Simon C. Gandevia

Neurobiology of Exercise

Voluntary physical activity and exercise training can favorably influence brain plasticity by facilitating neurogenerative, neuroadaptive, and neuroprotective processes. At least some of the processes are mediated by neurotrophic factors. Motor skill training and regular exercise enhance executive functions of cognition and some types of learning, including motor learning in the spinal cord. These adaptations in the central nervous system have implications for the prevention and treatment of obesity, cancer, depression, the decline in cognition associated with aging, and neurological disorders such as Parkinsons disease, Alzheimers dementia, ischemic stroke, and head and spinal cord injury. Chronic voluntary physical activity also attenuates neural responses to stress in brain circuits responsible for regulating peripheral sympathetic activity, suggesting constraint on sympathetic responses to stress that could plausibly contribute to reductions in clinical disorders such as hypertension, heart failure, oxidative stress, and suppression of immunity. Mechanisms explaining these adaptations are not as yet known, but metabolic and neurochemical pathways among skeletal muscle, the spinal cord, and the brain offer plausible, testable mechanisms that might help explain effects of physical activity and exercise on the central nervous system.

Measurement of muscle contraction with ultrasound imaging.

To investigate the ability of ultrasonography to estimate muscle activity, we measured architectural parameters (pennation angles, fascicle lengths, and muscle thickness) of several human muscles (tibialis anterior, biceps brachii, brachialis, transversus abdominis, obliquus internus abdominis, and obliquus externus abdominis) during isometric contractions of from 0 to 100% maximal voluntary contraction (MVC). Concurrently, electromyographic (EMG) activity was measured with surface (tibialis anterior only) or fine‐wire electrodes. Most architectural parameters changed markedly with contractions up to 30% MVC but changed little at higher levels of contraction. Thus, ultrasound imaging can be used to detect low levels of muscle activity but cannot discriminate between moderate and strong contractions. Ultrasound measures could reliably detect changes in EMG of as little as 4% MVC (biceps muscle thickness), 5% MVC (brachialis muscle thickness), or 9% MVC (tibialis anterior pennation angle). They were generally less sensitive to changes in abdominal muscle activity, but it was possible to reliably detect contractions of 12% MVC in transversus abdominis (muscle length) and 22% MVC in obliquus internus (muscle thickness). Obliquus externus abdominis thickness did not change consistently with muscle contraction, so ultrasound measures of thickness cannot be used to detect activity of this muscle. Ultrasound imaging can thus provide a noninvasive method of detecting isometric muscle contractions of certain individual muscles. Muscle Nerve 27: 682–692, 2003

Supraspinal factors in human muscle fatigue: evidence for suboptimal output from the motor cortex.

1. Voluntary activation of elbow flexor muscles can be optimal during brief maximal voluntary contractions (MVCs), although central fatigue, a progressive decline in the ability to drive the muscle maximally, develops during sustained or repeated efforts. We stimulated the motor cortex and motor point in human subjects to investigate motor output during fatigue. 2. The increment in force (relative to the voluntary force) produced by stimulation of the motor point of biceps brachii increased during sustained isometric MVCs of the elbow flexors. Motoneuronal output became suboptimal during the contraction, i.e. central fatigue developed and accounted for a small but significant loss of maximal voluntary force. During 3 min MVCs, voluntary activation of biceps fell to an average of 90.7% from an average of > 99%. 3. The increment in force (relative to the voluntary force) produced by magnetic cortical stimulation was initially small (1.0%) but also increased during sustained MVCs to 9.8% (with a 2 min MVC). Thus, cortical output was not optimal at the time of stimulation nor were sites distal to the motor cortex already acting maximally. 4. A sphygmomanometer cuff around the upper arm blocked blood supply to brachioradialis near the end of a sustained MVC and throughout subsequent brief MVCs. Neither maximal voluntary force nor voluntary activation recovered during ischaemia after the sustained MVC. However, fatigue‐induced changes in EMG responses to magnetic cortical stimulation recovered rapidly despite maintained ischaemia. 5. In conclusion, during sustained MVCs, voluntary activation becomes less than optimal so that force can be increased by stimulation of the motor cortex or the motor nerve. Complex changes in excitability of the motor cortex also occur with fatigue, but can be dissociated from the impairment of voluntary activation. We argue that inadequate neural drive effectively ‘upstream’ of the motor cortex must be one site involved in the genesis of central fatigue.

