On-line flexibility of the cognitive tuning of corticospinal excitability: a TMS study in human gait

Human subjects have been found to be able to cognitively prepare themselves to resist to a TMS-induced central perturbation by selectively modulating the corticospinal excitability (CS). The aim of this study was to investigate the on-line adaptability of this cognitive tuning of CS excitability during human gait. Transcranial magnetic stimulation (TMS) was used both as a central perturbation evoking a movement and as a tool for quantifying the CS excitability before the movement was evoked. TMS was applied at mid-stance (evoking additional hip extension) or at the beginning of the swing (evoking hip flexion) with a random phase, thus evoking unpredictable flexion or extension movement. This was compared to a condition of fixed phase, in which the subjects knew in advance the direction of the evoked movement. In both conditions, we compared the amplitude of the TMS-evoked movement and the motor-evoked potentials (MEPs) of the muscles acting at the hip joint (RF/BF) according to two opposite instructions, either to cognitively prepare to "let go", or to cognitively prepare to "compensate" for the evoked movements. The results showed that the subjects were able to compensate for random TMS-evoked movements, but with a lower performance level in comparison to the fixed TMS-evoked movements. When they succeeded in the random-phase condition, the subjects used the same preparation strategy as in the fixed-phase condition; preparing to compensate resulted in a selective increase in the CS excitability to those muscles which would be involved in counteracting the possible central perturbation. This requires continuous change in the tuning of CS excitability within the stride and thus reveals the high flexibility of the cognitive tuning of CS excitability during gait.     

Direct evidence for a binding between cognitive and motor functions in humans: a TMS study

During voluntary motor actions, the cortico-spinal (CS) excitability is known to be modulated, on the one hand by cognitive (intention-related) processes and, on the other hand, by motor (performance-related) processes. Here, we studied the way these processes interact in the tuning of CS excitability during voluntary wrist movement. We used transcranial magnetic stimulation (TMS) both as a reliable tool for quantifying the CS excitability, through the motor-evoked potentials (MEPs), and as a central perturbation evoking a movement (because the stimulation intensity was above threshold) with subjects instructed to prepare (without changing their muscle activation) either to "let go" or to "resist" to this evoked movement. We studied the simultaneous evolution of both the motor performance and the MEPs in the wrist flexor and extensor, separately for the successful trials (on average, 66% of the trials whatever the condition) and the unsuccessful trials; this allowed us to dissociate the intention- and performance-related processes. To their great surprise, subjects were found able to cognitively prepare themselves to resist a TMS-induced central perturbation; they all reported an important cognitive effort on the evoked movement. Moreover, because TMS only evoked short-latency MEPs (and no long-latency components), the amplitude of these short-latency MEPs was found to be related in a continuous way to the actual movement whatever the prior intention. These results demonstrate that prior intention allows an anticipatory modulation of the CS excitability, which is not only selective (as already known) but also efficient, giving the intended motor behavior a real chance to be realized. This constitutes a direct evidence of the role of the CS excitability in the binding between cognitive and motor processes in humans.     

Task-induced modulation of motor evoked potentials in upper-leg muscles during human gait: a TMS study

The aim of this study was to determine the relative involvement of the corticospinal (CS) pathway in voluntarily controlled walking compared to unconstrained walking. In the voluntarily controlled walking condition, subjects had to walk at the same speed as in unconstrained walking with a mechanical constraint, which is known to affect specifically the upper-leg muscles. The motor cortex was activated transcranially using a focal magnetic stimulation coil in order to elicit motor evoked potentials (MEPs) in the rectus femoris (RF) and the biceps femoris (BF). The magnetic stimulation was delivered at the end of the swing (at 90% of the cycle duration), when the EMG backgrounds were similar in the two experimental conditions. For each subject in each condition, MEPs were measured for several stimulus intensities in order to establish the input/output (I/O) curve (MEPs amplitude plotted against stimulus strength). The results showed a significant increase in the MEPs amplitude of both the RF and BF in voluntarily controlled walking compared to unconstrained walking, which is the first evidence of cofacilitation of MEPs in antagonist upper-leg muscles during human gait. In conclusion, although a lot of studies have emphasized a privileged input of the corticospinal pathway to the distal lower-leg muscles, this study shows that, if a locomotory task requires fine control of the proximal upper-leg muscles, a selective facilitation of MEPs is observed in these muscles.     

