNS activity and carotid d P/dt, because of loose links in the causal chain (SNS activity affects carotid d P/dt), or there might be a very strong relationship because the intervening links are so tightly coupled that information about proximal causes is redundant to information about SNS activity (carotid d P/d t indexes SNS activity). Construction and empirical evaluation of a comparable model describing the events that mediate sympathetic effects on TWA would seem prerequisite to Furedy et al’s claims regarding the meaning of TWA changes. 2.2. Specificity of cause Rather than advancing any one model, Contrada et al. (1989) pointed out that processes whereby drug administration affected T-wave amplitude take one of two general forms. If T-wave changes were specific to alterations in beta-sympathetic activity, then the mediating link was one that can only be brought into operation by altering beta-sympathetic activity. This rather strong conclusion would seem to be preferred by Furedy et al. However, results of the Contrada et al. study are perfectly compatible with an alternative interpretation, in which T-wave changes were nonspecific with respect to beta-sympathetic influences. In this view, events consequent to alterations in beta-sympathetic activity, but for which change in beta-sympathetic activity is not a necessary cause, mediated the effects of the pharmacological manipulations. We suggested, as an example of a nonspecificity interpretation, the notion that alteration in heart rate might have mediated the effects of drug administration on T-wave amplitude. Under this hypothesis, tachycardia produced by parasympathetic blockade, like that produced by increased beta-sympathetic input, would be expected to attenuate T-wave amplitude. This is precisely what was observed in a study by Dauchot & Gravenstein (1971). Although there may be alternative interpretations (see Furedy & Heslegrave, 19831, the most parsimonious explanation of the Dauchot and Gravenstein study is that TWA can be influenced by alterations in parasympathetic input (see also Muranaka et al., 1988). Curiously, Furedy and colleagues (Furedy, Heslegrave & Scher, 1984) appear quite sensitized to the specificity issue as it pertains to carotid d P/d t. They assert that “. . . an adequate candidate SNS measure should not be influenced by non-SNS factors” and then point to evidence that “. . . carotid
252
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d P/d t was significantly influenced by pre- and after-load factors, as well as parasympathetic influences” (Furedy et al., 1984, pp. 184). Their conclusion is that violation of the specificity principle undermines the “valid use” of dP/dt to index sympathetic effects on the heart. It would seem that application of the same principle to the Dauchot and Gravenstein (1971) data should lead Furedy et al. to the same conclusion regarding TWA. Note, however, that we did not claim support for either the specificity or nonspecificity hypothesis. Either conclusion would most certainly go beyond the data, and our position on this is clearly evident from the statement that resolution of the specificity-sensitivity issue “awaits further research” (Contrada et al., 1989, p. 491). It should be noted, however, that ruling out all forms of the nonspecificity hypothesis challenges the powers of experimentation. Alternatives to the specificity hypothesis can only be supported by research in which plausible nonspecific mediators are controlled experimentally. As noted by Contrada et al., this analytic strategy is exemplified in research on pulse transit time (PTT; Weiss et al., 19801, in which pharmacological manipulations were employed to tease apart the contributions of beta-sympathetic and parasympathetic influences. 2.3. Generalizability Experiments permit conclusions regarding the existence of a phenomenon, not its preualence. Thus, evidence of fractional dissociation between HR and TWA demonstrates that fractional dissociation is possible, not that it is typical. It does not, as Furedy et al. (this issue) assert, “refute the view that TWA changes are merely a function, or artifact, of HR changes”. Instead, it demonstrates only that there exist conditions under which TWA can change independently of HR changes. The problem with the Furedy et al. argument can be illustrated by applying it to a well-understood phenomenon: it would be tantamount to the conclusion that, because HR variations can be induced in an atropinized subject, parasympathetic input never affects HR.
