Depression and recovery of reflex amplitude during electrical stimulation after spinal cord injury.

OBJECTIVE: The aim of this study was to quantify, for the first time, H-reflexes evoked during prolonged trains of wide-pulse neuromuscular electrical stimulation (WP-NMES) in individuals with chronic spinal cord injury (SCI). We hypothesised that after the first H-reflex, reflex amplitudes would be depressed (due to post-activation depression), but would recover and this recovery would be enhanced after a "burst" of 100 Hz WP-NMES. METHODS: Soleus M-waves and H-reflexes evoked during WP-NMES (1 ms pulse width) of the tibial nerve were quantified in nine individuals with SCI. WP-NMES was delivered in two patterns: "constant-frequency" (15 or 20 Hz for 12 s) and "burst-like" (15-100-15 Hz or 20-100-20 Hz; 4 s each phase) at an intensity that evoked an M-wave between 10% and 15% of the maximal M-wave (M(max)). RESULTS: During constant frequency stimulation, after the initial depression from the first to the second H-reflex (1st: 57% M(max); 2nd: 25% M(max)), H-reflexes did not recover significantly and were 37% M(max) at the end of the stimulus train. During the burst-like pattern, after the initial depression (1st: 62% M(max); 2nd: 30%), reflexes recovered completely by the end of the stimulation (to 55% M(max)) as they were not significantly different from the first H-reflex. M-waves were initially depressed (1st: 12% M(max); 2nd: 7% M(max)) then did not change throughout the stimulation and were not significantly different between stimulation patterns. An analysis of covariance indicated that the depression in M-wave amplitude did not account for the depression in H-reflex amplitude. CONCLUSIONS: Relatively large H-reflexes were recorded during both patterns of NMES. The brief burst of 100 Hz stimulation restored H-reflexes to their initial amplitudes, effectively reversing the effects of post-activation depression. SIGNIFICANCE: For individuals with chronic SCI, generating contractions through central pathways may help reduce muscle atrophy and produce contractions that are more fatigue-resistant for rehabilitation, exercise programs, or to perform activities of daily living.

Loss of short-latency afferent inhibition and emergence of afferent facilitation following neuromuscular electrical stimulation.

Neuromuscular electrical stimulation (NMES) increases the excitability of corticospinal (CS) pathways by altering circuits in motor cortex (M1). How NMES affects circuits interposed between the ascending afferent volley and descending CS pathways is not known. Presently, we hypothesized that short-latency afferent inhibition (SAI) would be reduced and afferent facilitation (AF) enhanced when NMES increased CS excitability. NMES was delivered for 40 min over the ulnar nerve. To assess CS excitability, motor evoked potentials (MEPs) were evoked using transcranial magnetic stimulation (TMS) delivered at 120% resting threshold for first dorsal interosseus muscle. These MEPs increased by ∼1.7-fold following NMES, demonstrating enhanced CS excitability. SAI and AF were tested by delivering a "conditioning" electrical stimulus to the ulnar nerve 18-25 ms and 28-35 ms before a "test" TMS pulse, respectively. Conditioned MEPs were compared to unconditioned MEPs evoked in the same trials. TMS was adjusted so unconditioned MEPs were not different before and after NMES. At the SAI interval, conditioned MEPs were 25% smaller than unconditioned MEPs before NMES but conditioned and unconditioned MEPs were not different following NMES. At the AF interval, conditioned MEPs were not different from unconditioned MEPs before NMES, but were facilitated by 33% following NMES. Thus, when NMES increases CS excitability there are concurrent changes in the effect of afferent input on M1 excitability, resulting in a net increase in the excitatory effect of the ascending afferent volley on CS circuits. Maximising this excitatory effect on M1 circuits may help strengthen CS pathways and improve functional outcomes of NMES-based rehabilitation programs.

Motor unit recruitment when neuromuscular electrical stimulation is applied over a nerve trunk compared with a muscle belly: quadriceps femoris.

