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Bilateral hand movements are assumed to be coordinated by a neural coupling mechanism. Neural coupling is experimentally reflected in complex electromyographic (EMG) responses in the forearm muscles of both sides to unilateral electrical arm nerve stimulation (ES). The aim of this study was to examine a potential involvement of the reticulospinal system in neural coupling by the application of loud acoustic stimuli (LAS) known to activate neurons of this system. LAS, ES and combined LAS/ES were applied to healthy subjects during visually guided bilateral hand flexion-extension movements. Muscle responses to the different stimuli were evaluated by electrophysiological recordings. Unilateral electrical ulnar nerve stimulation resulted in neural coupling responses in the forearm extensors (FE) of both sides. Interestingly, LAS evoked bilateral EMG responses that were similar in their configuration to those induced by ES. The presence of startles was associated with a shift of the onset and enhanced amplitude of LAS-induced coupling-like responses. Upon combined LAS/ES application, ES facilitated ipsilateral startles and coupling-like responses. Modulation of coupling-like responses by startles, the similarity of the responses to ES and LAS, and their interaction following combined stimulation suggests that both responses are mediated by the reticulospinal system. Our findings provide novel indirect evidence that the reticulospinal system is involved in the neural coupling of hand movements. This becomes clinically relevant in subjects with a damaged corticospinal system where a dominant reticulospinal system leads to involuntary limb coupling, referred to as associated movements. KEY POINTS: Automatic coordination of hand movements is assumed to be mediated by a neural coupling mechanism reflected by bilateral reflex responses in forearm muscles to unilateral electrical arm nerve stimulation (ES). Loud acoustic stimuli (LAS) were applied to assess a potential involveme

Background: The description of the natural course of recovery from a spinal cord injury (SCI) with spontaneous improvement of neurological, neurophysiological, and functional measures is an important prerequisite in appraising effects of upcoming interventional therapies. Objective: To describe the spontaneous evolution of motor-evoked potentials of the anterior tibial muscle (TA-MEP) and their relation to outcomes of lower extremity motor scores (LEMS) and walking function in patients recovering from an acute SCI. Methods: TA-MEPs were assessed in 255 SCI subjects within 5 time intervals throughout the first year after SCI with combined neurological and functional measures. Tibial nerve conduction studies were performed to screen for peripheral nerve damage. Results: TA-MEP allowed stratification of SCI according to lesion severity and outcome. As MEP amplitudes increased over 12 months after SCI, this was paralleled by a significant improvement of LEMS and walking function. TA-MEP latencies remained usually stable. Conclusion: Clinical outcome and walking function after SCI can be predicted independent of clinical measures by assessment of TA-MEP reflecting corticospinal tract integrity.

The application of rehabilitation therapy technologies in children with neurological impairments appears promising. Characteristics of these robotic-supported and computer-assisted therapies are in line with principles of motor learning. They include high numbers of repetitions, prolonged training durations, and online feedback about the patient’s active participation. When applied by experienced therapists, the technologies provide a safe and simultaneously fun and motivating therapy to young patients. Furthermore, the evidence of the effectiveness for lower and upper limb applications is rising. We wrote this chapter to account for the lack of knowledge concerning the implementation and evidence-based application of such technologies. We discuss in this chapter the complementary role of rehabilitation therapy technologies and present general considerations for their implementation and application. Furthermore, we propose a conceptual ordering of categories of lower and upper limb rehabilitation therapy technologies, based on whether the systems provide weight support, physical assistance, or ‘only’ augmented feedback. Finally, we present some of these technologies representing the categories in more detail and summarize the research and evidence of these technologies.