3. Principles
of validity in measurement
Furedy et al. arrive at a positive evaluation of TWA by distinguishing between its linkages with three types of criteria: psychological processes (“psychophysiologic index” criterion), autonomic inputs (“physiologic index” criterion), and myocardial events (“physiologic mechanism” criterion). This approach so fractionates the system of variables in which TWA is embedded that claims of psychophysiologic validity are advanced without invoking any specific physiologic event. It also leads to mutually contradictory assertions in which alteration in TWA is simultaneously viewed as a measure of mental
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253
effort, sympathetic nervous system activity, and the synchrony of ventricular repolarization. Furedy et al. argue that TWA has validity as a psychophysiological index because it is affected by behavioral challenges, thereby demonstrating “reacand because it responds to some behavioral processes tive sensitivity,” (performing arithmetic operations) but not others (encoding arithmetic problems), thereby demonstrating “specific sensitivity”. They argue further that (1) the psychophysiologic index criterion requires no assumptions regarding the relationship between sympathetic activity and TWA, and (2) with respect to specific sensitivity, it is the superiority of TWA over HR (which is responsive to both encoding and operation) that is critical to establishing psychophysiological validity. The hypothesis that TWA reflects sympathetic activity clearly is essential to psychophysiologic index validity. It is this assumption that leads to an examination of the effects of behavioral challenge on TWA. To interpose a “black box” between task instructions and the magnitude of oscillograph deflections is to take a blindly empirical approach to experimentation that belies the very notion that gave impetus to the investigation. Moreover, it is contradictory to deny claims regarding the mediating role of sympathetic activity in one context, while elsewhere invoking “increased sympathetic activity” and consequent “nonuniform, asynchronous shortening of the refractory periods in various areas of the myocardium” (Scher, Hartman, Furedy & Heslegrave, 1986, p. 166) to explain behavioral influences on TWA. One cannot have a “psychophysiological” index without making at least tentative assumptions about physiology. The notion that a significant effect of encoding on one measure (HR) lends psychophysiologic validity to another measure (TWA) that appears unaffected by encoding is also problematic. Furedy et al. (1984) argue that by responding to arithmetic operations, but not to the encoding of arithmetic problems, TWA provides additional, “complementary information to that provided by HR, and in this sense allows us to interpret the experiments with greater psychophysiological sensitivity” (p. 18.5). The logic underlying this assertion is as follows. Any measure that shows greater discrimination between encoding and operation than that shown by HR has value as a psychophysiologic index. By this reasoning, a valid psychophysiologic index could be had by instructing the subject to depress a button while attending to arithmetic problems, and release the button while solving the problems. Button pressing (or, say, consequent alterations in forearm EMG activity), would provide “additional, complementary information” regarding behavioral activity. The problem with this logic is twofold. First, there must be some hypothesis linking the encoding-operation distinction to TWA. As Furedy et al. themselves point out, the possibilities are numerous, as they include mental
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254
/ T-wa~v amplitude
effort, motor (speaking) output, general somatic activity, posture, and the quality or intensity of affective response. It remains to be determined whether alterations in TWA are specific to one of the behavioral parameters mentioned above, or reflect a final common pathway whereby a number of such parameters influence TWA. Information gain cannot be claimed until the information is characterized. Second, there is little basis for setting up HR as the standard for comparison in these studies. It is very curious that Furedy et al. elevate HR to the status of a criterion index in this context, while at the same time criticizing our comparison of TWA and PTT. Useful evaluative standards should be derived from hypotheses regarding the process in question. The performance of PTT in the Weiss et al. (1980) study is consistent with the hypothesis that PTT reflects beta-sympathetic influences. Thus, there is a theoretical basis for considering the performance of PTT in this research as a standard against which to evaluate TWA. Under what specific hypothesis about the cognitive processes involved in encoding and performing arithmetic problems is a psychophysiologic index validated by showing it exceeds HR in its ability to discriminate these two processes? Rather than compartmentalizing validity criteria, it would seem preferable to view the meaning of TWA within a unitary conceptual framework. Such a framework would begin with an analysis of relevant psychological and pharmacological events, whose effects on the autonomic nervous system, as well as on other potential mediating mechanisms, might be expected to alter the synchrony of ventricular repolarization. A broader focus on a system of related variables provides a more accurate representation of the phenomenon than narrow, oversimplified assertions concerning bivariate, measurement-level relationships. It also constitutes a necessary first step toward the goal of integrating disparate research findings. Such findings are likely to remain isolated if the problem is cast in terms of three disjunctive sets of evaluative criteria.
4. Precision
in language
Furedy et al. concede that, in principle, their notion of “sympathetic myocardial influence” is insufficiently precise. However, they argue that the distinction between alpha- and beta-adrenergic activity is of little import in the study of TWA because, in their view, sympathetic myocardial influences are primarily mediated by beta-adrenergic innervation. Instead, Furedy et al. wish to focus on the sympathetic-parasympathetic distinction. As discussed above, there is cause to question the “purity” of TWA with respect to parasympathetic influences (Dauchot & Gravenstein, 1971; Muranaka et al., 1988). Setting this issue aside, however, there remains another
R.J. Contrada / T-wave amplitude
255
reason why it would be a mistake to drop the alpha/beta distinction at this point. Quite distinct from the direct effects of sympathetic stimulation on the myocardium are possible indirect effects that may involve both alpha- and beta-adrenergic activity. As Furedy et al. (this issue, Footnote 1) assert, in addition to beta-sympathetic influences, “ . . . under some conditions, TWA is and alpha-adrenergic) and affected.. . by other neural (e.g. parasympathetic non-neural factors”. Complex effects involving multiple inputs are particularly relevant to studies of behavioral challenges that may produce both alpha- and beta-sympathetic responses (e.g. Heslegrave & Furedy, 1979). Even if the proximal cause of such TWA changes exclusively involves beta-sympathetic influences on the myocardium, a complete account of events mediating those changes may include the more distal effects of non-beta-sympathetic mechanisms. To focus exclusively on the sympathetic/parasympathetic distinction is misleading because it combines under one label (“sympathetic”) both proximal and distal influences involving alpha-adrenergic effects, beta-adrenergic effects, and non-adrenergic effects.
