Mechanical and focal electrical stimuli applied to the skin of the index fingertip induce both inhibition and excitation in low-threshold flexor carpi radialis motor units

It has been observed that mechanical stimulation of the skin of the index fingertip causes a weak short-latency inhibition followed by a strong long-lasting facilitation of the flexor carpi radialis (FCR) H-reflex. Based on threshold and latency, these cutaneous reflexes are thought to be routed to motoneurons by parallel pathways. As recent studies have shown predominant inhibitory potentials in slow motoneurons and predominant excitatory potentials in faster ones, the question arises as to whether or not the two cutaneous pathways converge onto the same motoneuron. The poststimulus time histogram technique was used to investigate the changes in firing frequency of low-threshold FCR motor units (MUs), induced by passive mechanical or focal electrical stimuli to the index skin. After gently tapping the finger pulp a small sharp inhibition appeared in 20 MUs. On average, inhibition started 10.2 +/- 1.6 ms from the homonymous Ia monosynaptic effect, and its central delay was estimated to be 1.2 +/- 1.6 ms. The subsequent facilitation, more consistent, had a mean latency of 13.5 +/- 1.7 ms. Inhibition and excitation were statistically significant (P < 0.05). A similar biphasic effect was observed in seven other FCR-MUs, also after focal electrical stimulation of the same skin area. Comparison with the time course of the H-reflex, representing the whole population of MUs, showed striking similarities in time course and latency to the present MU effect. It is thus suggested that cutaneous spinal pathways may have a homogeneous distribution within the FCR motoneuron pool, and that the skewed distribution of cutaneous afferents onto motoneurons should be not taken as a rule.     

Changes in motoneuron excitability during postnatal life in the mouse

H-reflex recovery, H-amplitude and H/M ratio were recorded in 54 mice aged 3-12 weeks to study the motoneuron excitability and changes in it during various stages of development. The H-reflex recovery curve at 12 wk showed 3 phases: an early, relative facilitation (before 10 ms), an almost total inhibition at 10 ms and a rapid recovery thereafter. At 3 wk, however, there was only slow recovery after 10 ms and the H-reflex recovery was significantly low during the 40-100 ms period as compared to those in the other age groups, indicating that between 3 and 6 wk, there was a significant increase in the motoneuron excitability. The H-reflex amplitude also showed a significant increase during the 3-6 wk period. However, the H/M ratio did not show any significant increase either during the 3-6 wk period or thereafter. It is concluded that the H-reflex recovery at 3 wk suggests hypoexcitability of the motoneurons, possibly due to immaturity. Since there was a significant increase in the H-reflex recovery during the 3-6 wk period without any parallel increase in the H/M ratio, it is concluded that presynaptic and polysynaptic mechanisms acting on the motoneurons develop during this period. The increase in the H-reflex amplitude is possibly due to the increase in the muscle mass. The H-reflex recovery pattern at 12 wk, without the phase of late inhibition observed in man, is suggestive of less supra-spinal control mechanisms acting upon the motoneurons.     

There is a close relationship between hand skill and the excitability of motor neurons innervating the postural soleus muscle in left-handed subjects

The claim that there is not a consistent inhibition of the H-reflex from the dominant leg was examined and rejected. It was re-established that there is an inverse relationship between hand skill and the excitability of motoneurons innervating the postural soleus muscle in left-handed subjects. In left-handers with significantly better left-hand skill, the height of the H-reflex recovery curve was significantly higher on the right leg (nondominant) than the left leg (dominant). There was a positive linear correlation between the asymmetries of hand skill greater than zero (better left-hand skill) and the H-reflex recovery curves from the right and left legs greater than zero (right dominance in reflex excitability). In left-handers with no significant difference between the right- and left-hand skills, there was no significant difference between the mean recovery curves from the right and left legs for the interstimulus intervals from 40 to 100 ms; the height of the left recovery curve was found to be significantly higher than the height of the right recovery curve for the interstimulus intervals from 150 to 1000 ms. It was concluded that there is close relationship between hand skill and motoneuronal excitability from right and left soleus muscle with regard to support and operative functions of legs in left-handers.     

The effect of quadriceps-electrocutaneous stimulation on the T-reflex and the H-reflex of the soleus muscle.

