David Burke

The responses of human muscle spindle endings to vibration of non‐contracting muscles.

1. In micro‐electrode recordings from the human peroneal and tibial nerves, the responses of thirty‐two primary spindle endings, thirteen secondary spindle endings and three Golgi tendon organs were studied during vibration of the tendons of the receptor‐bearing muscles in the leg. The amplitude of the applied vibration was 1‐5 mm and the frequency was varied from 20 to 220 Hz. As checked with e.m.g. and torque measurements, the muscles of the leg were relaxed during the sequences analysed. 2. Providing that the vibrator was accurately applied, all endings responded with discharges phase‐locked to the vibration cycles, the discharge rates being at the vibration frequency or at subharmonics of that frequency. The response to vibration was of abrupt onset and offset, was maintained for the duration of vibration, and was not subject to fluctuation with changes in attention or with remote muscle contraction. 3. The maximal discharge rate that could be achieved varied from one ending to the next, and increased with the length of the receptor‐bearing muscle. For endings driven at their maximal rate an increase in vibration frequency produced a decrease in discharge rates as the ending changed to a subharmonic pattern of response. The converse occurred on decreasing vibration frequency. 4. For any given muscle length, primary endings could generally be driven to higher rates than secondary endings but there was a wide range of responsiveness within each group and a significant overlap between the groups. At medium muscle length, the most responsive primary endings could be driven up to 220 Hz but secondary endings did not reach discharge rates higher than 100 Hz. 5. With combined vibration and passive movements, primary endings exhibited maximal vibration responsiveness during the stretching phases, sometimes firing twice per vibration cycle. During the shortening phases, however, they usually ceased responding to the vibratory stimulus. The vibration responsiveness of secondary endings was not potentiated to the same extent by on‐going muscle stretch or reduced to the same extent by on‐going muscle shortening. Thus, during shortening, secondary endings may be more responsive than primary endings. 6. The responses of primary endings to tendon taps were reduced during muscle vibration, a reduction which probably contributes to vibration‐induced suppression of tendon jerks. Additionally, as the muscle shortened after tendon percussion, there was a transient pause in the response to vibration.

Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee

These guidelines provide an up-date of previous IFCN report on “Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application” (Rossini et al., 1994). A new Committee, composed of international experts, some of whom were in the panel of the 1994 “Report”, was selected to produce a current state-of-the-art review of non-invasive stimulation both for clinical application and research in neuroscience. Since 1994, the international scientific community has seen a rapid increase in non-invasive brain stimulation in studying cognition, brain–behavior relationship and pathophysiology of various neurologic and psychiatric disorders. New paradigms of stimulation and new techniques have been developed. Furthermore, a large number of studies and clinical trials have demonstrated potential therapeutic applications of non-invasive brain stimulation, especially for TMS. Recent guidelines can be found in the literature covering specific aspects of non-invasive brain stimulation, such as safety (Rossi et al., 2009), methodology (Groppa et al., 2012) and therapeutic applications (Lefaucheur et al., 2014). This up-dated review covers theoretical, physiological and practical aspects of non-invasive stimulation of brain, spinal cord, nerve roots and peripheral nerves in the light of more updated knowledge, and include some recent extensions and developments.

Threshold tracking techniques in the study of human peripheral nerve.

Conventional electrophysiological tests of nerve function focus on the number of conducting fibers and their conduction velocity. These tests are sensitive to the integrity of the myelin sheath, but provide little information about the axonal membrane. Threshold tracking techniques, in contrast, test nerve excitability, which depends on the membrane properties of the axons at the site of stimulation. These methods are sensitive to membrane potential, and to changes in membrane potential caused by activation of ion channels and electrogenic ion pumps, including those under the myelin sheath. This review describes the range of threshold tracking techniques that have been developed for the study of human nerves in vivo: resting threshold is compared with the threshold altered by a change in environment (e.g., ischemia), by a preceding single impulse (e.g., refractoriness, superexcitability) or impulse train, or by a subthreshold current (e.g., threshold electrotonus). Few clinical studies have been reported so far, mainly in diabetic neuropathy and motor neuron disease. Threshold measurements seem well suited for studies of metabolic and toxic neuropathies but insensitive to demyelination. Until suitable equipment becomes more widely available, their full potential is unlikely to be realized.

