Conditioned Motor Evoked Potentials Research Articles

The recent history of afferent stimulation modulates corticospinal excitability

BackgroundTranscranial magnetic stimulation (TMS) is widely used to probe corticospinal excitability and fast sensorimotor integration in the primary motor hand area (M1-HAND). A conditioning electrical stimulus, applied to the contralateral hand, can suppress the motor evoked potential (MEP) elicited by TMS of M1-HAND when the afferent stimulus arrives in M1-HAND at the time of TMS. The magnitude of this short-latency afferent inhibition (SAI) is expressed as the ratio between the conditioned and unconditioned MEP amplitude. Objective/HypothesisWe hypothesized that corticospinal excitability and SAI are influenced by the recent history of peripheral electrical stimulation. MethodsIn twenty healthy participants, we recorded MEPs from the right first dorsal interosseus muscle. MEPs were evoked by single-pulse TMS of the left M1-HAND alone (unconditioned TMS) or by TMS preceded by electrical stimulation of the right index finger (“homotopic” conditioning) or little finger (“heterotopic” conditioning). The three conditions were either pseudo-randomly intermixed or delivered in blocks in which a single condition was repeated five or ten times. MEP amplitudes and SAI magnitudes were compared using linear mixed-effect models and one-way ANOVAs. ResultsAll stimulation protocols consistently produced SAI, which was stronger after homotopic stimulation. Randomly intermingling the three stimulation conditions reduced the relative magnitude of homotopic and heterotopic SAI as opposed to blocked stimulation. The apparent attenuation of SAI was caused by a suppression of the unconditioned but not the conditioned MEP amplitude during the randomly intermixed pattern. Conclusion(s): The recent history of afferent stimulation modulates corticospinal excitability. This “history effect” impacts on the relative magnitude of SAI depending on how conditioned and unconditioned responses are intermixed and needs to be taken into consideration when probing afferent inhibition and corticospinal excitability.

The correspondence between EMG and EEG measures of changes in cortical excitability following transcranial magnetic stimulation.

TMS is commonly used to study excitatory/inhibitory neurotransmission in cortical circuits. Changes in cortical excitability following TMS are typically measured from hand (using EMG; limited to motor cortex) or scalp (using EEG); however, it is unclear whether these two measures represent the same activity when assessing motor cortex. We found that TMS-EMG and TMS-EEG measures of motor cortex excitability are differentially affected by sensory confounds at different time points, masking any actual relationship between them in the time domain. In the frequency domain, local high-frequency oscillations in EEG recordings were minimally confounded by sensory artefacts and demonstrated strong correlations with EMG measures of cortical excitability across time, regardless of TMS intensity or waveform. Therefore, despite the effects of sensory artefacts, the two measures of motor cortex excitability share a response component, suggesting that they index a similar cortical activity and perhaps the same neuronal population. Transcranial magnetic stimulation (TMS) is a powerful tool for investigating cortical circuits. Changes in cortical excitability following TMS are typically assessed by measuring changes in either conditioned motor-evoked potentials (MEPs) following paired-pulse TMS over motor cortex or evoked potentials measured with electroencephalography following single-pulse TMS (TEPs). However, it is unclear whether these two measures of cortical excitability index the same cortical response. Twenty-four healthy participants received local and interhemispheric paired-pulse TMS over motor cortex with eight inter-pulse intervals, sub- and suprathreshold conditioning intensities, and two different pulse waveforms, while MEPs were recorded from a hand muscle. TEPs were also recorded in response to single-pulse TMS using the conditioning pulse alone. The relationships between TEPs and conditioned-MEPs were evaluated using metrics sensitive to both their magnitude at each time point and their overall shape across time. The impacts of undesired sensory potentials resulting from TMS pulse and muscle contractions were also assessed on both measures. Both conditioned-MEPs and TEPs were sensitive to re-afferent somatosensory activity following motor-evoked responses, but over different post-stimulus time points. Moreover, the amplitude of low-frequency oscillations in TEPs was strongly correlated with the sensory potentials, whereas early and local high-frequency responses showed minimal relationships. Accordingly, conditioned-MEPs did not correlate with TEPs in the time domain but showed high shape similarity with the amplitude of high-frequency oscillations in TEPs. Therefore, despite the effects of sensory confounds, the TEP and MEP measures share a response component, suggesting that they index a similar cortical response and perhaps the same neuronal populations.

