The effect of pyramidal stimulation upon tail muscle motoneurons in the decerebrate cat

This study aimed to determine the effects of the corticospinal tract (CST) on the motoneurons innervating the tail muscles in cats. The stimulation of the pyramidal tract predominantly evoked excitatory postsynaptic potentials (EPSPs; 48/90 motoneurons: 53%). Single-pulse stimulation produced EPSPs in 18 of 48 motoneurons, but double shocks evoked postsynaptic potentials in most of the remaining cells (26/48). Monosynaptic excitatory connections between pyramidal tract fibers and tail motoneurons were confirmed in 4 motoneurons. Inhibitory postsynaptic potentials (IPSPs) were recorded from motoneurons innervating long tendinous tail muscles (7/90: 8%) and the shortest neuronal pathways of IPSPs were shown to be disynaptic pathways. Interactions between the CST and reflex pathways from low-threshold muscle and cutaneous afferents innervating the tail and hindlimbs were observed.     

Concurrent excitation of the opposite motor cortex during transcranial magnetic stimulation to activate the abdominal muscles

The study investigated the potential for stimulation of both motor cortices during transcranial magnetic stimulation (TMS) to evoke abdominal muscle responses. Electromyographic activity (EMG) of transversus abdominis (TrA) was recorded bilaterally in eleven healthy volunteers using fine-wire electrodes. TMS at 120% motor threshold (MT) was delivered at rest and during 10% activation at 1 cm intervals from the midline to 5 cm lateral, along a line 2 cm anterior to the vertex. The optimal site to evoke responses in TrA is located 2 cm lateral to the vertex. When bilateral abdominal responses were evoked at or lateral to this site, onset of ipsilateral motor evoked potentials (MEPs) were 3–4 ms longer than contralateral MEPs. The difference between latencies is consistent with activation of faster crossed-, and slower uncrossed-corticospinal pathways from one hemisphere. However, latencies of MEPs were similar between sides when stimulation was applied more medially and were consistent with concurrent activation of crossed corticospinal tracts on both sides. The findings suggest that stimulation of both motor cortices is possible when TMS is delivered less than 2 cm from midline. Concurrent stimulation of both motor cortices can be minimised if TMS is delivered at least 2 cm lateral to midline.     

Electrical stimulation of human corticospinal axons at the level of the lumbar spinal segments

Electrical stimulation over the mastoids or thoracic spinous processes has been used to assess subcortical contribution to corticospinal excitability, but responses are difficult to evoke in the resting lower limbs or are limited to only a few muscle groups. This might be mitigated by delivering the stimuli lower on the spinal column, where the descending tracts contain a greater relative density of motoneurons projecting to lower limb muscles. We investigated activation of the corticospinal axons innervating tibialis anterior (TA) and rectus femoris (RF) by applying a single electrical stimulus over the first lumbar spinous process (LS). LS was paired with transcranial magnetic stimulation (TMS) at interstimulus intervals (ISIs) of ?16 (TMS before LS) to 14 ms (LS before TMS). The relationship between muscle contraction strength (10%–100% maximal) and the amplitude of single‐pulse TMS and LS responses was also investigated. Compared to the responses to TMS alone, responses to paired stimulation were significantly occluded in both muscles for ISIs ≥?8 ms (p ≤ 0.035), consistent with collision of descending volleys from TMS with antidromic volleys originating from LS. This suggests that TMS and LS activate some of the same corticospinal axons. Additionally, the amplitude of TMS and LS responses increased with increasing contraction strengths with no change in onset latency, suggesting responses to LS are evoked transsynaptically and have a monosynaptic component. Taken together, these experiments provide evidence that LS is an alternative method that could be used to discern segmental changes in the corticospinal tract when targeting lower limb muscles.     

Motor-evoked potentials: unusual findings.