Neuromuscular electrical stimulation (NMES) can be delivered over a nerve trunk or muscle belly and both can generate contractions through peripheral and central pathways. Generating contractions through peripheral pathways is associated with a nonphysiological motor unit recruitment order, which may limit the efficacy of NMES rehabilitation. Presently, we compared recruitment through peripheral and central pathways for contractions of the knee extensors evoked by NMES applied over the femoral nerve vs. the quadriceps muscle. NMES was delivered to evoke 10 and 20% of maximum voluntary isometric contraction torque 2-3 s into the NMES (time(1)) in two patterns: 1) constant frequency (15 Hz for 8 s); and 2) step frequency (15-100-15 Hz and 25-100-25 Hz for 3-2-3 s, respectively). Torque and electromyographic activity recorded from vastus lateralis and medialis were quantified at the beginning (time(1)) and end (time(2); 6-7 s into the NMES) of each pattern. M-waves (peripheral pathway), H-reflexes, and asynchronous activity (central pathways) during NMES were quantified. Torque did not differ regardless of NMES location, pattern, or time. For both muscles, M-waves were ∼7-10 times smaller and H-reflexes ∼8-9 times larger during NMES over the nerve compared with over the muscle. However, unlike muscles studied previously, neither torque nor activity through central pathways were augmented following 100 Hz NMES, nor was any asynchronous activity evoked during NMES at either location. The coefficient of variation was also quantified at time(2) to determine the consistency of each dependent measure between three consecutive contractions. Torque, M-waves, and H-reflexes were most variable during NMES over the nerve. In summary, NMES over the nerve produced contractions with the greatest recruitment through central pathways; however, considering some of the limitations of NMES over the femoral nerve, it may be considered a good complement to, as opposed to a replacement for, NMES over the quadriceps muscle for maintaining muscle quality and reducing contraction fatigue during NMES rehabilitation.

The effects of wide pulse neuromuscular electrical stimulation on elbow flexion torque in individuals with chronic hemiparetic stroke.

OBJECTIVE: Neuromuscular electrical stimulation that incorporates wide pulse widths (1ms) and high frequencies (100Hz; wide pulse-NMES (WP-NMES)) augments contractions through an increased reflexive recruitment of motoneurons in individuals without neurological impairments and those with spinal cord injury. The current study was designed to investigate whether WP-NMES also augments contractions after stroke. We hypothesized that WP-NMES would generate larger contractions in the paretic arm compared to the non-paretic arm due to increased reflex excitability for paretic muscles after stroke. METHODS: The biceps brachii muscles were stimulated bilaterally in 10 individuals with chronic hemiparetic stroke. Four stimulation patterns were delivered to explore the effects of pulse width and frequency on contraction amplitude: 20-100-20Hz (4s each phase, 1ms pulse width); 20-100-20Hz (4s each phase, 0.1ms); 20Hz for 12s (1ms); and 100Hz for 12s (1ms). Elbow flexion torque and electromyography were recorded. RESULTS: Stimulation that incorporated 1ms pulses evoked more torque in the paretic arm than the non-paretic arm. When 0.1ms pulses were used there was no difference in torque between arms. For both arms, torque declined significantly during the constant frequency 100Hz stimulation and did not change during the constant frequency 20Hz stimulation. CONCLUSIONS: The larger contractions generated by WP-NMES are likely due to increased reflexive recruitment of motoneurons, resulting from increased reflex excitability on the paretic side. SIGNIFICANCE: NMES that elicits larger contractions may allow for development of more effective stroke rehabilitation paradigms and functional neural prostheses.

Neuromuscular electrical stimulation: implications of the electrically evoked sensory volley.

Neuromuscular electrical stimulation (NMES) generates contractions by depolarising axons beneath the stimulating electrodes. The depolarisation of motor axons produces contractions by signals travelling from the stimulation location to the muscle (peripheral pathway), with no involvement of the central nervous system (CNS). The concomitant depolarisation of sensory axons sends a large volley into the CNS and this can contribute to contractions by signals travelling through the spinal cord (central pathway) which may have advantages when NMES is used to restore movement or reduce muscle atrophy. In addition, the electrically evoked sensory volley increases activity in CNS circuits that control movement and this can also enhance neuromuscular function after CNS damage. The first part of this review provides an overview of how peripheral and central pathways contribute to contractions evoked by NMES and describes how differences in NMES parameters affect the balance between transmission along these two pathways. The second part of this review describes how NMES location (i.e. over the nerve trunk or muscle belly) affects transmission along peripheral and central pathways and describes some implications for motor unit recruitment during NMES. The third part of this review summarises some of the effects that the electrically evoked sensory volley has on CNS circuits, and highlights the need to identify optimal stimulation parameters for eliciting plasticity in the CNS. A goal of this work is to identify the best way to utilize the electrically evoked sensory volley generated during NMES to exploit mechanisms inherent to the neuromuscular system and enhance neuromuscular function for rehabilitation.

