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What determines the effectiveness of neurorehabilitation approaches on the outcome of function in stroke or spinal cord injured subjects? Many studies claim that an improvement of function is based on the intensity of training, while some actual studies indicate no additional gain in function by a more intensive training after a stroke. Inherent factors seem to determine outcome, such as damage of specific tracts in stroke and level of lesion in spinal cord injured subjects, while the improvement of function achieved by an intensive training is small in relation to the spontaneous recovery. It is argued that an individual capacity of recovery exists depending on such factors. This capacity can be exploited by a repetitive execution of functional movements (supported as far as required), irrespective of the intensity and technology applied. Elderly subjects have difficulties to translate the recovery of motor deficit into function. Alternative, non-training approaches to restore motor function, such as epidural or deep brain stimulation as well as CNS repair are still in an early clinical or in a translational stage., Inherent factors determine outcome of function after a CNS lesion, i.e. damage of specific tracts in stroke and level of lesion in SCI subjects. There exists an individual capacity of recovery. This capacity can be exploited by a repetitive execution of functional movements irrespective of the intensity or technology applied., Graphical Abstract Graphical Abstract

This study deals with the coordination of bilateral synchronous and asynchronous hand movements. Cooperative hand movements (e.g. opening a bottle) were shown to be coordinated by a neural coupling, reflected in the appearance of reflex responses in forearm muscles of both sides to unilateral arm nerve stimulation. The mechanical effect of this neural coupling was investigated during bilateral synchronous and asynchronous sinusoidal tracking tasks. During the synchronous tracking task, right handed corrective movements were mirrored by the left hand, suggesting a neural coupling. During the asynchronous tracking task, large non-coupled bilateral corrective hand movements dominated. The findings indicate that during synchronous hand movements an automatic coordination of bilateral hand movements occurs. In contrast, asynchronous tasks require independent hand movements. These appear to be visually guided and voluntarily controlled, leading to larger movement errors and corrections.

The aim of this study was to evaluate whether the effect of longer training times (50 instead of 25 min per day) using a robotic device results in a better outcome of walking ability of subjects with a subacute motor complete (American Spinal Injury Association Impairment Scale [AIS]-B) and incomplete (AIS-C) spinal cord injury. Twenty-one patients were enrolled in the study, whereof 18 completed, on average, 34 trainings in 8 weeks. Longer training times resulted in better locomotor function. The second important result of the study is that a beneficial effect can be achieved by the application of a robotic device for prolonged training sessions without requiring more personal resources. It has to remain open whether even longer training times (more than 50 min) would result in a still better outcome. In any case, the extent of possible recovery in an individual patient is determined by the level and severity of spinal cord damage.

We investigated the role of ipsilateral ascending pathways in the neural coupling underlying cooperative hand movements of stroke subjects. Ipsi‐ and contralateral somatosensory evoked potentials (SSEP) were recorded following ulnar nerve stimulation during cooperative and non‐cooperative hand movements. The amplitude ratio, that is, ipsilateral divided by contralateral amplitude, was highest during the cooperative task when the affected arm was stimulated, reflecting an enhanced afferent volley to the unaffected hemisphere. The presence of ipsilateral SSEP from the paretic arm was closely related with the patients' hand function. This shows for the first time a laterality in ascending pathways after unilateral stroke and implies an involvement of the unaffected hemisphere in the control of paretic hand movements.

In recent years it has become evident that, in a number of functional movements, synergistically acting limbs become task-specifically linked by a soft-wired ‘neural coupling’ mechanism (e.g., the legs during balancing, the arms and legs during gait [1, 2] and both arms during cooperative hand movements [3]). Experimentally this mechanism became evident by the analysis of reflex responses as a marker for a neural coupling. It is reflected by the task-specific appearance of reflex EMG responses to non-noxious nerve stimulation, not only in muscles of the stimulated limb, but also, with same long latency, in muscles of meaningful coupled (contralateral) limb(s). After a stroke, nerve stimulation of the unaffected limb during such cooperative tasks is followed by EMG responses in muscles of the (contralateral) coupled affected limb, i.e. unaffected motor centres support synergistically acting movements of the paretic limb. In contrast, following stimulation of the affected limb, no contralateral responses appear due to defective processing of afferent input [4]. As a consequence, it may be therapeutically possible to strengthen the influence of unaffected motor centres on the performance of affected limb movements through training of cooperative limb movements required during activities of daily living.