This chapter focuses on robotic gait training. As a basis, it summarizes the neurophysio-logical rationale for such training. These neurophysiological findings are mostly based on animal studies. The observations from these studies led to the development of theories such as the spinal central pattern generator (CPG). In a deductive manner, studies have then also been performed on human participants showing similar phenomena. Based on the neurophysiological mechanisms, robot-assisted locomotor training is justified even in patients with severe functional limitations.Those patients would not be able to maintain an upright posture while performing stepping movements in a conventional training condition.The clinical application of robotic gait training is, therefore, another focus of this chapter. Different robotic devices and their relevant characteristics are introduced. Not all devices are designed to purely assist locomotor training by maximally exploiting the neuroplastic potential of the central nervous system. Some devices can also be considered assistive technologies which support patients in their daily life mobility. General aspects which are relevant for robotic gait training during rehabilitation are summarized. Then the chapter takes the translation of the fundamental principles one step further and addresses the application of robotic gait training in specific neurological conditions, that is, in stroke, traumatic brain injury (TBI), spinal cord injury (SCI), multiple sclerosis (MS), and Parkinson’s disease. These parts are written by experts in their respective fields. Every section follows the same structure and informs the reader about the condition in general, specific gait limitations, and the rehabilitation thereof. If available, the latter is supported by recent high-level evidence. In the other cases, relevant primary studies are summarized. Because specific clinical guidelines for the application of robotic gait training are largely missing, the e

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.

Cooperative hand movements (e.g., opening a bottle) require a close coordination of the hands. This is reflected in a neural coupling between the two sides. The aim of this study was to investigate in how far neural coupling is present not only during bilateral hand but also during bilateral finger movements. For this purpose unilateral mechanical and electrical nerve stimuli were delivered during bilateral sequentially and synchronously performed finger movements on a keyboard and, for comparison, during bilateral hand flexion movements. Electromyographic (EMG) activity and reflex responses in forearm flexor and extensor muscles of both sides were recorded and analyzed. Confounding EMG activity related to hand movements during the finger task was limited by wrist fixating braces. During the hand flexion task, complex reflex responses appeared in the forearm muscles of both sides to unilateral stimulation of the ulnar nerve (mean latency 57 ms), reflecting neural coupling between the two hands. In contrast, during the bilateral finger movement task, unilateral electrical nerve or mechanical stimulation of the right index finger was followed by dominant ipsilateral reflex responses (latency 45 and 58 ms, respectively). The results indicate that in contrast to the coupled hand movements, finger movements may not be coupled but can move independently on each side. Functionally this makes sense because during most activities of daily living, a close cooperation of the hands but not of individual fingers is needed. This independence of individual finger movements may rely on strong, specific, contralateral cortico-motoneuronal control.

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.

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.

Background: A large proportion of patients with spinal cord injury (SCI) regain ambulatory function. However, during the first 3 months most patients are unable to walk without support. To enable ambulatory training at such an early stage the body weight is partially relieved and leg movement assisted by two therapists. A more recent approach is the application of robotic-based assistance, which allows for longer training duration. From the science of motor learning and studies including patients with stroke, it is known that training effects depend on the duration of the training. Longer training results in a better walking function. Purpose: The aim of the present study is to evaluate whether prolonged robot-assisted walking training leads to a better walking outcome in patients with incomplete SCI, who are initially unable to walk independently (i.e. B and C according to the International Standards for Neurological Classification of SCI-ISNCSCI), and whether such training is feasible or is associated with undesirable effects. Methods: Patients from three sites with an acute incomplete SCI (within 60 days after injury) were randomized to either standard training (session duration 25 minutes) or intensive training (session duration 50 minutes). After 8 weeks of training walking ability (Walking Index for SCI-WISCI, scale 0-20: 0=not able to walk, 20= able to walk independently), the occurrence of adverse events and the rate of perceived exertion (RPE, scale 1-10: 1=very light, 10= very, very hard), as well as patients’ global impression of change (PGIC, scale 0 -10: 0= much better, 5= no change, 10= much worse) were compared between groups. Results: Seventeen patients with incomplete SCI were randomly assigned either to standard training (ISNCSCI B: n=6; C: n=2) or to intensive training (B: n=3; C: n=6). The average duration of training of the standard group was half the length of the intensive group (24.9±0.6 minutes vs. 48.3±3.2 minutes; p=0.01). Both groups perf

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.

