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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.

Background One problem in the mobilization of patients with neurological diseases, such as spinal cord injury, is the circulatory collapse that occurs while changing from supine to vertical position because of the missing venous pump due to paralyzed leg muscles. Therefore, a tilt table with integrated stepping device (tilt stepper) was developed, which allows passive stepping movements for performing locomotion training in an early state of rehabilitation. The aim of this pilot study was to investigate if passive stepping and cycling movements of the legs during tilt table training could stabilize blood circulation and prevent neurally-mediated syncope in healthy young adults. Methods In the first experiment, healthy subjects were tested on a traditional tilt table. Subjects who had a syncope or near-syncope in this condition underwent a second trial on the tilt stepper. In the second experiment, a group of healthy subjects was investigated on a traditional tilt table, the second group on the tilt ergometer, a device that allows cycling movements during tilt table training. We used the chi-square test to compare the occurrence of near-syncope/syncope in both groups (tilt table/tilt stepper and tilt table/tilt ergometer) and ANOVA to compare the blood pressure and heart rate between the groups at the four time intervals (supine, at 2 minutes, at 6 minutes and end of head-up tilt). Results Separate chi-square tests performed for each experiment showed significant differences in the occurrence of near syncope or syncope based on the device used. Comparison of the two groups (tilt stepper/ tilt table) in experiment one (ANOVA) showed that blood pressure was significantly higher at the end of head-up tilt on the tilt stepper and on the tilt table there was a greater increase in heart rate (2 minutes after head-up tilt). Comparison of the two groups (tilt ergometer/tilt table) in experiment 2 (ANOVA) showed that blood pressure was significantly higher on the tilt ergometer at the end of head-up tilt and on the tilt table the increase in heart rate was significantly larger (at 6 min and end of head-up tilt). Conclusions Stabilization of blood circulation and prevention of benign syncope can be achieved by passive leg movement during a tilt table test in healthy adults.

A number of diseases of the brain and spinal cord are associated with substantial neural cell death and/or disruption of correct and functional neural networks. In the past, a variety of therapeutic strategies to rescue these systems have been proposed along with agents to induce functional plasticity within the remaining central nervous system (CNS) structures. In the case of injury or neurodegenerative disease these approaches have only met with limited success, indicating the need for novel approaches to treat diseases of the adult CNS. Recently, the idea of recruiting endogenous or transplanting stem cells to replace lost structures within the adult brain or spinal cord has gained significant attention, along with in situ reprogramming, and opened up novel therapeutic avenues in the context of regenerative medicine. Here we review recent advances in our understanding of how endogenous stem cells may be a part of pathological processes in certain neuropsychiatric diseases and summarize recent clinical and preclinical data suggesting that stem cell-based therapies hold great promise as a future treatment option in a number of diseases disrupting the proper function of the adult CNS.

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., The coordination of bilateral hand movements is reflected by a neural coupling. In contrast bilateral finger movements can move independently on each side. This independence of finger movements may rely on strong, specific, contralateral cortico‐motoneuronal control.

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.

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.

After a spinal cord injury (SCI) of the cat or rat, neuronal centers below the level of lesion exhibit plasticity than can be exploited by specific training paradigms. In individuals with complete or incomplete SCI, human spinal locomotor centers can be activated and modulated by locomotor training (facilitating stepping movements of the legs using body weight support on a treadmill to provide appropriate sensory cues) (for review see [2], [3]). Individuals with incomplete SCI benefit from locomotor training such that they improve their ability to walk over ground. Load- or hip joint-related afferent input seems to be of crucial importance for both the generation of a locomotor pattern and the effectiveness of the training [2]. However, it may be a critical combination of afferent signals that is needed to generate a locomotor pattern after severe SCI.

In recent decades, several novel approaches of spinal cord repair have revealed promising findings in animal models. However, for a successful translation of these into a clinical trial in humans the specific conditions pertaining to human spinal cord injuries (SCI) have to be appreciated. Firstly, transection of the spinal cord is commonly applied in animal models, whereas spinal cord contusion is the predominant type of injury in humans, and generally leads to more extensive injury in two to three spinal cord segments. Secondly, the quadrupedal organization of locomotion in animals and the more complex autonomic functions in humans challenge the translation of animal behavior into recovery from human SCI. Thirdly, so far, no adequate animal model has been developed to resemble spastic movement disorder in human SCI. Fourthly, the extensive damage to spinal motor neurons and nerve roots in human cervical and thoracolumbar in spine trauma is but little addressed in current translational studies. This damage has direct implications for rehabilitation and repair strategies. Fifthly, there is increasing evidence for a neuronal dysfunction below the level of the lesion in chronic complete SCI. The relevance of this dysfunction for a regeneration-inducing treatment needs to be investigated. Lastly, an approach to facilitate an appropriate reconnection of regenerating tract fibers by functional training in the postacute stage has yet to be confirmed.