Motoneuron pool excitability of hemiplegic patients: assessing recovery stages by using H-reflex and M response.

OBJECTIVES: To compare the excitability of the motoneuron pools of both the spastic and the unimpaired sides of patients with hemiplegia with a new method by using H-reflexes and M responses. The method determines the ratio of the developmental slope of the H-reflex (Hslp) to the slope of the M response (Mslp). We also examined the relation between the Brunnstrom stages and the Hslp/Mslp. DESIGN: Experiment. SETTING: Electrophysiologic experimental laboratory in a Japanese medical school. PATIENTS: Fifteen hemiplegic patients (9 men, 6 women; age range, 48-71yr; mean, 60yr) with spasticity caused by a stroke. INTERVENTIONS: The subject was instructed to relax while seated in a reclining chair with his foot fixed on an immobile pedal. After the soleus H-reflex and M responses on one side were recorded, the same experimental procedures were carried out on the other side. MAIN OUTCOME MEASURES: Hslp/Mslp Brunnstrom stages. RESULTS: Hslp/Mslp had better predictive value than conventional indicators of motoneuron pool excitability. Hslp/Mslp appeared to be a better match for the bell-shaped pattern of the Brunnstrom stages. CONCLUSION: Hslp/Mslp is the preferred index for evaluating the motoneuron pool excitability of the spastic side of hemiplegic patients.

Patterns of muscle activation in human hopping.

In the present study, we examined the electromyogram (EMG) patterns of the soleus and medial gastrocnemius (MG) muscles during rhythmical, two-legged hopping to investigate the contributions of the monosynaptic short- and long-latency stretch reflexes during such a natural movement in human. During rhythmical hopping, soleus muscle is activated reflexly at near-monosynaptic latency by stretch resulting from passive ankle flexion upon landing. Soleus muscle also contracts voluntarily in order to launch the body into the next hop. This is part of the rhythmical bursts of activity producing the hops. Depending on the hopping interval, this phase of activation can follow the short-latency phase or precede landing at very short hopping intervals. In MG, there is an initial phase of activity that stiffens the muscle in preparation for landing, and continues through the contact phase. The monosynaptic reflex response to landing is usually superimposed on this activity. Depending on the hopping interval, both of these responses may be overlaid with activity that is time-locked to the take-off into the next hop, and serves to launch the body into the next hop. However, no evidence for a long-latency stretch reflex was found. In addition, the preferred hopping frequency for all subjects was about 2 Hz. This frequency is associated with a pattern of EMG activity the timing of which indicates that it balances the requirement for a comfortable landing from a hop with the optimal muscle activation required for launching the following hop.

Trial-to-trial fluctuations in H-reflexes and motor evoked potentials in human wrist flexor.

The H-reflexes and the motor potentials (MEPs) evoked by electromagnetic brain stimulation in the human wrist flexor were recorded over many trials. The responses from each stimulus at two steady levels of muscle activation were sorted into three groups, based on their amplitudes. The electromyogram (EMG) in each of these groups was rectified and averaged. The level of pre-response muscle activity was found to correlate with the amplitude of both the averaged H-reflexes and the averaged MEPs. This suggests that much of the amplitude fluctuations of both H-reflexes and MEPs can be attributed to moment-to-moment changes in the level of activity of the motoneurone pool. Overall, however, the amplitude of MEPs increased more rapidly than the amplitude of H-reflexes as the pre-stimulus EMG activity increased. This is probably because, while the amplitude of H-reflexes depends primarily on the level of motoneurone pool excitability, the amplitude of an MEP depends not only on this, but also on the excitability of the motor cortex, and the former is to some extent also dependent on the latter.

Observations on the variability of the H reflex in human soleus.

H reflexes were evoked in human soleus by stimulating the tibial nerve at a constant intensity. Each trial was then assigned to one of three groups on the basis of the amplitude of its H reflex; all trials in each group were then full-wave rectified and reaveraged. There was a strong positive relationship between the amplitude of the H reflex and the level of electromyographic activity in the muscle at the time of onset of the H reflex, which reflects the activity of the motoneuronal pool when the afferent volley arrived. Thus, much of the variability of the H reflex is due to small changes in the level of activation of the motoneuronal pool during repeated trials. The steady torque preceding the H reflex was a poor predictor of the H-reflex amplitude, presumably because of the delay between the changes in the electrical activity of motoneurons and the mechanical outcome thereof.

