Kana Endo

Increased oxygenation of the cerebral prefrontal cortex prior to the onset of voluntary exercise in humans

To determine whether output from the forebrain (termed central command) may descend early enough to increase cardiac and renal sympathetic outflows at the onset of voluntary exercise, we examined the changes in regional tissue blood flows of bilateral prefrontal cortices with near-infrared spectroscopy, precisely identifying the onset of voluntary ergometer 30-s exercise at 41 ± 2% of the maximal exercise intensity in humans. Prefrontal oxygenated-hemoglobin (Oxy-Hb) concentration was measured as index of regional blood flow unless deoxygenated-hemoglobin concentration remained unchanged. Prefrontal Oxy-Hb concentration increased significantly (P < 0.05) 5 s prior to the onset of exercise with arbitrary start, whereas such increase in prefrontal Oxy-Hb was absent before exercise abruptly started by a verbal cue. Furthermore, the increase in prefrontal Oxy-Hb observed at the initial 15-s period of exercise was greater with arbitrary start than cued start. The prefrontal Oxy-Hb, thereafter, decreased during the later period of exercise, irrespective of either arbitrary or cued start. The reduction in prefrontal Oxy-Hb had the same time course and response magnitude as that during motor-driven passive exercise. Cardiac output increased at the initial period of exercise, whereas arterial blood pressure and total peripheral resistance decreased. The depressor response was more pronounced (P < 0.05) with arbitrary start than cued start. Taken together, it is suggested that the increase in prefrontal Oxy-Hb observed prior to the onset of voluntary exercise may be in association with central command, while the later decrease in the Oxy-Hb during exercise may be in association with feedback stimulated by mechanical limb motion.

Evidence for centrally induced cholinergic vasodilatation in skeletal muscle during voluntary one‐legged cycling and motor imagery in humans

We have recently reported that central command contributes to increased blood flow in both noncontracting and contracting vastus lateralis (VL) muscles at the early period of voluntary one‐legged cycling. The purpose of this study was to examine whether sympathetic cholinergic vasodilatation mediates the increases in blood flows of both muscles during one‐legged exercise. Following intravenous administration of atropine (10 μg/kg), eight subjects performed voluntary 1‐min one‐legged cycling (at 35% of maximal voluntary effort) and mental imagery of the exercise. The relative concentrations of oxygenated‐ and deoxygenated‐hemoglobin (Oxy‐ and Deoxy‐Hb) in the bilateral VL were measured as an index of muscle tissue blood flow with near‐infrared spectroscopy (NIRS). The Oxy‐Hb in both noncontracting and contracting VL increased at the early period of one‐legged cycling, whereas the Deoxy‐Hb did not alter at that period. Atropine blunted (P < 0.05) the Oxy‐Hb responses of both VL muscles but did not affect the Deoxy‐Hb responses. The time course and magnitude of the atropine‐sensitive component in the Oxy‐Hb response were quite similar between the noncontracting and contracting VL muscles. With no changes in the Deoxy‐Hb and hemodynamics, imagery of one‐legged cycling induced the bilateral increases in the Oxy‐Hb, which were completely abolished by atropine. In contrast, imagery of a circle (with no relation to exercise) did not alter the NIRS signals, irrespective of the presence or absence of atropine. It is concluded that central command evokes cholinergic vasodilatation equally in bilateral VL muscles during voluntary one‐legged cycling and motor imagery.

Have we missed that neural vasodilator mechanisms may contribute to exercise hyperemia at onset of voluntary exercise

Whether neurally-mediated vasodilatation may contribute to exercise hyperemia has not been completely understood. Bülbring and Burn (1935) found for the first time the existence of sympathetic cholinergic nerve to skeletal muscle contributing to vasodilatation in animals. Blair et al. (1959) reported that atropine-sensitive vasodilatation in skeletal muscle appeared during arousal behavior or mental stress in humans. However, such sympathetic vasodilator mechanism for muscle vascular bed in humans is generally denied at present, because surgical sympathectomy, autonomic blockade, and local anesthesia of sympathetic nerves cause no substantial influence on vasodilatation in muscle not only during mental stress but also during exercise. On the other hand, neural mechanisms may play an important role in regulating blood flow to non-contracting muscle. Careful consideration of the neural mechanisms may lead us to an insight about a possible neural mechanism responsible for exercise hyperemia in contracting muscle. Referring to our recent study measuring muscle tissue blood flow with higher time resolution, this review has focused on whether or not central command may transmit vasodilator signal to skeletal muscle especially at the onset of voluntary exercise.