Neuromuscular electrical stimulation has a global effect on corticospinal excitability for leg muscles and a focused effect for hand muscles.

The afferent volley generated during neuromuscular electrical stimulation (NMES) can increase the excitability of human corticospinal (CS) pathways to muscles of the leg and hand. Over time, such increases can strengthen CS pathways damaged by injury or disease and result in enduring improvements in function. There is some evidence that NMES affects CS excitability differently for muscles of the leg and hand, although a direct comparison has not been conducted. Thus, the present experiments were designed to compare the strength and specificity of NMES-induced changes in CS excitability for muscles of the leg and hand. Two hypotheses were tested: (1) For muscles innervated by the stimulated nerve (target muscles), CS excitability will increase more for the hand than for the leg. (2) For muscles not innervated by the stimulated nerve (non-target muscles), CS excitability will increase for muscles of the leg but not muscles of the hand. NMES was delivered over the common peroneal (CP) nerve in the leg or the median nerve at the wrist using a 1-ms pulse width in a 20 s on, 20 s off cycle for 40 min. The intensity was set to evoke an M-wave that was ~15% of the maximal M-wave in the target muscle: tibialis anterior (TA) in the leg and abductor pollicis brevis (APB) in the hand. Ten motor-evoked potentials (MEPs) were recorded from the target muscles and from 2 non-target muscles of each limb using transcranial magnetic stimulation delivered over the "hotspot" for each muscle before and after the NMES. MEP amplitude increased significantly for TA (by 45 ± 6%) and for APB (56 ± 8%), but the amplitude of these increases was not different. In non-target muscles, MEPs increased significantly for muscles of the leg (42 ± 4%), but not the hand. Although NMES increased CS excitability for target muscles to the same extent in the leg and hand, the differences in the effect on non-target muscles suggest that NMES has a "global" effect on CS excitability for the leg and a "focused" effect for the hand. These differences may reflect differences in the specificity of afferent projections to the cortex. Global increases in CS excitability for the leg could be advantageous for rehabilitation as NMES applied to one muscle could strengthen CS pathways and enhance function for multiple muscles.

Motor unit recruitment when neuromuscular electrical stimulation is applied over a nerve trunk compared with a muscle belly: triceps surae.

Neuromuscular electrical stimulation (NMES) can be delivered over a nerve trunk or muscle belly and can generate contractions by activating motor (peripheral pathway) and sensory (central pathway) axons. In the present experiments, we compared the peripheral and central contributions to plantar flexion contractions evoked by stimulation over the tibial nerve vs. the triceps surae muscles. Generating contractions through central pathways follows Henneman's size principle, whereby low-threshold motor units are activated first, and this may have advantages for rehabilitation. Statistical analyses were performed on data from trials in which NMES was delivered to evoke 10-30% maximum voluntary torque 2-3 s into the stimulation (Time(1)). Two patterns of stimulation were delivered: 1) 20 Hz for 8 s; and 2) 20-100-20 Hz for 3-2-3 s. Torque and soleus electromyography were quantified at the beginning (Time(1)) and end (Time(2); 6-7 s into the stimulation) of each stimulation train. H reflexes (central pathway) and M waves (peripheral pathway) were quantified. Motor unit activity that was not time-locked to each stimulation pulse as an M wave or H reflex ("asynchronous" activity) was also quantified as a second measure of central recruitment. Torque was not different for stimulation over the nerve or the muscle. In contrast, M waves were approximately five to six times smaller, and H reflexes were approximately two to three times larger during NMES over the nerve vs. the muscle. Asynchronous activity increased by 50% over time, regardless of the stimulation location or pattern, and was largest during NMES over the muscle belly. Compared with NMES over the triceps surae muscles, NMES over the tibial nerve produced contractions with a relatively greater central contribution, and this may help reduce muscle atrophy and fatigue when NMES is used for rehabilitation.

