Tadaaki Mano

Microneurography as a tool in clinical neurophysiology to investigate peripheral neural traffic in humans.

Microneurography is a method using metal microelectrodes to investigate directly identified neural traffic in myelinated as well as unmyelinated efferent and afferent nerves leading to and coming from muscle and skin in human peripheral nerves in situ. The present paper reviews how this technique has been used in clinical neurophysiology to elucidate the neural mechanisms of autonomic regulation, motor control and sensory functions in humans under physiological and pathological conditions. Microneurography is particularly important to investigate efferent and afferent neural traffic in unmyelinated C fibers. The recording of efferent discharges in postganglionic sympathetic C efferent fibers innervating muscle and skin (muscle sympathetic nerve activity; MSNA and skin sympathetic nerve activity; SSNA) provides direct information about neural control of autonomic effector organs including blood vessels and sweat glands. Sympathetic microneurography has become a potent tool to reveal neural functions and dysfunctions concerning blood pressure control and thermoregulation. This recording has been used not only in wake conditions but also in sleep to investigate changes in sympathetic neural traffic during sleep and sleep-related events such as sleep apnea. The same recording was also successfully carried out by astronauts during spaceflight. Recordings of afferent discharges from muscle mechanoreceptors have been used to understand the mechanisms of motor control. Muscle spindle afferent information is particularly important for the control of fine precise movements. It may also play important roles to predict behavior outcomes during learning of a motor task. Recordings of discharges in myelinated afferent fibers from skin mechanoreceptors have provided not only objective information about mechanoreceptive cutaneous sensation but also the roles of these signals in fine motor control. Unmyelinated mechanoreceptive afferent discharges from hairy skin seem to be important to convey cutaneous sensation to the central structures related to emotion. Recordings of afferent discharges in thin myelinated and unmyelinated fibers from nociceptors in muscle and skin have been used to provide information concerning pain. Recordings of afferent discharges of different types of cutaneous C-nociceptors identified by marking method have become an important tool to reveal the neural mechanisms of cutaneous sensations such as an itch. No direct microneurographic evidence has been so far proved regarding the effects of sympathoexcitation on sensitization of muscle and skin sensory receptors at least in healthy humans.

Long-term dry immersion: review and prospects

Dry immersion, which is a ground-based model of prolonged conditions of microgravity, is widely used in Russia but is less well known elsewhere. Dry immersion involves immersing the subject in thermoneutral water covered with an elastic waterproof fabric. As a result, the immersed subject, who is freely suspended in the water mass, remains dry. For a relatively short duration, the model can faithfully reproduce most physiological effects of actual microgravity, including centralization of body fluids, support unloading, and hypokinesia. Unlike bed rest, dry immersion provides a unique opportunity to study the physiological effects of the lack of a supporting structure for the body (a phenomenon we call ‘supportlessness’). In this review, we attempt to provide a detailed description of dry immersion. The main sections of the paper discuss the changes induced by long-term dry immersion in the neuromuscular and sensorimotor systems, fluid–electrolyte regulation, the cardiovascular system, metabolism, blood and immunity, respiration, and thermoregulation. The long-term effects of dry immersion are compared with those of bed rest and actual space flight. The actual and potential uses of dry immersion are discussed in the context of fundamental studies and applications for medical support during space flight and terrestrial health care.

Role of sympathetic nerve activity in the process of fainting

Syncope is defined as a transient loss of consciousness and postural tone, characterized by rapid onset, short duration, and spontaneous recovery, and the process of syncope progression is here described with two types of sympathetic change. Simultaneous recordings of microneurographically-recorded muscle sympathetic nerve activity (MSNA) and continuous and noninvasive blood pressure measurement has disclosed what is going on during the course of syncope progression. For vasovagal or neurally mediated syncope, three stages are identified in the course of syncope onset, oscillation, imbalance, and catastrophe phases. Vasovagal syncope is characterized by sympathoexcitation, followed by vagal overcoming via the Bezold-Jarisch reflex. Orthostatic syncope is caused by response failure or a lack of sympathetic nerve activity to the orthostatic challenge, followed by fluid shift and subsequent low cerebral perfusion. Four causes are considered for the compensatory failure that triggers orthostatic syncope: hypovolemia, increased pooling in the lower body, failure to activate sympathetic activity, and failure of vasoconstriction against sympathetic vasoconstrictive stimulation. Many pathophysiological conditions have been described from the perspectives of (1) exaggerated sympathoexcitation and (2) failure to activate the sympathetic nerve. We conclude that the sympathetic nervous system can control cardiovascular function, and its failure results in syncope; however, responses of the system obtained by microneurographically-recorded MSNA would determine the pathophysiology of the onset and progression of syncope, explaining the treatment effect that could be achieved by the analysis of this mechanism.

