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The neural influence on the occurrence of locomotor–respiratory coordination
Respiratory Physiology & Neurobiology 173 (2010) 23–28
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The neural influence on the occurrence of locomotor–respiratory coordination Erika Iwamoto ∗ , Shunsuke Taito, Toshihiro Kawae, Kiyokazu Sekikawa, Makoto Takahashi, Tsutomu Inamizu Graduate School of Health Sciences, Hiroshima University, Japan
a r t i c l e
i n f o
Article history: Accepted 4 June 2010 Keywords: Locomotor–respiratory coordination Neural influence Respiratory rhythm
a b s t r a c t This study focused on the neurogenic mechanisms of coordination between locomotor and respiratory rhythms. The aim of the present study was to investigate the influence of peripheral neurogenic drive from moving limbs, and the level of consciousness, on locomotor–respiratory coordination. Subjects performed movement for 20 min in a supine position using a bicycle ergometer. The movement comprised three types of leg movements: active (loadless) movement, passive movement while awake and passive movement during sleep. We found no difference between active and passive movement in the degree of coordination. However, the degree of coordination during sleep was significantly lower than that while awake (p < 0.05). We conclude that peripheral neurogenic drive from moving limbs is able to generate locomotor–respiratory coordination, and that the level of consciousness may influence the degree of coordination. © 2010 Elsevier B.V. All rights reserved.
1. Introduction During dynamic exercise, the respiratory rhythm can occasionally become coordinated with the exercise rhythm. The mechanism underlying this locomotor–respiratory coordination is still not completely understood. Several studies have investigated the factors that influence the coordination, and a number of different hypotheses, such as mechanical, chemical, metabolic and neurogenic interactions, have been proposed (Viala, 1997). First, locomotion might have a mechanical influence on breathing. It has been suggested that the forces acting on the trunk and thorax, i.e., the piston-like activity of the visceral contents, concussive forces from limb impact and abdominal compressive forces, are relevant to enhancing expiratory air flow (Bramble and Carrier, 1983). However, although this mechanical visceral piston hypothesis may apply to quadrupeds, it cannot account for harmonic locomotor–respiratory coordination (i.e., 2:1, 4:1 or 5:2), and in bipedal humans there seems to be less mechanical impact of locomotion on breathing (Banzett et al., 1992). Second, chemical or metabolic stimuli have been proposed to interfere with locomotor–respiratory coordination. For instance, an increase in chemical drive to breathe can occur under hypoxic conditions. Previous experiments have tested the hypothesis that entrainment of breathing frequency by exercise rhythm may be
∗ Corresponding author. Present address: Graduate School of Medicine, Research Center of Health, Physical Fitness and Sports, Nagoya University, Furocho, Chikusaku, Nagoya 464-8601, Japan. Tel.: +81 52 789 5751; fax: +81 52 789 3957. E-mail address: [email protected] (E. Iwamoto). 1569-9048/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.resp.2010.06.002
affected by enhanced peripheral chemoreceptor activity in hypoxia. Paterson et al. (1987) observed less coordination with increasing hypoxia. However, Seebauer et al. (2003) observed no influence of hypoxia on coordination. Recently, Fabre et al. (2007) suggested that neuro-mechanical locomotion-linked respiratory stimuli are stronger than peripheral chemoreceptor-linked respiratory stimuli induced by hypoxia. Numerous neural mechanisms have been demonstrated or postulated to contribute to locomotor frequency entraining respiratory frequency. Viala and Freton (1983) and Viala (1986) observed that direct central (i.e., from the subcortical and spinal areas) interactions do exist between the respiratory and the locomotor rhythms in decorticate rabbits. Additionally, neural influences have peripheral neurogenic drive and feed-forward mechanisms (from the higher centers such as the cortex and cerebellum). Iscoe and Polosa (1976) and Palisses et al. (1988) suggested that periodic activation of the limbs plays a supportive role in locomotor–respiratory coordination in a completely isolated in vitro preparation. Morin and Viala (2002) reported that respiratory motor activity could be fully entrained (1:1 coupling) over a range of periodic electrical stimulation applied to low-threshold sensory pathways originating from the hindlimb muscles. Previous studies have reported that peripheral neurogenic drive from moving limbs influences locomotor–respiratory coordination; however, there are no data regarding coordination in freely moving humans. In humans, peripheral neurogenic drives are effectively isolated during passive movement (Kao, 1977; Miyamura, 1994; Kaufman and Forster, 1996). Rassler and Raabe (2003) investigated coordination of breathing with active horizontal head and eye movements and with passive body turning, although with no limb movement. The
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primary purpose of this study was to compare the degree of coordination during active and passive limb movement, to investigate the influence of peripheral neurogenic drive from moving limbs on locomotor–respiratory coordination in humans. It is presumed that higher centers (feed-forward mechanisms) also play some role in coordination. Previous studies have reported that familiarity with a given type of exercise is important for locomotor–respiratory coordination (Kohl et al., 1981; Paterson et al., 1986; Mahler et al., 1991). It is not clear that familiarity affects locomotor–respiratory coordination during passive movement while awake. However, it is possible that, in awake humans, even if passively moved, the subjects may consciously or unconsciously modulate respiration because the higher centers are still active (Ishida et al., 1993). The activity of the higher centers changes according to the level of consciousness. Thus, the second purpose of this study was to examine the degree of coordination during wakefulness or sleep, to investigate the influence of the level of consciousness on locomotor–respiratory coordination. 2. Methods 2.1. Subjects The subjects, three males and nine females (age: 23.4 ± 3.3 years, height: 164.4 ± 10.7 cm, body weight: 58.5 ± 12.8 kg) volunteered for this study after giving written informed consent. The study was approved by the Ethics Committee of Hiroshima University Graduate School of Health Science. Subjects were informed in detail about the experimental procedures, but were not told the purpose of the study. 2.2. Experimental protocol Sessions followed three patterns: active movement (loadless pedaling), passive movement while awake and passive movement during sleep. The subject exercised using a cycle ergometer (the motor-assisted movement therapy trainer MOTOmed letto, RECKTechnik GmbH&Co. KG., Betzenweiler, Germany) in the supine position. The cycle ergometer has leg guides composed of calf shells and foot holders that decrease the weight of the lower limbs. The lower limbs were fixed with Velcro straps at the calf, ankle and toe level. During movement, care was taken to decrease the movement of the head and trunk as much as possible to avoid voluntary contractions and motion artifacts. In passive movement while awake, the subject was instructed to relax and not to resist the motion, while the motor device rotated the crank at a constant cycling frequency. First, the subject performed active and passive movement while awake. Both protocols were 5 min of rest followed by 20 min of movement. In active movement, the subject was free to choose his or her own cycling frequency within 50 ± 10 rpm. Once the cycling frequency was established, the subjects had to maintain this frequency throughout the movement period. In passive movement, the cycling frequency was set at 50 rpm. Second, the subject performed passive movement during sleep. The measurements started at 11:00 p.m. and finished at 6:00 a.m. the next morning. All lights in the experimental room were turned off and noise was eliminated to avoid waking the subject or disturbing his or her sleep. The bispectral index (BIS), electrooculograms and electromyographic activity of the mentalis muscle were recorded for evaluation of sleep stages. The BIS was recorded with a BIS monitor (A-2000 BIS Monitor, Aspect Medical Systems, Inc., Newton, MA, United States). Changes in the depth of natural sleep are reflected sensitively by changes in the BIS. Stages 3 and 4 of non-rapid eye movement sleep are associated with BIS levels
