Upper limb movement quality measures: comparing IMUs and optical motion capture in stroke patients performing a drinking task.

Introduction: Clinical assessment of upper limb sensorimotor function post-stroke is often constrained by low sensitivity and limited information on movement quality. To address this gap, recent studies proposed a standardized instrumented drinking task, as a representative daily activity combining different components of functional arm use. Although kinematic movement quality measures for this task are well-established, and optical motion capture (OMC) has proven effective in their measurement, its clinical application remains limited. Inertial Measurement Units (IMUs) emerge as a promising low-cost and user-friendly alternative, yet their validity and clinical relevance compared to the gold standard OMC need investigation. Method: In this study, we conducted a measurement system comparison between IMUs and OMC, analyzing 15 established movement quality measures in 15 mild and moderate stroke patients performing the drinking task, using five IMUs placed on each wrist, upper arm, and trunk. Results: Our findings revealed strong agreement between the systems, with 12 out of 15 measures demonstrating clinical applicability, evidenced by Limits of Agreement (LoA) below the Minimum Clinically Important Differences (MCID) for each measure. Discussion: These results are promising, suggesting the clinical applicability of IMUs in quantifying movement quality for mildly and moderately impaired stroke patients performing the drinking task.

Investigating the Association of Wallerian Degeneration and Diaschisis After Ischemic Stroke With BOLD Cerebrovascular Reactivity.

INTRODUCTION: Wallerian degeneration and diaschisis are considered separate remote entities following ischemic stroke. They may, however, share common neurophysiological denominators, since they are both related to disruption of fiber tracts and brain atrophy over time. Therefore, with advanced multimodal neuroimaging, we investigate Wallerian degeneration and its association with diaschisis. METHODS: In order to determine different characteristics of Wallerian degeneration, we conducted examinations on seventeen patients with chronic unilateral ischemic stroke and persisting large vessel occlusion, conducting high-resolution anatomical magnetic resonance imaging (MRI) and blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) tests, as well as Diamox 15(O)-H2O-PET hemodynamic examinations. Wallerian degeneration was determined using a cerebral peduncle asymmetry index (% difference of volume of ipsilateral and contralateral cerebral peduncle) of more than two standard deviations away from the average of age-matched, healthy subjects (Here a cerebral peduncle asymmetry index > 11%). Diaschisis was derived from BOLD-CVR to assess the presence of ipsilateral thalamus diaschisis and/or crossed cerebellar diaschisis. RESULTS: Wallerian degeneration, found in 8 (47%) subjects, had a strong association with ipsilateral thalamic volume reduction (r 2 = 0.60) and corticospinal-tract involvement of stroke (p < 0.001). It was also associated with ipsilateral thalamic diaschisis (p = 0.021), No cerebral peduncular hemodynamic differences were found in patients with Wallerian degeneration. In particular, no CBF decrease or BOLD-CVR impairment was found. CONCLUSION: We show a strong association between Wallerian degeneration and ipsilateral thalamic diaschisis, indicating a structural pathophysiological relationship.

Clinical value of assessing motor performance in postacute stroke patients.

BACKGROUND: Rehabilitative treatment plans after stroke are based on clinical examinations of functional capacity and patient-reported outcomes. Objective information about daily life performance is usually not available, but it may improve therapy personalization. OBJECTIVE: To show that sensor-derived information about daily life performance is clinically valuable for counseling and the planning of rehabilitation programs for individual stroke patients who live at home. Performance information is clinically valuable if it can be used as a decision aid for the therapeutic management or counseling of individual patients. METHODS: This was an observational, cross-sectional case series including 15 ambulatory stroke patients. Motor performance in daily life was assessed with body-worn inertial sensors attached to the wrists, shanks and trunk that estimated basic physical activity and various measures of walking and arm activity in daily life. Stroke severity, motor function and activity, and degree of independence were quantified clinically by standard assessments and patient-reported outcomes. Motor performance was recorded for an average of 5.03 ± 1.1 h on the same day as the clinical assessment. The clinical value of performance information is explored in a narrative style by considering individual patient performance and capacity information. RESULTS: The patients were aged 59.9 ± 9.8 years (mean ± SD), were 6.5 ± 7.2 years post stroke, and had a National Institutes of Health Stroke Score of 4.0 ± 2.6. Capacity and performance measures showed high variability. There were substantial discrepancies between performance and capacity measures in some patients. CONCLUSIONS: This case series shows that information about motor performance in daily life can be valuable for tailoring rehabilitative therapy plans and counseling according to the needs of individual stroke patients. Although the short recording time (average of 5.03 h) limited the scope of the conclusions, this study highlights the usefulness of objective measures of daily life performance for the planning of rehabilitative therapies. Further research is required to investigate whether information about performance in daily life leads to improved rehabilitative therapy results.

