Tibialis Anterior Motor Evoked Potentials Research Articles

Modulation of lower limb muscle corticospinal excitability during various types of motor imagery

Motor imagery (MI) is used for rehabilitation and sports training. Previous studies focusing on the upper limb have investigated the effects of MI on corticospinal excitability in the muscles involved in the imagined movement (i.e., the agonist muscles). The present study focused on several lower-limb movements and investigated the influences of MI on corticospinal excitability in the lower limb muscles. Twelve healthy individuals (ten male and two female individuals) participated in this study. Motor-evoked potentials (MEP) from the rectus femoris (RF), biceps femoris (BF), tibialis anterior (TA), and soleus (SOL) muscles were elicited through transcranial magnetic stimulation (TMS) to the primary motor cortex during MI of knee extension, knee flexion, ankle dorsiflexion, and ankle plantarflexion and at rest. The results showed that the RF MEPs were significantly increased during MI in knee extension, ankle dorsiflexion, and ankle plantarflexion but not in knee flexion, compared with those at rest. The TA MEPs were significantly increased during MI in knee extension and foot dorsiflexion, while MEPs were not significantly different during MI in knee flexion and foot dorsiflexion than those at rest. For the BF and SOL muscles, there was no significant MEP modulation in either MI. These results demonstrated that corticospinal excitability of the RF and TA muscles was facilitated during MI of movements in which they are active and during MI of lower-limb movements in which they are not involved. On the contrary, corticospinal excitability of the BF and SOL muscles was not facilitated by MI of lower-limb movements. These results suggest that facilitation of corticospinal excitability depends on the muscle and the type of lower-limb MI.

Operant Conditioning of the Motor Evoked Potentials for Sensorimotor Rehabilitation

<h3>Research Objectives</h3> The corticospinal pathway and its plasticity are essential in sensorimotor function recovery after neuromuscular injuries. To determine if operant up-conditioning of the motor evoked potential (MEP) elicited by transcranial magnetic stimulation (TMS) can increase corticospinal excitability and enhance sensorimotor rehabilitation, we are testing this neuromodulation approach in three different ongoing subprojects. We hypothesized that MEP up-conditioning can improve corticospinal activation of the targeted muscle and thereby improve functions in which that muscle participates. <h3>Design</h3> Each subproject utilizes operant MEP up-conditioning methodology. Standard MEP conditioning protocol consists of 6 baseline and 24 conditioning sessions (3/week, 30-45 min each). In each session, 250 single-pulse MEPs are elicited using TMS with or without operant conditioning (i.e., feedback on performance). Before and after conditioning, electrophysiological, kinematic, and functional assessments are performed. <h3>Setting</h3> Controlled laboratory. <h3>Participants</h3> Volunteers with chronic incomplete spinal cord injury (SCI), or with early-stage knee osteoarthritis (OA). <h3>Interventions</h3> See Design. <h3>Main Outcome Measures</h3> Target muscle MEP size, EMG, kinematics. <h3>Results</h3> Dorsiflexor MEP conditioning in people with chronic incomplete SCI: We hypothesize up-conditioning of the tibialis anterior (TA) MEP induces CNS plasticity that affects TA activation and improves locomotion. Initial studies found up-conditioning can increase TA MEP size and improve locomotion. Our current work aims to characterize cortical and corticospinal mechanisms of changes in MEP, locomotor EMG, and kinematics. Forearm extensor MEP conditioning in people with SCI: We hypothesize that corticospinal excitability for the wrist extensors can be increased through MEP conditioning and that it will help improve forearm motor function. Initial results support such possibilities in individuals with chronic incomplete cervical SCI. Quadriceps MEP conditioning in people with knee OA: We hypothesize that up-conditioning can increase quadriceps MEP size and improve quadriceps activation in individuals with early-stage knee OA. We are developing a protocol to examine the effects of MEP up-conditioning on quadriceps activation and function. <h3>Conclusions</h3> These projects will facilitate the dissemination of MEP conditioning as a neurorehabilitation tool to enhance functional recovery after neuromuscular injuries. <h3>Author(s) Disclosures</h3> Authors listed have no conflicts of interest to declare.