59 ± 10; BIS levels while awake are 92 ± 3 (Sleigh et al., 1999). When the subject had fallen into stage 3 or 4 of non-rapid eye movement sleep, the passive movement was started and maintained until the subject woke up. The same procedure was repeated throughout the night. 2.3. Measurements During rest and movement, respiratory parameters and leg ˙ movements were continuously recorded. Expired ventilation (VE), ˙ 2 ), carbon dioxide production (VCO ˙ oxygen uptake rate (VO ), tidal 2 volume (VT ) and respiratory frequency (fR ) were measured by the breath-by-breath method using a gas analyzer (MINATO AE-300S, Minato Ikagaku Co., Ltd., Osaka, Japan). Cardiac frequency (fH ) was continuously monitored by a heart rate monitor (Dynascope-3140, Fukuda Denshi Co., Ltd., Tokyo, Japan). An electrogoniometer was attached to the lateral side of the knee joint to measure its angle. Respiration rhythms were assessed by respiratory air flow and exercise rhythms were assessed by knee joint angle. All signals were converted from analog to digital by an A–D converter (Power Lab 16/s, ADInstruments Co., Ltd., Bella Vista, NSW, Australia), stored on computer hard disk and synchronized using software (Chart ver. 5, ADInstruments Co., Ltd.). 2.4. Data analysis All values were analyzed after constant cycling frequency was reached. We analyzed the physiological variables during each experiment in three conditions: at rest, during the immediate response to movement and during the steady-state response to movement. The immediate response was the average of all subjects’ measurements over the first 20 s, and the steady-state response was the average of all the movement values after the immediate response. We determined the time between an arbitrarily chosen point of the leg movement cycle (the point of maximum knee flexion) and the onset of expiration in the breathing cycle; this time was called the phase interval (Fig. 1). Coordination was considered to be present when the phase interval displayed a constant value ±0.10 s for at least four consecutive breaths (Hill et al., 1988). The degree of coordination (%COORD) corresponded to the percentage of breaths fulfilling this criterion compared with the total number of breaths recorded in a segment. We analyzed %COORD for the first 10 breaths independently as one segment, and then the following 3 min as another segment followed by the remainder of the 20-min interval. In addition, we analyzed %COORD for the movement period after the first 10 breaths. 2.5. Statistical analysis All results are presented as mean ± standard deviation (S.D.). To examine the behavior of observed physiological variables during active or passive movement in the two movement modes, we used two-way repeated measures (RM) ANOVA with Bonferroni’s posthoc testing. The movement mode (active vs. passive) was one factor considered in the analysis, with limb movement status (rest vs. immediate response vs. steady-state response) as the second factor. To examine the behavior of observed physiological variables and %COORD during passive movement in the two background conditions, we used two-way RM ANOVA with Bonferroni’s posthoc testing. The level of consciousness (awake vs. asleep) was one factor considered in the analysis, with limb movement status (rest vs. immediate response vs. steady-state response) as the second factor. We used one-way RM ANOVA to test for any significant effects of the movement status on %COORD. The paired Student’s t-test was used to compare %COORD during active and passive movement, and
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Fig. 1. Respiratory air flow (upper graph) and knee angle (lower graph) during different experimental conditions: ((A) active movement, (B) passive movement while awake, (C) passive movement during sleep) for one female subject. (a) the onset of expiration, (b) the point of maximum knee flex, (c) phase interval. Phase interval represents the time between the point of maximum knee flex and the onset of the expiration cycle.
the unpaired t-test was used to compare %COORD during wakefulness and sleep. All the statistical analyses were performed using statistical software (SPSS version 12.0J for Windows, SPSS Japan, Inc., Tokyo, Japan). Statistical significance was accepted at p < 0.05. 3. Results 3.1. The respiratory air flow and knee angle Fig. 1 shows the respiratory air flow and knee angle for active and passive movement in different conditions, for one subject. In the awake condition, respiration during movement was more stable than during sleep. 3.2. Comparison between active and passive movement The average cycling frequency in active movement was 53.0 ± 1.2 rpm, and in passive movement was 50 rpm. Table 1 shows the change in physiological variables for active and passive movement while awake. Two-way RM ANOVA indicated that ˙ limb movement status was a significant factor in determining VE ˙ 2 (p = 0.007), VCO ˙ (p < 0.001), fR (p < 0.001), VO (p = 0.001) and fH 2 (p < 0.001), demonstrating that physiological parameters increased after the start of active or passive movement. In addition, twoway RM ANOVA indicated that movement mode was a significant ˙ (p < 0.001), fR (p = 0.016), VO ˙ 2 (p = 0.001) factor in determining VE and fH (p = 0.034). There were interaction effects between the factors of movement status and movement mode for the physi˙ (p = 0.002), VT (p = 0.047), VO ˙ 2 (p = 0.003), ological parameters VE ˙ VCO 2 (p = 0.002) and fH (p = 0.003). In other words, movement mode
affected the transition from rest to active or passive movement in ˙ 2 , VCO ˙ ˙ VT , VO terms of the VE, 2 and fH . During active movement, ˙ fR and VO ˙ 2 increased significantly from rest to the immediate VE, response (p < 0.001, p < 0.001 and p < 0.001, respectively) and from rest to the steady-state response (p < 0.001, p < 0.001 and p < 0.001, respectively). fH increased significantly from rest to the steadystate response (p < 0.001) and fH at the steady-state response was significantly greater than that at the immediate response. During passive movement, only fR increased significantly from rest to the immediate response (p = 0.015). During both active and passive movement, no subject showed coordination between breathing and movement rhythms within the first 10 breaths of the onset of movement. We analyzed the time course of %COORD during active and passive movement. The data are 3-min binned averages of all the subjects’ measurements (Table 3). One-way RM ANOVA indicated no main effect of movement status (time) during active movement (p = 0.819) or passive movement (p = 0.806). There was no main effect of movement status, so we analyzed %COORD in the steady state for a 20-min movement period after the first 10 breaths. Fig. 2 shows %COORD during active movement and passive movement. There was no significant difference between the %COORD for active movement and passive movement (20.1 ± 21.7 and 19.1 ± 22.2%, respectively; p = 0.911). 3.3. Comparison between wakefulness and sleep Twelve subjects participated in both the awake and asleep experiments. Recordings could be made from all 12 subjects while they were awake. Only six subjects could perform any passive movement during sleep and two of them performed passive move-
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Fig. 2. The degree of coordination (%COORD) during active and passive movement. There was no significant difference in %COORD between active and passive movement.
Fig. 3. The degree of coordination (%COORD) while awake and during sleep. * denotes a significant difference in %COORD between wakefulness and sleep (p < 0.05).
ment for only 2.5 and 2.7 min, respectively. We were able to record 20 min of passive movement from four sleeping subjects, and in two of those subjects, we were able to make two recordings between 11:00 p.m. and 6:00 a.m. the next morning. Among the six subjects for whom we could not record passive movement during sleep, for three, we could not start the passive movement because the BIS did not decrease to the level that corresponds to stage 3 or 4 of non-rapid eye movement sleep. For the other three subjects, the onset of the movement quickly aroused them from sleep. Table 2 shows the change in physiological variables during wakefulness and sleep. Two-way RM ANOVA indicated that there were no interaction effects between the factors of movement status and the level of consciousness for all physiological parameters. Limb movement status was a significant factor in determining ˙ (p = 0.012), fR (p < 0.001), VO ˙ 2 (p = 0.029) and VCO ˙ VE 2 (p = 0.025), ˙ fR , VO ˙ 2 and VCO ˙ demonstrating that VE, 2 increased after passive movement. fR increased significantly at the immediate response while awake and during sleep (p = 0.005 and p < 0.001, respectively). ˙ also increased significantly at the immediate During sleep, VE response (p = 0.015). Two-way RM ANOVA indicated that the level ˙ 2 of consciousness was a significant factor in determining VO ˙ 2 val(p = 0.014). Both at rest and for the steady-state response, VO
For both levels of consciousness (awake and asleep), no subject showed coordination between breathing and movement rhythms during the first 10 breaths after the onset of movement. We analyzed the time course of %COORD during active and passive movement. The data are 3-min binned averages of all the subjects’ measurements (Table 3). One-way RM ANOVA indicated no main effect of movement status (time) while awake (p = 0.806) and during sleep (p = 0.330). There was no main effect of movement status, so we analyzed %COORD in the steady state for a 20-min movement period after the first 10 breaths. Fig. 3 shows %COORD while awake and asleep. %COORD during sleep was significantly lower than that while awake (19.1 ± 22.2 and 4.2 ± 4.9%, respectively; p = 0.046).
ues during sleep were significantly lower than those while awake.
