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J Appl Physiol 97: 2112-2120, 2004. First published July 23, 2004; doi:10.1152/japplphysiol.00302.2004
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Respiratory response to passive limb movement is suppressed by a cognitive task

Harold J. Bell1 and James Duffin1,2

Departments of 1Physiology and 2Anaesthesia, University of Toronto, Toronto, Ontario, Canada M5S 1A8

Submitted 19 March 2004 ; accepted in final form 21 July 2004


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
Feedback from muscles stimulates ventilation at the onset of passive movement. We hypothesized that central neural activity via a cognitive task source would interact with afferent feedback, and we tested this hypothesis by examining the fast changes in ventilation at the transition from rest to passive leg movement, under two conditions: 1) no task and 2) solving a computer-based puzzle. Resting breathing was greater in condition 2 than in condition 1, evidenced by an increase in mean ± SE breathing frequency (18.2 ± 1.1 vs. 15.0 ± 1.2 breaths/min, P = 0.004) and ventilation (10.93 ± 1.16 vs. 9.11 ± 1.17 l/min, P < 0.001). In condition 1, the onset of passive movement produced a fast increase in mean ± SE breathing frequency (change of 2.9 ± 0.4 breaths/min, P < 0.001), tidal volume (change of 233 ± 95 ml, P < 0.001), and ventilation (change of 6.00 ± 1.76 l/min, P < 0.001). However, in condition 2, the onset of passive movement only produced a fast increase in mean ± SE breathing frequency (change of 1.3 ± 0.4 breaths/min, P = 0.045), significantly smaller than in condition 1 (P = 0.007). These findings provide evidence for an interaction between central neural cognitive activity and the afferent feedback mechanism, and we conclude that the performance of a cognitive task suppresses the respiratory response to passive movement.

exercise hyperpnea; wakefulness drive; afferent feedback

AT THE ONSET OF EXERCISE, ventilation (E) increases immediately (25), and the rapid onset of this drive to breathe has led to it being assigned a neural origin, since it is too fast for a humoral source (15, 26). This "exercise drive to breathing" is hypothesized to result from two sources: one is "peripheral neurogenic drive," whereby afferent feedback from the exercising limbs leads to increased respiration (21); the other is "central command," whereby motor commands to the limbs initiate a parallel activation of respiration (17, 49).

In the integrated system, both of these mechanisms are initiated simultaneously; therefore, any interaction between them could affect their respective contributions toward the control of breathing. Indeed, animal model studies have provided evidence of interactions between central motor commands and afferent feedback (2, 13, 37). Such findings support the idea that, at the onset of exercise, neural drives to breathe via distinct mechanisms are incorporated to provide the drive to breathe that is observed in the integrated system.

The onset of exercise also involves an increase in central neural activity via cortical brain activity (23, 32) that is not solely related to the motor outflow to the muscles itself. For example, during imagined exercise where both central motor command and afferent feedback mechanisms are absent, significant increases in cortical activity occur and this activity is able to increase breathing (47). The effect of this brain activity or arousal, which is independent of actual motor command, on the afferent feedback mechanism is presently unknown.

We do know that forms of neural arousal apart from exercise affect respiratory control in humans (34, 40). Such arousal-related influences are ambient light and sound (19, 44), and cognitive tasks, such as solving puzzles and mathematical problems (24, 41, 43). A withdrawal of such central neural arousal occurs in sleep (33, 40, 42, 48), and the drive to breathe that is related to this arousal or behavior is therefore also withdrawn, leading to it being referred to as a "wakefulness drive to breathe" (18). Interestingly, a reduction in arousal can also be effected through meditation, and the resulting decreases in respiratory rate and tidal volume (VT) (46, 51) demonstrate that the wakefulness drive to breathe is also affected. We therefore use the term "wakefulness" to describe a central neural phenomenon that is similar to alertness or awareness, attributing it to increased central neural activity or arousal.

Given the evidence suggesting there is interaction between central motor activity and afferent feedback in animal preparations, we wished to investigate whether central neural activity related to the state of wakefulness would also affect the afferent feedback mechanism in humans. To increase wakefulness in our experimental subjects, we used a cognitive task, solving a puzzle; to stimulate the afferent feedback mechanism, we used passive leg extension movements. With passive movement of a subject's limbs in a rhythmic, exercise-like fashion, mechanical changes in the skeletal muscles can generate afferent feedback and thereby increase E (5). Because central motor command is absent during this process, the transition from rest to passive limb movement allows the discrete study of afferent feedback and how its contribution to respiratory control may be affected by increased wakefulness via a cognitive task.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
In conformation with Canadian Tri-Council on Human Experimentation Policy, the methods and techniques used in this study were approved by the Office of Research Services at the University of Toronto (protocol reference no. 10303). Nine subjects, five men and four women, were recruited for this study, and their informed consent was obtained. All were healthy nonsmokers with no history of cardiorespiratory illness. Their mean (SD) age, weight, and height were 24.0 (1.3) yr, 67.5 (4.0) kg, and 173.8 (3.9) cm, respectively.

