Percutaneous electrical stimulation of corticospinal pathways at the level of the pyramidal decussation in humans

Stimulation over the base of the skull can activate descending motor pathways to produce electromyographic (EMG) responses in muscles of the arm and leg. The evoked EMG responses were larger when the muscles were preactivated by a small voluntary contraction compared to when they were completely relaxed. The latency of these responses in preactivated muscles was approximately midway between that produced by electrical stimulation over the motor cortex, and by electrical stimulation over the cervical enlargements. With horizontally spaced electrodes, the latency difference between cortical and brainstem stimulation was 1.8 milliseconds in all muscles tested. The latency difference between cervical and brainstem stimulation was 3.9 milliseconds for the first dorsal interosseous and 2.6 milliseconds for tibialis anterior muscles. These values suggest that brainstem stimulation occurs at the level of the cervicomedullary junction. With vertically spaced electrodes in the midline, stimulation often occurs at a higher level. The EMG responses from brainstem stimulation differed from those following cortical stimulation in two ways: (1) They were simpler in form, and (2) their onset latency was the same in active as it was in relaxed muscles. This suggests that brainstem stimulation evoked a large descending motor volley in comparison with the multiple volleys that cortical stimulation can produce. Collision experiments between cortical and brainstem volleys indicated that the major part of the responses evoked by brainstem stimulation were conducted via the large-diameter component of the corticospinal tract.     

Descending volleys evoked by transcranial magnetic stimulation of the brain in conscious humans: effects of coil shape.

OBJECTIVES: To directly compare the volleys evoked by figure-of-eight and circular magnetic coil stimulation of the motor cortex and to correlate the descending volleys with the EMG responses in distal hand muscles. METHODS: Descending corticospinal volleys were recorded from an electrode inserted into the cervical epidural space of two conscious human subjects after transcranial stimulation of the hand area of the motor cortex. We compared volleys evoked by stimulation with (a) a figure-of-eight coil inducing posterior-anterior or latero-medial currents in the brain, (b) a large circular coil centred at the vertex inducing clockwise currents in the brain, and (c) anodal electric pulses. RESULTS: For a given amplitude of EMG response in the first dorsal interosseous muscle, volleys were larger after stimulation with a circular than a figure-of-eight coil. In addition, the D wave evoked by circular coil stimulation had a longer latency than the anodal D wave, and increased in amplitude when stimulation was given during voluntary contraction. CONCLUSIONS: We conclude that stimulation with a large circular coil activates descending outputs less selectively than figure-of-eight coil stimulation and that it is capable of activating pyramidal neurones at the initial segment region.     

Functional differentiation of motor units in human opponens pollicis muscle.

Studies were made on the parameters of the single contraction and the size of the summated equivalent potential determined through location of motor units in human opponens pollicis muscles upon electrical stimulation and during voluntary activity. The investigation of the single contraction parameters upon electrical stimulation was performed before and after stimulation with a frequency of 30 impulses/sec for 3 min. Three types of motor units were differentiated in the opponens pollicis: fast contracting, resistant to fatigue (FR); slow contracting, resistant to fatigue (S); fast contracting, fatiguable (FF). The motor units of type FR were the smallest, those of type S were middle in size, those of type FF were the largest. During voluntary activity the lowest-threshold motor units were of types S and FR.     

Sonographic imaging of muscle contraction and fasciculations: a correlation with electromyography

Precise quantitation of fasciculations with EMG is difficult because of their random location and discharge frequency in muscle. We studied the clinical value of real-time ultrasound in the study of normal voluntary muscle contraction and in the identification of fasciculations in 22 patients. Sonography effectively imaged fasciculations, demonstrating them in both resting and actively contracting extremity muscles and in less accessible muscles such as the tongue. In two instances ultrasound identified fasciculations not apparent on EMG. Analysis of the video images generated quantitative data on fasciculation duration (averaging 500 msec), size, and location and provided unique insight into the process of normal muscle contraction and motor unit physiology.     

Multiple firing of motoneurones is produced by cortical stimulation but not by direct activation of descending motor tracts.

In the present report we have tested whether stimulation of the motor descending tracts at the brain-stem level could set up repetitive motor unit discharges in a similar manner to that described for motor cortical stimulation. We have seen that a large descending motor volley, evoked by brain-stem stimulation, cannot produce repetitive firing of motor units. Repetitive motoneurone firing is therefore produced by multiple excitatory volleys set up by single cortical shocks.     