4. Discussion Locomotor–respiratory coordination is likely to be influenced by a variety of physiological factors acting synergistically. As mentioned previously, various mechanisms, such as mechanical, chemical/metabolic and neurogenic interactions could underlie locomotor–respiratory coordination (Viala, 1997). The purpose of this study was to focus on the neurogenic mechanisms. Subjects exercised in the supine position; the active exercise was loadless pedaling to eliminate the effect of mechanical influences, i.e.,
Table 1 Relevant physiological variables during active and passive exercise. Active
Passive
Rest
Movement Immediate response
˙ VE VT fR ˙ 2 VO ˙ VCO 2 fH
L min−1 mL breaths min−1 mL min−1 kg−1 mL min−1 kg−1 beats min−1
6.32 422.9 15.6 3.1 2.7 62.3
± ± ± ± ± ±
1.20 80.0 2.8 0.2 0.2 7.0
7.91 427.8 19.1 3.7 3.3 62.2
± ± ± ± ± ±
1.38* 82.0 3.4* 0.5* 0.4 6.2
Rest
Movement
Steady-state response 8.16 455.4 18.5 3.8 3.4 67.6
± ± ± ± ± ±
1.61‡ 91.6 3.4‡ 0.4‡ 0.3 7.4‡ , §
Immediate response 6.65 433.9 15.8 3.1 3.2 62.2
± ± ± ± ± ±
1.48 104.9 2.7 0.2 1.6 7.3
7.15 410.9 17.7 3.3 3.5 61.7
± ± ± ± ± ±
1.59 78.4 3.6† 0.5 2.0 7.9
Steady-state response 6.77 417.9 16.7 3.1 3.3 63.3
± ± ± ± ± ±
1.15|| 74.0¶ 2.5|| 0.2|| 1.9 7.2||
˙ expired ventilation; VT , tidal volume; fR , respiratory frequency; VO ˙ 2 , oxygen uptake rate; VCO ˙ Values are expressed as mean ± S.D. VE, 2 , carbon dioxide production; fH , cardiac frequency. * Significant between rest vs. immediate response, p < 0.001. † Significant between rest vs. immediate response, p = 0.015. ‡ Significant between rest vs. steady-state response, p < 0.001. § Significant between immediate response vs. steady-state response, p < 0.001. || Significant between active vs. passive, p < 0.001. ¶ Significant between active vs. passive, p = 0.002.
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Table 2 Relevant physiological variables while awake and during sleep. Awake
Asleep
Rest
Movement
Rest
Immediate response ˙ VE VT fR ˙ 2 VO ˙ VCO 2 fH
−1
L min mL breaths min−1 mL min−1 kg−1 mL min−1 kg−1 beats min−1
6.65 433.9 15.8 3.1 3.2 62.2
± ± ± ± ± ±
1.48 104.9 2.7 0.2 1.6 7.3
7.15 410.9 17.7 3.3 3.5 61.7
± ± ± ± ± ±
1.59 78.4 3.6† 0.5 2.0 7.9
Movement
Steady-state response 6.77 417.9 16.7 3.1 3.3 63.3
± ± ± ± ± ±
1.15 74.0 2.5 0.2 1.9 7.2
Immediate response 5.24 350.8 14.8 2.4 2.0 60.9
± ± ± ± ± ±
1.13 61.0 0.9 0.3§ 0.2 15.9
7.24 390.9 18.2 3.1 2.7 64.0
± ± ± ± ± ±
Steady-state response
‡
2.85 108.7 2.7* 1.0 1.1 16.9
5.98 359.7 16.2 2.5 2.1 63.2
± ± ± ± ± ±
2.07 71.4 2.5 0.6|| 0.6 17.3
˙ expired ventilation; VT , tidal volume; fR , respiratory frequency; VO ˙ 2 , oxygen uptake rate; VCO ˙ Values are expressed as mean ± S.D. VE, 2 , carbon dioxide production; fH , cardiac frequency. * Significant between rest vs. immediate response, p < 0.001. † Significant between rest vs. immediate response, p = 0.005. ‡ Significant between rest vs. immediate response, p = 0.015. § Significant between awake vs. asleep, p < 0.001. || Significant between awake vs. asleep, p = 0.06.
abdominal compressive force, impact on the thorax and flexion and extension of the axial skeleton. In our data, the oxygen uptake rate and carbon dioxide production did not increase during passive movement. During passive movement, there is an absence of volitional control, and minimal metabolic changes are observed. We consider that mechanical and chemical/metabolic factors have little influence on the locomotor–respiratory coordination in this study. We obtained the following two major findings: (1) while awake, the degree of coordination showed no difference between active and passive movement and (2) for passive movement, the degree of coordination during sleep was significantly lower than that while awake.
4.1. The early adaptation and steady-state phase of the coordination The results of the present study showed that the respiratory rhythm was barely coordinated with exercise rhythm at the onset of movement for any movement mode or level of consciousness. At the onset of movement, peripheral neurogenic drive may be the main cause for the rapid change in ventilation. In our study, fR was immediately increased at the onset of movement in all conditions. A previous study showed that fR was immediately increased at the onset of passive movement, even during sleep (Ishida et al., 1993). fR was affected by the movement frequency and peripheral neurogenic drive at the onset of movement. However, it was postulated that fR was unstable in the transitional phase during the early adaptation to the movement, so it was barely coordinated with movement rhythms in this phase. Additionally, we examined the time course of %COORD in all conditions, and found that the occurrence of coordination during the steady-state phase did not vary with time. However, in the present study, the modes of exercise were steady state active loadless pedaling and passive movement. Thus, it is possible that %COORD would vary with time during movement of different intensity or incremental exercise.
4.2. Comparison between active and passive limb movement During passive movement, there is an absence of conscious drive to the motor units and therefore a lack of central command that may influence breathing (Eldridge and Waldrop, 1991; Waldrop et al., 1996). In other words, the peripheral neurogenic drives are effectively isolated (Kao, 1977; Kaufman and Forster, 1996). In our experiments, the degree of coordination showed no difference between active and passive movement. These results suggest that even proprioceptive afferents from moving limbs are able to generate coordination between exercise and respiratory rhythm in humans. Previous studies have also reported that proprioceptive activation of the limbs plays a supportive role in coordination between the locomotor and respiratory rhythms (Iscoe and Polosa, 1976; Palisses et al., 1988; Morin and Viala, 2002). However, previous studies used an isolated in vitro preparation of the vertebrate nervous system, to allow precise control of sensory feedback activation, and thus they cannot exclude the possibility that in freely moving vertebrates, other factors such as mechanical constraints, central neurogenic control or metabolic conditions could influence locomotor–respiratory coordination. Additionally, exercise rhythm was controlled by external input during passive movement. Our results suggested that volitional control of exercise rhythm is not an essential factor for coordination. This complements the findings of Rassler and Raabe (2003), who investigated the coordination of breathing with active horizontal head and eye movements and with passive body turning. They reported that rhythmic vestibular stimulation could induce coordination with breathing to the same extent as could active movement. Similarly, our results showed that, even during limb exercise, coordination is possible in the absence of active voluntary movement. 4.3. Comparison between wakefulness and sleep The results of the present study showed that locomotor– respiratory coordination rarely occurs during sleep. Little is known about ventilatory responses to passive movement during sleep.
Table 3 The time course of the occurrence of locomotor–respiratory coordination. %COORD
1st response
2nd response
3rd response
4th response
5th response
6th response
Active movement while awake (%) Passive movement while awake (%) Passive movement during sleep (%)
22.3 ± 29.0 21.6 ± 22.0 1.7 ± 4.1
16.9 ± 22.8 19.1 ± 25.1 8.7 ± 11.8
17.8 ± 25.2 18.3 ± 23.2 4.8 ± 5.2
24.9 ± 31.2 16.7 ± 25.4 6.0 ± 10.0
16.9 ± 25.2 20.1 ± 25.5 2.4 ± 6.0
21.8 ± 28.0 18.6 ± 24.1 1.7 ± 4.3
Values are expressed as mean ± S.D. We analyzed %COORD for the first 10 breaths independently as one segment, and then the following 3 min as another sixth segment followed by the remainder of the 20-min interval.