Stimulus Intensity Affects Variability of Motor Evoked Responses of the Non-Paretic, but Not Paretic Tibialis Anterior Muscle in Stroke.

Background: Transcranial magnetic stimulus induced motor evoked potentials (MEPs) are quantified either with a single suprathreshold stimulus or using a stimulus response curve. Here, we explored variability in MEPs influenced by different stimulus intensities for the tibialis anterior muscle in stroke. Methods: MEPs for the paretic and non-paretic tibialis anterior (TA) muscle representations were collected from 26 participants with stroke at seven intensities. Variability of MEP parameters was examined with coefficients of variation (CV). Results: CV for the non-paretic TA MEP amplitude and area was significantly lower at 130% and 140% active motor threshold (AMT). CV for the paretic TA MEP amplitude and area did not vary with intensity. CV of MEP latency decreased with higher intensities for both muscles. CV of the silent period decreased with higher intensity for the non-paretic TA, but was in reverse for the paretic TA. Conclusion: We recommend a stimulus intensity of greater than 130% AMT to reduce variability for the non-paretic TA. The stimulus intensity did not affect the MEP variability of the paretic TA. Variability of MEPs is affected by intensity and side tested (paretic and non-paretic), suggesting careful selection of experimental parameters for testing.

Effects of Leg Motor Imagery Combined With Electrical Stimulation on Plasticity of Corticospinal Excitability and Spinal Reciprocal Inhibition.

Motor imagery (MI) combined with electrical stimulation (ES) enhances upper-limb corticospinal excitability. However, its after-effects on both lower limb corticospinal excitability and spinal reciprocal inhibition remain unknown. We aimed to investigate the effects of MI combined with peripheral nerve ES (MI + ES) on the plasticity of lower limb corticospinal excitability and spinal reciprocal inhibition. Seventeen healthy individuals performed the following three tasks on different days, in a random order: (1) MI alone; (2) ES alone; and (3) MI + ES. The MI task consisted of repetitive right ankle dorsiflexion for 20 min. ES was percutaneously applied to the common peroneal nerve at a frequency of 100 Hz and intensity of 120% of the sensory threshold of the tibialis anterior (TA) muscle. We examined changes in motor-evoked potential (MEP) of the TA (task-related muscle) and soleus muscle (SOL; task-unrelated muscle). We also examined disynaptic reciprocal inhibition before, immediately after, and 10, 20, and 30 min after the task. MI + ES significantly increased TA MEPs immediately and 10 min after the task compared with baseline, but did not change the task-unrelated muscle (SOL) MEPs. MI + ES resulted in a significant increase in the magnitude of reciprocal inhibition immediately and 10 min after the task compared with baseline. MI and ES alone did not affect TA MEPs or reciprocal inhibition. MI combined with ES is effective in inducing plastic changes in lower limb corticospinal excitability and reciprocal Ia inhibition.

Cortical and Subcortical Contributions to Neuroplasticity after Repetitive Transspinal Stimulation in Humans

The objectives of this study were to establish cortical and subcortical contributions to neuroplasticity induced by noninvasive repetitive transspinal stimulation in human subjects free of any neurological disorder. To meet our objectives, before and after 40 minutes of transspinal stimulation we established changes in tibialis anterior (TA) motor-evoked potentials (MEPs) in response to paired transcranial magnetic stimulation (TMS) pulses at interstimulus intervals (ISIs) consistent with I-wave periodicity. In order to establish to what extent similar actions are exerted at the spinal cord and motor axons, changes in soleus H-reflex and transspinal evoked potential (TEP) amplitude following transspinal and group Ia afferent conditioning stimulation, respectively, were established. After 40 min of transspinal stimulation, the TA MEP consecutive peaks of facilitation produced by paired TMS pulses were significantly decreased supporting for depression of I-waves. Additionally, the soleus H-reflex and ankle TEP depression following transspinal and group Ia afferent conditioning stimulation was potentiated at intervals when both responses interacted at the spinal cord and nerve axons. These findings support the notion that repetitive transspinal stimulation decreases corticocortical inputs onto corticospinal neurons and promotes a surround inhibition in the spinal cord and nerve axons. This novel method may be a suitable neuromodulation tool to alter excitability at cortical and subcortical levels in neurological disorders.

