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Biomedical subjects

Richard B Stein

Publications and source records attributed to Richard B Stein.

16 recordsLinked to original sources

Short-term effects of functional electrical stimulation on spinal excitatory and inhibitory reflexes in ankle extensor and flexor muscles.

The purpose of this study was to investigate short-term effects of walking with functional electrical stimulation (FES) on inhibitory and excitatory spinal reflexes in healthy subjects. The FES was applied to the common peroneal (CP) nerve during the swing phase of the step cycle when the ankle flexors are active. We have previously shown that corticospinal excitability for the tibialis anterior (TA) muscle increased after 30 min of FES-assisted walking. An increase of corticospinal excitability could be due to the changes in spinal and/or cortical excitability. Thus, we wished to examine whether a short-term application of FES would increase spinal motoneuronal excitability. Changes could also result from effects on inhibitory as well as excitatory pathways, but to our knowledge no studies have investigated short-term effects of FES on spinal inhibitory pathways. Therefore, we measured reciprocal and presynaptic inhibition, as well as reflex excitability, before and after FES-assisted walking. As controls, effects of FES-like stimulation at rest and walking without stimulation were tested in separate sessions. The TA H-reflex amplitude did not increase after FES in any of the conditions tested, so we have no evidence that FES increases spinal excitability for the TA. The soleus H-reflex decreased slightly (10%) after FES-assisted walking, and remained decreased for at least 30 min. However, the control experiment indicated that this decrease was associated with walking and not with stimulation. Thirty minutes of FES did not produce any significant effects on spinal inhibitory pathways examined in the present study. In conclusion, the soleus H-reflex showed a small but consistent decrease and no spinal circuits examined showed an increase, as was observed in the corticospinal excitability. Thus, we suggest that a short-term application of FES increases the excitability of the cortex or its connections to the spinal cord more effectively than that of spinal pathways.

Adult↗

Reanimating limbs after injury or disease.

Many diseases and injuries lead to loss of motor function. Can we reanimate paralyzed limbs to produce effective, graceful movements? Recent insights into the function of the motor system and greatly improved computing capabilities have made this a realistic goal, even in the absence of regeneration of motor pathways. Some approaches involve stimulating muscles, nerves or the spinal cord below the level of a lesion. Others involve recording a subject's intention from the cortex, and using this intention to control computers, robots or systems for stimulating the limbs. Here, we critically analyze the possibilities and limitations of various approaches for restoring motor function based on recent human trials and underlying neuroscience research.

Animals↗

Neuronal variability: noise or part of the signal?

Sensory, motor and cortical neurons fire impulses or spikes at a regular, but slowly declining, rate in response to a constant current stimulus. Yet, the intervals between spikes often vary randomly during behaviour. Is this variation an unavoidable effect of generating spikes by sensory or synaptic processes ('neural noise') or is it an important part of the 'signal' that is transmitted to other neurons? Here, we mainly discuss this question in relation to sensory and motor processes, as the signals are best identified in such systems, although we also touch on central processes.

Action Potentials↗

BIONic WalkAide for correcting foot drop.

The goal of this study was to test the feasibility and efficacy of using microstimulators (BIONs) to correct foot drop, the first human application of BIONs in functional electrical stimulation (FES). A prototype BIONic foot drop stimulator was developed by modifying a WalkAide2 stimulator to control BION stimulation of the ankle dorsiflexor muscles. BION stimulation was compared with surface stimulation of the common peroneal nerve provided by a normal WalkAide2 foot drop stimulator. Compared to surface stimulation, we found that BION stimulation of the deep peroneal nerve produces a more balanced ankle flexion movement without everting the foot. A three-dimensional motion analysis was performed to measure the ankle and foot kinematics with and without stimulation. Without stimulation, the toe on the affected leg drags across the ground. The BIONic WalkAide elevates the foot such that the toe clears the ground by 3 cm, which is equivalent to the toe clearance in the unaffected leg. The physiological cost index (PCI) was used to measure effort during walking. The PCI is high without stimulation (2.29 +/- 0.37; mean +/- S.D.) and greatly reduced with surface (1.29 +/- 0.10) and BION stimulation (1.46 +/- 0.24). Also, walking speed is increased from 9.4 +/- 0.4 m/min without stimulation to 19.6 +/- 2.0 m/min with surface and 17.8 +/- 0.7 m/min with BION stimulation. We conclude that functional electrical stimulation with BIONs is a practical alternative to surface stimulation and provides more selective control of muscle activation.