Selective modification of somatosensory evoked potential during voluntary finger movement in humans.

We examined changes in somatosensory evoked potentials (SEPs) during voluntary movement of fingers innervated by the stimulated nerve and those not innervated by the stimulated nerve and the relationship to the kind of movement modality. Analysis showed that the amplitude of most components at F3, C3', and P3, except for P45 at C3, N35 and P45 at P3, decreased during voluntary finger movement tasks. Further, we found that the components of P40 at F3, P45 at C3', and N35 at P3 were increased during the voluntary pulling movement of the second and the third digits compared to those during the voluntary pushing movement of the fourth and the fifth digits, whereas all other components were decreased at F3, C3', and P3. We also found that not all components of SEPs were decreased while some SEPs in middle latency were increased. In conclusion, we confirmed the selectivity in attenuation of the SEPs. Moreover, we noted an interesting finding that the selectivity of attenuation of the SEPs was most frequently observed in the N20, P30 (P25 at F3), N35 (N30 at F3), and P45 (P40 at F3) components at F3, C3', and P3.

Changes in central motor-sensory system following voluntary movement of stimulated finger.

OBJECTIVE: We examined which components of somatosensory evoked potentials (SEP) were modulated during the voluntary movement of stimulated fingers and discuss our findings with respect to the decrease in SEPs in terms of both centrifugal and centripetal mechanisms. METHODS: The study was performed in the Laboratory of Physiology, Institute of Health and Sport Sciences, University of Tsukuba. Experiments were performed on 10 healthy young male subjects, aged 19-21 years. All subjects were right-handed and were free of neurological disease. RESULTS: We found that N20-P25 (P22 at frontal area) -N35-(N30 at frontal) P45 (P40 at frontal area) components at the F3, the C3' and the P3 were consistently evoked, but N35 was increased at P3 and N30 attenuation at F3 during a sustained voluntary movement. Furthermore, the present experiments showed that frontal N30 was markedly decreased during a sustained voluntary movement. We also found that all SEPs components, except for parictal N35, were significantly decreased during sustained voluntary movement tasks. CONCLUSIONS: We concluded that the suppression of SEPs appeared to be due to the interaction of both centrifugal and centripatal mechanisms. Namely, in a particular type of movement task, more prenounced afferent mechanisms may contribute to the decrease in SEPs, while in the other types of tasks, more pronounced afferent activities may contribute to the decrease in SEPs.

Inhibition of the soleus H-reflex during dorsiflexion is dependent on individual differences in maximal soleus H-reflex as a test reflex.

The quantitative differences among individuals in the natural reciprocal inhibition of the soleus H-reflex during dorsiflexion were examined, in conjunction with the maximal H-reflex as the test reflex size in each individual. Maximal H-reflex was expressed relative to the maximal M-response (H(max)) when compared among individuals. Analysis showed that with increases in H(max) at rest in each individual, the inhibitory effect was first enhanced, then reached a peak, and was finally alleviated. This pattern was similar to the intraindividual pattern of the inhibitory effect induced by specific conditioning stimulus as a function of the test reflex size.

Somatosensory evoked potentials following voluntary movement during upper arm compression.

We examined the modulation of somatosensory evoked potentials (SEPs) during upper arm compression and following voluntary movement during upper arm compression. Most SEPs were significantly decreased, although some SEPs showed a slight, non-significant diminution. SEPs are mediated not only by myelinated fibers but also by mixed nerves and afferents from cutaneous, joints, and deep tissues, these being dependent upon the dorsal column-medical lemniscal system. Therefore, most of the diminution in SEPs found here may have been due to afferent occlusion from muscle, cutaneous, joints, and deep tissues, since normal SEPs are selectively modulated, corresponding to motor or mental tasks, regardless of whether gating is centrifugal or centripetal. In addition, the present experiments showed that all the SEPs at FZ, C3' and CZ were significantly decreased following voluntary movement at a pressure 25%-30% higher than the subject's systolic blood pressure. Comparing SEPs during upper arm compression and those following voluntary movement during upper arm compression at these pressures, we found that the SEPs at C3' were significantly diminished following voluntary movement during upper arm compression, with other SEPs showing slight, non-significant attenuation. In conclusion, it is possible that the diminution in SEPs following voluntary movement could be responsible for sensory inputs, however, when sensory inputs are present, centrifugal modulation would also be responsible for this diminution.