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We analyzed three phases of ventilatory responses: rest, immediate response to passive movement and steady-state response to passive movement. For the steady-state response, the ventilatory response caused by passive movement was not different between wakefulness and sleep. However, for the immediate response, we found that the increase in fR at the onset of passive movement while ˙ was also increased asleep was greater than that while awake. VE significantly at the immediate response only during sleep. Concerning passive movement during sleep, Ishida et al. (1993) investigated the ventilatory response at the onset of passive leg movements in ˙ and fR were more than dousleeping humans. They found that VE bled during stage 3 or 4 of sleep compared with the responses while the subjects were conscious. This is in agreement with our present results. Ishida et al. concluded that the respiratory center might be inhibited by higher centers while awake, but that during sleep, such inhibition might disappear so that the ventilation response to afferent information from moving limbs at the onset of movement would be different between wakefulness and sleep. In the present study, we also presume that the inhibition from higher centers to respiratory centers ceases during sleep. While awake, influences from higher centers such as the cortex and cerebellum may play a role in breathing control under different conditions (Guz, 1997). During wakefulness, respiration is modulated by higher centers, consciously or unconsciously; however, during deep sleep, these respiratory centers might be barely affected by the higher centers. During deep sleep, the higher centers such as the pons and the thalamus show remarkable deactivation (Kajimura et al., 1999). In the present study, we cannot suggest which higher center(s) were responsible for influencing coordination. We do, however, suggest that the degree of coordination was affected by the level of consciousness. In the present study, only four subjects remained asleep during passive movement for 20 min. We postulate that the reason only four subjects remained asleep during passive movement was because these subjects have some peripheral or central neurological predisposition. If these four subjects had some peripheral neurological predisposition that differed from the other eight subjects who did not remain asleep, then these four subjects would have show characteristic ventilatory responses to passive movement while awake. The results from the present study ˙ at rest, during the immediate response to moveshowed that VE ment and during the steady-state response to movement were 5.49 ± 1.94, 6.13 ± 2.16 and 5.68 ± 2.13 L min−1 for four subjects, and 6.95 ± 1.72, 7.28 ± 1.91 and 6.93 ± 1.39 L min−1 for eight subjects. There were no significant differences between the two groups in three conditions (p = 0.353, p = 0.719 and p = 0.520, respectively, unpaired t-test). We could not find any unique characteristic ventilatory responses in these four subjects during passive movement while awake as compared with the others. From this, it is conceivable that a peripheral neurological predisposition could not have contributed to the ability of these subjects to remain asleep. Therefore, we assumed that the difference of an individual central neurological predisposition could play a role in the ability of the subjects to remain asleep during passive movement. In this study, we presumed that the higher centers might have some influence on the degree of coordination. So, there is a possibility that the lower degree of coordination to the passive movement during sleep might be biased by an individual central neurological predisposition. However, we do not have definitive data on the central neurological predisposition, and thus further investigations are needed to clarify this possibility. 5. Conclusion The present study demonstrates that locomotor–respiratory coordination occurs during passive movement as well as during
active loadless movement, and that locomotor–respiratory coordination is rarely established during sleep. We conclude that voluntary control of exercise rhythm does not necessarily have a strong influence on the degree of coordination, because even a peripheral neurogenic drive from moving limbs can generate locomotor–respiratory coordination. The ventilatory response varies with the level of consciousness, implying that higher centers might have some influence on coordination. References Banzett, R.B., Mead, J., Reid, M.B., Topulos, G.P., 1992. Locomotion in men has no appreciable mechanical effect on breathing. J. Appl. Physiol. 72, 1922– 1926. Bramble, D.M., Carrier, D.R., 1983. Running and breathing in mammals. Science 219, 251–256. Eldridge, F.L., Waldrop, T.G., 1991. Neural control of breathing during exercise. In: Whipp, B.J., Wasserman, K. (Eds.), Exercise: Pulmonary Physiology and Pathophysiology. Marcel Dekker, New York, pp. 309–370. Fabre, N., Perrey, S., Passelergue, P., Rouillon, J.D., 2007. No influence of hypoxia on coordination between respiratory and locomotor rhythms during rowing at moderate intensity. J. Sports Sci. Med. 6, 526–531. Guz, A., 1997. Brain, breathing and breathlessness. Respir. Physiol. 109, 197– 204. Hill, A.R., Adams, J.M., Parker, B.E., Rochester, D.F., 1988. Short-term entrainment of ventilation to the walking cycle in humans. J. Appl. Physiol. 65, 570– 578. Iscoe, S., Polosa, C., 1976. Synchronization of respiratory frequency by somatic afferent stimulation. J. Appl. Physiol. 40, 138–148. Ishida, K., Yasuda, Y., Miyamura, M., 1993. Cardiorespiratory response at the onset of passive leg movements during sleep in humans. Eur. J. Appl. Physiol. Occup. Physiol. 66, 507–513. Kajimura, N., Uchiyama, M., Takayama, Y., Uchida, S., Uema, T., Kato, M., Sekimoto, M., Watanabe, T., Nakajima, T., Horikoshi, S., Ogawa, K., Nishikawa, M., Hiroki, M., Kudo, Y., Matsuda, H., Okawa, M., Takahashi, K., 1999. Activity of midbrain reticular formation and neocortex during the progression of human non-rapid eye movement sleep. J. Neurosci. 19, 10065–10073. Kao, F.F., 1977. The peripheral neurogenic drive: an experimental study. In: Dempsey, J.A., Deed, C.E. (Eds.), Muscular Exercise and the Lung. University of Wisconsin Press, Madison, WI, pp. 71–85. Kaufman, M.P., Forster, H.V., 1996. Reflexes controlling circulatory, ventilatory and airway responses to exercise. In: Rowell, L.B., Shepherd, J.T. (Eds.), Handbook of Physiology: Section 12. Oxford University Press, Oxford, pp. 381–447 (Chapter 10). Kohl, J., Koller, E.A., Jager, M., 1981. Relation between pedalling- and breathing rhythm. Eur. J. Appl. Physiol. Occup. Physiol. 47, 223–237. Mahler, D.A., Shuhart, C.R., Brew, E., Stukel, T.A., 1991. Ventilatory responses and entrainment of breathing during rowing. Med. Sci. Sports Exerc. 23, 186– 192. Miyamura, M., 1994. Control of ventilation during exercise in man with special reference to the feature at the onset. Jpn. J. Physiol. 44, 123–139. Morin, D., Viala, D., 2002. Coordinations of locomotor and respiratory rhythms in vitro are critically dependent on hindlimb sensory inputs. J. Neurosci. 22, 4756–4765. Palisses, R., Persegol, L., Viala, D., Viala, G., 1988. Reflex modulation of phrenic activity through hindlimb passive motion in decorticate and spinal rabbit preparation. Neuroscience 24, 719–728. Paterson, D.J., Wood, G.A., Marshall, R.N., Morton, A.R., Harrison, A.B., 1987. Entrainment of respiratory frequency to exercise rhythm during hypoxia. J. Appl. Physiol. 62, 1767–1771. Paterson, D.J., Wood, G.A., Morton, A.R., Henstridge, J.D., 1986. The entrainment of ventilation frequency to exercise rhythm. Eur. J. Appl. Physiol. Occup. Physiol. 55, 530–537. Rassler, B., Raabe, J., 2003. Co-ordination of breathing with rhythmic head and eye movements and with passive turnings of the body. Eur. J. Appl. Physiol. 90, 125–130. Seebauer, M., Siller, T., Kohl, J., 2003. Influence of hypoxia on coordination between breathing and cycling rhythms in women. Eur. J. Appl. Physiol. 89, 90–94. Sleigh, J.W., Andrzejowski, J., Steyn-Ross, A., Steyn-Ross, M., 1999. The bispectral index: a measure of depth of sleep? Anesth. Analg. 88, 659–661. Viala, D., 1986. Evidence for direct reciprocal interactions between the central rhythm generators for spinal “respiratory” and locomotor activities in the rabbit. Exp. Brain Res. 63, 225–232. Viala, D., 1997. Coordination of locomotion and respiration. In: Miller, A.D., Bianchi, A.L., Bishop, B.P. (Eds.), Neural Control of the Respiratory Muscles. CRC, New York, pp. 285–296. Viala, D., Freton, E., 1983. Evidence for respiratory and locomotor pattern generators in the rabbit cervico-thoracic cord and for their interactions. Exp. Brain Res. 49, 247–256. Waldrop, T.G., Eldridge, F.L., Iwamoto, G.A., Mitchell, J.H., 1996. Central neural control of respiration and circulation during exercise. In: Rowell, L.B., Shepherd, J.T. (Eds.), Handbook of Physiology. Oxford University Press, New York, pp. 333–380.