OBJECTIVE: To investigate the effect of ipsilateral quadriceps-electrocutaneous stimulation on the T-reflex and the H-reflex of the soleus muscle, and to examine the interactions in human cutaneous sensation - the soleus motoneuron pathway. METHODS: The T-reflex and H-reflex tests were performed bilaterally on 50 able-bodied adults with a standardized technique using the soleus muscle. The reflexes were conditioned by electrocutaneous stimuli applied to the ipsilateral quadriceps using the optimal transcutaneous electrical nerve stimulation (TENS) machine (3 x perception, intensity 15-30 mA). The conditioning stimuli were followed by reflex tests by 30-50 ms (conditioning A) and 80-100 ms (conditioning B). The latency and amplitude of the T-reflex and H-reflex were measured before (control) and after conditioning stimuli (A and B) and at sham (placebo). RESULTS: There were no significant differences between the right and left sides and between the control and placebo in both T-reflex and H-reflex. There were significant differences in both latency and amplitude of the T-reflex only between control and conditioning A. There were no significant differences between control and conditioning tests in the H-reflex. CONCLUSIONS: The above results suggest that supraspinal center and cutaneous fusimotor reflexes, which increase the sensitivity of the soleus muscle spindle, mediate the observed motoneuron excitability changes.     

The effects of conditioning stimuli on the F-response.

The effect of conditioning stimuli on the F-response was investigated in normal subjects using stimulus pairs with interstimulus intervals of 1 to 400 ms. The "recovery curve" for the F-response was found to be similar to that for the H-reflex but differences were found between male and female subjects. The significance of these findings is discussed.     

Effects of transcranial magnetic stimulation on the H reflex and F wave in the hand muscles.

OBJECTIVE: In 14 healthy subjects, we studied the effects of transcranial magnetic stimulation (TMS) on the excitability of spinal motoneurons in the abductor pollicis brevis muscle (ABP), by testing the F wave and H reflex. METHODS: TMS pulses were delivered with the subjects at rest and at various motor threshold (Mth) intensities. Electrical stimuli were delivered to the median nerve at the wrist at two different intensities. High-intensity pulse was used to evoke an F wave and low-intensity paired pulse to evoke an H reflex in the ABP muscle. The effects of TMS were studied using a conditioning-test paradigm. The tests F wave and H reflex were conditioned by TMS (120% Mth) at various interstimulus intervals (ISIs) (30-100ms) and intensities (90-200% Mth). RESULTS: At 30ms but not at ISIs from 40 to 100ms, conditioning TMS (120% Mth) significantly increased the F-wave area. At the 30ms ISI, conditioning TMS at 120% Mth intensity significantly increased the F-wave area whereas higher intensities (140-180% Mth) did not. At 200% Mth intensity, the F-wave area decreased significantly. At 30 and 40ms ISIs, conditioning TMS at 120% Mth significantly reduced the H-reflex area. At 50-100ms ISIs, the H-reflex area almost matched the control value. At the 30ms ISI, conditioning TMS at >or=100% Mth intensity significantly decreased the H-reflex area. CONCLUSIONS: In conclusion, our findings suggest that the distinct changes in the TMS-conditioned F wave and H reflex reflect changing excitability in the motoneuronal populations activated by the cortical input.     

Extraocular muscle motor units characterized by spike-triggered averaging in alert monkey

Single-unit recording in macaque monkeys has been widely used to study extraocular motoneuron behavior during eye movements. However, primate extraocular motor units have only been studied using electrical stimulation in anesthetized animals. To study motor units in alert, behaving macaques, we combined chronic muscle force transducer (MFT) and single-unit extracellular motoneuron recordings. During steady fixation with low motoneuron firing rates, we used motoneuron spike-triggered averaging of MFT signals (STA-MFT) to extract individual motor unit twitches, thereby characterizing each motor unit in terms of twitch force and dynamics. It is then possible, as in conventional studies, to determine motoneuron activity during eye movements, but now with knowledge of underlying motor unit characteristics.We demonstrate the STA-MFT technique for medial rectus motor units. Recordings from 33 medial rectus motoneurons in three animals identified 20 motor units, which had peak twitch tensions of 0.5-5.25 mg, initial twitch delays averaging 2.4 ms, and time to peak contraction averaging 9.3 ms. These twitch tensions are consistent with those reported in unanesthetized rabbits, and with estimates of the total number of medial rectus motoneurons and twitch tension generated by whole-nerve stimulation in monkey, but are substantially lower than those reported for lateral rectus motor units in anesthetized squirrel monkey. Motor units were recruited in order of twitch tension magnitude with stronger motor units reaching threshold further in the muscle's ON-direction, showing that, as in other skeletal muscles, medial rectus motor units are recruited according to the “size principle”.     

