Identification of nonlinear model of ankle joint dynamics during electrical stimulation of soleus

The mechanical impedance of the ankle joint was estimated in two conditions: during submaximal surface electrical stimulation of the soleus muscle, and with no stimulation applied. Both neurologically intact (n=5) and spinal cord injured subjects (n=4) were used. The mechanical impedance was measured by applying angular step and constant velocity (13–100° s⁻¹) perturbations at 10° to the ankle and measuring the resulting changes in torque. A five-element lumped model consisting of an inertial element, a parallel elastic element, and an elastic element in series with a viscous element and a pure tension generator produced a good fit for predicting the compliance characteristics of the ankle for both the relaxed and stimulated conditions. The elastic elements were piecewise linear with different values for the dorsiflexion and plantarflexion directions. The viscous element was velocity-dependent and it decreased in value as the velocity increased. The average torque error between the measured and model's response during soleus stimulation was 10·56% for the dorsiflexed and 11·93% for the plantarflexed perturbations. However, the average error was skewed by several subjects who had excessive error, due to volitional intervention or flexor withdrawal reflex. The average model error for the perturbations without stimulation was 7·12% for dorsiflexed and 5·58% for plantarflexed perturbations.     

Age related skeletal muscle response to electrical stimulation

We hypothesized that the conditioned muscles of elderly and growing organisms have different responses to electrical stimulation from that of young adult organisms. Five day old lambs, 1 year old sheep, and 8 year old elderly sheep were used for this investigation. The latissimus dorsi muscle (LDM) was partially mobilized and left in situ. Two electrodes were implanted and electrical stimulation (ES) was begun for 8 weeks; it was then stopped for 2 weeks. Biopsies were taken before ES, after 8 weeks of ES, and after the 2 week delay period. The LDM of old sheep has less fatigue resistance than the LDM of younger animals. Conditioned LDM of the lamb continued to be fatigue resistant after a 2 week delay compared with adult sheep. In all animals, lactate dehydrogenase (LDH) fraction five decreased and LDH-1 + 2 fractions increased after ES. After a 2 week delay, the data returned to baseline values only in adult animals. The percentage area occupied by mitochondria in old sheep was less after ES than in younger animals. In all animals, the mitochondrial area increased after ES and reverted to baseline values after the delay. The number of nuclei and fibers considerably increased after ES. Only in the lamb did the number of nuclei and fibers continue to be elevated after the delay. There are more changes in young skeletal muscle than in adult (1 year or 8 year old) muscle during ES, and they "remember" these properties. Elderly skeletal muscle does not convert to a fatigue resistant state as completely as adult skeletal muscle during a conventional 8 week ES protocol. It is necessary to change and prolong the ES protocol for elderly patients.     

Characterization and control of muscle response to electrical stimulation

The maintenance of upright posture in neurologically intact human subjects is mediated by two major nervous pathways. The first, leading from the cerebral cortex through the spinal cord to motor neurons, activates muscles which produce postural movements. The second, leading from various sensory organs to higher centers, provides sensory feedback regarding the postural state. The path through the spinal cord is no longer intact in victims of spinal cord injury and loss of normal control of muscle activity results. Functional neuromuscular stimulation (FNS) has been shown as a feasible method for obtaining muscle contraction in paraplegic and has been proposed as a means for control of antero-posterior sway to make upright posture possible for these individuals. Before muscle can be controlled through the use of FNS, the response of muscle to electrical stimulation must be understood. In past studies, linear control theory has been applied to the analysis of this response and to the testing of various controllers. The aim of this study was to demonstrate some control issues in FNS using linear control theory, as it applies to electrical stimulation of muscle for stabilization of posture. The linearity of the muscle response was improved through closed-loop control using pole compensation techniques. The excess phase shift of the system due to the time delay in the muscle response, however, limits the ability to increase the open-loop gain in order to obtain improved performance. A suggestion for further study is the application of this methodology for uses in posture control.     