Excitability changes in resting forearm muscles during voluntary foot movements depend on hand position: a neural substrate for hand-foot isodirectional coupling

When associating hand and foot voluntary oscillations, isodirectional coupling is preferred irrespective of hand position (prone or supine). To investigate the neural correlates of this coupling modality, excitability of the motor projections innervating the resting forearm was tested during cyclic voluntary flexion-extensions of the ipsilateral foot. H-reflexes, in some experiments facilitated by subliminal Transcranial Magnetic Stimulation (TMS), and Compound Muscle Action Potentials (CMAPs), evoked by supraliminal TMS, were elicited in Flexor Carpi Radialis (FCR) and Extensor Carpi Radialis (ECR) muscles at five intervals during the foot movement cycle. With the hand prone, a sinusoidal excitability modulation was observed in wrist flexors and extensors, but reversed in phase: in FCR, excitability increased during plantar-flexion and decreased during dorsiflexion, while in ECR the opposite occurred. This reciprocal organisation was confirmed by the excitability modulation of CMAPs evoked simultaneously in the two antagonists. When the hand was supinated, the H-reflex modulation reversed in phase, i.e., FCR excitability increased during foot dorsiflexion and decreased during plantar-flexion. In both muscles and hand positions tested, when the muscle-to-movement phase-lag was increased by inertial loading of the foot, H-reflex excitability modulations remained phase linked to muscular contractions, not to movement. Together, these results suggest that the subliminal excitability modulation of hand movers has a common central origin with the parallel overt activation of foot movers, is reciprocally organised, and is direction- not muscle-dependent. It may therefore represent the neural substrate for isodirectional coupling of hand (prone or supine) with the foot.     

Distal muscle activity alterations during the stance phase of gait in restless leg syndrome (RLS) patients

ObjectiveTo assess if there is a circadian variation in electromyographical (EMG) muscle activity during gait in restless legs syndrome (RLS) patients and healthy control participants.MethodsGait assessment was done in 14 RLS patients and 13 healthy control participants in the evening (PM) and the morning (AM). Muscle activity was recorded bilaterally from the tibialis anterior (TA), lateral gastrocnemius (GL), rectus femoris (RF) and biceps femoris (BF) muscles.ResultsA circadian variation during the stance phase in only TA (PM > AM, p < 0.005) and BF (PM < AM, p = 0.008) activity was observed in control participants. Conversely no circadian variation was seen in any muscles in the RLS patients. RLS patients had an increased TA and GL activity (RLS > Controls, p < 0.05) during early stance and decreased GL activity (RLS < Controls, p < 0.01) during terminal stance in comparison to control participants in the evening. No other significant differences were noted between RLS patients and control participants. Activation of GL during the swing phase was noted in 79% of RLS patients and in 23% of control participants in the morning compared to 71% and 38% in the evening, respectively.ConclusionEMG muscle activity shows no circadian variation in RLS patients. Evening differences in gait muscle activation patterns between RLS patients and control participants are evident. These results extend our knowledge about alterations in spinal processing during gait in RLS. A possible explanation for these findings is central pattern generator sensitization caused by increased sensitivity in cutaneous afferents in RLS patients.     

Interactions between cognitive and sensorimotor functions in the motor cortex: evidence from the preparatory motor sets anticipating a perturbation