5. Relevance of the single case Furedy et al. reject the cautionary note sounded by Contrada et al. (1989) on the basis of their observation that 2 of 12 individual cases showed TWA augmentation (rather than attenuation) to isoproterenol infusion. Their argument is that (1) reversals of direction in a single clinical case must be taken seriously for medical reasons, whereas psychophysiology does not deal with data from individual cases but with the statistical analysis of group data, and (2) cardiological manipulations produce larger magnitude changes than those of psychophysiology. These arguments ignore several important considerations. First, we drew no conclusion from the two instances of reversal. The observations were simply mentioned, following our discussion of the specificity issue, as an added caution regarding the meaning and generalizability of our results. It is disconcerting when results for even one or two cases fall in a direction opposite to that expected under the hypothesis being tested. Individual cases of reversal are especially troubling to claims regarding the use of a variable as an index of a particular, cardiac event. Such claims are stronger than those asserting merely that an experimental manipulation had a statistically significant impact on a dependent measure, and therefore must be evaluated against more stringent criteria. At a minimum, these individual differences provide useful information regarding the consistency of the drug effects, and therefore on the reliability with which TWA responds to alterations in
256
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beta-sympathetic activity. Reliability is, of course, a sine qua non of measurement. Second, our concerns appear to have been borne out. Our most recent investigation indicates that initial TWA attenuation following low-dose infusion of isoproterenol is followed by a significant reversal of this effect at higher doses (Contrada et al., 1991). That is, rather than indexing the graded increases in beta-sympathetic stimulation-as heart rate does in this paradigm-high doses of isoproterenol caused TWA to recover to values obtained at much lower levels of stimulation. These data suggest that the two cases showing reversals in the Contrada et al. (1989) study may have experienced a higher “effective” dose of isoproterenol than the majority of subjects as a consequence of endogenous factors influencing beta-sympathetic activity. This very line of reasoning from pharmacological data in a clinical population led Taggart et al. (1979) to hypothesize a curvilinear relationship between beta-sympathetic stimulation and TWA of the form that was observed by Contrada et al. (1991). To be sure, there is no direct evidence that individual cases of reversal in Contrada et al. (1989) reflect the same phenomenon that was responsible for the Contrada et al. (1991) findings. It seems equally certain, however, that examination of outliers was of heuristic value in suggesting that a dose-response study be undertaken. The results of that study, in turn, have drawn seriously into question the hypothesis that TWA tracks degree of beta-sympathetic stimulation-the hypothesis that lies at the very heart of this controversy. A third point worth mentioning in this context is that cardiological research is not the only arena in which the magnitude of experimental manipulations may not be representative of the naturalistic state to which results ultimately must be generalized. This is certainly the case in work involving pharmacological manipulations, in which nonbiological levels of neural activity or the artificial blockade of normally intact neural inputs may produce results of limited generalizability. Heslegrave and Furedy (1980) appear concerned with this issue as it pertains to the study of carotid dP/dt (see pp. 488-491). Yet they do not raise it in their comments on the Contrada et al. (1989) study, which yielded results consistent with their views. The external validity of all findings, whether reflecting the effects of pharmacological or behavioral manipulations, is a matter to be resolved by empirical analysis, not by argument.
6. Phrasing
of evaluative
statements
Furedy et al. object to evaluative statements made in previous articles in which the notion of TWA as an index of “cardiac sympathetic activity” has been described as a “misleading concept” and in which “further serious
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257
consideration of TWA as an adequate index of sympathetic nervous system” has been discouraged. Yet they themselves employed very similar language in a critique of carotid dP/dt: “Our overall conclusion will be that carotid d P/d t, at least as it has been employed in the cited papers, is of such limited utility that it should be abandoned in future research as an index of ventricular contractility and beta-adrenergic influences on the myocardium” (Heslegrave & Furedy, 1980, p. 483). One issue here is the correspondence of empirical observation and overall, evaluative conclusion. Is either of the foregoing quotes completely justified by the facts? Or do the recommendations speak more about the hunches, biases and intuitions of the authors? And in either case, would we be better off keeping judgments to ourselves, and sticking to the facts? On the question of accuracy, it would seem incumbent upon the reader to agree or disagree based upon his or her own independent consideration of relevant theory, empirical findings, and the social and historical context in which strongly phrased conclusions are stated. However one judges the correspondence between data and conclusions in the literature on TWA, it is difficult to find fault with the maxim that the facts never speak for themselves. They must be accompanied by interpretation, evaluation and recommendation if they are to have meaning, impact and scientific merit. By the same token, the hunches, biases and intuitions of investigators are of value only if they stimulate empirical observation, and are ultimately responsive to the resulting data. The recent studies by Contrada et al. (1989), Contrada et al. (19911, Muller, Schandry, Montoya, and Gsellhofer (1991), and Rau (1991) suggest that the polemics may, indeed, have given way to a more experimental approach to this problem.
Acknowledgment I thank Theodore this article.
