Tibialis Anterior Motor Units Research Articles

Adjustments in the motor unit discharge behavior following neuromuscular electrical stimulation compared to voluntary contractions.

Introduction: The application of neuromuscular electrical stimulation superimposed on voluntary muscle contractions (NMES+) has demonstrated a considerable potential to enhance or restore muscle function in both healthy and individuals with neurological or orthopedic disorders. Improvements in muscle strength and power have been commonly associated with specific neural adaptations. In this study, we investigated changes in the discharge characteristics of the tibialis anterior motor units, following three acute exercises consisting of NMES+, passive NMES and voluntary isometric contractions alone. Methods: Seventeen young participants participated in the study. High-density surface electromyography was used to record myoelectric activity in the tibialis anterior muscle during trapezoidal force trajectories involving isometric contractions of ankle dorsi flexors with target forces set at 35, 50% and 70% of maximal voluntary isometric contraction (MVIC). From decomposition of the electromyographic signal, motor unit discharge rate, recruitment and derecruitment thresholds were extracted and the input-output gain of the motoneuron pool was estimated. Results: Global discharge rate increased following the isometric condition compared to baseline at 35% MVIC while it increased after all experimental conditions at 50% MVIC target force. Interestingly, at 70% MVIC target force, only NMES + led to greater discharge rate compared to baseline. Recruitment threshold decreased after the isometric condition, although only at 50% MVIC. Input-output gain of the motoneurons of the tibialis anterior muscle was unaltered after the experimental conditions. Discussion: These results indicated that acute exercise involving NMES + induces an increase in motor unit discharge rate, particularly when higher forces are required. This reflects an enhanced neural drive to the muscle and might be strongly related to the distinctive motor fiber recruitment characterizing NMES+.

The Role of Transcranial Magnetic Stimulation, Peripheral Electrotherapy, and Neurophysiology Tests for Managing Incomplete Spinal Cord Injury

Efforts to find therapeutic methods that support spinal cord functional regeneration continue to be desirable. Natural recovery is limited, so high hopes are being placed on neuromodulation methods which promote neuroplasticity, such as repetitive transcranial magnetic stimulation (rTMS) and electrical stimulation used as treatment options for managing incomplete spinal cord injury (iSCI) apart from kinesiotherapy. However, there is still no agreement on the methodology and algorithms for treatment with these methods. The search for effective therapy is also hampered by the use of different, often subjective in nature, evaluation methods and difficulties in assessing the actual results of the therapy versus the phenomenon of spontaneous spinal cord regeneration. In this study, an analysis was performed on the database of five trials, and the cumulative data are presented. Participants (iSCI patients) were divided into five groups on the basis of the treatment they had received: rTMS and kinesiotherapy (N = 36), peripheral electrotherapy and kinesiotherapy (N = 65), kinesiotherapy alone (N = 55), rTMS only (N = 34), and peripheral electrotherapy mainly (N = 53). We present changes in amplitudes and frequencies of the motor units' action potentials recorded by surface electromyography (sEMG) from the tibialis anterior-the index muscle for the lower extremity and the percentage of improvement in sEMG results before and after the applied therapies. The increase in values in sEMG parameters represents the better ability of motor units to recruit and, thus, improvement of neural efferent transmission. Our results indicate that peripheral electrotherapy provides a higher percentage of neurophysiological improvement than rTMS; however, the use of any of these additional stimulation methods (rTMS or peripheral electrotherapy) provided better results than the use of kinesiotherapy alone. The best improvement of tibialis anterior motor units' activity in iSCI patients provided the application of electrotherapy conjoined with kinesiotherapy and rTMS conjoined with kinesiotherapy. We also undertook a review of the current literature to identify and summarise available works which address the use of rTMS or peripheral electrotherapy as neuromodulation treatment options in patients after iSCI. Our goal is to encourage other clinicians to implement both types of stimulation into the neurorehabilitation program for subjects after iSCI and evaluate their effectiveness with neurophysiological tests such as sEMG so further results and algorithms can be compared across studies. Facilitating the motor rehabilitation process by combining two rehabilitation procedures together was confirmed.

Intrinsic motoneuron excitability is reduced in soleus and tibialis anterior of older adults.

