Convergence of nociceptive and non-nociceptive inputs onto spinal reflex pathways to the tibialis anterior muscle in humans

The interaction of low-threshold mechanoreceptive and nociceptive inputs onto spinal neurones probably plays a major role in the pathophysiology of the clinical sign of allodynia. This phenomenon was investigated by modulation of the early component of the flexor reflex (FR) in the tibialis anterior (TA) muscle, elicited by electrical stimulation of the medial plantar nerve at the sole of the foot, by homotopically applied painful heat in humans. This early reflex with an electrical threshold of 2.7-fold the detection threshold and a mean afferent conduction velocity of 49 m s^?1 is a non-nociceptive FR. When applying conditioning painful heat (46 °C) to the sole of the foot this reflex was significantly increased by a factor of 3.4 (non-painful electrical stimuli; n = 5) and 2.0 (painful electrical stimuli; n = 11). The onset latencies were significantly shortened from 74.2 to 64.0 ms and 69.6 to 63.7 ms, respectively. A late nociceptive FR was also facilitated. While the Hoffmann reflex (HR) in the TA muscle was nearly abolished by painful heat, the HR in the soleus (SO) muscle remained unchanged. These data suggest a convergence of low-threshold mechanoreceptive and nociceptive inputs onto spinal reflex pathways in humans, probably at an interneuronal level in humans.     

Facilitation of the soleus stretch reflex induced by electrical excitation of plantar cutaneous afferents located around the heel

Previous studies have demonstrated that plantar cutaneous afferents can adjust motoneuronal excitability, which may contribute significantly to the control of human posture and locomotion. However, the role of plantar cutaneous afferents with respect to their location specificity in modulating the mechanically induced stretch reflex still remains unclear. In the present study, it was hypothesized that electrical stimulation of the ipsilateral heel region of the foot is followed by a modulation of spinal excitability, leading to a facilitation of the soleus motor output. The study was performed to investigate the effect of excitation of plantar cutaneous afferents located around the heel on the soleus stretch reflex. The soleus stretch reflex was evoked by rotating the ankle joint in dorsiflexion direction at two different angular velocities of 50 and 200 degrees s(-1). A conditioning pulse train of non-noxious electrical stimulation was delivered to the plantar surface of the heel at different conditioning test intervals ranging from 5 to 100 ms. Excitation of plantar cutaneous afferents around the heel resulted in a pronounced facilitation of the soleus stretch reflex with magnitude and time course comparable for both velocities. This facilitation was manifested by a significant increase of reflex size for conditioning test intervals from 30 to 70 ms. The observed effect implies a potential functional role of cutaneous afferents in balance control conditions where the ankle is naturally disturbed, e.g., during step reactions to external perturbations.     

Specific modulation of the Hoffmann reflex cutaneous facilitation during a reaction-time task

Summary The Hoffmann (H) reflex and its facilitation produced by electrical stimulation of the sural area were examined before a ballistic extension of the right foot. Modulations of the cutaneous facilitation of the H reflex (CFH) were used to assess the control exerted over the transmission of low threshold cutaneous afferents. The time-course of H and CFH changes were investigated at the end of the foreperiod and during the premotor period, i.e. between the response signal and the onset of the electromyogram (EMG) of the soleus muscle. Four stimulation conditions were set up depending on whether the H reflex was elicited on the contracting or non-contracting limb, and whether cutaneous stimulation was ipsilateral or contralateral to the reflex. During the 100 ms preceding the response signal, the inhibition of the H reflex was more marked in the contracting limb than in the noncontracting limb. At the end of the foreperiod, the CFHs had a symmetric time course: the CFHs evoked by conditioning stimulation of the contracting limb were facilitated just before the response signal, while those produced by conditioning stimulation to the non-contracting limb were depressed. It is suggested that these variations are related to postural adjustments taking place before the movement is performed. As previously reported, the H reflex of the contracting limb exhibited a marked increase in amplitude over the 50 ms preceding the EMG. Reflex facilitations showed specific variations according to the ankle stimulated and the soleus muscle tested. The CFHs produced by stimulation of the non-contracting limb regained, at the end of the premotor period, a value close to their reference level recorded in trials without movement. The CFHs, produced by conditioning stimulation of the contracting limb were modulated differently according to whether the tested soleus muscle was contracting or not: when the CFH was tested on the contracting muscle, it was found to be depressed throughout the premotor period; this contrasted significantly with the isolated depression recorded on the non-contracting muscle. Therefore, only the cutaneous afferents from the mobilized limb, modulating the H reflex of the same limb, were subject to a specific inhibition during the premotor period. Throughout the preparatory and premotor periods, negative correlations were observed between H and CFH amplitude, except just before the EMG onset in the condition where the H reflex was delivered to the contracting muscle and the cutaneous stimulation to the ankle of the non-contracting limb: in this case, CFH amplitude increase paralleled that of the reflex amplitude. The negative correlations between these two variables are discussed in terms of a central control regulating the balance between proprioceptive and cutaneous input.     