The aim of this study was to examine whether older adults use the same task-specific brain activation patterns during two different bimanual hand movement tasks as younger adults. Functional magnetic resonance brain imaging was performed in 18 younger (mean age: 30.3 ± 3.6 years) and 11 older adults (62.6 ± 6.8 years) during the execution of cooperative (mimicking opening a bottle) or non-cooperative (bimanual pro-/supination) hand movements. We expected to see a stronger task-specific involvement of the secondary somatosensory cortex (S2) during cooperative hand movements in older compared to younger adults. However, S2 activation was present in both groups during the cooperative task and was only significantly stronger compared to the non-cooperative task in younger adults. In a whole brain-analysis, the contrast between older and younger adults revealed a hyperactivation of the bilateral dorsal premotor cortex (precentral gyrus), right thalamus, right frontal operculum, anterior cingulate cortex, and supplementary motor areas in older adults ( < 0.001), with some of them being visible after correcting for age. Age was positively associated with fMRI signal changes in these regions across the whole sample. Older adults showed reduced gray matter volume but not in regions showing task-related fMRI group differences. We also found an increase in functional connectivity between SMA, M1, thalamus, and precentral gyri in older adults. In contrast, younger adults showed hyperconnectivity between S2 and S1. We conclude that older compared to younger adults show age-related functional neuroplastic changes in brain regions involved in motor control and performance.

The past decades have seen rapid and vast developments of robots for the rehabilitation of sensorimotor deficits after damage to the central nervous system (CNS). Many of these innovations were technology-driven, limiting their clinical application and impact. Yet, rehabilitation robots should be designed on the basis of neurophysiological insights underlying normal and impaired sensorimotor functions, which requires interdisciplinary collaboration and background knowledge.Recovery of sensorimotor function after CNS damage is based on the exploitation of neuroplasticity, with a focus on the rehabilitation of movements needed for self-independence. This requires a physiological limb muscle activation that can be achieved through functional arm/hand and leg movement exercises and the activation of appropriate peripheral receptors. Such considerations have already led to the development of innovative rehabilitation robots with advanced interaction control schemes and the use of integrated sensors to continuously monitor and adapt the support to the actual state of patients, but many challenges remain. For a positive impact on outcome of function, rehabilitation approaches should be based on neurophysiological and clinical insights, keeping in mind that recovery of function is limited. Consequently, the design of rehabilitation robots requires a combination of specialized engineering and neurophysiological knowledge. When appropriately applied, robot-assisted therapy can provide a number of advantages over conventional approaches, including a standardized training environment, adaptable support and the ability to increase therapy intensity and dose, while reducing the physical burden on therapists. Rehabilitation robots are thus an ideal means to complement conventional therapy in the clinic, and bear great potential for continued therapy and assistance at home using simpler devices.This review summarizes the evolution of the field of rehabilitation robotics, as well as

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.

During recent years, evidence has come up that bipedal locomotion is based on a quadrupedal limb coordination. A task-dependent neuronal coupling of upper and lower limbs allows one to involve the arms during gait but to uncouple this connection during voluntarily guided arm/hand movements. Hence, despite the evolution of a strong cortico-spinal control of hand/arm movements in humans, a quadrupedal limb coordination persists during locomotion. This has consequences for the limb coordination in movement disorders such as in Parkinson's disease (PD) and after stroke. In patients suffering PD, the quadrupedal coordination of gait is basically preserved. The activation of upper limb muscles during locomotion is strong, similar as in age-matched healthy subjects although arm swing is reduced. This suggests a contribution of biomechanical constraints to immobility. In post-stroke subjects a close interactions between unaffected and affected sides with an impaired processing of afferent input takes place. An afferent volley applied to a leg nerve of the unaffected leg leads to a normal reflex activation of proximal arm muscles of both sides. In contrast, when the nerve of the affected leg was stimulated, neither on the affected nor in the unaffected arm muscles EMG responses appear. Muscle activation on the affected arm becomes normalized by influences of the unaffected side during locomotion. These observations have consequences for the rehabilitation of patients suffering movement disorders

