Prefrontal oxygenation is quantified with time-resolved near-infrared spectroscopy: effect of sex on baseline oxygenation and the response during exercise.

With the use of time-resolved near-infrared spectroscopy that enables quantitative analysis of optical properties and oxygenation in cerebral tissues and thereby subject-to-subject comparisons in the variables, this study examined the influence of sex on baseline optical properties and oxygenation in the prefrontal cortex (PFC) and the responses during cycling exercise. Absolute levels of oxygenated- and deoxygenated-hemoglobin concentration (Oxy-Hb and Deoxy-Hb) in bilateral PFC were measured at rest and during unilateral cycling at low and moderate intensity in young participants (8 women and 10 men). Unilateral cycling was utilized to evaluate no lateralization of the prefrontal oxygenation responses during exercise. Baseline optical properties of bilateral PFC, defined optical path length and reduced scattering coefficient, and their responses during cycling were not different between the sexes. Baseline absolute Oxy-Hb of bilateral PFC was significantly lower in women (37 ± 3 µM) than in men (47 ± 7 µM), whereas absolute Deoxy-Hb revealed no sex-related difference. The absolute Oxy-Hb levels in bilateral PFC during low- and moderate-intensity cycling were also lower in women. However, no sex difference was observed when using changes against the baseline levels to normalize baseline differences. No laterality-related differences were observed in the changes in prefrontal Oxy-Hb and Deoxy-Hb during unilateral cycling. Ascertaining no sex-related difference in optical properties of the PFC, the current findings suggest that baseline absolute level of oxygenation in the PFC is lower in women than in men, likely due to lower oxygen supply rather than higher oxygen utilization, and that prefrontal oxygenation responds similarly during exercise independently of sex.

Exaggerated renal sympathetic nerve and pressor responses during spontaneously occurring motor activity in hypertensive rats.

Stimulation of the mesencephalic locomotor region elicits exaggerated sympathetic nerve and pressor responses in spontaneously hypertensive rats (SHR) as compared with normotensive Wistar-Kyoto rats (WKY). This suggests that central command or its influence on vasomotor centers is augmented in hypertension. The decerebrate animal model possesses an ability to evoke intermittent bouts of spontaneously occurring motor activity (SpMA) and generates cardiovascular responses associated with the SpMA. It remains unknown whether the changes in sympathetic nerve activity and hemodynamics during SpMA are altered by hypertension. To test the hypothesis that the responses in renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) during SpMA are exaggerated with hypertension, this study aimed to compare the responses in decerebrate, paralyzed SHR, WKY, and normotensive Sprague-Dawley (SD) rats. In all strains, an abrupt increase in RSNA occurred in synchronization with tibial motor discharge (an index of motor activity) and was followed by rises in MAP and heart rate. The centrally evoked increase in RSNA and MAP during SpMA was much greater (306 ± 110%) in SHR than WKY (187 ± 146%) and SD (165 ± 44%). Although resting baroreflex-mediated changes in RSNA were not different across strains, mechanically or pharmacologically induced elevations in MAP attenuated or abolished the RSNA increase during SpMA in WKY and SD but had no effect in SHR. It is likely that the exaggerated sympathetic nerve and pressor responses during SpMA in SHR are induced along a central command pathway independent of the arterial baroreflex and/or result from central command-induced inhibition of the baroreflex.

Central command suppresses pressor-evoked bradycardia at the onset of voluntary standing up in conscious cats.

NEW FINDINGS: What is the central question of this study? Standing up can cause hypotension and tachycardia. Accumulated evidence poses the simple question, does the cardiac baroreflex operate at the onset of standing up? If the cardiac baroreflex is suppressed, what mechanism is responsible for baroreflex inhibition? What is the main finding and its importance? In cats, we found blunting of cardiac baroreflex sensitivity in the pressor range at the onset of voluntary hindlimb standing, but not of passive hindlimb standing. This finding suggests that central command suppresses pressor-evoked bradycardia at the onset of standing up, probably in advance, to prevent or buffer orthostatic hypotension. ABSTRACT: It remains unclear whether cardiac baroreflex function is preserved or suppressed at the onset of standing up. To answer the question and, if cardiac baroreflex is suppressed, to investigate the mechanism responsible for the suppression, we compared the sensitivity of the arterial cardiac baroreflex at the onset of voluntary and passive hindlimb standing in conscious cats. Cardiac baroreflex sensitivity was estimated from the maximal slope of the baroreflex curve between the responses of systolic arterial blood pressure and heart rate to a brief occlusion of the abdominal aorta. The systolic arterial blood pressure response to standing up without aortic occlusion was greater in the voluntary case than in the passive case. Cardiac baroreflex sensitivity was clearly decreased at the onset of voluntary standing up compared with rest (P = 0.005) and the onset of passive standing up (P = 0.007). The cardiac baroreflex sensitivity at the onset of passive standing up was similar to that at rest (P = 0.909). The findings suggest that central command would transmit a modulatory signal to the cardiac baroreflex system during the voluntary initiation of standing up. Furthermore, the present data tempt speculation on a close relationship between central inhibition of the cardiac baroreflex and the centrally induced tachycardiac response to standing up.

