Magnetic Motor-evoked Potentials Research Articles

Both Dorsal and Ventral Spinal Cord Pathways Contribute to Overground Locomotion in the Adult Rat

Identification of long tracts responsible for spontaneous locomotion is critical for spinal cord injury (SCI) repair strategies. We recently demonstrated that extensive demyelination of adult rat thoracic ventral columns, ventromedial, and ventrolateral white matter produces persistent, significant open-field hindlimb locomotor deficits. Locomotor movements resulting from stimulation of the pontomedullary locomotor region are inhibited by dorsolateral funiculus (DLF) lesions suggesting that important pathways for locomotion may also exist in the dorsal white matter. However, dorsal hemisections that interrupt dorsal columns/dorsal corticospinal tract (DC/CST) and DLF pathways do not produce persistent, severe locomotor deficits in the adult rat. We studied the contributions of myelinated tracts in the DLF and DC/CST to overground locomotion following complete conduction blockade of axons in the ventrolateral funiculus (VLF), a region important for locomotor movements and for transcranial magnetic motor-evoked potentials (tcMMEP). Animals received ethidium bromide plus photon irradiation to produce discrete demyelinating lesions sufficient to stop axonal conduction in the VLF, combined VLF + DLF, or combined VLF + DC/CST. Open-field BBB scores and tcMMEPs were studied at 1, 2, 3, and 4 weeks postlesion. VLF lesions resulted in mean BBB scores of 17 at 4 weeks. VLF + DC/CST and VLF + DLF lesions resulted in mean BBB scores of 15.9 and 11.1, respectively. TcMMEPs were absent in all lesion types confirming VLF conduction blockade throughout the study. Our data indicate that significant contributions to locomotion from myelinated pathways within the rat DLF can be revealed when combined with simultaneous compromise of the VLF.

Functional Redundancy of Ventral Spinal Locomotor Pathways

Identification of long tracts responsible for the initiation of spontaneous locomotion is critical for spinal cord injury (SCI) repair strategies. Pathways derived from the mesencephalic locomotor region and pontomedullary medial reticular formation responsible for fictive locomotion in decerebrate preparations project to the thoracolumbar levels of the spinal cord via reticulospinal axons in the ventrolateral funiculus (VLF). However, white matter regions critical for spontaneous over-ground locomotion remain unclear because cats, monkeys, and humans display varying degrees of locomotor recovery after ventral SCIs. We studied the contributions of myelinated tracts in the VLF and ventral columns (VC) to spontaneous over-ground locomotion in the adult rat using demyelinating lesions. Animals received ethidium bromide plus photon irradiation producing discrete demyelinating lesions sufficient to stop axonal conduction in the VLF, VC, VLF-VC, or complete ventral white matter (CV). Behavior [open-field Basso, Beattie, and Bresnahan (BBB) scores and grid walking] and transcranial magnetic motor-evoked potentials (tcMMEP) were studied at 1, 2, and 4 weeks after lesion. VLF lesions resulted in complete loss or severe attenuation of tcMMEPs, with mean BBB scores of 18.0, and no grid walking deficits. VC lesions produced behavior similar to VLF-lesioned animals but did not significantly affect tcMMEPs. VC-VLF and CV lesions resulted in complete loss of tcMMEP signals with mean BBB scores of 12.7 and 6.5, respectively. Our data support a diffuse arrangement of axons within the ventral white matter that may comprise a system of multiple descending pathways subserving spontaneous over-ground locomotion in the intact animal.

Lasting paraplegia caused by loss of lumbar spinal cord interneurons in rats: no direct correlation with motor neuron loss.

The aims of this study were to investigate further the role played by lumbar spinal cord interneurons in the generation of locomotor activity and to develop a model of spinal cord injury suitable for testing neuron replacement strategies. Adult rats received intraspinal injections of kainic acid (KA). Locomotion was assessed weekly for 4 weeks by using the Basso, Beattie, and Bresnahan (BBB) 21-point locomotor scale, and transcranial magnetic motor evoked potentials (MMEPs) were recorded in gastrocnemius and quadriceps muscles at 1 and 4 weeks. No changes in transcranial MMEP latency were noted following KA injection, indicating that the descending motor pathways responsible for these responses, including the alpha motor neurons, were not compromised. Rats in which KA injections included much of the L-2 segment (10 animals) showed severe locomotor deficits, with a mean BBB score of 4.5 +/- 3.6 (+/- standard deviation). Rats that received lesions rostral to the L-2 segment (four animals) were able to locomote and had a mean BBB score of 14.6 +/- 2.6. Three rats that received only one injection bilaterally centered at L-2 (three animals) had a mean BBB score of 3.2 +/- 2. Histological examination revealed variable loss of motor neurons limited to the injection site. There was no correlation between motor neuron loss and BBB score. Interneuron loss centered on the L-2 segment induces lasting paraplegia independent of motor neuron loss and white matter damage, supporting earlier suggestions that circuitry critical to the generator of locomotor activity (the central pattern generator) resides in this area. This injury model may prove ideal for studies of neuron replacement strategies.