Age-related deterioration within both motoneuron and monoaminergic systems should theoretically reduce neuromodulation by weakening motoneuronal persistent inward current (PIC) amplitude. However, this assumption remains untested. Surface electromyographic signals were collected using two 32-channel electrode matrices placed on soleus and tibialis anterior of 25 older adults (70 ± 4 years) and 17 young adults (29 ± 5 years) to investigate motor unit discharge behaviors. Participants performed triangular-shaped plantar and dorsiflexion contractions to 20% of maximum torque at a rise-decline rate of 2%/s of each participant’s maximal torque. Pairwise and composite paired-motor unit analyses were adopted to calculate delta frequency (ΔF), which has been used to differentiate between the effects of synaptic excitation and intrinsic motoneuronal properties and is assumed to be proportional to PIC amplitude. Soleus and tibialis anterior motor units in older adults had lower ΔFs calculated with either the pairwise [-0.99 and -1.46 pps; -35.4 and -33.5%, respectively] or composite (-1.18 and -2.28 pps; -32.1 and -45.2%, respectively) methods. Their motor units also had lower peak discharge rates (-2.14 and -2.03 pps; -19.7 and -13.9%, respectively) and recruitment thresholds (-1.50 and -2.06% of maximum, respectively) than young adults. These results demonstrate reduced intrinsic motoneuron excitability during low-force contractions in older adults, likely mediated by decreases in the amplitude of persistent inward currents. Our findings might be explained by deterioration in the motoneuron or monoaminergic systems and could contribute to the decline in motor function during aging; these assumptions should be explicitly tested in future investigations.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11357-021-00478-z.

Estimates of persistent inward currents in tibialis anterior motor units during standing ramped contraction tasks in humans.

Persistent inward currents (PICs) play an essential role in setting motor neuron gain and shaping motor unit firing patterns. Estimates of PICs in humans can be made using the paired motor unit analysis technique, which quantifies the difference in discharge rate of a lower threshold motor unit at the recruitment onset and offset of a higher threshold motor unit (ΔF). Because PICs are highly dependent on the level of neuromodulatory drive, ΔF represents an estimate of level of neuromodulation at the level of the spinal cord. Most of the estimates of ΔF are performed under constrained, isometric, seated conditions. In the present study, we used high-density surface EMG arrays to discriminate motor unit firing patterns during isometric seated conditions with torque or EMG visual feedback and during unconstrained standing anterior-to-posterior movements with root mean square EMG visual feedback. We were able to apply the paired motor unit analysis technique to the decomposed motor units in each of the three conditions. We hypothesized that ΔF would be higher during unconstrained standing anterior-to-posterior movements compared with the seated conditions, reflecting an increase in the synaptic input to motoneurons drive while standing. In agreement with previous work, we found that there was no evidence of a difference in ΔF between the seated and standing postures, although slight differences in the initial and peak discharge rates were observed. Taken together, our results suggest that both the standing and seated postures are likely not sufficiently different, both being "upright" postures, to result in large changes in neuromodulatory drive.NEW & NOTEWORTHY In the present study, we show that the discharge rate of a lower threshold motor unit at the recruitment onset and offset of a higher threshold motor unit (ΔF) is similar between standing and seated conditions in human tibialis anterior motor units, suggesting that at least for these two upright postures neuromodulatory drive is similar. We also highlight a proposed technological development in using high-density EMG arrays for real-time muscle activity feedback to accomplish standing ramped contraction tasks and demonstrate the validity of the paired motor unit analysis technique during these conditions.

Non-uniform Effects of Nociceptive Stimulation to Motoneurones during Experimental Muscle Pain

Nociceptive stimulation is predicted to uniformly inhibit motoneurone pools of painful muscles and those producing painful movements. Although reduced motoneurone discharge rate during pain provides some evidence, recent data show evidence of increased excitability of some motoneurones. These observations suggest non-uniform effects of nociception on motoneurone excitability. More direct measures are required, but this is difficult to assess as few measures enable in vivo evaluation of motoneurone excitability in humans. We investigated changes in motoneurone excitability during experimental pain using two methods in separate experiments: (i) estimation of the time-course of motoneurone afterhyperpolarization (AHP) from interval death rate analysis of interspike intervals of single motor unit discharge; and (ii) probability of early motoneurone discharge to a descending volley excited using transcranial magnetic stimulation (TMS). Tibialis anterior motor units were recorded with fine-wire electrodes before, during and after painful infusion of 5% hypertonic saline into the muscle. Activation of 17 units (16 participants) could be used for AHP analysis. Data show shortened (n = 11) and lengthened (n = 6) AHP time-course. Increased (n = 6) and decreased (n = 6) probability of early motoneurone discharge were observed in the TMS experiment. These convergent observations suggest non-uniform effects of nociceptive stimulation on motoneurone pools. This does not support the hypothesis that nociceptive input induces uniform inhibition of painful muscle. Instead, interpretation of results implies redistribution of activity between motor units, with possible benefit for unloading painful tissues. This finding supports an interpretation that differs from the generally accepted view in pain physiology regarding adaptation to motor function in pain.

