Changes In Motor-evoked Potential Size Research Articles

Crossed corticospinal facilitation between arm and trunk muscles in humans.

A voluntary contraction of muscles with one arm increases the excitability of corticospinal projections to the contralateral resting arm, a phenomenon known as crossed facilitation. Although many motor tasks engage simultaneous activation of the arm and trunk, interactions between corticospinal projections targeting these segments remain largely unknown. Using transcranial magnetic stimulation over the trunk representation of the primary motor cortex, we examined motor-evoked potentials (MEPs) in the resting erector spinae (ES) muscle when the contralateral arm remained at rest or performed 20% of isometric maximal voluntary contraction (MVC) into index finger abduction, thumb abduction, elbow flexion, and elbow extension. We found that MEP size in the ES increased during all voluntary contractions, with greater facilitation occurring during elbow flexion and index finger abduction. To further examine the origin of changes in MEP size, we measured short-interval intracortical inhibition (SICI) and cervicomedullary MEPs (CMEPs) in the ES muscle during elbow flexion and index finger abduction and when the arm remained at rest. Notably, SICI decreased and CMEPs remained unchanged in the ES during both voluntary contractions compared with rest, suggesting a cortical origin for the effects. Our findings reveal crossed facilitatory interactions between trunk extensor and proximal and distal arm muscles, particularly for elbow flexor and index finger muscles, likely involving cortical mechanisms. These interactions might reflect the different role of these muscles during functionally relevant arm and trunk movements. NEW & NOTEWORTHY Many of the tasks of daily life involve simultaneous activation of the arm and trunk. We found that responses in the erector spinae muscles evoked by motor cortical stimulation increased in size during elbow flexion and extension and during index finger abduction and thumb abduction. Crossed facilitation with the trunk was more pronounced during elbow flexion and index finger abduction. These results might reflect the different role of these muscles during arm and trunk movements.

Distinct influence of hand posture on cortical activity during human grasping.

We recently showed that subcortical circuits contribute to control the gain of motor cortical inputs to spinal motoneurons during precision grip of a small object. Here, we examine whether the involvement of the motor cortex could be revealed by grasping with different hand postures. Using noninvasive cortical, cervicomedullary, and peripheral nerve stimulation we examined in humans motor-evoked potentials (MEPs) and the activity in intracortical circuits (suppression of voluntary electromyography) and spinal motoneurons (F-waves) in intrinsic hand muscles when grasping a 6 mm cylinder with the index finger and thumb while the hand was held in the neutral position or during full pronation and supination. We demonstrate that the size of cortically evoked MEPs in the first dorsal interosseous, but not in the abductor pollicis brevis and abductor digit minimi muscles, was reduced to a similar extent during grasping with the hand pronated or supinated compared with the neutral position. Notably, the suppression of MEPs was present from the MEP onset, suggesting that indirect corticospinal pathways were less likely to be involved than direct connections. There was less intracortical inhibition targeting the first dorsal interosseous during hand pronation and supination compared with neutral and this negatively correlated with changes in MEP size. In contrast, cervicomedullary MEPs and F-waves remained unchanged across conditions, as did MEPs evoked during unopposed weak flexion of the index finger. Our findings reveal a distinct influence of the posture of the hand on the activity of cortical pathways controlling different hand muscles during grasping.

A Closed-Loop Brain–Computer Interface Triggering an Active Ankle–Foot Orthosis for Inducing Cortical Neural Plasticity

In this paper, we present a brain-computer interface (BCI) driven motorized ankle-foot orthosis (BCI-MAFO), intended for stroke rehabilitation, and we demonstrate its efficacy in inducing cortical neuroplasticity in healthy subjects with a short intervention procedure (∼15 min). This system detects imaginary dorsiflexion movements within a short latency from scalp EEG through the analysis of movement-related cortical potentials (MRCPs). A manifold-based method, called locality preserving projection, detected the motor imagery online with a true positive rate of 73.0 ± 10.3%. Each detection triggered the MAFO to elicit a passive dorsiflexion. In nine healthy subjects, the size of the motor-evoked potential (MEP) elicited by transcranial magnetic stimulation increased significantly immediately following and 30 min after the cessation of this BCI-MAFO intervention for ∼15 min ( p = 0.009 and , respectively), indicating neural plasticity. In four subjects, the size of the short latency stretch reflex component did not change following the intervention, suggesting that the site of the induced plasticity was cortical. All but one subject also performed two control conditions where they either imagined only or where the MAFO was randomly triggered. Both of these control conditions resulted in no significant changes in MEP size (p = 0.38 and p = 0.15). The proposed system provides a fast and effective approach for inducing cortical plasticity through BCI and has potential in motor function rehabilitation following stroke.