Regional difference in prefrontal oxygenation before and during overground walking in humans: a wearable multichannel NIRS study.

Using wireless multichannel near-infrared spectroscopy, regional difference in cortical activity over the prefrontal cortex (PFC) was examined before and during overground walking and in response to changes in speed and cognitive demand. Oxygenated-hemoglobin concentration (Oxy-Hb) as index of cortical activity in ventrolateral PFC (VLPFC), dorsolateral PFC (DLPFC), and frontopolar cortex (FPC) was measured in 14 subjects, whereas heart rate was measured as estimation of exercise intensity in six subjects. The impact of mental imagery on prefrontal Oxy-Hb was also explored. On both sides, Oxy-Hb in VLPFC, DLPFC, and lateral FPC was increased before the onset of normal-speed walking, whereas Oxy-Hb in medial FPC did not respond before walking onset. During the walking, Oxy-Hb further increased in bilateral VLPFC, whereas Oxy-Hb was decreased in DLPFC and lateral and medial FPC. Increasing walking speed did not alter the increase in Oxy-Hb in VLPFC but counteracted the decrease in Oxy-Hb in DLPFC (but not in lateral and medial FPC). Treadmill running evoked a greater Oxy-Hb increase in DLPFC (n = 5 subjects). Furthermore, increasing cognitive demand during walking, by deprivation of visual feedback, counteracted the decrease in Oxy-Hb in DLPFC and lateral and medial FPC, but it did not affect the increase in Oxy-Hb in VLPFC. Taken together, the profound and localized Oxy-Hb increase is a unique response for the VLPFC. The regional heterogeneity of the prefrontal Oxy-Hb responses to natural overground walking was accentuated by increasing walking speed or cognitive demand, suggesting functional distinction within the PFC.

Central command-related increases in blood velocity of anterior cerebral artery and prefrontal oxygenation at the onset of voluntary tapping.

The anterior cerebral artery (ACA) supplies blood predominantly to the frontal lobe including the prefrontal cortex. Our laboratory reported that prefrontal oxygenated-hemoglobin concentration (Oxy-Hb) increased before and at exercise onset, as long as exercise is arbitrarily started. Moreover, the increased prefrontal oxygenation seems independent of both exercise intensity and muscle mass. If so, mean blood velocity of the ACA (ACABV) should increase with "very light motor effort," concomitantly with the preexercise and initial increase in prefrontal Oxy-Hb. This study aimed to examine the responses in ACABV and vascular conductance index (ACAVCI) of the ACA as well as prefrontal Oxy-Hb during arbitrary or cued finger tapping in 12 subjects, an activity with a Borg scale perceived exertion rating of 7 (median). With arbitrary start, ACABV increased at tapping onset (14 ± 9%) via an elevation in ACAVCI. Likewise, prefrontal Oxy-Hb increased at the onset of tapping with a time course resembling that of ACABV. A positive cross correlation between the initial changes in ACABV and prefrontal Oxy-Hb was found significant in 67% of subjects, having a time lag of 2 s, whereas a positive linear regression between them was significant in 75% of subjects. When tapping was forced to start by cue, the initial increases in ACABV, ACAVCI, and prefrontal Oxy-Hb were delayed and blunted as compared with an arbitrary start. Thus, active vasodilatation of the ACA vascular bed occurs at tapping onset, as long as tapping is arbitrarily started, and contributes to immediate increases in blood flow and prefrontal oxygenation.NEW & NOTEWORTHY Anterior cerebral artery blood velocity and vascular conductance index along with prefrontal oxygenated-hemoglobin concentration all increased at the onset of finger tapping, peaking immediately after tapping onset, as long as tapping was arbitrarily started. Positive cross correlation and linear regression between the increases in ACABV and prefrontal Oxy-Hb were significant in 67%-75% of subjects. Active vasodilatation of the ACA vascular bed occurs with arbitrary tapping onset and contributes to increased ACABV and prefrontal oxygenation.