Do nociceptive stimulation intensity and temporal predictability influence pain-induced corticospinal excitability modulation?

Temporal predictability and intensity of an impending nociceptive input both shape pain experience and modulate laser-evoked potentials (LEPs) amplitude. However, it remains unclear whether and how these two factors could influence pain-induced corticospinal excitability modulation. The current study investigated the influence of nociceptive stimulation intensity and temporal predictability on motor-evoked potentials (MEPs) modulation, in parallel to their effect on pain perception and LEPs amplitude. Twenty participants completed electroencephalographic and transcranial magnetic stimulation experiments during which two laser nociceptive stimulation intensities (high and low) were either unpredictably delivered (random delay) or preceded by a fixed-timing cue (fixed delay). The amplitude of the conditioned MEPs was significantly reduced only for the high nociceptive stimulation and was not affected by the temporal predictability of pain (despite the fact that temporal predictability modulated the amplitude of P2 LEP component amplitude). However, a posteriori analyses based on patterns of pain-induced MEPs modulation revealed that participants in which nociceptive stimulation resulted in an increase in corticospinal excitability were more affected by the predictability of pain (i.e. increasing corticospinal excitability even more when pain occurrence was predictable), regardless of the nociceptive stimulation intensity; whereas participants in which nociceptive stimulation resulted in a decrease in corticospinal excitability were sensitive to the intensity of the stimulation but not its predictability. These results suggest a potential influence of cognitive factors such as temporal predictability on the response of the motor system in the presence of pain for some participants, contributing to explain, at least in part, the high variability highlighted in a number of previous studies.

The Sexes Do Not Differ for Neural Responses to Submaximal Elbow Extensor Fatigue.

To investigate possible sex-related differences in group III/IV muscle afferent feedback with isometric fatigue, we aimed to assess the effect of a sustained submaximal elbow extensor contraction on motoneuronal excitability (cervicomedullary motor evoked potential [CMEP]) and voluntary activation (VA). Twenty-four participants (12 females) performed a 15-min contraction at the level of EMG activity recorded at 15% of maximal torque. Each minute, CMEP were elicited by cervicomedullary stimulation with and without conditioning transcranial magnetic stimulation (TMS) delivered 100 ms earlier. Unconditioned and conditioned motor evoked potentials (MEP) in response to TMS were also recorded to assess motor cortical excitability. CMEP and MEP were normalized for changes in downstream excitability and expressed as percentage of their prefatigue (control) values. Postfatigue, VA was calculated from superimposed and resting tetani evoked by stimulation over triceps brachii. Males were twice as strong as females, but the sexes did not differ for any variable during the fatigue protocol. On a 0-10 scale, RPE increased from ~2.5 to 9. The unconditioned CMEP did not change, whereas the conditioned CMEP was reduced by ~50%. By contrast, the unconditioned and conditioned MEP increased to ~200% and ~320% of the control values, respectively. At task termination, maximal torque was reduced ~40%, and VA was ~80%, down from a prefatigue value of ~96%. Results support the scant published data on the elbow extensors and indicate no sex-related differences for isometric fatigue of this muscle group. The motoneuronal and VA data suggest that metabolite buildup and group III/IV muscle afferent activity were similar for females and males.

Fatigue-related group III/IV muscle afferent feedback facilitates intracortical inhibition during locomotor exercise.