Adult↗

A comparison of models of force production during stimulated isometric ankle dorsiflexion in humans.

In this paper, we compare seven models on their ability to fit isometric muscle force. We stimulated the ankle dorsiflexors of eight subjects at seven ankle angles (85 degrees-120 degrees). Three different stimulation patterns (twitch, triangular, and random) were applied at all ankle angles. Four additional patterns (doublets, steady rates, "catch property," and walking-like) were applied at 95 degrees. Parameter values were optimized for each model at each angle. Parameters for the general linear model were calculated using a novel least-squares algorithm. A linear, second-order critically damped model gave the poorest fits (average root mean square (rms) error: 15 N). The models of Ding et al. (2002) and Bobet and Stein (1998) gave the best fits (average rms errors: 9.2 and 9.4 N). The other models (general linear second-order model, Wiener model, Zhou et al. (1995) model, general linear model) gave intermediate results. Results were similar at all ankle angles. We conclude that the Ding and Bobet-Stein models are the best overall for isometric contractions, that no linear model of any kind will give an error less than 9% of maximum force, and that the models tested are consistent across lengths.

Ankle Joint↗

Short-term effects of functional electrical stimulation on motor-evoked potentials in ankle flexor and extensor muscles.

Stimulating sensory afferents can increase corticospinal excitability. Intensive use of a particular part of the body can also induce reorganization of neural circuits (use-dependent plasticity) in the central nervous system (CNS). What happens in the CNS when the nerve stimulation is applied in concert with the use of particular muscle groups? The purpose of this study was to investigate short-term effects of electrical stimulation of the common peroneal (CP) nerve during walking on motor-evoked potentials (MEPs) in the ankle flexors and extensors in healthy subjects. Since the stimulation was applied during the swing phase of the step cycle when the ankle flexors are active, this is referred to as functional electrical stimulation (FES). The following questions were addressed: (1) can FES during walking increase corticospinal excitability more effectively than passively received repetitive nerve stimulation and (2) does walking itself improve the descending connection. FES was delivered using a foot drop stimulator that activates ankle dorsiflexors during the swing phase of the step cycle. MEPs in the tibialis anterior (TA) and soleus muscles were measured before, between, and after periods of walking with or without FES, using transcranial magnetic stimulation. After 30 min of walking with FES, the half-maximum peak-to-peak MEP (MEP(h)) in the TA increased in amplitude and this facilitatory effect lasted for at least 30 min. In contrast, walking had no effects on the TA MEP(h) without FES. The increase in the TA MEP(h) with FES (approximately 40%) was similar to that with repetitive CP nerve stimulation at rest. The soleus MEP(h) was also increased after walking with FES, but not without FES, which differs from the previous observation with CP nerve stimulation at rest. With FES, the TA silent period at MEP(h) was unchanged or slightly decreased, while it increased after walking without FES. Increased cortical excitability accompanied by unchanged cortical inhibition (no changes in the silent period with FES) suggests that FES did not simply increase general excitability of the cortex, but had specific effects on particular cortical neurons.

Adult↗

Editing trains of action potentials from multi-electrode arrays.

When recording from multi-electrode arrays, only a short period around the time of a threshold crossing is generally saved for later analysis. Then, waveforms are often sorted automatically to identify templates of spikes from individual neurons near an electrode. As spikes sum from different neurons and noise is present, some spikes may be missed and others erroneously accepted. This paper describes methods for identifying and correcting errors in recorded spike trains to recover the pattern of spikes from each neuron as faithfully as possible. These methods are complementary to, but distinct from methods to reconstruct waveforms that arise from summation of individual templates that overlap one another. Our methods are based on the local statistics of the firing rates or inter-spike intervals and the methods work best for neurons that fire regularly (small standard deviation relative to the mean interval). First, we test whether accepting more spikes, whose waveforms are close to the templates that have been identified, will increase the regularity or smoothness of the firing rates. Then, after accepting spikes that increase regularity, we test whether individual intervals are sufficiently longer (or shorter) than their neighbors to identify spikes that have been omitted (or accepted) erroneously. The methods are tested on simulated spike trains, where spikes have been inserted or deleted at random, and on spike trains recorded from multi-electrode arrays in dorsal root ganglia of cats walking on a treadmill.

