Comparison of muscle MEPs from transcranial magnetic and electrical stimulation and appearance of reflexes in horses

Introduction Transcranial electrical (TES) and magnetic stimulation (TMS) are both used for assessment of the motor function of the spinal cord in horses. Muscular motor evoked potentials (mMEP) were compared intra-individually for both techniques in five healthy horses. mMEPs were measured twice at increasing stimulation intensity steps over the extensor carpi radialis (ECR), tibialis cranialis (TC), and caninus muscles. Significance was set atp< 0.05. To support the hypothesis that both techniques induce extracranially elicited mMEPs, literature was also reviewed. Results Both techniques show the presence of late mMEPs below the transcranial threshold appearing as extracranially elicited startle responses. The occurrence of these late mMEPs is especially important for interpretation of TMS tracings when coil misalignment can have an additional influence. Mean transcranial motor latency times (MLT; synaptic delays included) and conduction velocities (CV) of the ECR and TC were significantly different between both techniques: respectively, 4.2 and 5.5 ms (MLTTMS--MLTTES), and -7.7 and -9.9 m/s (CVTMS-CVTES). TMS and TES show intensity-dependent latency decreases of, respectively, -2.6 (ECR) and -2.7 ms (TC)/30% magnetic intensity and -2.6 (ECR) and -3.2 (TC) ms/30V. When compared to TMS, TES shows the lowest coefficients of variation and highest reproducibility and accuracy for MLTs. This is ascribed to the fact that TES activates a lower number of cascaded interneurons, allows for multipulse stimulation, has an absence of coil repositioning errors, and has less sensitivity for varying degrees of background muscle tonus. Real axonal conduction times and conduction velocities are most closely approximated by TES. Conclusion Both intracranial and extracranial mMEPs inevitably carry characteristics of brainstem reflexes. To avoid false interpretations, transcranial mMEPs can be identified by a stepwise latency shortening of 15-20 ms when exceeding the transcranial motor threshold at increasing stimulation intensities. A ring block around the vertex is advised to reduce interference by extracranial mMEPs. mMEPs reflect the functional integrity of the route along the brainstem nuclei, extrapyramidal motor tracts, propriospinal neurons, and motoneurons. The corticospinal tract appears subordinate in horses. TMS and TES are interchangeable for assessing the functional integrity of motor functions of the spinal cord. However, TES reveals significantly shorter MLTs, higher conduction velocities, and better reproducibility

State-dependent modulation of cortico-spinal networks

Beta-band rhythm (13-30 Hz) is a dominant oscillatory activity in the sensorimotor system. Numerous studies reported on links between motor performance and the cortical and cortico-spinal beta rhythm. However, these studies report divergent beta-band frequencies and are, additionally, based on differently performed motor-tasks (e.g., motor imagination, muscle contraction, reach, grasp, and attention). This diversity blurs the role of beta in the sensorimotor system. It consequently challenges the development of beta-band activity-dependent stimulation protocols in the sensorimotor system. In this vein, we studied the functional role of beta-band cortico-cortical and cortico-spinal networks during a motor learning task. We studied how the contribution of cortical and spinal beta changes in the course of learning, and how this modulation is affected by afferent feedback to the sensorimotor system. We furthermore researched the relationship to motor performance. Consider that we made our study in the absence of any residual movement to allow our findings to be translated into rehabilitation programs for severely affected stroke patients. This thesis, at first, investigates evoked responses after transcranial magnetic stimulation (TMS). This revealed two different beta-band networks, i.e., in the low and high beta-band reflecting cortical and cortico-spinal activity. We, then, used a broader frequency range in the beta-band to trigger passive opening of the hand (peripheral feedback) or cortical stimulation (cortical feedback). While a unilateral hemispheric increase in cortico-spinal synchronization was observed in the group with peripheral feedback, a bilateral hemispheric increase in cortico-cortical and cortico-spinal synchronization was observed for the group with cortical feedback. An improvement in motor performance was found in the peripheral group only. Additionally, an enhancement in the directed cortico-spinal synchronization from cortex to periphery was observed for the peripheral group. Similar neurophysiological and behavioral changes were observed for stroke patients receiving peripheral feedback. The results 6 suggest two different mechanisms for beta-band activity-dependent protocols depending on the feedback modality. While the peripheral feedback appears to increase the synchronization among neural groups, cortical stimulation appears to recruit dormant neurons and to extend the involved motor network. These findings may provide insights regarding the mechanism behind novel activity-dependent protocols. It also highlights the importance of afferent feedback for motor restoration in beta-band activity-dependent rehabilitation programs

