Chemical lesions of the nucleus isthmi increase the hypoxic and hypercarbic drive to breathing of toads

The nucleus isthmi (NI) is a mesencephalic structure of the amphibian brain that has recently been reported to participate in the hypoxic and hypercarbic drive to breathing. However, previous studies used electrolytic and kainic lesions, which causes diffuse and nonspecific destruction. Thus, in the present study, we assessed the participation of NI in the respiratory response to hypoxia and hypercarbia using lesions produced with ibotenic acid (a substance that selectively destroys cell bodies but spares fibers of passage) into the NI of toads (Bufo paracnemis). Our results demonstrated that, under resting breathing, NI plays no role in pulmonary ventilation. Hypoxia and hypercarbia caused hyperventilation in all groups. Chemical lesions in the NI elicited an increase in ventilatory response to hypoxia and hypercarbia, due to a higher tidal volume. We conclude that NI cell bodies do not participate in the control of pulmonary ventilation under resting conditions, but exert an inhibitory modulation of hypoxic and hypercarbic drive to breathing, acting on tidal volume.     

Compartmental chest wall volume changes during volitional hyperpnoea with constant tidal volume in healthy individuals

Prolonged high-intensity ventilation is associated with the development of rapid shallow breathing with decreased end-inspiratory volumes of all chest wall compartments. During respiratory muscle endurance training using normocapnic hyperpnoea, tidal volume (V_T) is normally kept constant. The aim of this study was to investigate possible changes in muscle recruitment during constant-V_T hyperpnoea, to assess potential mechanisms related to rapid shallow breathing. Ten healthy subjects performed 1 h of normocapnic hyperpnoea at 70% of maximal voluntary ventilation. Chest wall volume changes were assessed by optoelectronic plethysmography. End-inspiratory (1.08 ± 0.18 versus 0.96 ± 0.27 l, p = 0.017) and end-expiratory volumes (−0.13 ± 0.15 versus −0.31 ± 0.19 l, p = 0.007) of the pulmonary ribcage decreased significantly and lung function and respiratory muscle strength were reduced (all p < 0.05). Since with forced, constant V_T only the inspiratory rib cage muscles were unable to sustain end-inspiratory volume of their compartment, inspiratory rib cage muscles are the most likely candidate responsible for the development of rapid shallow breathing.     

Dopaminergic modulation of exercise hyperpnoea via D(2) receptors in mice

Dopamine is related to behaviour (including arousal, motivation and motor control of locomotion), and its turnover in the brain is increased during exercise. We examined the hypothesis that dopamine D(2) receptors contribute to exercise hyperpnoea via central neural pathways using the D(2)-like receptor antagonist, raclopride. We simultaneously measured ventilation and pulmonary gas exchange for the first time in mice. Mice injected with saline and raclopride (2 mg (kg body weight)(-1); i.p.) were compared for respiratory responses to constant-load exercise at 6 m min(-1). Each mouse was set in an airtight treadmill chamber. In the resting state, raclopride-treated mice had reduced respiratory frequency (f(R)) and minute ventilation (V) compared with saline-treated mice, but arterial P(CO(2)) and pulmonary gas exchange were not affected, showing that alveolar ventilation was maintained. Inhalation of hyperoxic gas maintained V in saline-treated mice, and hypercapnic ventilatory responses between the two groups were similar. Treadmill exercise produced an abrupt increase in V to a maximal level within 1 min and declined to a steady-state level in both groups. Raclopride-treated mice had reduced f(R) and V compared with saline-treated mice during steady states, but showed a similar increase in f(R) and V at exercise onset. Minute ventilation in the steady state was controlled, along with the increase in pulmonary O(2) uptake in both groups, but was lowered in raclopride-treated mice. Thus, D(2) receptors participate in resting breathing patterns to raise f(R) and exercise hyperpnoea in the steady state, probably through behavioural control and not central motor command, at exercise onset.     