Predictors for affected stroke territory and outcome of acute stroke treatments are different for posterior versus anterior circulation stroke.

Distinct patient characteristics have been proposed for ischaemic stroke in the anterior versus posterior circulation. However, data on functional outcome according to stroke territory in patients with acute stroke treatment are conflicting and information on outcome predictors is scarce. In this retrospective study, we analysed functional outcome in 517 patients with stroke and thrombolysis and/or thrombectomy treated at the University Hospital Zurich. We compared clinical factors and performed multivariate logistic regression analyses investigating the effect of outcome predictors according to stroke territory. Of the 517 patients included, 80 (15.5%) suffered a posterior circulation stroke (PCS). PCS patients were less often female (32.5% vs. 45.5%, p = 0.031), received thrombectomy less often (28.7% vs. 48.3%, p = 0.001), and had lower median admission NIHSS scores (5 vs. 10, p < 0.001) as well as a better median three months functional outcome (mRS 1 vs. 2, p = 0.010). Predictors for functional outcome were admission NIHSS (OR 0.864, 95% CI 0.790-0.944, p = 0.001) in PCS and age (OR 0.952, 95% CI 0.935-0.970, p < 0.001), known symptom onset (OR 1.869, 95% CI 1.111-3.144, p = 0.018) and admission NIHSS (OR 0.840, 95% CI 0.806-0.876, p < 0.001) in ACS. Acutely treated PCS and ACS patients differed in their baseline and treatment characteristics. We identified specific functional outcome predictors of thrombolysis and/or thrombectomy success for each stroke territory.

Motor Learning Induces Profound but Delayed Dendritic Plasticity in M1 Layer II/III Pyramidal Neurons.

Motor learning depends on plastic reorganization of neural networks within the primary motor cortex (M1). In the circuitry of M1, integration and processing of afferent inputs is executed by pyramidal neurons of layer II/III. Thus, an involvement of these layer II/III pyramids in learning-induced changes is highly plausible. We therefore analyzed dendritic plasticity in layer II/III pyramidal cells on Golgi-Cox silver-impregnated sections after training of a forelimb reaching task. Based on their location within layer II/III, neurons were assigned to either a superficial or a deep population. After training, morphological changes occurred in both superficial and deep layer II/III pyramids. Overall, a decrease in dendritic length could be observed. In detail, superficial cells showed a significant reduction in the length of the apical dendrite after training ended in contrast to deep layer II/III pyramids, where dendritic length initially remained stable. Both types of neurons showed a transient increment in complexity of the distal apical dendrite 30 days after training. Findings were different in basal dendrites: length and complexity continuously decreased in superficial and deep layer II/III pyramids. Spine density increased in apical and basal dendrites of both superficial and deep layer II/III neurons, likely an effect of ageing that occurred independently from motor learning. This increase in spine density was accompanied with a morphological change towards stubby- and mushroom-like spines. Thus, profound but delayed changes occurred within the dendritic compartment of layer II/III pyramidal cells.

Embolization of tumor cells is rare in patients with systemic cancer and cerebral large vessel occlusion.

BACKGROUND AND PURPOSE: Stroke is a dreaded complication in patients with cancer. Besides paraneoplastic coagulopathy, chemotherapy, radiotherapy and tumor-directed invasive procedures, circulating cancer cells may contribute to thrombus formation and embolic stroke. However, the incidence of tumor cells within the blood clots of cancer patients with stroke is unknown and the role of circulating tumor cells in the formation of cerebrovascular thrombi remains unclear. METHODS: All patients who had undergone cerebrovascular thrombectomy at the University Hospital Zurich between 2014 and 2017 were screened for history of cancer. Clinical information was retrieved from the local stroke registry and the electronic charts and thrombi underwent a thorough histopathological re-review. RESULTS: Thirty-two of 182 patients (18%) with thrombectomy had a history of cancer. The majority of patients had advanced stage cancer. However, even after extensive histopathological re-review, only one specimen revealed tumor cells in the thrombus: a 75-year-old patient with acute occlusion of the middle cerebral artery who had been diagnosed with non-small-cell lung cancer 8.1 months prior to stroke. CONCLUSIONS: The presence of cancer cells in clots from cerebrovascular thrombectomy, indicative of a direct involvement of circulating tumor cells in the causation of stroke, is rare.