IS 22. Coupling of motor imagination and nervous system stimulation to induce cortical plasticity

We recently developed a novel technique for inducing plasticity in the human motor cortex by combining the physiologically generated signal when a person imagines a simple dorsiflexion task with the peripheral stimulation of the nerve that innervates the muscle involved in the task ( Mrachacz-Kersting et al., 2012 ). The subject activates the relevant brain areas via imagination and is provided with the expected afferent feedback via the single peripheral electrical stimulation to the target nerve. This protocol induced significant plasticity only when the afferent volley was timed to arrive during the peak negativity (PN) of the movement-related cortical potential (MRCP) generated in the corresponding brain area during the imagined task. The changes were specific to the target muscle, long lasting and rapidly evolving. These changes could be induced independent of if the subject was cued to start the movement or self-selected when to perform ( [Mrachacz-Kersting et al., 2012] , [Niazi et al., 2012] ). Only 50 repetitions of this combined stimulation paradigm are required to have an effect that outlasts the intervention. In a recent study with our collaborator Professor Kostic of the Department of Neurology, University of Belgrade, Serbia, we applied this intervention in a group of 13 chronic stroke subjects and evaluated neural plasticity and functional changes as quantified by the 10 m walk test and a foot tapping task. Patients attended five separate sessions. In the first and last session clinical measures and the MRCP during 50 attempted dorsiflexion movements were collected. In sessions two to four they were exposed to the intervention as described above. Across all subjects the motor evoked potentials (MEPs), quantified prior to and following the interventions increased significantly (80% on average). Patients were able to walk faster (on average 8% in 10 m walk test) and improved foot tapping frequency by 18%. Interestingly a finger tapping task showed no changes, thus further supporting the specificity of this intervention. Our initial results using the novel BCI interface leave a number of open issues. Firstly, the MRCP generated during task execution or imagination has several generators that differ depending on whether the task is cue based or self-paced ( Lu et al., 2012 ), yet our results show that our intervention is successful in both paradigms ( [Mrachacz-Kersting et al., 2012] , [Niazi et al., 2012] ). In an ongoing study we are randomly exposing healthy subjects to either paradigm following a selective blocking of either PMd or SMA to further enhance our understanding of the generators of the MRCP. Secondly, we have shown in the past that we can differentiate between ballistic versus slow movements as well as between low force and high force movements ( [do Nascimento and Farina, 2008] , [Gu et al., 2009] ), also from single trial MRCPs. The implications for the development of a brain-driven electrical stimulator that will provide the exact amount of afferent feedback necessary during an imagined movement are substantial. It will allow a more engaging approach to the rehabilitation of affected function that is tailored to the exact need of the patient. Current work aims at refining our BCI to allow this. The goal is to ask subjects to imagine a dorsiflexion consisting of different movement parameters (force and speed) and to provide the afferent feedback that would have been generated had the movement been performed rather than imagined. We alter both the rate and intensity of the peripheral nerve stimulation to meet this demand. Preliminary results show that cortical plasticity as assessed by changes in MEP size is further enhanced when the afferent feedback is matched to the characteristics of the imagined movement.