The prefrontal oxygenation and ventilatory responses at start of one-legged cycling exercise have relation to central command

When performing exercise arbitrarily, activation of central command should start before the onset of exercise, but when exercise is forced to start with cue, activation of central command should be delayed. We examined whether the in-advance activation of central command influenced the ventilatory response and reflected in the prefrontal oxygenation, by comparing the responses during exercise with arbitrary and cued start. The breath-by-breath respiratory variables and the prefrontal oxygenated-hemoglobin concentration (Oxy-Hb) were measured during one-legged cycling. Minute ventilation (V̇e) at the onset of arbitrary one-legged cycling was augmented to a greater extent than cued cycling, while end-tidal carbon dioxide tension (ETco2) decreased irrespective of arbitrary or cued start. Symmetric increase in the bilateral prefrontal Oxy-Hb occurred before and at the onset of arbitrary one-legged cycling, whereas such an increase was absent with cued start. The time course and magnitude of the increased prefrontal oxygenation were not influenced by the extent of subjective rating of perceived exertion and were the same as those of the prefrontal oxygenation during two-legged cycling previously reported. Mental imagery or passive performance of the one-legged cycling increased V̇e and decreased ETco2 Neither intervention, however, augmented the prefrontal Oxy-Hb. The changes in ETco2 could not explain the prefrontal oxygenation response during voluntary or passive one-legged cycling. Taken together, it is likely that the in-advance activation of central command influenced the ventilatory response by enhancing minute ventilation at the onset of one-legged cycling exercise and reflected in the preexercise increase in the prefrontal oxygenation.

Differential contribution of ACh‐muscarinic and β‐adrenergic receptors to vasodilatation in noncontracting muscle during voluntary one‐legged exercise

We have demonstrated the centrally induced cholinergic vasodilatation in skeletal muscle at the early period of voluntary one‐legged exercise and during motor imagery in humans. The purpose of this study was to examine whether central command may also cause β‐adrenergic vasodilatation during the exercise and motor imagery. Relative changes in oxygenated hemoglobin concentration (Oxy‐Hb) of bilateral vastus lateralis (VL) muscles, as index of tissue blood flow, and femoral blood flow to nonexercising limb were measured during one‐legged cycling and mental imagery of the exercise for 1 min before and after propranolol (0.1 mg/kg iv). The Oxy‐Hb of noncontracting muscle increased (P < 0.05) at the early period of exercise and the increase was sustained throughout exercise, whereas the Oxy‐Hb of contracting muscle increased at the early period but thereafter decreased. We subtracted the Oxy‐Hb response with propranolol from the control response in individual subjects to identify the propranolol‐sensitive component of the Oxy‐Hb response during exercise. In both noncontracting and contracting VL muscles, the increase in Oxy‐Hb at the early period of one‐legged exercise did not involve a significant propranolol‐sensitive component. However, as the exercise proceeded, the propranolol‐sensitive component of the Oxy‐Hb response was developed during the later period of exercise. Propranolol also failed to affect the initial increases in femoral blood flow and vascular conductance of nonexercising leg but significantly attenuated (P < 0.05) their later increases during exercise. Subsequent atropine (10–15 μg/kg iv) abolished the initial increases in Oxy‐Hb of both VL muscles. Mental imagery of the one‐legged exercise caused the bilateral increases in Oxy‐Hb, which were not altered by propranolol but abolished by subsequent atropine. It is likely that the rapid cholinergic and delayed β‐adrenergic vasodilator mechanisms cooperate to increase muscle blood flow during exercise.

Central command differentially affects aortic and carotid sinus baroreflexes at the onset of spontaneous motor activity.

Our laboratory has recently demonstrated that central command provides selective inhibition of the cardiomotor component of aortic (AOR) baroreflex during exercise, preserving carotid sinus (CS) baroreflex. To further explore the differential effects of central command on the arterial baroreflexes, we surgically separated the AOR and CS baroreflex systems, to identify the input-output relationship of each baroreflex system using brief occlusion of the abdominal aorta in decerebrate cats. Baroreflex sensitivity for heart rate (HR) was estimated from the baroreflex ratio between the pressor and bradycardia responses during aortic occlusion and from the slope of the baroreflex curve between the changes in mean arterial blood pressure (ΔMAP) and ΔHR. Spontaneous motor activity accompanied the abrupt increases in HR and MAP. When aortic occlusion was given at the onset of spontaneous motor activity, the baroreflex ratio was blunted to 11-25% of the preexercise value in either intact or AOR baroreflex. The slope of the ΔMAP-ΔHR curve was similarly attenuated at the onset of spontaneous motor activity to 11-18% of the slope during the preexercise period. In contrast, in the CS baroreflex, the baroreflex ratio and curve slope were not significantly (P>0.05) altered by spontaneous motor activity. An upward shift of the baroreflex curve appeared at the onset of spontaneous motor activity, irrespective of the intact, AOR, and CS baroreflex conditions. Taken together, it is concluded that central command provides selective inhibition for the cardiomotor limb of the aortic baroreflex at the onset of exercise, which in turn contributes to an instantaneous increase in HR.