Action Potentials↗

Long-term stimulation and recording with a penetrating microelectrode array in cat sciatic nerve.

We studied the consequences of long-term implantation of a penetrating microelectrode array in peripheral nerve over the time course of 4-6 mo. Electrode arrays without lead wires were implanted to test the ability of different containment systems to protect the array and nerve during contractions of surrounding muscles. Treadmill walking was monitored and the animals showed no functional deficits as a result of implantation. In a different set of experiments, electrodes with lead wires were implanted for up to 7 mo and the animals were tested at 2-4 week intervals at which time stimulation thresholds and recorded sensory activity were monitored for every electrode. It was shown that surgical technique highly affected the long-term stimulation results. Results between measurement sessions were compared, and in the best case, the stimulation properties stabilized in 80% of the electrodes over the course of the experiment (162 days). The recorded sensory signals, however, were not stable over time. A histological analysis performed on all implanted tissues indicated that the morphology and fiber density of the nerve around the electrodes were normal.

Action Potentials↗

Movements elicited by electrical stimulation of muscles, nerves, intermediate spinal cord, and spinal roots in anesthetized and decerebrate cats.

Electrical stimulation offers the possibility of restoring motor function of paralyzed limbs after spinal-cord injury or stroke, but few data are available to compare possible sites of stimulation, such as muscle, nerve, spinal roots, or spinal cord. The aim of this study was to establish some characteristics of stimulation at these sites in the anesthetized and midcollicular decerebrate cat. The hind limb was constrained to move in the sagittal plane against a spring load. Ventral-root stimulation only produced movements down and back; the direction moved systematically backward the more caudal the stimulated roots. In contrast, dorsal-root stimulation only produced movements up and forward. Thus, neither method alone could produce the full range of normal movements. Muscle, nerve, and intraspinal stimulation within the intermediate regions of the gray matter generated discrete, selective movements in a wide range of directions. Muscle stimulation required an order of magnitude more current. Single microwire electrodes located in the spinal gray matter could activate a synergistic group of muscles, and generally had graded recruitment curves, but the direction of movement occasionally changed abruptly as stimulus strength increased. Nerve stimulation produced the largest movements against the spring load (>80% of the passive range of motion) and was the most reproducible from animal to animal. However, recruitment curves with nerve stimulation were quite steep, so fine control of movement might be difficult. The muscle, nerve, and spinal cord all seem to be feasible sites to restore motor function. The pros and cons from this study may be helpful in deciding the best site for a particular application, but further tests are needed in the chronically transected spinal cord to assess the applicability of these results to human patients.

Anesthesia↗

Spinal excitation and inhibition decrease as humans age.

Although changes in the soleus H-reflex (an electrical analog of the tendon jerk) with age have been examined in a number of studies, some controversy remains. Also, the effect of age on inhibitory reflexes has received little attention. The purpose of this paper was to examine some excitatory and inhibitory reflexes systematically in healthy human subjects having a wide range of ages. We confirmed that both the maximum H-reflex (Hmax) and the maximum M-wave (Mmax) (from direct stimulation of motor axons) decrease gradually with age. The decrease in Hmax was larger so the Hmax/Mmax ratio decreased dramatically with age. Interestingly, the modulation of the H-reflex during walking was essentially the same at all ages, suggesting that the pathways that modulate the H-reflex amplitude during walking are relatively well preserved during the aging process. We showed for the first time that the short-latency, reciprocal inhibitory pathways from the common peroneal nerve to soleus muscle and from the tibial nerve to the tibialis anterior muscle also decreased with age, when measured as a depression of ongoing voluntary activity. These results suggest that there may be a general decrease in excitability of spinal pathways with age. Thus, the use of age-matched controls is particularly important in assessing abnormalities resulting from disorders that occur primarily in the elderly.