Modelling the response of scalp sensory receptors to transcranial electrical stimulation

Transcranial electrical stimulation of the brain cause considerable discomfort to the patient. The purpose of the study was to find out whether this could be affected by the choice of stimulation parameters. A spherical volume conductor model of the head and active compartmental models of a pyramidal motor nerve and scalp nociceptor were used in combination to simulate the scalp nociception to transcranial electrical stimulation. Scalp nociceptors were excited at distances of several centimetres from the electrodes. The size of the excited scalp area correlated with the length of the stimulation pulse. The area was 12.3, 20.4 and 26.0 cm², for a 10μs, 100μs and 1 ms constant current pulse, respectively. With a 100 μs constant current pulse, the threshold for motor excitation was 205 mA and, for nociception, it was 51 mA. There was no significant difference between constant current and capacitor discharge pulses or between electrodes of different sizes. The results imply that the use of very short stimulation pulses can reduce the pain. If a topical anaesthesia is used to reduce the pain, it has to be applied on a large area around the electrodes.     

Motor response thresholds to electrical stimulation at the wrist in human newborns

Two studies of motor response thresholds (RTs) to electricalstimulation at the wrist in newborns were done. Adult controls were employed. Strength-duration curves for infant and adult RTs and adult sensory thresholds (STs) were plotted. RTs of infants are approximately 1.75 times higher than those for adults. Adult RTs are consistently 3 to 4 times higher than STs. Test-retest reliabilities were satisfactory. RTs of half of the newborns were notably variable. No relationship between RT variability and stages of the neonatal wakefulness-sleep cycle could be established, but RTs were significantly, although not markedly, higher during rapid-eye-movement (REM) episodes than during nREM. For evoked potential studies with newborns it has been decided to use as a stimulus a constant-current square-wave electrical pulse of 0.5 msec duration at RT during nREM sleep.     

Delayed drinking in response to electrical and thermal stimulation of the medial forebrain

Water intake in response to electrical and thermal stimulation of the medial forebrain was studied in the goat. When the frontal wall of the third cerebral ventricle was included in a field of bipolar electrical stimulation a dipsogenic response was obtained after discontinuation of the stimulation. Release of antidiuretic hormone (ADH) was apparently also elicited. The water intake was roughly proportional to the amount of current which had been applied during the stimulation period. Water consumption in response to stimulation attenuated the dipsogenic effect of subsequent stimulation, as did also pre-stimulatory hydration by stomach tube. A 2 C elevation of he temperature of parts of the preoptic/anterior hypothalamic region for 40 min periods induced cumulative drinking starting after 2.5 to 18 min. There were great interindividual differences in the amount of water consumed in response to the thermal stimulation, possibly due to variations in thermo-couple electrode placement. The dipsogenic effect of forebrain warming was inhibited by pre-hydration, and by lowering of the environmental temperature. The delayed thirst responses are discussed in relation to stimulus-bound drinking previously observed in the same and other species. It appears possible that the delayed drinking was a manifestation of artificially induced excitation of juxtaventricular “thirst” receptors.     

Non-linearity of skin resistance response to intraneural electrical stimulation of sudomotor nerves

Intraneural electrical stimuli (0.3 mA, 0.2 ms) were delivered via a tungsten micro-electrode inserted into a cutaneous fascicle in the median nerve at the wrist in 16 normal subjects, and the effects on the sweat glands within the innervation zone were recorded as changes of skin resistance. In order to examine the relationship between the skin resistance level and the amplitude of transient resistance responses, trains of high frequency stimulation were used to reduce the skin resistance level and then transient resistance responses were evoked by single stimuli at 0.1 Hz. Regional anaesthesia of the brachial plexus in the axilla eliminated spontaneous sympathetic activity and reflex effects. At high skin resistance levels response amplitudes to single stimuli were low but they increased successively to a maximum at intermediate levels and then decreased again at low resistance levels. Repeated stimulation sequences evoked qualitatively similar response curves but quantitatively both response amplitudes and skin resistance levels were slightly reduced upon repetition. We suggest that the changes of response amplitudes are due to variable resistivity of the corneal layer. The shifts of the response curves with repetition of stimulation may result from increased hydration of the corneum. It is concluded that the variability of response amplitudes to constant stimuli makes the amplitude of a skin resistance response unsuitable as an indicator of the strength of sympathetic sudomotor nerve traffic.     