Increased oxygenation in the non-contracting forearm muscle during contralateral skilful hand movement.

NEW FINDINGS: What is the central question of this study? When performing skilful hand movement, motor command descends especially towards distal arm muscles. Does central command evoke a vascular response selectively in the distal arm muscles during skilful hand movement? What is the main finding and its importance? We found, using near-infrared spectroscopy, that unilateral skilful hand movement evoked a greater increase in oxygenation of the contralateral forearm muscle compared with that of the upper arm muscles. Mental imagery of the hand movement also increased oxygenation of the forearm muscle. These findings suggest that central command might contribute to the vasodilator response in the non-contracting forearm muscle during contralateral skilful hand movement. ABSTRACT: The human hand is a special organ to perform skilful movement in daily life. To meet metabolic demands of the working distal arm muscles, central command might evoke neurogenic vasodilatation in the muscles. Based on our previous demonstration that a centrally generated vasodilator signal is transmitted bilaterally to skeletal muscles during exercise, centrally induced vasodilatation might occur in the non-contracting distal arm muscles during contralateral skilful hand movement. To examine this possibility, we used near-infrared spectroscopy to measure the relative concentrations of oxygenated haemoglobin (Oxy-Hb; as an index of regional blood flow) in the non-contracting arm muscles during skilful hand movement (two-ball rotation) in 22 subjects. Two-ball rotation increased Oxy-Hb of both forearm and upper arm muscles, with little changes in perfusion pressure and cardiac output. The increased Oxy-Hb was greater in the forearm muscle than in the upper arm muscles. The increased Oxy-Hb of the forearm muscle during two-ball rotation was greater than that during one-armed cranking performed with no load. Mental imagery of two-ball rotation increased Oxy-Hb of the forearm and biceps muscles. The increases in Oxy-Hb of both forearm and upper arm muscles during two-ball rotation were reduced by decreasing the level of task difficulty. Intravenous administration of atropine attenuated the increases in Oxy-Hb of the arm muscles during two-ball rotation. It is likely that contralateral skilful hand movement evokes a selective increase in Oxy-Hb of the non-contracting forearm muscle via a sympathetic cholinergic mechanism and that the increase in oxygenation might be mediated, at least in part, by central command.

Feedforward- and motor effort-dependent increase in prefrontal oxygenation during voluntary one-armed cranking.

KEY POINTS: Some cortical areas are believed to transmit a descending signal in association with motor intention and/or effort that regulates the cardiovascular system during exercise (termed central command). However, there was no evidence for the specific cortical area responding prior to arbitrary motor execution and in proportion to the motor effort. Using a multichannel near-infrared spectroscopy system, we found that the oxygenation of the dorsolateral and ventrolateral prefrontal cortices on the right side increases in a feedforward- and motor effort-dependent manner during voluntary one-armed cranking with the right arm. This finding may suggest a role of the dorsolateral and ventrolateral prefrontal cortices in triggering off central command and may help us to understand impaired regulation of the cardiovascular system in association with lesion of the prefrontal cortex. ABSTRACT: Output from higher brain centres (termed central command) regulates the cardiovascular system during exercise in a feedforward- and motor effort-dependent manner. This study aimed to determine a cortical area responding prior to arbitrarily started exercise and in proportion to the effort during exercise. The oxygenation responses in the frontal and frontoparietal areas during one-armed cranking with the right arm were measured using multichannel near-infrared spectroscopy, as indexes of regional blood flow responses, in 20 subjects. The intensity of voluntary exercise was 30% and 60% of the maximal voluntary effort (MVE). At the start period of both voluntary cranking tasks, the oxygenation increased (P < 0.05) only in the lateral and dorsal part of the dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC) and sensorimotor cortices. Then, the oxygenation increased gradually in all cortical areas during cranking at 60% MVE, while oxygenation increased only in the frontoparietal area and some of the frontal area during cranking at 30% MVE. The rating of perceived exertion to the cranking tasks correlated (P < 0.05) with the oxygenation responses on the right side of the lateral-DLPFC (r = 0.46) and VLPFC (r = 0.48) and the frontopolar areas (r = 0.47-0.49). Motor-driven passive one-armed cranking decreased the oxygenation in most cortical areas, except the contralateral frontoparietal areas. Accordingly, the lateral-DLPFC and VLPFC on the right side would respond in a feedforward- and motor effort-dependent manner during voluntary exercise with the right arm. Afferent inputs from mechanosensitive afferents may decrease the cortical oxygenation.