Effects of extensor and flexor group I afferent volleys on the excitability of individual soleus motoneurones in man

The contour of the postsynaptic potential (PSP) produced in a neurone by an afferent volley can be derived from the contour of the post-stimulus time histogram (PSTH) of that neurone when it is discharging rhythmically. In the present study the PSTH of the firing of individual soleus motor units after stimulation of the popliteal or peroneal nerve was used to explore the effects of extensor and flexor group I afferent volleys on the excitability of single soleus motoneurones in man. Extensor group I volleys resulted in an early peak of increased impulse density in the PSTH of 75% of soleus motoneurones. The latency suggests an analogy with the Ia EPSP. The mean duration of the peak of increased impulse density, equivalent to the rise time of the EPSP, was 3.6 ms. Flexor group I volleys result in a period of reduced impulse density in the PSTH of five out of nine soleus motoneurones. The latency suggests an analogy with the Ia IPSP. We conclude that this method could be used to explore the afferent connections to single motoneurones in man and to derive some of the characteristics of the postsynaptic potentials from a variety of afferent nerve fibres in single human motoneurones.     

Percutaneous electric and magnetic stimulation of the motor cortex in man. Physiological aspects and clinical applications

The new techniques of percutaneous electric and magnetic stimulation of the motor cortex in conscious man provide a unique opportunity of functional testing of the central motor pathways. These techniques seem to be safe and no immediate or delayed adverse reactions have been reported. The physiological studies so far performed suggest that the structures which are preferentially excited by these methods are the fast conducting pyramidal neurones. It has been shown that a single cortical stimulus is able to activate spinal motoneurones repeatedly. This phenomenon can easily be explained if the cortical stimulus generates multiple descending volleys in the central motor pathways. By comparison with experiments of stimulation of the exposed motor cortex in animals, it is likely that electric brain stimulation directly activates the axons of the pyramidal neurons at their origin and to a lesser extent also recruits these neurons transsynaptically, via some cortical interneurones. Magnetic stimulation of the brain at the vertex seems to act mostly by the latter mechanism. These different modes of action of the two methods of cortical stimulation explain the latency differences of the EMG responses obtained with either technique. Increased excitability of the spinal motoneurones and the existence of multiple descending volleys in response to a single cortical stimulus result in shortening of the latencies and greater amplitude of the responses recorded during voluntary contraction of the target muscle. Stimulation of the motor cortex has been used in pilot studies conducted on patients suffering from various disorders of the central motor pathways, such as multiple sclerosis, cervical spondylosis, motor neurone disease or stroke. The sensitivity of the technique looks promising. In M.S., the EMG responses usually show an increased central conduction latency, a reduced amplitude and a prolonged duration. The severity of the electrophysiological abnormalities is not very well correlated with clinical weakness, but the correlations seems to be better with hyperreflexia and the presence of brisk finger flexor jerks. The same abnormalities are observed in cervical spondylosis, although to a lesser extent. In motor neurone disease, the responses have a moderately increased latency and their size and duration are markedly reduced. Patients with acute hemispheric stroke usually show absent responses on the contralateral side. Finally, electric cortical stimulation can be very useful in monitoring the functional integrity of descending motor tracts during surgical operations performed on the spinal cord.     

MEP latency shift after implantation of deep brain stimulation systems in the subthalamic nucleus in patients with advanced Parkinson's disease.

Deep brain stimulation (DBS) into the subthalamic nucleus (STN) is a highly effective treatment for advanced Parkinson's disease (PD). The consequences of STN stimulation on intracortical and corticospinal excitability have been addressed in a few studies using transcranial magnetic stimulation (TMS). Although excitability measurements were compared between the STN stimulation OFF and ON condition, in these experiments, there are no longitudinal studies examining the impact of electrode implantation per se on motor excitability. Here, we explored the effects of STN electrode implantation on resting motor thresholds (RMT), motor evoked potential (MEP) recruitment curves, and MEP onset latencies on 2 consecutive days before and shortly after STN surgery with the stimulator switched off, thus avoiding the effects of chronic DBS on the motor system, in 8 PD patients not taking any dopaminergic medication. After surgery, RMT and MEP recruitment curves were unchanged. In contrast, MEP onset latencies were significantly shorter when examined in relaxed muscles but were unchanged under preactivation. We hypothesize that postoperatively TMS pulses induced small currents in scalp leads underneath the TMS coil connecting the external stimulator with STN electrodes leading to inadvertent stimulation of fast-conducting descending neural elements in the vicinity of the STN, thereby producing submotor threshold descending volleys. These "conditioning" volleys probably preactivated spinal motor neurons leading to earlier suprathreshold activation by the multiple corticospinal volleys produced by TMS of the motor cortex. These TMS effects need to be considered when interpreting results of excitability measurements in PD patients after implantation of STN electrodes.     