The relative strength of common synaptic input to motor neurons is not a determinant of the maximal rate of force development in humans.

Correlation between motor unit discharge times, often referred to as motor unit synchronization, is determined by common synaptic input to motor neurons. Although it has been largely speculated that synchronization should influence the rate of force development, the association between the degree of motor unit synchronization and rapid force generation has not been determined. In this study, we examined this association with both simulations and experimental motor unit recordings. The analysis of experimental motor unit discharges from the tibialis anterior muscle of 20 healthy individuals during rapid isometric contractions revealed that the average motor unit discharge rate was associated with the rate of force development. Moreover, the extent of motor unit synchronization was entirely determined by the average motor unit discharge rate (R > 0.7, P < 0.0001). The simulation model demonstrated that the relative proportion of common synaptic input received by motor neurons, which determines motor unit synchronization, does not influence the rate of force development (R = 0.03, P > 0.05). Nonetheless, the estimates of correlation between motor unit spike trains were significantly correlated with the rate of force generation (R > 0.8, P < 0.0001). These results indicate that the average motor unit discharge rate, but not the degree of motor unit synchronization, contributes to most of the variance of human contractile speed among individuals. In addition, estimates of correlation between motor unit discharge times depend strongly on the number of identified motor units and therefore are not indicative of the strength of common input. NEW & NOTEWORTHY It is commonly assumed that motor unit synchronization has an impact on the rate of force development of a muscle. Here we present computer simulations and experimental data of human tibialis anterior motor units during rapid contractions that show that motor unit synchronization is not a determinant of the rate of force production. This conclusion clarifies the neural determinants of rapid force generation.

Motor unit activity, force steadiness, and perceived fatigability are correlated with mobility in older adults.

The purpose of our study was to examine the associations between the performance of older adults on four tests of mobility and the physical capabilities of the lower leg muscles. The assessments included measures of muscle strength, muscle activation, and perceived fatigability. Muscle activation was quantified as the force fluctuations-a measure of force steadiness-and motor unit discharge characteristics of lower leg muscles during submaximal isometric contractions. Perceived fatigability was measured as the rating of perceived exertion achieved during a test of walking endurance. Twenty participants (73 ± 4 yr) completed one to four evaluation sessions that were separated by at least 3 wk. The protocol included a 400-m walk, a 10-m walk at maximal and preferred speeds, a chair-rise test, and the strength, force steadiness, and discharge characteristics of motor units detected by high-density electromyography of lower leg muscles. Multiple-regression analyses yielded statistically significant models that explained modest amounts of the variance in the four mobility tests. The variance explained by the regression models was 39% for 400-m walk time, 33% for maximal walk time, 42% for preferred walk time, and 27% for chair-rise time. The findings indicate that differences in mobility among healthy older adults were partially associated with the level of perceived fatigability (willingness of individuals to exert themselves) achieved during the test of walking endurance and the discharge characteristics of soleus, medial gastrocnemius, and tibialis anterior motor units during steady submaximal contractions with the plantar flexor and dorsiflexor muscles. NEW & NOTEWORTHY Differences among healthy older adults in walking endurance, walking speed, and ability to rise from a chair can be partially explained by the performance capabilities of lower leg muscles. Assessments comprised the willingness to exert effort (perceived fatigability) and the discharge times of action potentials by motor units in calf muscles during submaximal isometric contractions. These findings indicate that the nervous system contributes significantly to differences in mobility among healthy older adults.

Reciprocal inhibition between motor neurons of the tibialis anterior and triceps surae in humans.