Task-Specific Motor Rehabilitation Therapy After Stroke Improves Performance in a Different Motor Task: Translational Evidence.

While the stroke survivor with a motor deficit strives for recovery of all aspects of daily life movements, neurorehabilitation training is often task specific and does not generalize to movements other than the ones trained. In rodent models of post-stroke recovery, this problem is poorly investigated as the training task is often the same as the one that measures motor function. The present study investigated whether motor training by pellet reaching translates into enhancement of different motor functions in rats after stroke. Adult rats were subjected to 60-min middle cerebral artery occlusion (MCAO). Five days after stroke, animals received either training consisting of 7 days of pellet reaching with the affected forelimb (n = 18) or no training (n = 18). Sensorimotor deficits were assessed using the sticky tape test and a composite neuroscore. Infarct volumes were measured by T2-weighted MRI on day 28. Both groups of rats showed similar lesion volume and forelimb impairment after stroke. Trained animals improved in the sticky tape test after day 7 post-stroke reaching peak performance on day 14. More reaching attempts during rehabilitation were associated with a better performance in the sticky tape removal time. Task-oriented motor training generalizes to other motor functions after experimental stroke. Training intensity correlates with recovery.

Temporal course of gene expression during motor memory formation in primary motor cortex of rats.

Motor learning is associated with plastic reorganization of neural networks in primary motor cortex (M1) that depends on changes in gene expression. Here, we investigate the temporal profile of these changes during motor memory formation in response to a skilled reaching task in rats. mRNA-levels were measured 1h, 7h and 24h after the end of a training session using microarray technique. To assure learning specificity, trained animals were compared to a control group. In response to motor learning, genes are sequentially regulated with high time-point specificity and a shift from initial suppression to later activation. The majority of regulated genes can be linked to learning-related plasticity. In the gene-expression cascade following motor learning, three different steps can be defined: (1) an initial suppression of genes influencing gene transcription. (2) Expression of genes that support translation of mRNA in defined compartments. (3) Expression of genes that immediately mediates plastic changes. Gene expression peaks after 24h - this is a much slower time-course when compared to hippocampus-dependent learning, where peaks of gene-expression can be observed 6-12h after training ended.

Sympathetic activity and early mobilization in patients in intensive and intermediate care with severe brain injuries: a preliminary prospective randomized study.

BACKGROUND: Patients who experience severe brain injuries are at risk of secondary brain damage, because of delayed vasospasm and edema. Traditionally, many of these patients are kept on prolonged bed rest in order to maintain adequate cerebral blood flow, especially in the case of subarachnoid hemorrhage. On the other hand, prolonged bed rest carries important morbidity. There may be a clinical benefit in early mobilization and our hypothesis is that early gradual mobilization is safe in these patients. The aim of this study was to observe and quantify the changes in sympathetic activity, mainly related to stress, and blood pressure in gradual postural changes by the verticalization robot (Erigo®) and after training by a lower body ergometer (MOTOmed-letto®), after prolonged bed rest of minimum 7 days. METHODS: Thirty patients with severe neurological injuries were randomized into 3 groups with different protocols of mobilization: Standard, MOTOmed-letto® or Erigo® protocol. We measured plasma catecholamines, metanephrines and blood pressure before, during and after mobilization. RESULTS: Blood pressure does not show any significant difference between the 3 groups. The analysis of the catecholamines suggests a significant increase in catecholamine production during Standard mobilization with physiotherapists and with MOTOmed-letto® and no changes with Erigo®. CONCLUSIONS: This preliminary prospective randomized study shows that the mobilization of patients with severe brain injuries by means of Erigo® does not increase the production of catecholamines. It means that Erigo® is a well-tolerated method of mobilization and can be considered a safe system of early mobilization of these patients. Further studies are required to validate our conclusions. TRIAL REGISTRATION: The study was registered in the ISRCTN registry with the trial registration number ISRCTN56402432 . Date of registration: 08.03.2016. Retrospectively registered.

The effect of surgery and intracerebral injections on motor skill learning in rats: results from a database analysis.