The Proprioceptive Senses: Their Roles in Signaling Body Shape, Body Position and Movement, and Muscle Force

This is a review of the proprioceptive senses generated as a result of our own actions. They include the senses of position and movement of our limbs and trunk, the sense of effort, the sense of force, and the sense of heaviness. Receptors involved in proprioception are located in skin, muscles, and joints. Information about limb position and movement is not generated by individual receptors, but by populations of afferents. Afferent signals generated during a movement are processed to code for endpoint position of a limb. The afferent input is referred to a central body map to determine the location of the limbs in space. Experimental phantom limbs, produced by blocking peripheral nerves, have shown that motor areas in the brain are able to generate conscious sensations of limb displacement and movement in the absence of any sensory input. In the normal limb tendon organs and possibly also muscle spindles contribute to the senses of force and heaviness. Exercise can disturb proprioception, and this has implications for musculoskeletal injuries. Proprioceptive senses, particularly of limb position and movement, deteriorate with age and are associated with an increased risk of falls in the elderly. The more recent information available on proprioception has given a better understanding of the mechanisms underlying these senses as well as providing new insight into a range of clinical conditions.

Experimental muscle pain changes feedforward postural responses of the trunk muscles

Many studies have identified changes in trunk muscle recruitment in clinical low back pain (LBP). However, due to the heterogeneity of the LBP population these changes have been variable and it has been impossible to identify a cause-effect relationship. Several studies have identified a consistent change in the feedforward postural response of transversus abdominis (TrA), the deepest abdominal muscle, in association with arm movements in chronic LBP. This study aimed to determine whether the feedforward recruitment of the trunk muscles in a postural task could be altered by acute experimentally induced LBP. Electromyographic (EMG) recordings of the abdominal and paraspinal muscles were made during arm movements in a control trial, following the injection of isotonic (non-painful) and hypertonic (painful) saline into the longissimus muscle at L4, and during a 1-h follow-up. Movements included rapid arm flexion in response to a light and repetitive arm flexion-extension. Temporal and spatial EMG parameters were measured. The onset and amplitude of EMG of most muscles was changed in a variable manner during the period of experimentally induced pain. However, across movement trials and subjects the activation of TrA was consistently reduced in amplitude or delayed. Analyses in the time and frequency domain were used to confirm these findings. The results suggest that acute experimentally induced pain may affect feedforward postural activity of the trunk muscles. Although the response was variable, pain produced differential changes in the motor control of the trunk muscles, with consistent impairment of TrA activity.

Changes in motor cortical excitability during human muscle fatigue.

1. The excitability of the motor cortex was investigated during fatiguing con of the elbow flexors in human subjects. During sustained contractions at 30 and 1 voluntary force (MVC), the short‐latency electromyographic responses (EMG) evoke brachii and brachioradialis by transcranial magnetic stimulation increased in si EMG in the elbow flexors following the evoked muscle potential (silent period), duration during a sustained MVC but not during 30% MVCs nor during a sustained M muscle (adductor pollicis). 2. When the blood supply to brachioradialis was blocked with sphygmomanometer cuff sustained MVC, the changes in EMG responses to transcranial stimulation rapidly control values, This suggests that changes in these responses during fatigue wer small‐diameter muscle afferents. 3. Tendon vibration during sustained MVCs indicated that the changes in the resp cortial stimulation were not mediated by reduced muscle spindle inputs. 4. Muscle action potentials evoked in brachioradialis by electrical stimulation cervicomedullary junction did not increase in size during sustained MVCs. Thus, cortically evoked responses during sustained MVCs reflects a change in cortical Although the silent period following cervicomedullary stimulation lengthened, it substantially shorter than the cortically evoked silent period. 5. The altered EMG responses to transcranial stimulation during fatigue suggest exitation and increased inhibition in the motor cortex. As these changes were un manipulation of afferent input they presumably result from intrinsic cortical pr altered voluntary drive to the motor cortex.