Adult↗

Spinal reciprocal inhibition in human locomotion.

The purpose of this paper was to study spinal inhibition during several different motor tasks in healthy human subjects. The short-latency, reciprocal inhibitory pathways from the common peroneal (CP) nerve to the soleus muscle and from the tibial nerve to the tibialis anterior muscle were studied as a depression of ongoing voluntary electromyograph (EMG) activity. First, the effect of stimulus intensity on the amount of inhibition was examined to decide an appropriate stimulation to study the task-dependent modulation of inhibition. Then, the inhibition at one level of stimulation (1.5 x motor threshold) was investigated during standing, walking, and running. The change in slope of inhibition vs. EMG level, which approximates the fraction of ongoing activity that is inhibited, decreased with CP stimulation from 0.52 during standing to 0.30 during fast walking (6 km/h) to 0.17 during running at 9 km/h. Similarly, the slope decreased with tibial nerve stimulation from 0.68 (standing) to 0.42 (fast walking) to 0.35 (running at 9 km/h). All differences, except the last one, were highly significant (P < 0.01, Student's t-test). However, the difference between walking (0.42) and running (0.36) at the same speed (6 km/h) was not significant with tibial nerve stimulation and only significant at P < 0.05 with CP nerve stimulation (0.30, 0.20). Also, the difference between standing (0.52) and slow walking (3 km/h; 0.41) with CP stimulation was not significant, but it was significant (P < 0.01) with tibial nerve stimulation (0.68, 0.49). In conclusion, our findings indicate that spinal reciprocal inhibition decreases substantially with increasing speed and only changes to a lesser extent with task.

Adult↗

Capabilities of a penetrating microelectrode array for recording single units in dorsal root ganglia of the cat.

The recording capability of a microelectrode array in the cat dorsal root ganglion (DRG) was studied in 11 acute experiments, 373 single, discriminable sensory units were recorded on 587 electrodes (0.64 units/electrode). Sensory action potentials as large as 1750 microV were obtained (mean=132 microV). These were comparable to literature reports of the best DRG extracellular recordings made with conventional electrodes. We were able simultaneously to activate and record over 50 discriminable, time-varying units from L6 and L7 DRGs during a cyclic ankle displacement. We also successfully recorded stable, phase dependent multiple sensory units with very little artifact or electromyographic (EMG) contamination during decerebrate walking. Thus, the array is capable of recording more effectively from more DRGs neurons than has been achieved by conventional recording techniques. The recording selectivity and stability of the array, coupled with the large number of neurons that can be recorded simultaneously, provide attractive features for better understanding sensorimotor control principles.

Action Potentials↗

Electrical stimulation of the human common peroneal nerve elicits lasting facilitation of cortical motor-evoked potentials.

Motor-evoked potentials (MEP) in the tibialis anterior (TA) muscle were shown to be facilitated by repetitive electrical stimulation of the common peroneal (CP) nerve at intensities above motor threshold. The TA electromyogram (EMG) and ankle flexion force were recorded in response to transcranial magnetic stimulation (TMS) of the leg area of the motor cortex to evaluate the excitability of cortico-spinal-muscular pathways. Repetitive stimulation of the CP nerve at 25 Hz for 30 min increased the MEP by 50.3 +/- 13.6% (mean +/- S.E.) at a TMS intensity that initially gave a half-maximum MEP (MEPh). In contrast the maximum MEP (MEPmax) did not change. Ankle flexion force (103 +/- 21.9%) and silent period duration (75.3 +/- 12.9%) also increased. These results suggest an increase in corticospinal excitability, rather than total connectivity due to repetitive CP stimulation. Facilitation was evident after as little as 10 min of stimulation and persisted without significant decrement for at least 30 min after stimulation. The long duration of silent period following CP stimulation (99.2 +/- 14.8 ms) suggests that this form of stimulation may have effects on the motor cortex. To exclude the possibility that MEPh facilitation was primarily due to sensory fibre activation, we performed several control experiments. Preferentially activating Ia muscle afferents by vibration in the absence of motor activity had no significant effect. Cutaneous afferent activation via stimulation of the superficial peroneal nerve increased the amplitude of responses at MEPmax rather than MEPh. Concurrent tendon vibration and superficial peroneal nerve stimulation failed to facilitate TA MEP responses. In summary, repetitive electrical stimulation of the CP nerve elicits lasting changes in corticospinal excitability, possibly as a result of co-activating motor and sensory fibres.