The role of directly applied hypothermia in spinal cord injury.

The effect of intense local hypothermia was evaluated in a precision model of spinal canal narrowing and spinal cord injury in rats. The spinal cord injury was cooled with a custom cooling well used over the epidural surface. Basso, Beattie, and Bresnahan (BBB) motor scores and transcranial magnetic motor-evoked potential (tcMMEP) responses were used after injury to accurately evaluate neurologic recovery. This study was undertaken to determine whether the prognosis for neurologic recovery in a standardized rat spinal cord injury model is altered by the direct application of precisely controlled hypothermia to the area of injury. The role of hypothermia in the treatment of spinal cord injuries with neurologic deficits remains undefined. Hypothermia may decrease an area of spinal cord injury and limit secondary damage, therefore improving neurologic recovery. However, it has been difficult to consistently apply localized cooling to an area of spinal cord injury, and the use of systemic hypothermia is fraught with complications. This fact, along with the unavailability of a precise spinal cord injury model, has resulted in inconsistent results, both clinically and in the laboratory. In a rat model of spinal cord injury, 37 C and 19 C temperatures were used to study the role of hypothermia on neurologic recovery. Male Spraque-Dawley rats (n = 52; weight, 277.7 g) were anesthetized with pentobarbital and subjected to laminectomy at T10. The rats were divided into three groups: 1) placement of a 50% spacer in the epidural space (16 rats), 2) severe (25 g/cm) spinal cord injury (16 rats), 3) 50% spacer in combination with spinal cord injury (16 rats). Eight rats in each group were tested at two temperatures: normothermic (37 C) and hypothermic (19 C). With the use of a specially designed hypothermic pool placed directly over the spinal cord for 2 hours, epidural heating to 37 C, and epidural cooling to 19 C was accomplished. Simultaneous measurements of spinal cord and body temperatures were performed. The rats underwent behavior testing using the BBB motor scores and serial tcMMEPs for 5 weeks. Statistical methods consisted of Student's t tests, one-way analysis of variance, Tukey post hoc t tests and chi2 tests. There was a significant improvement in motor scores in rats subjected to hypothermia compared with those that were normothermic after insertion of a 50% spacer. This improvement was observed during the 5-week duration of follow-up. In the severe spinal cord injury group and the spinal cord injury-spacer groups, no significant improvement in motor scores were obtained when the spinal cord was exposed to hypothermia. The results demonstrate that there is a statistically significant (P < 0.05) improvement in neurologic function in rats subjected to hypothermia (19 C) after insertion of a spacer that induced an ischemic spinal cord injury. This indicates that directly applied hypothermia may be beneficial in preventing injury secondary to ischemic cellular damage. The data demonstrated minimal therapeutic benefit of hypothermia (19 C) after a severe spinal cord injury.

Topographic differences in task-dependent facilitation of magnetic motor evoked potentials.

To look for differences in task-dependent facilitation of magnetic motor evoked potentials (MEPs) in proximal and distal upper extremity muscles. Postexercise facilitation of MEPs has been demonstrated repeatedly in forearm muscles. Proximal muscles are prominently involved in limb stabilization, a largely isometric activity. In contrast, distal hand muscles specialize in precision movements. Based on these functional differences between proximal and distal muscles, we postulated that there might be topographic differences in task-dependent facilitation of MEPs. We studied the effects of isometric exercise and a precision grip task on MEPs in proximal and distal upper extremity muscles. Isometric exercise of the target muscle was associated with significant facilitation of MEPs in biceps and extensor carpi radialis muscles, but not in first dorsal interosseous or abductor digiti minimi muscles. In contrast, a precision grip task was associated with significant post-task facilitation of MEPs in first dorsal interosseous, but not in extensor carpi radialis. These differences in the facilitation of MEPs depending on the motor task and whether the muscle is proximal or distal may reflect the relative importance of proximal muscles in maintaining posture.