Male Long-Evans rats are often used to investigate neural mechanisms of learning in the motor system. Successful acquisition of a skilled motor task is influenced by various variables such as animal supplier and batch membership. In this retrospective analysis of our laboratory database, we investigate how head and brain surgery as well as intracerebral injections that were performed to address particular scientific questions affect motor learning. Overall, invasive interventions (n=90) slow the acquisition of a skilled-reaching task when compared to naïve animals (n=184; P=0.01). With respect to subgroups, this detrimental effect widely differs between particular procedures: whereas epidural implantations of thin-film electrode arrays and punctual injection through pre-implanted cannulas into primary motor cortex (M1) do not interfere with learning, skill acquisition is slowed after chronic infusion using osmotic minipumps into M1 and skill acquisition is lastingly impaired after bilateral cannula implantation within the dorsal striatum. In line with previous reports, breeder-specific differences could be observed in the analysis of the overall population. In summary, interventions may impair learning-behavior in an unpredictable fashion. Thus, a comparison of behavioral data to a naïve population is recommended to be aware of these drawbacks.

Impaired implicit learning and feedback processing after stroke.

The ability to learn is assumed to support successful recovery and rehabilitation therapy after stroke. Hence, learning impairments may reduce the recovery potential. Here, the hypothesis is tested that stroke survivors have deficits in feedback-driven implicit learning. Stroke survivors (n=30) and healthy age-matched control subjects (n=21) learned a probabilistic classification task with brain activation measured using functional magnetic resonance imaging in a subset of these individuals (17 stroke and 10 controls). Stroke subjects learned slower than controls to classify cues. After being rewarded with a smiley face, they were less likely to give the same response when the cue was repeated. Stroke subjects showed reduced brain activation in putamen, pallidum, thalamus, frontal and prefrontal cortices and cerebellum when compared with controls. Lesion analysis identified those stroke survivors as learning-impaired who had lesions in frontal areas, putamen, thalamus, caudate and insula. Lesion laterality had no effect on learning efficacy or brain activation. These findings suggest that stroke survivors have deficits in reinforcement learning that may be related to dysfunctional processing of feedback-based decision-making, reward signals and working memory.

Biphasic plasticity of dendritic fields in layer V motor neurons in response to motor learning.

Motor learning is associated with plastic reorganization of neural networks in primary motor cortex (M1) that advances through stages. An initial increment in spine formation is followed by pruning and maturation one week after training ended. A similar biphasic course was described for the size of the forelimb representation in M1. This study investigates the evolution of the dendritic architecture in response to motor skill training using Golgy-Cox silver impregnation in rat M1. After learning of a unilateral forelimb-reaching task to plateau performance, an increase in dendritic length of layer V pyramidal neurons (i.e. motor neurons) was observed that peaked one month after training ended. This increment in dendritic length reflected an expansion of the distal dendritic compartment. After one month dendritic arborization shrinks even though animals retain task performance. This pattern of evolution was observed for apical and basal dendrites alike - although the increase in dendritic length occurs faster in basal than in apical dendrites. Dendritic plasticity in response to motor training follows a biphasic course with initial expansion and subsequent shrinkage. This evolution takes fourth as long as the biphasic reorganization of spines or motor representations.

Sub-processes of motor learning revealed by a robotic manipulandum for rodents.

Rodent models are widely used to investigate neural changes in response to motor learning. Usually, the behavioral readout of motor learning tasks used for this purpose is restricted to a binary measure of performance (i.e. "successful" movement vs. "failure"). Thus, the assignability of research in rodents to concepts gained in human research - implying diverse internal models that constitute motor learning - is still limited. To solve this problem, we recently introduced a three-degree-of-freedom robotic platform designed for rats (the ETH-Pattus) that combines an accurate behavioral readout (in the form of kinematics) with the possibility to invasively assess learning related changes within the brain (e.g. by performing immunohistochemistry or electrophysiology in acute slice preparations). Here, we validate this platform as a tool to study motor learning by establishing two forelimb-reaching paradigms that differ in degree of skill. Both conditions can be precisely differentiated in terms of their temporal pattern and performance levels. Based on behavioral data, we hypothesize the presence of several sub-processes contributing to motor learning. These share close similarities with concepts gained in humans or primates.

Region and task-specific activation of Arc in primary motor cortex of rats following motor skill learning.