The Contribution of Chemoreflex Drives to Resting Breathing in Man

The contribution of automatic drives to breathing at rest, relative to behavioural drives such as "wakefulness", has been a subject of debate. We measured the combined central and peripheral chemoreflex contribution to resting ventilation using a modified rebreathing method that included a prior hyperventilation and addition of oxygen to maintain isoxia at a P(ET,O2) (end-tidal partial pressure of oxygen) of 100 mmHg. During rebreathing, ventilation was unrelated to P(ET,CO2) (end-tidal partial pressure of carbon dioxide) in the hypocapnic range, but after a threshold P(ET,CO2) was exceeded, ventilation increased linearly with P(ET,CO2). We considered the sub-threshold ventilation to be an estimate of the behavioural drives to breathe (mean +/- S.E.M. = 3.1 +/- 0.5 l min(-1)), and compared it to ventilation at rest (mean +/- S.E.M. = 9.1 +/- 0.7 l min(-1)). The difference was significant (Student's paired t test, P < 0.001). We also considered the threshold P(CO2) observed during rebreathing to be an estimate of the chemoreflex threshold at rest (mean +/- S.E.M. = 42.0 +/- 0.5 mmHg). However, P(ET,CO2) during rebreathing estimates mixed venous or tissue P(CO2), whereas the resting P(ET,CO2) during resting breathing estimates P(a,CO2) (arterial partial pressure of carbon dioxide). The chemoreflex threshold measured during rebreathing was therefore reduced by the difference in P(ET,CO2) at rest and at the start of rebreathing (the plateau estimates the mixed venous P(CO2) at rest) in order to make comparisons. The corrected chemoreflex thresholds (mean +/- S.E.M. = 26.0 +/- 0.9 mmHg) were significantly less (paired Student's t test, P < 0.001) than the resting P(ET,CO2) values (mean +/- S.E.M. = 34.3 +/- 0.5 mmHg). We conclude that both the behavioural and chemoreflex drives contribute to resting ventilation. Experimental Physiology (2001) 86.1, 109-116.     

Inspiratory muscle training reduces blood lactate concentration during volitional hyperpnoea

Although reduced blood lactate concentrations ([lac(-)](B)) have been observed during whole-body exercise following inspiratory muscle training (IMT), it remains unknown whether the inspiratory muscles are the source of at least part of this reduction. To investigate this, we tested the hypothesis that IMT would attenuate the increase in [lac(-)](B) caused by mimicking, at rest, the breathing pattern observed during high-intensity exercise. Twenty-two physically active males were matched for 85% maximal exercise minute ventilation (.V(E) max) and divided equally into an IMT or a control group. Prior to and following a 6 week intervention, participants performed 10 min of volitional hyperpnoea at the breathing pattern commensurate with 85% .V(E) max. The IMT group performed 6 weeks of pressure-threshold IMT; the control group performed no IMT. Maximal inspiratory mouth pressure increased (mean +/- SD) 31 +/- 22% following IMT and was unchanged in the control group. Prior to the intervention in the control group, [lac(-)](B) increased from 0.76 +/- 0.24 mmol L(-1) at rest to 1.50 +/- 0.60 mmol L(-1) (P < 0.05) following 10 min volitional hyperpnoea. In the IMT group, [lac(-)](B) increased from 0.85 +/- 0.40 mmol L(-1) at rest to 2.02 +/- 0.85 mmol L(-1) following 10 min volitional hyperpnoea (P < 0.05). After 6 weeks, increases in [lac(-)](B) during volitional hyperpnoea were unchanged in the control group. Conversely, following IMT the increase in [lac(-)](B) during volitional hyperpnoea was reduced by 17 +/- 37% and 25 +/- 34% following 8 and 10 min, respectively (P < 0.05). In conclusion, increases in [lac(-)](B) during volitional hyperpnoea at 85% .V(E) max were attenuated following IMT. These findings suggest that the inspiratory muscles were the source of at least part of this reduction, and provide a possible explanation for some of the IMT-mediated reductions in [lac(-)](B), often observed during whole-body exercise.     