OBJECTIVE: The aims of this study were to present rare findings of motor evoked potentials (MEPs) in 3 patients with spastic paraparesis and to show that careful interpretation is indispensable in experiments done with very high intensity stimulation. METHODS: The conduction along several segments of the descending tracts was studied by our previously published method in 3 patients with spastic paraparesis. RESULTS: The threshold for activation of descending tracts was markedly increased in all the patients. In one patient, both transcranial electrical and magnetic cortical stimulation elicited responses with 4 different latencies. They were compatible with the latencies of I1-, D(D1)-, D2- or D3-waves. Very high intensity stimulation elicited D2 waves (activation around the cerebral peduncle) or D3 waves (activation at the foramen magnum level). In the other two patients, unexpectedly, the latency of responses to foramen magnum level stimulation was longer than the cortical latency. Foramen magnum and spinal cord stimulation could not excite the corticospinal tract but activated other slowly conducting descending tracts (about 20 m/s), whereas cortical stimulation activated the corticospinal tract. CONCLUSIONS: The site of activation following cortical stimulation was variable when very high intensity stimulation is used. The descending tracts that contribute to the onset of electromyographic (EMG) responses may not be the same after cortical and spinal stimulation in patients with severely affected corticospinal tract, especially when using very high intensities of stimulation. Such factors complicate the interpretation of EMG responses obtained in patients with severely affected corticospinal tracts.     

Postsynaptic potentials of motor neurons in the nucleus of the hypoglossal nerve in cats, evoked by rubrofugal impulses

The effects of ipsi- and contralateral red nuclei stimulation on the hypoglossal motoneurons were studied in the cats under chloralose-nembutal anesthesia. Repetitive ipsi- and contralateral rubrofugal volleys evoked PSPs in 35 (69%) from 51 investigated motoneurons (3-5 stimuli of threshold intensity at frequency 500-600 per/s were used). EPSPs appeared in 33 motoneurons with latencies from 3.5 to 14.0 ms (mean value 5.7 +/- 0.75 ms for ipsilateral and 6.8 +/- 0.8 ms for contralateral rubral stimulations). In two motoneurons IPSPs were observed with latency 6.2 ms. Stimulation of the lingual nerve evoked EPSPs and action potentials in 31 motoneurons and IPSPs in 4 motoneurons. 16 motoneurons which could not be activated by rubral stimulation also responded by IPSPs to lingual nerve stimulation. The presented data testify to the existence of two rubrobulbar systems connected by polysynaptic pathways mainly with motoneurons of tongue retractor muscle.     

Potentiating paired corticospinal-motoneuronal plasticity after spinal cord injury

Background

Paired corticospinal-motoneuronal stimulation (PCMS) increases corticospinal transmission in humans with chronic incomplete spinal cord injury (SCI).Objective/Hypothesis: Here, we examine whether increases in the excitability of spinal motoneurons, by performing voluntary activity, could potentiate PCMS effects on corticospinal transmission.

Subthreshold corticospinal control of anticipatory actions in humans

Previous findings suggest that, by influencing the subthreshold state of motoneurons, the corticospinal pathways can set and reset the threshold position at which wrist muscle recruitment begins. Here we assumed that the corticospinal system can change the threshold position in a similar way before anticipated perturbation to pre-determine an appropriate emerging response to it. We first analyzed motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) applied to the wrist area of motor cortex before unloading of preloaded wrist flexors, i.e. before the subsequent involuntary wrist motion to another position (natural unloading). Subjects then learned to diminish the post-unloading movement extent without activating antagonist (extensor) muscles before unloading or making intentional movement corrections after unloading (adjusted unloading). Although activity levels of wrist muscles before unloading were similar, MEPs of extensor but not pre-loaded flexor muscles were higher before adjusted unloading. We also applied TMS in combination with a torque pulse that shortened extensor muscles such that the MEP occurred when the motoneuronal excitability was minimized. Although diminished following muscle shortening, MEPs before adjusted unloading were still higher than before natural unloading. Results suggest that the corticospinal system, possibly together with other descending systems participated in the tonic subthreshold facilitation of antagonist motoneurons before adjusted unloading, which appears sufficient in modifying motor commands and motion leading to adjusted unloading. This study reinforces previous findings that descending systems, in particular, the corticospinal system can employ threshold position control during and after learning a novel action.     

Pseudo-bilateral hand motor responses evoked by transcranial magnetic stimulation in patients with deep brain stimulators.