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The neural influence on the occurrence of locomotor–respiratory coordination Erika Iwamoto ∗ , Shunsuke Taito, Toshihiro Kawae, Kiyokazu Sekikawa, Makoto Takahashi, Tsutomu Inamizu Graduate School of Health Sciences, Hiroshima University, Japan
a r t i c l e
i n f o
Article history: Accepted 4 June 2010 Keywords: Locomotor–respiratory coordination Neural influence Respiratory rhythm
a b s t r a c t This study focused on the neurogenic mechanisms of coordination between locomotor and respiratory rhythms. The aim of the present study was to investigate the influence of peripheral neurogenic drive from moving limbs, and the level of consciousness, on locomotor–respiratory coordination. Subjects performed movement for 20 min in a supine position using a bicycle ergometer. The movement comprised three types of leg movements: active (loadless) movement, passive movement while awake and passive movement during sleep. We found no difference between active and passive movement in the degree of coordination. However, the degree of coordination during sleep was significantly lower than that while awake (p < 0.05). We conclude that peripheral neurogenic drive from moving limbs is able to generate locomotor–respiratory coordination, and that the level of consciousness may influence the degree of coordination. © 2010 Elsevier B.V. All rights reserved.
1. Introduction During dynamic exercise, the respiratory rhythm can occasionally become coordinated with the exercise rhythm. The mechanism underlying this locomotor–respiratory coordination is still not completely understood. Several studies have investigated the factors that influence the coordination, and a number of different hypotheses, such as mechanical, chemical, metabolic and neurogenic interactions, have been proposed (Viala, 1997). First, locomotion might have a mechanical influence on breathing. It has been suggested that the forces acting on the trunk and thorax, i.e., the piston-like activity of the visceral contents, concussive forces from limb impact and abdominal compressive forces, are relevant to enhancing expiratory air flow (Bramble and Carrier, 1983). However, although this mechanical visceral piston hypothesis may apply to quadrupeds, it cannot account for harmonic locomotor–respiratory coordination (i.e., 2:1, 4:1 or 5:2), and in bipedal humans there seems to be less mechanical impact of locomotion on breathing (Banzett et al., 1992). Second, chemical or metabolic stimuli have been proposed to interfere with locomotor–respiratory coordination. For instance, an increase in chemical drive to breathe can occur under hypoxic conditions. Previous experiments have tested the hypothesis that entrainment of breathing frequency by exercise rhythm may be
∗ Corresponding author. Present address: Graduate School of Medicine, Research Center of Health, Physical Fitness and Sports, Nagoya University, Furocho, Chikusaku, Nagoya 464-8601, Japan. Tel.: +81 52 789 5751; fax: +81 52 789 3957. E-mail address: [email protected] (E. Iwamoto). 1569-9048/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.resp.2010.06.002
affected by enhanced peripheral chemoreceptor activity in hypoxia. Paterson et al. (1987) observed less coordination with increasing hypoxia. However, Seebauer et al. (2003) observed no influence of hypoxia on coordination. Recently, Fabre et al. (2007) suggested that neuro-mechanical locomotion-linked respiratory stimuli are stronger than peripheral chemoreceptor-linked respiratory stimuli induced by hypoxia. Numerous neural mechanisms have been demonstrated or postulated to contribute to locomotor frequency entraining respiratory frequency. Viala and Freton (1983) and Viala (1986) observed that direct central (i.e., from the subcortical and spinal areas) interactions do exist between the respiratory and the locomotor rhythms in decorticate rabbits. Additionally, neural influences have peripheral neurogenic drive and feed-forward mechanisms (from the higher centers such as the cortex and cerebellum). Iscoe and Polosa (1976) and Palisses et al. (1988) suggested that periodic activation of the limbs plays a supportive role in locomotor–respiratory coordination in a completely isolated in vitro preparation. Morin and Viala (2002) reported that respiratory motor activity could be fully entrained (1:1 coupling) over a range of periodic electrical stimulation applied to low-threshold sensory pathways originating from the hindlimb muscles. Previous studies have reported that peripheral neurogenic drive from moving limbs influences locomotor–respiratory coordination; however, there are no data regarding coordination in freely moving humans. In humans, peripheral neurogenic drives are effectively isolated during passive movement (Kao, 1977; Miyamura, 1994; Kaufman and Forster, 1996). Rassler and Raabe (2003) investigated coordination of breathing with active horizontal head and eye movements and with passive body turning, although with no limb movement. The
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primary purpose of this study was to compare the degree of coordination during active and passive limb movement, to investigate the influence of peripheral neurogenic drive from moving limbs on locomotor–respiratory coordination in humans. It is presumed that higher centers (feed-forward mechanisms) also play some role in coordination. Previous studies have reported that familiarity with a given type of exercise is important for locomotor–respiratory coordination (Kohl et al., 1981; Paterson et al., 1986; Mahler et al., 1991). It is not clear that familiarity affects locomotor–respiratory coordination during passive movement while awake. However, it is possible that, in awake humans, even if passively moved, the subjects may consciously or unconsciously modulate respiration because the higher centers are still active (Ishida et al., 1993). The activity of the higher centers changes according to the level of consciousness. Thus, the second purpose of this study was to examine the degree of coordination during wakefulness or sleep, to investigate the influence of the level of consciousness on locomotor–respiratory coordination. 2. Methods 2.1. Subjects The subjects, three males and nine females (age: 23.4 ± 3.3 years, height: 164.4 ± 10.7 cm, body weight: 58.5 ± 12.8 kg) volunteered for this study after giving written informed consent. The study was approved by the Ethics Committee of Hiroshima University Graduate School of Health Science. Subjects were informed in detail about the experimental procedures, but were not told the purpose of the study. 2.2. Experimental protocol Sessions followed three patterns: active movement (loadless pedaling), passive movement while awake and passive movement during sleep. The subject exercised using a cycle ergometer (the motor-assisted movement therapy trainer MOTOmed letto, RECKTechnik GmbH&Co. KG., Betzenweiler, Germany) in the supine position. The cycle ergometer has leg guides composed of calf shells and foot holders that decrease the weight of the lower limbs. The lower limbs were fixed with Velcro straps at the calf, ankle and toe level. During movement, care was taken to decrease the movement of the head and trunk as much as possible to avoid voluntary contractions and motion artifacts. In passive movement while awake, the subject was instructed to relax and not to resist the motion, while the motor device rotated the crank at a constant cycling frequency. First, the subject performed active and passive movement while awake. Both protocols were 5 min of rest followed by 20 min of movement. In active movement, the subject was free to choose his or her own cycling frequency within 50 ± 10 rpm. Once the cycling frequency was established, the subjects had to maintain this frequency throughout the movement period. In passive movement, the cycling frequency was set at 50 rpm. Second, the subject performed passive movement during sleep. The measurements started at 11:00 p.m. and finished at 6:00 a.m. the next morning. All lights in the experimental room were turned off and noise was eliminated to avoid waking the subject or disturbing his or her sleep. The bispectral index (BIS), electrooculograms and electromyographic activity of the mentalis muscle were recorded for evaluation of sleep stages. The BIS was recorded with a BIS monitor (A-2000 BIS Monitor, Aspect Medical Systems, Inc., Newton, MA, United States). Changes in the depth of natural sleep are reflected sensitively by changes in the BIS. Stages 3 and 4 of non-rapid eye movement sleep are associated with BIS levels