Decreased prefrontal oxygenation elicited by stimulation of limb mechanosensitive afferents during cycling exercise.

Our laboratory reported using near-infrared spectroscopy that feedback from limb mechanoafferents may decrease prefrontal oxygenated-hemoglobin concentration (Oxy-Hb) during the late period of voluntary and passive cycling. To test the hypothesis that the decreased Oxy-Hb of the prefrontal cortex would be augmented depending on the extent of limb mechanoafferent input, the prefrontal Oxy-Hb response was measured during motor-driven one- and two-legged passive cycling for 1 min at various revolutions of pedal movement in 19 subjects. Furthermore, we examined whether calculated tissue oxygenation index (TOI) decreased during passive cycling as the Oxy-Hb did, simultaneously assessing blood flows of extracranial cutaneous tissue and the common and internal carotid arteries (CCA and ICA) with laser and ultrasound Doppler flowmetry. Minute ventilation and cardiac output increased and peripheral resistance decreased during passive cycling, depending on both revolutions of pedal movement and number of limbs, whereas mean arterial blood pressure did not change. Passive cycling did not change end-tidal CO2, suggesting absence of a hypocapnic change. Prefrontal Oxy-Hb decreased during passive cycling, being in proportion to revolution of pedal movement but not number of cycling limbs. In addition, prefrontal TOI decreased during passive cycling as Oxy-Hb did, whereas blood flows of forehead cutaneous tissue, CCA, and ICA did not change significantly. Thus, a decrease in Oxy-Hb reflected a decrease in tissue blood flow of the intracerebral vasculature but not the extracerebral compartment. It is likely that feedback from mechanoafferents decreased regional cerebral blood flow of the prefrontal cortex in relation to the revolutions of pedal movement.

An increase in prefrontal oxygenation at the start of voluntary cycling exercise was observed independently of exercise effort and muscle mass.

PURPOSE: We have reported using near-infrared spectroscopy that an increase in prefrontal oxygenated-hemoglobin concentration (Oxy-Hb) at the start of cycling exercise has relation to central command, defined as a feedforward signal descending from higher brain centers. The final output of central command evokes the exercise effort-dependent cardiovascular responses. If the prefrontal cortex may output the final signal of central command toward the autonomic nervous system, the prefrontal oxygenation should increase depending on exercise effort. To test the hypothesis, we investigated the effects of exercise intensity and muscle mass on prefrontal oxygenation in 13 subjects. METHODS: The subjects performed one- or two-legged cycling at various relative intensities for 1 min. The prefrontal Oxy-Hb and cardiovascular variables were simultaneously measured during exercise. RESULTS: The increase in cardiac output and the decrease in total peripheral resistance at the start of one- and two-legged cycling were augmented in proportion to exercise intensity and muscle mass recruitment. The prefrontal Oxy-Hb increased at the start of voluntary cycling, while such increase was not developed during passive cycling. Mental imagery of cycling also increased the prefrontal Oxy-Hb, concomitantly with peripheral muscle vasodilatation. However, the increase in prefrontal Oxy-Hb at the start of voluntary cycling seemed independent of exercise intensity and muscle mass recruitment. CONCLUSIONS: It is likely that the increased prefrontal activity at the start of cycling exercise is not representative of the final output signal of central command itself toward the autonomic nervous system but may trigger neuronal activity in the caudal brain responsible for the generation of central command.

Cardiac parasympathetic outflow during dynamic exercise in humans estimated from power spectral analysis of P-P interval variability.