Subjects were asked to visit the laboratory on two occasions. During the first visit, a familiarization session, subjects were shown the equipment and techniques that we would use, introduced to the sensation of passive leg movements in the tandem chair apparatus, and familiarized with a computer-based puzzle called "The Tower of Hanoi" (Fig. 1). A second visit, no more than 1 wk later, was arranged to perform the experimental protocol in which the subjects completed two passive leg movement sessions, identical except that during one they relaxed and during the other they solved the computer-based puzzle.



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  		Fig. 1. The Tower of Hanoi puzzle consists of a tower of rings, initially stacked in increasing size on 1 of 3 pegs. The objective is to move the stack of rings from the first post to the third post stacked in the same order. All posts can be used during the transfer, but only smaller rings may be placed on top of larger rings. The puzzle may be solved in a minimum number of moves with difficulty increasing with the number of rings used.

 
General procedures.   The common elements of the two sessions involved monitoring the subject during rest and passive leg movements on a tandem chair apparatus. The tandem chair is able to provide a form of passive leg extension movement and has previously been described in detail (4, 5). Passive movements were performed at a leg frequency of 70 cycles per minute per leg in an alternating fashion. Passive limb movement was started during the "late-expiratory" phase of the ventilatory cycle, and the range of motion of the lower leg defined a change in angle of ~70° (270° at maximum flexion to 200° at maximum extension). E, VT, breathing frequency (fB), heart rate, mean arterial blood pressure (MAP), end-tidal PCO2 (PETCO2), mixed expired PCO2 and PO2, leg movement frequency (fLM), and leg muscle activity (EMG) were monitored noninvasively throughout all procedures. Subjects were comfortably seated in the chair apparatus and were monitored for 3 min at rest before beginning 3 min of passive leg extensions. Monitoring continued through another 3 min of rest after the cessation of passive movement. This common procedure was performed twice, under the following two conditions.

For condition 1, the subject is awake, seated in the chair, and wearing a blindfold and ear protectors ("ear-muff" type, –29 decibels) to minimize arousal via visual and auditory stimuli, throughout this entire data collection interval. This condition will be referred to as the low wakefulness (LW) protocol.

For condition 2, the subject is awake and is seated in the tandem chair while solving a computer-based puzzle called the "Tower of Hanoi" on a notebook computer to increase arousal throughout this entire data collection interval. This condition will be referred to as the high wakefulness (HW) protocol.

Computer-based puzzle.   In the HW protocol, subjects were solving a puzzle called the Tower of Hanoi, shown schematically in Fig. 1. Subjects controlled the game using a mouse connected to a laptop computer placed at eye level ~4 ft in front of them, while they sat in the tandem chair. The mouse was placed on the right-hand side of the chair on a mouse pad that was fixed to the frame of the chair. The specific program was, at the time of this study, available as freeware on the internet (http://www.mazeworks.com/hanoi/, Copyright 2002 David Herzog; based on the puzzle invented by French mathematician Edouard Lucas in 1883).

Equipment.   Subjects breathed through an air-cushioned facemask (model KM201/202/203, Vacu·Med, Ventura, CA), and breathing was monitored with a turbine (universal ventilation meter, model 17125, Vacu·Med). The turbine was connected to a two-way non-rebreathing valve (model 2630, Hans Rudolph, Kansas City, MO), enabling the subject to inspire room air while their expirate was collected in a 7-liter compliant mixing bag that passively emptied into the room. We monitored PETCO2 using an anesthetic gas monitor (type 1304, Bruel and Kajer) that sampled via a port on the inspired side of the turbine. Mixed expired PO2 and PCO2 were monitored via gas analyzers (models CD-3A and S-3A/1, respectively, Applied Electrochemistry, Pittsburg, PA) sampling via a catheter within the mixing bag. We monitored heart rate and MAP on a beat-to-beat basis using a Portapres (model 2.0, FMS, Arnhem, The Netherlands). Root-mean-squared leg muscle EMG was monitored via surface electrodes (Meditrace 133, Ludlow LP, Chicopee, MA) placed over the vastus lateralis of the left leg, using the suprailiac region of the lateral abdomen as a ground site. The raw EMG signal was passed through a two-stage preamplifier (Neurolog model NL 100 and NL 104 in series, Digitimer, Hertfordshire, UK) and a custom-built downstream AC filter (high pass >10 Hz, low pass <500 Hz).