Respiratory modulation of human autonomic function on Earth

We studied healthy supine astronauts on Earth with electrocardiogram, non‐invasive arterial pressure, respiratory carbon dioxide concentrations, breathing depth and sympathetic nerve recordings. The null hypotheses were that heart beat interval fluctuations at usual breathing frequencies are baroreflex mediated, that they persist during apnoea, and that autonomic responses to apnoea result from changes of chemoreceptor, baroreceptor or lung stretch receptor inputs. R‐R interval fluctuations at usual breathing frequencies are unlikely to be baroreflex mediated, and disappear during apnoea. The subjects’ responses to apnoea could not be attributed to changes of central chemoreceptor activity (hypocapnia prevailed); altered arterial baroreceptor input (vagal baroreflex gain declined and muscle sympathetic nerve burst areas, frequencies and probabilities increased, even as arterial pressure climbed to new levels); or altered pulmonary stretch receptor activity (major breathing frequency and tidal volume changes did not alter vagal tone or sympathetic activity). Apnoea responses of healthy subjects may result from changes of central respiratory motoneurone activity.

Respiratory modulation of human autonomic function: long‐term neuroplasticity in space

We studied healthy astronauts before, during and after the Neurolab Space Shuttle mission with controlled breathing and apnoea, to identify autonomic changes that might contribute to postflight orthostatic intolerance. Measurements included the electrocardiogram, finger photoplethysmographic arterial pressure, respiratory carbon dioxide levels, tidal volume and peroneal nerve muscle sympathetic activity. Arterial pressure fell and then rose in space, and drifted back to preflight levels after return to Earth. Vagal metrics changed in opposite directions: vagal baroreflex gain and two indices of vagal fluctuations rose and then fell in space, and descended to preflight levels upon return to Earth. Sympathetic burst frequencies (but not areas) were greater than preflight in space and on landing day, and astronauts’ abilities to modulate both burst areas and frequencies during apnoea were sharply diminished. Spaceflight triggers long‐term neuroplastic changes reflected by reciptocal sympathetic and vagal motoneurone responsiveness to breathing changes.

Muscle Sympathetic Nerve Activity and Syncope

Syncope is defined as a transient loss of consciousness and postural tone, characterized by rapid onset, short duration, and spontaneous recovery; the process of syncope progression is here described with two types of sympathetic change. Simultaneous recording of microneurographically recorded muscle sympathetic nerve activity (MSNA) and continuous and noninvasive blood pressure measurement have disclosed what is going on during the course of syncope progression. For vasovagal or neurally mediated syncope, three stages are identified in the course of syncope onset, oscillation, imbalance, and catastrophe phases. Vasovagal syncope is characterized by sympathoexcitation, followed by vagal overcoming via the Bezold-Jarisch reflex. Orthostatic syncope is caused by response failure or a lack of sympathetic nerve activity to orthostatic challenge, followed by fluid shift and subsequent low cerebral perfusion. Four causes of the compensatory failure that trigger orthostatic syncope are considered: hypovolemia, increased pooling in the lower body, failure to activate sympathetic activity, and failure of vasoconstriction against sympathetic vasoconstrictive stimulation. Many pathophysiological conditions have been described from the perspectives of (1) exaggerated sympathoexcitation and (2) failure to activate the sympathetic nerve. We conclude that the sympathetic nervous system can control cardiovascular function, and its failure results in syncope; however, responses of the system obtained by microneurographically recorded MSNA would determine the pathophysiology of the onset and progression of syncope, explaining the treatment effect that could be achieved by the analysis of this mechanism.

Introduction to Sympathetic Microneurography

Sympathetic microneurography is an electrophysiological method to record directly from human peripheral nerves’ sympathetic neural traffic leading to the muscle and skin called muscle sympathetic nerve activity (MSNA) and skin sympathetic nerve activity (SSNA). In this chapter, the author explains (1) what is microneurography, (2) the recording technique of microneurography, (3) how to identify MSNA and SSNA, and (4) applications of sympathetic microneurography. Sympathetic microneurography is very useful to analyze sympathetic neural functions in humans by observing directly neural traffic in postganglionic multiple and single sympathetic efferent fibers innervating the muscle and skin under physiological and pathological conditions. MSNA which regulates peripheral vascular resistance in skeletal muscles is particularly important for controlling blood pressure homeostasis, while SSNA which regulates mainly sweat glands and skin blood vessels plays important roles in thermoregulation. Recordings of MSNA and SSNA have been widely applied to analyze sympathetic mechanisms in various disease conditions, as well as stressful situations when the human body is exposed to various environmental conditions.

S6-4 Conduction velocity of C-fibers in humans

Patients with cortical myoclonus have motor cortex hyperexcitability, expressed neurophysiologically in the form of high-amplitude waves in the cortical components of the somatosensory-evoked potentials (giant SSEPs). We recently studied the HFOs in a group of 20 patients with cortical myoclonus of different origins, comparing the results obtained with the amplitude and latency of the classical SSEPs waves. Nine patients had no HFOs, and another nine patients had low-amplitude and/or delayed HFOs. The remaining two patients, the only without ataxia, had very high-amplitude HFOs with a long latency. These results suggest a heterogeneity in the pathophysiology of cortical myoclonus, and point toward a possible contribution of the cerebellum in the build-up of cortical high-frequency oscillations. On the other hand, the use of deep brain stimulation has allowed the direct recording of oscillatory activity from subcortical structures in human patients. During the last years, we have recorded high-frequency activity in the SSEPs in deep structures, like the VIM nucleus of the thalamus and the subthalamic nucleus, in several patients with deep brain stimulators implanted, including two subjects with cortical myoclonus.