Weiss for his valuable
comments
on an earlier
draft of
References Contrada, R.J., Dimsdale, J., Levy, L., & Weiss, T. (1991). Effects of isoproterenol on T-wave amplitude and heart rate: A dose-response study. Psychophysiology, 28, 458-462. Contrada, R.J., Krantz, D.S., Durel, L.A., Levy, L., LaRiccia, P.J., & Weiss, T. (1989). Effects of beta-adrenergic activity on T-wave amplitude. Psychophysiology, 26, 488-492. Dauchot, P., & Gravenstein, J.S. (1971). Effects of atropine on the electrocardiogram in different age groups. Clinical Pharmacology and Therapeutics, 12, 274-280. Furedy, J.J., & Heslegrave, R.J. (1983). A consideration of recent criticisms of the T-wave amplitude index of myocardial sympathetic activity. Psychophysiology, 20, 204-211.
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Furedy, J.J., Heslegrave, R.J., & Scher, H. (1984). Psychophysiological and physiological aspects of T-wave amplitude in the objective study of behavior. Paulouian Journal of Biological Science, 19, 182-194. Heslegrave, R.J., & Furedy, J.J. (1979). Sensitivities of HR and T-wave amplitude for detecting cognitive and anticipatory stress. Physiology and Behauior, 22, 17-23. Heslegrave, R.J., & Furedy, J.J. (1980). Carotid dP/dt as a psychophysiological index of sympathetic myocardial effects: Some considerations. Psychophysiology, 17, 482-494. Muller, A., Schandry, R., Montoya, P., & Gsellhofer, B. (1991). Differential effects of two stressors on heart rate, respiratory sinus arrhythmia, and T-wave amplitude. Journal of Psychophysiology, in press. Muranaka, M., Monou, H., Suzuki, J., Lane, J.D., Anderson, N.B., Kuhn, CM., Schanberg, S. M., McCown, N., & Williams, R.B. (1988). Physiological responses to catecholamine infusions in Type A and Type B, men. Health Psychology, 7 (SuppI.), 145-163. Rau, H. (1991). Responses of the T-wave amplitude as a function of active and passive tasks and beta-adrenergic blockade. Psychophysiology, 28, 231-239. Scher, H., Hartman, L.M., Furedy, J.J., & Heslegrave, R.J. (1986). Electrocardiographic T-wave changes are more pronounced in Type A than in Type B men during mental work. Psychosomatic Medicine, 48, 159-166. Schwartz, P.J., & Weiss, T. (1983). T-wave amplitude as an index of cardiac sympathetic activity: A misleading concept. Psychophysiology, 20, 696-701. Taggart, P., Carruthers, M., Joseph, S., Kelly, H.B., Marcomichelakis, J., Noble, D., O’Neill, O., & Somerville, W. (1979). Electrocardiographic changes resembling myocardial ischaemia in asymptomatic men with normal coronary arteriograms. British Heart Journal, 41, 214-225. Weiss, T., Del Bo, A., Reichek, N., & Engelman, K. (1980). Pulse transit time in the analysis of autonomic nervous system effects on the cardiovascular system. Psychophysiology, 17, 202207.
249 0301.0511/92/$05.00
Reply
T-wave amplitude: On the meaning of a psychophysiological index Richard Rutgers-The
J. Contrada State Unicersity of New Jersey, New Brunswick, NJ, USA
The preceding article by Furedy, Heslegrave and Scher presents a positive evaluation of T-wave amplitude (TWA) as a psychophysiologic index, and rejects the more cautious and less favorable view contained in a paper by Contrada et al. (1989). In this article I propose that the Furedy et al. perspective rests on: (1) a questionable approach to the logic of causal inference; (2) an unsatisfactory view of measurement validity; (3) the use of imprecise and therefore misleading language; (4) a disregard of valuable observations that can be drawn from the data of individual research subjects; (5) an objection to evaluative conclusions that can provide a useful stimulus to empirical inquiry. Close examination of these issues argues for a skeptical view of the state of knowledge regarding the meaning of TWA alterations. Keywords: T-wave amplitude, psychophysiologic sympathetic activity, parasympathetic
measurement, activity
beta-sympathetic
activity,
alpha-
1. Introduction In the preceding paper, Furedy, Heslegrave and Scher take exception to portions of an article by Contrada, Krantz, Durel, Levy, LaRiccia and Weiss (1989). The underlying question concerns the meaning of alterations in T-wave amplitude (TWA). Furedy and colleagues (e.g. this issue; Furedy & Heslegrave, 1983) have advanced strong claims concerning the validity of TWA as a measure of certain psychological and physiological processes. My colleagues and I have advanced more cautious and less favorable evaluations (e.g. Contrada et al., 1989; Contrada, Dimsdale, Levy & Weiss, 1991; Schwartz & Weiss, 1983; Weiss, Del Bo, Reichek & Engelman, 1980). In this paper I give a critique of five elements of the perspective advanced by Furedy et al.: (1) an approach to causal inference that leads to demonstrably premature conclusions; (2) a view of measurement that artificially compartmentalizes sources of evidence that must be considered jointly in assessCorrespondence to: Richard J. Contrada, Department University New Brunswick, NJ 08903, USA.
of Psychology,
Rutgers-The
State
250
R.J. Contrada / T-wace amplitude
ing validity; (3) a preference for imprecise language that can result in misleading theoretical assertions; (4) a disregard of data from individual subjects that might otherwise usefully inform more systematic investigation; (5) an objection to evaluative conclusions that actually play a constructive role in stimulating empirical research and scientific discourse.