The response of vestibulo-ocular reflex pathways to electrical stimulation after canal plugging

The vestibulo-ocular reflex (VOR) allows clear vision during head movements by generating compensatory eye movements. Its response to horizontal rotation is reduced after one horizontal semicircular canal is plugged, but recovers partially over time. The majority of VOR interneurons contribute to the shortest VOR pathway, the so-called three-neuron arc, which includes only two synapses in the brainstem. After a semicircular canal is plugged, transmission of signals by the three-neuron arc originating from the undamaged side may be altered during recovery. We measured the oculomotor response to single current pulses delivered to the vestibular labyrinth of alert cats between 9 h and 1 month after plugging the contralateral horizontal canal. The same response was also measured after motor learning induced by continuously-worn telescopes (optically induced motor learning). Optically induced learning did not change the peak velocity of the evoked eye movement (PEEV) significantly but, after a canal plug, the PEEV increased significantly, reaching a maximum during the first few post-plug days and then decreasing. VOR gain also showed transient changes during recovery. Because the PEEV occurred early in the eye movement evoked by a current pulse, we think the observed increase in PEEV represented changes in transmission by the three-neuron arc. Sham surgery did not result in significant changes in the response to electrical stimulation or in VOR gain. Our data suggest that different pathways and processes may underlie optically induced motor learning and recovery from plugging of the semicircular canals. Electronic Publication     

Depolarization of cortical glial cells in response to electrical stimulation of the cortical surface

The responses of 155 neurones and 91 glial cells to the electrical stimulation of the cortex were recorded in the suprasylvian gyrus of 20 cats under pentobarbital anaesthesia. Glial cells were identified by electrophysiological criteria: absence of action potentials and postsynaptic potentials; high membrane potential; slow depolarization during the electrical stimulation of the cortex. 50 glial cells showed membrane potentials between 80 and 100 mV. Stimuli of low intensity which evoked only excitatory postsynaptic potentials of apical dendrites, the so-called dendritic potentials, failed to evoke glial depolarization. However, glial depolarization could be elicited at high-frequency stimulation. Stimuli, which evoked not only the dendritic potential but also subsequent slow negativity, could usually bring about glial depolarization too. The amplitude of glial depolarization in response to one stimulus did not exceed 2 mV, the latency being 3–5 ms. A phenomenon of decrementai summation of glial depolarization was observed. The stronger and more frequent the stimulation, the larger was glial depolarization. However, at frequencies over 50/s glial depolarization decay was observed already during the stimulation and in some cases, membrane potential was drastically reduced to zero. After cessation of stimulation, glial depolarization decayed exponentially in 3–4 s; in some cases the decay was prolonged up to 10s and slow irregular fluctuations of the membrane potential were recorded; at the same time, spikes of the neighbouring neurone could be recorded from the glial cell. With a decrease of the membrane potential glial depolarization was attenuated, but it could be elicited even at membrane potential below 20 mV.The results are interpreted in relation to the potassium ion hypothesis. It is suggested that glial depolarization is determined by release of K⁺, which is associated with excitation of non-myelinated fibres and with excitatory postsynaptic potentials generated in the cortical neuropile. Significant increases in the concentration of extracellular potassium ions could provoke actual movement of glial cells. It is supposed that glial depolarization of small magnitude which is recorded occasionally at the membrane potential below 30 mV is the result of electronic spread of glial depolarization from the neighbouring glial cells.     

Suprarhinal cortex response to electrical stimulation of the lateral amygdala nucleus in the rat

Summary Electrical stimulation of the lateral amygdala nucleus was found to evoke field potentials and influence unitary activity in the suprarhinal cortex of anesthetized rats. Laminar distributions of the field responses consisted of positive waves in superficial layers, that reversed to electronegatives from a depth of 0.4–0.5 mm. This response was followed by a shallow electropositive wave deeper than 0.7–0.8 mm. Extracellularly recorded units were studied in the posterior agranular insular area of the suprarhinal cortex. The data revealed that stimulation of the lateral amygdala produced a train of small amplitude spikes in association with a negative slow potential. Furthermore, such stimulation invariably elicited an inhibition of the spontaneous firing of large amplitude spikes, in association with a positive slow potential. The onset of this inhibitory response always occurred at longer latency than the excitatory one. The small amplitude spikes may well represent the firing of inhibitory interneurons after lateral amygdala stimulation. The study suggests that a feedforward system of inhibition appears to be present in the connection between lateral amygdala and posterior agranular insular area of the suprarhinal cortex.     