Effects of hip joint angle changes on intersegmental spinal coupling in human spinal cord injury

Pathological expression of movement and muscle tone in human upper motor neuron disorders has been partly associated with impaired modulation of spinal inhibitory mechanisms, such as reciprocal or presynaptic inhibition. In addition, input from specific afferent systems contributes significantly to spinal reflex circuits coupled with posture or locomotion. Accordingly, the objectives of this study were to identify the involved afferents and their relative contribution to soleus H-reflex modulation induced by changes in hip position, and to relate these effects with activity of spinal interneuronal circuits. Specifically, we investigated the actions of group I synergistic and antagonistic muscle afferents (e.g. common peroneal nerve, CPN; medial gastrocnemius, MG) and tactile plantar cutaneous afferents on the soleus H-reflex during controlled hip angle variations in 11 motor incomplete spinal cord injured (SCI) subjects. It has been postulated in healthy subjects that CPN stimulation evokes an inhibition on the soleus H-reflex at a conditioning test (C-T) interval of 2–4 ms. This short latency reflex depression is caused mainly by activation of the reciprocal Ia inhibitory pathway. At longer C-T intervals (beyond 30 ms) the soleus H-reflex is again depressed, and is generally accepted to be caused by presynaptic inhibition of soleus Ia afferents. Similarly, MG nerve stimulation depresses soleus H-reflex excitability at the C-T interval of 6 ms, involving the pathway of non-reciprocal group I inhibition, while excitation of plantar cutaneous afferents affects the activity of spinal reflex pathways in the extensors. In this study, soleus H-reflexes recorded alone or during CPN stimulation at either short (2, 3, 4 ms) or long (80, 100, 120 ms) C-T intervals, and MG nerve stimulation delivered at 6 ms were elicited via conventional methods and similar to those adopted in studies conducted in healthy subjects. Plantar skin conditioning stimulation was delivered through two surface electrodes placed on the metatarsals at different C-T intervals ranging from 3 to 90 ms. CPN stimulation at either short or long C-T intervals and MG nerve stimulation resulted in a significant facilitation of the soleus H-reflex, regardless of the hip angle tested. Plantar skin stimulation delivered with hip extended at 10° induced a bimodal facilitation reflex pattern, while with hip flexed (10°, 30°) the reflex facilitation increased with increments in the C-T interval. This study provides evidence that in human chronic SCI, classically key inhibitory reflex actions are switched to facilitatory, and that spinal processing of plantar cutaneous sensory input and actions of synergistic/antagonistic muscle afferents interact with hip proprioceptive input to facilitate soleus H-reflex excitability. These actions might be associated with the pathological expression of neural control of movement in individuals with SCI, and potentially could be considered in rehabilitation programs geared to restore sensorimotor function in these patients.     

Conditioning of heteronymous H reflex in human temporalis muscle by stimulation of perioral afferents

A heteronymous H reflex in the temporalis muscle can be elicited by selective stimulation of the masseteric nerve. The present study aimed at defining the optimal amplitude of the H reflex to detect inhibitory changes induced by stimulation of the perioral afferents and at providing new information on the control of masticatory muscles. Sixteen healthy volunteers participated in the experiment. A conditioning stimulus (CS) to the perioral skin was applied at various delays before an ipsilateral selective masseteric nerve stimulation (test stimulus: TS) while the subject was clenching the teeth at 25% of the maximal voluntary contraction. Two intensities of CS and TS were employed, high and low. The peak-to-peak amplitude of the H reflex (TS) and the root-mean-square value of the preceding electromyography were measured and the data analyzed by three-way analysis of variance and Tukey's posthoc tests. For both intensities used the heteronymous H reflex in the temporalis muscle was significantly decreased by prior activation of perioral afferents for delays from 5 to 60 ms. With a delay of 5 and 35 ms the preceding EMG level was not changed, while it was reduced at 20 and 60 ms delay. The intensities used to elicit the heteronymous H reflex of the temporalis muscle were appropriate to detect a reduction in motoneuron excitability. The reduction in the H reflex without a change in the preceding EMG at 5 and 35 ms delays could be due to presynaptic inhibition of the masseteric afferents exerted by the ipsilateral perioral afferents.     