2. Experimentation
and causal inference
2.1. Proximal versus distal causation Experiments document causal relationships between operations designed to influence the organism in some way and measures reflecting that influence. Intervening between operations and dependent measures are events that are not directly manipulated or observed, but that are invoked to provide tentative explanations for observed cause-effect relationships. Thus, in the Contrada et al. study, propranolol, isoproterenol and placebo were administered to subjects, and it appears from the results that “. . . T-wave amplitude is affected by beta-sympathetic activity” (Contrada et al., 1989, p. 491, emphasis added). This conclusion was carefully worded. In the absence of any direct information regarding the causal sequence that was initiated by drug administration, the Contrada et al. (1989) study cannot be taken as support for or against any specific hypothesis regarding the nature of the mechanisms that culminated in changes in TWA. Indeed, use of the term “beta-sympathetic” is inferential, because it is conceivable, albeit unlikely, that drug administration exerted its effects through other pathways. Moreover, Contrada et al. employed only single doses of a beta-adrenergic agonist and a beta-adrenergic antagonist. To have concluded that TWA was not merely affected by beta-sympathetic activity, but faithfully indexed the degree of beta-sympathetic activity, would clearly have been premature. Much more strongly worded conclusions regarding the meaning of TWA changes can be found in the writings of Furedy and colleagues. For example, Furedy and Heslegrave (1983) conclude their evaluation of TWA with the assertion that “. . . laboratories should, at present, consider TWA as an adequate index of SNS activity” (p. 210). To be sure, these authors have elsewhere urged that additional research is needed on this point. But underlying the controversy in this area is not merely disagreement as to whether the preponderance of the evidence points in one direction or another. The problem is in the qualitative distinction between a statistically significant effect (beta-sympathetic activity affects TWA), and so close a coupling between operation and physiologic process that the one is claimed as a measure of the other (TWA indexes SNS activity).
R.J. Contrada / T-waue amplitude
251
Ironically, an excellent illustration of this point can be found in an article by Heslegrave and Furedy (1980). The diagram in Fig. 1 of that article depicts sympathetic and parasympathetic inputs as distal causes of alterations in carotid dP/dt. These effects depend upon a number of intervening events that are more proximal to carotid dP/dt changes. The illustration makes it clear that there might be a real, but relatively weak, relationship between SNS activity and carotid d P/dt, because of loose links in the causal chain (SNS activity affects carotid d P/dt), or there might be a very strong relationship because the intervening links are so tightly coupled that information about proximal causes is redundant to information about SNS activity (carotid d P/d t indexes SNS activity). Construction and empirical evaluation of a comparable model describing the events that mediate sympathetic effects on TWA would seem prerequisite to Furedy et al’s claims regarding the meaning of TWA changes. 2.2. Specificity of cause Rather than advancing any one model, Contrada et al. (1989) pointed out that processes whereby drug administration affected T-wave amplitude take one of two general forms. If T-wave changes were specific to alterations in beta-sympathetic activity, then the mediating link was one that can only be brought into operation by altering beta-sympathetic activity. This rather strong conclusion would seem to be preferred by Furedy et al. However, results of the Contrada et al. study are perfectly compatible with an alternative interpretation, in which T-wave changes were nonspecific with respect to beta-sympathetic influences. In this view, events consequent to alterations in beta-sympathetic activity, but for which change in beta-sympathetic activity is not a necessary cause, mediated the effects of the pharmacological manipulations. We suggested, as an example of a nonspecificity interpretation, the notion that alteration in heart rate might have mediated the effects of drug administration on T-wave amplitude. Under this hypothesis, tachycardia produced by parasympathetic blockade, like that produced by increased beta-sympathetic input, would be expected to attenuate T-wave amplitude. This is precisely what was observed in a study by Dauchot & Gravenstein (1971). Although there may be alternative interpretations (see Furedy & Heslegrave, 19831, the most parsimonious explanation of the Dauchot and Gravenstein study is that TWA can be influenced by alterations in parasympathetic input (see also Muranaka et al., 1988). Curiously, Furedy and colleagues (Furedy, Heslegrave & Scher, 1984) appear quite sensitized to the specificity issue as it pertains to carotid d P/d t. They assert that “. . . an adequate candidate SNS measure should not be influenced by non-SNS factors” and then point to evidence that “. . . carotid
252
R.J. Contrada / T-wace amplitude
d P/d t was significantly influenced by pre- and after-load factors, as well as parasympathetic influences” (Furedy et al., 1984, pp. 184). Their conclusion is that violation of the specificity principle undermines the “valid use” of dP/dt to index sympathetic effects on the heart. It would seem that application of the same principle to the Dauchot and Gravenstein (1971) data should lead Furedy et al. to the same conclusion regarding TWA. Note, however, that we did not claim support for either the specificity or nonspecificity hypothesis. Either conclusion would most certainly go beyond the data, and our position on this is clearly evident from the statement that resolution of the specificity-sensitivity issue “awaits further research” (Contrada et al., 1989, p. 491). It should be noted, however, that ruling out all forms of the nonspecificity hypothesis challenges the powers of experimentation. Alternatives to the specificity hypothesis can only be supported by research in which plausible nonspecific mediators are controlled experimentally. As noted by Contrada et al., this analytic strategy is exemplified in research on pulse transit time (PTT; Weiss et al., 19801, in which pharmacological manipulations were employed to tease apart the contributions of beta-sympathetic and parasympathetic influences. 2.3. Generalizability Experiments permit conclusions regarding the existence of a phenomenon, not its preualence. Thus, evidence of fractional dissociation between HR and TWA demonstrates that fractional dissociation is possible, not that it is typical. It does not, as Furedy et al. (this issue) assert, “refute the view that TWA changes are merely a function, or artifact, of HR changes”. Instead, it demonstrates only that there exist conditions under which TWA can change independently of HR changes. The problem with the Furedy et al. argument can be illustrated by applying it to a well-understood phenomenon: it would be tantamount to the conclusion that, because HR variations can be induced in an atropinized subject, parasympathetic input never affects HR.