Neuronal response to local electrical stimulation in rat thalamus: physiological implications for mechanisms of deep brain stimulation

High-frequency deep brain stimulation (DBS) of sensorimotor thalamus containing "tremor cells" leads to tremor arrest in humans with parkinsonian and essential tremor. To examine the possible underlying mechanism(s), we recorded in vitro intracellular responses of rat thalamic neurons to local intrathalamic stimulation. Such simulated DBS (sDBS) induced a sustained membrane depolarization accompanied by an increase in apparent membrane conductance in both motor and sensory neurons. With stimulation frequency above approximately 100 Hz, the sDBS-induced depolarization most typically led to repetitive neuronal firing or less frequently resulted in a complete blockade of action potential genesis. When regular intracellular current pulses were injected into cells to mimic "tremor" activity, such rhythmic discharges were invariably disrupted or abolished by the random spike firing induced during high-frequency sDBS. Low-frequency sDBS left rhythmicity unaffected.We conclude that clinical thalamic DBS may lead to a neuronal de-rhythmicity and tremor stoppage through masking and/or blocking rhythmic firing of tremor cells.     

Glycogen depletion of human skeletal muscle fibers in response to high-frequency electrical stimulation.

The purpose of the present study was to evaluate the pattern of change in muscular glycogen content in response to high-frequency electrical stimulation (HFES). Muscle biopsies were taken from the vastus lateralis muscle of 7 healthy young men before, 15 min after, and 30 min after electrical stimulation delivered at a 50-Hz frequency (15 s on, 45 s off) at an intensity of 100 mA. The glycogen content of type I, IIA, and IIB muscle fibres was evaluated using microphotometry of periodic acid Schiff (PAS) stained fibres. After 15 min of electrical stimulation, the glycogen content in type I, IIA, and IIB muscle fibres significantly decreased from 113 +/- 10 (mean +/- SE) to 103 +/- 10 (p < or = 0.05), 129 +/- 9 to 102 +/- 12 (p < or = 0.01), and 118 +/- 8 to 90 +/- 13 (p < or = 0.01) arbitrary relative units, respectively. No further decrement in glycogen content was observed in all three fibre types following an additional 15 min of HFES. In addition, isometric force decreased by approximately 50%, from 125.9 +/- 20.0 N to 64.2 +/- 7.7 N (p < or = 0.01), during the first 15 contractions. No further decrease in isometric force was observed following an additional 15 contractions of HFES. These results reveal that significant reductions in isometric force of knee extensor muscles and glycogen content of all human skeletal muscle fibre types in vastus lateralis muscle are observable after 15 min of neuromuscular high-frequency transcutaneous electrical stimulation.     

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 (~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.     

Non-linearity of skin resistance response to intraneural electrical stimulation of sudomotor nerves.

Intraneural electrical stimuli (0.3 mA, 0.2 ms) were delivered via a tungsten microelectrode inserted into a cutaneous fascicle in the median nerve at the wrist in 16 normal subjects, and the effects on the sweat glands within the innervation zone were recorded as changes of skin resistance. In order to examine the relationship between the skin resistance level and the amplitude of transient resistance responses, trains of high frequency stimulation were used to reduce the skin resistance level and then transient resistance responses were evoked by single stimuli at 0.1 Hz. Regional anaesthesia of the brachial plexus in the axilla eliminated spontaneous sympathetic activity and reflex effects. At high skin resistance levels response amplitudes to single stimuli were low but they increased successively to a maximum at intermediate levels and then decreased again at low resistance levels. Repeated stimulation sequences evoked qualitatively similar response curves but quantitatively both response amplitudes and skin resistance levels were slightly reduced upon repetition. We suggest that the changes of response amplitudes are due to variable resistivity of the corneal layer. The shifts of the response curves with repetition of stimulation may result from increased hydration of the corneum. It is concluded that the variability of response amplitudes to constant stimuli makes the amplitude of a skin resistance response unsuitable as an indicator of the strength of sympathetic sudomotor nerve traffic.     

Mechanical activity of frog esophagus muscle in response to electrical stimulation of intramural nerves.