59 ± 10; BIS levels while awake are 92 ± 3 (Sleigh et al., 1999). When the subject had fallen into stage 3 or 4 of non-rapid eye movement sleep, the passive movement was started and maintained until the subject woke up. The same procedure was repeated throughout the night. 2.3. Measurements During rest and movement, respiratory parameters and leg ˙ movements were continuously recorded. Expired ventilation (VE), ˙ 2 ), carbon dioxide production (VCO ˙ oxygen uptake rate (VO ), tidal 2 volume (VT ) and respiratory frequency (fR ) were measured by the breath-by-breath method using a gas analyzer (MINATO AE-300S, Minato Ikagaku Co., Ltd., Osaka, Japan). Cardiac frequency (fH ) was continuously monitored by a heart rate monitor (Dynascope-3140, Fukuda Denshi Co., Ltd., Tokyo, Japan). An electrogoniometer was attached to the lateral side of the knee joint to measure its angle. Respiration rhythms were assessed by respiratory air flow and exercise rhythms were assessed by knee joint angle. All signals were converted from analog to digital by an A–D converter (Power Lab 16/s, ADInstruments Co., Ltd., Bella Vista, NSW, Australia), stored on computer hard disk and synchronized using software (Chart ver. 5, ADInstruments Co., Ltd.). 2.4. Data analysis All values were analyzed after constant cycling frequency was reached. We analyzed the physiological variables during each experiment in three conditions: at rest, during the immediate response to movement and during the steady-state response to movement. The immediate response was the average of all subjects’ measurements over the first 20 s, and the steady-state response was the average of all the movement values after the immediate response. We determined the time between an arbitrarily chosen point of the leg movement cycle (the point of maximum knee flexion) and the onset of expiration in the breathing cycle; this time was called the phase interval (Fig. 1). Coordination was considered to be present when the phase interval displayed a constant value ±0.10 s for at least four consecutive breaths (Hill et al., 1988). The degree of coordination (%COORD) corresponded to the percentage of breaths fulfilling this criterion compared with the total number of breaths recorded in a segment. We analyzed %COORD for the first 10 breaths independently as one segment, and then the following 3 min as another segment followed by the remainder of the 20-min interval. In addition, we analyzed %COORD for the movement period after the first 10 breaths. 2.5. Statistical analysis All results are presented as mean ± standard deviation (S.D.). To examine the behavior of observed physiological variables during active or passive movement in the two movement modes, we used two-way repeated measures (RM) ANOVA with Bonferroni’s posthoc testing. The movement mode (active vs. passive) was one factor considered in the analysis, with limb movement status (rest vs. immediate response vs. steady-state response) as the second factor. To examine the behavior of observed physiological variables and %COORD during passive movement in the two background conditions, we used two-way RM ANOVA with Bonferroni’s posthoc testing. The level of consciousness (awake vs. asleep) was one factor considered in the analysis, with limb movement status (rest vs. immediate response vs. steady-state response) as the second factor. We used one-way RM ANOVA to test for any significant effects of the movement status on %COORD. The paired Student’s t-test was used to compare %COORD during active and passive movement, and
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Fig. 1. Respiratory air flow (upper graph) and knee angle (lower graph) during different experimental conditions: ((A) active movement, (B) passive movement while awake, (C) passive movement during sleep) for one female subject. (a) the onset of expiration, (b) the point of maximum knee flex, (c) phase interval. Phase interval represents the time between the point of maximum knee flex and the onset of the expiration cycle.
the unpaired t-test was used to compare %COORD during wakefulness and sleep. All the statistical analyses were performed using statistical software (SPSS version 12.0J for Windows, SPSS Japan, Inc., Tokyo, Japan). Statistical significance was accepted at p < 0.05. 3. Results 3.1. The respiratory air flow and knee angle Fig. 1 shows the respiratory air flow and knee angle for active and passive movement in different conditions, for one subject. In the awake condition, respiration during movement was more stable than during sleep. 3.2. Comparison between active and passive movement The average cycling frequency in active movement was 53.0 ± 1.2 rpm, and in passive movement was 50 rpm. Table 1 shows the change in physiological variables for active and passive movement while awake. Two-way RM ANOVA indicated that ˙ limb movement status was a significant factor in determining VE ˙ 2 (p = 0.007), VCO ˙ (p < 0.001), fR (p < 0.001), VO (p = 0.001) and fH 2 (p < 0.001), demonstrating that physiological parameters increased after the start of active or passive movement. In addition, twoway RM ANOVA indicated that movement mode was a significant ˙ (p < 0.001), fR (p = 0.016), VO ˙ 2 (p = 0.001) factor in determining VE and fH (p = 0.034). There were interaction effects between the factors of movement status and movement mode for the physi˙ (p = 0.002), VT (p = 0.047), VO ˙ 2 (p = 0.003), ological parameters VE ˙ VCO 2 (p = 0.002) and fH (p = 0.003). In other words, movement mode
affected the transition from rest to active or passive movement in ˙ 2 , VCO ˙ ˙ VT , VO terms of the VE, 2 and fH . During active movement, ˙ fR and VO ˙ 2 increased significantly from rest to the immediate VE, response (p < 0.001, p < 0.001 and p < 0.001, respectively) and from rest to the steady-state response (p < 0.001, p < 0.001 and p < 0.001, respectively). fH increased significantly from rest to the steadystate response (p < 0.001) and fH at the steady-state response was significantly greater than that at the immediate response. During passive movement, only fR increased significantly from rest to the immediate response (p = 0.015). During both active and passive movement, no subject showed coordination between breathing and movement rhythms within the first 10 breaths of the onset of movement. We analyzed the time course of %COORD during active and passive movement. The data are 3-min binned averages of all the subjects’ measurements (Table 3). One-way RM ANOVA indicated no main effect of movement status (time) during active movement (p = 0.819) or passive movement (p = 0.806). There was no main effect of movement status, so we analyzed %COORD in the steady state for a 20-min movement period after the first 10 breaths. Fig. 2 shows %COORD during active movement and passive movement. There was no significant difference between the %COORD for active movement and passive movement (20.1 ± 21.7 and 19.1 ± 22.2%, respectively; p = 0.911). 3.3. Comparison between wakefulness and sleep Twelve subjects participated in both the awake and asleep experiments. Recordings could be made from all 12 subjects while they were awake. Only six subjects could perform any passive movement during sleep and two of them performed passive move-
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Fig. 2. The degree of coordination (%COORD) during active and passive movement. There was no significant difference in %COORD between active and passive movement.
Fig. 3. The degree of coordination (%COORD) while awake and during sleep. * denotes a significant difference in %COORD between wakefulness and sleep (p < 0.05).
ment for only 2.5 and 2.7 min, respectively. We were able to record 20 min of passive movement from four sleeping subjects, and in two of those subjects, we were able to make two recordings between 11:00 p.m. and 6:00 a.m. the next morning. Among the six subjects for whom we could not record passive movement during sleep, for three, we could not start the passive movement because the BIS did not decrease to the level that corresponds to stage 3 or 4 of non-rapid eye movement sleep. For the other three subjects, the onset of the movement quickly aroused them from sleep. Table 2 shows the change in physiological variables during wakefulness and sleep. Two-way RM ANOVA indicated that there were no interaction effects between the factors of movement status and the level of consciousness for all physiological parameters. Limb movement status was a significant factor in determining ˙ (p = 0.012), fR (p < 0.001), VO ˙ 2 (p = 0.029) and VCO ˙ VE 2 (p = 0.025), ˙ fR , VO ˙ 2 and VCO ˙ demonstrating that VE, 2 increased after passive movement. fR increased significantly at the immediate response while awake and during sleep (p = 0.005 and p < 0.001, respectively). ˙ also increased significantly at the immediate During sleep, VE response (p = 0.015). Two-way RM ANOVA indicated that the level ˙ 2 of consciousness was a significant factor in determining VO ˙ 2 val(p = 0.014). Both at rest and for the steady-state response, VO
For both levels of consciousness (awake and asleep), no subject showed coordination between breathing and movement rhythms during the first 10 breaths after the onset of movement. We analyzed the time course of %COORD during active and passive movement. The data are 3-min binned averages of all the subjects’ measurements (Table 3). One-way RM ANOVA indicated no main effect of movement status (time) while awake (p = 0.806) and during sleep (p = 0.330). There was no main effect of movement status, so we analyzed %COORD in the steady state for a 20-min movement period after the first 10 breaths. Fig. 3 shows %COORD while awake and asleep. %COORD during sleep was significantly lower than that while awake (19.1 ± 22.2 and 4.2 ± 4.9%, respectively; p = 0.046).
ues during sleep were significantly lower than those while awake.