Operant conditioning of the tibialis anterior motor evoked potential in people with and without chronic incomplete spinal cord injury.

The activity of corticospinal pathways is important in movement control, and its plasticity is essential for motor skill learning and re-learning after central nervous system (CNS) injuries. Therefore, enhancing the corticospinal function may improve motor function recovery after CNS injuries. Operant conditioning of stimulus-induced muscle responses (e.g., reflexes) is known to induce the targeted plasticity in a targeted pathway. Thus, an operant conditioning protocol to target the corticospinal pathways may be able to enhance the corticospinal function. To test this possibility, we investigated whether operant conditioning of the tibialis anterior (TA) motor evoked potential (MEP) to transcranial magnetic stimulation can enhance corticospinal excitability in people with and without chronic incomplete spinal cord injury (SCI). The protocol consisted of 6 baseline and 24 up-conditioning/control sessions over 10 wk. In all sessions, TA MEPs were elicited at 10% above active MEP threshold while the sitting participant provided a fixed preset level of TA background electromyographic activity. During baseline sessions, MEPs were simply measured. During conditioning trials of the conditioning sessions, the participant was encouraged to increase MEP and was given immediate feedback indicating whether MEP size was above a criterion. In 5/8 participants without SCI and 9/10 with SCI, over 24 up-conditioning sessions, MEP size increased significantly to ~150% of the baseline value, whereas the silent period (SP) duration decreased by ~20%. In a control group of participants without SCI, neither MEP nor SP changed. These results indicate that MEP up-conditioning can facilitate corticospinal excitation, which is essential for enhancing motor function recovery after SCI. NEW & NOTEWORTHY We investigated whether operant conditioning of the motor evoked potential (MEP) to transcranial magnetic stimulation can systematically increase corticospinal excitability for the ankle dorsiflexor tibialis anterior (TA) in people with and without chronic incomplete spinal cord injury. We found that up-conditioning can increase the TA MEP while reducing the accompanying silent period (SP) duration. These findings suggest that MEP up-conditioning produces the facilitation of corticospinal excitation as targeted, whereas it suppresses inhibitory mechanisms reflected in SP.

Operant Up-Conditioning of the Tibialis Anterior Motor-Evoked Potential in Multiple Sclerosis: Feasibility Case Studies.

Damage to the corticospinal pathway often results in weak dorsiflexion of the ankle, thereby limiting the mobility of people with multiple sclerosis (MS). Thus, strengthening corticospinal connectivity may improve locomotion. Here, we investigated the feasibility of tibialis anterior (TA) motor-evoked potential (MEP) operant conditioning and whether it can enhance corticospinal excitability and alleviate locomotor problems in people with chronic stable MS. The protocol consisted of 6 baseline and 24 up-conditioning sessions over 10 weeks. In all sessions, TA MEPs were elicited at 10% above active threshold while the sitting subject provided 30–35% maximum voluntary contraction (MVC) level of TA background EMG. During baseline sessions, MEPs were simply measured. During conditioning trials of the conditioning sessions, the subject was encouraged to increase MEP and was given immediate feedback indicating whether MEP size was above a criterion. In 3/4 subjects, TA MEP increased 32–75%, MVC increased 28–52%, locomotor EMG modulation improved in multiple leg muscles, and foot drop became less severe. In one of them, MEP and MVC increases were maintained throughout 3 years of extensive follow-up sessions. These initial results support a therapeutic possibility of MEP operant conditioning for improving locomotion in people with MS or other CNS disorders, such as spinal cord injury and stroke.

Paired Associative Stimulation Delivered by Pairing Movement-Related Cortical Potentials With Peripheral Electrical Stimulation: An Investigation of the Duration of Neuromodulatory Effects