Microscopic observation of intramural nerves in the frog esophagus, fixed and stained with OsO(4) and ZnI(2), revealed that nerve cell bodies and bundles connecting the nerve cell bodies formed loose and irregular networks. The nerve cell bodies were mostly lying singly in the nerve bundles, with occasional observations of two closely linked nerve cell bodies. Isolated circular and longitudinal segments of esophageal muscle were spontaneously rhythmically contractile, with a frequency of 2.2-3.0 per min. This was not altered by tetrodotoxin (TTX). In longitudinal muscle segments, transmurally applied electrical stimulation produced contractile responses which were not inhibited by atropine or guanethidine, but were reduced in amplitude by TTX, suggesting a nonadrenergic-noncholinergic (NANC) excitatory innervation in the esophagus muscle. In circular muscle segments, transmural application of brief electrical stimulation evoked two types of mechanical response: a biphasic response consisting of an initial relaxation and a following contraction (type I) and a contraction alone (type II). These mechanical responses were not modulated by either atropine or guanethidine. In the type I response, TTX abolished the relaxation component, suggesting that this was produced by non-adrenergic non-cholinergic (NANC) inhibitory nerve excitation. In about half of the type II responses, the amplitude of the contraction was significantly reduced by TTX, suggesting that a part of the contraction was produced by activation of NANC excitatory nerves. Thus, the esophageal smooth muscle of the frog demonstrates myogenic activity, and is innervated by both excitatory and inhibitory NANC nerves.     

Adaptation of energy metabolism of canine latissimus dorsi muscle in response to chronic electrical stimulation

Transformation of the latissimus dorsi (LD) muscle from a fast-twitch, fatigue-prone to a fatigue-resistant (heart-like) muscle, necessary to allow its application in cardiac assist devices, can be induced by chronic electrical stimulation. In adult dogs we studied the nature and time course of myofibrillar and metabolic adaptations in the LD muscle when exposed in situ to 24 weeks of continuous electrical stimulation. In addition, the metabolic properties of the stimulated muscle were compared with those of canine cardiac muscle. The proportion of immunohistochemically identified type I fibres increased on stimulation from 28% to 80%, while that of type II fibres decreased from 69% to 16%. Fibres of intermediate type (IIC and IC) appeared transiently; the highest levels were found between 4 and 8 weeks of stimulation. The activities of fructose-6-phosphate kinase and lactate dehydrogenase (LDH), which before stimulation were similar to those in heart, decreased to 18% and 34% of their initial values respectively. However, the LDH isozyme pattern changed towards that typical for cardiac muscle. These changes indicate a markedly decreased flux capacity through the glycolytic pathway which, however, is directed more towards the oxidative conversion of substrates. The mitochondrial capacity (maximal palmitate oxidation and pyruvate dehydrogenase complex activities) of the muscle did not change and remained at a level less than half of that of cardiac ventricular muscle. Contents of adenine nucleotides and endogenous substrates were maintained during stimulation. No further changes in the observed adaptations occurred after week 12 of stimulation. In conclusion, electrical stimulation of canine LD muscle induces a conversion to predominantly slow-twitch fibres, but the metabolic system of the stimulated muscle remains still markedly different from that of the heart.A preliminary report of this study was presented at the 3rd International Symposium on Transformed Skeletal Muscle for Cardiac Assist and Repair, Banff, Canada, October 1988 (see [11, 14])     

Schwann cell response on polypyrrole substrates upon electrical stimulation

Current injury models suggest that Schwann cell (SC) migration and guidance are necessary for successful regeneration and synaptic reconnection after peripheral nerve injury. The ability of conducting polymers such as polypyrrole (PPy) to exhibit chemical, contact and electrical stimuli for cells has led to much interest in their use for neural conduits. Despite this interest, there has been very little research on the effect that electrical stimulation (ES) using PPy has on SC behavior. Here we investigate the mechanism by which SCs interact with PPy in the presence of an electric field. Additionally, we explored the effect that the adsorption of different serum proteins on PPy upon the application of an electric field has on SC migration. The results indicate an increase in average displacement of the SC with ES, resulting in a net anodic migration. Moreover, indirect effects of protein adsorption due to the oxidation of the film upon the application of ES were shown to have a larger effect on migration speed than on migration directionality. These results suggest that SC migration speed is governed by an integrin- or receptor-mediated mechanism, whereas SC migration directionality is governed by electrically mediated phenomena. These data will prove invaluable in optimizing conducting polymers for their different biomedical applications such as nerve repair.