The many signs of cognitive processes in the activation pattern of the primary motor cortex or in corticospinal (CS) excitability gave rise to the idea that the motor cortex is a crucial node in the processing of cognitive information related to sensorimotor functions. Moreover, it became clear that the preparatory motor sets offer a privileged window to investigate the interaction between cognitive and sensorimotor function in the motor cortex. In the present review, we examine how the study of the preparatory motor sets anticipating a mechanical movement perturbation contributes to enlightening this question. Following the initial observation made by Hammond that some components of the stretch reflex can be modulated by a prior intention either to resist or to relax in response to a subsequent perturbation, first evidence of the phenomenon was obtained in behaving monkeys. Moreover, this study related this peripheral fact to the observed anticipatory activity of motor cortex neurons after a prior instruction telling the animal how to respond to the subsequent perturbation, which triggered the instructed movement. Indeed, this anticipatory activity was found to be different according to the instruction. In the 1980s, this work inspired a lot of studies in human beings that brought support to the idea of a cognitive tuning of the long latency stretch response (LLSR). Specifically, the MI component of the response was shown to be modulated by a prior intent to resist versus to let go when faced with the perturbation. Recently, new approaches have been developed to obtain evidence of a cognitive tuning of CS excitability, thanks to transcranial magnetic stimulation (TMS). TMS has been used both as a reliable tool for quantifying the CS excitability via the motor evoked potentials (MEPs), and to centrally perturb the organization of movement. Such central perturbations offer the unique opportunity to activate the descending motor tracts while shunting, for a short time period, the ascending tracts assisting the movement. Thus, CS excitability was measured before the movement was perturbed. These studies demonstrated the readiness of the CS tract to be involved in anticipatory compensatory responses to central movement perturbations induced by TMS in relation to the subject's cognitive attitudes. The question of the cerebral regions upstream of the motor cortex that could be responsible for this modulation in CS excitability remains largely open.     

Evidence of phase-dependent nociceptive reflexes during locomotion in man

In 10 healthy subjects freely walking along a straightline, the effects of painful sural nerve stimulation, applied in different phases of the step cycle, were investigated on two antagonistic muscles of the ipsilateral lower limb acting on the knee joint: vastus lateralis (VL) and biceps femoris caput breve (BF). A clear-cut modulation in the amplitude (area) of the net reflex responses was consistently observed in both the motor nuclei explored. The extensor muscle, VL, exhibited a long-latency (mean 122 ms) reflex response, which was maximally increased by stimuli applied toward the end of the swing and in the first half of the stance phase of the stride, whereas the response appeared to be gated during the transition from the foot-flat to forefoot-contact phase. A second facilitation period was brought about by stimuli delivered in the early swing. When the response occurred superimposed on the VL locomotor activity, suppression of the ongoing EMG preceded the reflex discharge. In the flexor, BF, the same stimulus elicited a short-latency (mean 57 ms) and a long-latency (mean 132 ms) reflex response. The former was maximal after stimulation around the toe-off phase and the latter was strikingly enhanced in the late swing, where it was preceded by suppression of the background locomotor EMG activity. Responses with intermediate features (latency 70 to 80 ms, duration 90 to 120 ms), probably resulting from the merging of the early and late components, might be evoked in addition, being greatest in the last swing and in the period preceding toe-off. The findings show that in man the reflex pattern evoked by a painful cutaneous stimulus during locomotion is determined by the phase of the step cycle during which the stimulus is delivered. A functional role in maintenance of postural balance during destabilizing withdrawal reactions is conceivable.     

Tibialis Anterior and Soleus Withdrawal Reflexes Elicited by Electrical Stimulation of the Sole of the Foot during Gait

The aim of the present study was to investigate the modulation and functional importance of nociceptive withdrawal reflexes elicited from the sole of the foot and recorded from the soleus (SOL) and tibialis anterior (TA) muscles during gait. Cutaneous electrical stimulation delivered at four locations of the sole of the foot was used to elicit the withdrawal reflex. Reflexes were recorded from eight healthy subjects during treadmill walking. The reflexes were elicited at heel‐contact, during foot‐flat, at heel‐off, and during mid‐swing. The reflexes evoked in TA were largest when the arch of the foot was stimulated, and smallest following stimulation of the heel (significant difference during stance, p ≤ 0.002). The largest soleus responses were elicited when the arch of the foot was stimulated (significant difference compared with the fifth metatarsophalangeal joint, stimulation after heel‐contact, p < 0.05). The TA reflex, expressed as a proportion of the electromyogram during unperturbed gait, was smallest during swing (p < 0.05, compared with stance) whereas the SOL reflex was maximal during swing (p < 0.05, compared with stance). The results suggest that the modulation of the reflex promotes an appropriate withdrawal while preserving balance and continuity of motion. These results may have applications in assisting gait of hemiplegics.     