4. Discussion Locomotor–respiratory coordination is likely to be influenced by a variety of physiological factors acting synergistically. As mentioned previously, various mechanisms, such as mechanical, chemical/metabolic and neurogenic interactions could underlie locomotor–respiratory coordination (Viala, 1997). The purpose of this study was to focus on the neurogenic mechanisms. Subjects exercised in the supine position; the active exercise was loadless pedaling to eliminate the effect of mechanical influences, i.e.,
Table 1 Relevant physiological variables during active and passive exercise. Active
Passive
Rest
Movement Immediate response
˙ VE VT fR ˙ 2 VO ˙ VCO 2 fH
L min−1 mL breaths min−1 mL min−1 kg−1 mL min−1 kg−1 beats min−1
6.32 422.9 15.6 3.1 2.7 62.3
± ± ± ± ± ±
1.20 80.0 2.8 0.2 0.2 7.0
7.91 427.8 19.1 3.7 3.3 62.2
± ± ± ± ± ±
1.38* 82.0 3.4* 0.5* 0.4 6.2
Rest
Movement
Steady-state response 8.16 455.4 18.5 3.8 3.4 67.6
± ± ± ± ± ±
1.61‡ 91.6 3.4‡ 0.4‡ 0.3 7.4‡ , §
Immediate response 6.65 433.9 15.8 3.1 3.2 62.2
± ± ± ± ± ±
1.48 104.9 2.7 0.2 1.6 7.3
7.15 410.9 17.7 3.3 3.5 61.7
± ± ± ± ± ±
1.59 78.4 3.6† 0.5 2.0 7.9
Steady-state response 6.77 417.9 16.7 3.1 3.3 63.3
± ± ± ± ± ±
1.15|| 74.0¶ 2.5|| 0.2|| 1.9 7.2||
˙ expired ventilation; VT , tidal volume; fR , respiratory frequency; VO ˙ 2 , oxygen uptake rate; VCO ˙ Values are expressed as mean ± S.D. VE, 2 , carbon dioxide production; fH , cardiac frequency. * Significant between rest vs. immediate response, p < 0.001. † Significant between rest vs. immediate response, p = 0.015. ‡ Significant between rest vs. steady-state response, p < 0.001. § Significant between immediate response vs. steady-state response, p < 0.001. || Significant between active vs. passive, p < 0.001. ¶ Significant between active vs. passive, p = 0.002.
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Table 2 Relevant physiological variables while awake and during sleep. Awake
Asleep
Rest
Movement
Rest
Immediate response ˙ VE VT fR ˙ 2 VO ˙ VCO 2 fH
−1
L min mL breaths min−1 mL min−1 kg−1 mL min−1 kg−1 beats min−1
6.65 433.9 15.8 3.1 3.2 62.2
± ± ± ± ± ±
1.48 104.9 2.7 0.2 1.6 7.3
7.15 410.9 17.7 3.3 3.5 61.7
± ± ± ± ± ±
1.59 78.4 3.6† 0.5 2.0 7.9
Movement
Steady-state response 6.77 417.9 16.7 3.1 3.3 63.3
± ± ± ± ± ±
1.15 74.0 2.5 0.2 1.9 7.2
Immediate response 5.24 350.8 14.8 2.4 2.0 60.9
± ± ± ± ± ±
1.13 61.0 0.9 0.3§ 0.2 15.9
7.24 390.9 18.2 3.1 2.7 64.0
± ± ± ± ± ±
Steady-state response
‡
2.85 108.7 2.7* 1.0 1.1 16.9
5.98 359.7 16.2 2.5 2.1 63.2
± ± ± ± ± ±
2.07 71.4 2.5 0.6|| 0.6 17.3
˙ expired ventilation; VT , tidal volume; fR , respiratory frequency; VO ˙ 2 , oxygen uptake rate; VCO ˙ Values are expressed as mean ± S.D. VE, 2 , carbon dioxide production; fH , cardiac frequency. * Significant between rest vs. immediate response, p < 0.001. † Significant between rest vs. immediate response, p = 0.005. ‡ Significant between rest vs. immediate response, p = 0.015. § Significant between awake vs. asleep, p < 0.001. || Significant between awake vs. asleep, p = 0.06.
abdominal compressive force, impact on the thorax and flexion and extension of the axial skeleton. In our data, the oxygen uptake rate and carbon dioxide production did not increase during passive movement. During passive movement, there is an absence of volitional control, and minimal metabolic changes are observed. We consider that mechanical and chemical/metabolic factors have little influence on the locomotor–respiratory coordination in this study. We obtained the following two major findings: (1) while awake, the degree of coordination showed no difference between active and passive movement and (2) for passive movement, the degree of coordination during sleep was significantly lower than that while awake.
4.1. The early adaptation and steady-state phase of the coordination The results of the present study showed that the respiratory rhythm was barely coordinated with exercise rhythm at the onset of movement for any movement mode or level of consciousness. At the onset of movement, peripheral neurogenic drive may be the main cause for the rapid change in ventilation. In our study, fR was immediately increased at the onset of movement in all conditions. A previous study showed that fR was immediately increased at the onset of passive movement, even during sleep (Ishida et al., 1993). fR was affected by the movement frequency and peripheral neurogenic drive at the onset of movement. However, it was postulated that fR was unstable in the transitional phase during the early adaptation to the movement, so it was barely coordinated with movement rhythms in this phase. Additionally, we examined the time course of %COORD in all conditions, and found that the occurrence of coordination during the steady-state phase did not vary with time. However, in the present study, the modes of exercise were steady state active loadless pedaling and passive movement. Thus, it is possible that %COORD would vary with time during movement of different intensity or incremental exercise.
4.2. Comparison between active and passive limb movement During passive movement, there is an absence of conscious drive to the motor units and therefore a lack of central command that may influence breathing (Eldridge and Waldrop, 1991; Waldrop et al., 1996). In other words, the peripheral neurogenic drives are effectively isolated (Kao, 1977; Kaufman and Forster, 1996). In our experiments, the degree of coordination showed no difference between active and passive movement. These results suggest that even proprioceptive afferents from moving limbs are able to generate coordination between exercise and respiratory rhythm in humans. Previous studies have also reported that proprioceptive activation of the limbs plays a supportive role in coordination between the locomotor and respiratory rhythms (Iscoe and Polosa, 1976; Palisses et al., 1988; Morin and Viala, 2002). However, previous studies used an isolated in vitro preparation of the vertebrate nervous system, to allow precise control of sensory feedback activation, and thus they cannot exclude the possibility that in freely moving vertebrates, other factors such as mechanical constraints, central neurogenic control or metabolic conditions could influence locomotor–respiratory coordination. Additionally, exercise rhythm was controlled by external input during passive movement. Our results suggested that volitional control of exercise rhythm is not an essential factor for coordination. This complements the findings of Rassler and Raabe (2003), who investigated the coordination of breathing with active horizontal head and eye movements and with passive body turning. They reported that rhythmic vestibular stimulation could induce coordination with breathing to the same extent as could active movement. Similarly, our results showed that, even during limb exercise, coordination is possible in the absence of active voluntary movement. 4.3. Comparison between wakefulness and sleep The results of the present study showed that locomotor– respiratory coordination rarely occurs during sleep. Little is known about ventilatory responses to passive movement during sleep.
Table 3 The time course of the occurrence of locomotor–respiratory coordination. %COORD
1st response
2nd response
3rd response
4th response
5th response
6th response
Active movement while awake (%) Passive movement while awake (%) Passive movement during sleep (%)
22.3 ± 29.0 21.6 ± 22.0 1.7 ± 4.1
16.9 ± 22.8 19.1 ± 25.1 8.7 ± 11.8
17.8 ± 25.2 18.3 ± 23.2 4.8 ± 5.2
24.9 ± 31.2 16.7 ± 25.4 6.0 ± 10.0
16.9 ± 25.2 20.1 ± 25.5 2.4 ± 6.0
21.8 ± 28.0 18.6 ± 24.1 1.7 ± 4.3
Values are expressed as mean ± S.D. We analyzed %COORD for the first 10 breaths independently as one segment, and then the following 3 min as another sixth segment followed by the remainder of the 20-min interval.