Corticospinal Integration in Healthy Humans

Synchronized arrival of neuronal signals from the periphery and motor cortex has been associated with neuronal plasticity and motor learning. The main objective of this study was to examine neuronal interactions following excitation of descending motor axons from the primary motor cortex (M1) and spinal neuronal circuits via transcranial magnetic stimulation (TMS) and transcutaneous electric stimulation of the spine (tsESS) in 15 healthy humans while seated semiprone. TMS was delivered below or above the resting motor evoked potential (MEP) threshold, for the tibialis anterior (TA) muscle, while tsESS was delivered at the lowest stimulation intensity that evoked responses in most or all leg muscles. TMS was delivered either alone or with tsESS at different interstimulus intervals ranging from negative 50 ms to positive 50 ms. tsESS induced a biphasic excitability pattern of MEPs recorded from the distal ankle muscles of the right leg with negative interstimulus intervals showing depression of MEPs followed by a non significant effect at the interstimulus interval of 0 ms, and potentiation of MEPs at positive interstimulus intervals. These findings suggest that 1) cortical descending motor volleys can either be potentiated or depressed based on the time that cortical and spinal signals meet at the spinal cord level, and 2) MEPs and tsESS-induced compound action muscle potentials likely share common neuronal pathways. These findings constitute the first evidence that synchronized neuronal signals from the primary motor cortex and spine can potentiate corticospinal motor output

Cortical mapping of the neuronal circuits modulating the muscle tone. Introduction to the electrophysiological treatment of the spastic hand

L'objectiu d'aquest estudi es investigar l'organització cortical junt amb la connectivitat còrtico-subcortical en subjectes sans, com a estudi preliminar. Els mapes corticals s'han fet per TMS navegada, i els punts motors obtinguts s'han exportant per estudi tractogràfic i anàlisi de las seves connexions. El coneixement precís de la localització de l'àrea cortical motora primària i les seves connexions es la base per ser utilitzada en estudis posteriors de la reorganització cortical i sub-cortical en pacients amb infart cerebral. Aquesta reorganització es deguda a la neuroplasticitat i pot ser influenciada per els efectes neuromoduladors de la estimulació cerebral no invasiva.The purpose of this study is to investigate the motor cortex organisation together with the cortico-subcortical connectivity in healthy subjects, as a preliminary study. Cortical maps have been performed by navigated TMS and the motor points have been exported to DTI to study their subcortical connectivity. The precise knowledge of localization of the primary motor cortex area and its connectivity is the base to be used in later studies of cortical and subcortical re-organisation in stroke patients. This re-organisation is due to the neuroplascity and can be influenced by the neuromodulation effects of the non-invasive cerebral stimulation therapy by TMS

Motor system plasticity induced by non-invasive stimuli

MD ThesisPrecisely timed paired stimulation protocols can change cortical and subcortical excitability. In the first study, induction of plastic changes in the long-latency stretch reflex (LLSR) by pairing non-invasive stimuli was attempted, at timings predicted to cause spiketiming dependent plasticity (STDP) in the brainstem. LLSR in human elbow muscles depends on multiple pathways; one possible contributor is the reticulospinal tract. The stimuli used are known to activate reticulospinal pathways. In healthy human subjects, reflex responses in flexor muscles were recorded following extension perturbations at the elbow. Subjects were then fitted with a portable device which delivered auditory click stimuli, and electrical stimuli to biceps muscle. The LLSR was significantly enhanced or suppressed in the biceps muscle depending on the intervention protocol. No changes were observed in the unstimulated brachioradialis muscle. Although contributions from the spinal or cortical pathways cannot be excluded, the results were consistent with STDP in reticulospinal circuits. In the second study, baseline TMS responses were recorded from two intrinsic hand muscles, flexor digitorum superficialis (FDS) and extensor digitorum communis (EDC). In the first phase, paired associative stimulation (PAS) was delivered by pairing motor point stimulation of FDS or EDC with TMS. Responses were then remeasured. Increases were greatest in the hand muscles, smaller in FDS, and non-significant in EDC. In the second phase, intermittent theta-burst rapid-rate TMS was applied instead of PAS. In this case, all muscles showed similar increases in TMS responses. This study showed that potential plasticity in motor cortical output has a gradient: hand muscles > flexors > extensors. However, this was only seen in a protocol which requires integration of sensory input (PAS), and not when plasticity was induced purely by cortical stimulation (rapid rate TMS). In the third study, motor imagery was paired with TMS in healthy human subjects. They were asked to imagine wrist flexion or extension movement, while TMS was delivered to the motor cortex. Six different protocols were tested, but only flexor imagination with TMS and extensor imagination with TMS showed significant facilitation following the test. Flexor imagination with TMS increased motor evoked potential (MEP) in all four Abstract 2 muscles with maximum changes towards flexor, whereas extensor imagination with TMS increased MEP only in extensor. Above changes in the cortical or subcortical excitability evoked by non-invasive stimulation protocols were consistent with long term potentiation and long-term depression mediated plastic change