Electromyographic evaluation of the sound and involved side during gait of spastic hemiplegic children with cerebral palsy

The purpose of this study was to investigate the surface electromyogram (EMG) of the lower limbs of hemiplegic children with spastic cerebral palsy during gait. The EMG of seven muscles was analyzed for 17 children (5-12 years old). The EMG of the involved side was decreased for the examined shank muscles and increased for the hamstrings, during certain phases of the gait cycle, compared with the sound side. The rectus femoris of the involved side showed prolonged activation during the swing phase. The enhanced activation of the hamstrings may be beneficial/compensatory, preventing knee hyperextension. The presence of equinus foot obstructs the foot clearance and hence the prolonged rectus femoris EMG activity during the swing phase may contribute to shorten the lower limb by flexing the hip. Possible compensatory mechanisms of the proximal muscles of the involved lower limb that can be measured with instrumented gait analysis should be taken into account before the decision for a specific treatment.     

Forelimb responses to cutaneous nerve stimulation during locomotion in intact cats

The reflex responses of forelimb muscles to electrical stimulation of the cutaneous superficial radial nerve were recorded during treadmill locomotion in chronically implanted cats. In brachialis and cleidobrachialis (muscles which are active mainly during the swing phase) the responses were maximal during the swing phase and minimal or absent during the stance phase. In the long head of triceps which is active mainly during the stance phase, responses were also minimal during stance and maximal during swing. It is concluded that, for some muscles, the period of maximal reflex responsiveness can be out of phase with the period of the step cycle during which they are normally active.     

Facilitation of corticospinal excitability in the tibialis anterior muscle during robot-assisted passive stepping in humans

Although phasic modulation of the corticospinal tract excitability to the lower limb muscles has been observed during normal walking, it is unclear to what extent afferent information induced by walking is related to the modulation. The purpose of this study was to test the corticospinal excitability to the lower limb muscles by using transcranial magnetic stimulation (TMS) and transcranial electrical stimulation of the motor cortex while 13 healthy subjects passively stepped in a robotic driven-gait orthosis. Specifically, to investigate the effect of load-related afferent inputs on the corticospinal excitability during passive stepping, motor evoked potentials (MEPs) in response to the stimulation were compared between two passive stepping conditions: 40% body weight unloading on a treadmill (ground stepping) and 100% body weight unloading in the air (air stepping). In the rectus femoris, biceps femoris and tibialis anterior (TA) muscles, electromyographic activity was not observed throughout the step cycle in either stepping condition. However, the TMS-evoked MEPs of the TA muscle at the early- and late-swing phases as well as at the early-stance phase during ground stepping were significantly larger than those observed during air stepping. The modulation pattern of the transcranial electrical stimulation-evoked MEPs was similar to that of the TMS-evoked MEPs. These results suggest that corticospinal excitability to the TA is facilitated by load-related afferent inputs. Thus, these results might be consistent with the notion that load-related afferent inputs play a significant role during locomotor training for gait disorders.     

Reflex responses of human thigh muscles to non-noxious sural stimulation during stepping

An investigation of reflex responses of leg muscles to sural stimulation during stepping was performed on human subjects. Non-noxious electrical stimulation applied during the swing phase or the latter half of the stance phase produced a mixed increase and decrease of EMG activity in the hamstring muscles. No response or very weak response was observed when the same stimulus was applied during either quiet standing or various levels of constant voluntary effort at varying hip and knee joint angles.     

Cortical voluntary activation of the human knee extensors can be reliably estimated using transcranial magnetic stimulation

The objective of this study was to determine if a transcranial magnetic stimulation (TMS) method of quantifying the degree to which the motor cortex drives the muscles during voluntary efforts can be reliably applied to the human knee extensors. Although the technique for estimating “cortical” voluntary activation (VA) is valid and reliable for elbow flexors and wrist extensors, evidence that it can be applied to muscles of the lower limb is necessary if twitch interpolation with TMS is to be widely used in research or clinical practice. Eight subjects completed two identical test sessions involving brief isometric knee extensions at forces ranging from rest to maximal voluntary contraction (MVC). Electromyographic (EMG) responses to TMS of the motor cortex and electrical stimulation of the femoral nerve were recorded from the rectus femoris (RF) and biceps femoris (BF) muscles, and knee extension twitch forces evoked by stimulation were measured. The amplitude of TMS‐evoked twitch forces decreased linearly between 25% and 100% MVC (r² > 0.9), and produced reliable estimations of resting twitch and VA (ICC_2,1 > 0.85). The reliability and size of cortical measures of VA were comparable to those derived from motor nerve stimulation when the resting twitches were estimated on the basis of as few as three TMS trials. Thus, TMS measures of VA may provide a reliable and valid tool in studies investigating central fatigue due to exercise and neurological deficits in neural drive in the lower limbs. © 2008 Wiley Periodicals, Inc. Muscle Nerve 2008     