Facilitatory effect of thinking about movement on magnetic motor-evoked potentials

To investigate the facilitatory effect of thinking about movement on motor evoked potential (MEP) amplitude, we recorded MEPs in two test muscles during rest, with the subject thinking about contracting the test muscle but without subsequent contraction, and during 10% maximum voluntary contraction. Stimuli were delivered at 10% above resting motor threshold and at 90–100% stimulator output. H-reflexes, recorded in flexor carpi radialis, were obtained during rest and think conditions. MEP threshold was lower during the think condition ( P=0.004). At both stimulus intensities, median MEP amplitudes and areas were significantly ( P<0.001) larger during the think paradigm compared with rest. This effect was greater at the lower stimulus intensity. There was no significant difference in latency ( P=0.15). In 4/8 subjects, H-reflex amplitudes were mildly facilitated ( P<0.05) during the think condition. We conclude that thinking about movement without detectable EMG activity has a facilitatory effect on magnetic MEPs. The absence of a MEP latency shift between rest and think conditions and absence of a consistent increase in H-reflex amplitude suggests this effect occurs largely at the cortical level. In some subjects, however, an increase in spinal motoneuron excitability may also contribute.

Transcranial magnetic stimulation as a prognostic tool in stroke

Our aims were to evaluate the prognostic usefulness of magnetic motor evoked potentials (MMEPs) in ischemic stroke, to study the evolution of MMEP abnormalities and the relationships between MMEP abnormalities and infarction topography. We prospectively analyzed 50 consecutive ischemic stroke patients who were followed up to 1 year. MMEPs were recorded 1, 3, 30 and 90 days after stroke and we measured amplitudes and latencies/central motor conduction times (CMCTs) of MMEPs from hypothenar, biceps brachiallis, gastrocnemius and quadriceps. Univariate and multivariate analyses of the clinical and MMEPs data were performed. Patients with Rankin 0–3 at 1 year had had acutely MMEPs with shorter latencies and higher amplitudes than patients with Rankin 4–5 or deceased patients. Increased blood pressure correlated with increased survival, whereas increased heart rate and hyperglycemia correlated with increased mortality. The variables infarction size on second CT, age, and first day CMCT-S1 correctly classified 1 year outcome on discriminant analysis. The inclusion of MMEPs values increased the probability of correct classification from 76% to 84%. We conclude that in patients with nondisabling strokes MMEPs may have an independent value in the prediction of prognosis, increasing the accuracy of prognosis calculations made employing clinical and laboratory data. Topography of lesions should be considered when analyzing MMEP abnormalities after stroke.

Magnetic stimulation of the motor cortex: Clinical applications

Transcranial magnetic cortical stimulation provides the clinical neurophysiologist with a method to examine alterations in the function of central motor pathways in diseases affecting the motor system. The technique has great research potential and has led to increased understanding of intracortical physiology, corticospinal tract function, motor system plasticity and motor control. Subclinical cerebral and spinal cord lesions may be demonstrated, and the technique has a potential role for quantification and monitoring of disease progression, and for early prognostication after stroke. Intraoperative monitoring of motor evoked potentials (MEP) is of value during spinal cord surgery, but due to attenuation of magnetic MEPs during anaesthesia, transcranial electrical stimulation is more appropriate for intraoperative recordings.

The syndrome of delayed posthemiplegic hemidystonia, hemiatrophy, and partial seizure: clinical, neuroimaging, and motor-evoked potential studies