3. Principles
of validity in measurement
Furedy et al. arrive at a positive evaluation of TWA by distinguishing between its linkages with three types of criteria: psychological processes (“psychophysiologic index” criterion), autonomic inputs (“physiologic index” criterion), and myocardial events (“physiologic mechanism” criterion). This approach so fractionates the system of variables in which TWA is embedded that claims of psychophysiologic validity are advanced without invoking any specific physiologic event. It also leads to mutually contradictory assertions in which alteration in TWA is simultaneously viewed as a measure of mental
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effort, sympathetic nervous system activity, and the synchrony of ventricular repolarization. Furedy et al. argue that TWA has validity as a psychophysiological index because it is affected by behavioral challenges, thereby demonstrating “reacand because it responds to some behavioral processes tive sensitivity,” (performing arithmetic operations) but not others (encoding arithmetic problems), thereby demonstrating “specific sensitivity”. They argue further that (1) the psychophysiologic index criterion requires no assumptions regarding the relationship between sympathetic activity and TWA, and (2) with respect to specific sensitivity, it is the superiority of TWA over HR (which is responsive to both encoding and operation) that is critical to establishing psychophysiological validity. The hypothesis that TWA reflects sympathetic activity clearly is essential to psychophysiologic index validity. It is this assumption that leads to an examination of the effects of behavioral challenge on TWA. To interpose a “black box” between task instructions and the magnitude of oscillograph deflections is to take a blindly empirical approach to experimentation that belies the very notion that gave impetus to the investigation. Moreover, it is contradictory to deny claims regarding the mediating role of sympathetic activity in one context, while elsewhere invoking “increased sympathetic activity” and consequent “nonuniform, asynchronous shortening of the refractory periods in various areas of the myocardium” (Scher, Hartman, Furedy & Heslegrave, 1986, p. 166) to explain behavioral influences on TWA. One cannot have a “psychophysiological” index without making at least tentative assumptions about physiology. The notion that a significant effect of encoding on one measure (HR) lends psychophysiologic validity to another measure (TWA) that appears unaffected by encoding is also problematic. Furedy et al. (1984) argue that by responding to arithmetic operations, but not to the encoding of arithmetic problems, TWA provides additional, “complementary information to that provided by HR, and in this sense allows us to interpret the experiments with greater psychophysiological sensitivity” (p. 18.5). The logic underlying this assertion is as follows. Any measure that shows greater discrimination between encoding and operation than that shown by HR has value as a psychophysiologic index. By this reasoning, a valid psychophysiologic index could be had by instructing the subject to depress a button while attending to arithmetic problems, and release the button while solving the problems. Button pressing (or, say, consequent alterations in forearm EMG activity), would provide “additional, complementary information” regarding behavioral activity. The problem with this logic is twofold. First, there must be some hypothesis linking the encoding-operation distinction to TWA. As Furedy et al. themselves point out, the possibilities are numerous, as they include mental
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effort, motor (speaking) output, general somatic activity, posture, and the quality or intensity of affective response. It remains to be determined whether alterations in TWA are specific to one of the behavioral parameters mentioned above, or reflect a final common pathway whereby a number of such parameters influence TWA. Information gain cannot be claimed until the information is characterized. Second, there is little basis for setting up HR as the standard for comparison in these studies. It is very curious that Furedy et al. elevate HR to the status of a criterion index in this context, while at the same time criticizing our comparison of TWA and PTT. Useful evaluative standards should be derived from hypotheses regarding the process in question. The performance of PTT in the Weiss et al. (1980) study is consistent with the hypothesis that PTT reflects beta-sympathetic influences. Thus, there is a theoretical basis for considering the performance of PTT in this research as a standard against which to evaluate TWA. Under what specific hypothesis about the cognitive processes involved in encoding and performing arithmetic problems is a psychophysiologic index validated by showing it exceeds HR in its ability to discriminate these two processes? Rather than compartmentalizing validity criteria, it would seem preferable to view the meaning of TWA within a unitary conceptual framework. Such a framework would begin with an analysis of relevant psychological and pharmacological events, whose effects on the autonomic nervous system, as well as on other potential mediating mechanisms, might be expected to alter the synchrony of ventricular repolarization. A broader focus on a system of related variables provides a more accurate representation of the phenomenon than narrow, oversimplified assertions concerning bivariate, measurement-level relationships. It also constitutes a necessary first step toward the goal of integrating disparate research findings. Such findings are likely to remain isolated if the problem is cast in terms of three disjunctive sets of evaluative criteria.