Motor neurons innervating antagonist muscles receive reciprocal inhibitory afferent inputs to facilitate the joint movement in the two directions. The present study investigates the mutual transmission of reciprocal inhibitory afferent inputs between the tibialis anterior (TA) and triceps surae (soleus and medial gastrocnemius) motor units. We assessed this mutual mechanism in large populations of motor units for building a statistical distribution of the inhibition amplitudes during standardized input to the motor neuron pools to minimize the effect of modulatory pathways. Single motor unit activities were identified using high-density surface electromyography (HDsEMG) recorded from the TA, soleus (Sol), and medial gastrocnemius (GM) muscles during isometric dorsi- and plantarflexion. Reciprocal inhibition on the antagonist muscle was elicited by electrical stimulation of the tibial (TN) or common peroneal nerves (CPN). The probability density distributions of reflex strength for each muscle were estimated to examine the strength of mutual transmission of reciprocal inhibitory input. The results showed that the strength of reciprocal inhibition in the TA motor units was fourfold greater than for the GM and the Sol motor units. This suggests an asymmetric transmission of reciprocal inhibition between ankle extensor and flexor muscles. This asymmetry cannot be explained by differences in motor unit type composition between the investigated muscles since we sampled low-threshold motor units in all cases. Therefore, the differences observed for the strength of inhibition are presumably due to a differential reciprocal spindle afferent input and the relative contribution of nonreciprocal inhibitory pathways. NEW & NOTEWORTHY We investigated the mutual transmission of reciprocal inhibition in large samples of motor units using a standardized input (electrical stimulation) to the motor neurons. The results demonstrated that the disynaptic reciprocal inhibition exerted between ankle flexor and extensor muscles is asymmetric. The functional implication of asymmetric transmission may be associated with the neural strategies of postural control.

Motor Unit Discharge Characteristics And Walking Performance Of Individuals With Multiple Sclerosis.

PURPOSE: To examine the associations between strength, force steadiness, and motor unit discharge characteristics of lower leg muscle with assessments of walking performance and disability status in individuals with multiple sclerosis (MS). METHODS: Persons with MS (n=23, 9 men, 53 ± 7 yrs) attended 1 to 3 evaluation sessions that were performed before, immediately after, and 4 wks after a clinical trial of neuromuscular electrical stimulation. Outcomes included 3 questionnaires (Patient Determined Disease Steps [PDDS], Modified Fatigue Impact Scale [MFIS], and MS Walking Scale-12 [MSWS-12]), 25-ft walk test, 6-min walk test, and maximal torque and force steadiness (10 and 20% MVC) for lower leg muscles. High-density surface EMG recordings were obtained from the tibialis anterior (TA), soleus (Sol), and medial gastrocnemius (MG) during the steady contractions and decomposed into discharge times of motor unit action potentials. RESULTS: Greater levels of self-reported disability (PDDS, MFIS, MSWS-12) were associated with less distance walked in 6 min and longer times to walk 25 ft. Mean interspike intervals (ISI) were 110 ± 23 ms and 102 ± 22 ms (10% and 20% MVC force, respectively) for TA motor units (n= 1,634), 138 ± 36 ms and 135 ± 34 ms for MG motor units (n=696), and 150 ± 33 ms and 145 ± 34 ms for Sol motor units (n = 902). A multiple regression model explained 40% (P=0.001) of the variance in 6-min distance with two predictor variables: mean ISI of MG (partial r = -0.48) and MVC dorsiflexor torque of the more affected leg (partial r=0.37). Similarly, another multiple regression model explained 47% of the variance (P<0.001) in 25-ft time with three predictor variables: mean ISI of soleus (partial r=0.51), MVC dorsiflexor torque of the more affected leg (partial r = -0.43), and force steadiness of the plantar flexors (partial r = 0.39). CONCLUSION: Moderate amounts of the variance in two walking tests for persons with MS were explained by mean discharge times of action potentials by motor units in plantar flexor muscles during steady submaximal contractions, the strength of the dorsiflexor muscles in the more affected leg, and force steadiness during an isometric contraction. This research was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the NIH (R03HD079508).