The regulation of respiratory resistance in exercising horses

Horses display remarkable aerobic capabilities, attaining during muscular exercise a maximal rate of oxygen consumption about 30-fold higher than the resting value, and 2.5-fold higher than that of other mammals of similar body mass. Under these circumstances an enormous mechanical burden is expected to impinge on the equine respiratory pump and regulatory mechanisms aiming to minimize this load may play an important role in determining the adequacy of the respiratory system to the metabolic requirements. The behaviour of the respiratory system has been investigated in horses at rest and during treadmill locomotion at different velocities and gaits. During exercise hyperpnoea, horses exhibit a significant reduction in the lung viscous resistance not observed in other mammals, such as dogs and humans. Therefore, the exercise-dependent increase in the rate of mechanical work of breathing is lower in the horse than in other mammals. This increase in the equine airway patency during exercise appeared to be mainly determined by the pattern of laryngeal movements. In fact, during exercise, the laryngeal cross-sectional area, determined with a video-endoscopic imaging technique at the level of rima glottidis (CSArg), undergoes during inspiration an increase averaging up to over 4 times the resting expiratory values. Although a significant linear correlation was found between CSArg and minute ventilation (_E), the laryngeal activation contributes to increase lung conductance only when CSArg is narrower than the tracheal section. It appears therefore that in exercising horses pulmonary resistive features are finely controlled to reduce the mechanical load supported by the respiratory muscles and to counterbalance the increase in the ventilatory energetic requirements inherent in the remarkably enhanced aerobic performance observed in this species.     

The Importance of Ventilation in Exercise-Induced Asthma

The degree of post treadmill-running decrease in pulmonary function (Exercise-Induced Asthma) in 11 adult asthmatics was compared with the decrease in pulmonary function followed by resting isocapnic hyperventilation. It was checked that ventilation during the hyperventilation was kept identical to the ventilation during treadmill-running by continuous recording of respiratory frequency, minute ventilation, tidal volume and accumulated ventilation. The temperature of the inspired air was identical in the two situations and the relative humidity was 40% during treadmill-running and 15% during hyperventilation. The average accumulated ventilation during treadmill-running and hyperventilation was 411 1/6 min in both events. The decrease in peak expiratory flow after treadmill-running was 25% and after isocapnic hyperventilation 24%. It is concluded that the ventilation is of more importance for the decrease in pulmonary function after exercise, than the work load.     

Restoration of reflex ventilatory response to hypoxia after removal of carotid bodies in the cat

In mammals there are two sets of peripheral arterial chemoreceptors, the carotid bodies innervated by the sinus branch of the glossopharyngeal nerve and the aortic bodies innervated by the vagus nerves. The afferent impulse discharge from both receptors increases during hypoxia and there is a reflexly mediated increase in ventilation (hypoxic hyperventilation). In the present study we tested this response by exposing anesthetized cats to decreased inspired O₂ concentration before and up to 315 days after bilateral resection of the carotid bodies. Acutely after removing the carotid bodies, hypoxic hyperventilation was abolished. This observation supports the view that the reflex pathway from the aortic body receptors normally contributes minimally to hypoxic hyperventilation. Subsequently, there was a restoration of hypoxic hyperventilation. Restoration was significant 30–43 days after removing the carotid bodies, it reached 70% of the preoperative value at 93–111 days and was essentially complete in terminal experiments 260–315 days after carotid body resection. In terminal experiments, hypoxic hyperventilation was not affected by recutting the regenerated carotid sinus nerves but was abolished completely by bilateral transection of the cervical vagosympathetic trunks. The restored ventilatory response was due predominantly to an increase in rate of breathing while an increase in tidal volume was predominant before carotid body resection. Resting ventilation breathing room air was not consistently decreased after carotid body resection while expired CO₂ was elevated from day 20 to day 111 and at the preoperative level in terminal experiments.It is concluded that restoration of hypoxic hyperventilation in the cat after carotid body resection is mediated by the reflex pathway from aortic body chemoreceptors. The possible contribution of chemo-receptive regenerated carotid sinus nerve axons was excluded. It is suggested that restoration may be a consequence of the central reorganization of chemoreceptor afferent pathways consequent to interruption of the carotid body reflex pathway and that as a result the ‘gain’ of the aortic body ventilatory chemoreflex is enhanced.     

Stretch receptor activity during irritant-induced tachypnoea in the rabbit

The activity in single vagal fibres arising from lung stretch receptors was recorded in rabbits during normal breathing at rest and during tachypnoea caused by inhalation of histamine or ammonia. The rate of argon elimination from the lungs was analysed to estimate the accompanying changes of lung ventilation.The results show that the majority of stretch receptors increased their activity during irritant-induced tachypnoea, the discharge frequency being always higher during inspiration than during expiration. Only a few fibres did not change or decreased their activity.The comparison of the results with previous findings in guinea-pig revealed that the discharge pattern of stretch receptors following inhalation of irritants was different in these two species, whereas the respiratory reactions and the unevenness of ventilation were comparable. It is suggested that the differences in the discharge pattern of stretch receptor fibres during irritant-induced hyperpnoea in rabbit and guinea-pig are due to differences in the location of the stretch receptors concerned.     