NEW FINDINGS: What is the central question of this study? Should we use the high-frequency (HF) component of P-P interval as an index of cardiac parasympathetic nerve activity during moderate exercise? What is the main finding and its importance? The HF component of P-P interval variability remained even at a heart rate of 120-140 beats min(-1) and was further reduced by atropine, indicating incomplete cardiac vagal withdrawal during moderate exercise. The HF component of R-R interval is invalid as an estimate of cardiac parasympathetic outflow during moderate exercise; instead, the HF component of P-P interval variability should be used. The high-frequency (HF) component of R-R interval variability has been widely used as an indirect estimate of cardiac parasympathetic (vagal) outflow to the sino-atrial node of the heart. However, we have recently found that the variability of the R-R interval becomes much smaller during dynamic exercise than that of the P-P interval above a heart rate (HR) of ∼100 beats min(-1). We hypothesized that cardiac parasympathetic outflow during dynamic exercise with a higher intensity may be better estimated using the HF component of P-P interval variability. To test this hypothesis, the HF components of both P-P and R-R interval variability were analysed using a Wavelet transform during dynamic exercise. Twelve subjects performed ergometer exercise to increase HR from the baseline of 69 ± 3 beats min(-1) to three different levels of 100, 120 and 140 beats min(-1). We also examined the effect of atropine sulfate on the HF components in eight of the 12 subjects during exercise at an HR of 140 beats min(-1) . The HF component of P-P interval variability was significantly greater than that of R-R interval variability during exercise, especially at the HRs of 120 and 140 beats min(-1). The HF component of P-P interval variability was more reduced by atropine than that of R-R interval variability. We conclude that cardiac parasympathetic outflow to the sino-atrial node can be estimated better by the HF component of P-P interval variability during exercise and that cardiac parasympathetic nerve activity exists during moderate dynamic exercise.

Signal transduction of aortic and carotid sinus baroreceptors is not modified by central command during spontaneous motor activity in decerebrate cats.

Our laboratory has suggested that central command provides selective inhibition of the cardiomotor component of aortic baroreflex at the start of exercise, preserving carotid sinus baroreflex. It is postulated that central command may modify the signal transduction of aortic baroreceptors, so as to decrease aortic baroreceptor input to the cardiovascular centers, and, thereby, can cause the selective inhibition of aortic baroreflex. To test the hypothesis, we directly analyzed the responses in multifiber aortic nerve activity (AoNA) and carotid sinus nerve activity (CsNA) during spontaneous motor activity in decerebrate, paralyzed cats. The increases of 62-104% in mean AoNA and CsNA were found during spontaneous motor activity, in proportion to a rise of 35 ± 3 mmHg (means ± SE) in mean arterial blood pressure (MAP), and had an attenuating tendency by restraining heart rate (HR) at the lower intrinsic frequency of 154 ± 6 beats/min. Brief occlusion of the abdominal aorta was conducted before and during spontaneous motor activity to produce a mechanically evoked increase in MAP and, thereby, to examine the stimulus-response relationship of arterial baroreceptors. Although the sensitivity of the MAP-HR baroreflex curve was markedly blunted during spontaneous motor activity, the stimulus-response relationships of AoNA and CsNA were not influenced by spontaneous motor activity, irrespective of the absence or presence of the HR restraint. Thus, it is concluded that aortic and carotid sinus baroreceptors can code beat-by-beat blood pressure during spontaneous motor activity in decerebrate cats and that central command is unlikely to modulate the signal transduction of arterial baroreceptors.

Unilateral imagined movement increases interhemispheric inhibition from the contralateral to ipsilateral motor cortex.

Whether a cortical drive to one limb modulates interhemispheric inhibition (IHI) from the active targeting to the non-active motor cortex (M1) remained unclear. The present study using a conditioning-test transcranial magnetic stimulation (TMS) paradigm aimed to directly demonstrate the modulation of IHI during unilateral voluntary or imagined movement in humans. Subjects were asked to actually perform right index-finger abduction (10-70% of the maximum voluntary contraction) or to imagine the movement. Conditioning and test TMS with an interstimulus interval of 5, 10, and 15 ms were applied over the left and right M1, respectively, and the test motor evoked potential (MEP) was recorded from the left first dorsal interosseous (FDI) muscle. The conditioning TMS intensity was adjusted ranging from 0.6 to 1.4 (in 0.2 steps) times the resting motor threshold (rMT). With test TMS alone, MEP in the left FDI muscle significantly increased during voluntary or imagined movement of the right index-finger. MEP amplitude was significantly reduced in proportion to increments of the conditioning TMS intensity at rest (1.2 and 1.4 times the rMT, P < 0.05, respectively). Importantly, the MEP inhibition was markedly enhanced during voluntary or imagined movement in comparison with that at rest. The regression analysis revealed that IHI varied depending on the intensity of the impulses conveyed from left to right M1, but not on the corticospinal excitability of the active right hand. Our results suggest that IHI from the active to non-active M1 is enhanced during unilateral volitional motor activity.

Differential effect of central command on aortic and carotid sinus baroreceptor-heart rate reflexes at the onset of spontaneous, fictive motor activity.