Changes in corticospinal excitability evoked by common peroneal nerve stimulation depend on stimulation frequency.

The afferent volley generated during neuromuscular electrical stimulation (NMES) can increase the excitability of the human corticospinal (CS) pathway. This study was designed to determine the effect of different frequencies of NMES applied over the common peroneal nerve on changes in CS excitability for the tibialis anterior (TA) muscle. We hypothesized that higher frequencies of stimulation would produce larger increases in CS excitability than lower frequencies. NMES was applied at 10, 50, 100, or 200 Hz during separate sessions held at least 48 h apart. The stimulation was delivered in a 20 s on, 20 s off cycle for 40 min using a 1 ms pulse width. The intensity of stimulation was set to evoke an M-wave in response to a single pulse that was 15% of the maximal M-wave. CS excitability was evaluated by the amplitude of motor-evoked potentials (MEPs) in TA evoked by transcranial magnetic stimulation. MEPs were recorded immediately before and after the 40 min of NMES and in each 20 s "off" period. For each subject, MEPs recorded during three successive "off" periods were averaged together (n = 9 MEPs), providing a temporal resolution of 2 min for assessing changes in CS excitability. When delivering NMES at 100 Hz, MEPs became significantly elevated from those evoked before the stimulation at the 24th min, and there was a twofold increase in MEP amplitude after 40 min. NMES delivered at 10, 50, and 200 Hz did not significantly alter MEP amplitude. The amplitude of MEPs evoked in soleus and vastus medialis followed similar patterns as those evoked simultaneously in TA, but these changes were mostly not of statistical significance. There were no changes in the ratio of maximal H-reflex to maximal M-wave in TA or soleus. These experiments demonstrate a frequency-dependent effect of NMES on CS excitability for TA and show that, under the conditions of the present study, 100-Hz stimulation was more effective than 10, 50, and 200 Hz. This effect of NMES on CS excitability was strongest in the stimulated muscle and may be mediated primarily at a supraspinal level. These results contribute to a growing body of knowledge about how the afferent volley generated during NMES influences the CNS and have implications for identifying optimal NMES parameters to augment CS excitability for rehabilitation of dorsiflexion after CNS injury.

Reflex pathways connect receptors in the human lower leg to the erector spinae muscles of the lower back.

Reflex pathways connect all four limbs in humans. Presently, we tested the hypothesis that reflexes also link sensory receptors in the lower leg with muscles of the lower back (erector spinae; ES). Taps were applied to the right Achilles' tendon and electromyographic activity was recorded from the right soleus and bilaterally from ES. Reflexes were compared between sitting and standing and between standing with the eyes open versus closed. Reflexes were evoked bilaterally in ES and consisted of an early latency excitation, a medium latency inhibition, and a longer latency excitation. During sitting but not standing, the early excitation was larger in the ES muscle ipsilateral to the stimulation (iES) than in the contralateral ES (cES). During standing but not sitting, the longer latency excitation in cES was larger than in iES. This response in cES was also larger during standing compared to sitting. Responses were not significantly different between the eyes open and eyes closed conditions. Taps applied to the lateral calcaneus (heel taps) evoked responses in ES that were not significantly different in amplitude or latency than those evoked by tendon taps, despite a 75-94% reduction in the amplitude of the soleus stretch reflex evoked by the heel taps. Electrical stimulation of the sural nerve, a purely cutaneous nerve at the ankle, evoked ES reflexes that were not significantly different in amplitude but had significantly longer latencies than those evoked by the tendon and heel taps. These results support the hypothesis that reflex pathways connect receptors in the lower leg with muscles of the lower back and show that that the amplitude of these reflexes is modulated by task. Responses evoked by stimulation of the sural nerve establish that reflex pathways connect the ES muscles with cutaneous receptors of the foot. In contrast, the large volley in muscle spindle afferents induced by the tendon taps compared to the heel taps did not alter the ES responses, suggesting that the reflex connection between triceps surae muscle spindles and the ES muscles may be relatively weak. These heteronymous reflexes may play a role in stabilizing the trunk for maintaining posture and balance.