The responses of human muscle spindle endings to vibration during isometric contraction.

1. An human subjects, vibration of amplitude 1‐5 mm and frequency 20‐220 Hz was applied to the tendons of muscles in the leg to examine the effects on the discharge of primary and secondary endings during manoeuvres designed to alter the level of fusimotor drive. 2. In four experiments, the peroneal nerve was completely blocked with lidocaine proximal to the recording site in order to de‐efferent spindle endings temporarily. The responses to muscle stretch and vibration, as seen in multi‐unit recordings and in single unit recordings, were similar during the block as in the relaxed state prior to the block. Thus, these experiments provided no evidence for a functionally effective resting fusimotor drive. 3. The responses to vibration of nine primary endings and four secondary endings were examined during isometric voluntary contractions of the receptor‐bearing muscles. Providing that the endings were responding submaximally in the relaxed state, voluntary contraction enhanced the response to vibration, suggesting co‐activation of the fusimotor system sufficient to compensate for mechanical unloading. Unloading effects were observed during contractions of neighbouring synergistic muscles, indicating a close spatial relationship between the co‐activated skeletomotor and fusimotor outflows. 4. Recordings were obtained from ten primary endings and seven secondary endings during isometric reflex contractions resulting from the vibratory stimulus (TVR contractions). For twelve endings, the appearance of the tonic vibration reflex in the receptor‐bearing muscle resulted in a significant decrease in the response to vibration, suggesting that the endings were unloaded by the extrafusal contraction. On voluntary suppression of the reflex contraction spindle responses reverted to their previous levels. 5. These results suggest that the tonic vibration reflex, like the tendon jerk reflex, operates predominantly or exclusively on alpha motoneurones and that it does not utilize the same cortically originating efferent pathways as are used in the performance of voluntary contractions.

Multiple measures of axonal excitability: a new approach in clinical testing.

From measurements of nerve excitability and the changes in excitability produced by nerve impulses and conditioning currents, it is possible to infer information about the membrane potential and biophysical properties of peripheral axons. Such information cannot be obtained from conventional nerve conduction studies. This article describes a new method that enables several such measurements to be made on a motor nerve quickly and reproducibly, with minimal operator intervention. The protocol measures stimulus–response behavior using two stimulus durations (from which the distribution of strength–duration time constants can be estimated), threshold electrotonus to 100‐ms polarizing currents, a current–threshold relationship (indicating inward and outward rectification), and the recovery of excitability following supramaximal activation. The method was tested on 30 healthy volunteers, stimulating the median nerve at the wrist and recording from the abductor pollicis brevis. The results were comparable with previously published normal data, but the recordings took less than 10 min. The convenience and brevity of the new method make it appropriate for routine clinical use.

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)

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.

Perceptual responses to microstimulation of single afferents innervating joints, muscles and skin of the human hand.

1. Microneurographic techniques were used to isolate single afferent axons within cutaneous and motor fascicles of the median and ulnar nerves at the wrist in thirteen subjects. Of the sixty‐five identified afferents, eleven innervated the interphalangeal and metacarpophalangeal joints, sixteen innervated muscle spindles, three innervated Golgi tendon organs and thirty‐five supplied the glabrous skin of the hand. 2. Intrafascicular stimulation through the recording microelectrode, using trains of constant‐voltage positive pulses (0.3‐0.8 V, 0.1‐0.2 ms, 1‐100 Hz) or constant‐current biphasic pulses (0.4‐13.0 microA, 0.2 ms, 1‐100 Hz), evoked specific sensations from sites associated with some afferent species but not others. 3. Microstimulation of eight of the eleven joint afferent sites (73%) evoked specific sensations. With four, subjects reported innocuous deep sensations referred to the relevant joint. With the other four, the subjects reported a sensation of joint displacement that partially reflected the responsiveness of the afferents to joint rotation. 4. Microstimulation of fourteen of the sixteen muscle spindle afferent sites (88%) generated no perceptions when the stimuli did not produce overt movement. However, subjects could correctly detect the slight movements generated when the stimuli excited the motor axons to the parent muscle. 5. With seven of the nine rapidly adapting (type RA or FAI) cutaneous afferents (88%) microstimulation evoked sensations of ‘flutter‐vibration’, and with two of eight slowly adapting (type SAI) afferents (25%) it evoked sensations of sustained pressure’. Of the eighteen SAII afferents, which were classified as such by their responses to planar skin stretch, the majority (83%) generated no perceptions, confirming previous work, but three evoked sensations of movements or pressure. 6. The present results suggest a relatively secure transmission of joint afferent traffic to perceptual levels, and it is concluded that the human brain may be able to synthesize meaningful information on joint displacement on the basis of impulses in a single joint afferent. This could partly compensate for the low responsiveness of individual joint afferents within the physiological range of joint displacements. Although single muscle spindle afferents can adequately encode joint position and movement, the results suggest that the brain needs the information from more than one muscle spindle afferent to perceive changes in joint angle.