Experimental skin pain and muscle pain induce distinct changes in human trigeminal motoneuronal excitability

Seeking information on the physiological properties of the trigeminal motoneuronal pool we investigated changes in the excitability of trigeminal motor system induced by two types of experimental pain (muscle and skin). In one session, we studied the effect of muscle pain induced by hypertonic saline infusion into the masseter muscle on the recovery cycle of the heteronymous H-reflex in the temporalis muscle and the homonymous silent period (SP) in the masseter muscle, both elicited by stimulation of the masseteric nerve in ten-healthy subjects. In another session, we studied the effect of laser stimuli applied to the perioral region, at conditioning intervals from 20 to 160 ms, on the temporalis H-reflex and masseter SP in nine healthy subjects. Whereas laser-induced skin pain significantly inhibited the temporalis H-reflex and facilitated the masseter SP (P < 0.01), muscle pain left the time course of the temporalis H-reflex and masseter SP unchanged (P > 0.05). The timing of temporalis H-reflex suppression and masseter-SP enhancement induced by laser stimuli indicates that facial skin nociceptors inhibit trigeminal motoneurones via multysynaptic reflex pathways. Hypertonic saline, a stimulus that predominantly activates group III and IV afferents, left both variables reflecting trigeminal motoneuron excitability unchanged. Due to the differences between the two experimental models, we cannot conclude that such inhibitory reflex pathway does not exist from muscle nociceptors to trigeminal motoneurones.     

Blink reflex to supraorbital nerve stimulation in the cat

 Neurophysiological studies of the blink reflex to supraorbital nerve stimulation were conducted in eight alert, adult male cats. The cat, like other mammals, shows both short-latency (R1) and long-latency (R2) orbicularis oculi electromyographic (OOemg) components. Measures of OOemg latency, duration, integrated area, and maximum amplitude (MA) were obtained at a stimulus magnitude of 1.5×R2 threshold. The mean (±SE) minimal latencies for R1 and R2 were 8.26±0.85 and 22.97±1.53 ms, respectively. On average, R1 MA was larger than R2 MA. R1 and R2 area measures were similar. Three stimulus paradigms were tested. In a paired-stimulus paradigm, the interstimulus interval (ISI) was randomly varied from 100 to 1200 ms. Ratios were constructed for the OOemg area and MA by dividing the test response by the conditioning response. In this paradigm, although a significant linear relationship was observed only between ISI and R2 MA, conditioning effects were noted on both R1 and R2 area and MA test responses at several ISIs. In a habituation paradigm, both R2 and R1 showed habituation at stimulus frequencies from 0.5 to 2 Hz. In a stimulus-response paradigm, stimulus magnitude was randomly varied between threshold and 2×threshold. In this paradigm, OOemg area and MA of both R1 and R2 were linearly related to stimulus magnitude. Neither the systemically administered centrally acting α₂-adrenergic antagonist yohimbine nor agonist clonidine had significant effects on blink reflex parameters, habituation, or the paired-stimulus paradigm. Overall, these results suggest that there are important similarities in the control and modulation of the R1 and R2 components of the blink reflex to supraorbital nerve stimulation in cats. Received: 18 June 1996 / Accepted: 21 February 1997     

Inhibitory actions from low and high threshold cutaneous afferents on groups II and III muscle afferent pathways in the spinal cat

The inhibitory effects caused by volleys in cutaneous afferents on the transmission through some polysynaptic segmental pathways activated by high threshold muscle afferents were studied in chloralose anesthetized, spinal cats. Pathways studied were groups II and III to motoneurones as well as group II to primary afferents. The results suggested that two different mechanisms were involved. One mechanism, with a very slow time course (duration more than 400 ms), is suggested to be an example of presynaptic inhibition between different primary afferent systems. This mechanism required high threshold (≥ 1.6T) conditioning shocks, and appeared simultaneously with the component II dorsal root potential being evoked by the cutaneous afferent volley. The other mechanism, with a faster time course (duration always below 300 ms), was dependent upon low threshold (≥ 1.5T) cutaneous conditioning volleys. This inhibitory interaction could not be ascribed to the same presynaptic mechanism, but is suggested to be an example of postsynaptic inhibition at an interneuronal level. The presumed disynaptic excitatory pathway from group II muscle afferents to flexor motoneurones was not inhibited by cutaneous conditioning shocks, but could on the contrary be facilitated by activity in low threshold cutaneous afferents, probably at the only intemeurone involved in this group II pathway.     