Relationship between ventilatory constraint and muscle fatigue during exercise in COPD.

Dynamic hyperinflation and leg muscle fatigue are independently associated with exercise limitation in patients with chronic obstructive pulmonary disease (COPD). The aims of the present study were to examine 1) the relationship between these limitations and 2) the effect of delaying ventilatory limitation on exercise tolerance and leg muscle fatigue. In total, 11 patients with COPD (with a forced expiratory volume in one second of 52% predicted) completed two cycling bouts breathing either room air or heliox, and one bout breathing heliox but stopping at room air isotime. End-expiratory lung volume (EELV), leg muscle fatigue and exercise time were measured. On room air, end-exercise EELV was negatively correlated with leg fatigue. Heliox increased exercise time (from 346 to 530 s) and leg fatigue (by 15%). At isotime, there was no change in leg fatigue, despite a reduction in EELV compared with end-exercise, in both room air and heliox. The change in exercise time with heliox was best correlated with room air leg fatigue and end-inspiratory lung volume. Patients with chronic obstructive pulmonary disease who had greater levels of dynamic hyperinflation on room air had less muscle fatigue. These patients were more likely to increase exercise tolerance with heliox, which resulted in greater leg muscle fatigue.

Turning off the central contribution to contractions evoked by neuromuscular electrical stimulation.

Neuromuscular electrical stimulation can generate contractions through both peripheral and central mechanisms. The peripheral mechanism involves the direct activation of motor axons, while the central mechanism involves the activation of sensory axons that recruit spinal neurons through a reflex pathway. For use in functional electrical stimulation. One must have control over turning the central mechanism on and off. We investigated whether inhibition developed through antagonist muscle (tibialis anterior, TA) contractions elicited by electrical stimulation or by volition can turn off the central mechanism in triceps surae. Both electrical stimulation and voluntary contractions of TA reduced or eliminated plantar flexion torque produced by the central mechanism, indicating that inhibition induced via these contractions can effectively turn off the central contribution to force. These findings suggest that patterns of electrical stimulation may be able to generate periodic muscle contractions by turning the central contribution to muscular contractions on and off.

Turning on the central contribution to contractions evoked by neuromuscular electrical stimulation.

Neuromuscular electrical stimulation can generate contractions through peripheral and central mechanisms. Direct activation of motor axons (peripheral mechanism) recruits motor units in an unnatural order, with fatigable muscle fibers often activated early in contractions. The activation of sensory axons can produce contractions through a central mechanism, providing excitatory synaptic input to spinal neurons that recruit motor units in the natural order. Presently, we quantified the effect of stimulation frequency (10-100 Hz), duration (0.25-2 s of high-frequency bursts, or 20 s of constant-frequency stimulation), and intensity [1-5% maximal voluntary contraction (MVC) torque generated by a brief 100-Hz train] on the torque generated centrally. Electrical stimulation (1-ms pulses) was delivered over the triceps surae in eight subjects, and plantar flexion torque was recorded. Stimulation frequency, duration, and intensity all influenced the magnitude of the central contribution to torque. Central torque did not develop at frequencies < or = 20 Hz, and it was maximal at frequencies > or = 80 Hz. Increasing the duration of high-frequency stimulation increased the central contribution to torque, as central torque developed over 11 s. Central torque was greatest at a relatively low contraction intensity. The largest amount of central torque was produced by a 20-s, 100-Hz train (10.7 +/- 5.5 %MVC) and by repeated 2-s bursts of 80- or 100-Hz stimulation (9.2 +/- 4.8 and 10.2 +/- 8.1% MVC, respectively). Therefore, central torque was maximized by applying high-frequency, long-duration stimulation while avoiding antidromic block by stimulating at a relatively low intensity. If, as hypothesized, the central mechanism primarily activates fatigue-resistant muscle fibers, generating muscle contractions through this pathway may improve rehabilitation applications.

Cutaneous receptors contribute to kinesthesia at the index finger, elbow, and knee.