This study investigated the influence of group III/IV muscle afferents on corticospinal excitability during cycling exercise and focused on GABAB neuron-mediated inhibition as a potential underlying mechanism. The study provides novel evidence to demonstrate that group III/IV muscle afferent feedback facilitates inhibitory intracortical neurons during whole body exercise. Firing of these interneurons probably contributes to the development of central fatigue during physical activity. We investigated the influence of group III/IV muscle afferents in determining corticospinal excitability during cycling exercise and focused on GABAB neuron-mediated inhibition as a potential underlying mechanism. Both under control conditions (CTRL) and with lumbar intrathecal fentanyl (FENT) impairing feedback from group III/IV leg muscle afferents, subjects (n=11) cycled at a comparable vastus-lateralis EMG signal (∼0.26mV) before (PRE; 100W) and immediately after (POST; 90±2W) fatiguing constant-load cycling exercise (80% Wpeak; 221±10W; ∼8min). During, PRE and POST cycling, single and paired-pulse (100ms interstimulus interval) transcranial magnetic stimulations (TMS) were applied to elicit unconditioned and conditioned motor-evoked potentials (MEPs), respectively. To distinguish between cortical and spinal contributions to the MEPs, cervicomedullary stimulations (CMS) were used to elicit unconditioned (CMS only) and conditioned (TMS+CMS, 100ms interval) cervicomedullary motor-evoked potentials (CMEPs). While unconditioned MEPs were unchanged from PRE to POST in CTRL, unconditioned CMEPs increased significantly, resulting in a decrease in unconditioned MEP/CMEP (P<0.05). This paralleled a reduction in conditioned MEP (P<0.05) and no change in conditioned CMEP. During FENT, unconditioned and conditioned MEPs and CMEPs were similar and comparable during PRE and POST (P>0.2). These findings reveal that feedback from group III/IV muscle afferents innervating locomotor muscle decreases the excitability of the motor cortex during fatiguing cycling exercise. This impairment is, at least in part, determined by the facilitating effect of these sensory neurons on inhibitory GABAB intracortical interneurons.

Modulation of short-latency afferent inhibition and short-interval intracortical inhibition by test stimulus intensity and motor-evoked potential amplitude.

The present study aimed to investigate the effects of changes in motor-evoked potential (MEP) amplitude on short-latency afferent inhibition (SAI) and short-interval intracortical inhibition (SICI). MEPs in response to transcranial magnetic stimulation (TMS) of the left primary motor cortex were measured from the right first dorsal interosseous muscle of 10 healthy participants. SAI was evaluated by measuring MEPs in response to variable-intensity test TMS pulses delivered 22 ms following electrical stimulation of the right ulnar nerve (intensity fixed at the motor threshold). SICI was evaluated by pairing a constant conditioning TMS pulse [80% of resting motor threshold (RMT)] with a second variable-intensity TMS test pulse (interstimulus interval of 2 ms). The intensity of the test stimulus was set at 110, 115, 120, 125, or 130%RMT on a given trial. SAI was significantly reduced when evoked by a 125%RMT test TMS pulse compared with 110%RMT, and absent at 130%RMT. There was no significant difference in SICI at 110-130%RMT. Significant positive correlations were detected between the unconditioned and conditioned MEP amplitudes at both SAI and SICI. This study demonstrated that SAI and SICI are highly sensitive to the MEP amplitude and SAI decreases with increasing MEP amplitude, whereas SICI does not change. The different responses for SAI and SICI to the increasing MEP amplitude is interpreted as evidence that different inhibitory neural circuits may be involved in SAI and SICI.

Short-interval cortical inhibition and intracortical facilitation during submaximal voluntary contractions changes with fatigue.

This study determined whether short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) change during a sustained submaximal isometric contraction. On 2days, 12 participants (6 men, 6 women) performed brief (7-s) elbow flexor contractions before and after a 10-min fatiguing contraction; all contractions were performed at the level of integrated electromyographic activity (EMG) which produced 25% maximal unfatigued torque. During the brief 7-s and 10-min submaximal contractions, single (test) and paired (conditioning-test) transcranial magnetic stimuli were applied over the motor cortex (5s apart) to elicit motor-evoked potentials (MEPs) in biceps brachii. SICI and ICF were elicited on separate days, with a conditioning-test interstimulus interval of 2.5 and 15ms, respectively. On both days, integrated EMG remained constant while torque fell during the sustained contraction by ~51.5% from control contractions, perceived effort increased threefold, and MVC declined by 21-22%. For SICI, the conditioned MEP during control contractions (74.1±2.5% of unconditioned MEP) increased (less inhibition) during the sustained contraction (last 2.5min: 86.0±5.1%; P<0.05). It remained elevated in recovery contractions at 2min (82.0±3.8%; P<0.05) and returned toward control at 7-min recovery (76.3±3.2%). ICF during control contractions (conditioned MEP 129.7±4.8% of unconditioned MEP) decreased (less facilitation) during the sustained contraction (last 2.5min: 107.6±6.8%; P<0.05) and recovered to 122.8±4.3% during contractions after 2min of recovery. Both intracortical inhibitory and facilitatory circuits become less excitable with fatigue when assessed during voluntary activity, but their different time courses of recovery suggest different mechanisms for the fatigue-related changes of SICI and ICF.