The experimenter controlled a data-acquisition computer (Inspiron 8100, Dell) from a seated position in the rear seat of the tandem chair, interfaced via a mouse, and maintained the pace of limb movement (fLM) by following a visual metronome integrated into the data-acquisition software. fLM was monitored with a mercury switch mounted to the left extension arm of the chair and connected to a digital input on the data-acquisition system. The continuous analog output from all monitoring devices was also passed through a pulse-code modulation recording adapter (model 4000A, A. R. Vetter) to allow archiving of data on VHS tape (JVC Hi-Fi Stereo VCR, model HR-D840U 500C, JVC Americas). Analog signals were fed to a 16-bit data-acquisition card (DAQCard-AI-16XE-50, National Instruments, Austin, TX) installed in the data-acquisition computer. Data-acquisition software was custom designed (LabVIEW 6.1, National Instruments; source code available on request). Signals were displayed in real time (sampling rate = 20 Hz), and data were analyzed and collected on a breath-by-breath basis and written to a text array file for further analysis. The exception to this breath-by-breath analysis of data was the collection of metabolic gas-exchange data, which was performed by the software on the basis of mixed-expired values as averaged over intervals corresponding to the collection of 4 liters of expired air in the mixing bag.

Data analysis.   Data collected during the experiment were analyzed with a specially written analysis software (Labview 6.1, National Instruments). This software uses a line-fitting technique that minimizes the mean standard error to determine an equation that best describes the data over each of the three discrete intervals of the test: 1) rest, 2) passive limb movement, and 3) recovery. Data collection began for a subject once all monitored parameters appeared to be stable; thus the resting parameters (E, VT, etc.) were fitted with a straight line of zero slope. The software then used the Levenberg-Marquardt algorithm to fit an exponential rise or decline or a dual-exponential rise or decline to the data of the passive movement and recovery. The equation that better described the data (smaller mean squared error) was chosen as the representative equation. From these line equations, data points were then calculated for times corresponding to the start of the phase, and each 15 s thereafter, up to and including the 3-min mark (i.e., 180 s) for that interval. In other words, data points were determined along the regression lines at times of 0, 15, 30, 45, ..., 180 s for the first rest interval. For the interval of passive limb movement, data points were determined at times of 180, 195, 210, ..., 360 s. For the 3-min interval after the cessation of passive limb movement, data points were calculated at times corresponding to times of 360, 375, 390, ..., 540 s.

To determine whether our method of altering wakefulness drive to breathe was effective, we compared resting (premovement) values for E, VT, fB, PETCO2, heart rate, MAP, and metabolic gas exchange [oxygen uptake (O2) and carbon dioxide production (CO2)] between the two conditions (HW vs. LW). Subjects were self-matched for comparison; therefore, all statistical testing involved repeated measures (RM) analysis. We used one-way RM ANOVA testing and Bonferroni's post hoc analysis to test for any significant effects of the background cognitive state on the resting measures. Tests were conducted using an a priori level of significance ({alpha}) set at 0.05.

To examine the behavior of observed parameters during passive movement in the two background conditions, we used two-way RM ANOVA, again with Bonferroni's post hoc testing. Experimental condition (LW and HW) was one factor considered in analysis, with limb movement status (rest and passive movement) as a second factor. Again, all analyses were performed with an a priori level of significance ({alpha}) set at 0.05. Analysis was performed with the binned data calculated from the fitted equations at 15-s intervals. E, VT, fB, heart rate, and MAP were analyzed for evidence of fast changes at the onset and cessation of passive movements by performing a two-way RM ANOVA on four data points corresponding to 1) the end of the premovement rest interval, 2) the beginning of the passive movement interval, 3) the end of the passive movement interval, and 4) the beginning of the postmovement rest interval. Significant changes in these parameters at the onset and cessation of passive movements were interpreted to be an index of the drive to breathing provided by peripheral neurogenic drive.

Leg movement pace, fLM, and leg muscle activity (EMG) for the two background conditions (LW and HW) were compared between states (rest and passive movement) with a two-way RM ANOVA, using data points corresponding to the last point of rest before passive movement and the last point of passive movement. PETCO2, O2, and CO2 were analyzed in the same manner, enabling a comparison between parameters at rest and values closest to what would be considered "steady-state" passive movement, in both LW and HW conditions.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
All volume-based measurements are stated as BTPS values, and all experimental measures are reported as means ± SE. Raw E, fB, and VT data for one subject in both LW and HW conditions are shown in Figs. 2 and 3. Figure 4 shows data for respiratory measures averaged across all nine subjects in both LW and HW conditions.