Evidence suggesting that a transcortical reflex pathway contributes to cutaneous reflexes in the tibialis anterior muscle during walking in man

Stimulation of cutaneous foot afferents has been shown to evoke a facilitation of the tibialis anterior (TA) EMG-activity at a latency of 70–95 ms in the early and middle swing phase of human walking. The present study investigated the underlying mechanism for this facilitation. In those subjects in whom it was possible to elicit a reflex during tonic dorsiflexion while seated (6 out of 17 tested), the facilitation in the TA EMG evoked by stimulation of the sural nerve (3 shocks, 3-ms interval, 2.0–2.5× perception threshold) was found to have the same latency in the swing phase of walking. The facilitation observed during tonic dorsiflexion has been suggested to be – at least partly – mediated by a transcortical pathway. To investigate whether a similar mechanism contributes to the facilitation observed during walking, magnetic stimulation of the motor cortex (1.2× motor threshold) was applied in the early swing phase at different intervals in relation to the cutaneous stimulation in 17 subjects. In 13 of the subjects, the motor potentials evoked by the magnetic stimulation (MEPs) were more facilitated by prior sural-nerve stimulation (conditioning-test intervals of 50–80 ms) than the algebraic sum of the control MEP and the cutaneous facilitation in the EMG when evoked separately. In four of these subjects, a tibialis anterior H-reflex could also be evoked during walking. In none of the subjects was an increase of the H-reflex similar to that for the MEP observed. In five experiments on four subjects, MEPs evoked by magnetic and electrical cortical stimulation were compared. In four of these experiments, only the magnetically induced MEPs were facilitated by prior stimulation of the sural nerve. We suggest that a transcortical pathway may also contribute to late cutaneous reflexes during walking. Received: 24 September 1997 / Accepted: 2 June 1998     

Complete suppression of voluntary motor drive during the silent period after transcranial magnetic stimulation

 To evaluate changes in the motor system during the silent period (SP) induced by transcranial magnetic stimulation (TMS) of the motor cortex, we investigated motor thresholds as parameters of the excitability of the cortico-muscular pathway after a suprathreshold conditioning stimulus in the abductor digiti minimi muscle (ADM) of normal humans. Since the unconditioned motor threshold was lower during voluntary tonic contraction than at rest (31.9±5.4% vs. 45.6±7.5%), it is suggested that the difference between active and resting motor threshold indicates the magnitude of the voluntary drive on the cortico-muscular pathway. Therefore, we compared conditioned resting and active motor threshold (cRMT and cAMT) during the SP. cRMT showed an intensity-dependent period of elevation of more than 200 ms in duration and approximately 17% of the maximum stimulator output above the unconditioned threshold, due to decreased excitability of the cortico-muscular pathway after the conditioning stimulus. Some 30–40 ms after the conditioning stimulus, cAMT approximated cRMT, indicating complete suppression of the voluntary motor drive. This suppression did not start directly after the conditioning stimulus since cAMT was still significantly lower than the cRMT within the first 30–40 ms. Threshold elevation was significantly longer than the SP (220±41 vs. 151±28 ms). Recovery of the voluntary motor drive started late in the SP and was nearly complete at the end of the SP, although thresholds were still significantly elevated. We conclude that the SP is largely due to a suppression of voluntary motor drive, while the threshold elevation is a different inhibitory phenomenon that is of less importance for the generation of the SP, at least in its late part. It is argued that the pathway of fast cortico-spinal fibers activated by TMS is partially different from the pathway involved in the maintenance of tonic voluntary muscle activation. Received: 24 November 1997 / Accepted: 11 August 1998     