The influence of short-interval intracortical facilitation when assessing developmental changes in short-interval intracortical inhibition

Objective: Measures of short-interval intracortical inhibition (SICI) can be contaminated by excitatory influences of short-interval intracortical facilitation (SICF), unless examined at individually-optimized interstimulus intervals (ISIs). We hypothesized that age-related differences in SICF would explain previously reported reduced SICI in children and adolescents compared with adults. Methods: Fifty-one participants, aged 8–29years, underwent transcranial magnetic stimulation. SICF curves were constructed to determine the ISI at which SICF was minimal (i.e. the first trough). SICI curves were constructed at this individually-determined ISI with conditioning stimulus (S1) intensities of 60–110% of active motor threshold. Results: There was no effect of age on the ISI corresponding with the SICF trough. However, there was a main effect of age on the amplitude of the conditioned motor-evoked potential at the different ISIs, such that children aged 8–12years demonstrated greater SICF than those aged 16–18 and 19–21years. There was no effect of age on SICI, and no interaction between age group and S1 intensity. Conclusions: Compared with that in older adolescents and young adults, SICF is enhanced in children aged 8–12years. Surprisingly, this enhanced SICF does not appear to reduce the degree of SICI that can be evoked at the first trough in this age group. Significance: This is the first report of enhanced SICF in young children. It remains possible that enhanced SICF may have confounded earlier reports of reduced SICI in children less than 8years.

Late cortical disinhibition in relaxed versus active hand muscles

Recent research suggests that long-interval intracortical inhibition (LICI) is followed by a transitory period of late cortical disinhibition (LCD) that can even lead to a net increase in cortical excitability. The relationship between LICI/LCD and voluntary drive remains poorly understood. Our study aims at investigating the influence of index abduction on LICI and LCD in an actively engaged muscle and a neighboring muscle, while varying the intensity of the conditioning stimulus (CS). Motor-evoked potentials (MEPs) were recorded from the first dorsal interosseus (FDI) and abductor digiti minimi (ADM) muscles in 13 subjects. Paired-pulses were delivered with 10 different interstimulus intervals (ranging from 60 to 290ms). Whatever the condition (relaxed or active FDI), the test stimulus was set to evoke an MEP of 1mV. The time course of conditioned MEP amplitude was compared for relaxed and active conditions when the CS intensity was set to (i) 130% of the rest motor threshold (RMT) or (ii) to evoke the same size of MEP under both conditions. LICI lasted longer (i.e. disinhibition occurred later) at rest than during abduction when evoked either by similar or matched conditioning stimuli. No post-LICI facilitation was observed at rest – even when the CS intensity was set to 160% RMT. In contrast, long-interval intracortical facilitation (LICF) was observed in the quiescent ADM when FDI was active. LICF may then be associated with voluntary activity albeit with lack of topographic specificity.

Whole-body water flow stimulation to the lower limbs modulates excitability of primary motor cortical regions innervating the hands: a transcranial magnetic stimulation study.

Whole-body water immersion (WI) has been reported to change sensorimotor integration. However, primary motor cortical excitability is not affected by low-intensity afferent input. Here we explored the effects of whole-body WI and water flow stimulation (WF) on corticospinal excitability and intracortical circuits. Eight healthy subjects participated in this study. We measured the amplitude of motor-evoked potentials (MEPs) produced by single transcranial magnetic stimulation (TMS) pulses and examined conditioned MEP amplitudes by paired-pulse TMS. We evaluated short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) using the paired-TMS technique before and after 15-min intervention periods. Two interventions used were whole-body WI with water flow to the lower limbs (whole-body WF) and whole-body WI without water flow to the lower limbs (whole-body WI). The experimental sequence included a baseline TMS assessment (T0), intervention for 15 min, a second TMS assessment immediately after intervention (T1), a 10 min resting period, a third TMS assessment (T2), a 10 min resting period, a fourth TMS assessment (T3), a 10 min resting period, and the final TMS assessment (T4). SICI and ICF were evaluated using a conditioning stimulus of 90% active motor threshold and a test stimulus adjusted to produce MEPs of approximately 1–1.2 mV, and were tested at intrastimulus intervals of 3 and 10 ms, respectively. Whole-body WF significantly increased MEP amplitude by single-pulse TMS and led to a decrease in SICI in the contralateral motor cortex at T1, T2 and T3. Whole-body WF also induced increased corticospinal excitability and decreased SICI. In contrast, whole-body WI did not change corticospinal excitability or intracortical circuits.