Deep and superficial fibers of the lumbar multifidus muscle are differentially active during voluntary arm movements.

Study Design. A cross-sectional study was conducted. Objective. To determine the activity of the deep and superficial fibers of the lumbar multifidus during voluntary movement of the arm. Summary of Background Data. The multifidus contributes to stability of the lumbar spine. Because the deep and superficial parts of the multifidus are near the center of lumbar joint rotation, the superficial fibers are well suited to control spine orientation, and the deep fibers to control intervertebral movement. However, there currently are limited in vivo data to support this distinction. Methods. Electromyographic activity was recorded in both the deep and superficial multifidus, transversus abdominis, erector spinae, and deltoid using selective intramuscular electrodes and surface electrodes during single and repetitive arm movements. The latency of electromyographic onset in each muscle during single movements and the pattern of electromyographic activity during repetitive movements were compared between muscles. Results. With single arm movements, the onset of electromyography in the erector spinae and superficial multifidus relative to the deltoid was dependent on the direction of movement, but the onset in the deep multifidus and transversus abdominis was not. With repetitive arm movements, peaks in superficial multifidus and erector spinae electromyography occurred only during flexion for most subjects, whereas peaks in deep multifidus electromyography occurred during movement in both directions. Conclusions. The deep and superficial fibers of the multifidus are differentially active during single and repetitive movements of the arm. The data from this study support the hypothesis that the superficial multifidus contributes to the control of spine orientation, and that the deep multifidus has a role in controlling intersegmental motion.

Task-dependent reflex responses and movement illusions evoked by galvanic vestibular stimulation in standing humans.

1. To identify the vestibular contribution to human standing, responses in leg muscles evoked by galvanic vestibular stimulation were studied. Step impulses of current were applied between the mastoid processes of normal subjects and the effects on the soleus and tibialis anterior electromyograms (EMGs), ankle torque, and body sway were identified by post‐stimulus averaging. The responses were measured when subjects stood on a stable platform or on an unstable platform and the effects of eye closure were also assessed. Responses were also recorded during voluntary contraction of the leg muscles and when subjects balanced a load equivalent to their own body in a situation where vestibular postural reflexes would not be useful. 2. At a mean post‐stimulus latency of 56 ms, there were reciprocal changes in soleus and tibialis anterior muscle activity followed, at 105 ms, by larger responses of opposite sign. These were termed the short‐ and middle‐latency responses, respectively. Both responses increased with stimulus intensity, but the short‐latency response had a higher threshold. The early response had a similar latency to EMG responses evoked by rapid postural perturbations. Both responses were larger when the eyes were closed, but eye closure was associated with increased sway and EMG activity, and the responses were of similar magnitude when scaled to background EMG level. 3. Both short‐ and middle‐latency EMG responses in soleus and tibialis anterior muscles produced small transient postural sways. The transient changes in EMG activity were followed by a larger prolonged sway which was not attributable to the activity in these muscles but rather to reflex or volitional adjustments to movements at other body segments. When subjects were prevented from swaying, the galvanic stimulus produced illusory movements in the opposite direction to the sway evoked when standing, and it is possible that the prolonged sway is a reaction to the illusion of sway. 4. The short‐ and middle‐latency responses were modified during different postural tasks according to the dependence on vestibular reflexes. When the support platform was unstable, the EMG responses to galvanic stimulation were larger. There were no vestibular‐evoked responses when seated subjects made voluntary contractions of the leg muscles or when they stood upright with the trunk supported, using the ankles to balance a body‐like load.(ABSTRACT TRUNCATED AT 400 WORDS)

Measurement of voluntary activation of fresh and fatigued human muscles using transcranial magnetic stimulation