Muscle spindle activity in man during shortening and lengthening contractions.

1. The responses of forty‐one muscle spindle endings, mostly in tibialis anterior, were studied in human subjects during voluntary movements of the ankle joint performed at various speeds against different external loads. 2. During slow shortening contractions, the discharge rates of spindle endings in the contracting muscle accelerated after the appearance of the first e.m.g. potentials but before sufficient force had been generated to move the limb. With some endings, the discharge rate decreased during the shortening movement while the e.m.g. activity was increasing, but it always remained higher than before the onset of contraction. If the speed of the movement was increased fewer spindle discharges were seen during muscle shortening. If the shortening contraction was opposed by an external load, so that greater effort was required to perform the same movement, more discharges were seen and the discharge pattern became less modulated by the change in muscle length. 3. These findings indicate that during shortening contractions the fusimotor system is activated together with the skeletomotor system. However, the fusimotor drive is generally insufficient to maintain a significant spindle discharge unless movement is slow or the muscle is shortening against an external load. 4. During lengthening contractions the spindle responses were greater than to passive stretch of similar amplitude and velocity, suggesting heightened fusimotor outflow. 5. During shortening and lengthening contractions small iregularities in the speed of movement occurred commonly. Unintended acceleration of a shortening movement caused a pause in spindle firing, and unintended acceleration of a lengthening movement caused an increased discharge from spindle endings. These spindle responses were associated with corresponding alterations in the discharge pattern of the voluntarily activated motor units at latencies consistent with the operation of spinal reflex mechanisms. 6. It is suggested that a functional role for the fusimotor activation during slow shortening contractions is to provide spindle endings with a background discharge so that they can detect irregularities in the movement and initiate the appropriate reflex correction.

Decline in spindle support to alpha-motoneurones during sustained voluntary contractions.

1. To address whether the muscle spindle support to alpha‐motoneurones is maintained during prolonged isometric voluntary contractions, the discharge of eighteen muscle spindle afferents, originating in the dorsiflexors of the ankle or toes, was recorded from the common peroneal nerve in eight subjects. Isometric contractions were generally sustained for 1 min, usually below 30% of the maximal voluntary dorsiflexion force. 2. Once the afferent had been identified, subjects were instructed to dorsiflex the foot slowly to recruit the spindle ending, to continue the ramp contraction until a predetermined target force was reached, and then to hold that force until requested to relax. 3. Five muscle spindle afferents maintained a constant discharge frequency during the hold phase of the isometric contraction. Following relaxation of the contraction two spindle afferents from tibialis anterior, exhibited a post‐contraction discharge despite the absence of detectable electromyographic activity (EMG). 4. The discharge frequency of most of the spindle afferents (72%) declined progressively during the isometric contraction. The mean firing rates had declined to two‐thirds of those at the onset of the contraction by 30 s, and to half after 1 min. The decline in spindle firing rate commenced during the ramp phase of the contraction and was statistically significant by 10 s, when force was held constant. The extent of the decline was greater for those units with the higher initial firing rates and for those units studied after many preceding contractions. 5. In the same contractions a progressive increase in EMG was required to maintain force and consequently the change in EMG was inversely related to the change in spindle discharge. While many mechanisms may contribute to the decline in spindle discharge during a sustained isometric contraction, it is argued that the result will be a progressive disfacilitation of alpha‐motoneurones, which may contribute to the decline in motor unit firing rates during a sustained contraction.