Gait pattern in two rare genetic conditions characterized by muscular hypotonia: Ehlers-Danlos and Prader-Willi syndrome

This study aimed to quantify and compare the gait pattern in Ehlers-Danlos (EDS) and Prader-Willi syndrome (PWS) patients to provide data for developing evidence-based rehabilitation strategies. Twenty EDS and 19 PWS adult patients were evaluated with an optoelectronic system and force platforms for measuring kinematic and kinetic parameters during walking. The results were compared with those obtained in a group of 20 normal-weight controls (CG). The results showed that PWS patients walked with longer stance duration and reduced velocity than EDS, close to CG. Both EDS and PWS showed reduced anterior step length than CG. EDS kinematics evidenced a physiological position at proximal joints (pelvis and hip joint) while some deficits were displayed at knee (reduced flexion in swing phase) and ankle level (plantar flexed position in stance and reduced dorsal flexion in swing). PWS showed a forward tilted pelvis in the sagittal plane, excessive hip flexion during the whole gait cycle and an increased hip movement in the frontal plane. Their knees were flexed at initial contact with reduced range of motion while ankle joints showed a plantar flexed position during stance. No differences were found in terms of ankle kinetics and joint stiffness. Our data showed that EDS and PWS patients were characterized by a different gait strategy: PWS showed functional limitations at every level of the lower limb joints, whereas in EDS limitations, greater than PWS, were reported mainly at the distal joints. PWS patients should be encouraged to walk for its positive impact on muscle mass and strength and energy balance. For EDS patients the rehabilitation program should be focused on ankle strategy improvement.     

Effect of Electrical Stimulation of Hamstrings and L3/4 Dermatome on Gait in Spinal Cord Injury

Objective. To determine the effect of electrical stimulation of hamstrings and L3/4 dermatome on the swing phase of gait. Materials and Methods. Five subjects with incomplete spinal cord injury (SCI) with spasticity were included. Two electrical stimulation methods were investigated, i.e., hamstrings and L3/4 dermatome stimulation. Both interventions were applied during the swing phase of gait. The main outcome measures were step length, maximum hip, and knee flexion during the swing phase of gait. In three subjects changes of spinal inhibition during gait were evaluated using the Hoffman reflex/m (motor)–wave (H/M) ratio at mid swing. Results. The hip flexion decreased 4.6° (p < 0.05) when the hamstrings were stimulated during the swing phase, whereas the knee flexion was not changed. The step length did not change significantly. One subject showed a decrease of the H/M ratio to a nonpathologic level during hamstrings stimulation. Conclusion. It was concluded that hamstrings stimulation during the swing phase results in a reduction of the hip flexion in all five SCI subjects. The H/M ratio of the vastus lateralis was normalized using hamstrings stimulation in one of three subjects. Stimulation of the L3/4 dermatome provides no significant changes in gait performance, but in one subject the H/M ratio increased.     

Transcranial magnetic stimulation of motor pathways directed to muscles supplied by cranial nerves in amyotrophic lateral sclerosis.

OBJECTIVES: In amyotrophic lateral sclerosis (ALS), transcranial magnetic stimulation (TMS) detects remarkable abnormalities of central motor circuits: cortical excitability threshold, silent period (SP) duration and intra-cortical inhibition. TMS directed to cranio-facial musculature was performed in ALS patients in order: (1) to document the neurophysiological involvement of motor central and peripheral cranial pathways by evaluating changes of threshold and SP; (2) to discover a possible correlation between the clinical picture and abnormal excitability properties. METHODS: Motor evoked potentials (MEPs) were recorded from masseter, genioglossus and orbicularis oris muscles of both sides in 25 ALS patients and 25 controls, in response to TMS delivered over the face M1 area and the vertex. RESULTS: TMS gave rise to two orders of responses: bilateral MEPs during contraction represented the central responses, and motor action potentials (MAPs) during rest represented the peripheral responses. MEPs were followed by SPs, which increased linearly with increasing TMS intensity (r=0.8). At least one of the analyzed parameters was abnormal in all patients: central abnormalities (increased active threshold, delayed MEPs, reduced SP) were found in 96% of patients, alone or combined with abnormalities of the MAPs (reduced area and/or prolonged latency). The reduction of SP was linearly related to the Norris score (r=0.95). CONCLUSIONS: Our study shows that TMS is able to detect the involvement of multiple cranial muscles in ALS. This finding offers often pre-clinical information about the disease picture. Therefore, it can be employed as a valuable means for early diagnosis.     