To characterize remote secondary neurodegeneration of spinal tracts and neurons below a cervical spinal cord injury (SCI) and its relation to the severity of injury, the integrity of efferent and afferent pathways, and clinical impairment.A comprehensive high-resolution MRI protocol was acquired in 17 traumatic cervical SCI patients and 14 controls at 3T. At the cervical lesion, a sagittal T2-weighted scan provided information on the width of preserved midsagittal tissue bridges. In the lumbar enlargement, high-resolution T2*-weighted and diffusion-weighted scans were used to calculate tissue-specific cross-sectional areas and diffusion indices, respectively. Regression analyses determined associations between MRI readouts and the electrophysiologic and clinical measures.At the cervical injury level, preserved midsagittal tissue bridges were present in the majority of patients. In the lumbar enlargement, neurodegeneration-in terms of macrostructural and microstructural MRI changes-was evident in the white matter and ventral and dorsal horns. Patients with thinner midsagittal tissue bridges had smaller ventral horn area, higher radial diffusivity in the gray matter, smaller motor evoked potential amplitude from the lower extremities, and lower motor score. In addition, smaller width of midsagittal tissue bridges was also associated with smaller tibialis sensory evoked potential amplitude and lower light-touch score.This study shows extensive tissue-specific cord pathology in infralesional spinal networks following cervical SCI, its magnitude relating to lesion severity, electrophysiologic integrity, and clinical impairment of the lower extremity. The clinical eloquence of remote neurodegenerative changes speaks to the application of neuroimaging biomarkers in diagnostic workup and planning of clinical trials.

Experimental Brain Research, 186 (1), ISSN:0014-4819, ISSN:1432-1106

Objectives : Motor evoked potential (MEP) amplitudes have the disadvantage of a high variability when repeatedly assessed. This affects the reliability of MEP amplitude measurements taken during the course of motor incomplete spinal cord injury (iSCI). The study investigated the reliability of anterior tibial (TA) MEP measures controlled for dorsal flexion torque and motor task. Methods : TA MEPs were recorded at 10, 20, 40 and 60% of maximal voluntary contraction (MVC) during a static and dynamic (isometric increase of dorsal flexion torque) motor task. To determine reliability, 20 healthy and five chronic iSCI subjects were tested twice (≥7 days) by the same investigator. Intraclass correlation coefficients (ICCs) were calculated. MEP amplitudes and latencies were compared between 20 healthy and 29 iSCI subjects. Results : The reliability of MEP amplitude was in general good (ICC ≥ 0.52) and was highest during the static task at 40% MVC (ICC = 0.77). The increased facilitation by the dynamic motor task showed the best reliability at 20% MVC (ICC = 0.48). The reliability was good to excellent for MEP latency (0.46 ≥ ICC ≥ 0.81), MVC (ICC ≥ 0.90) and for the TMS threshold required to evoke a MEP response (ICC ≥ 0.77). The torque generated by the MEP response ()0.02 ≥ ICC ≥ 0.55) and the duration of the silent period (0.07 ≥ ICC ≥ 0.50) were not reliable. Both MEP amplitudes and latencies differed significantly between healthy and iSCI subjects. Conclusions : Controlling for torque generation and motor task establishes a reliability of TA MEP amplitudes that is sufficient for longitudinal assessments in motor incomplete SCI

Objectives To evaluate whether the task-specific neural coupling mechanism during the performance of cooperative hand movements is preserved in tetraplegic subjects. Methods Recordings of ipsilateral and contralateral electromyographic reflex responses in activated forearm muscles and bilateral somatosensory potentials (SSEP) to unilateral ulnar nerve stimulations during rest, cooperative and non-cooperative hand movements. Results Contralateral reflex responses were present in almost all patients during cooperative hand movements but small in amplitude when hand function was severely impaired. Ipsilateral SSEP potentials were enhanced during both cooperative and, in contrast to healthy subjects, also non-cooperative bimanual movements. Conclusions Both results indicate a strong involvement of ipsilateral non-damaged cervical tracts and hemispheres in the control of bimanual hand movements in tetraplegic subjects. Significance This study on the neural control of bimanual movements in patients suffering a cervical injury allows designing therapeutic approaches for the improvement of hand function that are based on physiological insights.