Our laboratory has reported that central command blunts the sensitivity of the aortic baroreceptor-heart rate (HR) reflex at the onset of voluntary static exercise in conscious cats and spontaneous contraction in decerebrate cats. The purpose of this study was to examine whether central command attenuates the sensitivity of the carotid sinus baroreceptor-HR reflex at the onset of spontaneous, fictive motor activity in paralyzed, decerebrate cats. We confirmed that aortic nerve (AN)-stimulation-induced bradycardia was markedly blunted to 26 ± 4.4% of the control (21 ± 1.3 beats/min) at the onset of spontaneous motor activity. Although the baroreflex bradycardia by electrical stimulation of the carotid sinus nerve (CSN) was suppressed (P < 0.05) to 86 ± 5.6% of the control (38 ± 1.2 beats/min), the inhibitory effect of spontaneous motor activity was much weaker (P < 0.05) with CSN stimulation than with AN stimulation. The baroreflex bradycardia elicited by brief occlusion of the abdominal aorta was blunted to 36% of the control (36 ± 1.6 beats/min) during spontaneous motor activity, suggesting that central command is able to inhibit the cardiomotor sensitivity of arterial baroreflexes as the net effect. Mechanical stretch of the triceps surae muscle never affected the baroreflex bradycardia elicited by AN or CSN stimulation and by aortic occlusion, suggesting that muscle mechanoreflex did not modify the cardiomotor sensitivity of aortic and carotid sinus baroreflex. Since the inhibitory effect of central command on the carotid baroreflex pathway, associated with spontaneous motor activity, was much weaker compared with the aortic baroreflex pathway, it is concluded that central command does not force a generalized modulation on the whole pathways of arterial baroreflexes but provides selective inhibition for the cardiomotor component of the aortic baroreflex.

Central command: control of cardiac sympathetic and vagal efferent nerve activity and the arterial baroreflex during spontaneous motor behaviour in animals.

Feedforward control by higher brain centres (termed central command) plays a role in the autonomic regulation of the cardiovascular system during exercise. Over the past 20 years, workers in our laboratory have used the precollicular-premammillary decerebrate animal model to identify the neural circuitry involved in the CNS control of cardiac autonomic outflow and arterial baroreflex function. Contrary to the traditional idea that vagal withdrawal at the onset of exercise causes the increase in heart rate, central command did not decrease cardiac vagal efferent nerve activity but did allow cardiac sympathetic efferent nerve activity to produce cardiac acceleration. In addition, central command-evoked inhibition of the aortic baroreceptor-heart rate reflex blunted the baroreflex-mediated bradycardia elicited by aortic nerve stimulation, further increasing the heart rate at the onset of exercise. Spontaneous motor activity and associated cardiovascular responses disappeared in animals decerebrated at the midcollicular level. These findings indicate that the brain region including the caudal diencephalon and extending to the rostral mesencephalon may play a role in generating central command. Bicuculline microinjected into the midbrain ventral tegmental area of decerebrate rats produced a long-lasting repetitive activation of renal sympathetic nerve activity that was synchronized with the motor nerve discharge. When lidocaine was microinjected into the ventral tegmental area, the spontaneous motor activity and associated cardiovascular responses ceased. From these findings, we conclude that cerebral cortical outputs trigger activation of neural circuits within the caudal brain, including the ventral tegmental area, which causes central command to augment cardiac sympathetic outflow at the onset of exercise in decerebrate animal models.

Central modulation of cardiac baroreflex moment-to-moment sensitivity during treadmill exercise in conscious cats.

It remains undetermined whether the cardiac component of the entire arterial baroreflex is blunted even at the onset of low-intensity exercise. We sought to examine the moment-to-moment sensitivity of the cardiac baroreflex during walking at different speeds and the presumed mechanisms responsible for baroreflex modulation in conscious cats. Arterial baroreflex sensitivity for heart rate was estimated from the baroreflex ratio between changes in systolic arterial blood pressure and heart rate and from the slope of the baroreflex curve between the cardiovascular responses to brief occlusion of the abdominal aorta. Treadmill walking was performed for 1 min at three levels of speed (low: 20-30 m/min, moderate: 40 m/min, and high: 50-60 m/min) or for 3 min at the stepwise change of speed (low to high to low transition). Cardiac baroreflex sensitivity was blunted at the onset of walking, irrespective of speed. Thereafter, the blunted cardiac baroreflex sensitivity was restored around 15 s of walking at any speed, while the blunting occurred again at 45 s of high-speed walking. The inhibition of cardiac baroreflex sensitivity also occurred (1) during the speed transition from low to high and (2) at 45 s of high-speed exercise of the stepwise exercise. The blunted cardiac baroreflex sensitivity was restored immediately to the resting level during the speed transition from high to low, despite sustained pressor and tachycardiac responses. Therefore, moment-to-moment modulation of the cardiac baroreflex during exercise would occur in association with motor intention (i.e., exercise onset) and effort (i.e., treadmill speed).