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

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

The purpose of the present study was to explore factors that influence the occurrence of the Babinski sign (BS) in complete spinal cord injury patients. At Balgrist University Hospital, Zurich, Switzerland, thirty-five subjects suffering from a complete traumatic spinal cord injury (ASIA A) were examined for the occurrence of the BS, tendon reflex excitability and spastic muscle tone (Modified Ashworth Scale). Five subjects were acute/subacute (1-6months after spinal cord injury (SCI)), 30 were chronic (SCI>1year). In one subject, the measures were examined before and after injection of intrathecal Baclofen. Subjects with a negative BS were investigated electrophysiologically for possible peripheral nerve damage. In 17 subjects (49%), the BS was present, while it was absent in 18 subjects (51%). The occurrence of the BS did not depend on the level of lesion. Most patients with a positive BS also presented a high spastic muscle tone, while those with a negative BS showed low level or absent spastic muscle tone. In 11 SCI subjects, absence of the BS was associated with peripheral nerve damage. In one patient, the BS along with spastic signs disappeared after intrathecal injection of Baclofen. In complete SCI subjects, the occurrence of the BS is connected with spastic muscle tone. The absence of the BS is frequently due to associated peripheral nerve damage

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

Severe spinal cord injury in humans leads to a progressive neuronal dysfunction in the chronic stage of the injury. This dysfunction is characterized by premature exhaustion of muscle activity during assisted locomotion, which is associated with the emergence of abnormal reflex responses. Here, we hypothesize that undirected compensatory plasticity within neural systems caudal to a severe spinal cord injury contributes to the development of neuronal dysfunction in the chronic stage of the injury. We evaluated alterations in functional, electrophysiological and neuromorphological properties of lumbosacral circuitries in adult rats with a staggered thoracic hemisection injury. In the chronic stage of the injury, rats exhibited significant neuronal dysfunction, which was characterized by co-activation of antagonistic muscles, exhaustion of locomotor muscle activity, and deterioration of electrochemically-enabled gait patterns. As observed in humans, neuronal dysfunction was associated with the emergence of abnormal, long-latency reflex responses in leg muscles. Analyses of circuit, fibre and synapse density in segments caudal to the spinal cord injury revealed an extensive, lamina-specific remodelling of neuronal networks in response to the interruption of supraspinal input. These plastic changes restored a near-normal level of synaptic input within denervated spinal segments in the chronic stage of injury. Syndromic analysis uncovered significant correlations between the development of neuronal dysfunction, emergence of abnormal reflexes, and anatomical remodelling of lumbosacral circuitries. Together, these results suggest that spinal neurons deprived of supraspinal input strive to re-establish their synaptic environment. However, this undirected compensatory plasticity forms aberrant neuronal circuits, which may engage inappropriate combinations of sensorimotor networks during gait execution

The aim of this study was to evaluate the course of spinal neuronal activity following spinal cord injury (SCI). In patients with a complete SCI, the leg muscle EMG activity early and up to 33 years after an SCI was analysed during locomotor movements induced and assisted by a driven gait orthosis (DGO). Only in chronic SCI patients did a premature exhaustion of neuronal activity occur. This was reflected in a reduced density and fading of leg muscle EMG activity. The early exhaustion of EMG activity was more pronounced in the leg flexor (e.g. biceps femoris) than extensor (e.g. gastrocnemius) muscles. The timing of the leg muscle pattern remained unchanged in the chronic patients. A preserved amplitude of motor action potentials following repetitive peripheral nerve stimulation and during spasms indicated an interneuronal site of impairment. In patients who participated in a locomotor training programme lasting up to 13 weeks, no positive effect on the slope of exhaustion was seen. It is concluded that a degradation of spinal neuronal activity takes place following an SCI. If in the future regeneration of spinal tract fibres becomes feasible in patients with complete SCI, such an approach can only become functionally successful if neuronal activity below the level of the lesion is maintained. This might be achieved by a continuous training approach starting early after injury

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 'sunaffected' 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