Magnetic motor-evoked potential (MEP) study of patients with the syndrome of delayed posthemiplegic hemidystonia, hemiatrophy, and partial or hemi-seizures ‘4-hemi’ syndrome) has not been described. Among 35 patients investigated for posthemiplegic movement disorders from February 1988 to January 1995, seven showed ‘4-hemi’ syndrome. Clinical work-up, magnetic resonance images (MRI) and/or computed tomography (CT) were performed in all. Transcranial MEP studies were done in five patients. The remote causes of `4-hemi' syndrome were neonatal stroke, trauma, and encephalitis in infancy. The dystonia may occur as long as a decade alter the initial insult. MRI or CT showed destructive lesion in the contralateral putamen (five patients), caudate (four), thalamus (five), and atrophy of the contralateral hemisphere (five). Other associations were porencephalic cyst, Wallerian degeneration, and asymmetric compensatory ventriculomegaly. MEP showed abnormalities in the affected upper limbs in four of five patients. The abnormalities were reduced amplitude of the compound muscle action potential following cortical stimulations with or without temporal dispersion, and with or without prolongation of its latency. The peripheral motor conductions following cervical stimulations were normal. MEP abnormalities may not be related to the hemiatrophy and the size of brain lesion per se. The hemidystonia is static after the second decade of life, and it is often difficult to treat.

Corticospinal direct response to transcranial magnetic stimulation in humans

The corticospinal motor evoked potential (MEP) response to transcranial magnetic stimulation of the motor cortex was investigated in comparison with the direct (D) response to electrical stimulation of the exposed motor cortex from the spinal epidural space in 7 neurologically normal patients during brain tumor surgery. The D response during operation was obtained by transcranial magnetic stimulation of the scalp over the areas of the cerebral motor cortex, the hand or arm areas. The magnetic induced D response showed a conduction velocity of 50.5–72.7 m/sec and was resistant to anesthesia and unaffected by muscle relaxants and tolerant to high frequency (500 Hz) paired magnetic stimulus, and the latencies of magnetic MEPs corresponded to those with direct electrical stimulation. Thus, recording of the D response by transcranial magnetic stimulation are useful for not only identifying the location of the motor cortex during intracranial surgery but also for non-invasive recording of pyramidal tract activity during extracranial surgery under general anesthesia.

Facilitation of magnetic motor evoked potentials during the mixed nerve silent period.

We studied motor neuron excitability during the mixed nerve silent period (MNSP) in a hand muscle using magnetic motor evoked potentials (MEPs) and F-waves. MEPs elicited between the V1 and V2 potentials of the MNSP were much larger than control MEPs elicited at rest, and were even comparable in size to control MEPs elicited during voluntary contraction. This facilitation of MEPs occurred without shortening of MEP latency, suggesting a supraspinal mechanism. MEPs were facilitated during the MNSP when elicited with a figure-8-shaped coil in a posterior-anterior orientation, but not when MEPs of the same size were elicited with the coil held in a lateral-medial orientation. F-waves elicited during the MNSP were variable between subjects, and not consistently different from control F-waves elicited at rest. Our findings may reflect increased cortical motor excitability during the MNSP, possibly related to activation of muscle afferents by mixed nerve stimulation.

The effects of propofol on rat transcranial magnetic motor evoked potentials.

INTRAOPERATIVE MONITORING OF motor evoked potentials (MEPs) may become a valuable test of spinal cord function during surgery. Unfortunately, MEP responses are affected by most common anesthetics. We studied the effect of intravenous propofol on transcranial magnetic MEPs (tcMMEPs) in the rat. Baseline tcMMEPs were recorded before administration of the drug. Each rat then received three induction doses of propofol, 10, 5, and 5 mg/kg (totaling 10, 15, and 20 mg/kg) and three successive 20-minute infusion doses at rates of 10, 20, and 40 mg/kg/h, respectively. An MEP intensity series was performed after each induction dose, during each infusion, and during a 20-minute recovery period. tcMMEPs recorded during the induction period demonstrated a significant, dose-dependent increase in onset latency and a marked decrease in amplitude. Infusion tcMMEPs displayed increased onset latencies but demonstrated a significant change in amplitudes only after the largest infusion dose. The MEPs approached baseline levels after discontinuation of the propofol. This study demonstrates that tcMMEPs can be successfully recorded from the rat during propofol anesthesia.

TRANSCRANIAL MAGNETIC MOTOR-EVOKED POTENTIALS IN SCOLIOSIS SURGERY

Spinal cord monitoring using SSEPs is an accepted adjunct in the surgical correction of spinal deformities, but does not directly assess motor function. Motor-evoked potentials have been introduced in an effort to meet this important need. In this series of 18 patients, the feasibility of intraoperative monitoring using transcranial magnetic motor-evoked potentials is documented. The potential value of this neurophysiologic monitoring technique, as well as the pitfalls in interpretation, are reviewed.