Novel paired associative stimulation (novel-PAS), delivered by pairing movement-related cortical potentials (MRCPs) with electrical stimulation of somatosensory afferents, is an innovative neuromodulatory intervention. Novel-PAS results in increased corticomotor excitability and has potential as a rehabilitative adjunct to improve outcomes following stroke. The duration of its excitatory effect has important implications for how this novel PAS intervention might be applied within a traditional therapy session, but previous research has not explored its effects beyond 30 min post-intervention. The objective was to explore changes in corticomotor excitability in healthy participants, over a 60-min period following a single session of novel-PAS. Ten healthy adults completed a single session of novel-PAS, delivered by pairing 50 MRCPs with peripheral electrical stimulation. TMS was used to elicit motor evoked potentials (MEPs) of the tibialis anterior (TA) muscle, immediately prior to the intervention, and at 0, 30, 45, and 60 min post-intervention. When compared with pre-intervention, there was a statistically significant increase in the mean TA MEP amplitudes at 0 (p = 0.006), 30 (p = 0.006), 45 (p = 0.027), and 60 min post-intervention (p = 0.020). Corticomotor excitability is increased for 60 min following this novel-PAS intervention. Future research could investigate the optimal method of combining this neuromodulatory technique with traditional therapy.

Effects of posture and coactivation on corticomotor excitability of ankle muscles.

The use of transcranial magnetic stimulation (TMS) to evaluate corticomotor excitability of lower limb (LL) muscles can provide insights about neuroplasticity mechanisms underlying LL rehabilitation. However, to date, a majority of TMS studies have focused on upper limb muscles. Posture-related activation is an important under-investigated factor influencing corticomotor excitability of LL muscles. The purpose of this study was to evaluate effects of posture and background activation on corticomotor excitability of ankle muscles. Fourteen young neurologically-unimpaired participants (26.1±4.1 years) completed the study. TMS-evoked motor evoked potentials (MEPs) were recorded from the tibialis anterior (TA) and soleus during 4 conditions - standing, standing coactivation, sitting, and sitting coactivation. TA and soleus MEP amplitudes were compared during: (1) standing versus sitting;(2) standing coactivation (standing while activating both TA and soleus) versus sitting coactivation; and (3) standing coactivation versus standing. For each comparison, background EMG for TA and soleus were matched. Trial-to-trial coefficient of variation of MEP amplitude and coil-positioning errors were additional dependent variables. No differences were observed in TA or soleus MEP amplitudes during standing versus sitting. Compared to sitting coactivation, larger MEPs were observed during standing coactivation for soleus but not TA. Compared to standing, the standing coactivation task demonstrated larger MEPs and reduced trial-to-trial MEP variability. Our findings suggest that incorporation of measurements in standing in future TMS studies may provide novel insights into neural circuits controlling LL muscles. Standing and standing coactivation tasks may be beneficial for obtaining functionally-relevant neuroplasticity assessments of LL musculature.

Modulation of corticospinal input to the legs by arm and leg cycling in people with incomplete spinal cord injury.

The spinal cervico-lumbar interaction during rhythmic movements in humans has recently been studied; however, the role of arm movements in modulating the corticospinal drive to the legs is not well understood. The goals of this study were to investigate the effect of active rhythmic arm movements on the corticospinal drive to the legs (study 1) and assess the effect of simultaneous arm and leg training on the corticospinal pathway after incomplete spinal cord injury (iSCI) (study 2). In study 1, neurologically intact (NI) participants or participants with iSCI performed combinations of stationary and rhythmic cycling of the arms and legs while motor evoked potentials (MEPs) were recorded from the vastus lateralis (VL) muscle. In the NI group, arm cycling alone could facilitate the VL MEP amplitude, suggesting that dynamic arm movements strongly modulate the corticospinal pathway to the legs. No significant difference in VL MEP between conditions was found in participants with iSCI. In study 2, participants with iSCI underwent 12 wk of electrical stimulation-assisted cycling training: one group performed simultaneous arm and leg (A&L) cycling and the other legs-only cycling. MEPs in the tibialis anterior (TA) muscle were compared before and after training. After training, only the A&L group had a significantly larger TA MEP, suggesting increased excitability in the corticospinal pathway. The findings demonstrate the importance of arm movements in modulating the corticospinal drive to the legs and suggest that active engagement of the arms in lower limb rehabilitation may produce better neural regulation and restoration of function.NEW & NOTEWORTHY This study aimed to demonstrate the importance of arm movements in modulating the corticospinal drive to the legs. It provides direct evidence in humans that active movement of the arms could facilitate corticospinal transmission to the legs and, for the first time, shows that facilitation is absent after spinal cord injury. Active engagement of the arms in lower limb rehabilitation increased the excitability of the corticospinal pathway and may produce more effective improvement in leg function.