The neural mechanisms underlying the sense of joint position and movement remain controversial. While cutaneous receptors are known to contribute to kinesthesia for the fingers, the present experiments test the hypothesis that they contribute at other major joints. Illusory movements were evoked at the interphalangeal (IP) joints of the index finger, the elbow, and the knee by stimulation of populations of cutaneous and muscle spindle receptors, both separately and together. Subjects matched perceived movements with voluntary movements of homologous joints on the contralateral side. Cutaneous receptors were activated by stretch of the skin (using 2 intensities of stretch) and vibration activated muscle spindle receptors. Stimuli were designed to activate receptors that discharge during joint flexion. For the index finger, vibration was applied over the extensor tendons on the dorsum of the hand, to evoke illusory metacarpophalangeal (MCP) joint flexion, and skin stretch was delivered around the IP joints. The strong skin stretch evoked the illusion of flexion of the proximal IP joint in 6/8 subjects (12 +/- 5 degrees, mean +/- SE). For the group, strong skin stretch delivered during vibration increased the perceived flexion of the proximal IP joint by eight times with a concomitant decrease in perceived flexion of the MCP joint compared with vibration alone (P < 0.05). For the elbow, vibration was applied over the distal tendon of triceps brachii and skin stretch over the dorsal forearm. When delivered alone, strong skin stretch evoked illusory elbow flexion in 5/10 subjects (9 +/- 4 degrees). Simultaneous strong skin stretch and vibration increased the illusory elbow flexion for the group by 1.5 times compared with vibration (P < 0.05). For the knee, vibration was applied over the patellar tendon and skin stretch over the thigh. Skin stretch alone evoked illusory knee flexion in 3/10 subjects (8 +/- 4 degrees) and when delivered during vibration, perceived knee flexion increased for the group by 1.4 times compared with vibration (P < 0.05). Hence inputs from cutaneous receptors, muscle receptors, and combined inputs from both receptors likely subserve kinesthesia at joints throughout the body.

Forces consistent with plateau-like behaviour of spinal neurons evoked in patients with spinal cord injuries.

Percutaneous electrical stimulation over tibialis anterior and triceps surae was performed in 14 patients with traumatic spinal cord injury (SCI) to look for evidence that 'extra contractions' can develop, beyond those due to activation of the motor axons beneath the stimulating electrodes. Criteria for the extra contractions included marked asymmetry of force with respect to stimulation, progressively rising force during stimulation of constant amplitude and frequency, and force remaining high after stimulation frequency had returned to the control level following a high-frequency burst. Twelve of the 14 patients showed evidence of such behaviour, more frequently in triceps surae than tibialis anterior. Force or electromyographic activity commonly outlasted the stimulation in these patients. There was no apparent correlation between the completeness or level of injury and the ability to induce the behaviour. Evidence of force potentiation and 'habituation' was also seen. Eleven of the 14 patients exhibited hyper-reflexia and reported spontaneous spasms, but there was no obvious association with the extra contractions. It is concluded that non-classical behaviour of neurons within the spinal cord can contribute to the extra contractions evoked by electrical stimulation over muscles in spinal cord-injured subjects. This central contribution is less easy to obtain than in intact healthy subjects, all of whom showed the phenomenon. These contractions are consistent with the activation of plateau potentials in spinal neurons and, if so, plateau potentials may contribute to a patient's clinical manifestations.

The detection of human finger movement is not facilitated by input from receptors in adjacent digits.

These experiments were designed to determine whether cutaneous input from a digit provides a general facilitation of the detection of movements applied to an adjacent digit. The ability to detect passive movements at the proximal interphalangeal joint of the right index finger was measured when cutaneous (and joint) input was removed (using local anaesthesia) from the tip of one or both digits adjacent to the test finger (16 subjects). The same parameter was also measured when input was artificially increased by stimulation of the adjacent digits at three intensities: below, above and at perceptual threshold (PT; 15 subjects). Detection of flexion or extension movements was not altered by anaesthesia of one or both adjacent digits. Since it was possible that too few tonically active afferents in the hand had been blocked to reveal an effect, the median nerve was blocked, with movements applied to the little finger, causing no measurable impairment in acuity (three subjects). Simultaneous electrical stimulation of the tips of the adjacent digits at intensities above PT impaired movement detection, but had no effect when delivered at or below PT. To test whether the effect of detectable electrical stimuli was due to a specific interaction between the artificial input and the input evoked by moving the digit, or due to mental distraction, stimuli were delivered above PT to either the left or right little finger, or the test index finger during movement of the index finger. Electrical stimulation of the index finger significantly reduced detection by approximately 50%, but stimulation of the remote little fingers did not. Electrical stimulation is a non-natural stimulus, so a "natural" stimulus was applied by continuously stroking the tips of the adjacent digits with a brush (10 subjects). The natural stimulus also significantly reduced movement detection by approximately 50%. Together, these findings suggest that tonic inputs from digital nerve afferents adjacent to, or more remote from the passively moved finger do not facilitate movement detection. However, the reduced detection during stimulation of the adjacent digits shows that there is nevertheless some interaction between the various proprioceptive inputs from the digits.