Task-dependent modulation of inhibitory actions within the primary motor cortex

 In 11 healthy subjects motor-evoked potentials (MEPs) and silent periods (SPs) were measured in the right first dorsal interosseus (FDI) and abductor pollicis brevis muscles (APB): (1) when transcranial magnetic cortex stimulation (TMS) was applied at tonic isometric contraction of 20% of maximum force, (2) when TMS was applied during tactile exploration of a small object in the hand, (3) when TMS was applied during visually guided goal-directed isometric ramp and hold finger flexion movements, and (4) when at tonic isometric contraction peripheral electrical stimulation (PES) of the median nerve was delivered at various intervals between PES and TMS. Of the natural motor tasks, duration of SPs of small hand muscles was longest during tactile exploration (APB 205±42 ms; FDI 213±47 ms). SP duration at tonic isometric contraction amounted to 172±35 ms in APB and 178±31 ms in FDI, respectively. SP duration in FDI was shortest when elicited during visually guided isometric finger movements (159±15 ms). At tonic isometric contraction, SP was shortened when PES was applied at latencies –30 to +70 ms in conjunction with TMS. The latter effect was most pronounced when PES was applied 20 ms before TMS. PES-induced effects increased with increasing stimulation strength up to a saturation level which appeared at the transition to painful stimulation strengths. Both isolated stimulation of muscle afferents and of low-threshold cutaneous afferents shortened SP duration. However, PES of the contralateral median nerve had no effect on SPs. Amplitudes of MEPs did not change significantly in any condition. Inhibitory control of motor output circuitries seems to be distinctly modulated by peripheral somatosensory and visual afferent information. We conclude that somatosensory information has privileged access to inhibitory interneuronal circuits within the primary motor cortex. Received: 24 November 1997 / Accepted: 11 August 1998     

Dissociation of nociceptive modulation of a human jaw reflex from the influence of stress

In human beings, inhibitory jaw reflexes can be depressed by painful stimulation of remote parts of the body. Since similar effects can be produced by the stress of anticipating pain, we wished to investigate whether the effects of remote painful stimuli are dependent on stress. EMG recordings were made from a masseter muscle while subjects maintained activity in the muscle at ∼12.5% of maximum using visual feedback. The protocols involved three sequences: (1) “standard controls” in which reflexes were evoked by electrical test stimuli applied to the upper lip; (2) “standard conditioning” in which painful electrical conditioning stimuli were applied over the sural nerve 100 ms before the test stimuli; (3) “random sequences” in which test-only and conditioning-test combinations were employed in a double-blind, random, order. Data are presented as means ± SEMs. In the standard controls, the stimuli evoked clear inhibitory reflexes (latency 37 ± 1.3 ms, duration 62 ± 5.6 ms; n = 10) in all the subjects. During standard conditioning, the reflex magnitude was reduced significantly (by 50.0 ± 8.5%, P = 0.0002, one-sample t-test). When the test-only and conditioning-test responses were extracted from the random sequences, there was also a significant reduction in the reflex magnitude following conditioning (by 34.6 ± 5.5%, P = 0.0002, one-sample t-test) albeit less so than between the standard sequences (P = 0.03, paired t-test). A second series of experiments suggested that these lesser effects during the random sequences were not substantially due to any loss of temporal summation of the conditioning mechanisms. The evidence for this was that application of pairs of conditioning stimuli did not produce a significantly greater effect than single conditioning stimuli within a random sequence (39.9 ± 9.6% as opposed to 32.7 ± 9.1% reductions in the reflex, P = 0.117, paired t-test). Therefore since any stress in the random sequences would not have been “tied” to the conditioned responses alone, the effects of remote painful stimuli on this inhibitory jaw reflex cannot be entirely secondary to stress.     

Modulation of corticomuscular coherence by peripheral stimuli

The purpose of this study was to investigate the effects of peripheral afferent stimuli on the synchrony between brain and muscle activity as estimated by corticomuscular coherence (CMC). Electroencephalogram (EEG) from sensorimotor cortex and electromyogram (EMG) from two intrinsic hand muscles were recorded during a key grip motor task, and the modulation of CMC caused by afferent electrical and mechanical stimulation was measured. The particular stimuli used were graded single-pulse electrical stimuli, above threshold for perception and activating cutaneous afferents, applied to the dominant or non-dominant index finger, and a pulsed mechanical displacement of the gripped object causing the subject to feel as if the object may be dropped. Following electrical stimulation of the dominant index finger, the level of β-range (14–36 Hz) CMC was reduced in a stimulus intensity-dependent fashion for up to 400 ms post-stimulus, then returned with greater magnitude before falling to baseline levels over 2.5 s, outlasting the reflex and evoked changes in EMG and EEG. Subjects showing no baseline β-range CMC nevertheless showed post-stimulus increases in β-range CMC with the same time course as those with baseline β-range CMC. The mechanical stimuli produced similar modulation of β-range CMC. Electrical stimuli to the non-dominant index finger produced no significant increase in β-range CMC. The results suggest that both cutaneous and proprioceptive afferents have access to circuits generating CMC, but that only a functionally relevant stimulus produces significant modulation of the background β-range CMC, providing further evidence that β-range CMC has an important role in sensorimotor integration.     