Modulation of motor cortex excitability after upper limb immobilization.

OBJECTIVE: To examine the mechanisms of disuse-induced plasticity following long-term limb immobilization. METHODS: We studied 9 subjects, who underwent left upper limb immobilization for unilateral wrist fractures. All subjects were examined immediately after splint removal. Cortical motor maps, resting motor threshold (RMT), motor evoked potential (MEP) latency and MEP recruitment curves were studied from abductor pollicis brevis (APB) and flexor carpi radialis (FCR) muscles with single pulse transcranial magnetic stimulation (TMS). Paired pulse TMS was used to study intracortical inhibition and facilitation. Compound muscle action potentials (CMAPs) and F waves were obtained after median nerve stimulation. In 4/9 subjects the recording was repeated after 35-41 days. RESULTS: CMAP amplitude and RMT were reduced in APB muscle on the immobilized sides in comparison to the non-immobilized sides and controls after splint removal. CMAP amplitude and RMT were unchanged in FCR muscle. MEP latency and F waves were unchanged. MEP recruitment was significantly greater on the immobilized side at rest, but the asymmetry disappeared during voluntary muscle contraction. Paired pulse TMS showed an imbalance between inhibitory and excitatory networks, with a prevalence of excitation on the immobilized sides. A slight, non-significant change in the strength of corticospinal projections to the non-immobilized sides was found. TMS parameters were not correlated with hand dexterity. These abnormalities were largely normalized at the time of retesting in the four patients who were followed-up. CONCLUSIONS: Hyperexcitability occurs within the representation of single muscles, associated with changes in RMT and with an imbalance between intracortical inhibition and facilitation. These findings may be related to changes in the sensory input from the immobilized upper limb and/or in the discharge properties of the motor units. SIGNIFICANCE: Different mechanisms may contribute to the reversible neuroplastic changes, which occur in response to long-term immobilization of the upper-limbs.     

An electrophysiological study of the corticospinal projections in amyotrophic lateral sclerosis.

OBJECTIVE: To elucidate the pattern of corticospinal tract involvement in patients with amyotrophic lateral sclerosis (ALS), we analyzed motor evoked potential (MEP) waveforms and their relationship to the behaviour of single motor units using the peristimulus time histogram (PSTH) technique. METHODS: Abnormality of the corticospinal pathways was studied in 35 ALS patients using MEPs. PSTHs were also constructed to assess the effect of magnetic cortical stimulation on the discharge pattern of a voluntarily activated motor unit. RESULTS: MEPs showed a complex waveform in 10 out of 18 (56%) ALS patients with upper motor neuron signs (UMN). PSTHs revealed double primary peaks (PPs), PP1 and PP2, in 6 out of 16 motor units (38%) in ALS with UMN, as compared to only 2 out of 16 (13%) motor units in multiple sclerosis or cerebrovascular disease with UMN. None of the patients with lower motor neuron diseases or ALS without UMN had these abnormalities. The late component of complex MEPs showed a good correlation to PP2 (P < 0.0001), both probably being mediated by relatively preserved slower conducting corticospinal volleys. CONCLUSIONS: These findings suggest preferential involvement of the fast conducting direct corticospinal tracts, sparing the slower or polysynaptic projections in ALS.     

Characteristics of motor unit discharge in subjects with hemiparesis

We studied the discharge rates recruitment characteristics of single motor units in paratic and contralateral arm muscles of 6 hemiparetic subjects. Motor unit activity in bicapes brachii was recorded at different elbow torques, and the activity related both to the mean level of surface electromyographic activity, and to the degree of weakness. In 3 of the 6 subjects, there were significant reductions in mean discharge rate of motor units in the paretic muscle. All 6 subjects showed compression of the range of motoneuron recuitment forces, and a failure to increase motor unit discharge rate during voluntary force increases in paretic muscles. These rate reductions could potentially alter the precise match of motoneuron properties to the mechanical properties of the innerved muscle fibers, and reduce the efficiency of muscle contraction. This reduction could lead, in turn to increased effort, to fatigue, and ultimately to a sense of weaknes for voluntary force generation.© 1995 John Wiley & Sons, Inc.     