Loss of short-latency afferent inhibition and emergence of afferent facilitation following neuromuscular electrical stimulation

Neuromuscular electrical stimulation (NMES) increases the excitability of corticospinal (CS) pathways by altering circuits in motor cortex (M1). How NMES affects circuits interposed between the ascending afferent volley and descending CS pathways is not known. Presently, we hypothesized that short-latency afferent inhibition (SAI) would be reduced and afferent facilitation (AF) enhanced when NMES increased CS excitability. NMES was delivered for 40min over the ulnar nerve. To assess CS excitability, motor evoked potentials (MEPs) were evoked using transcranial magnetic stimulation (TMS) delivered at 120% resting threshold for first dorsal interosseus muscle. These MEPs increased by ∼1.7-fold following NMES, demonstrating enhanced CS excitability. SAI and AF were tested by delivering a “conditioning” electrical stimulus to the ulnar nerve 18–25ms and 28–35ms before a “test” TMS pulse, respectively. Conditioned MEPs were compared to unconditioned MEPs evoked in the same trials. TMS was adjusted so unconditioned MEPs were not different before and after NMES. At the SAI interval, conditioned MEPs were 25% smaller than unconditioned MEPs before NMES but conditioned and unconditioned MEPs were not different following NMES. At the AF interval, conditioned MEPs were not different from unconditioned MEPs before NMES, but were facilitated by 33% following NMES. Thus, when NMES increases CS excitability there are concurrent changes in the effect of afferent input on M1 excitability, resulting in a net increase in the excitatory effect of the ascending afferent volley on CS circuits. Maximising this excitatory effect on M1 circuits may help strengthen CS pathways and improve functional outcomes of NMES-based rehabilitation programs.

Spinal inhibition of descending command to soleus motoneurons is removed prior to dorsiflexion

It has recently been demonstrated that soleus motor-evoked potentials (MEPs) are facilitated prior to the onset of dorsiflexion. The purpose of this study was to examine if this could be explained by removal of spinal inhibition of the descending command to soleus motoneurons. To test this, we investigated how afferent inputs from the tibialis anterior muscle modulate the corticospinal activation of soleus spinal motoneurons at rest, during static contraction and prior to movement. MEPs activated by transcranial magnetic stimulation (TMS) and Hoffmann reflexes (H-reflexes), activated by electrical stimulation of the posterior tibial nerve (PTN), were conditioned by prior stimulation of the common peroneal nerve (CPN) at a variety of conditioning-test (CT) intervals. MEPs in the precontracted soleus muscle were inhibited when the TMS pulse was preceded by CPN stimulation with a CT interval of 35 ms, and they were facilitated for CT intervals of 50-55 ms. A similar inhibition of the soleus H-reflex was not observed. To investigate which descending pathways might be responsible for the afferent-evoked inhibition and facilitation, we examined the effect of CPN stimulation on short-latency facilitation (SLF) and long-latency facilitation (LLF) of the soleus H-reflex induced by a subthreshold TMS pulse at different CT intervals. SLF is known to reflect the excitability of the fastest conducting, corticomotoneuronal cells whereas LLF is believed to be caused by more indirect descending pathways. At CT intervals of 40-45 ms, the LLF was significantly more inhibited compared to the SLF when taking the effect on the H-reflex into account. Finally, we investigated how the CPN-induced inhibition and facilitation of the soleus MEP were modulated prior to dorsiflexion. Whereas the late facilitation (CT interval: 55 ms) was similar prior to dorsiflexion and at rest, no inhibition could be evoked at the earlier latency (CT interval: 35 ms) prior to onset of dorsiflexion. The observation that the CPN-induced inhibition of soleus MEPs disappears prior to onset of dorsiflexion may explain why soleus MEPs are facilitated prior to onset of dorsiflexion contraction. A possible mechanism involves the removal of inhibition of the descending command to the motoneurons at a spinal interneuronal level because the inhibition was seen in LLF and not in SLF, and the MEP inhibition was not observed in the H-reflex. The data illustrate that spinal interneuronal pathways modify descending commands to human spinal motoneurons and influence the size of MEPs elicited by TMS.