Contralateral influences on triceps surae motoneuron excitability.

In an effort to more fully investigate spinal reflex pathways in humans, we measured the isometric force-time curve of the tibial nerve H-reflex in 12 college age subjects. We also conditioned the reflex with a contralateral H-reflex stimulus or a contralateral tendon-tap, to ascertain the effects of crossed spinal segmental inputs on alpha motoneuron excitability. The conditioning stimulus preceded the test reflex by 10, 25, 40, 55, 70, 85, 100, 115, 130 or 145 msec. The results demonstrate that a conditioning tibial nerve H-reflex produced marked facilitation onto the contralateral triceps surae motoneurons, predominantly at longer-latency intervals. Conversely, a conditioning Achilles tendon-tap produced long-latency inhibition to the triceps surae. These results demonstrate that differential motoneuron excitability changes can be produced by electrical and mechanical conditioning stimuli. Moreover, these excitability changes may be long lasting and only appear after a relatively long latency. Several neurophysiological mechanisms are proposed to contribute to these changes.     

The refractory period of fast conducting corticospinal tract axons in man and its implications for intraoperative monitoring of motor evoked potentials.

OBJECTIVE: To determine the absolute and relative refractory period (RRP) of fast conducting axons of the corticospinal tract in response to paired high intensity (HI or supramaximal) and moderate intensity (MI or submaximal) electrical stimuli. The importance of the refractory period of fast conducting corticospinal tract axons has to be considered if repetitive transcranial electrical stimulation (TES) is to be effective for eliciting motor evoked potentials (MEPs) intraoperatively. METHODS: Direct (D) waves were recorded from the epidural space of the spinal cord in 14 patients, undergoing surgical correction of spinal deformities. To assess the absolute and RRPs of the corticospinal tract, paired transcranial electrical stimuli at interstimulus intervals (ISI) from 0.7 to 4.1 ms were applied. Recovery of conditioned D wave at short (2 ms) and long (4 ms) ISI was correlated with muscle MEP threshold. The refractory period for peripheral nerve was tested in comparison to that for the corticospinal tract. In four healthy subjects sensory nerve action potentials of the median nerve were studied after stimulation with paired stimuli. RESULTS: HI TES revealed a mean duration of 0.82 ms for the absolute refractory period of the corticospinal tract, while MI stimulation resulted in a mean refractory period duration of 1.47 ms. Stimuli of HI produced faster recovery of D wave amplitude during the RRP. Furthermore, short trains of transcranial electrical stimuli did not elicit MEPs when D wave showed incomplete recovery. A similar influence of stimulus intensity on recovery time was found for the refractory period of peripheral nerve. CONCLUSIONS: The recovery of D wave amplitude is dependent upon stimulus intensity. High intensity produces fast recovery. This is an important factor for the generation of MEPs. When HI TES is used to elicit MEPs, short and long ISIs are equally effective. When MI TES is used to elicit MEPs, only a long ISI of 4 ms is effective.     

Neurophysiological mechanisms underlying motor evoked potentials in anesthetized humans. Part 2. Relationship between epidurally and muscle recorded MEPs in man.

OBJECTIVE AND METHODS: Direct (D) and transynaptic, (i.e. indirect) (I) corticospinal tract (CT) discharges were simultaneously recorded epidurally with muscle motor evoked potentials (MEPs) in patients under different levels of anesthesia. The effects of the one, two or more equal electrical stimuli, applied transcranially or directly to the motor cortex, were studied at different interstimulus intervals (ISIs) to determine the optimal conditions for eliciting I and MEP responses. RESULTS AND CONCLUSION: At anesthetic levels permiting large D and I responses to single stimuli, optimal D and I wave facilitation and MEPs occurred with two stimuli at ISIs greater than 4 ms (e.g. at 5.9 and 8 ms). When single electrical stimuli elicit only a D response, optimal MEP responses are determined by the number of stimuli and the recovery of CT fibers excitability (e.g. at an ISI of 4 ms).     