Longitudinal estimation of intramuscular Tibialis Anterior coherence during subacute spinal cord injury: relationship with neurophysiological, functional and clinical outcome measures

BackgroundEstimation of surface intramuscular coherence has been used to indirectly assess pyramidal tract activity following spinal cord injury (SCI), especially within the 15-30 Hz bandwidth. However, change in higher frequency (>40 Hz) muscle coherence during SCI has not been characterised. Thus, the objective of this study was to identify change of high and low frequency intramuscular Tibialis Anterior (TA) coherence during incomplete subacute SCI.MethodsFifteen healthy subjects and 22 subjects with motor incomplete SCI (American Spinal Injury Association Impairment Scale, AIS, C or D grade) were recruited and tested during 4 sessions performed at 2-week intervals up to 8 months after SCI. Intramuscular TA coherence estimation was calculated within the 10–60 Hz bandwidth during controlled maximal isometric and isokinetic foot dorsiflexion. Maximal voluntary dorsiflexion torque, gait function measured with the WISCI II scale, and TA motor evoked potentials (MEP) were recorded.ResultsDuring subacute SCI, significant improvement in total lower limb manual muscle score, TA muscle strength and gait function were observed. No change in TA MEP amplitude was identified. Significant increase in TA coherence was detected in the 40–60 Hz, but not the 15–30 Hz bandwidth. The spasticity syndrome was associated with lower 15-30 Hz TA coherence during maximal isometric dorsiflexion and higher 10–60 Hz coherence during fast isokinetic movement (p < 0.05).ConclusionsLongitudinal estimation of neurophysiological and clinical measures during subacute SCI suggest that estimation of TA muscle coherence during controlled movement provides indirect information regarding adaptive and maladaptive motor control mechanisms during neurorehabilitation.

Spike-timing-dependent plasticity in lower-limb motoneurons after human spinal cord injury.

Recovery of lower-limb function after spinal cord injury (SCI) likely depends on transmission in the corticospinal pathway. Here, we examined whether paired corticospinal-motoneuronal stimulation (PCMS) changes transmission at spinal synapses of lower-limb motoneurons in humans with chronic incomplete SCI and aged-matched controls. We used 200 pairs of stimuli where corticospinal volleys evoked by transcranial magnetic stimulation (TMS) over the leg representation of the motor cortex were timed to arrive at corticospinal-motoneuronal synapses of the tibialis anterior (TA) muscle 2 ms before antidromic potentials evoked in motoneurons by electrical stimulation of the common peroneal nerve (PCMS+) or when antidromic potentials arrived 15 or 28 ms before corticospinal volleys (PCMS-) on separate days. Motor evoked potentials (MEPs) elicited by TMS and electrical stimulation were measured in the TA muscle before and after each stimulation protocol. After PCMS+, the size of MEPs elicited by TMS and electrical stimulation increased for up to 30 min in control and SCI participants. Notably, this was accompanied by increases in TA electromyographic activity and ankle dorsiflexion force in both groups, suggesting that this plasticity has functional implications. After PCMS-, MEPs elicited by TMS and electrical stimulation were suppressed if afferent input from the common peroneal nerve reduced TA MEP size during paired stimulation in both groups. In conclusion, PCMS elicits spike-timing-dependent changes at spinal synapses of lower-limb motoneurons in humans and has potential to improve lower-limb motor output following SCI.NEW & NOTEWORTHY Approaches that aim to enhance corticospinal transmission to lower-limb muscles following spinal cord injury (SCI) are needed. We demonstrate that paired corticomotoneuronal stimulation (PCMS) can enhance plasticity at spinal synapses of lower-limb motoneurons in humans with and without SCI. We propose that PCMS has potential for improving motor output in leg muscles in individuals with damage to the corticospinal tract.

Paired Associative Stimulation Targeting the Tibialis Anterior Muscle using either Mono or Biphasic Transcranial Magnetic Stimulation.