Facilitation of the human nociceptive reflex by stimulation of Aβ-fibres in a secondary hyperalgesic area sustained by nociceptive input from the primary hyperalgesic area

Hyperalgesia was induced in healthy volunteers by topical capsaicin applied on the dorsum of the foot within the receptive field of the sural nerve. Under presence of hyperalgesia different normally non-noxious conditioning stimuli were applied to the hyperalgesic area and the polysynaptic nociceptive spinal reflex and pain ratings were used to assess central excitability. The nociceptive reflex was measured in the knee extensor and flexor muscles evoked by electrical stimulation of the sural nerve trunk at an intensity of 1.5 times the initial reflex threshold (an intensity above the pain threshold). Thermal stimulation of the primary hyperalgesic area (re)established both on-going spontaneous pain and secondary hyperalgesia. Thus, increased nociceptive reflexes were recorded and increased pain intensity reported when Aβ-fibres in the secondary hyperalgesic area were activated concurrently with the reflex testing after a non-noxious thermal stimulation of the primary hyperalgesic area. The Aβ-fibre activation was achieved by continuous low-intensity electrical stimulation (40 Hz) that was initiated after on-going pain produced by the thermal stimulation had waned. The same measurement without prior thermal conditioning stimulation of the primary area resulted in no reflex facilitation, indicating rapid changes in the central excitability with existence of on-going nociceptive activity. This indicates that the development and maintenance of secondary hyperalgesia are dependent on sustained peripheral nociceptive activity. The study also shows that a central summation of nociceptive and non-nociceptive afferent activity can occur once secondary hyperalgesia is present.     

Cutaneomotor integration in humans is somatotopically organized at various levels of the nervous system and is task dependent

Integration of tactile afferent signals with motor commands is crucial for the performance of purposeful movements such as during manipulation of an object in the hand. To study the somatotopic organization of sensorimotor integration we applied electrical peripheral conditioning stimuli to a digit located near (homotopic stimulation) or distant from (heterotopic stimulation) relaxed or isometrically contracted intrinsic hand muscles at variable time intervals prior to transcranial magnetic stimulation (TMS). Cutaneous stimulation has previously been shown to modulate the amplitude of the motor evoked potential (MEP) and to shorten the duration of the silent period (SP) evoked by TMS. In relaxed target muscles the time-dependent modulation of TMS-evoked motor responses by homotopic conditioning stimulation differed from modulation by heterotopic stimulation. Similar differences in the modulation pattern evoked by homotopic and heterotopic conditioning stimulation were observed for two distinct target muscles of the hand (abductor digiti minimi, abductor pollicis brevis muscle). Differences in modulation were maximal when the conditioning stimulation was applied 25–30 ms and 150–200 ms prior to TMS. Comparison of the modulation of the amplitudes of MEPs evoked by transcranial electrical stimulation (TES) and the modulation of those evoked by TMS suggests that differences between homotopic and heterotopic stimulation originate subcortically at 25- to 30-ms and, at least partially, cortically at 150- to 200-ms interstimulus intervals. In isometrically contracted intrinsic hand muscles the degree to which the SP was shortened reflected the location and the timing of the conditioning stimulus. Shortening was maximal when the conditioning stimulus was applied nearest to the contracted target muscle and 20 ms prior to the test stimulus. In contrast to the SP duration, the MEP size in voluntarily contracted target muscles was unaffected by the location of the conditioning stimulus. The somatotopic gradient of SP shortening was abolished when the two target muscles were simultaneously activated isometrically. Together, our findings suggest that somatotopy of input-output relationships is implemented at both a spinal and a cortical level in the human central nervous system and may also depend on the motor task involved. Received: 25 August 1998 / Accepted: 11 June 1999     