Recently, transcranial magnetic stimulation of the motor cortex (TMS) revealed impaired voluntary activation of muscles during maximal efforts. Hence, we evaluated its use as a measure of voluntary activation over a range of contraction strengths in both fresh and fatigued muscles, and compared it with standard twitch interpolation using nerve stimulation. Subjects contracted the elbow flexors isometrically while force and EMG from biceps and triceps were recorded. In one study, eight subjects made submaximal and maximal test contractions with rests to minimise fatigue. In the second study, eight subjects made sustained maximal contractions to reduce force to 60 % of the initial value, followed by brief test contractions. Force responses were recorded following TMS or electrical stimulation of the biceps motor nerve. In other contractions, EMG responses to TMS (motor evoked potentials, MEPs) or to stimulation at the brachial plexus (maximal M waves, Mmax) were recorded. During contractions of 50 % maximum, TMS elicited large MEPs in biceps (> 90 % Mmax) which decreased in size (to ≈70 % Mmax) with maximal efforts. This suggests that faster firing rates made some motor units effectively refractory. With fatigue, MEPs were also smaller but remained > 70 % Mmax for contractions of 50–100 % maximum. For fresh and fatigued muscle, the superimposed twitch evoked by motor nerve and motor cortex stimulation decreased with increasing contraction strength. For nerve stimulation the relation was curvilinear, and for TMS it was linear for contractions of 50‐100 % maximum (r2= 1.00). Voluntary activation was derived using the expression: (1 – superimposed twitch/resting twitch) × 100. The resting twitch was measured directly for nerve stimulation and for TMS, it was estimated by extrapolation of the linear regression between the twitch and voluntary force. For cortical stimulation, this resulted in a highly linear relation between voluntary activation and force. Furthermore, the estimated activation corresponded well with contraction strength. Using TMS or nerve stimulation, voluntary activation was high during maximal efforts of fresh muscle. With fatigue, both measures revealed reduced voluntary activation (i.e. central fatigue) during maximal efforts. Measured with TMS, this central fatigue accounted for one‐quarter of the fall in maximal voluntary force. We conclude that TMS can quantify voluntary activation for fresh or fatigued muscles at forces of 50–100 % maximum. Unlike standard twitch interpolation of the elbow flexors, voluntary activation measured with TMS varies in proportion to voluntary force, it reveals when extra output is available from the motor cortex to increase force, and it elicits force from all relevant synergist muscles.

Responses to passive movement of receptors in joint, skin and muscle of the human hand.

1. Microneurographic techniques were employed to record unitary activity from afferents associated with digital joints of six conscious human subjects. Of 120 single afferents sampled from the median and ulnar nerves at the wrist, eighteen (15%) were classified as joint afferents; the majority of the sample (72.5%) were of cutaneous origin, and 12.5% were from muscle spindles and tendon organs. 2. Of the eighteen joint afferents six were tonically active in the rest position of the hand. All except two were recruited or accelerated their background discharge during passive joint movement. Three tonically active afferents were responsive to passive movement throughout the physiological range. The majority of the afferents, including the other three tonically active units, responded only towards the limits of joint rotation. 3. As a group, the sample of joint afferents had a limited capacity to signal the direction of joint movement. Nine of the sixteen joint afferents sensitive to movement responded in two axes of angular displacement, and two responded in all three axes. In any one axis of rotation eight afferents were activated in both directions of movement. However, one afferent, associated with the interphalangeal joint of the thumb, responded uni‐directionally throughout the physiological range of joint movement and was thereby capable of adequately encoding joint position and movement. 4. Twenty‐one of twenty‐nine slowly adapting and eleven of eighteen rapidly adapting cutaneous afferents tested were activated by joint movement, but only towards the limits of joint rotation; half of the thirty‐two movement‐sensitive afferents were bi‐directionally responsive. Muscle spindle afferents responded to stresses applied to the joint only if the resulting passive movement stretched the parent muscle. 5. It is concluded that human joint afferents possess a very limited capacity to provide kinaesthetic information, and that this is likely to be of significance only when muscle spindle afferents cannot contribute to kinaesthesia.