Central command does not decrease cardiac parasympathetic efferent nerve activity during spontaneous fictive motor activity in decerebrate cats.

To examine whether withdrawal of cardiac vagal efferent nerve activity (CVNA) predominantly controls the tachycardia at the start of exercise, the responses of CVNA and cardiac sympathetic efferent nerve activity (CSNA) were directly assessed during fictive motor activity that occurred spontaneously in unanesthetized, decerebrate cats. CSNA abruptly increased by 71 ± 12% at the onset of the motor activity, preceding the tachycardia response. The increase in CSNA lasted for 4-5 s and returned to the baseline, even though the motor activity was not ended. The increase of 6 ± 1 beats/min in heart rate appeared with the same time course of the increase in CSNA. In contrast, CVNA never decreased but increased throughout the motor activity, in parallel with a rise in mean arterial blood pressure (MAP). The peak increase in CVNA was 37 ± 9% at 5 s after the motor onset. The rise in MAP gradually developed to 21 ± 2 mmHg and was sustained throughout the spontaneous motor activity. Partial sinoaortic denervation (SAD) blunted the baroreflex sensitivity of the MAP-CSNA and MAP-CVNA relationship to 22-33% of the control. Although partial SAD blunted the initial increase in CSNA to 53% of the control, the increase in CSNA was sustained throughout the motor activity. In contrast, partial SAD almost abolished the increase in CVNA during the motor activity, despite the augmented elevation of 31 ± 1 mmHg in MAP. Because afferent inputs from both muscle receptors and arterial baroreceptors were absent or greatly attenuated in the partial SAD condition, only central command was operating during spontaneous fictive motor activity in decerebrate cats. Therefore, it is likely that central command causes activation of cardiac sympathetic outflow but does not produce withdrawal of cardiac parasympathetic outflow during spontaneous motor activity.

Centrally evoked increase in adrenal sympathetic outflow elicits immediate secretion of adrenaline in anaesthetized rats.

To examine whether feedforward control by central command activates preganglionic adrenal sympathetic nerve activity (AdSNA) and releases catecholamines from the adrenal medulla, we investigated the effects of electrical stimulation of the hypothalamic locomotor region on preganglionic AdSNA and secretion rate of adrenal catecholamines in anaesthetized rats. Pre- or postganglionic AdSNA was verified by temporary sympathetic ganglionic blockade with trimethaphan. Adrenal venous blood was collected every 30 s to determine adrenal catecholamine output and blood flow. Hypothalamic stimulation for 30 s (50 Hz, 100-200 microA) induced rapid activation of preganglionic AdSNA by 83-181% depending on current intensity, which was followed by an immediate increase of 123-233% in adrenal adrenaline output. Hypothalamic stimulation also increased postganglionic AdSNA by 42-113% and renal sympathetic nerve activity by 94-171%. Hypothalamic stimulation induced preferential secretion of adrenal adrenaline compared with noradrenaline, because the ratio of adrenaline to noradrenaline increased greatly during hypothalamic stimulation. As soon as the hypothalamic stimulation was terminated, preganglionic AdSNA returned to the prestimulation level in a few seconds, and the elevated catecholamine output decayed within 30-60 s. Adrenal blood flow and vascular resistance were not affected or slightly decreased by hypothalamic stimulation. Thus, it is likely that feedforward control of catecholamine secretion from the adrenal medulla plays a role in conducting rapid hormonal control of the cardiovascular system at the beginning of exercise.

Pivotal role of the ventral tegmental area in spontaneous motor activity and concomitant cardiovascular responses in decerebrate rats.