4. Precision
in language
Furedy et al. concede that, in principle, their notion of “sympathetic myocardial influence” is insufficiently precise. However, they argue that the distinction between alpha- and beta-adrenergic activity is of little import in the study of TWA because, in their view, sympathetic myocardial influences are primarily mediated by beta-adrenergic innervation. Instead, Furedy et al. wish to focus on the sympathetic-parasympathetic distinction. As discussed above, there is cause to question the “purity” of TWA with respect to parasympathetic influences (Dauchot & Gravenstein, 1971; Muranaka et al., 1988). Setting this issue aside, however, there remains another
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reason why it would be a mistake to drop the alpha/beta distinction at this point. Quite distinct from the direct effects of sympathetic stimulation on the myocardium are possible indirect effects that may involve both alpha- and beta-adrenergic activity. As Furedy et al. (this issue, Footnote 1) assert, in addition to beta-sympathetic influences, “ . . . under some conditions, TWA is and alpha-adrenergic) and affected.. . by other neural (e.g. parasympathetic non-neural factors”. Complex effects involving multiple inputs are particularly relevant to studies of behavioral challenges that may produce both alpha- and beta-sympathetic responses (e.g. Heslegrave & Furedy, 1979). Even if the proximal cause of such TWA changes exclusively involves beta-sympathetic influences on the myocardium, a complete account of events mediating those changes may include the more distal effects of non-beta-sympathetic mechanisms. To focus exclusively on the sympathetic/parasympathetic distinction is misleading because it combines under one label (“sympathetic”) both proximal and distal influences involving alpha-adrenergic effects, beta-adrenergic effects, and non-adrenergic effects.
5. Relevance of the single case Furedy et al. reject the cautionary note sounded by Contrada et al. (1989) on the basis of their observation that 2 of 12 individual cases showed TWA augmentation (rather than attenuation) to isoproterenol infusion. Their argument is that (1) reversals of direction in a single clinical case must be taken seriously for medical reasons, whereas psychophysiology does not deal with data from individual cases but with the statistical analysis of group data, and (2) cardiological manipulations produce larger magnitude changes than those of psychophysiology. These arguments ignore several important considerations. First, we drew no conclusion from the two instances of reversal. The observations were simply mentioned, following our discussion of the specificity issue, as an added caution regarding the meaning and generalizability of our results. It is disconcerting when results for even one or two cases fall in a direction opposite to that expected under the hypothesis being tested. Individual cases of reversal are especially troubling to claims regarding the use of a variable as an index of a particular, cardiac event. Such claims are stronger than those asserting merely that an experimental manipulation had a statistically significant impact on a dependent measure, and therefore must be evaluated against more stringent criteria. At a minimum, these individual differences provide useful information regarding the consistency of the drug effects, and therefore on the reliability with which TWA responds to alterations in
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beta-sympathetic activity. Reliability is, of course, a sine qua non of measurement. Second, our concerns appear to have been borne out. Our most recent investigation indicates that initial TWA attenuation following low-dose infusion of isoproterenol is followed by a significant reversal of this effect at higher doses (Contrada et al., 1991). That is, rather than indexing the graded increases in beta-sympathetic stimulation-as heart rate does in this paradigm-high doses of isoproterenol caused TWA to recover to values obtained at much lower levels of stimulation. These data suggest that the two cases showing reversals in the Contrada et al. (1989) study may have experienced a higher “effective” dose of isoproterenol than the majority of subjects as a consequence of endogenous factors influencing beta-sympathetic activity. This very line of reasoning from pharmacological data in a clinical population led Taggart et al. (1979) to hypothesize a curvilinear relationship between beta-sympathetic stimulation and TWA of the form that was observed by Contrada et al. (1991). To be sure, there is no direct evidence that individual cases of reversal in Contrada et al. (1989) reflect the same phenomenon that was responsible for the Contrada et al. (1991) findings. It seems equally certain, however, that examination of outliers was of heuristic value in suggesting that a dose-response study be undertaken. The results of that study, in turn, have drawn seriously into question the hypothesis that TWA tracks degree of beta-sympathetic stimulation-the hypothesis that lies at the very heart of this controversy. A third point worth mentioning in this context is that cardiological research is not the only arena in which the magnitude of experimental manipulations may not be representative of the naturalistic state to which results ultimately must be generalized. This is certainly the case in work involving pharmacological manipulations, in which nonbiological levels of neural activity or the artificial blockade of normally intact neural inputs may produce results of limited generalizability. Heslegrave and Furedy (1980) appear concerned with this issue as it pertains to the study of carotid dP/dt (see pp. 488-491). Yet they do not raise it in their comments on the Contrada et al. (1989) study, which yielded results consistent with their views. The external validity of all findings, whether reflecting the effects of pharmacological or behavioral manipulations, is a matter to be resolved by empirical analysis, not by argument.