Tendon vibration does not alter decreased responsiveness of motoneurones in the absence of motor cortical input during fatigue

Tendon vibration does not alter decreased responsiveness of motoneurones in the absence of motor cortical input during fatigue

A motor cortex excitability and gait analysis on Parkinsonian patients

Transcranial magnetic stimulation (TMS) parameters were recorded in a lower limb muscle and correlated with the gait parameters of 25 patients with Parkinson's disease (PD) with and without dopamine substitution treatment (DST) and 10 control subjects. Single and paired-pulse TMS were recorded in the tibialis anterior muscle (TA). Gait analysis was performed using a 3D motion analysis system. Parkinsonian patients (PP) did not differ from the control subjects (CS) in terms of relaxed motor threshold, active motor threshold (AMT), cortical silent period (CSP), motor-evoked potential (MEP) amplitude and area, or paired-pulse TMS with short interstimulus intervals (ISI). At longer ISIs, paired-pulse TMS showed that the amplitudes of the conditioned MEPs were lower in untreated PP than in CS. DST partially compensated for this difference. Gait analysis showed that the gait of PP undergoing no treatment was slower and the stride length shorter than normal. Both of these parameters improved under DST, however. Analysis of data obtained on all the subjects combined showed that both of the latter parameters were correlated with the paired-pulse MEP amplitude and area at longer ISIs. In PP, the cortical areas responsible for the lower limb movements seem to undergo intracortical facilitation (ICF) impairments, whereas the intracortical inhibition process is normal. The ICF level was found to be associated to the stride length and the velocity. The fact that only these two gait parameters were found to be dopa responsive indicates that dopaminergic treatment may improve gait disorders by restoring the ICF.

The response to paired motor cortical stimuli is abolished at a spinal level during human muscle fatigue

During maximal exercise, supraspinal fatigue contributes significantly to the decline in muscle performance but little is known about intracortical inhibition during such contractions. Long-interval inhibition is produced by a conditioning motor cortical stimulus delivered via transcranial magnetic stimulation (TMS) 50-200 ms prior to a second test stimulus. We aimed to delineate changes in this inhibition during a sustained maximal voluntary contraction (MVC). Eight subjects performed a 2 min MVC of elbow flexors. Single test and paired (conditioning-test interval of 100 ms) stimuli were delivered via TMS over the motor cortex every 7-8 s throughout the effort and during intermittent MVCs in the recovery period. To determine the role of spinal mechanisms, the protocol was repeated but the TMS test stimulus was replaced by cervicomedullary stimulation which activates the corticospinal tract. TMS motor evoked potentials (MEPs) and cervicomedullary motor evoked potentials (CMEPs) were recorded from biceps brachii. Unconditioned MEPs increased progressively with fatigue, whereas CMEPs increased initially but returned to the control value in the final 40 s of contraction. In contrast, both conditioned MEPs and CMEPs decreased rapidly with fatigue and were virtually abolished within 30 s. In recovery, unconditioned responses required <30 s but conditioned MEPs and CMEPs required 90 s to return to control levels. Thus, long-interval inhibition increased markedly as fatigue progressed. Contrary to expectations, subcortically evoked CMEPs were inhibited as much as MEPs. This new phenomenon was also observed in the first dorsal interosseous muscle. Tested with a high intensity conditioning stimulus during a fatiguing maximal effort, long-interval inhibition of MEPs was increased primarily by spinal rather than motor cortical mechanisms. The spinal mechanisms exposed here may contribute to the development of central fatigue in human muscles.