PS-11-1 Inhibitory effect onto magnetic motor evoked potentials (MEPs) by peripheral nerve conditioning stimulus

PS-11-1 Inhibitory effect onto magnetic motor evoked potentials (MEPs) by peripheral nerve conditioning stimulus

Modulation of motor activity by cutaneous input: inhibition of the magnetic motor evoked potential by digital electrical stimulation

We examined the inhibitory effect of a brief train of digital (D2) electrical stimuli at 4 times perception threshold on transcranial magnetic motor evoked potentials (MEPs) recorded from abductor pollicis brevis (APB) and flexor carpi radialis (FCR) muscles ipsilateral to the side of D2 stimulation. We compared this to the inhibitory effect of ipsilateral D2 stimulation on averaged rectified EMG recorded at 10% maximum voluntary contraction and on F-responses and H-reflexes recorded from these same muscles. We also compared MEPs recorded following D2 stimulation just above perception threshold to MEPs following higher intensity D2 stimulation. As well, we assessed the effect of preceding D2 stimulation on MEPs recorded from a relaxed versus tonically contracted hand muscle. D2 stimulation elicited a triphasic response of modest MEP facilitation followed by inhibition and further facilitation. The duration and onset of MEP inhibition correlated with those of the initial period of rectified EMG inhibition, however, the magnitude of MEP inhibition was generally less than the magnitude of EMG inhibition, consistent with a greater inhibitory effect of digital afferents on smaller motor neurons. MEN were not facilitated during the rebound of EMG activity (the E2 period) that usually followed the initial period of EMG inhibition (I1 period). The behavior of H-reflexes and F-responses following ipsilateral D2 stimulation suggested that inhibition of both EMG and MEPs is not mediated via presynaptic inhibition of la afferents, and that inhibition is augmented by descending rather than segmental input to spinal motor neurons. Tonic contraction of the target muscle during D2 stimulation decreased the inhibitory effect of the preceding digital stimulus possibly due to recruitment of larger spinal motor neurons less likely to be inhibited by cutaneous input.

Magnetic Motor Evoked Potentials during Methohexital Anesthesia in the Dog

MAGNETIC MOTOR EVOKED potentials (MMEPs) were recorded from the right cranial tibial muscle after magnetic stimulation of the left motor cortex in six dogs sedated with oxymorphone. Anesthesia was induced with an intravenous bolus of 5.5 mg/kg of methohexital and maintained with a methohexital infusion. The dogs inspired 100% oxygen during anesthesia. Blood pressure, heart rate, respiratory rate, esophageal temperature, and end-tidal carbon dioxide tension were recorded. The depth of anesthesia was increased until the amplitude of the MMEP was less than 5% of the control value, and the dogs were then allowed to recover. Every 5 minutes during anesthesia, a blood sample was taken for methohexital assay and at the same time, four replicate MMEPs were recorded. Plasma methohexital levels were significantly (P < 0.05) correlated with heart rate (ρ = 0.38) and end-tidal carbon dioxide tension (ρ = 0.49) and negatively correlated with respiratory rate (ρ = −0.74). There was no significant correlation between blood pressure and methohexital levels. The dogs regained consciousness at a plasma methohexital level of 10.4 ± 3.8 μg/ml (mean ± SD). The amplitude of the MMEP decreased significantly with increasing methohexital levels. In four dogs, the relationship was reasonably linear. The MMEP disappeared at a plasma methohexital level of 23 ± 6.6 μg/ml. The latency of onset of the MMEP increased significantly from its control value of 14.7 ± 1.0 ms to 17.5 ± 1.3 ms at the highest methohexital levels at which MMEPs were recordable. This study demonstrated that MMEPs can be reliably recorded under methohexital anesthesia.

