BACKGROUND:Spastic muscle tone, often observed after spinal cord injury (SCI), is thought to contribute to body support during walking at a lower level of neural organisation. Understanding the link between damage to specific spinal tracts and the development of spastic muscle tone and mobility could enhance our knowledge of the neural structures crucial for recovery of function after SCI. METHODS:In this retrospective observational study, MRI-based assessments of descending spinal tract damage were related to the development of spastic muscle tone and mobility. Focal damage to the corticospinal (CST) and reticulospinal tracts (RST) was assessed on transversal T2-weighted scans of 49 patients with SCI one month post-injury. The extent of tract damage was then associated with the degree of spastic muscle tone measured by the Modified Ashworth Scale (MAS), and changes in mobility subscore of the Spinal Cord Independence Measure (SCIM). FINDINGS:The extent of CST damage was predictive for the level of MAS score with a positive relationship (β = 0.043, SE = 0.016, OR: 1.044, 95% CI: 1.014-1.080, P = 0.006). This association was negatively modulated by the interaction between CST and RST damage (β = -0.002, SE = 0.001, OR: 0.998, 95% CI: 0.997-0.999, P = 0.004)-i.e. extensive RST damage weakened the relationship between CST damage and MAS score. The extent of RST damage was related to the change in SCIM mobility subscore, independent of MAS score (β: -0.683, SE = 0.231, 95% CI: -1.135 to -0.230, P = 0.007). INTERPRETATION:The extent of CST damage, along with the preservation of the RST, reliably predicts spastic muscle tone, while preserved RST structure alone serves as an independent predictor of mobility outcomes. These observations highlight the role of the reticulospinal system in the functional recovery of mobility and may have broader relevance for other neurological conditions with spinal cord involvement. FUNDING:Swiss National Science Foundation.

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 combinedLAS/ESwere 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 thatwere 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.

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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.

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.

A central nervous system lesion can lead to remote structural and functional changes which may limit functional recovery. For example, after a spinal cord injury (SCI) structural and functional alterations of spinal neuronal networks take place: in the first weeks after an SCI, neither locomotor nor spinal reflex (SR) activity can be evoked. Once spinal shock has resolved, an early SR component can be re-evoked and locomotor electromyography (EMG) activity re-appears when appropriate proprioceptive input is provided. In a more chronic stage of SCI alterations in SR components are accompanied by a decline of EMG amplitude in the leg muscles during assisted locomotion. According to rodent experiments it is assumed that the deprivation of supraspinal input and the lack of meaningful proprioceptive input to spinal neuronal networks account for such alterations. A critical combination of sensory cues through physiological training strategies might prevent the development of an undirected neural plasticity.

The dexterity of hands and fingers is related to the strength of control by cortico-motoneuronal connections which exclusively exist in primates. The cortical command is associated with a task-specific, rapid proprioceptive adaptation of forces applied by hands and fingers to an object. This neural control differs between "power grip" movements (e.g., reach and grasp of a cup) where hand and fingers act as a unity and "precision grip" movements (e.g., picking up a raspberry) where fingers move independently from the hand. In motor tasks requiring hands and fingers of both sides a "neural coupling" (reflected in bilateral reflex responses to unilateral stimulations) coordinates power grip movements (e.g., opening a bottle). In contrast, during bilateral precision movements, such as playing piano, the fingers of both hands move independently, due to a direct cortico-motoneuronal control, while the hands are coupled (e.g., to maintain the rhythm between the two sides). While most studies on prehension concern unilateral hand movements, many activities of daily life are tackled by bilateral power grips where a neural coupling serves for an automatic movement performance. In primates this mode of motor control is supplemented by a system that enables the uni- or bilateral performance of skilled individual finger movements.

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.

Introduction: Pain is a prominent complication in spinal cord injury (SCI). It can either occur as a direct or as an indirect consequence of SCI and it often heavily influences the quality of life of affected individuals. In SCI, nociceptive and neuropathic pain can equally emerge at the same time above or below the level of injury. Thus, classification and grading of pain is frequently difficult. Effective treatment of SCI-related pain in general and of neuropathic pain in particular is challenging. Current treatment options are sparse and their evidence is considered to be limited. Considering these aspects, a clinical practice guideline was developed as basis for an optimized, comprehensive and standardized pain management in SCI-related pain. Methods: The German-Speaking Medical Society for Spinal Cord Injury (Deutschsprachige Medizinische Gesellschaft für Paraplegiologie - DMGP) developed a clinical practice guideline that received consensus from seven further German-speaking medical societies and one patient organization. The evidence base from clinical trials and meta-analyses was summarized and subjected to a structured consensus-process in accordance with the regulations of the Association of Scientific Medical Societies in Germany (AWMF) and the methodological requirements of the "German instrument for methodological guideline appraisal". Results: This consensus-based guideline (S2k classification according to the AWMF guidance manual and rules) resulted in seven on-topic statements and 17 specific recommendations relevant to the classification, assessment and therapy of pain directly or indirectly caused by SCI. Recommended therapeutic approaches comprise pharmacological (e.g. nonsteroidal anti-inflammatory drugs or anticonvulsants) and non-pharmacological (e.g. physical activity or psychotherapeutic techniques) strategies for both nociceptive and neuropathic pain. Discussion: Assessment of SCI-related pain is standardized and respective methods in terms of examination, classification and grading of pain are already in use and validated in German language. In contrast, valid, evidence-based and efficient therapeutic options are limited and ask for further clinical studies, ideally randomized controlled trials and meta-analyses.

Objective 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. Methods 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. Results 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. Conclusions 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.

This chapter deals with the manifestation of spasticity in Spinal Cord Injury (SCI) and how it can be beneficial or detrimental to function. It describes particular features of SCI spasticity based on spinal syndromes and their pathophysiology. The anatomy of a human spinal lesion results in phenotypes with implications for functional deficits that have more effect on spasticity treatment than underlying pathophysiology of presumed neural interaction at the spinal segmental level. Spasticity in SCI as much as in other central nervous system (CNS) pathologies may be seen as a compensatory state of a deficit of sensory-motor control that is usually associated with a lower level of functional CNS organisation. Clinical signs of spasticity are not related to spastic movement disorder. In most surveys, spasticity is rated as the most disabling complication, followed by pain, sexual, bowel, and bladder dysfunction and pressure ulcers. There is an interrelation of spasticity, pain, reduced mobility, contractures, and pressure sores.

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'.

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 current state of clinical evidence. It highlights fundamental neurophysiological factors influencing the recovery of sensorimotor function after a stroke or spinal cord injury, and discusses their implications for the development of effective rehabilitation robots. It thus provides insights on essential neurophysiological mechanisms to be considered for a successful development and clinical inclusion of robots in rehabilitation.

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 (p < 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.

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. (C) 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.