Intracortical inhibition of lower limb motor-evoked potentials after paired transcranial magnetic stimulation

The aim of the present study was to determine the characteristics of intracortical inhibition in the motor cortex areas representing lower limb muscles using paired transcranial magnetic (TMS) and transcranial electrical stimulation (TES) in healthy subjects. In the first paradigm (n=8), paired magnetic stimuli were delivered through a double cone coil and motor evoked potentials (MEPs) were recorded from quadriceps (Q) and tibialis anterior (TA) muscles during relaxation. The conditioning stimulus strength was 5% of the maximum stimulator output below the threshold MEP evoked during weak voluntary contraction of TA (33±5%). The test stimulus (67±2%) was 10% of the stimulator output above the MEP threshold in the relaxed TA. Interstimulus intervals (ISIs) from 1–15 ms were examined. Conditioned TA MEPs were significantly suppressed (P<0.01) at ISIs of less than 5 ms (relative amplitude from 20–50% of the control). TA MEPs tended to be only slightly facilitated at 9-ms and 10-ms ISIs. The degree of MEP suppression was not different between right and left TA muscles despite the significant difference in size of the control responses (P<0.001). Also, conditioned MEPs were not significantly different between Q and TA. The time course of TA MEP suppression, using electrical test stimuli, was similar to that found using TMS. In the second paradigm (n=2), the suppression of TA MEPs at 2, 3, and 4 ms ISIs was examined at three conditioning intensities with the test stimulation kept constant. For the pooled 2- to 4-ms ISI data, relative amplitudes were 34±6%, 61±5%, and 98±9% for conditioning intensities of 0.95, 0.90, and 0.85× active threshold, respectively (P<0.01). In conclusion, the suppression of lower limb MEPs following paired TMS showed similar characteristics to the intracortical inhibition previously described for the hand motor area. Received: 21 June 1996 / Accepted: 23 May 1997     

Jaw-opening reflex after CO2 laser stimulation of the perioral region in man

CO₂ laser pulses selectively excite A-δ and C mechano-thermal nociceptors in the superficial layers of the skin. To study the jaw-opening reflex elicited by a purely nociceptive input, we delivered laser pulses to the perioral region in 15 subjects. Sensory threshold was very low (9 mJ/mm²). High-intensity noxious laser pulses (more than 4 × sensory threshold) evoked a single phase of electromyogram suppression (laser silent period, LSP) at an onset latency of 70 ms in the contracted masseter and temporal muscles, bilaterally. Even maximum-intensity laser pulses failed to activate the suprahyoid muscles. The recovery curves to paired laser stimuli showed that at short interstimulus intervals the test LSP was strongly suppressed. At about 380 ms it recovered to 50%, i.e. its recovery curve resembled that of the masseter late silent period after electrical mental nerve stimulation (SP2). In experiments studying the interaction with heterotopic stimuli and non-nociceptive responses, chin-taps or electrical shocks delivered to the supraorbital, infraorbital or mental nerves before laser stimulation strongly suppressed the LSP. A preceding perioral laser pulse strongly suppressed the masseter SP evoked by supraorbital stimulation and the SP2 evoked by mental stimulation, but left SP1 unaffected. We conclude that the perioral A-δ fibre input elicits a jaw-opening reflex simply by inhibiting the jaw-closers. The LSP response is mediated by a multisynaptic chain of brainstem interneurons and shares with the masseter SP2 part of the central circuit in the ponto-medullary region. We also propose that a common centre processes the various inputs for jaw opening. Received: 18 July 1997 / Accepted: 20 October 1997     