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  		Fig. 2. Breath-by-breath data and the regressions lines fitted to minimize mean squared error for one 55.9-kg, 162-cm, female subject in the low wakefulness (LW) condition. Shown are ventilation (E; A), breathing frequency (fB; B), and tidal volume (VT; C). Vertical dashed lines indicate time points where values were determined on regression lines. br·min–1, Breaths/min. See Fig. 4 for average response across all subjects.

 


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  		Fig. 3. Corresponding data from the high wakefulness (HW) condition for the same subject displayed in Fig. 2. Again, shown are E (A), fB (B), and VT (C). Vertical dashed lines indicate time points where values were determined on regression lines. See Fig. 4 for average response across all subjects.

 


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  		Fig. 4. A comparison of resting E (A), fB (B), and VT (C) between LW and HW conditions. Each subject is represented by a unique symbol that is common to both conditions and to each graph.

 
Ventilatory measures.   Values for E, VT, and fB averaged across all subjects in both HW and LW conditions at the four points of interest in the protocol are shown in Table 1. Mean resting E and fB were higher during HW than during LW (P < 0.001 and P < 0.004, respectively). There were no differences in resting VT between LW and HW conditions (P = 1.00). All subjects exhibited greater E at rest during HW compared with LW (Fig. 4).


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  		Table 1. Measurements of respiratory and cardiovascular parameters

 
Two-way RM ANOVA indicated that limb movement status was a significant factor in determining E (P < 0.001), fB (P = 0.001), and VT (P = 0.017), demonstrating that all three respiratory parameters increased at the start of passive movement (see Figs. 5 and 6). There was an interaction effect between the factors of movement status and the wakefulness condition present for the three respiratory measurements of E (P = 0.002), fB (P = 0.004), and VT (P = 0.002). In other words, background wakefulness condition affected the size of the fast changes in E, fB, and VT that resulted from the passive leg movement. In the LW condition, fast increases were observed in all three parameters at the onset of passive leg movement (see Table 2 and Fig. 6). In the HW condition, only fB increased significantly, but this increase was smaller than the corresponding increase in the LW condition.



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  		Fig. 5. Effects of passive leg movement (shaded area) on respiratory measures under LW ({circ}) and HW ({bullet}) conditions. A: E. B: fB. C: VT. D: end-tidal PCO2 (PETCO2). Data are 15-s binned averages of all subjects' measurements.

 


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  		Fig. 6. Bar graphs of the fast changes at the onset of passive leg movement in the LW and HW conditions. A: E. B: fB. C: VT. Symbols denote significant differences as follows: {ddagger}significant between HW and LW groups, P ≤ 0.004; **significant between rest vs. the start of passive leg movement, P ≤ 0.001; *significant between rest vs. the start of passive leg movement, P ≤ 0.045.

 

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  		Table 2. Changes in respiratory parameters

 
When passive leg movements were stopped in the LW condition, there was a fast decrease in both E (P = 0.011) and fB ( P < 0.001) but not in VT (P = 0.53). In the HW condition, neither E (P = 1.000) nor its components fB (P = 0.074) and VT (P = 1.000) demonstrated significant fast changes at the end of passive leg movement.

PETCO2.   The behavior of PETCO2 is illustrated in Fig. 5D. Resting PETCO2 was significantly lower (P = 0.002) during HW (36.8 ± 0.6 Torr) than during LW (38.6 ± 0.8 Torr). There was neither evidence of significant treatment effects for the factors of wakefulness condition or movement status nor evidence of an interaction between these factors.

Cardiovascular measurements.   Average heart rate and MAP for all subjects during both HW and LW conditions at the four points of interest in the protocol are shown in Table 1. Resting heart rate was significantly higher in HW than during LW (P = 0.017); no such differences were present in resting MAP (P = 0.860). Passive leg movements had a significant effect on heart rate (P < 0.001), but the fast changes at the start and end of passive movement were not significant (P = 0.197 and P = 1.00, respectively). Rather, a significant difference was present between heart rate at the start and end of the 3 min of passive leg movement (P < 0.001). Passive movements had no significant effect on MAP (P = 0.763). There was no effect of wakefulness condition on either heart rate (P = 0.111) or MAP (P = 0.994). In addition, there was no evidence of interaction effect between passive movement status and wakefulness condition for heart rate (P = 0.205) or MAP (P = 0.910)

Metabolic gas exchange.   Metabolic gas-exchange data are summarized in Fig. 7. There were no significant differences at rest during LW and HW in terms of either O2 (P = 0.214) or CO2 (P = 0.190). Neither wakefulness condition nor passive movement status significantly affected O2 (P = 0.288 and P = 0.724, respectively) or CO2 (P = 0.529 and P = 0.141, respectively), and these factors did not interact (P = 0.994 and P = 0.471, respectively).