Human stretch reflex pathways reexamined

Reflex responses of tibialis anterior motor units to stretch stimuli were investigated in human subjects. Three types of stretch stimuli were applied (tap-like, ramp-and-hold, and half-sine stretch). Stimulus-induced responses in single motor units were analyzed using the classical technique, which involved building average surface electromyogram (SEMG) and peristimulus time histograms (PSTH) from the discharge times of motor units and peristimulus frequencygrams (PSF) from the instantaneous discharge rates of single motor units. With the use of SEMG and PSTH, the tap-like stretch stimulus induced five separate reflex responses, on average. With the same single motor unit data, the PSF technique indicated that the tap stimulus induced only three reflex responses. Similar to the finding using the tap-like stretch stimuli, ramp-and-hold stimuli induced several peaks and troughs in the SEMG and PSTH. The PSF analyses displayed genuine increases in discharge rates underlying the peaks but not underlying the troughs. Half-sine stretch stimuli induced a long-lasting excitation followed by a long-lasting silent period in SEMG and PSTH. The increase in the discharge rate, however, lasted for the entire duration of the stimulus and continued during the silent period. The results are discussed in the light of the fact that the discharge rate of a motoneuron has a strong positive linear association with the effective synaptic current it receives and hence represents changes in the membrane potential more directly and accurately than the other indirect measures. This study suggests that the neuronal pathway of the human stretch reflex does not include inhibitory pathways.

Motor unit loss and weakness in association with diabetic neuropathy in humans

Diabetes mellitus can be associated with peripheral neuropathy which may affect numbers of functioning motor units (MUs) of limb muscles. Direct quantitative assessment of MU numbers and muscle strength have not been performed in humans. We compared the estimated number of MUs of individuals with diabetic polyneuropathy (DPN) versus controls. Patients with signs/symptoms of DPN were studied using decomposition-enhanced quantitative electromyography of the tibialis anterior (TA). Motor unit number estimates were derived from this analysis. Dorsiflexion strength was ∼60% less in DPN than controls (P < 0.05). Additionally, the estimated number of functioning TA MUs was ∼60% fewer in patients with DM (∼46) versus controls (∼111) (P < 0.05). These data directly measure MU loss associated with DPN in a proximal muscle in humans. It remains to be determined whether quantifying MU loss has clinical utility in monitoring the progression or management of DPN.

Discharge properties of motor units during steady isometric contractions performed with the dorsiflexor muscles

The purpose of this study was to record the discharge characteristics of tibialis anterior motor units over a range of target forces and to import these data, along with previously reported observations, into a computational model to compare experimental and simulated measures of torque variability during isometric contractions with the dorsiflexor muscles. The discharge characteristics of 44 motor units were quantified during brief isometric contractions at torques that ranged from recruitment threshold to an average of 22 ± 14.4% maximal voluntary contraction (MVC) torque above recruitment threshold. The minimal [range: 5.8-19.8 pulses per second (pps)] and peak (range: 8.6-37.5 pps) discharge rates of motor units were positively related to the recruitment threshold torque (R(2) ≥ 0.266; P < 0.001). The coefficient of variation for interspike interval at recruitment was positively associated with recruitment threshold torque (R(2) = 0.443; P < 0.001) and either decreased exponentially or remained constant as target torque increased above recruitment threshold torque. The variability in the simulated torque did not differ from the experimental values once the recruitment range was set to ∼85% MVC torque, and the association between motor twitch contraction times and peak twitch torque was defined as a weak linear association (R(2) = 0.096; P < 0.001). These results indicate that the steadiness of isometric contractions performed with the dorsiflexor muscle depended more on the distributions of mechanical properties than discharge properties across the population of motor units in the tibialis anterior.

A study of synaptic connection between low threshold afferent fibres in common peroneal nerve and motoneurones in human tibialis anterior