The aim of this study was to evaluate the influence of unilateral reduction of afferent input on the 'neural coupling' mechanism during cooperative hand movements. This 'neural coupling' is reflected in the task-specific appearance of contralateral reflex responses in forearm muscles to unilateral arm nerve stimulation. Sensory input from the right hand was reduced by ischemic nerve block at the right wrist. Ipsilateral and contralateral reflex responses elicited by stimulation of the ulnar nerve either at the left or the right wrist proximal to the nerve block were recorded in forearm extensors during the performance of cooperative hand movements. During ischemia of the right hand, a significant difference was found in the magnitude of the contralateral responses, that is, contralateral reflex responses in the right arm were significantly higher compared with the left arm (P=0.04). Ipsilateral reflex responses were not affected by ischemic nerve block. The reduced afference from the ischemic hand during cooperative hand movements is assumed to weaken the activity in ipsilateral pathways involved in the neural coupling mechanism. Consequently, a shift in the interhemispheric balance might lead to the relative increase and decrease in the contralateral responses to left and right nerve stimulation, respectively. The study provides novel information on the involvement of ipsilateral hemispheres in the performance of cooperative hand movements.

Cooperative hand movements (e.g. opening a bottle) are controlled by a task-specific neural coupling, reflected in EMG reflex responses contralateral to the stimulation site. In this study the contralateral reflex responses in forearm extensor muscles to ipsilateral ulnar nerve stimulation was analyzed at various resistance and velocities of cooperative hand movements. The size of contralateral reflex responses was closely related to the level of forearm muscle activation required to accomplish the various cooperative hand movement tasks. This indicates an automatic gain control of neural coupling that allows a rapid matching of corrective forces exerted at both sides of an object with the goal ‘two hands one action’., Scientific Reports, 8, ISSN:2045-2322

This retrospective study was designed to examine the influence of age on the outcome of motor function and activities of daily living (ADLs) in patients with a cervical spinal cord injury (SCI). The study is based on the data registry of the European Multicenter Study of Spinal Cord Injury (EMSCI) study group. Initial upper-extremity motor score (UEMS) and its change over 5 months, as well as the initial Spinal Cord Independence Measure (SCIM) score, did not differ between younger adults (20-39 years) and elderly (60-79 years) patients. However, the change in SCIM score over 5 months was significantly greater in the younger patient group. Initial UEMS, SCIM, and ulnar compound motor action potentials (CMAP), reflecting peripheral nerve damage (motoneurons and roots), were significantly greater in incomplete, compared to complete, SCI, regardless of age group. The initial assessment of UEMS in combination with CMAP recordings allows an early prediction of ADLs outcomes in both younger adults and elderly subjects. The impaired translation of gain in motor score into increased ADL independence in elderly patients requires specifically tailored rehabilitation programs.

In healthy subjects, functionally appropriate modulation of short latency leg muscle reflexes occurs during gait. This modulation has been ascribed, in part, to changes in presynaptic inhibition of Ia afferents. The changes in modulation of quadriceps tendon jerk reflexes during gait of healthy subjects were compared with those of hemi- or paraparetic spastic patients. The spasticity was due to unilateral cerebral infarction or traumatic spinal cord injury, respectively. The modulation of the quadriceps femoris tendon jerk reflex at 16 phases of the step cycle was studied. The reflex responses obtained during treadmill walking were compared with control values obtained during gait-mimicking standing postures with corresponding levels of voluntary muscle contraction and knee angles. In healthy subjects the size of the reflexes was profoundly modulated and was generally depressed throughout the step cycle. In patients with spinal lesion the reflex depression during gait was almost removed and was associated with weak or no modulation during the step cycle. In patients with cerebral lesion there was less depression of the reflex size associated with a reduced reflex modulation on the affected side compared with healthy subjects. On the `unaffected' side of these patients reflex modulation was similar to that of healthy subjects, but the reflex size during gait was not significantly different from standing control values. These observations suggest that the mechanisms responsible for the depression of reflex size and the modulation normally seen during gait in healthy subjects are impaired to different extents in spasticity of spinal or cerebral origin, possibly due to the unilateral preservation of fibre tracts in hemiparesis.