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  		Fig. 7. A comparison of gas-exchange parameters during rest (open bars) and after 3 min of passive leg movement (shaded bars) in the LW and HW conditions. A: oxygen uptake. B: carbon dioxide production.

 
Movement frequency.   The average fLM during passive movement was 70.6 ± 0.2 s–1 per leg during LW and 70.9 ± 0.3 s–1 per leg during HW. There was no effect of wakefulness condition on fLM (P = 0.389); movement pace was the same in both conditions.

Leg muscle activity.   The EMG signal changed significantly during passive movement, independent of wakefulness condition (P = 0.024). There was no independent effect of wakefulness condition (P = 0.659), and no interaction effect was present between wakefulness condition and movement status (P = 0.436). The average EMG activity at rest for both conditions combined was 1.6 ± 0.2 µV, which increased to 2.1 ± 0.3 µV during passive movement.


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
General observations.   At rest in the HW condition, subjects exhibited increased E, resulting from an increase in fB, compared with the LW condition. The start of passive leg movements in the LW condition caused a fast increase in E, fB, and VT. In the HW condition, the respiratory response to the onset of passive leg movement was different; there was no increase in either E or VT, and the increase in fB was significantly smaller. There were no apparent effects of passive leg movements on the cardiovascular measurements of heart rate and MAP, apart from a decline in heart rate during the 3 min of passive limb movement in either condition.

Wakefulness condition.   In the LW condition, subjects were blindfolded and wore ear protectors that minimized auditory and visual stimuli. In the HW condition, subjects solved a computer-based puzzle game with minimal incentive to quickly move the hand or fingers so as to minimize the use of musculature during the protocol; indeed metabolic gas exchange at rest was not significantly affected by the wakefulness condition.

In previous studies reporting the effect of wakefulness on resting E, VT appeared to be less affected than fB (3, 10, 41, 44), and our findings agree; E was ~20% greater during rest during HW than during LW, and this was achieved through an elevated fB with VT unaffected. The higher resting E during HW compared with LW was sufficient to cause significantly lower PETCO2 levels. These findings are consistent with the present knowledge of the effect of wakefulness on the control of breathing at rest; therefore, we are confident that we provided subjects with two conditions with the desired difference in background wakefulness drive.

The additional central stimulation of E in the HW condition caused a mild hyperventilation at rest, lowering PETCO2 by ~2 Torr compared with the LW condition. Although such a difference between conditions provided a mechanism that may have altered the ventilatory response at the start of passive leg movements, the literature suggests otherwise. There are three studies that suggest that hypocapnia may reduce or eliminate the fast increase in E at the start of exercise attributed to fast neural drives to breathe (1, 22, 50). However, the present consensus in literature suggests that the decrease in PETCO2 that we observed in the HW condition at rest was unlikely to affect the fast changes in E observed at the onset of limb movement (8, 9, 16, 28–30). These studies collectively show that mild to moderate acute hypocapnia does not affect the fast neural drives to breathe at the start of exercise. A thorough discussion of the issues surrounding this topic appears in the most recent of these papers (27). We are therefore confident that the differences that we observed between the LW and HW conditions cannot be attributed to a difference of 1.8 Torr in PETCO2 before passive movements.

Effectiveness of passive leg movement.   We used a method of passive movement that we have previously described and validated (4, 5). The onset of passive leg movement is likely to cause a return of pooled venous blood from the lower limbs into the central circulation that will transiently alter respiratory control. However, we were interested in the fast (nearly immediate) changes in E at the onset of passive limb movement. Such fast changes occur before the pooled venous blood alters central arterial PO2 and PCO2, thereby stimulating E. Therefore, although passive leg extension movements do not isolate afferent feedback from all other respiratory drives throughout the movement period, they do isolate afferent feedback from central motor drive during the rapid phase of ventilatory adjustment at the start of limb movement.

Passive leg extensions were effective, increasing E over resting values. Because these changes were observed at the onset of passive leg movement, we attribute them to peripheral neurogenic drive due to stimulation of mechanically sensitive, lightly myelinated or nonmyelinated afferent fibers in skeletal muscles (21).

That the leg movements were passive is attested to by the small increase in EMG activity. Although EMG activity was significantly increased by 1 µV on average, this was far less than the 20–50 µV that we routinely observe during light to moderate active exercise of the same modality and frequency. We therefore attribute the observed increase to movement artifact and not to an active exercise component. Further corroboration of the passive nature of the movement was the lack of increase in O2 and CO2.