Adult↗

Stretch reflex gain in cat triceps surae muscles with compliant loads.

The triceps surae (TS) stretch reflex was measured in decerebrate cats during crossed extensor stimulation (tonic contractions) and after spinalization during rhythmic locomotor activity. The TS reflex force in response to a short pulse stretch measured during tonic contractions at low level of background activity was greater than when more background activity was present at the time of application of stretch. In contrast, the reflex force measured during rhythmic contractions was very small at low level of background force (flexion phase) and increased at moderate and high levels of background activity (extension phase). Thus, even in reduced preparations, a task modulation of the stretch reflex occurs. Throughout the experimental procedure, the torque motor used to stretch the muscles behaved like a spring of a preset compliance (from isometric to very compliant). A reflex model was used to simulate the responses obtained experimentally. The gain of the stretch reflex loop was estimated for each load condition and both behavioural tasks. The reflex loop gain was significantly larger as the compliance of the external load increased for both tonic and rhythmic contractions, although to a lesser extent in the phasically activated muscles. During rhythmic locomotor contractions the gain was less than 1, assuring stability of the system. In contrast, during tonic contractions against a compliant load the gain exceeded 1, consistent with the instability (oscillations, clonus) seen at times under these load conditions. However, the high gain and instability was only transient, since repeated stretch reduced the gain. Thus, non-linearities in the system assured vigorous responses at the onset of perturbations, but then weaker responses to ongoing perturbations to reduce the chance of feedback instability (clonus).

Animals↗

Electrical stimulation for therapy and mobility after spinal cord injury.

This article reviews the use of therapeutic and functional electrical stimulation in subjects after a spinal cord injury (SCI). Muscles become much weaker and more fatigable, while bone density decreases dramatically after SCI. Therapeutic stimulation of paralyzed muscles for about 1 h/day can reverse the atrophic changes and markedly increase muscle strength and endurance as well as bone density. Functional electrical stimulation can also improve the speed and efficiency of walking in people with an incomplete SCI. Finally, a modified wheelchair is described in which electrical stimulation or residual voluntary activation of leg muscles can produce movements of a footrest that is coupled to the wheels. The wheelchair can provide greater mobility and fitness to persons who are not functional walkers and currently use their arms to propel a wheelchair.

Electric Stimulation Therapy↗

The resilience of the size principle in the organization of motor unit properties in normal and reinnervated adult skeletal muscles.

Henneman's size principle relates the input and output properties of motoneurons and their muscle fibers to size and is the basis for size-ordered activation or recruitment of motor units during movement. After nerve injury and surgical repair, the relationship between motoneuron size and the number and size of the muscle fibers that the motoneuron reinnervates is initially lost but returns with time, irrespective of whether the muscles are self- or cross-reinnervated by the regenerated axons. Although the return of the size relationships was initially attributed to the recovery of the cross-sectional area of the reinnervated muscle fibers and their force per fiber, direct enumeration of the innervation ratio and the number of muscle fibers per motoneuron demonstrated that a size-dependent branching of axons accounts for the size relationships in normal muscle, as suggested by Henneman and his colleagues. This same size-dependent branching accounts for the rematching of motoneuron size and muscle unit size in reinnervated muscles. Experiments were carried out to determine whether the daily amount of neuromuscular activation of motor units accounts for the size-dependent organization and reorganization of motor unit properties. The normal size-dependent matching of motoneurons and their muscle units with respect to the numbers of muscle fibers per motoneuron was unaltered by synchronous activation of all of the motor units with the same daily activity. Hence, the restored size relationships and rematching of motoneuron and muscle unit properties after nerve injuries and muscle reinnervation sustain the normal gradation of muscle force during movement by size-ordered recruitment of motor units and the process of rate coding of action potentials. Dynamic modulation of size of muscle fibers and their contractile speed and endurance by neuromuscular activity allows for neuromuscular adaptation in the context of the sustained organization of the neuromuscular system according to the size principle.

Animals↗