Erworben im Rahmen der Schweizer Nationallizenzen (http://www.nationallizenzen.ch), The neural control of "cooperative" hand movements reflecting "opening a bottle" was explored in human subjects by electromyographic (EMG) and functional magnetic resonance imaging (fMRI) recordings. EMG responses to unilateral nonnoxious ulnar nerve stimulation were analyzed in the forearm muscles of both sides during dynamic movements against a torque applied by the right hand to a device which was compensated for by the left hand. For control, stimuli were applied while task was performed in a static/isometric mode and during bilateral synchronous pro-/supination movements. During the dynamic cooperative task, EMG responses to stimulations appeared in the right extensor and left flexor muscles, regardless of which side was stimulated. Under the control conditions, responses appeared only on the stimulated side. fMRI recordings showed a bilateral extra-activation and functional coupling of the secondary somatosensory cortex (S2) during the dynamic cooperative, but not during the control, tasks. This activation might reflect processing of shared cutaneous input during the cooperative task. Correspondingly, it is assumed that stimulation-induced unilateral volleys are processed in S2, leading to a release of EMG responses to both forearms. This indicates a task-specific neural coupling during cooperative hand movements, which has consequences for the rehabilitation of hand function in poststroke patients.

Summary Background Arm hemiparesis secondary to stroke is common and disabling. We aimed to assess whether robotic training of an affected arm with ARMin—an exoskeleton robot that allows task-specific training in three dimensions—reduces motor impairment more effectively than does conventional therapy. Methods In a prospective, multicentre, parallel-group randomised trial, we enrolled patients who had had motor impairment for more than 6 months and moderate-to-severe arm paresis after a cerebrovascular accident who met our eligibility criteria from four centres in Switzerland. Eligible patients were randomly assigned (1:1) to receive robotic or conventional therapy using a centre-stratified randomisation procedure. For both groups, therapy was given for at least 45 min three times a week for 8 weeks (total 24 sessions). The primary outcome was change in score on the arm (upper extremity) section of the Fugl-Meyer assessment (FMA-UE). Assessors tested patients immediately before therapy, after 4 weeks of therapy, at the end of therapy, and 16 weeks and 34 weeks after start of therapy. Assessors were masked to treatment allocation, but patients, therapists, and data analysts were unmasked. Analyses were by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT00719433. Findings Between May 4, 2009, and Sept 3, 2012, 143 individuals were tested for eligibility, of whom 77 were eligible and agreed to participate. 38 patients assigned to robotic therapy and 35 assigned to conventional therapy were included in analyses. Patients assigned to robotic therapy had significantly greater improvements in motor function in the affected arm over the course of the study as measured by FMA-UE than did those assigned to conventional therapy ( F =4·1, p=0·041; mean difference in score 0·78 points, 95% CI 0·03–1·53). No serious adverse events related to the study occurred. Interpretation Neurorehabilitation therapy including task-oriented training with an exoskeleton robot can enhance improvement of motor function in a chronically impaired paretic arm after stroke more effectively than conventional therapy. However, the absolute difference between effects of robotic and conventional therapy in our study was small and of weak significance, which leaves the clinical relevance in question. Funding Swiss National Science Foundation and Bangerter-Rhyner Stiftung.

Introduction De nombreuses etudes montrent que le reapprentissage de tâches motrices depend considerablement de l’intensite de l’entrainement. Dans le cadre hospitalier, un entrainement quotidien intensif reste un defi, entre autres pour des questions de frais de personnel. L’utilisation de nouvelles technologies peut completer ce potentiel de maniere complementaire. Cette etude a evalue si de plus longs temps d’entrainement (50 minutes par entrainement au lieu de 25 minutes) sont possibles et s’ils conduisent a une meilleure capacite a marcher. Methode Vingt et un patients atteints de paraplegie motrice non aigue complete (American Spinal Injury Association Impairment Scale [ASIA B]) et incomplete (ASIA C) ont ete inclus dans cette etude et repartis aleatoirement en un groupe d’entrainement standard (max. 25 minutes) ou intensif (au moins 50 minutes) avec un robot d’aide a la marche (Lokomat, Hocoma SA, Volketswil/CH). L’entrainements a dure 8 semaines et comprenait 3–5 entrainements par semaine. Resultats Dix-huit patients ont termine l’entrainement (moyenne 34 entrainements). Les entrainements plus longs sont significativement et clairement associes a une meilleure capacite a se deplacer (Spinal Cord Independence Measure, domaine de mobilite 20/40 vs 10/40). Aucun resultat indesirable n’a ete observe. Conclusions Les resultats valident l’hypothese selon laquelle un entrainement appuye par une technologie est possible et que des entrainements prolonges conduisent a de meilleurs resultats. Il n’a pas encore pu etre montre si des entrainements encore plus longs peuvent encore ameliorer ces resultats. Chez les patients examines, le retablissement des fonctions neurologiques et fonctionnelles depend de l’entrainement, mais aussi du niveau et de la gravite de la lesion de la moelle epiniere. Signification La mise a profit de l’ensemble du potentiel de readaptation doit etre consideree au moyen de formes d’entrainement assistees par des moyens technologiques.