We have induced H-reflex responses in human tibialis anterior motor units and analysed the results using the classical technique, peristimulus time histogram (PSTH), and a new technique, peristimulus frequencygram (PSF). The PSF has recently been shown to be more reliable than the PSTH for indicating the synaptic connections on motoneurones, and therefore we wished to examine the differences between the two analysis methods. Experiments were conducted on eleven healthy subjects (7 males and 4 females) who did not have any known neurological disorder. The subject sat comfortably on a dental chair and the common peroneal nerve was stimulated. In each experiment, about 600 electrical stimuli were applied to the nerve randomly between 1 and 2 s. The recordings were taken with both by surface electromyogram (SEMG) and as single motor unit potentials. We found that, when a stimulus induces an H-reflex, it also generates a period of reduced activity (silent period) and a long latency excitation in the PSTH. However, the PSF records in general do not match the indications of the PSTH records. For example, when the PSTH indicated existence of a silent period immediately following the H-reflex response, the discharge rate of the unit was in fact higher than the prestimulus rate. On the contrary, during the PSTH illustrated long latency excitatory response, the discharge rate was lower than the prestimulus rate. Our findings suggest that PSF gives significantly different results compared with the PSTH in determining the synaptic connection of the low threshold muscle afferents to the motoneurones. While PSTH indicated that there was a silent period immediately after the H-reflex, the PSF demonstrated that the silent period was actually a continuation of the net excitatory effect and not a genuine inhibition since the small number of action potentials occured during this period displayed higher discharge rates than the prestimulus level. Furthermore, the long latency excitation, as it was indicated in the PSTH; was actually a net inhibitory effect since the large number of spikes that occured during that period had lower discharge rates than the prestimulus average. In the lights of the recent brain slice findings and completely different results obtained using the two analysis techniques, we suggest that the PSF analysis should be used along with the PSTH to illustrate the net synaptic connection between peripheral receptors and motoneurones in the human nervous system.

Ia-afferent input to motoneurons during shortening and lengthening muscle contractions in humans

The central nervous system employs different strategies to execute specific motor tasks. Because afferent feedback during shortening and lengthening muscle contractions differs, the neural strategy underlying these tasks may be quite distinct. Cortical drive may be adjusted or afferent input regulated. The exact mechanisms are not clear. Here, we examine the control of synaptic transmission across the Ia synapse during shortening and lengthening muscle contractions. Subjects were instructed to maintain isolated activity in a single tibialis anterior (TA) motor unit while muscle length was varied from flexion to extension and back. At a fixed interval after a firing of the active motor unit, a single electrical stimulus was applied to the common peroneal nerve to activate Ia afferents from the TA muscle. We investigated the stimulus-induced change in firing probability of 19 individual low-threshold TA motor units during shortening and lengthening contractions. Any change in firing probability depends on both pre- and postsynaptic mechanisms. In this experiment, motoneuron firing rate was similar during both contraction types. There was no difference in the firing probability between shortening and lengthening contractions (0.23 +/- 0.03 and 0.20 +/- 0.02, respectively). We suggest that there is no contraction type-specific control of Ia input to the motoneurons during shortening and lengthening muscle contractions. Cortical adjustments may have occurred.

Reduction of Common Synaptic Drive to Ankle Dorsiflexor Motoneurons During Walking in Patients With Spinal Cord Lesion

It is possible to obtain information about the synaptic drive to motoneurons during walking by analyzing motor-unit coupling in the time and frequency domains. The purpose of the present study was to compare motor-unit coupling during walking in healthy subjects and patients with incomplete spinal cord lesion to obtain evidence of differences in the motoneuronal drive that result from the lesion. Such information is of importance for development of new strategies for gait restoration. Twenty patients with incomplete spinal cord lesion (SCL) participated in the study. Control experiments were performed in 11 healthy subjects. In all healthy subjects, short-term synchronization was evident in the discharge of tibialis anterior (TA) motor units during the swing phase of treadmill walking. This was identified from the presence of a narrow central peak in cumulant densities constructed from paired EMG recordings and from the presence of significant coherence between these signals in the 10- to 20-Hz band. Such indicators of short-term synchrony were either absent or very small in the patient group. The relationship between the amount of short-term synchrony and the magnitude of the 10- to 20-Hz coherence in the patients is discussed in relation to gait ability. It is suggested that supraspinal drive to the spinal cord is responsible for short-term synchrony and coherence in the 10- to 20-Hz frequency band during walking in healthy subjects. Absence or reduction of these features may serve as physiological markers of impaired supraspinal control of gait in SCL patients. Such markers could have diagnostic and prognostic value in relation to the recovery of locomotion in patients with central motor lesions.

Corticospinal transmission to leg motoneurones in human subjects with deficient glycinergic inhibition.