Multipulse transcranial electrical stimulation (TES):Normative data for motor evoked potentials in healthy horses

Background: There are indications that transcranial electrical stimulation (TES) assesses the motor function of the spinal cord in horses in a more sensitive and reproducible fashion than transcranial magnetic stimulation (TMS). However, no normative data of TES evoked motor potentials (MEP) is available. In this prospective study normative data of TES induced MEP wave characteristics (motor latency times (MLT); amplitude and waveform) was obtained from the extensor carpi radialis (ECR) and tibial cranialis (TC) muscles in a group of healthy horses to create a reference frame for functional diagnostic purposes. For the 12 horses involved in the study 95% confidence intervals for MLTs were 16.1-22.6 ms and 31.9-41.1 ms for ECR and TC muscles respectively. Intraindividual coefficients of variation (CV) and mean of MLTs were: ECR: 2.2-8,2% and 4.5% and TC: 1.4-6.3% and 3.5% respectively. Inter-individual CVs for MLTs were higher, though below 10% on all occasions. The mean +/- sd of MEP amplitudes was respectively 3.61 +/- 2.55 mV (ECR muscle left) and 4.53 +/- 3.1 mV (right) and 2.66 +/- 2.22 mV (TC muscle left) and 2.55 +/- 1.85 mV (right). MLTs showed no significant left versus right differences. All MLTs showed significant (p < 0.05) voltage dependent decreases with slope coefficients of linear regression for ECR: 0.049; - 0.061 ms/V and TC: - 0.082; - 0.089 ms/V (left; right). There was a positive correlation found between height at withers and MLTs in all 4 muscle groups. Finally, reliable assessment of MEP characteristics was for all muscle groups restricted to a transcranial time window of approximately 15-19 ms. Conclusions: TES is a novel and sensitive technique to assess spinal motor function in horses. It is easy applicable and highly reproducible. This study provides normative data in healthy horses on TES induced MEPs in the extensor carpi radialis and tibialis cranialis muscles bilaterally. No significant differences between MLTs of the left and right side could be demonstrated. A significant effect of stimulation voltage on MLTs was found. No significant effect of height at the withers could be found based upon the results of the current study. A study in which both TMS and TES are applied on the same group of horses is needed

Increased Bilateral Interactions in Middle-Aged Subjects

A hallmark of the age-related neural reorganization is that old versus young adults execute typical motor tasks by a more diffuse neural activation pattern including stronger ipsilateral activation during unilateral tasks. Whether such changes in neural activation are present already at middle age and affect bimanual interactions is unknown. We compared the amount of associated activity, i.e., muscle activity and force produced by the non-task hand and motor evoked potentials (MEPs) produced by magnetic brain stimulation between young (mean 24 years, n = 10) and middle-aged (mean 50 years, n = 10) subjects during brief unilateral (seven levels of % maximal voluntary contractions, MVCs) and bilateral contractions (4 × 7 levels of % MVC combinations), and during a 120-s-long MVC of sustained unilateral index finger abduction. During the force production, the excitability of the ipsilateral (iM1) or contralateral primary motor cortex (cM1) was assessed. The associated activity in the “resting” hand was ~2-fold higher in middle-aged (28% of MVC) versus young adults (11% of MVC) during brief unilateral MVCs. After controlling for the background muscle activity, MEPs in iM1 were similar in the two groups during brief unilateral contractions. Only at low (bilateral) forces, MEPs evoked in cM1 were 30% higher in the middle-aged versus young adults. At the start of the sustained contraction, the associated activity was higher in the middle-aged versus young subjects and increased progressively in both groups (30 versus 15% MVC at 120 s, respectively). MEPs were greater at the start of the sustained contraction in middle-aged subjects but increased further during the contraction only in young adults. Under these experimental conditions, the data provide evidence for the reorganization of neural control of unilateral force production as early as age 50. Future studies will determine if the altered neural control of such inter-manual interactions are of functional significance