OBJECTIVE: Spinal neuronal function is impaired after a severe spinal cord injury (SCI) and can be assessed by the analysis of spinal reflex (SR) behavior. We applied transcutaneous spinal direct current stimulation (tsDCS) and locomotor activity, to determine whether the excitability of spinal neuronal circuitries underlying locomotion can be modulated after motor complete SCI. METHOD: SRs were evoked by non-noxious electrical stimulation of the tibial nerve. SR behavior was assessed before, immediately after, and 20min after four different interventions (anodal, cathodal, sham tsDCS, or locomotion) in subjects with motor complete SCI and healthy subjects. RESULTS: SR amplitudes in SCI subjects were increased after anodal tsDCS by 84% (p

Item does not contain fulltext Facilitation of leg muscle activity by active arm movements during locomotor tasks could be beneficial during gait rehabilitation after spinal cord injury. The present study explored the effects of arm movements on leg muscle activity during submaximal recumbent stepping. Healthy subjects exercised on a recumbent stepping machine both with and without arm movements. Activity of five leg muscles was recorded and compared for stepping with and without arm movements. To determine which arm movements are optimal for leg muscle facilitation, subjects were instructed to step with 1) mechanically coupled vs. decoupled arm and leg movements, 2) synchronous vs. asynchronous arm movements, and 3) at 50 vs. 70 RPM. Leg muscle activity was increased by active arm movements in all muscles, except the vastus lateralis muscle. Activity of other extensors (soleus, medial gastrocnemius, and biceps femoris) was primarily increased during the extension phase, whereas activity of flexors (tibialis anterior) was also increased during the flexion phase. Facilitation was more or less consistent for both frequencies and for synchronous and asynchronous movements. For coupled arm movements, facilitation tended to be diminished or absent. The observed facilitation in the present study is probably of neuromuscular rather than biomechanical origin, since the arms are probably hardly involved in postural control or weight-bearing during recumbent stepping. Further studies in patients should explore the possibility to integrate neuromuscular facilitation in rehabilitation programs. 01 juli 2013

In recent years it has become evident that, in a number of functional movements, synergistically acting limbs become task-specifically linked by a soft-wired 'neural coupling' mechanism (e.g. the legs during balancing, the arms and legs during gait and both arms during cooperative hand movements). Experimentally this mechanism became evident by the analysis of reflex responses as a marker for a neural coupling. It is reflected by the task-specific appearance of reflex EMG responses to non-noxious nerve stimulation, not only in muscles of the stimulated limb, but also, with same long latency, in muscles of meaningful coupled (contralateral) limb(s). After a stroke, nerve stimulation of the unaffected limb during such cooperative tasks is followed by EMG responses in muscles of the (contralateral) coupled affected limb, i.e. unaffected motor centres support synergistically acting movements of the paretic limb. In contrast, following stimulation of the affected limb, no contralateral responses appear due to defective processing of afferent input. As a consequence, it may be therapeutically possible to strengthen the influence of unaffected motor centres on the performance of affected limb movements through training of cooperative limb movements required during activities of daily living.

Recent research indicates that a task-specific, interhemispheric neural coupling is involved in the control of cooperative hand movements required for activities of daily living. This neural coupling is manifested in bilateral electromyographic reflex responses in the arm muscles to unilateral arm nerve stimulation. In addition, fMRI recordings show a bilateral task-specific activation and functional coupling of the secondary somatosensory cortical areas (S2) during the cooperative, but not during bimanual control tasks. This activation is suggested to reflect processing of shared cutaneous input during the cooperative task in both cortical areas. In chronic poststroke patients, arm nerve stimulation of the unaffected arm also leads to bilateral electromyographic responses, similar to those seen in healthy subjects in the cooperative task. However, stimulation of the affected side is frequently followed only by ipsilateral responses. The presence/absence of contralateral electromyographic responses correlates with the clinical motor impairment measured by the Fugl-Meyer score. The observations suggest impaired processing of afferent input from the affected side leading to defective neural coupling during cooperative hand movements after stroke. In moderately affected patients, movement execution seems to rely on the involvement of the ipsilateral corticospinal tract arising in the non-damaged hemisphere. According to these results, hand rehabilitation of stroke patients, currently focused on reach and grasp movements of the affected side, should be supplemented with the training of cooperative hand movements required during activities of daily living.