Interaction between peripheral neurogenic drive and wakefulness.   These experiments provide the first evidence in awake humans that the ventilatory response to the afferent feedback mechanism is altered by the level of cognitive activity. Ishida et al. (20) measured the ventilatory response to passive leg movements during sleep and awake states in human subjects and found that the fast changes were greater during sleep; however, these differences were not statistically significant. Nonetheless, their study does provide corroborative support for our observations. Our study only differs in that our subjects were awake in both conditions; we varied the level of arousal or wakefulness via a cognitive task, and significant changes in respiratory control were observed.

We have also shown that the background wakefulness condition affected the behavior of both the VT and fB components of E during passive movement; there were fast changes evident in all three measures during LW. By contrast, in the HW condition, fast changes at the onset of passive movement were only evident in fB and absent in both VT and E.

Mechanism and site of interaction.   Whereas our results suggest that the wakefulness associated with a cognitive task suppresses the afferent feedback mechanism that increases E during passive movement, the nature and location of this interaction remain speculative. Increased wakefulness appears to produce two independent changes in respiratory control: it both augments E at rest and suppresses the ventilatory response to afferent feedback. There is therefore likely a site of interaction outside the respiratory rhythm generation network because inhibition or disfacilitation of the respiratory rhythm generation network itself would result in a decrease in E at rest.

A cognitive task has been shown to affect the H reflex in humans (38). It is therefore possible that neural activity via a cognitive task may modulate other neural signals at the level of the spinal cord in a manner similar to the way in which central motor command that has been shown to interact with afferent feedback (14). Alternatively, the interaction could take place in higher regions of the central nervous system, which would agree with the view of Ishida et al. (20). Sites that influence respiratory control that are known to receive sensory input and/or respond to states of arousal include medullary reticular neurons (6, 11, 45), the retrotrapezoid nucleus (7, 12, 31), the nucleus reticularis gigantocellularis (37), and the nucleus tractus solitarius (35, 36, 39).

Potential significance for exercise hyperpnea.   If the respiratory response to the afferent feedback of passive limb movement is suppressed when wakefulness is increased, is afferent feedback an effective drive to breathing during active exercise in humans? During active exercise, there is central nervous system activity that is not directly related to the generation of central motor command but rather is concerned with the planning of movement, goal-oriented behavior, anticipation of events, and other thought processes. Therefore, there is likely to be a significant increase in cognitive activity independent of the central command mechanism at the start of active exercise. We therefore speculate that such increased arousal or wakefulness during exercise may effectively suppress the peripheral neurogenic drive to breathe from afferent feedback, rendering that mechanism ineffective during active exercise in the integrated system.

Nevertheless, we emphasize the following caveats. First, the wakefulness associated with exercise may be quite different from that associated with solving a puzzle, and thus the respiratory consequences may be equally different. Second, there may be differences in the quantitative and/or qualitative nature of the afferent feedback and how it interacts with wakefulness drives during normal exercise.

Conclusion.   Increased wakefulness via a cognitive task suppresses the respiratory response to passive limb movement. However, the relevance of this finding toward the control of exercise hyperpnea will require future investigation into the nature and behaviors of central neural arousal and afferent feedback during exercise.


   GRANTS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
ACKNOWLEDGMENTS
 REFERENCES
 
H. J. Bell is supported by a Toronto Rehabilitation Institute/Ontario Graduate Scholarship in Science and Technology Student Scholarship.


   ACKNOWLEDGMENTS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
REFERENCES
 
We thank Laila Nurmohamed for assistance in performing these experiments.


   FOOTNOTES
 

Address for reprint requests and other correspondence: J. Duffin, Dept. of Physiology, Univ. of Toronto, 1 King's College Circle, Toronto, ON, Canada M5S 1A8 (E-mail: j.duffin{at}utoronto.ca)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 