Central command, a feedforward signal from higher brain centers, regulates the cardiovascular system in association with exercise. Previous evidence suggests that nucleus (or nuclei) around the midbrain may contribute to generating spontaneous motor activity and concomitant cardiovascular responses. To examine which area within the midbrain is important for the spontaneous and synchronized responses, 18 rats were decerebrated at three levels (pre-midbrain, rostroventral midbrain, and caudal midbrain levels) and paralyzed with a neuromuscular blocker. Individual brain sections showed decerebration rostral to the pre-collicular level in the pre-midbrain preparation and, additionally, removal of the periaqueductal gray in the rostroventral midbrain preparation, and decerebration around the midcollicular level in the caudal midbrain preparation. Spontaneous motor activity occurred at frequency of 69 ± 27 times/h and accompanied increases in heart rate (by 15 ± 4 beats/min) and mean arterial blood pressure (by 54 ± 4 mmHg) in the pre-midbrain preparation. Similar motor and cardiovascular responses took place in the rostroventral midbrain preparation, while such responses hardly occurred in the caudal midbrain preparation. We next examined whether injection of a GABAergic receptor agonist (muscimol) in the ventral tegmental area (VTA) inhibits the spontaneous motor and cardiovascular responses in 6 pre-midbrain preparations. The occurrence of spontaneous motor activity and concomitant cardiovascular responses was inhibited clearly (P < 0.05) by injection of muscimol, but not saline. It is concluded that the VTA plays a pivotal role in the spontaneous and synchronized activation of the motor and cardiovascular systems in decerebrate rats.

Increased prefrontal oxygenation prior to and at the onset of over-ground locomotion in humans.

Our laboratory has reported with near-infrared spectroscopy (NIRS) that prefrontal oxygenated-hemoglobin concentration (Oxy-Hb), measured as index of regional cerebral blood flow, increased before and at the onset of arbitrary (i.e., noncued) ergometer exercise in a laboratory environment. In the current study, we hypothesized that naturally occurring over-ground locomotion, despite "very light" motor effort, as indicated by a Borg scale of 8.0 ± 0.3, likewise causes preexercise activation of the prefrontal cortex. Using wireless NIRS, we examined in this study how early and to what extent prefrontal activity changed before the onset of arbitrary walking in 13 subjects. Prefrontal Oxy-Hb increased 2 s before the onset of arbitrary walking, and the increased Oxy-Hb reached a peak at 5 s from walking onset. The preexercise and initial increase in prefrontal Oxy-Hb was absent when over-ground walking was forced to start by cue. The difference in the Oxy-Hb response between arbitrary and cued start, which was considered to be related to central command, became significant 2 s before walking onset, preceding the difference in the heart rate (HR) response by 8 s. This demonstrated a positive relationship with the HR difference in 69% of subjects. Imagery of arbitrary walking was, likewise, able to increase prefrontal oxygenation to the same extent as actual walking. Thus, it is likely that prefrontal oxygenation increases before the onset of naturally occurring walking in daily life, despite "very light" effort. The increased prefrontal oxygenation may contribute at least partly to cardiac adjustment, synchronized with the beginning of motor performance.NEW & NOTEWORTHY We found using wireless near-infrared spectroscopy that prefrontal oxygenation increased before the onset of arbitrary over-ground walking, whereas the preexercise increase was absent when walking was suddenly started by cue. The difference in prefrontal oxygenation between start modes (considered related to central command) preceded heart rate response variances and demonstrated a positive relationship with the difference in heart rate. The central command-related prefrontal activity may contribute to cardiac adjustment, synchronized with the beginning of over-ground walking.

Muscle mechanosensitive reflex is suppressed in the conscious condition: effect of anesthesia.

To test the hypothesis that a muscle mechanosensitive reflex is suppressed in the conscious condition, we examined the effect of anesthesia on the cardiovascular responses to passive mechanical stretch of the hindlimb triceps surae muscle in six conscious cats. The triceps surae muscle was manually stretched for 30 s by extending the hip and knee joints and subsequently by dorsiflexing the ankle joint; the lateral gastrocnemius muscle was lengthened by 19 +/- 2.6 mm. Heart rate (HR) and mean arterial blood pressure (MAP) did not change significantly during passive stretch of the muscle in the conscious condition. At 10-40 min after intravenously administering pentobarbital sodium (20-25 mg/kg), the identical passive stretch of the triceps surae muscle was able to induce the cardiovascular responses; HR and MAP were increased by 14 +/- 1.3 beats/min and 14 +/- 1.4 mmHg, respectively, and the cardiovascular responses were sustained throughout the passive stretch. In contrast, stretching skin on the triceps surae muscle evoked no significant changes in HR and MAP in the anesthetized condition. When anesthesia became light 40-90 min after injection of pentobarbital and the animals started to show spontaneous body movement, the cardiovascular response to passive muscle stretch tended to be blunted again. It is therefore concluded that passive mechanical stretch of skeletal muscle is capable of evoking the reflex cardiovascular response, which is suppressed in the conscious condition but exaggerated by anesthesia.