In patients suffering from a movement disorder after a damage of the central nervous system, improvement in walking or hand function can be achieved by providing functional training. After a stroke or a spinal cord injury (SCI), neuronal centers at and below the level of lesion exhibit plasticity that can be exploited by functional training paradigms that include assisting stepping or hand/arm movements of the affected side. Training of locomotor function, the focus of this chapter, requires body-weight support (BWS), while the subjects stand on a moving treadmill. In these individuals, human spinal locomotor centers become activated if an appropriate afferent input is provided. The stroke/SCI subjects benefit from such locomotor training that enables them to walk over ground. Load- and hip joint-related afferent input seems to be of crucial importance for the generation of a locomotor pattern and, consequently, the effectiveness of the locomotor training. In severely affected stroke/SCI subjects, rehabilitation robots enable longer, i.e., more intensive training. In addition, they also offer the ability to standardize training approaches and to obtain objective feedback within training sessions allowing to monitor functional improvements over time. This chapter provides an overview of the clinical aspects for the successful application of robotic devices in the neurorehabilitation of stroke/SCI subjects. First, background information is given for the neural mechanisms of gait recovery after stroke/SCI. Second, the afferent input required for an effective training is discussed and, third, findings from clinical studies are presented covering the feasibility and efficacy of robot-assisted locomotor training.

Complex movements are programmed in the central nervous system (CNS) and adapted by proprioceptive feedback. The selection of and interaction between different sources of afferent input is task dependent. Simple stretch reflexes are thought to be involved primarily in the control of focal movement. For more complex motor behaviors such as locomotion, afferent input related to load and hip-joint position probably has an important role in the proprioceptive contribution to the activation pattern of the leg muscles. Advances in our understanding of movement control allow us to define more precisely the requirements for the rehabilitation of patients with movement disorders. Accordingly, acknowledging the discrepancy between spasticity as assessed by clinical bedside testing and spasticity as presented in movement disorders affecting gait is essential to appreciate the true impact of spasticity. Central motor lesions are associated with a loss of supraspinal drive and defective use of afferent input. These changes lead to paresis and maladaptation of the movement pattern. Secondary changes in mechanical muscle fiber and collagen tissue result in spastic muscle tone, which in part compensates for paresis and allows functional movements on a simpler level of organization. The respective contributions to an aberrant gait pattern are complex and the resolution benefits from applying detailed kinematic movement analyses complementary to clinical measures to reveal changes in motor control. The distinct capacity of subjects with an incomplete spinal cord injury (iSCI) to remain able to modulate time–distance parameters but revealing complex impairments of intralimb coordination and the dissimilar responsiveness to rehabilitative interventions reveal distinct domains of neural control of walking. More sensitive outcome measures will be essential to uncover the respective contributions of restitution (i.e., repair of damaged neural structures) and mechanisms attributable to adaptation and compensatory movement strategies to rehabilitation-dependent functional improvements.

Uncontrolled muscle spasms often develop after spinal cord injury. Structural and functional maladaptive changes in spinal neuronal circuits below the lesion site were postulated as an underlying mechanism but remain to be demonstrated in detail. To further explore the background of such secondary phenomena, rats received a complete sacral spinal cord transection at S(2) spinal level. Animals progressively developed signs of tail spasms starting 1 week after injury. Immunohistochemistry was performed on S(3/4) spinal cord sections from intact rats and animals were sacrificed 1, 4 and 12 weeks after injury. We found a progressive decrease of cholinergic input onto motoneuron somata starting 1 week post-lesion succeeded by shrinkage of the cholinergic interneuron cell bodies located around the central canal. The number of inhibitory GABAergic boutons in close contact with Ia afferent fibers was greatly reduced at 1 week after injury, potentially leading to a loss of inhibitory control of the Ia stretch reflex pathways. In addition, a gradual loss and shrinkage of GAD65 positive GABAergic cell bodies was detected in the medial portion of the spinal cord gray matter. These results show that major structural changes occur in the connectivity of the sacral spinal cord interneuronal circuits below the level of transection. They may contribute in an important way to the development of spastic symptoms after spinal cord injury, while reduced cholinergic input on motoneurons is assumed to result in the rapid exhaustion of the central drive required for the performance of locomotor movements in animals and humans.