Facilitation and recovery of the H-reflex in children]

Facilitation and recovery of the H-reflex were studied in 63 children with cerebral palsy, and the results were compared with those obtained for 60 normal children. H waves were recorded from the gastrocnemius with surface electrodes, after applying paired stimulations to the tibial nerve in the midpopliteal crease. In normal children, both the facilitation and the recovery showed a tendency to decrease with their development, while those for children with cerebral palsy were more marked than normal children in all age groups. The present study indicated that the excitability of spinal alpha motoneurons and the subliminal fringe in the motoneuron pool might change due to the maturation of and the damage to the central nervous system in children. We consider that H-reflex examination provides useful information for the supraspinal control to the spinal mechanism to regulate muscle contraction in children as well as in adults.     

Enhanced intracortical inhibition in cerebellar patients

OBJECTIVE: The aim of the study was to examine intracortical excitability in cerebellar patients. METHODS: Short-latency intracortical inhibition (SICI), long-latency intracortical inhibition (LICI) and intracortical facilitation (ICF) to paired transcranial magnetic stimulation (TMS) were investigated in 8 patients with 'pure' cerebellar syndromes and in 14 age-matched normal controls. The conditioning stimulus for short-latency intracortical inhibition and intracortical facilitation was set at 70% of the resting motor threshold (RMT) and preceded the test stimulus (110-120% of the resting motor threshold) by interstimulus intervals (ISIs) of 1-30 ms. For the long-latency intracortical inhibition determinations, the conditioning stimulus was set at 120% of the resting motor threshold and preceded the test stimulus (also 120% of the resting motor threshold) by interstimulus intervals of 30-500 ms. RESULTS: No statistically significant differences were found between patients and controls as regards either short-latency intracortical inhibition or intracortical facilitation. A significant prevalence of long-latency intracortical inhibition was present in cerebellar patients at interstimulus intervals of 200-500 ms (conditioned MEP amplitude=29-41% of test MEP) as compared to controls (71-96% of test MEP). The amplitude of conditioned MEPs was persistently less than 45% of the test MEP in six patients, who were studied at interstimulus intervals up to 1000 ms. CONCLUSIONS: Long-latency intracortical inhibition was prevalent and abnormally longer-lasting in patients. Tonic hyperactivation of a subpopulation of GABAergic interneurons in the motor cortex of patients may be the mechanism responsible for this abnormality. Our findings seem to be specific to cerebellar diseases and are the opposite of those found in movement disorders such as dystonia and Parkinson's disease. These data suggest that the cerebellum and the basal ganglia may have opposite influences in tuning the excitability of the motor cortex.     

The cutaneous silent period is mediated by spinal inhibitory reflex

High-intensity cutaneous stimuli inhibit tonically firing motor neurons resulting in a silent period (CSP) in EMG activity. To determine the central nervous system (CNS) circuitry of this inhibitory reflex, soleus H reflexes evoked by tibial nerve stimuli were conditioned by high-intensity sural stimuli in 5 normal men and 5 men with complete, traumatic cervical myelopathy. The sural-tibial interstimulus interval (ISI) was varied between 0 and 200 ms. In normals, the CSP in the tonically contracted soleus muscle began 90-100 ms after sural stimuli and had a duration of 60-80 ms. In the relaxed soleus, the conditioned soleus H-reflex amplitude was correspondingly reduced at ISIs of 60-120 ms. In patients, conditioned H-reflex amplitude was also reduced over the same ISI range, but the degree of inhibition was significantly less than in normals. These data support the hypothesis that the CSP is mediated by a spinal inhibitory reflex that is subject to supraspinal descending control.     

Neurophysiological mechanisms underlying motor evoked potentials in anesthetized humans. Part 1. Recovery time of corticospinal tract direct waves elicited by pairs of transcranial electrical stimuli.