Secretory immunoglobulin A and cardiovascular activity during mental arithmetic and paced breathing.

The role of the autonomic nervous system in secretory immunoglobulin A (sIgA) responses to laboratory challenge was explored in a study in which sIgA and cardiovascular activity were recorded at rest and during mental arithmetic and paced breathing. These tasks were selected to preferentially engage the sympathetic and parasympathetic nervous systems, respectively. Mental arithmetic elicited a mixed pattern of increased alpha- and beta-adrenergic activity and a reduction in parasympathetic activity; diastolic blood pressure, total peripheral resistance, and systolic blood pressure increased, preejection period shortened, and heart rate variability decreased. In contrast, paced breathing primarily elicited an increase in parasympathetic activity; heart rate variability increased. Mental arithmetic also provoked an increase in sIgA concentration but no change in saliva volume, whereas paced breathing affected neither sIgA concentration nor saliva volume. These data suggest that sIgA responses to laboratory challenges are mediated by sympathetic rather than parasympathetic processes.     

Effects of hyperventilation on the circulatory response of the rabbit to arterial hypoxia

1. The circulatory effects of artificial hyperventilation with air and low oxygen mixtures were studied in rabbits anaesthetized with chloralose-urethane and given decamethonium iodide. The role of vagal afferents in the response to hypoxia was also assessed in spontaneously breathing unanaesthetized and anaesthetized animals.2. In the anaesthetized rabbit artificial hyperventilation inhibited all the changes in autonomic activity to the heart and peripheral circulation resulting from stimulation of the arterial chemoreceptors, and also reduced vagal efferent tone. In animals with section of the carotid sinus and aortic nerves the changes in autonomic activity observed during hypoxia and hyperventilation were much smaller than in normal animals and affected only cardiac autonomic activity.3. The effects of hyperventilation during hypoxia were mediated chiefly through vagal afferents rather than through the effects of hypocapnia. In the absence of changes in autonomic activity (e.g. during artificial hyperventilation with air) the circulatory effects were small and less clearly related to afferent vagal activity.4. In the spontaneously breathing anaesthetized and unanaesthetized rabbit vagal afferent activity resulting from the respiratory response to hypoxia inhibits sympatho-adrenal activity in the same way as during hypoxia with artificial hyperventilation.5. The importance of the vagal afferent input in the rabbit is discussed in relation to the qualitative differences in circulatory response with increasing severity of hypoxia, and in relation to the effects of anaesthesia.     

Interoceptive threat leads to defensive mobilization in highly anxiety sensitive persons

To study defensive mobilization elicited by the exposure to interoceptive arousal sensations, we exposed highly anxiety sensitive students to a symptom provocation task. Symptom reports, autonomic arousal, and the startle eyeblink response were monitored during guided hyperventilation and a recovery period in 26 highly anxiety sensitive persons and 22 controls. Normoventilation was used as a non-provocative comparison condition. Hyperventilation led to autonomic arousal and a marked increase in somatic symptoms. While high and low anxiety sensitive persons did not differ in their defensive activation during hyperventilation, group differences were detected during early recovery. Highly anxiety sensitive students exhibited a potentiation of startle response magnitudes and increased autonomic arousal after hyper- as compared to after normoventilation, indicating defensive mobilization evoked by the prolonged presence of feared somatic sensations.     

Daytime sleepiness and neural cardiac modulation in sleep-related breathing disorders

Sleep-related breathing disorders are common causes of excessive daytime sleepiness, a socially and clinically relevant problem. Mechanisms responsible for daytime sleepiness are still largely unknown. We investigated whether specific alterations in autonomic cardiac modulation during sleep, commonly associated with sleep-related breathing disorders, are related to excessive daytime sleepiness. Fifty-three patients with sleep-related breathing disorders underwent nocturnal polysomnography. Excessive daytime sleepiness was diagnosed as a Multiple Sleep Latency Test response less than or equal to 600 s. We explored the relation of excessive daytime sleepiness, objectively determined, with indices of autonomic cardiac regulation, such as baroreflex sensitivity and heart rate variability, with polysomnographic indices of the severity of sleep-related breathing disorders and with quality of sleep. Patients with excessive daytime sleepiness, when compared with patients without, had significantly lower baroreflex sensitivity and significantly higher low-to-high frequency power ratio of heart rate variability during the different stages of nocturnal sleep. By contrast, no differences were found in indices quantifying the severity of sleep-related breathing disorders or sleep quality. We demonstrated that excessive daytime sleepiness is accompanied by a deranged cardiac autonomic control at night, the latter probably reflecting autonomic arousals not detectable in the EEG. As abnormal autonomic regulation is also known to be associated with increased cardiovascular risk, a possible relation between excessive daytime sleepiness and cardiovascular events in patients with sleep-related breathing disorders deserves to be investigated in future studies.     