Evident difference in the excitability of the motoneuron pool between normal subjects and patients with spasticity assessed by a new method using H-reflex and M-response.

The excitability of the motoneuron (MN) pool in the resting state was compared between normal control subjects and patients with spasticity resulting from HTLV-I-associated myelopathy, using a new parameter, Hslp/Mslp, and the conventional parameters Hmax/Mmax and Hth/Mth. Differences in the excitability of the MN pool between these two groups reached a high degree of statistical significance only when assessed with the new parameter. This suggests the methodological advantage of the Hslp/Mslp over both Hmax/Mmax and Hth/Mth for evaluation of the excitability of the MN pool in the resting state.

Hemispace asymmetries and laterality effects in arm positioning.

Hemispace asymmetries and laterality effects were examined on an arm positioning reproduction task. Sixteen male subjects were asked to reproduce both abductive and adductive positioning movements with the left or right arm within either the left or the right hemispace. Hemispace was manipulated using a 90 degrees head-rotation paradigm. A left hemispace advantage in positioning accuracy was predicted for both left and right arm movements on the grounds that the perceptual-motor control of positioning movements made in left hemispace is primarily mediated by the right hemisphere which is known to be advantageous for tasks which are spatial in nature (Heilman, Bowers, & Watson, 1984). No arm laterality effects were predicted to occur because the proximal musculature involved in the control of arm movements is innervated from both contralateral and ipsilateral cerebral hemispheres (Brinkman & Kuypers, 1973). Results showed that the predicted left hemispace advantage was evident for the right arm on the positioning variability measure alone, whereas it was absent for all other possible conditions on all error measures. Laterality (arm) effects were absent as predicted. The experiment also demonstrated a greater degradation of reproduction performance under the "crossed" arm-hemispace conditions than under the "uncrossed" conditions. A plausible explanation for the uncrossed advantage for the task is that under normal conditions, a single hemisphere is primarily responsible for both controlling the contralateral arm and directing attention to the contralateral hemispace, and consequently potential interhemispheric interference is minimized. A clear response bias effect in movement reproduction was also evident as a function of the direction of concurrent arm movement and head rotation. Arm movements made in the same direction as head rotation were systematically undershot in reproduction to a much greater degree than arm movements made in the opposite direction to head rotation.

Frontal N30 potential following a sustained voluntary movement.

With 6 male subjects we investigated whether the decreased amplitude in the frontal N30 potential of Somatosensory Evoked Potentials is related to a sustained voluntary movement or not. We concluded that the diminution of frontal N30 was also closely related to the sustained voluntary movement.

Excitability of the soleus motoneuron pool revealed by the developmental slope of the H-reflex as reflex gain.

The excitability of a motoneuron (MN) pool was evaluated by the developmental slope of H-reflexes (Hslp) evoked at a range of a stimulus intensity less than the threshold of an M-response. The Hslp has been regarded as the "reflex gain", which is the changing rate in MN excitability as a function of the increase of Ia input to an MN pool. In a comparison of two parameters used in the H-reflex technique, such as the ratio of the maximal H-reflex to the maximal M-response and the ratio of the threshold of an H-reflex to that of an M-response, the Hslp was predicted to be a reasonable parameter to evaluate motoneuronal excitability, because the Hslp is free from the effect of any collision between the H-reflex discharge and the antidromic volley drived from the occurrence of an M-response within the alpha-efferents, and the Hslp can estimate the recruitment properties of a whole MN pool. The Hslp was alleviated during dorsi-flexion and steepened during plantar-flexion, according to the inhibitory or facilitatory synaptic modifications onto soleus MNs. The developmental slope of an M-response (Mslp), which shows the recruitment property of axons of soleus MNs, was alleviated especially in plantar-flexion. In order to exclude the peripheral neuromuscular factors in evaluating substantial MN excitability, the Hslp/Mslp is proposed as a more effective parameter than the Hslp.

Auditory middle latency responses under different task conditions.