The pudendal nerve-evoked response in axial muscle

Summary In 39 Urethane-anesthetized rats we have recorded the afferent volley in the dorsal roots and the electrical activity of the lateral longissimus muscle and its motor nerves during electrical stimulation of a cutaneous branch of the pudendal nerve. Male and female rats were used; the females were ovariectomized and either pretreated with estradiol or left without hormonal treatment. Conduction velocities in the pudendal nerve were 54 m/s for the largest Abeta fibers and averaged 10 m/s for A-delta fibers. Excitation of pudendal nerve afferents strongly potentiated the firing of axial motoneurons, at stimulus currents below threshold for A-delta fibers. Trains of three shocks to the pudendal nerve were considerably more effective than double or single shock trains. Repetition rates as low as 1/s had a long lasting excitatory effect on the lateral longissimus muscle and the magnitude of the responses increased gradually for several seconds with continued stimulation. Recordings from the axons of the epaxial motoneurons of female rats showed a strong activation of neuronal firing with an onset latency of 5.8 ms from the last shock of a three ms, three shock train; the onset in male rats, 8.4 ms, differed significantly. Peak spike activity occurred at mean latencies of 11, 22 and 102 ms in both sexes. A period of depressed firing was usually present from 34 to 50 ms. Males differed in having a larger peak in activity at 102 ms, but the overall profile of the responses was similar in males and females. No differences were seen in the overall response patterns of the estrogen-treated and untreated females. Responses of comparable magnitude were seen with ipsilateral or contralateral pudendal nerve stimulation; these were facilitated by bilateral stimulation. In electromyographic recordings, the onset of unit firings was seen at 6.4 ms latency in response to pudendal nerve stimulation. This unit activity was consistent with the firing pattern seen in the muscle nerves.Supported by US PHS grant HD13795     

Impairments in the initial horizontal vestibulo-ocular reflex of older humans

To determine age-related changes, the initial horizontal vestibulo-ocular reflex (VOR) of 11 younger normal subjects (aged 20–32 years) was compared with that of 12 older subjects (aged 58–69 years) in response to random transients of whole-body acceleration of 1,000 and 2,800°/s² delivered around eccentric vertical axes ranging from 10 cm anterior to 20 cm posterior to the eyes. Eye and head positions were sampled at 1,200 Hz using magnetic search coils. Subjects fixed targets 500 cm or 15 cm distant immediately before the unpredictable onset of rotation in darkness. For all testing conditions, younger subjects exhibited compensatory VOR slow phases with early gain (eye velocity/head velocity, interval 35–45 ms from onset of rotation) of 0.90±0.02 (mean ± SEM) for the higher head acceleration, and 0.79±0.02 for the lower acceleration. Older subjects had significantly (P<0.0001) lower early gain of 0.77±0.04 for the higher head acceleration and 0.70±0.02 for the lower acceleration. Late gain (125–135 ms from onset of rotation) was similar for the higher and lower head accelerations in younger subjects. Older subjects had significantly lower late gain at the higher head acceleration, but gain similar to the younger subjects at the lower acceleration. All younger subjects maintained slow-phase VOR eye velocity to values ≥200°/s throughout the 250-ms rotation, but, after an average of 120 ms rotation (mean eccentricity 13°), 8 older subjects consistently had abrupt declines (ADs) in slow-phase VOR velocity to 0°/s or even the anticompensatory direction. These ADs were failures of the VOR slow phase rather than saccades and were more frequent with the near target at the higher acceleration. Slow-phase latencies were 14.4±0.4 ms and 16.8±0.4 ms for older subjects at the higher and lower accelerations, significantly longer than comparable latencies of 10.0±0.5 ms and 12.0±0.6 ms for younger subjects. Late VOR gain modulation with target distance was significantly attenuated in older subjects only for the higher head acceleration. Electronic Publication     

Reciprocal changes of excitability between tibialis anterior and soleus during the sit-to-stand movement

The excitability of spinal motoneurons is modified by central preparatory commands before muscle activation. In relatively complex long duration motor tasks such as the sit-to-stand (STS) movement, the central nervous system commands have to take into account the inputs from muscle, skin, and joint afferents during muscle contraction. We have investigated the changes occurring in tibialis anterior (TA) and soleus (SOL) motoneuronal excitability prior to and during the STS movement in normal subjects. Twelve healthy volunteers received the instruction to rise from a chair at the perception of an acoustic 'go' signal. Cortical transcranial magnetic stimuli (TMS) or peripheral nerve electrical stimuli (PNS) were used as test stimuli to elicit, respectively, the motor evoked potential (MEP) and the H reflex, at intervals of 50–1500 ms after the 'go' signal. Both the MEP and the H reflex were enhanced in the TA between 100 and 900 ms after the 'go' signal. At the same time there was inhibition of the H reflex but not of the MEP in the SOL. At the end of the STS movement, during quiet standing, the size of both the H reflex and the MEP of the TA were not different from those obtained in the sitting position. However, in SOL, the H reflex was smaller, and the MEP was larger, than at rest. Our observations suggest the participation of several mechanisms of control of motoneuronal excitability during the STS, ultimately leading to a dominant role of presynaptic inhibitory mechanisms in SOL during standing. Electronic Publication