Diffusion tensor imaging (DTI) is rarely applied in spinal cord injury (SCI). The aim of this study was to correlate diffusion properties after SCI with electrophysiological and neurological measures. Nineteen traumatic cervical SCI subjects and 28 age-matched healthy subjects participated in this study. DTI data of the spinal cord were acquired with a Philips Achieva 3 T MR scanner using an outer volume suppressed, reduced field of view (FOV) acquisition with oblique slice excitation and a single-shot EPI readout. Neurological and electrophysiological measures, American Spinal Injury Association (ASIA) impairment scale scores, and motor (MEP) and somatosensory evoked potentials (SSEP) were assessed in SCI subjects. Fractional anisotropy (FA) values were decreased in the SCI subjects compared to the healthy subjects. In upper cervical segments, the decrease in FA was significant for the evaluation of the entire cross-sectional area of the spinal cord, and for corticospinal and sensory tracts. A decreasing trend was also found at the thoracic level for the corticospinal tracts. The decrease of DTI values correlated with the clinical completeness of SCI, and with SSEP amplitudes. The reduced DTI values seen in the SCI subjects are likely due to demyelination and axonal degeneration of spinal tracts, which are related to clinical and electrophysiological measures. A reduction in DTI values in regions remote from the injury site suggests their involvement with wallerian axonal degeneration. DTI can be used for the quantitative evaluation of the extent of spinal cord damage, and eventually to monitor the effects of future regeneration-inducing treatments.

The aim of this study was to explore the neural basis of adaptation, memory and skill transfer during human stepping over obstacles. Whilst walking on a treadmill, subjects had to perform uni- and bilateral obstacle steps. Acoustic feedback information about foot clearance was provided. Non-noxious electrical stimuli were applied to the right tibial nerve during the mid-stance phase of the right leg, i.e. 'prior' to the right or 'during' the left leg swing over the obstacle. The electromyogram (EMG) responses evoked by these stimuli in arm and leg muscles are known to reflect the neural coordination during normal and obstacle steps. The leading and trailing legs rapidly adapted foot clearance during obstacle steps with small further changes when the same obstacle condition was repeated. This adaptation was associated with a corresponding decrease in arm and leg muscle reflex EMG responses. Arm (but not leg) muscle EMG responses were greater when the stimulus was applied 'during' obstacle crossing by the left leg leading compared with stimulation 'prior' to right leg swing over the obstacle. A corresponding difference existed in arm muscle background EMG. The results indicate that, firstly, the somatosensory information gained by the performance and adaptation of uni- and bilateral obstacle stepping becomes transferred to the trailing leg in a context-specific manner. Secondly, EMG activity in arm and leg muscles parallels biomechanical adaptation of foot clearance. Thirdly, a consistently high EMG activity in the arm muscles during swing over the obstacle is required for equilibrium control. Thus, such a precision locomotor task is achieved by a context-specific, coordinated activation of arm and leg muscles for performance and equilibrium control that includes adaptation, memory and skill transfer.

Background. Alterations in the function of spinal neuronal circuits underlying locomotion after a spinal cord injury (SCI) are associated with changes in the behavior of spinal reflexes (SRs) in both rats and humans. In healthy subjects, the SR consists of a dominant early reflex component, whereas in chronic, severely affected SCI subjects, a later component dominates. Objective. The aim of this study was to investigate the relationship between SR behavior and walking ability in para-/tetraplegic subjects. Method. The SR was evoked by nonnoxious tibial nerve stimulation. Walking ability was assessed by functional tests and questionnaires. Results. There was a correlation between walking ability and SR behavior in chronic SCI: Severely affected SCI subjects unable to walk showed dominant late SR components, whereas in ambulatory SCI subjects an early SR component dominated. A functional training with an improvement of locomotor ability was accompanied by both a shift from a dominant to a smaller late and the appearance of an early SR component. Conclusions. Our findings indicate that SR can serve as a marker for the locomotor ability of SCI subjects. Neuronal plasticity exploited by a functional training is reflected in both an improvement of locomotor ability and a change in balance of SR components toward the early SR component.

Little is known about the impact of supraspinal centers on the control of human locomotion. Analyzing brain activity can help to clarify their impact and to improve the effects of locomotor training. A fMRI-compatible pneumatic robotic device is presented that can generate freely programmable, highly repetitive periodic active and passive leg movements comprised by hip, knee, and ankle joint displacements. Forces of up to 400N can be applied to each foot while the subject is lying in a supine position. Magnetic interference of the device with the magnetic field of the scanner is measurable, but does not affect the image quality as obtained by a usual image analysis procedure. In a first experiment, brain activity of one healthy subject was acquired during nine different gait-like movement conditions. Brain activity in the somatosensory and motor function related areas increased more when the subject actively moved the legs than when the legs were passively moved by the device. In almost all conditions, mean head motion could be limited to 2mm within the duration of one fMRI scan by a specifically developed head and trunk fixation system. Based on these results, it is concluded that our device will significantly contribute to a better understanding of human locomotor control and related therapeutic effects in spinal cord injured and stroke patients, and thereby, to improve training approaches.