Magnetic Motor Evoked Potentials during Methohexital Anesthesia in the Dog

Magnetic motor evoked potentials (MMEPs) were recorded from the right cranial tibial muscle after magnetic stimulation of the left motor cortex in six dogs sedated with oxymorphone. Anesthesia was induced with an intravenous bolus of 5.5 mg/kg of methohexital and maintained with a methohexital infusion. The dogs inspired 100% oxygen during anesthesia. Blood pressure, heart rate, respiratory rate, esophageal temperature, and end-tidal carbon dioxide tension were recorded. The depth of anesthesia was increased until the amplitude of the MMEP was less than 5% of the control value, and the dogs were then allowed to recover. Every 5 minutes during anesthesia, a blood sample was taken for methohexital assay and at the same time, four replicate MMEPs were recorded. Plasma methohexital levels were significantly (P < 0.05) correlated with heart rate (p = 0.38) and end-tidal carbon dioxide tension (p = 0.49) and negatively correlated with respiratory rate (p = 0.74). There was no significant correlation between blood pressure and methohexital levels. The dogs regained consciousness at a plasma methohexital level of 10.4 +/- 3.8 micrograms/ml (mean +/- SD). The amplitude of the MMEP decreased significantly with increasing methohexital levels. In four dogs, the relationship was reasonably linear. The MMEP disappeared at a plasma methohexital level of 23 +/- 6.6 micrograms/ml. The latency of onset of the MMEP increased significantly from its control value of 14.7 +/- 1.0 ms to 17.5 +/- 1.3 ms at the highest methohexital levels at which MMEPs were recordable. This study demonstrated that MMEPs can be reliably recorded under methohexital anesthesia.

A computer-controlled, closed-loop infusion system for infusing muscle relaxants: Its use during motor-evoked potential monitoring

A microcomputer-controlled closed-loop infusion system (MCCLIS) has been developed that provides stable intraoperative levels of partial neuromuscular blockade. Complete neuromuscular blockade interferes with intraoperative motorevoked potential (MEP) monitoring used for patients undergoing surgical procedures that place them at risk for spinal cord ischemia. Nine patients were studied during which the MCCLIS maintained stable levels of partial neuromuscular blockade and allowed transcranial magnetic motor-evoked potential (TcM-MEP) monitoring during thoracoabdominal aortic aneurysmectomy. The use of TcM-MEP for monitoring intraoperative spinal cord function was balanced against surgical considerations for muscle relaxation with 80% to 90% neuromuscular blockade fulfilling each requirement. Intraoperative adjustment of partial neuromuscular blockade to facilitate TcM-MEP monitoring was also possible with the MCCLIS. The MCCLIS should allow for further investigation into the sensitivity, specificity, and predictability of TcM-MEP monitoring for any patient at risk for intraoperative spinal cord ischemia including those undergoing thoracoobdominal aortic aneurysmectomy.

Motor Evoked Potential Study with Magnetic Stimulation In Ischemic Stroke Patients

This study was undertaken to evaluate the clinical usefulness of magnetic motor evoked potential (MEP) in the diagnosis of stroke and predicting the motor improvement following stroke. The cortical, cervical and lumbar stimulations were performed in the case of 24 healthy controls and 24 to a target muscle between after transcranial stimulation and after cervical or lumbar stimulation. There was no case showing no response in controls. But in 11 out of 24 ischemic patients, we could not get cortical MEP. Mean CMCT of abductor pollicis brevis muscle was not significantly different in controls and stroke patients in whom MEPs were recorded. There were significant differences between mean CMCT of normal controls and that of stroke patients showing MEPs in AH Muscle. MEP Results from testing the stroke patients were correlated with site of lesion, degree of motor weakness and motor improvement after 1 to 2 months. These results suggest that magnetic MEP is easy and useful in electrophysiological test of central motor pathway and is useful indicator for representing the motor weakness and predicting the motor outcome in acute ischemic stroke patients.

Facilitation of magnetic motor evoked potential; during the cortical stimulation silent period

We investigated the relationship between stimulus intensity and magnetic motor evoked potentials (MEPs) elicited 100 msec after a conditioning stimulus that was 25% of stimulator output above resting motor threshold (RMT) during tonic contraction of abductor pollicis brevis. In five subjects, MEPs elicited with stimuli less than 25% above RMT were inhibited during the EMG cortical stimulation silent period (CSSP) produced by the conditioning stimulus, relative to MEPs elicited with the test stimulus given at rest. However, increasing the intensity of the test stimulus increased the amplitude of MEPs elicited during the CSSP relative to MEPs elicited at rest, such that MEPs elicited with stimuli 30 to 45% above RMT were facilitated during the CSSP. Increasing the intensity of the test stimulus also increased the amplitude of MEPs elicited with paired stimulation at rest, and caused facilitation in one subject. Since facilitation of MEPs was never accompanied by shortening of MEP latency, our observations point to supraspinal facilitory mechanisms. We suggest that facilitation of MEPs during the CSSP reflects temporal and spatial summation of conditioning and test stimuli.