We examined the relationship between the Na and Pa components of human MLRs and the performance of different tasks. We also investigated whether MLRs are reliable indices of activity in the central motor-sensory system. The click stimuli we used consistently evoked the Na and Pa components. At CZ, the Na and Pa components significantly decreased for all tasks other than pegging with right hand while at FZ, these components were significantly decreased for all tasks. The Na and Pa latencies were slightly increased during task performances. These results indicate that the Na and Pa components of human MLRs decreased when various tasks were performed, while subjects were concentrating. A general principle of evoked potentials is that latencies decrease as amplitudes increase in excitation due to neural activation. Thus, it would appear that, under the conditions of this study, the pathways from the reticular formation and the thalamus to the primary auditory cortex were inhibited. Since the thalamus is considered to be the relay region for poly-sensory inputs, it is thought that the attenuation of the MLRs and SEPs occurs at the level of cerebral cortex, including the reticular formation, the thalamus, and the primary auditory cortex. Accordingly, since it is inferred that central factors are responsible for the attenuation of the MLRs, Na and Pa components observed during the performance of tasks carried out in the present experiment, it may be concluded that MLRs are reliable indices of activity in the central-motor system.

Reconsidering the 90 degrees head-rotation paradigm used in neuropsychological research: are there reflexive rather than hemispatial effects?

The 90 degrees head-rotation paradigm has often been used in neuropsychological studies to manipulate external hemispace (circumcorporeal space) relative to the head. Under the 90 degrees head-rotation paradigm, the performance of limb and hand movements carried out within the left or right hemispace as defined by head positions relative to the body is likely to be affected by the reflexive effect due to the neck and vestibular afferent inputs elicited by the head rotations, as well as by the hemispatial effect. Using the H-reflex technique, the present study examined whether the reflexive effect on the spinal motoneuron excitability occurred with head rotations under the 90 degrees head-rotation paradigm. The results showed that the amplitudes of H-reflexes evoked on both the thumb flexor and soleus muscles were not affected by head rotations, indicating no reflexive change in the spinal motoneuron excitability for both the thumb and soleus muscles. This finding suggests that the reflexive effect due to neck and vestibular afferent inputs can be ruled out from possible causal factors influencing the motor performance of limb and hand movements performed within the left or right hemispace as manipulated by the 90 degrees head-rotation paradigm.

Threshold of the soleus muscle H-reflex is less sensitive to the change in excitability of the motoneuron pool during plantarflexion or dorsiflexion in humans.

In the present study, we investigated whether weak (10% of maximal voluntary contraction) tonic dorsiflexion (DF) and plantarflexion (PF) affects the two conventional parameters used for evaluating the excitability of the soleus motoneuron (MN) pool, i.e. the ratio of the threshold of H-reflex to that of M-response (Hth:Mth) and the ratio of the maximal amplitude of H-reflex to that of M-response (Hmax:Mmax) in human subjects. The results showed that the Hmax:Mmax decreased during DF and increased during PF compared with that during rest, whereas no clear alteration was observed in Hth:Mth. These results are consistent with the scheme proposed by earlier workers, who have argued that neither inhibitory nor facilitatory effects of the conditioning stimulus apply to specific spinal reflex circuits occurring around the threshold of the test H-reflex. It is suggested, therefore, that the conventional use of the Hth:Mth ratio as a parameter reflecting the excitability of the MN pool should be reconsidered.

Information-processing mediating the location-distance interference in motor short-term memory.

We reviewed the literature on basic psychological correlates of the well-known phenomenon of the location-distance interference in motor short-term memory (Kerr, 1978; Walsh, Russell, Imanaka, & James, 1979). The location-distance interference in motor short-term memory has frequently been demonstrated as an unavoidable interference phenomenon observed in the reproduction of movement location and distance in arm positioning. The most important aspect of this phenomenon is that even when a subject concentrates on a specific cue (i.e., either end-location or distance) the other cue is also coded unintentionally and, as a result, the reproduction movement guided on the basis of the specific cue is unavoidably influenced by the other nonspecific cue. In this review article, we first reviewed the literature on the basic theories and nature of short-term memory, particularly on the limited processing capacity. We then referred to the unlimited, automatic processing in visual-verbal domains, referring to the Stroop phenomenon. Finally, in conjunction with the notion of automatic processing, we examined the possible aspects of information processing which may be responsible for mediating the location-distance interference in motor short-term memory.

Augmentation of bursting pacemaker activity by serotonin in an identified Achatina fulica neurone: an increase in sodium- and calcium-activated negative slope resistance via cyclic-AMP-dependent protein phosphorylation.