Normal coordinated movement requires that the activity of antagonistic motoneurones may be depressed at appropriate times during the movement. Both glycinergic and GABAergic inhibitory mechanisms participate in this control. Patients with the major form of hyperekplexia (hereditary startle disease) have impaired inhibition of spinal motoneurones from local glycinergic interneurones and represent an ideal opportunity for studying the role of glycinergic inhibition in the control of antagonistic muscles. In the present study we investigated whether impaired glycinergic inhibition affects the corticospinal control of antagonistic spinal motoneurones in 10 patients with hyperekplexia and whether there are mechanisms that may compensate for the lack of glycinergic inhibition. In healthy subjects transcranial magnetic stimulation (TMS) produced a short-latency inhibition of the soleus H-reflex at rest and during tonic dorsiflexion. This inhibition, which has been shown to be mediated by spinal (glycinergic) inhibitory interneurones, was absent in all four patients in whom this experiment was performed. This confirms that glycinergic transmission is impaired in the patients. During voluntary dorsiflexion subthreshold TMS produced a depression of the ongoing EMG activity in the tibialis anterior (TA) muscle in both healthy subjects and all of the six tested patients. This is consistent with the idea that this EMG depression is caused by activation of cortical (GABAergic) inhibitory interneurones. Cross-correlation analysis revealed normal short-term synchronization of TA motor units accompanied by coherence in the 8-12 Hz and 18-35 Hz frequency bands in the 10 patients. As in healthy subjects, 8-12 Hz coherence accompanied by decreased tendency to discharge synchronously (de-synchronization) was found in recordings from the antagonistic TA and soleus muscles in 2 of the 10 patients. This suggests that glycinergic inhibition is not responsible for de-synchronization of antagonistic motor units, but that other GABAergic-inhibitory mechanisms must be involved. We propose that such mechanisms may compensate for the lack of glycinergic reciprocal inhibition in the hyperekplectic patients and explain why voluntary movements are not more severely affected.

Responses of ankle extensor and flexor motoneurons to transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) of the motor cortex excites limb muscles of the contralateral side of the body. Reports of poorly defined, or a complete lack of systematic excitatory responses of soleus motoneurons compared with those of tibialis anterior (TA) motoneurons has led to the proposal that while all ankle flexor motoneurons receive strong corticomotoneuronal connections, very few soleus motoneurons do. In addition, the connections to these few motoneurons are weak. The nature of corticomotoneuronal connections onto these two motoneuron pools was re-evaluated in the following experiments. The leg area of the left motor cortex was stimulated with a large double-cone coil using Magstim 200, while surface electromyographic (EMG) and single motor unit (SMU) responses were recorded from soleus and TA muscles of healthy adult subjects. Under resting conditions, the onset (25-30 ms) and duration of concomitantly recorded short latency motor evoked potentials (MEPs) in surface EMG from both muscles were similar. The input-output relationships of the simultaneously recorded soleus and TA EMG responses showed much greater increases in TA MEPs compared with soleus MEPs with identical increases in stimulus intensity. Under resting and nonisometric conditions, a later peak with onset latency of approximately 100 ms was observed in soleus. During isometric conditions or with vibration of the TA tendon, the second soleus peak was abolished indicating reflex origin of this peak. Recordings from 42 soleus and 39 TA motor units showed clear response peaks in the peristimulus time histograms (PSTHs) of every unit. Two statistical tests were done to determine the onset and duration of response peaks in the PSTHs. With chi(2) test, the duration was 6.9 +/- 4.2 ms (mean +/- SD) for soleus and 5.1 +/- 2.1 ms for TA. Using the criterion of discerning a peak by bin counts being three SDs above background, the duration was 10.0 +/- 4.4 ms for soleus and 7.8 +/- 2.6 ms for TA. Results of these experiments do not suggest a lack of systematic corticomotoneuronal connections on soleus motoneurons when compared with those on TA, though some differences in the strengths of corticomotoneuronal connections onto the two pools do exist.

Group I projections from intrinsic foot muscles to motoneurones of leg and thigh muscles in humans.