OBJECTIVES: In 3 of 5 patients with dystonia and bilaterally implanted deep brain stimulating electrodes, focal transcranial magnetic stimulation (TMS) of one motor cortex elicited bilateral hand motor responses. The aim of this study was to clarify the origin of these ipsilateral responses. METHODS: TMS and electrical stimulation of corticospinal fibres by the implanted electrodes were performed and the evoked hand motor potentials were analysed. RESULTS: In comparison with responses elicited by contralateral motor cortex stimulation, ipsilateral responses were smaller in amplitude (3.0+/-1.4 versus 5.8+/-1.5 mV), had shorter peak latencies (first negative peak: 20.9+/-0.8 versus 25.1+/-0.4 ms) and were followed by a shorter-lasting silent period (46+/-4 versus 195+/-35 ms). Ipsilateral responses following TMS had similar peak latencies to responses elicited subcortically by deep brain stimulation (DBS) (20.4+/-0.9 ms). CONCLUSIONS: Hand motor responses ipsilateral to TMS result from a subcortical activation of corticospinal fibres, via the implanted electrode in the other hemisphere, secondary to currents induced by TMS in subcutaneous wire loops that underlie the magnetic coil. Studies of TMS in patients with DBS have to take this potential source of confounding into account.     

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.     

The triple stimulation technique to study central motor conduction to the lower limbs.

OBJECTIVE: To quantify the percentage of motor units of a foot muscle that can be activated by transcranial magnetic stimulation (TMS) in normal subjects and patients. METHODS: We adapted the recently described triple stimulation technique (TST) for recordings from abductor hallucis (AH). Conventional motor evoked potentials (MEPs) of this muscle are usually small and variable in shape, because of an important temporal desynchronization of the TMS induced spinal motor neuron discharges. The TST allows 'resynchronization' of these discharges and thereby a quantification of the proportion of motor units activated by TMS. The lower limb (LL-) TST was applied to 33 sides of 18 normal subjects and 51 sides of 46 patients with multiple sclerosis, amyotrophic lateral sclerosis, or spinal cord disorders. RESULTS: In healthy subjects, the LL-TST demonstrated that TMS achieves activation of virtually all motor neurons supplying the AH. In 33 of 51 patient sides, abnormal LL-TST responses suggested corticospinal conduction failures of various degrees. The LL-TST was 2.54 times more sensitive to detect central conduction failures than the conventional LL-MEPs. Combining the LL-TST with TST of the upper limbs further increased the sensitivity to detect a conduction failure by 1.50 times. CONCLUSION: The LL-TST markedly improves the examination of corticospinal pathways.     

A transcranial magnetic stimulation study for the investigation of corticospinal motor pathways in children with cerebral palsy

The aim of this study is to perform transcranial magnetic stimulation (TMS)-based investigation of corticospinal motor pathways in children with cerebral palsy (CP) secondary to hypoxic-ischemic encephalopathy (HIE). TMS parameters including motor evoked potentials (MEPs) and central motor conduction time (CMCT) were recorded in 38 children with CP and 46 age-matched healthy controls. The z-score of MEPs were analyzed with respect to the types of MRI patterns of cortical involvement in children with CP. MEP latency values were correlated with the weight and height of children and to reflect the maturation of the corticospinal pathway. TMS evoked MEPs with prolonged onset latencies in 64% of children with CP while 10% of the CP group failed to elicit MEPs. Related with the MRI pattern, multicystic encephalomalacia (89%) was associated with the highest rates of abnormal cortical MEPs, as followed by periventricular leukomalacia (80%), basal ganglia involvement (66%) and focal cortical involvement (60%) patterns. Children with CP as compared with healthy controls had similar CMCT values on the upper and lower extremities in children with all cortical MR patterns. MEP abnormalities with TMS were consistent with the extent of motor cortex lesions on MRI patterns in CP children with HIE.     