Reliability of TMS motor evoked potentials in quadriceps of subjects with chronic hemiparesis after stroke

Transcranial magnetic stimulation (TMS) non-invasively measures excitability of central motor pathways in humans and is used to characterize neuroplasticity after stroke. Using TMS to index lower extremity neuroplasticity after gait rehabilitation requires test-retest reliability. This study assesses the reliability of TMS-derived variables measured at bilateral quadriceps of chronic hemiparetic stroke survivors. Results support using measures of both paretic and nonparetic motor threshold, motor evoked potential (MEP) latencies; and nonparetic MEP amplitudes. Implications for longitudinal research are discussed.     

Robot-assisted training using Hybrid Assistive Limb® for cerebral palsy

Purpose

The Hybrid Assistive Limb® (HAL®, CYBERDYNE) is a wearable robot that provides assistance to a patient while they are walking, standing, and performing leg movements based on the wearer’s intended movement. The effect of robot-assisted training using HAL® for cerebral palsy (CP) is unknown. Therefore, we assessed the effect of robot-assisted training using HAL® on patients with CP, and compared walking and gross motor abilities between pre-intervention and post-intervention.

Leg muscle reflexes mediated by cutaneous A-beta fibres are normal during gait in reflex sympathetic dystrophy.

OBJECTIVES: Reflex sympathetic dystrophy (RSD) is, from the onset, characterized by various neurological deficits such as an alteration of sensation and a decrease in muscle strength. We investigated if afferent A-beta fibre-mediated reflexes are changed in lower extremities affected by acute RSD.METHODS: The involvement of these fibres was determined by analyzing reflex responses from the tibialis anterior (TA) and biceps femoris (BF) muscles after electrical stimulation of the sural nerve. The reflexes were studied during walking on a treadmill to investigate whether the abnormalities in gait of the patients were related either to abnormal amplitudes or deficient phase-dependent modulation of reflexes. In 5 patients with acute RSD of the leg and 5 healthy volunteers these reflex responses were determined during the early and late swing phase of the step cycle.RESULTS: No significant difference was found between the RSD and the volunteers. During early swing the mean amplitude of the facilitatory P2 responses in BF and TA increased as a function of stimulus intensity (1.5, 2 and 2.5 times the perception threshold) in both groups. At end swing the same stimuli induced suppressive responses in TA. This phase-dependent reflex reversal from facilitation in early swing to suppression in late swing occurred equally in both groups. CONCLUSIONS: In the acute phase of RSD of the lower extremity there is no evidence for abnormal A-beta fibre-mediated reflexes or for defective regulation of such reflexes. This finding has implications for both the theory on RSD pathophysiology and RSD models, which are based on abnormal functioning of A-beta fibres.     

Role of sensory feedback in the control of stance duration in walking cats

The rate of stepping in the hind legs of chronic spinal and decerebrate cats adapts to the speed of the treadmill on which the animals walk. This adaptive behavior depends on sensory signals generated near the end of stance phase controlling the transition from stance to swing. Two sensory signals have been identified to have this role: one from afferents activated by hip extension, most likely arising from muscle spindles in hip flexor muscles, and the other from group Ib afferents from Golgi tendon organs in the ankle extensor muscles. The relative importance of these two signals in controlling the stance to swing transition differs in chronic spinal cats and in decerebrate cats. Activation of hip afferents is necessary for controlling the transition in chronic spinal cats but not in decerebrate cats, while reduction in activity in group Ib afferents from GTOs is the primary factor controlling the transition in decerebrate cats. Possible mechanisms for this difference are discussed. The extent to which these two sensory signals control the stance to swing transition in normal walking cats is unknown, but it is likely that both could play an important role when animals are walking in a variable environment.