Motor Recovery after Spinal Cord Injury Enhanced by Strengthening Corticospinal Synaptic Transmission

The corticospinal tract is an important target for motor recovery after spinal cord injury (SCI) in animals and humans. Voluntary motor output depends on the efficacy of synapses between corticospinal axons and spinal motoneurons, which can be modulated by the precise timing of neuronal spikes. Using noninvasive techniques, we developed tailored protocols for precise timing of the arrival of descending and peripheral volleys at corticospinal-motoneuronal synapses of an intrinsic finger muscle in humans with chronic incomplete SCI. We found that arrival of presynaptic volleys prior to motoneuron discharge enhanced corticospinal transmission and hand voluntary motor output. The reverse order of volley arrival and sham stimulation did not affect or decreased voluntary motor output and electrophysiological outcomes. These findings are the first demonstration that spike timing-dependent plasticity of residual corticospinal-motoneuronal synapses provides a mechanism to improve motor function after SCI. Modulation of residual corticospinal-motoneuronal synapses may present a novel therapeutic target for enhancing voluntary motor output in motor disorders affecting the corticospinal tract.

Short-term and long-term plasticity interaction in human primary motor cortex

Repetitive transcranial magnetic stimulation (rTMS) over primary motor cortex (M1) elicits changes in motor evoked potential (MEP) size thought to reflect short- and long-term forms of synaptic plasticity, resembling short-term potentiation (STP) and long-term potentiation/depression (LTP/LTD) observed in animal experiments. We designed this study in healthy humans to investigate whether STP as elicited by 5-Hz rTMS interferes with LTP/LTD-like plasticity induced by intermittent and continuous theta-burst stimulation (iTBS and cTBS). The effects induced by 5-Hz rTMS and iTBS/cTBS were indexed as changes in MEP size. We separately evaluated changes induced by 5-Hz rTMS, iTBS and cTBS applied alone and those induced by iTBS and cTBS delivered after priming 5-Hz rTMS. Interactions between 5-Hz rTMS and iTBS/cTBS were investigated under several experimental conditions by delivering 5-Hz rTMS at suprathreshold and subthreshold intensity, allowing 1 and 5 min intervals to elapse between 5-Hz rTMS and TBS, and delivering one and ten 5-Hz rTMS trains. We also investigated whether 5-Hz rTMS induces changes in intracortical excitability tested with paired-pulse transcranial magnetic stimulation. When given alone, 5-Hz rTMS induced short-lasting and iTBS/cTBS induced long-lasting changes in MEP amplitudes. When M1 was primed with 10 suprathreshold 5-Hz rTMS trains at 1 min before iTBS or cTBS, the iTBS/cTBS-induced after-effects disappeared. The 5-Hz rTMS left intracortical excitability unchanged. We suggest that STP elicited by suprathreshold 5-Hz rTMS abolishes iTBS/cTBS-induced LTP/LTD-like plasticity through non-homeostatic metaplasticity mechanisms. Our study provides new information on interactions between short-term and long-term rTMS-induced plasticity in human M1.

Cerebellar brain inhibition is decreased in active and surround muscles at the onset of voluntary movement

Highly selective activation of the desired muscles for each movement and inhibition of adjacent muscles is attributed to surround inhibition (SI) which differentially modulates corticospinal excitability in active and surrounding muscles. Cerebellar brain inhibition (CBI) is another inhibitory neuronal network which is known to be active at rest and during tonic muscle contraction. The way in which CBI may be modulated at movement onset and its relationship with SI has not previously been investigated. We assessed motor evoked potential (MEP) size and CBI in first dorsal interosseus (FDI) and abductor digiti minimi (ADM) muscles at rest and during a simple motor task where FDI was an active muscle and ADM was not involved in the movement (surround muscle). At onset of movement, MEP size in ADM was significantly suppressed, confirming the existence of SI. In contrast, CBI in both muscles was found to be significantly decreased at the onset of the movement. This was confirmed even after adjustments for changes in MEP size occurring due to onset of muscle activity in FDI and the effects of SI in ADM. Our findings fail to functionally link SI with CBI, but they do indicate a non-topographically specific modulation of CBI in association with initiation of voluntary movement.

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.