  1. Asmussen E. Ventilation at transition from rest to exercise. Acta Physiol Scand 89: 68–78, 1973.
  2. Bauer RM, Waldrop TG, Iwamoto GA, and Holzwarth MA. Properties of ventrolateral medullary neurons that respond to muscular contraction. Brain Res Bull 28: 167–178, 1992.
  3. Bechbache RR, Chow HHK, Duffin J, and Orsini EC. The effects of hypercapnia, hypoxia, exercise and anxiety on the pattern of breathing in man. J Physiol 293: 285–300, 1979.
  4. Bell HJ and Duffin J. CO2 does not affect passive exercise ventilatory decline. J Appl Physiol 95: 322–329, 2003.
  5. Bell HJ, Ramsaroop DM, and Duffin J. The respiratory effects of two modes of passive exercise. Eur J Appl Physiol 88: 544–552, 2003.
  6. Billig I, Card JP, and Yates BJ. Neurochemical phenotypes of MRF neurons influencing diaphragm and rectus abdominis activity. J Appl Physiol 94: 391–398, 2003.
  7. Bodineau L, Frugiere A, Marlot D, and Wallois F. Connections between retrotrapezoid nucleus and nucleus tractus solitarii in cat. Neurosci Lett 280: 111–114, 2000.
  8. Casey K, Duffin J, Kelsey CJ, and McAvoy GV. The effect of treadmill speed on ventilation at the start of exercise in man. J Physiol 391: 13–24, 1987.
  9. Cerretelli P, Grassi B, Xi L, Schena F, Marconi C, Meyer M, and Ferretti G. The role of pulmonary CO2 flow in the control of the phase I ventilatory response to exercise in humans. Eur J Appl Physiol 71: 287–294, 1995.
  10. Chin K, Ohi M, Fukui M, Kita H, Tsuboi T, Noguchi T, Otsuka N, Hirata H, Mishima M, and Kuno K. Inhibitory effect of an intellectual task on breathing after voluntary hyperventilation. J Appl Physiol 81: 1379–1387, 1996.
  11. Craig AD. Distribution of brainstem projections from spinal lamina I neurons in the cat and the monkey. J Comp Neurol 361: 225–248, 1995.
  12. Cream C, Li A, and Nattie E. The retrotrapezoid nucleus (RTN): local cytoarchitecture and afferent connections. Respir Physiol Neurobiol 130: 121–137, 2002.
  13. Degtyarenko AM and Kaufman MP. Fictive locomotion and scratching inhibit dorsal horn neurons receiving thin fiber afferent input. Am J Physiol Regul Integr Comp Physiol 279: R394–R403, 2000.
  14. Degtyarenko AM and Kaufman MP. Stimulation of the MLR inhibits the discharge of dorsal horn neurons responsive to muscular contraction. Brain Res 880: 178–182, 2000.
  15. Dejours P. The regulation of breathing during muscular exercise in man: a neuro-humoral theory. In: The Regulation of Human Respiration, edited by Cunningham DJC and Lloyd BB. Oxford, UK: Blackwell Scientific, 1963, p. 535–547.
  16. Duffin J and McAvoy GV. The peripheral-chemoreceptor threshold to carbon dioxide in man. J Physiol 406: 15–26, 1988.
  17. Eldridge FL and Waldrop TG. Neural control of breathing during exercise. In: Exercise: Pulmonary Physiology and Pathophysiology, edited by Whipp BJ and Wasserman K. New York: Dekker, 1991, p. 309–370.
  18. Fink BR. Influence of cerebral activity in wakefulness on regulation of breathing. J Appl Physiol 16: 15–20, 1961.
  19. Haas F, Distenfeld S, and Axen K. Effects of perceived musical rhythm on respiratory pattern. J Appl Physiol 61: 1185–1191, 1986.
  20. Ishida K, Yasuda Y, and Miyamura M. Cardiorespiratory response at the onset of passive leg movements during sleep in humans. Eur J Appl Physiol 66: 507–513, 1993.
  21. Kaufman MP and Forster HV. Reflexes controlling circulatory, ventilatory, and airway responses to exercise. In: Handbook of Physiology. Exercise: Regulation and Integration of Multiple Systems. Bethesda, MD: Am. Physiol. Soc., 1996, sect. 12, chapt. 10, p. 381–447.
  22. Krogh A and Lindhard J. The regulation of respiration and circulation during the initial stages of muscular work. J Physiol 47: 112–136, 1913.
  23. Kubitz KA and Mott AA. EEG power spectral densities during and after cycle ergometer exercise. Res Q Exerc Sport 67: 91–96, 1996.
  24. Mador MJ and Tobin MJ. Effect of alterations in mental activity on the breathing pattern in healthy subjects. Am Rev Respir Dis 144: 481–487, 1991.
  25. Mateika JH and Duffin J. A review of the control of breathing during exercise. Eur J Appl Physiol 71: 1–27, 1995.
  26. Matell G. Time courses of changes in ventilation and arterial gas tensions in man induced by moderate exercise. Acta Physiol Scand 58: 1–53, 1963.
  27. McConnell A and Gardener WN. The ventilatory response to moderate hypocapnic exercise in human beings. Respir Physiol 103: 147–156, 1996.