The mechanism of serotonin (5-HT) action on bursting activity was examined in a bursting pacemaker neurone of the snail Achatina fulica. 5-HT augmented both the depolarizing and post-burst-hyperpolarizing phases of the bursting cycle in a dose-dependent manner. This biogenic amine also enhanced the negative slope resistance (NSR), which was normally detectable at membrane potentials between -40 and -20 mV, and produced another NSR at voltages between -20 and 0 mV. The former NSR disappeared in Na(+)-free saline and the latter was abolished by replacement with Co(2+)-substituted Ca(2+)-free saline. Both isobutylmethylxanthine, extracellular applied, and intracellularly applied cyclic AMP simulated a 5-HT effect on the current-voltage relationships. In contrast, the 5-HT effect was suppressed in a dose-dependent manner by prior treatment with a cyclic-AMP-dependent protein kinase inhibitor, isoquinoline sulphonamide. Similar suppression was observed after intracellular injection of a cyclic-AMP-dependent protein kinase inhibitor isolated from bovine muscle. These results suggest that 5-HT may augment the bursting pacemaker activity by its stimulatory effect on both the slow Na+ channels and the Ca2+ channels through cyclic-AMP-dependent protein phosphorylation.

Cyclic AMP elicits biphasic current whose activation is mediated through protein phosphorylation in snail neurons.

The involvement of protein phosphorylation in cAMP-induced transmembrane current was tested electrophysiologically and pharmacologically in identified neurons of the Japanese land snail, Euhadra peliomphala. Intracellular injection of cAMP elicited a biphasic transmembrane current (cAMP current) which consisted of inward and outward components. The inward component was blocked with Na(+)-free, Ca2(+)-free saline and the outward component abolished by either application of tetraethylammonium or a long-lasting exposure to caffeine in Ca2(+)-free saline. The cAMP current was completely suppressed by the protein kinase inhibitors, protein kinase inhibitor isolated from rabbit muscle or isoquinoline sulfonamide (H-8). The catalytic subunit of cAMP-dependent protein kinase transiently restored the cAMP current suppressed by H-8 nearly to pre-H-8 level. These findings suggest that protein phosphorylation may be an intermediate step in the activation process of the cAMP current.

Oxytocin-induced sodium current is mediated by cAMP-dependent protein phosphorylation in an identified snail neuron.

The intracellular biochemical process underlying oxytocin-induced change of membrane properties was analyzed in an identified neuron of Achatina fulica Férussac, using pressure injection technique and pharmacological tools. Oxytocin dose-dependently enhanced the negative slope resistance (NSR) region on the current-voltage relation. The oxytocin-induced current was attenuated by a reduction of extracellular Na+ and not influenced by the addition of 100 microM tetrodotoxin (TTX) to the medium, suggesting that this current is predominantly due to the activation of TTX-resistant Na+ channels. In the Ca2(+)-free state, substituted by an equivalent amount of Co2+, the amplitude of oxytocin-induced current was somewhat reduced at the NSR region but it was not influenced at less than -60 mV. Application of 100 microM isobutylmethylxanthine, a phosphodiesterase inhibitor, augmented the oxytocin-induced current. Pressure injection of 10 mM adenosine 3',5'-cyclic monophosphate (cAMP) elicited a Na(+)-dependent inward current similar to the oxytocin response. The further role of cAMP linked with the oxytocin-induced current was investigated using two kinds of cAMP-dependent protein kinase inhibitors, isoquinolinesulfonamide (H-8) and protein kinase inhibitor (PKI). Extracellular application of H-8 or pressure injection of PKI, prior to oxytocin application, both blocked the oxytocin-induced current. Based on these results, oxytocin-elicited inward currents may mediate cAMP-dependent protein phosphorylation mainly by activation of Na+ channels.

Achatin-I, an endogenous neuroexcitatory tetrapeptide from Achatina fulica Férussac containing a D-amino acid residue.

A tetrapeptide named achatin-I was purified from the suboesophageal and cerebral ganglia of the African giant snail Achatina fulica Férussac, and evoked a potent neuroexcitatory effect. The amino acid sequence of achatin-I is Gly-D-Phe-Ala-Asp. Achatin-I induced a voltage-dependent inward current, due to Na+, on the identifiable giant neuron, periodically oscillating neuron (PON), of the same snail. All possible isomers of achatin-I were synthesized using the solid-phase method. The sensitivity of the neuron to achatin-I and its isomers was strictly stereospecific; among the various isomers, only achatin-I showed marked effects (ED50 = 2.29 x 10(-6)M), while Gly-D-Phe-D-Ala-Asp, the synthetic D-Ala-isomer, was less than 10(-3) active.