Abnormal excitability of the corticospinal pathway in patients with amyotrophic lateral sclerosis: a single motor unit study using transcranial magnetic stimulation

The pathophysiology of corticospinal tract degeneration in amyotrophic lateral sclerosis (ALS) was investigated by studying the effect of transcranial magnetic stimulation on discharge characteristics of single motor units during voluntary activation. The motor units were recorded from the first dorsal interosseus muscles of 12 patients with ALS, 14 healthy subjects, 12 patients with upper motor neuron lesions and 9 with pure lower motor neuron diseases. More than 100 magnetic stimuli were delivered over the scalp during minimal muscle contraction. The occurrence of motor unit discharges was plotted in a peristimulus time histogram. An increase in discharge probability at latencies of 20–30 msec, that represents monosynaptic activation (primary peak) was found in normal units. Motor units from ALS patients with short disease durations had significantly increased discharge probabilities in the primary peak (P < 0.01). Motor units from 4 ALS patients with upper motor neuron signs showed double primary peaks: an initial synchronized peak followed by a dispersed peak. The latter was ascribed to a slow corticospinal pathway, which remains undetected or is functionally insignificant in healthy subjects. We conclude that the excitabilities of the surviving corticospinal tract pathways are abnormally increased in ALS, especially in the early stage.     

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.     

Facilitation of human first dorsal interosseous muscle responses to transcranial magnetic stimulation during voluntary contraction of the contralateral homonymous muscle

The size of compound motor evoked potentials (cMEPs) to transcranial magnetic stimulation of the motor cortex was measured in the relaxed first dorsal interosseous muscle of the nondominant hand (ndFDI) during different levels of voluntary contraction in the homonymous muscle of the dominant hand (dFDI). cMEP responses in the ndFDI became larger when the dFDI was contracted to forces ranging 10–70% of maximum voluntary contraction. Variability in the amplitude of the cMEP responses in ndFDI decreased when dFDI was contracted. Comparison with cMEPs to spinal cord stimulation suggested a large component of the facilitation was occurring at a cortical level. The amplitude of cMEP responses in ndFDI also increased when the tibialis anterior muscle of the leg on the contralateral side was contracted. The observed facilitation of motoneurons during contraction of contralateral muscles might involve a transcallosal pathway modulating the excitability of one cortex when the other is activated. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:1033–1039, 1998     

Disturbances in the voluntary recruitment order of anterior tibial motor units in ataxia.

The recruitment order of motor units was studied with an electromyographic technique for secure identification of single motor unit potentials. It has been shown in previous studies of normal subjects that the recruitment order in sustained voluntary contraction is predominantly stable, and that motor units which increase slowly in discharge rate with increasing contraction strength and which already attain regular discharge intervals at low frequencies are always recruited before motor units which increase more rapidly in discharge rate and which do not attain regular discharge intervals until at higher frequencies. In this study 15 patients with severe cerebellar ataxia were examined. It was shown that the recruitment order in sustained voluntary contraction in attaxia is unstable and that low- and high-frequency motor units may alternate as the unit of lowest threshold.     

Direct recording of the output of the motor cortex produced by transcranial magnetic stimulation in a patient with cerebral cortex atrophy.

OBJECTIVE: To examine the descending motor activity evoked by transcranial magnetic stimulation (TMS) in a chronic alcoholic patient with a slight atrophy of the peri-central cortex and compare with that observed in neurologically intact subjects. METHODS: EMGs from the first dorsal interosseous (FDI) muscle, and descending activity from an electrode implanted in the high cervical epidural space for relief of pain were recorded after TMS of the hand area of motor cortex. A figure-of-8 coil was used to induce either a posterior-anterior (PA) or a latero-medial (LM) flow across the central sulcus. RESULTS: In intact subjects, LM stimulation evoked the earliest volley, which we termed a D wave. This was followed by later, presumed I waves at intervals of about 1.5 ms. At a stimulus intensity of 120% resting threshold (RMT), up to 5 I waves were seen. PA stimulation rarely evoked D waves at intensities up to 120% RMT, but 3 or 4 I waves were visible in all subjects. The patient had an increased resting threshold, and the descending volleys were dominated by a D wave. I waves were unclear, with two possible small peaks at 5.5 and 7.2 ms. CONCLUSIONS: The lack of I waves in the patient was probably due to an impairment of interneuronal circuitry in the context of the brain damage related to chronic alcohol abuse, and is consistent with a trans-synaptic origin of the I waves in humans. The intact D wave is consistent with the assumption that the D wave represents direct stimulation of the axons of intact corticospinal neurones in the subcortical white matter. The patient's increased RMT reflects the fact that usually multiple descending volleys are needed to discharge resting spinal motoneurones.     