Direct (D) corticospinal tract discharges were recorded epidurally in patients at anesthetic depths suppressing indirect (I) activity and were elicited by two equal transcranial electrical stimuli. The recovery of amplitude of the second D wave (D2) was a function of the interstimulus interval (ISI) and the stimulus duration. For example, with a 100 micros pulse, there was no response at an ISI of 1.1 ms, but partial recovery occurred with a 500 micros pulse. This indicates a relative refractory component at this ISI. Both D2 amplitude and conduction time recovered completely using a 4 ms ISI, with evidence of increased amplitude and reduced conduction time (supernormality) at longer ISIs. These findings are relevant in explaining high frequency D and I discharges and facilitation of motor responses by two transcranial magnetic pulses. Furthermore, these data help to understand why an ISI of 4 ms would be optimal in eliciting limb muscle responses when a short train of transcranial stimuli elicits only D waves in anesthetized patients (Deletis et al., Clin Neurophysiol 112 (2001) 445).     

Modulation of upper extremity motor evoked potentials by cutaneous afferents in humans.

The excitability of motoneurons controlling upper limb muscles in humans may vary with cutaneous nerve stimulation. We investigated the effect of noxious and non-noxious conditioning stimuli applied to right and left digit II and right digit V on motor evoked potentials (MEPs) recorded from right thenar eminence, abductor digiti minimi, biceps and triceps brachii muscles in twelve healthy subjects. Transcranial magnetic stimulation (TMS) was applied at interstimulus intervals (ISI) ranging from 40 to 160 ms following conditioning distal digital stimulation. TMS and transcranial electrical stimulation (TES) were compared at ISI 80 ms. Painful digital stimulation caused differential MEP amplitude modulation with an early maximum inhibition in hand muscles and triceps brachii followed by a maximum facilitation in arm muscles. Stimulation of different digits elicited a similar pattern of MEP modulation, which largely paralleled the behavior of cutaneous silent periods in the same muscles. Contralateral digital stimulation was less effective. MEPs following TMS and TES did not differ in their response to noxious digital stimulation. MEP latencies were shortened by cutaneous stimuli. The observed effects were stimulus intensity dependent. We conclude that activation of A-alpha and A-delta fibers gives rise to complex modulatory effects on upper limb motoneuron pools. A-delta fibers initiate a spinal reflex resulting in MEP amplitude reduction in muscles involved in reaching and grasping, and MEP amplitude facilitation in muscles involved in withdrawal. These findings suggest a protective reflex mediated by A-delta fibers that protects the hand from harm. A-alpha fibers induce MEP latency shortening possibly via a transcortical excitatory loop.     

Velocity recovery cycles of human muscle action potentials and their sensitivity to ischemia

This study was undertaken to test whether recovery cycle measurements can provide useful information about the membrane potential of human muscle fibers. Multifiber responses to direct muscle stimulation through needle electrodes were recorded from the brachioradialis of healthy volunteers, and the latency changes measured as conditioning stimuli were applied at interstimulus intervals of 2–1000 ms. In all subjects, the relative refractory period (RRP), which lasted 3.27 ± 0.45 ms (mean ± SD, n = 12), was followed by a phase of supernormality, in which the velocity increased by 9.3 ± 3.4% at 6.1 ± 1.3 ms, and recovered over 1 s. A broad hump of additional supernormality was seen at around 100 ms. Extra conditioning stimuli had little effect on the early supernormality but increased the later component. The two phases of supernormality resembled early and late afterpotentials, attributable respectively to the passive decay of membrane charge and potassium accumulation in the t‐tubules. Five minutes of ischemia progressively prolonged the RRP and reduced supernormality, confirming that these parameters are sensitive to membrane depolarization. Velocity recovery cycles may provide useful information about altered muscle membrane potential and t‐tubule function in muscle disease. Muscle Nerve, 2008     

Action potentials of cat masseter muscle motor neurons evoked by stimulation of low-frequency infraorbital nerve afferents

The responses of masseter motoneurons evoked by stimulation of the low-threshold infraorbital afferents by different number of stimuli were investigated in cats under chloralose-nembutal anesthesia. It is shown that 3-4 succesive stimuli (1.2 of threshold) evoked action potentials in masseter motoneurons if their frequency was above 300/s. Stimulation of the infraorbital nerve by paired stimuli produced action potentials in these motoneurons when the interval between the stimuli was 1.3-4.0 ms. With longer intervals only facilitation of the second EPSP was observed, the degree of facilitation varying from 0.2 to 1.0. A conclusion is made that the masseter motoneurons discharges can be produced by activation of the infraorbital nerve. A -fibres probably connected to rapidly adapting receptors of the vibrissae.     