Electrical and magnetic repetitive transcranial stimulation of the primary motor cortex in healthy subjects

Repetitive transcranial magnetic stimulation (rTMS) delivered in short trains at 5 Hz frequency and suprathreshold intensity over the primary motor cortex (M1) in healthy subjects facilitates the motor-evoked potential (MEP) amplitude by increasing cortical excitability through mechanisms resembling short-term synaptic plasticity. In this study, to investigate whether rTES acts through similar mechanisms we compared the effects of rTMS and repetitive transcranial electrical stimulation (rTES) (10 stimuli-trains, 5 Hz frequency, suprathreshold intensity) delivered over the M1 on the MEP amplitude. Four healthy subjects were studied in two separate sessions in a relaxed condition. rTMS and anodal rTES were delivered in trains to the left M1 over the motor area for evoking a MEP in the right first dorsal interosseous muscle. Changes in MEP size and latency during the course of the rTMS and rTES trains were compared. The possible effects of muscle activation on MEP amplitude were evaluated, and the possible effects of cutaneous trigeminal fibre activation on corticospinal excitability were excluded in a control experiment testing the MEP amplitude before and after supraorbital nerve repetitive electrical stimulation. Repeated measures analysis of variance (ANOVA) showed that rTES and rTMS trains elicited similar amplitude first MEPs and a similar magnitude MEP amplitude facilitation during the trains. rTES elicited a first MEP with a shorter latency than rTMS, without significant changes during the course of the train of stimuli. The MEP elicited by single-pulse TES delivered during muscle contraction had a smaller amplitude than the last MEP in the rTES trains. Repetitive supraorbital nerve stimulation left the conditioned MEP unchanged. Our results suggest that 5 Hz-rTES delivered in short trains increases cortical excitability and does so by acting on the excitatory interneurones probably through mechanisms similar to those underlying the rTMS-induced MEP facilitation.

Raised corticomotor excitability of M1 forearm area following anodal tDCS is sustained during robotic wrist therapy in chronic stroke

Anodal transcranial direct current stimulation (tDCS) can transiently increase corticomotor excitability of intrinsic hand muscles and improve upper limb function in patients with chronic stroke. As a preliminary study, we tested whether increased corticomotor excitability would be similarly observed in muscles acting about the wrist, and remain present during robotic training involving active wrist movements, in six chronic stroke patients with residual motor deficit. Transcranial magnetic stimulation (TMS) generated motor evoked potentials (MEP) in the flexor carpi radialis (FCR) and provided a measure of corticomotor excitability and short-interval cortical inhibition (SICI) before and immediately after a period of tDCS (1 mA, 20 min, anode and TMS applied to the lesioned hemisphere), and robotic wrist training (1hr). Following tDCS, the same TMS current strength evoked an increased MEP amplitude (mean 168 +/- 22%SEM; p < 0.05), that remained increased after robot training (166 +/- 23%; p < 0.05). Conditioned MEPs were of significantly lower amplitude relative to unconditioned MEPs prior to tDCS (62 +/- 6%, p < 0.05), but not after tDCS (89 +/- 14%, p = 0.40), or robot training (91 +/- 8%, p = 0.28), suggesting that the increased corticomotor excitability is associated with reduced intracortical inhibition. The persistence of these effects after robotic motor training, indicates that a motor learning and retraining program can co-exist with tDCS-induced changes in cortical motor excitability, and supports the concept of combining brain stimulation with physical therapy to promote recovery after brain injury.

Reduction of Intracortical Inhibition in Soleus Muscle During Postural Activity

Short-interval intracortical inhibition (SICI) decreases during voluntary contraction of the target muscle. It is unknown whether this effect also occurs with postural contractions. We have compared the effects of voluntary and postural contractions on SICI in the soleus (SOL) muscle. We applied transcranial magnetic stimuli (TMS) in subjects under three tasks: sitting at rest (Rest), sitting while activating the SOL muscle (Voluntary), or standing quietly (Postural). In control trials, we applied suprathreshold TMS to obtain unconditioned motor-evoked potentials (MEPs). In test trials, the same TMS was preceded by a subthreshold TMS at different interstimulus intervals (ISIs), to obtain a conditioned MEP. SICI and intracortical facilitation (ICF) were expressed as the decrease or increase in MEP size relative to unconditioned MEPs. There was significant effect of task in mean SICI or mean ICF in SOL. Mean SICI in SOL was 52% in Rest and decreased to 21% in Voluntary and 15% in Postural. Mean ICF in SOL was 132% and decreased to 113% in Voluntary and to 108% in Postural. Mean SICI in SOL was not different in Voluntary and Postural tasks. There was no effect of task in mean SICI or mean ICF in TA. Our results indicate that decrease of SICI with muscle contraction occurs to a similar extent with tonic voluntary and postural activation, suggesting that those contractions require a similar type of cortical involvement. However, it cannot be excluded that some part of the SICI reduction with muscle contraction depends on changes in segmental excitability.