1. Group I projections from intrinsic plantar muscles to motoneurones (MNs) of human leg and thigh muscles were investigated. Changes in firing probability of single motor units (MUs) in the tibialis anterior (TA), peroneus brevis (Per brev), soleus (Sol), gastrocnemius medialis (GM), vastus lateralis (VL), semitendinosus (ST) and biceps (Bi) were studied after electrical stimuli applied to: (i) the tibial nerve (TN) at ankle level, (ii) the corresponding homonymous nerve, and (iii) the skin of the heel, to mimic the TN-induced cutaneous sensation. 2. Homonymous facilitation, attributable to monosynaptic Ia excitation, was found in all the sampled units. Early heteronymous excitation elicited by TN stimulation was found in many MUs. Later effects (3-5 ms central delay) were bigger and more frequently observed: excitation in most TA and Per brev MUs, and inhibition in most Sol, GM and Bi MUs and in many ST and VL MUs. The low threshold (approximately 0.5-0.6 x motor threshold) and the inability of a pure cutaneous stimulation to reproduce these effects (except the late excitation in TA MUs) indicate that they were due to stimulation of group I muscle afferents. 3. The early excitation was accepted to be monosynaptic when its central delay differed from that of the homonymous Ia excitation by less than 0.5 ms. Such a significant TN-induced monosynaptic Ia excitation was found in MUs belonging to all leg and thigh motor nuclei tested. Although its mean strength was relatively weak, it is argued that these monosynaptic connections might affect already depolarized MNs. 4. The late excitation found in TA and Per brev MUs is argued to be mediated through interneurones located rostral to MNs. 5. The late suppression, found in most Sol, GM and Bi MUs, and in many ST and VL MUs, was the dominant effect. It was accompanied by an inhibition of the Sol and quadriceps H reflexes at rest, and therefore reflects an inhibition directed to MNs. Its long latency is argued to reflect transmission by interneurones located rostral to MNs (the inhibitory counterpart of non-monosynaptic excitation). 6. The functional implications of these connections are discussed with respect to the requirements of the stance phase of human walking and running.

Muscle biopsy, macro EMG, and clinical characteristics in patients with schizophrenia

Background: In a previous study of motor unit properties in patients with schizophrenia, muscle fiber histologic and electrophysiologic abnormalities were observed. The present study was designed to compare patients with schizophrenia with healthy control subjects with regard to muscle fiber histology and motor unit function. A second objective was to relate these variables to clinical characteristics. Methods: Twelve patients with first-episode schizophrenia and fifteen patients with chronic schizophrenia (DSM-III-R) and 27 matched control subjects were included in the study. Muscle biopsies were performed either in m. tibialis anterior or m. vastus lateralis. Electromyographic recordings (macro EMG) were made from the m. tibialis anterior motor units. Psychiatric ratings included the PANSS and extrapyramidal side effects. Results: Seven of the muscle biopsy specimens from the patients and one from the control subjects were classified as abnormal ( p = .049). The most frequent abnormality was atrophic muscle fibers. Eight patients and no control subjects exhibited pathological macro EMG ( p = .032). The findings were present in chronic as well as in first-episode patients with schizophrenia. Conclusions: In approximately 50% of the patients, neuromuscular abnormalities were found either in the muscle biopsy or the macro EMG investigations.The results indicate that either a common pathologic process or different pathological processes are at hand in the neuromuscular system in patients with schizophrenia. The findings are compatible with a disturbed cell membrane function.

Evidence that a transcortical pathway contributes to stretch reflexes in the tibialis anterior muscle in man.

1. In human subjects, stretch applied to ankle dorsiflexors elicited three bursts of reflex activity in the tibialis anterior (TA) muscle (labelled M1, M2 and M3) at mean onset latencies of 44, 69 and 95 ms, respectively. The possibility that the later of these reflex bursts is mediated by a transcortical pathway was investigated. 2. The stretch evoked a cerebral potential recorded from the somatosensory cortex at a mean onset latency of 47 ms in nine subjects. In the same subjects a compound motor-evoked potential (MEP) in the TA muscle, evoked by magnetic stimulation of the motor cortex, had a mean onset latency of 32 ms. The M1 and the M2 reflexes thus had too short a latency to be caused by a transcortical pathway (minimum latency, 79 ms (47 + 32)), whereas the later part of the M2 and all of the M3 reflex had a sufficiently long latency. 3. When the transcranial magnetic stimulation was timed so that the MEP arrived in the TA muscle at the same time as the M1 or M2 reflexes, no extra increase in the potential was observed. However, when the MEP arrived at the same time as the M3 reflex a significant (P < 0.01) extra-facilitation was observed in all twelve subjects investigated. 4. Peaks evoked by transcranial magnetic stimulation in the post-stimulus time histogram of the discharge probability of single TA motor units (n = 28) were strongly facilitated when they occurred at the same time as the M3 response. This was not the case for the first peaks evoked by electrical transcranial stimulation in any of nine units investigated. 5. We suggest that these findings are explained by an increased cortical excitability following TA stretch and that this supports the hypothesis that the M3 response in the TA muscle is - at least partly - mediated by a transcortical reflex.