Peripheral Chemoreflex and Baroreflex Interactions in Cardiovascular Regulation in Humans

We tested the hypothesis that activation of peripheral chemoreceptors with acute isocapnic hypoxia resets arterial baroreflex control of both heart rate and sympathetic vasoconstrictor outflow to higher pressures, resulting in increased heart rate and muscle sympathetic nerve activity without changes in baroreflex sensitivity. We further hypothesized that this resetting would not occur during isocapnic hyperpnoea at the same breathing rate and depth as during isocapnic hypoxia. In 12 healthy, non-smoking, normotensive subjects (6 women, 6 men, 19-36 years), we assessed baroreflex control of heart rate and muscle sympathetic nerve activity using the modified Oxford technique during normoxia, isocapnic hyperpnoea, and isocapnic hypoxia (85 % arterial O₂ saturation). While isocapnic hyperpnoea did not alter heart rate, arterial pressure, or sympathetic outflow, hypoxia increased heart rate from 61.9 ± 1.8 to 74.7 ± 2.7 beats min⁻¹ (   P < 0.05  ), increased mean arterial pressure from 97.4 ± 2.0 to 103.9 ± 3.3 mmHg (   P < 0.05  ), and increased sympathetic activity 22 ± 13 % relative to normoxia and 72 ± 21 % (   P < 0.05  ) relative to hyperpnoea alone. The sensitivity for baroreflex control of both heart rate and sympathetic activity was not altered by either hypoxia or hyperpnoea. Thus, it appears that acute activation of peripheral chemoreceptors with isocapnic hypoxia resets baroreflex control of both heart rate and sympathetic activity to higher pressures without changes in baroreflex sensitivity. Furthermore, these effects appear largely independent of breathing rate and tidal volume.     

Interactions of Respiratory and Cardiovascular Adjustments to Behavioral Stressors

The relationships among a variety of cardiovascular and respiratory measures were examined in young college males subjected to a cold pressor task, reaction-time shock avoidance task, and three levels of graded exercise. As expected, the relationships between cardiovascular (e.g., heart rate and cardiac output) and respiratory (e.g., oxygen uptake and minute ventilation) variables were tightly linear when considering rest and exercise values. However, the range of individual cardiopulmonary responses during cold pressor and reaction time was considerable, often leading to disruptions in the cardiovascular/respiratory interactions. Analyses of extreme high and low ventilation reactors during both reaction time and cold pressor revealed that the excessive ventilation responders in cold pressor showed clear signs of hyperventilation. Increases in ventilation by the high reactors during reaction time were of smaller magnitude than during cold pressor, with potential hyperventilation much less clear. Increases in minute ventilation by reactors during the cold pressor task were primarily due to large increases in tidal volume, with only modest increases in respiratory rate. For reaction time, however, the increases in ventilation by reactive individuals stemmed from rate increases with tidal volume remaining essentially unchanged.     

Increased ventilation and CO2 chemosensitivity in acetylcholinesterase knockout mice

To investigate the effects of a permanent excess of acetylcholine (AChE) on respiration, breathing and chemosensitivity were analyzed from birth to adulthood in mice lacking the AChE gene (AChE-/-), in heterozygotes, and in control wild-type (AChE+/+) littermates. Breathing at rest and ventilatory responses to brief exposures to hypoxia (10% O2) and hypercapnia (3-5% CO2) were measured by whole-body plethysmography. At rest AChE-/- mice show larger tidal volumes (VT, + 96% in adults), overall ventilation (VE, + 70%), and mean inspiratory flow (+270%) than wild-type mice, with no change in breathing frequency (fR). AChE-/- mice have a slightly blunted response to hypoxia, but increased VE and fR responses to hypercapnia. Heterozygous animals present no consistent alterations of breathing at rest and chemosensitivity is normal. Adult AChE-/- mice have an increased VE/VO2 and a marginally higher normalized VO2. The results suggest that the hyperventilation and altered chemosensitivity in AChE-/- mice largely reflect alterations of central respiratory control.     