6. Phrasing
of evaluative
statements
Furedy et al. object to evaluative statements made in previous articles in which the notion of TWA as an index of “cardiac sympathetic activity” has been described as a “misleading concept” and in which “further serious
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consideration of TWA as an adequate index of sympathetic nervous system” has been discouraged. Yet they themselves employed very similar language in a critique of carotid dP/dt: “Our overall conclusion will be that carotid d P/d t, at least as it has been employed in the cited papers, is of such limited utility that it should be abandoned in future research as an index of ventricular contractility and beta-adrenergic influences on the myocardium” (Heslegrave & Furedy, 1980, p. 483). One issue here is the correspondence of empirical observation and overall, evaluative conclusion. Is either of the foregoing quotes completely justified by the facts? Or do the recommendations speak more about the hunches, biases and intuitions of the authors? And in either case, would we be better off keeping judgments to ourselves, and sticking to the facts? On the question of accuracy, it would seem incumbent upon the reader to agree or disagree based upon his or her own independent consideration of relevant theory, empirical findings, and the social and historical context in which strongly phrased conclusions are stated. However one judges the correspondence between data and conclusions in the literature on TWA, it is difficult to find fault with the maxim that the facts never speak for themselves. They must be accompanied by interpretation, evaluation and recommendation if they are to have meaning, impact and scientific merit. By the same token, the hunches, biases and intuitions of investigators are of value only if they stimulate empirical observation, and are ultimately responsive to the resulting data. The recent studies by Contrada et al. (1989), Contrada et al. (19911, Muller, Schandry, Montoya, and Gsellhofer (1991), and Rau (1991) suggest that the polemics may, indeed, have given way to a more experimental approach to this problem.
Acknowledgment I thank Theodore this article.
Weiss for his valuable
comments
on an earlier
draft of
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Furedy, J.J., Heslegrave, R.J., & Scher, H. (1984). Psychophysiological and physiological aspects of T-wave amplitude in the objective study of behavior. Paulouian Journal of Biological Science, 19, 182-194. Heslegrave, R.J., & Furedy, J.J. (1979). Sensitivities of HR and T-wave amplitude for detecting cognitive and anticipatory stress. Physiology and Behauior, 22, 17-23. Heslegrave, R.J., & Furedy, J.J. (1980). Carotid dP/dt as a psychophysiological index of sympathetic myocardial effects: Some considerations. Psychophysiology, 17, 482-494. Muller, A., Schandry, R., Montoya, P., & Gsellhofer, B. (1991). Differential effects of two stressors on heart rate, respiratory sinus arrhythmia, and T-wave amplitude. Journal of Psychophysiology, in press. Muranaka, M., Monou, H., Suzuki, J., Lane, J.D., Anderson, N.B., Kuhn, CM., Schanberg, S. M., McCown, N., & Williams, R.B. (1988). Physiological responses to catecholamine infusions in Type A and Type B, men. Health Psychology, 7 (SuppI.), 145-163. Rau, H. (1991). Responses of the T-wave amplitude as a function of active and passive tasks and beta-adrenergic blockade. Psychophysiology, 28, 231-239. Scher, H., Hartman, L.M., Furedy, J.J., & Heslegrave, R.J. (1986). Electrocardiographic T-wave changes are more pronounced in Type A than in Type B men during mental work. Psychosomatic Medicine, 48, 159-166. Schwartz, P.J., & Weiss, T. (1983). T-wave amplitude as an index of cardiac sympathetic activity: A misleading concept. Psychophysiology, 20, 696-701. Taggart, P., Carruthers, M., Joseph, S., Kelly, H.B., Marcomichelakis, J., Noble, D., O’Neill, O., & Somerville, W. (1979). Electrocardiographic changes resembling myocardial ischaemia in asymptomatic men with normal coronary arteriograms. British Heart Journal, 41, 214-225. Weiss, T., Del Bo, A., Reichek, N., & Engelman, K. (1980). Pulse transit time in the analysis of autonomic nervous system effects on the cardiovascular system. Psychophysiology, 17, 202207.