Paired associative stimulation (PAS) protocols induce plastic changes within the motor cortex. The objectives of this study were to investigate PAS effects targeting the tibialis anterior (TA) muscle using a biphasic transcranial magnetic stimulation (TMS) pulse form and, to determine whether a reduced intensity of this pulse would lead to significant changes as has been reported for hand muscles using a monophasic TMS pulse. Three interventions were investigated: (1) suprathreshold PAbi-PAS (n = 11); (2) suprathreshold PAmono-PAS (n = 11) where PAS was applied using a biphasic or monophasic pulse form at 120% resting motor threshold (RMT); (3) subthreshold PAbi-PAS (n = 10) where PAS was applied as for (1) at 95% active motor threshold (AMT). The peak-to-peak motor evoked potentials (MEPs) were quantified prior to, immediately following, and 30 min after the cessation of the intervention. TA MEP size increased significantly for all interventions immediately post (61% for suprathreshold PAbi-PAS, 83% for suprathreshold PAmono-PAS, 55% for subthreshold PAbi-PAS) and 30 min after the cessation of the intervention (123% for suprathreshold PAbi-PAS, 105% for suprathreshold PAmono-PAS, 80% for subthreshold PAbi-PAS. PAS using a biphasic pulse form at subthreshold intensities induces similar effects to conventional PAS.

Convergence of flexor reflex and corticospinal inputs on tibialis anterior network in humans

ObjectiveIntegration between descending and ascending inputs at supraspinal and spinal levels is a key characteristic of neural control of movement. In this study, we characterized convergence of the flexor reflex and corticospinal inputs on the tibialis anterior (TA) network in healthy human subjects. Specifically, we characterized the modulation profiles of the spinal TA flexor reflex following subthreshold and suprathreshold transcranial magnetic stimulation (TMS). We also characterized the modulation profiles of the TA motor evoked potentials (MEPs) following medial arch foot stimulation at sensory and above reflex threshold. MethodsTA flexor reflexes were evoked following stimulation of the medial arch of the foot with a 30ms pulse train at innocuous intensities. TA MEPs were evoked following TMS of the leg motor cortex area. ResultsTMS at 0.7 and at 1.2MEP resting threshold increased the TA flexor reflex when TMS was delivered 40–100ms after foot stimulation, and decreased the TA flexor reflex when TMS was delivered 25–110ms before foot stimulation. Foot stimulation at sensory and above flexor reflex threshold induced a similar time-dependent modulation in resting TA MEPs, that were facilitated when foot stimulation was delivered 40–100ms before TMS. The flexor reflex and MEPs recorded from the medial hamstring muscle were modulated in a similar manner to that observed for the TA flexor reflex and MEP. ConclusionCutaneomuscular afferents from the distal foot can increase the output of the leg motor cortex area. Descending motor volleys that directly or indirectly depolarize flexor motoneurons increase the output of the spinal FRA interneuronal network. The parallel facilitation of flexor MEPs and flexor reflexes is likely cortical in origin. SignificanceAfferent mediated facilitation of corticospinal excitability can be utilized to strengthen motor cortex output in neurological disorders.

Long-latency, inhibitory spinal pathway to ankle flexors activated by homonymous group 1 afferents

Inhibitory feedback from sensory pathways is important for controlling movement. Here, we characterize, for the first time, a long-latency, inhibitory spinal pathway to ankle flexors that is activated by low-threshold homonymous afferents. To examine this inhibitory pathway in uninjured, healthy participants, we suppressed motor-evoked potentials (MEPs), produced in the tibialis anterior (TA), by a prior stimulation to the homonymous common peroneal nerve (CPN). The TA MEP was suppressed by a triple-pulse stimulation to the CPN, applied 40, 50, and 60 ms earlier and at intensities of 0.5-0.7 times motor threshold (average suppression of test MEP was 33%). Whereas the triple-pulse stimulation was below M-wave and H-reflex threshold, it produced a long-latency inhibition of background muscle activity, approximately 65-115 ms after the CPN stimulation, a time period that overlapped with the test MEP. However, not all of the MEP suppression could be accounted for by this decrease in background muscle activity. Evoked responses from direct activation of the corticospinal tract, at the level of the brain stem or thoracic spinal cord, were also suppressed by low-threshold CPN stimulation. Our findings suggest that low-threshold muscle and cutaneous afferents from the CPN activate a long-latency, homonymous spinal inhibitory pathway to TA motoneurons. We propose that inhibitory feedback from spinal networks, activated by low-threshold homonymous afferents, helps regulate the activation of flexor motoneurons by the corticospinal tract.