Sensorimotor integration in patients with parkinsonian type multisystem atrophy

Sensorimotor integration is an essential feature of the central nervous system that contributes to the accurate performance of motor tasks. Some patients with multiple system atrophy with parkinsonian features (MSAp) exhibit clinical signs compatible with an abnormal central nervous system excitability to somatosensory inputs, such as action myoclonus or enhanced cutaneo-muscular reflexes. To investigate further the site where such dysfunction in sensorimotor integration takes place, we examined the inhibitory effects of a cutaneous afferent volley at two different levels of the motor system in 10 MSAp patients and in 10 age-matched healthy volunteers. Electrical digital nerve stimuli were given as the conditioning stimulus for the motor evoked potentials (MEP) elicited by transcranial magnetic stimulation in hand muscles, and for the blink reflex responses obtained in the orbicularis oculi muscles by supraorbital nerve stimulation. Intervals for the conditioning were 20 to 50 ms for the MEP and 90 to 110 ms for the blink reflex. The MEP was significantly inhibited in test trials in healthy volunteers, reaching a mean of 32% of the baseline values at the ISI of 35 ms. Significant inhibition occurred also in the blink reflex, in which the R2 response was a mean of 12% of baseline values at the ISI of 100 ms. The inhibitory effects were abnormally reduced in 8 patients on the MEP, and in 7 patients on the blink reflex. There were significant group differences between patients and control subjects in the size of the conditioned MEP and blink reflex. These results suggest that sensorimotor integration is abnormal in patients with MSAp in at least two central nervous system sites: the sensorimotor cortex, and the brainstem reticular formation.

Neurophysiological examination of the corticospinal system and voluntary motor control in motor-incomplete human spinal cord injury

This study employed neurophysiological methods to relate the condition of the corticospinal system with the voluntary control of lower-limb muscles in persons with motor-incomplete spinal cord injury. It consisted of two phases. In a group of ten healthy subjects, single and paired transcranial magnetic stimulation (TMS) of the motor cortex was used to study the behavior of the resulting motor evoked potentials (MEP) in lower-limb muscles. Interstimulus intervals (ISIs) of 15-100 ms were examined for augmentation of test MEPs by threshold or subthreshold conditioning stimuli. The second phase of this study examined eight incomplete spinal cord injured (iSCI) subjects, American Spinal Injury Association Impairment Scale C (n = 5) and D (n = 3) in whom voluntary motor control was quantified using the surface EMG (sEMG) based Voluntary Response Index (VRI). The VRI is calculated to characterize relative output patterns across ten lower-limb muscles recorded during a standard protocol of elementary voluntary motor tasks. VRI components were calculated by comparing the distribution of sEMG in iSCI subjects with prototype patterns collected from 15 healthy subjects using the same rigidly administered protocol, The resulting similarity index (SI) and magnitude values provided the measure of voluntary motor control. Corticospinal system connections were characterized by the thresholds for MEPs in key muscles. Key muscles were those that function as the prime-movers, or agonists for the voluntary movements from which the VRI data were calculated. Results include healthy-subject data that showed significant increases in conditioned MEP responses with paired stimuli of 15-50 ms ISI. Stimulus pairs of 75 and 100 ms showed no increase in MEP peak amplitude over that of the single-pulse conditioning stimulus alone, usually no response. For the iSCI subjects, 42% of the agonists responded to single-pulse TMS and 25% required paired-pulse TMS to produce an MEP. American Spinal Injury Association Impairment Scale component motor scores for agonist muscles, Quadriceps, Tibialis Anterior, and Triceps Surae, were significantly lower where MEPs could not be obtained (p < 0.05). VRI values were also significantly lower for motor tasks with agonists that had no resting MEP (p < 0.01). Therefore, the presence of a demonstrable connection between the motor cortex and spinal motor neurons in persons with SCI was related to the quality of post-injury voluntary motor control as assessed by the VRI.