Sustained contractions produced by plateau-like behaviour in human motoneurones.

Electrical stimulation over human muscle can generate force directly by activation of motor axons and indirectly by 'reflex' recruitment of spinal motoneurones. These experiments were designed to define the properties of the centrally generated 'reflex' force, including the optimal stimulus conditions for producing it in tibialis anterior (TA) and triceps surae (TS), and its interaction with volition. Subjects (n = 21) were seated with their foot strapped to an isometric myograph. Surface EMG was recorded from TS and TA. High-frequency electrical stimulation (100 Hz) of TS and TA with wide pulse widths (1 ms) was most effective to evoke the sustained centrally generated forces. The maximal force evoked by this mechanism during stimulation of TA for 40 s was approximately 42 % of that produced by a maximal voluntary contraction. For both muscle groups, ramp increases and decreases in stimulus frequency (from approximately 4 to 100 Hz and back to 4 Hz over 6 s) resulted in marked hysteresis in the force-frequency plot. After a single 'burst' of 100 Hz stimulation during prolonged stimulation at 25 Hz, force remained elevated. Repeated bursts often generated progressively larger force increments. These behaviours were abolished by an anaesthetic nerve block proximal to the stimulation site, confirming the central origin for the 'extra' force. After a brief voluntary contraction was performed during 25 Hz stimulation, force remained elevated, and this showed some gradation with voluntary contraction amplitude. Sometimes voluntary contractions alone initiated the sustained central motor output. Involuntary contractions often persisted for many seconds after electrical stimulation ceased. These were not terminated by brief inhibitory inputs to the active motoneurones but could be stopped by the voluntary command to 'relax completely'. Overall, these centrally generated contractions are consistent with activation of plateau potentials in motoneurones innervating the ankle dorsiflexors and plantarflexors. Large forces can be produced through this mechanism. The interaction with volitional drives suggests that plateau behaviour may contribute significantly to the normal output of human motoneurones.

Human interlimb reflexes evoked by electrical stimulation of cutaneous nerves innervating the hand and foot.

There is some discrepancy over the extent to which reflex pathways from different cutaneous nerves in the hand and foot link the cervical and lumbar spinal cord in neurologically intact humans. The present experiments were designed to determine whether stimulation of a cutaneous nerve in the foot or in the hand evoked reflexes in the non-stimulated limbs (interlimb reflexes). Reflexes were elicited by stimulating (5x1-ms pulses at 300 Hz) the superficial peroneal (SP; innervates the foot dorsum) or superficial radial (SR; innervates the dorsolateral portion of the hand) nerve while subjects (n=10) performed focused contractions of different upper and lower limb muscles. Reflex responses were divided into early (<75 ms), middle (75-120 ms), and late (>120 ms) epochs as determined from averages of 50 sweeps of stimulus-locked electromyographic activity. Significant interlimb reflexes were found at the early latency in 44/106 and 44/103 muscles sampled after SP and SR nerve stimulation, respectively. At the middle latency, significant interlimb reflexes were seen in 89/106 and 87/103 muscles sampled after SP and SR nerve stimulation, respectively. Interlimb reflexes were seen when stimulating at the wrist (i.e. SR nerve) and when stimulating at the ankle (i.e. SP nerve) with an equal probability. The results show that interlimb cutaneous reflexes are widely distributed in humans. The mean latency of the earliest response was quite short and may be mediated by a propriospinal pathway. Functionally, these pathways may provide a substrate for transferring information to coordinate movements between the limb segments.