Corticospinal excitability during walking in humans with absent and partial body weight support

ObjectiveTo establish changes in corticospinal excitability with absent and partial body weight support (BWS), and determine test–retest reliability of motor evoked potentials (MEPs) recordings during stepping in healthy humans. MethodsThe tibialis anterior (TA) and soleus MEPs during stepping at 0 and at 25 BWS were recorded in two experimental sessions in the same subjects. Transcranial magnetic stimulation was delivered randomly across the step cycle at 1.2×TA MEP resting threshold. The non-stimulated associated electromyogram (EMG) was subtracted from the TA and soleus MEPs at identical time windows and bins of the step cycle, and the resultant values were normalized to the maximal homologous EMG activity during stepping. The relationship between MEPs and background EMG activity was determined for each BWS level and session tested. ResultsThe TA MEPs were facilitated at heel contact, progressively decreased during the stance phase, and facilitated throughout the swing phase of the step cycle. In contrast, the soleus MEPs were progressively increased at early-stance, depressed at the stance-to-swing transition, and remained depressed throughout the swing phase. The TA and soleus MEPs were modulated in a similar pattern across sessions at 0 and at 25 BWS, and were linearly related to the associated background EMG activity. ConclusionsThese results provide evidence that reduced body weight loading does not alter the strength of corticospinal excitability, and that MEPs can be reliably recorded at different sessions during stepping in healthy humans. SignificanceA rehabilitation strategy to restore gait in neurological disorders utilizes BWS during stepping on a motorized treadmill. Based on our findings, the strength of corticospinal drive will not be affected negatively during stepping under conditions of partial body loading.

Rapid changes in corticospinal excitability during force field adaptation of human walking

Force field adaptation of locomotor muscle activity is one way of studying the ability of the motor control networks in the brain and spinal cord to adapt in a flexible way to changes in the environment. Here, we investigate whether the corticospinal tract is involved in this adaptation. We measured changes in motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in the tibialis anterior (TA) muscle before, during, and after subjects adapted to a force field applied to the ankle joint during treadmill walking. When the force field assisted dorsiflexion during the swing phase of the step cycle, subjects adapted by decreasing TA EMG activity. In contrast, when the force field resisted dorsiflexion, they increased TA EMG activity. After the force field was removed, normal EMG activity gradually returned over the next 5min of walking. TA MEPs elicited in the early swing phase of the step cycle were smaller during adaptation to the assistive force field and larger during adaptation to the resistive force field. When elicited 5min after the force field was removed, MEPs returned to their original values. The changes in TA MEPs were larger than what could be explained by changes in background TA EMG activity. These effects seemed specific to walking, as similar changes in TA MEP were not seen when seated subjects were tested during static dorsiflexion. These observations suggest that the corticospinal tract contributes to the adaptation of walking to an external force field.

Repetitive common peroneal nerve stimulation increases ankle dorsiflexor motor evoked potentials in incomplete spinal cord lesions

Plasticity of corticospinal tract (CST) activity likely plays a key role in motor function recovery after central nervous system (CNS) lesions. In non-injured adults, 30min of repetitive common peroneal nerve stimulation (rCPnS) increases CST excitability by 40-50% and the effect persists for at least 30min. The present study evaluated with transcranial magnetic stimulation (TMS) the changes in CST excitability after 30min of rCPnS in people with foot drop due to incomplete SCI. Suprathreshold rCPnS (25Hz, alternating 1s on 1s off stimulation cycle) was given for two 15-min periods, while the subject sat at rest with ankle and knee joints fixed. Before, between, and after the periods of stimulation, the tibialis anterior (TA) motor evoked potentials (MEPs) to TMS were measured at a TMS intensity that originally produced a half-maximum MEP (typically 10-20% above threshold) while the sitting subject provided 25-30% maximum voluntary TA contraction. In 10 subjects with SCI, the peak-to-peak TA MEP increased by 14±3% after rCPnS and the peak increase (+21±7%) occurred 15min after the cessation of rCPnS. The TA H-reflex, measured in separate experiments in 7 subjects, did not increase after rCPnS. The results indicate that rCPnS can increase CST excitability for the TA in people with incomplete SCI, although its effects appear smaller and shorter lasting than those found in non-injured control subjects. Such short-term plasticity in the CST excitability induced by rCPnS may contribute to long-term therapeutic effects of functional electrical stimulation previously reported in people with CNS lesions.