A single motor unit recording technique for studying the differential activation of corticospinal volleys by transcranial magnetic stimulation

The purpose of this method is to establish a single motor unit recording technique to study the differential activation of corticospinal volleys by various types of transcranial magnetic stimulation (TMS). TMS is performed with various coil orientations over the hand or leg motor areas and surface EMG, and single motor unit recordings are made either from the studied hand or leg muscle. Transcranial electrical stimulation (TES) is also performed over the motor cortex as well as at the foramen magnum level to determine the latency of D waves. The intensity of stimulation is set just above the motor threshold for each type of stimulation. This method makes it possible to activate some I volleys (especially I1 and I3 waves) preferentially, if not selectively, from the hand and leg motor areas. The obtained results accord well with recent epidural recording studies, which lends support to the validity of this method.     

Effects of premotion silent period on single motor unit firing at initiation of rapid contraction

We compared the single motor unit (SMU) activity between movements with a premotion silent period (PMSP) and without PMSP in EMG. Fourteen SMUs in the gastrocnemius muscle and 6 SMUs in the soleus muscle were recorded from 5 volunteers during isometric plantar flexion. Tonically firing SMUs failed to fire just before the onset of rapid contraction with PMSP more frequently than without PMSP. SMUs tended to fire within 10 msec (the gastrocnemius SMUs) or 20 msec (the soleus SMUs) from the onset of the phasic EMG discharge when PMSP occurred. In a rapid contraction without PMSP, the initial firing of SMUs occurred with longer latency than that in a rapid contraction with PMSP. The latency of the initial SMU firing in a rapid contraction related to the preceding time of the last SMU firing during a sustained contraction to the onset of the phasic EMG discharge. When the preceding firing was long enough, the latency distributed around 10 msec. On the other hand, for shorter preceding times, the latency lengthened with shortening of the preceding time. It is suggested that the PMSP makes the preceding time long and increases the susceptibility of motor units to the descending command at the initiation of a rapid contraction.     

Different patterns of excitation and inhibition of the small hand and forearm muscles from magnetic brain stimulation in humans.

OBJECTIVES: The objective of the present study is to quantify the effects of voluntary muscle contraction of the small hand (abductor pollicis brevis, first dorsal interosseus (FDI)) and forearm muscles (extensor carpi radialis (ECR), extensor carpi ulnaris (ECU), flexor carpi radialis (FCR) and flexor carpi ulnaris (FCU)) on motor evoked potentials (MEPs). METHODS: MEPs were recorded in 12 healthy subjects by a circular coil placed over the vertex at 1.2 times the resting motor threshold at different levels of the muscle contraction (0-100% of maximum voluntary contraction (MVC)). The effects of transcranial magnetic stimulation (TMS) on the onset latency, MEP area and silent period (SP) as a function of the %MVC were evaluated using a piecewise linear regression analysis. RESULTS: The MEP areas for the small hand muscles were almost completely saturated at 20% of MVC. In contrast, the MEP areas for radial muscles (ECR, FCR) had a dual increase at 40% of MVC while the ulnar muscles (ECU, FCU) had a dual increase at 20% of MVC. A uniform latency shift (1.5-3 ms reduction) was observed in all muscles with a changing point at 10% of MVC. The SPs were the longest for FDI and were not significantly influenced by MVC for any muscles. CONCLUSIONS: The excitatory and inhibitory effects of TMS on the MEPs differed for the small hand and forearm muscles and also between the ulnar and radial muscles. These results probably resulted from the different degrees of direct corticomotoneuronal inputs to each muscle and the inherent properties of the spinal motoneurons.     

Effect of transcranial magnetic stimulation on voluntary activation in patients with quadriceps weakness

Joint disease causes weakness and wasting of adjacent muscles, in part because of inability to fully activate these muscles voluntarily. Previous findings suggest that transcranial magnetic stimulation (TMS) paired with muscle contractions enhances maximal voluntary contraction force (MVC) in healthy subjects by improving voluntary activation (VA). The aim of the present study was to evaluate whether such an effect is also present in subjects suffering from diminished muscle force due to decreased VA. Three single TMS over resting motor threshold were applied in 10 patients with a mean age of 62 years after total-knee arthroplasty either during MVC or during muscle relaxation (control experiment) in a blinded randomized crossover study. MVC and VA were determined using a twitch-interpolation technique at 1, 15, 30, and 60 min after stimulation. There was a significant effect of TMS on MVC if applied in synchrony with muscle contraction, and this persisted for at least 60 min beyond stimulation. In patients suffering from joint disease, TMS might make physiotherapy more effective.