Depression of the human nociceptive withdrawal reflex by segmental and heterosegmental intramuscular electrical stimulation.

OBJECTIVE: To investigate the effects of intramuscular electrical conditioning in the modulation of nociceptive withdrawal reflex (NWR) and further to determine what muscle afferents are involved in the modulation of the nociceptive withdrawal reflex and the sites along the reflex pathway where the NWR modulation occurs in healthy humans. METHODS: The NWR elicited by a cutaneous test stimulus to the dorsal foot was modulated by a short (21 ms) intramuscular conditioning electrical stimulus at two times the pain threshold. At varying conditioning-test stimulus intervals, segmental conditioning stimulus was applied in the tibialis anterior muscle ipsilateral and contralateral to the test stimulus, and heterosegmental conditioning stimulus was applied in the contralateral trapezius muscle to modulate the NWR. Non-painful and painful intramuscular conditioning stimuli were also used to modulate the NWR and the soleus H-reflex. RESULTS: The NWR was depressed by preceding intramuscular conditioning stimuli, with a degree that depended on the conditioning-test stimulus intervals and on the conditioning site. Segmental conditioning depressed the NWR more quickly and gave a longer duration (15-1500 ms), and larger magnitude than heterosegmental conditioning, which depressed the NWR in a short temporal window (80-100 ms). No difference was seen in the magnitude of the NWR depression between the painful and non-painful intramuscular stimuli, and the soleus H-reflex was not affected. CONCLUSIONS: Our results suggest that segmental and heterosegmental conditionings of NWR are mediated by myelinated muscle afferents engaging central inhibitory mechanisms rather than direct changes in the excitability of motor neurons. SIGNIFICANCE: The therapeutic effects of electrotherapy could involve these mechanisms in the treatment of muscle pain syndromes.     

Modification of the silent period by double transcranial magnetic stimulation.

OBJECTIVES: To study the time course of the changes of the inhibitory network of the human motor system, we investigated the silent period (SP) in 7 healthy subjects by double suprathreshold transcranial magnetic stimulation (TMS). METHODS: SPs and motor evoked potentials (MEPs) were recorded from the voluntarily activated right abductor digiti minimi muscle. Conditioning and test stimuli were delivered with equal intensity, which was set to yield a baseline SP duration of 130 ms by a single pulse, and with various interstimulus intervals (ISIs). In addition, a control experiment with adjustment of the intensity of single stimuli was performed. RESULTS: At ISIs of 20 and 30 ms the test pulse SP duration was prolonged, without increasing the MEP amplitude. The SP duration shortened at longer ISIs and showed a significant depression between ISIs of 60-110 ms. The shortened SP was accompanied by a diminished MEP. The control experiment revealed that the SPs evoked by the adjusted pulses were significantly shorter than the test pulse SPs. CONCLUSIONS: A conditioning stimulus can prolong and shorten the test pulse SP duration at different ISIs. The prolongation is probably cortically generated, whereas the shortening is likely to occur at a cortical and spinal level.     

Segmental inhibitory reactions in the spinal cord of the frog in response to orthodromic motor neuron activation

Ventral root reflexes evoked by a single dorsal root volley were recorded in the isolated frog spinal cord. They varied from asynchronous, low-amplitude response to highly synchronized monosynaptic discharge in different preparations. The response to a testing stimulus could be facilitated or inhibited, respectively. The inhibition was weaker at interstimulus intervals of about 40-50 ms and stronger either at longer (60-100 ms) or at shorter (15-30 ms) intervals, thus testifying to the existence of at least two types of inhibition: early and late. Strychnine effectively blocked the late inhibition and facilitated the early one; d-tubocurarine considerably weakened both types of inhibition. A conclusion is made that the late (presynaptic) inhibition is produced by activation of the inhibitory systems through recurrent motoneuron axon collaterals. Recurrent activation may also take part in the origin of the early (postsynaptic) inhibition.