  28. McConnell AK and Semple ES. Ventilatory sensitivity to carbon dioxide: the influence of exercise and athleticism. Med Sci Sports Exerc 28: 685–691, 1996.
  29. Miyamura M, Ishida K, Kobayashi T, Ohkuwa T, and Itoh H. Effects of acute hypoxia on ventilatory response at the onset of cycle exercise in man. Jpn J Physiol 42: 823–829, 1992.
  30. Miyamura M, Xe L, Ishida K, Schena F, and Cerretelli P. Effects of acute hypoxia on ventilatory response at the onset of submaximal exercise. Jpn J Physiol 40: 417–422, 1990.
  31. Nattie EE. Central chemosensitivity, sleep, and wakefulness. Respir Physiol 129: 257–268, 2001.
  32. Nielsen B, Hyldig T, Bidstrup F, Gonzalez-Alonso J, and Christoffersen GR. Brain activity and fatigue during prolonged exercise in the heat. Pflügers Arch 442: 41–48, 2001.
  33. Orem J. Medullary respiratory neuron activity: relationship to tonic and phasic REM sleep. J Appl Physiol 48: 54–65, 1980.
  34. Orem J and Trotter RH. Behavioral control of breathing. News Physiol Sci 9: 228–232, 1994.
  35. Otake K and Nakamura Y. Forebrain neurons with collateral projections to both the interstitial nucleus of the posterior limb of the anterior commissure and the nucleus of the solitary tract in the rat. Neuroscience 119: 623–628, 2003.
  36. Potts JT. Exercise and sensory integration. Role of the nucleus tractus solitarius. Ann NY Acad Sci 940: 221–236, 2001.
  37. Richard CA, Waldrop TG, Bauer RM, Mitchell JH, and Stremel RW. The nucleus reticularis gigantocellularis modulates the cardiopulmonary responses to central and peripheral drives related to exercise. Brain Res 482: 49–56, 1989.
  38. Rossi-Durand C. The influence of increased muscle spindle sensitivity on Achilles tendon jerk and H-reflex in relaxed human subjects. Somatosens Mot Res 19: 286–295, 2002.
  39. Sequeira H, Viltart O, Ba-M'Hamed S, and Poulain P. Cortical control of somato-cardiovascular integration: neuroanatomical studies. Brain Res Bull 53: 87–93, 2000.
  40. Shea SA. Behavioural and arousal-related influences on breathing in humans. Exp Physiol 81: 1–26, 1996.
  41. Shea SA, Andres LP, Paydarfar D, Banzett RB, and Shannon DC. Effect of mental activity on breathing in congenital central hypoventilation syndrome. Respir Physiol 94: 251–263, 1993.
  42. Shea SA, Horner RL, Benchetrit G, and Guz A. The persistence of a respiratory "personality" into stage IV sleep in man. Respir Physiol 80: 33–44, 1990.
  43. Shea SA, Murphy K, Hamilton L, Benchetrit G, and Guz A. Do changes in respiratory pattern and ventilation seen with different behavioural situations reflect metabolic demands. In: Wenner-Green International Symposium Series, Respiration Psychophysiology, edited by von Euler C and Katz-Salamon M. Basingstoke, UK: MacMillan, 1988, p. 21–28.
  44. Shea SA, Walter J, Pelley C, Murphy K, and Guz A. The effect of visual and auditory stimuli upon resting ventilation in man. Respir Physiol 68: 345–357, 1987.
  45. Shintani T, Mori RL, and Yates BJ. Locations of neurons with respiratory-related activity in the ferret brainstem. Brain Res 974: 236–242, 2003.
  46. Telles S, Reddy SK, and Nagendra HR. Oxygen consumption and respiration following two yoga relaxation techniques. Appl Psychophysiol Biofeedback 25: 221–227, 2000.
  47. Thornton JM, Pederson DL, Kardos A, Guz A, Casadei B, and Paterson DJ. Ventilatory response to imagination of exercise and altered perception of exercise load under hypnosis. Adv Exp Med Biol 450: 195–197, 1998.
  48. Trinder J, Whitworth F, Kay A, and Wilkin P. Respiratory instability during sleep onset. J Appl Physiol 73: 2462–2469, 1992.
  49. Waldrop TG, Eldridge FL, Iwamoto GA, and Mitchell JH. Central neural control of respiration and circulation during exercise. In: Handbook of Physiology. Exercise: Regulation and Integration of Multiple Systems. Bethesda, MD: Am. Physiol. Soc., 1996, sect. 12, chapt. 9, p. 333–380.
  50. Ward SA, Whipp BJ, Koyal S, and Wasserman K. Influence of body CO2 stores on ventilatory dynamics during exercise. J Appl Physiol 55: 742–749, 1983.
  51. Wolkove N, Kreisman H, Darragh D, Cohen C, and Frank H. Effect of transcendental meditation on breathing and respiratory control. J Appl Physiol 56: 607–612, 1984.



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H. J. Bell, W. Feenstra, and J. Duffin
The initial phase of exercise hyperpnoea in humans is depressed during a cognitive task
Exp Physiol, May 1, 2005; 90(3): 357 - 365.
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