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We analyzed three phases of ventilatory responses: rest, immediate response to passive movement and steady-state response to passive movement. For the steady-state response, the ventilatory response caused by passive movement was not different between wakefulness and sleep. However, for the immediate response, we found that the increase in fR at the onset of passive movement while ˙ was also increased asleep was greater than that while awake. VE significantly at the immediate response only during sleep. Concerning passive movement during sleep, Ishida et al. (1993) investigated the ventilatory response at the onset of passive leg movements in ˙ and fR were more than dousleeping humans. They found that VE bled during stage 3 or 4 of sleep compared with the responses while the subjects were conscious. This is in agreement with our present results. Ishida et al. concluded that the respiratory center might be inhibited by higher centers while awake, but that during sleep, such inhibition might disappear so that the ventilation response to afferent information from moving limbs at the onset of movement would be different between wakefulness and sleep. In the present study, we also presume that the inhibition from higher centers to respiratory centers ceases during sleep. While awake, influences from higher centers such as the cortex and cerebellum may play a role in breathing control under different conditions (Guz, 1997). During wakefulness, respiration is modulated by higher centers, consciously or unconsciously; however, during deep sleep, these respiratory centers might be barely affected by the higher centers. During deep sleep, the higher centers such as the pons and the thalamus show remarkable deactivation (Kajimura et al., 1999). In the present study, we cannot suggest which higher center(s) were responsible for influencing coordination. We do, however, suggest that the degree of coordination was affected by the level of consciousness. In the present study, only four subjects remained asleep during passive movement for 20 min. We postulate that the reason only four subjects remained asleep during passive movement was because these subjects have some peripheral or central neurological predisposition. If these four subjects had some peripheral neurological predisposition that differed from the other eight subjects who did not remain asleep, then these four subjects would have show characteristic ventilatory responses to passive movement while awake. The results from the present study ˙ at rest, during the immediate response to moveshowed that VE ment and during the steady-state response to movement were 5.49 ± 1.94, 6.13 ± 2.16 and 5.68 ± 2.13 L min−1 for four subjects, and 6.95 ± 1.72, 7.28 ± 1.91 and 6.93 ± 1.39 L min−1 for eight subjects. There were no significant differences between the two groups in three conditions (p = 0.353, p = 0.719 and p = 0.520, respectively, unpaired t-test). We could not find any unique characteristic ventilatory responses in these four subjects during passive movement while awake as compared with the others. From this, it is conceivable that a peripheral neurological predisposition could not have contributed to the ability of these subjects to remain asleep. Therefore, we assumed that the difference of an individual central neurological predisposition could play a role in the ability of the subjects to remain asleep during passive movement. In this study, we presumed that the higher centers might have some influence on the degree of coordination. So, there is a possibility that the lower degree of coordination to the passive movement during sleep might be biased by an individual central neurological predisposition. However, we do not have definitive data on the central neurological predisposition, and thus further investigations are needed to clarify this possibility. 5. Conclusion The present study demonstrates that locomotor–respiratory coordination occurs during passive movement as well as during
active loadless movement, and that locomotor–respiratory coordination is rarely established during sleep. We conclude that voluntary control of exercise rhythm does not necessarily have a strong influence on the degree of coordination, because even a peripheral neurogenic drive from moving limbs can generate locomotor–respiratory coordination. The ventilatory response varies with the level of consciousness, implying that higher centers might have some influence on coordination. References Banzett, R.B., Mead, J., Reid, M.B., Topulos, G.P., 1992. Locomotion in men has no appreciable mechanical effect on breathing. J. Appl. Physiol. 72, 1922– 1926. Bramble, D.M., Carrier, D.R., 1983. Running and breathing in mammals. Science 219, 251–256. Eldridge, F.L., Waldrop, T.G., 1991. Neural control of breathing during exercise. In: Whipp, B.J., Wasserman, K. (Eds.), Exercise: Pulmonary Physiology and Pathophysiology. Marcel Dekker, New York, pp. 309–370. Fabre, N., Perrey, S., Passelergue, P., Rouillon, J.D., 2007. No influence of hypoxia on coordination between respiratory and locomotor rhythms during rowing at moderate intensity. J. Sports Sci. Med. 6, 526–531. Guz, A., 1997. Brain, breathing and breathlessness. Respir. Physiol. 109, 197– 204. Hill, A.R., Adams, J.M., Parker, B.E., Rochester, D.F., 1988. Short-term entrainment of ventilation to the walking cycle in humans. J. Appl. Physiol. 65, 570– 578. Iscoe, S., Polosa, C., 1976. Synchronization of respiratory frequency by somatic afferent stimulation. J. Appl. Physiol. 40, 138–148. Ishida, K., Yasuda, Y., Miyamura, M., 1993. Cardiorespiratory response at the onset of passive leg movements during sleep in humans. Eur. J. Appl. Physiol. Occup. Physiol. 66, 507–513. Kajimura, N., Uchiyama, M., Takayama, Y., Uchida, S., Uema, T., Kato, M., Sekimoto, M., Watanabe, T., Nakajima, T., Horikoshi, S., Ogawa, K., Nishikawa, M., Hiroki, M., Kudo, Y., Matsuda, H., Okawa, M., Takahashi, K., 1999. Activity of midbrain reticular formation and neocortex during the progression of human non-rapid eye movement sleep. J. Neurosci. 19, 10065–10073. Kao, F.F., 1977. The peripheral neurogenic drive: an experimental study. In: Dempsey, J.A., Deed, C.E. (Eds.), Muscular Exercise and the Lung. University of Wisconsin Press, Madison, WI, pp. 71–85. Kaufman, M.P., Forster, H.V., 1996. Reflexes controlling circulatory, ventilatory and airway responses to exercise. In: Rowell, L.B., Shepherd, J.T. (Eds.), Handbook of Physiology: Section 12. Oxford University Press, Oxford, pp. 381–447 (Chapter 10). Kohl, J., Koller, E.A., Jager, M., 1981. Relation between pedalling- and breathing rhythm. Eur. J. Appl. Physiol. Occup. Physiol. 47, 223–237. Mahler, D.A., Shuhart, C.R., Brew, E., Stukel, T.A., 1991. Ventilatory responses and entrainment of breathing during rowing. Med. Sci. Sports Exerc. 23, 186– 192. Miyamura, M., 1994. Control of ventilation during exercise in man with special reference to the feature at the onset. Jpn. J. Physiol. 44, 123–139. Morin, D., Viala, D., 2002. Coordinations of locomotor and respiratory rhythms in vitro are critically dependent on hindlimb sensory inputs. J. Neurosci. 22, 4756–4765. Palisses, R., Persegol, L., Viala, D., Viala, G., 1988. Reflex modulation of phrenic activity through hindlimb passive motion in decorticate and spinal rabbit preparation. Neuroscience 24, 719–728. Paterson, D.J., Wood, G.A., Marshall, R.N., Morton, A.R., Harrison, A.B., 1987. Entrainment of respiratory frequency to exercise rhythm during hypoxia. J. Appl. Physiol. 62, 1767–1771. Paterson, D.J., Wood, G.A., Morton, A.R., Henstridge, J.D., 1986. The entrainment of ventilation frequency to exercise rhythm. Eur. J. Appl. Physiol. Occup. Physiol. 55, 530–537. Rassler, B., Raabe, J., 2003. Co-ordination of breathing with rhythmic head and eye movements and with passive turnings of the body. Eur. J. Appl. Physiol. 90, 125–130. Seebauer, M., Siller, T., Kohl, J., 2003. Influence of hypoxia on coordination between breathing and cycling rhythms in women. Eur. J. Appl. Physiol. 89, 90–94. Sleigh, J.W., Andrzejowski, J., Steyn-Ross, A., Steyn-Ross, M., 1999. The bispectral index: a measure of depth of sleep? Anesth. Analg. 88, 659–661. Viala, D., 1986. Evidence for direct reciprocal interactions between the central rhythm generators for spinal “respiratory” and locomotor activities in the rabbit. Exp. Brain Res. 63, 225–232. Viala, D., 1997. Coordination of locomotion and respiration. In: Miller, A.D., Bianchi, A.L., Bishop, B.P. (Eds.), Neural Control of the Respiratory Muscles. CRC, New York, pp. 285–296. Viala, D., Freton, E., 1983. Evidence for respiratory and locomotor pattern generators in the rabbit cervico-thoracic cord and for their interactions. Exp. Brain Res. 49, 247–256. Waldrop, T.G., Eldridge, F.L., Iwamoto, G.A., Mitchell, J.H., 1996. Central neural control of respiration and circulation during exercise. In: Rowell, L.B., Shepherd, J.T. (Eds.), Handbook of Physiology. Oxford University Press, New York, pp. 333–380.