Modulation of single motor unit discharges using magnetic stimulation of the motor cortex in incomplete spinal cord injury

OBJECTIVES: Motor evoked potentials (MEPs) and inhibition of voluntary contraction to transcranial magnetic stimulation (TMS) of the motor cortex have longer latencies than normal in patients with incomplete spinal cord injury (iSCI) when assessed using surface EMG. This study now examines the modulation of single motor unit discharges to TMS with the aim of improving resolution of the excitatory and inhibitory responses seen previously in surface EMG recordings. METHODS: A group of five patients with iSCI (motor level C4-C7) was compared with a group of five healthy control subjects. Single motor unit discharges were recorded with concentric needle electrodes from the first dorsal interosseus muscle during weak voluntary contraction (2%-5% maximum). TMS was applied with a 9 cm circular stimulating coil centred over the vertex. Modulation of single motor unit discharges was assessed using peristimulus time histograms (PSTHs). RESULTS: Mean (SEM) threshold (expressed as percentage of maximum stimulator output (%MSO)) for the excitatory peak (excitation) or inhibitory trough (inhibition) in the PSTHs was higher (p<0.05) in the patients (excitation = 47.1 (5.9) %MSO; inhibition = 44.3 (3.2) %MSO) than in controls (excitation=31.6 (1.2) %MSO; inhibition = 27.4 (1.0) %MSO). Mean latencies of excitation and inhibition were longer (p<0.05) in the patients (excitation=35 (1.8) ms; inhibition = 47.1 (1.8) ms) than in the controls (excitation = 21.1 (1.6) ms; inhibition = 27 (0.4) ms). Furthermore, the latency difference (inhibition-excitation) was longer (p<0.05) in the patients (10.4 (2.1) ms) than in the controls (6.2 (0.6) ms). CONCLUSION: Increased thresholds and latencies of excitation and inhibition may reflect degraded corticospinal transmission in the spinal cord. However, the relatively greater increase in the latency of inhibition compared with excitation in the patients with iSCI may reflect a weak or absent early component of cortical inhibition. Such a change in cortical inhibition may relate to the restoration of useful motor function after iSCI.     

Nonspecific facilitation of responses to transcranial magnetic stimulation.

We examined the effect of facial muscle contraction and eye movements on motor evoked potentials (MEPs) from the abductor pollicis brevis muscle (APB) evoked by transcranial magnetic stimulation (TMS). The hypothesis was that activity of large cortical regions (face) influences the excitability of spinal motoneurons via cortical or subcortical pathways. MEPs were recorded in 12 healthy subjects during the following conditions: (1) rest; (2) facial muscle contraction; (3) eye movements; (4) 10% precontraction of the target muscle; and (5) simultaneous target muscle precontraction and facial muscle contraction. In 9 subjects, spinal motoneuron excitability was assessed by measurements of F waves during the same facilitation maneuvers. Activation of eye and facial muscles clearly facilitated MEPs from the APB. The facilitation of MEP size during nonspecific maneuvers was almost similar to that obtained by target muscle precontraction, whereas shortening of latencies was significantly smaller. The occurrence and amplitude of F waves increased in parallel with MEP size during specific and nonspecific facilitation, pointing to spinal motoneuronal threshold changes as a potential facilitatory mechanism by facial and eye muscle activation. The different MEP latencies during specific and nonspecific facilitation were not explained by different spinal motoneuron excitability, but raise the possibility that supraspinal mechanisms contributed to nonspecific facilitation.     

Postsynaptic potentials of motor neurons of neck muscles in the cat evoked by stimulation of the horizontal semicircular canals

PSPs, evoked by stimulation of the ipsi- and contralateral horizontal semicircular canals (HSC) in motoneurons of neck muscles, were studied in acute experiments on cats under chloralose-nembutal anesthesia. Ipsilateral stimulation evoked EPSP with latencies ranging from 1.8 to 10.0 ms in 25 motoneurons and IPSP with latencies 1.9-3.9 ms in 10 motoneurons. Calculation of conduction time from ipsilateral canal via Deiters nucleus to neck motoneurons gives reason to consider EPSP with latencies less than 3.8 ms as disynaptic, and those with greater latencies as polysynaptic. Contralateral stimulation evoked EPSP with latencies 1.8-6.0 ms in 19 motoneurons and IPSP with latencies 3.2 and 3.9 ms in 2 motoneurons. Possible pathways conducting these influences and their functional role are discussed.     

Neurophysiological observations on corticospinal projections to the upper limb in subjects with Rett syndrome.