Large involuntary forces consistent with plateau-like behavior of human motoneurons.

When electrical stimulation is applied over human muscle, the evoked force is generally considered to be of peripheral origin. However, in relaxed humans, stimulation (1 msec pulses, 100 Hz) over the muscles that plantarflex the ankle produced more than five times more force than could be accounted for by peripheral properties. This additional force was superimposed on the direct response to motor axon stimulation, produced up to 40% of the force generated during a maximal voluntary contraction, and was abolished during anesthesia of the tibial nerve proximal to the stimulation site. It therefore must have resulted from the activation of motoneurons within the spinal cord. The additional force could be initiated by stimulation of low-threshold afferents, distorted the classical relationship between force and stimulus frequency, and often outlasted the stimulation. The mean firing rate of 27 soleus motor units recorded during the sustained involuntary activity after the stimulation was 5.8 +/- 0.2 Hz. The additional force increments were not attributable to voluntary intervention because they were present in three sleeping subjects and in two subjects with lesions of the thoracic spinal cord. The phenomenon is consistent with activation of plateau potentials within motoneurons and, if so, the present findings imply that plateau potentials can make a large contribution to forces produced by the human nervous system.

Sensory integration in the perception of movements at the human metacarpophalangeal joint.

These experiments were designed to investigate illusions of movements of the fingers produced by combined feedback from muscle spindle receptors and receptors located in different regions of the skin of the hand. Vibration (100 Hz) applied in cyclic bursts (4 s 'on', 4 s 'off') over the tendons of the finger extensors of the right wrist produced illusions of flexion-extension of the fingers. Cutaneous receptors were activated by local skin stretch and electrical stimulation. Illusory movements at the metacarpophalangeal (MCP) joints were measured from voluntary matching movements made with the left hand. Localised stretch of the dorsal skin over specific MCP joints altered vibration-induced illusions in 8/10 subjects. For the group, this combined stimulation produced movement illusions at MCP joints under, adjacent to, and two joints away from the stretched region of skin that were 176 +/- 33, 122 +/- 9 and 67 +/- 11 % of the size of those from vibration alone, respectively. Innocuous electrical stimulation over the same skin regions, but not at the digit tips, also 'focused' the sensation of movement to the stimulated digit. Stretch of the dorsal skin and compression of the ventral skin around one MCP joint altered the vibration-induced illusions in all subjects. The illusions became more focused, being 295 +/- 57, 116 +/- 18 and 65 +/- 7 % of the corresponding vibration-induced illusions at MCP joints that were under, adjacent to, and two joints away from the stimulated regions of skin, respectively. These results show that feedback from cutaneous and muscle spindle receptors is continuously integrated for the perception of finger movements. The contribution from the skin was not simply a general facilitation of sensations produced by muscle receptors but, when the appropriate regions of skin were stimulated, movement illusions were focused to the joint under the stimulated skin. One role for cutaneous feedback from the hand may be to help identify which finger joint is moving.

Spinal cord microstimulation generates functional limb movements in chronically implanted cats.

Spinal cord injuries disrupt the communication between the brain and peripheral nerves, but leave motoneurons and networks of interneurons below the level of the lesion intact. It is therefore possible to restore some function following injury by providing an artificial stimulus to the surviving neurons below the level of the lesion. We report here on a novel approach for generating functional movements by electrically stimulating the spinal cord through chronically implanted ultrafine, hair-like electrodes. Six to 12 microwires were implanted in the lumbar enlargement of intact cats for 6 months. Twice a week, trains of stimuli were delivered through each microwire and the evoked electromyographic and torque responses were recorded. Strong coordinated hindlimb movements were obtained by stimulating through individual electrodes. The joint torques elicited were capable of supporting the animals' hindquarters. The responses were stable over time and the contractions caused no apparent discomfort to the animals. No obvious motor deficits were seen throughout the 6-month duration of implantation. The results demonstrate that microwires implanted in the spinal cord remain stably in place and stimulation through these electrodes produces strong, controllable movements. This provides a promising basis for the use of spinal cord neuroprostheses in restoring mobility following spinal cord injury.