Motor learning requires protein synthesis within the primary motor cortex (M1). Here, we show that the immediate early gene Arc/Arg3.1 is specifically induced in M1 by learning a motor skill. Arc mRNA was quantified using a fluorescent in situ hybridization assay in adult Long-Evans rats learning a skilled reaching task (SRT), in rats performing reaching-like forelimb movement without learning (ACT) and in rats that were trained in the operant but not the motor elements of the task (controls). Apart from M1, Arc expression was assessed within the rostral motor area (RMA), primary somatosensory cortex (S1), striatum (ST) and cerebellum. In SRT animals, Arc mRNA levels in M1 contralateral to the trained limb were 31% higher than ipsilateral (p<0.001), 31% higher than in the contralateral M1 of ACT animals (p<0.001) and 48% higher than in controls (p<0.001). Arc mRNA expression in SRT was positively correlated with learning success between two sessions (r=0.52; p=0.026). For RMA, S1, ST or cerebellum no significant differences in Arc mRNA expression were found between hemispheres or across behaviors. As Arc expression has been related to different forms of cellular plasticity, these findings suggest a link between M1 Arc expression and motor skill learning in rats.

[Stroke]. / Schlaganfall.

Ischemic stroke is a very frequent neurological disorder. It's incidence is increasing as western societies are aging. Effective therapies that reduce mortality and increase the chances of living symptom-free or, at least, in independence are available. Intravenous or intraarterial thrombolysis is an effective treatment with a number needed to treat of 6 if given within 4.5 hours after symptom onset. The safe use of thrombolysis requires an effective and repeatedly trained workflow established within a team of a neurologist and specialized nursing staff in an optimized environment (admission, imaging facility, laboratory, stroke unit). After peracute treatment, the patient should be transferred to a stroke unit. This unit is a spatially defined intermediate care unit with specifically trained personnel (physicians, nurses, therapists). Treating the patient in a stroke unit is as effective in improving outcome as thrombolysis and also reduces the length of hospital stay. In contrast to thrombolysis, which can be provided, on average, to only 5% of stroke patients, stroke unit care is applicable to most. The organization of medical care in most European countries and in Switzerland separate the acute phase from subacute rehabilitation and chronic stroke treatment. This can be highly confusing for the patient who, during the course of the disease, meets different physicians, nurses and therapists with often diverging opinions about prognosis and therapies. Consistent treatment approaches and patient/caregiver information is necessary and can only be implemented by providing a homogeneous pathway for continuous stroke care.

Dopaminergic modulation of motor maps in rat motor cortex: an in vivo study.

While the primary motor cortex (M1) is know to receive dopaminergic projections, the functional role of these projections is poorly characterized. Here, it is hypothesized that dopaminergic signals modulate M1 excitability and somatotopy, two features of the M1 network relevant for movement execution and learning. To test this hypothesis, movement responses evoked by electrical stimulation using an electrode grid implanted epidurally over the caudal motor cortex (M1) were assessed before and after an intracortical injection of D1- (R-(+),8-chloro,7-hydroxy,2,3,4,5,-tetra-hydro,3-methyl,5-phenyl,1-H,3-benzazepine maleate, SCH 23390) or D2-receptor (raclopride) antagonists into the M1 forelimb area of rats. Stimulation mapping of M1 was repeated after 24 h. D2-inhibition reduced the size of the forelimb representation by 68.5% (P<0.001). Movements thresholds, i.e., minimal currents required to induce movement responses increased by 37.5% (P<0.001), and latencies increased by 35.9% (P<0.01). Twenty-4 h after the injections these effects were reversed. No changes were observed with D1-antagonist or vehicle. By enhancing intracortical excitability and signal transduction, D2-mediated dopaminergic signaling may affect movement execution, e.g. by enabling task-related muscle activation synergies, and learning.

New insights into image processing of cortical blood flow monitors using laser speckle imaging.

Laser speckle imaging has increasingly become a viable technique for real-time medical imaging. However, the computational intricacies and the viewing experience involved limit its usefulness for real-time monitors such as those intended for neurosurgical applications. In this paper, we propose a new technique, tLASCA, which processes statistics primarily in the temporal direction using the laser speckle contrast analysis (LASCA) equation, proposed by Briers and Webster. This technique is thoroughly compared with the existing techniques for signal processing of laser speckle images, including, the spatial-based sLASCA and the temporal-based modified laser speckle imaging (mLSI) techniques. sLASCA is an improvement of the basic LASCA technique. In sLASCA, the derived contrasts are further averaged over a predetermined number of raw speckle images. mLSI, on the other hand, is the technique in which temporal statistics are processed using the equation described by Ohtsubo and Asakura. tLASCA preserves the original image resolution similar to mLSI. tLASCA outperforms sLASCA (window size M = 5) with faster convergence of K values (5.32 versus 20.56 s), shorter per-frame processing time (0.34 versus 2.51 s), and better subjective and objective quality evaluations of contrast images. tLASCA also outperforms mLSI with faster convergence of K values (5.32 s) compared to N values (10.44 s), shorter per-frame processing time (0.34 versus 0.91 s), smaller intensity fluctuations among frames (8%-10% versus 15%-35%), and better subjective and objective quality evaluations of contrast images. As laser speckle imaging becomes an important tool for real-time monitoring of blood flows and vascular perfusion, tLASCA is proven to be the technique of choice.