The aim of the present study was to investigate the excitability of corticospinal neurons and the integrity of their projections to the alpha motor neurons through the corticospinal tract in subjects of different ages with Rett syndrome. Electromagnetic stimulation of the motor cortex and cervical motor roots was used to evoke motor action potentials in the biceps brachii and hypothenar muscles. The phasic stretch reflex in the biceps brachii was also recorded to study the excitability of spinal alpha motor neurons. Motor cortex stimulation evoked motor action potentials at low threshold and with abnormally short latencies and prolonged durations. In contrast cervical motor root stimulation resulted in responses of normal latency and duration. The phasic stretch reflex had a low threshold, short latency and prolonged duration. It is concluded that in Rett syndrome the corticospinal pathway is intact. The results suggest disordered synaptic control of the Betz cell of the motor cortex and/or the spinal alpha motor neuron, although the involvement of the latter might be a consequence of dysfunction in supraspinal descending motor pathways.     

Direct demonstration of long latency cortico-cortical inhibition in normal subjects and in a patient with vascular parkinsonism.

OBJECTIVE: The motor evoked potential to a single suprathreshold transcranial magnetic stimulus (TMS) is suppressed by a preceding stimulus given 100-200 ms before (long latency intracortical inhibition, LICI). The effect is enhanced in patients with Parkinson's disease. Although previous studies have agreed that the effect is cortical, there is disagreement over exactly which cortical mechanisms are involved. The aim of this study was to provide further evidence for cortical involvement in LICI. METHODS: Recordings of corticospinal volleys evoked by the TMS stimulation were made from electrodes inserted into the cervical epidural space of 4 conscious subjects. Three of the patients had received the electrodes for treatment of lumbo-sacral pain; the other patient had vascular parkinsonism, and had the electrode implanted to evaluate its effect on cerebral blood flow. The number and amplitude of the volleys were compared with and without a conditioning stimulus. RESULTS: In 3 pain patients, a conditioning stimulus suppressed the later components of the corticospinal volley (I2 and later waves) when the interval between stimuli was 100-150 ms; at 50 ms the responses were enhanced. Early components of the volley were not affected. Inhibition was much more pronounced and involved all descending volleys except the D wave in the patient with vascular parkinsonism. CONCLUSIONS: LICI, which is conventionally described in EMG recordings, is also evident in recordings of descending corticospinal volleys and appears enhanced in a patient with vascular parkinsonism.     

A survey of spinal collateral actions of feline ventral spinocerebellar tract neurons

The aim of this study was to identify spinal target cells of spinocerebellar neurons, in particular the ventral spinocerebellar tract (VSCT) neurons, giving off axon collaterals terminating within the lumbosacral enlargement. Axons of spinocerebellar neurons were stimulated within the cerebellum while searching for most direct synaptic actions on intracellularly recorded hindlimb motoneurons and interneurons. In motoneurons the dominating effects were inhibitory [inhibitory postsynaptic potentials (IPSPs) in 67% and excitatory postsynaptic potentials (EPSPs) in 17% of motoneurons]. Latencies of most IPSPs indicated that they were evoked disynaptically and mutual facilitation between these IPSPs and disynaptic IPSPs evoked by group Ia afferents from antagonist muscles and group Ib and II afferents from synergists indicated that they were relayed by premotor interneurons in reflex pathways from muscle afferents. Monosynaptic EPSPs from the cerebellum were accordingly found in Ia inhibitory interneurons and intermediate zone interneurons with input from group I and II afferents but only oligosynaptic EPSPs in motoneurons. Monosynaptic EPSPs following cerebellar stimulation were also found in some VSCT neurons, indicating coupling between various spinocerebellar neurons. The results are in keeping with the previously demonstrated projections of VSCT neurons to the contralateral ventral horn, showing that VSCT neurons might contribute to motor control at a spinal level. They might thus play a role in modulating spinal activity in advance of any control exerted via the cerebellar loop.     

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.     

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.     

Synaptic interactions of individual motor neurons of the spinal cord of the carp

The interaction between motoneurons was studied in the isolated spinal cord of the fish (Cyprinus carpio) by the recording of elementary EPSPs evoked in a motoneuron by intracellular stimulation of adjacent motoneuron. These EPSPs are mediated mainly by electrical transmission as evidenced by their short or negligible latencies, stable amplitudes and bidirectional transmission between motoneurons. In some cells double-component elementary EPSPs were revealed which indicate dual (electro-chemical) mode of transmission between some motoneurons.