Voluntary activation of ankle muscles is accompanied by subcortical facilitation of their antagonists

Flexion and extension movements are organized reciprocally, so that extensor motoneurones in the spinal cord are inhibited when flexor muscles are active and vice versa. During and just prior to dorsiflexion of the ankle, soleus motoneurones are thus inhibited as evidenced by a depression of the soleus H-reflex. It is therefore surprising that soleus motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) have been found not to be reduced and even facilitated during a voluntary dorsiflexion. The objective of this study was to investigate if MEPs, evoked by TMS, show a similar facilitation prior to and at the onset of contraction of muscles that are antagonists to the muscle in which the MEP is evoked and if so, examine the origin of such a facilitatory motor programme. Eleven seated subjects reacted to an auditory cue by contracting either the tibialis anterior (TA) or soleus muscle of the left ankle. TMS was applied to the hotspot of TA and soleus muscles on separate days. Stimuli were delivered prior to and at the beginning of contraction. Soleus MEPs were significantly facilitated when TMS was applied 50 ms prior to onset of plantar flexion. Surprisingly, soleus MEPs were also facilitated (although to a lesser extent) at a similar time in relation to the onset of dorsiflexion. TA MEPs were facilitated 50 ms prior to onset of dorsiflexion and neither depressed nor facilitated prior to plantar flexion. No difference was found between the facilitation of the soleus MEP and motor evoked responses to cervicomedullary stimulation prior to dorsiflexion, suggesting that the increased soleus MEPs were not caused by changes at a cortical level. This was confirmed by the observation that short-latency facilitation of the soleus H-reflex by subthreshold TMS was increased prior to plantar flexion, but not prior to dorsiflexion. These findings suggest that voluntary contraction at the ankle is accompanied by preceding facilitation of antagonists by a subcortical motor programme. This may help to ensure that the direction of movement may be changed quickly and efficiently during functional motor tasks.

Afferent Regulation of Leg Motor Cortex Excitability After Incomplete Spinal Cord Injury

An incomplete spinal cord injury (SCI) impairs neural conduction along spared ascending sensory pathways to disrupt the control of residual motor movements. To characterize how SCI affects the activation of the motor cortex by spared ascending sensory pathways, we examined how stimulation of leg afferents facilitates the excitability of the motor cortex in subjects with incomplete SCI. Homo- and heteronymous afferents to the tibialis anterior (TA) representation in the motor cortex were electrically stimulated, and the responses were compared with uninjured controls. In addition, we examined if cortical excitability could be transiently increased by repetitively pairing stimulation of spared ascending sensory pathways with transcranial magnetic stimulation (TMS), an intervention termed paired associative stimulation (PAS). In uninjured subjects, activating the tibial nerve at the ankle 45-50 ms before a TMS pulse in a conditioning-test paradigm facilitated the motor-evoked potential (MEP) in the heteronymous TA muscle by twofold on average. In contrast, prior tibial nerve stimulation did not facilitate the TA MEP in individuals with incomplete SCI (n = 8 SCI subjects), even in subjects with less severe injuries. However, we provide evidence that ascending sensory inputs from the homonymous common peroneal nerve (CPN) can, unlike the heteronymous pathways, facilitate the motor cortex to modulate the TA MEP (n = 16 SCI subjects) but only in subjects with less severe injuries. Finally, by repetitively coupling CPN stimulation with coincident TA motor cortex activation during PAS, we show that 7 of 13 SCI subjects produced appreciable (>20%) facilitation of the MEP following the intervention. The increase in corticospinal tract excitability by PAS was transient (<20 min) and tended to be more prevalent in SCI subjects with stronger functional ascending sensory pathways.