Effects of long-lasting stimulation of extensor muscle nerves on pulmonary ventilation in cats

Increments in pulmonary ventilation were shown to occur in anaesthetized cats during long-lasting stimulation of a peripherally cut extensor muscle nerve at maximal intensity for group I afferent fibers. However, these increments tended to gradually adapt to a lower value when stimuli were delivered at high frequency and constant rate whereas a tendency to potentiation, up to a steady state, occurred when stimulation was intermittent. End-tidal initially decreased with a tendency to adaptation in the case of continuous stimulation, and decreased progressively in the case of intermittent stimulation. It is concluded that the nervous mechanisms producing hyperpnoea exhibit fatigue during their constant excitation while their effects sum up during intermittent stimulation.     

Resting sympathetic arousal moderates the association between parasympathetic reactivity and working memory performance in adults reporting high levels of life stress

The neurovisceral integration model stipulates that autonomic function plays a critical role in the regulation of higher‐order cognitive processes, yet most work to date has examined parasympathetic function in isolation from sympathetic function. Furthermore, the majority of work has been conducted on normative samples, which typically demonstrate parasympathetic withdrawal to increase arousal needed to complete cognitive tasks. Little is known about how autonomic regulation supports cognitive function in populations exposed to high levels of stress, which is critical given that chronic stress exposure alters autonomic function. To address this, we sought to characterize how parasympathetic (high‐frequency heart rate variability, HF‐HRV) and sympathetic (preejection period, PEP) measures of cardiac function contribute to individual differences in working memory (WM) capacity in a sample of high‐risk women. HF‐HRV and PEP were measured at rest and during a visual change detection measure of WM. Multilevel modeling was used to examine within‐person fluctuations in WM performance throughout the task concurrently with HF‐HRV and PEP, as well as between‐person differences as a function of resting HF‐HRV and PEP levels. Results indicate that resting PEP moderated the association between HF‐HRV reactivity and WM capacity. Increases in WM capacity across the task were associated with increases in parasympathetic activity, but only among individuals with longer resting PEP (lower sympathetic arousal). Follow‐up analyses showed that shorter resting PEP was associated with greater cumulative risk exposure. These results support the autonomic space framework, in that the relationship between behavior and parasympathetic function appears dependent on resting sympathetic activation.     

Mechanisms of ventilatory periodicities

The study of ventilatory periodicities is relevant to the problem of obstructive sleep apnea. Apneas occur at the nadirs of periodicities during sleep. Periodicities can be caused by chemical instability, related to unstable action of the closed loop feedback system for the chemical regulation of breathing. Such instability occurs when overall loop gain is greater than or equal to unity and the phase lag around the loop is 180°. Periodic breathing during hypoxia and in patients with congestive heart failure is likely to be explained by this mechanism. Periodic breathing can also be the result of state instability. Here ventilation declines at sleep onset and the resultant changes in blood gases trigger an arousal, i.e., sudden transition to a lighter stage of sleep. With arousal, ventilation increases. Thus, periodic breathing is secondary to these changes in sleep state. These processes, chemical instability and state instability, can interact and produce complex patterns of oscillation in ventilation.     

Relationships Between Behavioral Arousal and Some Components of Autonomic Arousal

The present experiment examined 11 male adolescents for relationships between the autonomic measures of heart rate (HR) and skin conductance (SC) and three rates of finger tapping, a) subject resting, b) DRL.5 sec, and c) FR5, as a measure of behavioral arousal. At each level of behavioral arousal, minimum, mean, and maximum HR were analyzed. Mean and maximum HR increased only at high arousal, while minimum HR increased with each increase in behavioral arousal. SC was higher during tapping than resting, but was uninfluenced by rate of tapping. The potential value of the maximum and minimum HR and SC measures as tools for inferring the role of parasympathetic versus sympathetic mechanisms in autonomic arousal was discussed. This paradigm provides a simple, nonaversive method for examining autonomic and behavioral arousal.