Central command generated prior to arbitrary motor execution induces muscle vasodilatation at the beginning of dynamic exercise

The purpose of this study was to examine the role of central command, generated prior to arbitrary motor execution, in cardiovascular and muscle blood flow regulation during exercise. Thirty two subjects performed 30 s of two-legged cycling or 1 min of one-legged cycling (66 ± 4% and 35% of the maximal exercise intensity, respectively), which was started arbitrarily or abruptly by a verbal cue (arbitrary vs. cued start). We measured the cardiovascular variables during both exercises and the relative changes in oxygenated-hemoglobin concentration (Oxy-Hb) of noncontracting vastus lateralis muscles as index of tissue blood flow and femoral blood flow to nonexercising leg during one-legged cycling. Two-legged cycling with arbitrary start caused a decrease in total peripheral resistance (TPR), which was smaller during the exercise with cued start. The greater reduction of TPR with arbitrary start was also recognized at the beginning of one-legged cycling. Oxy-Hb of noncontracting muscle increased by 3.6 ± 1% (P < 0.05) during one-legged cycling with arbitrary start, whereas such increase in Oxy-Hb was absent with cued start. The increases in femoral blood flow and vascular conductance of nonexercising leg were evident (P < 0.05) at 10 s from the onset of one-legged cycling with arbitrary start, whereas those were smaller or absent with cued start. It is likely that when voluntary exercise is started arbitrarily, central command is generated prior to motor execution and then contributes to muscle vasodilatation at the beginning of exercise. Such centrally induced muscle vasodilatation may be weakened and/or masked in the case of exercise with cued start.

Motor somatotopy of extensor indicis proprius and extensor pollicis longus

After tendon transfer of extensor indicis proprius (EIP) to extensor pollicis longus (EPL), rehabilitation is initiated to enhance motor cortex reorganization. However, patients have been described showing thumb extension immediately after the tendon transfer. At cortical level, no evidence supports either of these assumptions. We noninvasively investigated motor cortical source locations of EIP and EPL muscles. Magnetoencephalography was used to identify motor somatotopic map in healthy right-handed participants, who performed voluntary extension at index metacarpophalangeal joint and thumb interphalangeal joint. Motor cortical representation of EIP was more medial than cortical representation of EPL, with mean Euclidean distance of 15.4±2.7 mm. Motor somatotopic map of EIP/EPL that was obtained by magnetoencephalography supports ‘functional somatotopy’ representation of the finger in primary motor cortex.

Central command increases muscular oxygenation of the non‐exercising arm at the early period of voluntary one‐armed cranking

This study aimed to examine whether central command increases oxygenation in non‐contracting arm muscles during contralateral one‐armed cranking and whether the oxygenation response caused by central command differs among skeletal muscles of the non‐exercising upper limb. In 13 male subjects, the relative changes in oxygenated‐hemoglobin concentration (Oxy‐Hb) of the non‐contracting arm muscles [the anterior deltoid, triceps brachii, biceps brachii, and extensor carpi radialis (ECR)] were measured during voluntary one‐armed cranking (intensity, 35–40% of maximal voluntary effort) and mental imagery of the one‐armed exercise for 1 min. Voluntary one‐armed cranking increased (P < 0.05) the Oxy‐Hb of the triceps, biceps, and ECR muscles to the same extent (15 ± 4% of the baseline level, 17 ± 5%, and 16 ± 4%, respectively). The greatest increase in the Oxy‐Hb was observed in the deltoid muscle. Intravenous injection of atropine (10–15 μg/kg) and/or propranolol (0.1 mg/kg) revealed that the increased Oxy‐Hb of the arm muscles consisted of the rapid atropine‐sensitive and delayed propranolol‐sensitive components. Mental imagery of the exercise increased the Oxy‐Hb of the arm muscles. Motor‐driven passive one‐armed cranking had little influence on the Oxy‐Hb of the arm muscles. It is likely that central command plays a role in the initial increase in oxygenation in the non‐contracting arm muscles via sympathetic cholinergic vasodilatation at the early period of one‐armed cranking. The centrally induced increase in oxygenation may not be different among the distal arm muscles but may augment in the deltoid muscle.

Incremental rate of prefrontal oxygenation determines performance speed during cognitive Stroop test: the effect of ageing

Cognitive function declines with age. The underlying mechanisms responsible for the deterioration of cognitive performance, however, remain poorly understood. We hypothesized that an incremental rate of prefrontal oxygenation during a cognitive Stroop test decreases in progress of ageing, resulting in a slowdown of cognitive performance. To test this hypothesis, we identified, using multichannel near-infrared spectroscopy, the characteristics of the oxygenated-hemoglobin concentration (Oxy-Hb) responses of the prefrontal cortex to both incongruent Stroop and congruent word-reading test. Spatial distributions of the significant changes in the three components (initial slope, peak amplitude, and area under the curve) of the Oxy-Hb response were compared between young and elderly subjects. The Stroop interference time (as a difference in total periods for executing Stroop and word-reading test, respectively) approximately doubled in elderly as compared to young subjects. The Oxy-Hb in the rostrolateral, but not caudal, prefrontal cortex increased during the Stroop test in both age groups. The initial slope of the Oxy-Hb response, rather than the peak and area under the curve, had a strong correlation with cognitive performance speed. Taken together, it is likely that the incremental rate of prefrontal oxygenation may decrease in progress of ageing, resulting in a decline in cognitive performance.