Changes in Excitability of the Cortical Projections to the Human Tibialis Anterior After Paired Associative Stimulation

Paired associative stimulation (PAS) based on Hebb's law of association can induce plastic changes in the intact human. The optimal interstimulus interval (ISI) between the peripheral nerve and transcranial magnetic stimulus is not known for muscles of the lower leg. The aims of this study were to investigate the effect of PAS for a variety of ISIs and to explore the efficacy of PAS when applied during dynamic activation of the target muscle. PAS was applied at 0.2 Hz for 30 min with the tibialis anterior (TA) at rest. The ISI was varied randomly in seven sessions (n = 5). Subsequently, PAS was applied (n = 14, ISI = 55 ms) with the TA relaxed or dorsi-flexing. Finally, an optimized ISI based on the subject somatosensory evoked potential (SEP) latency plus a central processing delay (6 ms) was used (n = 13). Motor-evoked potentials (MEPs) were elicited in the TA before and after the intervention, and the size of the TA MEP was extracted. ISIs of 45, 50, and 55 ms increased and 40 ms decreased TA MEP significantly (P = 0.01). PAS during dorsi-flexion increased TA MEP size by 92% (P = 0.001). PAS delivered at rest resulted in a nonsignificant increase; however, when the ISI was optimized from SEP latency recordings, all subjects showed significant increases (P = 0.002). No changes in MEP size occurred in the antagonist. Results confirm that the excitability of the corticospinal projections to the TA but not the antagonist can be increased after PAS. This is strongly dependent on the individualized ISI and on the activation state of the muscle.

Analogous corticocortical inhibition and facilitation in ipsilateral and contralateral human motor cortex representations of the tongue.

How the human brain controls activation of the ipsilateral part of midline muscles is unknown. We studied corticospinal and corticocortical network excitability of both ipsilateral and contralateral motor representations of the tongue to determine whether they are under analogous or disparate inhibitory and facilitatory corticocortical control. Motor evoked potentials (MEPs) to unilateral focal transcranial magnetic stimulation (TMS) of the tongue primary motor cortex were recorded simultaneously from the ipsilateral and contralateral lingual muscles. Single-pulse TMS was used to assess motor threshold (MT) and MEP recruitment. Paired-pulse TMS was used to study intracortical inhibition (ICI) and intracortical facilitation (ICF) at various interstimulus intervals (ISIs) between the conditioning stimulus (CS) and the test stimulus (TS), and at different CS and TS intensities, respectively. Focal TMS invariably produced MEPs in both ipsilateral and contralateral lingual muscles. MT was lower and MEP recruitment was steeper when recorded from the contralateral muscle group. ICI and ICF were identical in the ipsilateral and contralateral representations, with inhibition occurring at short ISIs (2 and 3 ms) and facilitation occurring at longer ISIs (10 and 15 ms). Moreover, changing one stimulus parameter regularly produced analogous changes in MEP size bilaterally, revealing strong linear correlations between ipsilateral and contralateral ICI and ICF (P < 0.0001). These findings indicate that the ipsilateral and contralateral representations of the tongue are under analogous inhibitory and facilitatory control, possibly by a common intracortical network.

Central fatigue in sports and daily exercises. A magnetic stimulation study.

Previous transcranial magnetic stimulation (TMS) studies showed exercise-induced depression of motor evoked potentials (MEP). The purpose of the present study was to evaluate changes in MEP size and central motor conduction time (CMCT) after various kinds of exercise of daily life and sports. Changes of both central and peripheral motor conduction were recorded immediately after predominantly aerobic (climbing stairs and jogging) and anaerobic (press-ups, dumb-bell holding, and 400 m-run) exercise. Strength exercise resulted in a significant decrease of MEP amplitudes. Exhausting press-ups reduced the mean MEP amplitude by 33% as compared to pre-exercise value, exhausting dumb-bell holding reduced the mean MEP amplitude by 66%. Aerobic exercises (climbing 600 steps and jogging 50 minutes) did not significantly change MEP amplitudes. The compound motor action potentials (registered after supramaximal peripheral electrical stimulation) remained unchanged after each paradigm. CMCT was not significantly altered by any of the exercises under investigation. Peripheral motor conduction time (PMCT) was slightly lengthened by 4% after isometric dumb-bell holding. PMCT and total motor conduction time were decreased after aerobic exercises, probably due to an increase of temperature of the lower extremities. In conclusion, TMS is a suitable technique for objective evaluation of central fatigue. The present study is the first to show its possible use in sports medicine, indicating that only exhaustive or strength exercises result in reduced MEPs.