Frequency and predictors for angiographically improved inflow of contrast medium after carotid angioplasty and stenting.

Percutaneous transluminal carotid angioplasty and stenting (PTAS) can result in immediate improvement in cerebral blood flow (CBF) evident through faster transit of contrast medium on angiography. To evaluate frequency and predictors of changes in inflow of contrast medium before and after PTAS, we reviewed 86 patients (mean age 68.6 +/- 9.1 years) treated for symptomatic or asymptomatic carotid stenosis. Clinical data and lesion characteristics were extracted from charts and digital angiograms, respectively. Perfusion change was assessed qualitatively by comparing pre- and poststenting images matched for projection and time from injection. Improved inflow was defined on the basis of spatial or temporal distribution of contrast medium: grade -1: fewer vessels visible after stenting; 0: no change; 1: more distal small arteries visible; 2: time-matched poststenting image showing a capillary blush; 3: time-matched poststenting image showing small veins, 4 time-matched poststenting image showing large veins and sinuses. Faster inflow of contrast medium was observed in 74% of patients (grades 1: 34%,and 4: 4.7%). In linear regression analysis, higher degrees of ipsilateral stenosis were associated with greater changes in inflow of contrast medium (P < 0.05). Right internal carotid lesions were associated with greater change in inflow than left-sided lesions (P < 0.01). In 31 patients (36%) we initially showed contralateral anterior cerebral artery (ACA) filling, and in 39% of these, normal filling was restored after stenting. Lesser contralateral carotid stenosis was associated with crossed ACA filling and with restoration of normal filling pattern after stenting. Faster appearance of a contrast-medium blush is seen in most cases of carotid angioplasty and stenting and depends on the degree of hemodynamic inflow obstruction relieved by stenting.

Transcranial magnetic stimulation in the rat.

Transcranial magnetic stimulation (TMS) allows for quantification of motor system excitability. While routinely used in humans, application in other species is rare and little is known about the characteristics of animal TMS. The unique features of TMS, i.e., predominantly interneuronal stimulation at low intensity and non-invasiveness, are particularly useful in evaluating injury and recovery in animal models. This study was conducted to characterize the rodent motor evoked potential to TMS (MEPTMS) and to develop a methodology for reproducible assessment of motor excitability in the rat. MEPTMS were compared with responses evoked by electrical stimulation of cervical spinal cord (MEPCES) and peripheral nerve. MEP were recorded by subcutaneous electrodes implanted bilaterally over the calf. Animals remained under propofol infusion and restrained in a stereotactic frame while TMS followed by CES measurements were obtained before and after 2 h of idle time. TMS was applied using a 5-cm-diameter figure-of-eight coil. MEPTMS had onset latencies of 6.7+/-1.3 ms. Latencies decreased with higher stimulation intensity (r=-0.7, P<0.05). Two morphologies, MEPTMS, 1 and MEPTMS, 2, were distinguished by latency of the first negative peak (N1), overall shape, and amplitude. MEPTMS, 2 were more frequent at higher stimulation intensity. While recruitment curves for MEPTMS, 1 followed a sigmoid course, no supramaximal response was reached for MEPTMS, 2. Mid-cervical spinal transection completely abolished any response to TMS. MEPCES showed a significantly shorter latency (5.29+/-0.24, P<0.0001). Two types of MEPCES resembling MEPTMS, 1 and 2 were observed. Neither MEPTMS nor MEPCES changed on repeat assessment after 2 h. This study demonstrates the feasibility and reproducibility of TMS in the rat. Sigmoid recruitment curves for MEPTMS, 1 suggest input-output properties similar to those of the human corticospinal system. Latency differences between CES and TMS point to a supraspinal origin of the MEPTMS. The two morphologies likely reflect different cortical or subcortical origins of MEPTMS.