In complete spinal cord injured (cSCI) subjects a shift from dominant early (60–120 ms latency) to dominant late (120–450 ms latency) spinal reflex (SR) components occurs over time after injury. This shift is assumed to reflect a spinal neuronal dysfunction below the level of a spinal lesion. The neuronal pathways of SR are suggested to be closely connected with spinal locomotor circuits. The aim of this study was to explore the influence of the two SR components on the electromyographic (EMG) pattern induced by assisted locomotion in cSCI subjects. Leg muscle EMG activity was analysed during assisted locomotion in both healthy and motor cSCI subjects. SR were evoked by non-noxious tibial nerve stimulation during mid-stance phase of the gait cycle. Early and late SR components had a differential influence on the locomotor pattern. In healthy and cSCI subjects with a dominant early SR component the locomotor EMG pattern was modulated in the form of a short increase in leg flexors activity in the stance phase (tibialis anterior, biceps femoris). In contrast, in chronic cSCI subjects with a dominant late SR component no activation in biceps femoris but a long-lasting activation of tibialis anterior and rectus femoris muscles during the stance phase was evoked. It is concluded that the same tibial nerve stimuli activated two different neuronal pathways, resulting in divergent interactions with spinal locomotor circuitries. It is proposed that the two SR components have different physiological roles during locomotion.

This study investigated the interactions of supraspinal with spinal neuronal circuits during obstacle steps by recordings of electroencephalography (EEG), reflex activity and limb muscle electromyography (EMG). Subjects walking with reduced vision on a treadmill were acoustically informed about an approaching obstacle and received feedback about task performance. Only following a task-relevant acoustic signal, spinal reflex responses, evoked by tibial nerve stimulation during mid-stance, were enhanced in proximal arm and leg flexor muscles prior to obstacle compared to normal swing, reflecting the neuronal preparation of the task. During swing over the obstacle, limb muscle EMG activity was greater than in normal swing. Both the preparation and the performance (i.e. ascending movement slope of the obstacle-crossing leg) were associated with an enhanced EEG signal mainly in the prefrontal cortex of the right hemisphere. Adaptational changes in performance, reflex activity and muscle activation during repetitive obstacle stepping were not reflected in the EEG activity, probably due to an insufficient resolution of the EEG. The observations suggest that drive from supraspinal centers initiates and maintains spinal neuronal activity underlying obstacle task preparation and performance.

This review describes the changes of spinal neuronal function that occur after a motor complete spinal cord injury (cSCI) in humans. In healthy subjects, polysynaptic spinal reflex (SR) evoked by non-noxious tibial nerve stimulation consists of an early SR component and rarely a late SR component. Soon after a cSCI, SR and locomotor activity are absent. After spinal shock; however, an early SR component re-appears associated with the recovery of locomotor activity in response to appropriate peripheral afferent input. Clinical signs of spasticity take place in the following months, largely as a result of non-neuronal changes. After around 1 year, the locomotor and SR activity undergo fundamental changes, that is, the electromyographic amplitude in the leg muscles during assisted locomotion exhaust rapidly, accompanied by a shift from early to dominant late SR components. The exhaustion of locomotor activity is also observed in non-ambulatory patients with an incomplete spinal cord injury (SCI). At about 1 year after injury, in most cSCI subjects the neuronal dysfunction is fully established and remains more or less stable in the following years. It is assumed that in chronic SCI, the patient's immobility resulting in a reduced input from supraspinal and peripheral sources leads to a predominance of inhibitory drive within spinal neuronal circuitries underlying locomotor pattern and SR generation. Training of spinal interneuronal circuits including the enhancement of an appropriate afferent input might serve as an intervention to prevent neuronal dysfunction after an SCI.

This short review summarizes developments and achievements made during the last few years in spinal neurology and includes all relevant papers published in the Journal of Neurology during this time. A focus of the review concerns the debate about the significance of translational medicine in spinal cord injury with the introduction of new drugs directed to achieve some spinal cord repairs.