Neural coordination of bilateral hand movements: evidence for an involvement of brainstem motor centres.

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 involvement of the reticulospinal system in the neural coupling mechanism. LAS evoked a bilateral reflex response in the forearm extensors that was similar to the neural coupling response to ES, and which could be separated from the acoustic startle response. Combined application of LAS and ES resulted in a facilitation of startle and coupling-like responses ipsilateral to ES, thus indicating an interaction of afferences from both stimuli. These novel findings provide indirect evidence that the reticulospinal system is a key motor structure for the coupling of bilateral hand movements.

Restoration of motor function after CNS damage: is there a potential beyond spontaneous recovery?

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.

Neural coordination of bilateral power and precision finger movements.

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.

Differential neural coordination of bilateral hand and 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.

Management of pain in individuals with spinal cord injury: Guideline of the German-Speaking Medical Society for Spinal Cord Injury.

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.

In vivo evidence of remote neural degeneration in the lumbar enlargement after cervical injury.

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.

Rehabilitation robots for the treatment of sensorimotor deficits: a neurophysiological perspective.

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.

Cooperative hand movements: effect of a reduced afference on the neural coupling mechanism.

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.

Neuroplastic Changes in Older Adults Performing Cooperative Hand Movements.

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.

From the Rodent Spinal Cord Injury Model to Human Application: Promises and Challenges.

Repair of the spinal cord and improvement of mobility after injury has been a matter of basic and clinical research for several decades. A number of repair approaches were performed in animals, mainly rodent models of spinal cord injury (SCI). Some of these experimental therapies resulted in significant regeneration of tract fibers, formation of new connections and circuits, and associated improvement of mobility. Some clinical trials aiming at translating these approaches to the human condition of an SCI are currently on-going. The present therapy, however, remains rehabiliation: Mobility of patients with an SCI can be improved to a limited extent by the exploition of neuroplasticity. In this article the present state of the art in the field of SCI research will be discussed. Studies dealing with the promotion of spinal cord repair and those directed to improve mobility by exploition of neuroplasticity will be summarized. The promises and challenges of translational basic research in rodent SCI models will be presented.

Effect of Locomotor Training on Exhaustion of Leg Muscle Activity in Chronic Complete Spinal Cord Injury.

The aim of this study was to evaluate the effect of a continuous locomotor training on leg muscle electromyographic (EMG) exhaustion during assisted stepping movements in a patient with motor complete spinal cord injury (SCI). EMG exhaustion and loss of potentials starts to develop in untrained patients at ∼6 months after injury. In the trained patient examined in this study, exhaustion was also observed but occurred with a delay of several months. In contrast to an untrained patient, no more EMG exhaustion was observed in the very chronic stage. At this time (12 years after injury) a basic locomotor pattern of leg muscle activity of reduced amplitude could still be elicited, but it was resistant to exhaustion and unchanged in amplitude after 12 min of assisted stepping. It is suggested that fatigue-resistant motor units prevail at this stage and can still be activated during stepping as a result of the training.

Effectiveness of Automated Locomotor Training in Patients with Acute Incomplete Spinal Cord Injury: A Randomized, Controlled, Multicenter Trial.

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.

Neural coupling of cooperative hand movements after stroke: role of ipsilateral afference.

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.

Improving outcome of sensorimotor functions after traumatic spinal cord injury.

In the rehabilitation of a patient suffering a spinal cord injury (SCI), the exploitation of neuroplasticity is well established. It can be facilitated through the training of functional movements with technical assistance as needed and can improve outcome after an SCI. The success of such training in individuals with incomplete SCI critically depends on the presence of physiological proprioceptive input to the spinal cord leading to meaningful muscle activations during movement performances. Some actual preclinical approaches to restore function by compensating for the loss of descending input to spinal networks following complete/incomplete SCI are critically discussed in this report. Electrical and pharmacological stimulation of spinal neural networks is still in the experimental stage, and despite promising repair studies in animal models, translations to humans up to now have not been convincing. It is possible that a combination of techniques targeting the promotion of axonal regeneration is necessary to advance the restoration of function. In the future, refinement of animal models according to clinical conditions and requirements may contribute to greater translational success.

Control of functional movements in healthy and post-stroke subjects: Role of neural interlimb coupling.

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.

Cooperative hand movements in post-stroke subjects: Neural reorganization.

OBJECTIVE: Recent research indicates a task-specific neural coupling controlling cooperative hand movements reflected in bilateral electromyographic reflex responses in arm muscles following unilateral nerve stimulation. Reorganization of this mechanism was explored in post-stroke patients in this study. METHODS: Electromyographic reflex responses in forearm muscles to unilateral electrical ulnar nerve stimulation were examined during cooperative and non-cooperative hand movements. RESULTS: Stimulation of the unaffected arm during cooperative hand movements led to electromyographic responses in bilateral forearm muscles, similar to those seen in healthy subjects, while stimulation of the affected side was followed only by ipsilateral responses. No contralateral reflex responses could be evoked in severely affected patients. The presence of contralateral responses correlated with the clinical motor impairment as assessed by the Fugl-Meyer test. CONCLUSION: The observations suggest that after stroke an impaired processing of afferent input from the affected side leads to a defective neural coupling and is associated with a greater involvement of fiber tracts from the unaffected hemisphere during cooperative hand movements. SIGNIFICANCE: The mechanism of neural coupling underlying cooperative hand movements is shown to be defective in post-stroke patients. The neural re-organizations observed have consequences for the rehabilitation of hand function.

Neural coupling of cooperative hand movements: a reflex and fMRI study.

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.

Recovery of sensorimotor function and activities of daily living after cervical spinal cord injury: the influence of age.

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.