Computations underlying the execution of movement: a biological perspective.

To execute voluntary movements, the central nervous system must transform the neural representation of the direction, amplitude, and velocity of the limb, represented by the activity of cortical and subcortical neurons, into signals that activate the muscles that move the limb. This task is equivalent to solving an "ill-posed" computational problem because the number of degrees of freedom of the musculoskeletal apparatus is much larger than that specified in the plan of action. Some of the mechanisms and circuitry underlying the transformation of motor plans into motor commands are described. A central feature of this transformation is a coarse map of limb postures in the premotor areas of the spinal cord. Vectorial combination of motor outputs among different areas of the spinal map may produce a large repertoire of motor behaviors.

A Myoelectric Computer Interface for Reducing Abnormal Muscle Activations after Spinal Cord Injury.

Myoelectric Computer Interfaces (MCIs) are a viable option to promote the recovery of movements following spinal cord injury (SCI), stroke, or other neurological disorders that impair motor functions. We developed and tested a MCI interface with the goal of reducing abnormal muscular activations due to compensatory strategies or undesired co-contraction after SCI. The interface mapped surface electromyographic signals (sEMG) into the movement of a cursor on a computer monitor. First, we aimed to reduce the co-activation of muscles pairs: the activation of two muscles controlled orthogonal directions of the cursor movements. Furthermore, to decrease the undesired concurrent activation of a third muscle, we modulated the visual feedback related to the position of the cursor on the screen based on the activation of this muscle. We tested the interface with six unimpaired and two SCI participants. Participants were able to decrease the activity of the targeted muscle when it was associated with the visual feedback of the cursor, but, interestingly, after training, its activity increased again. As for the SCI participants, one successfully decreased the co-activation of arm muscles, while the other successfully improved the selective activation of leg muscles. This is a first proof of concept that people with SCI can acquire, through the proposed MCI, a greater awareness of their muscular activity, reducing abnormal muscle simultaneous activations.

Changes in neuromuscular activity during motor training with a body-machine interface after spinal cord injury.

Body machine interfaces (BMIs) are used by people with severe motor disabilities to control external devices, but they also offer the opportunity to focus on rehabilitative goals. In this study we introduced in a clinical setting a BMI that was integrated by the therapists in the rehabilitative treatments of 2 spinal cord injured (SCI) subjects for 5 weeks. The BMI mapped the user's residual upper body mobility onto the two coordinates of a cursor on a screen. By controlling the cursor, the user engaged in playing computer games. The BMI allowed the mapping between body and cursor spaces to be modified, gradually challenging the user to exercise more impaired movements. With this approach, we were able to change our subjects' behavior, who initially used almost exclusively their proximal upper body-shoulders and arms - for using the BMI. By the end of training, cursor control was shifted toward more distal body regions - forearms instead of upper arms - with an increase of mobility and strength of all the degrees of freedom involved in the control. The clinical tests and the electromyographic signals from the main muscles of the upper body confirmed the positive effect of the training. Encouraging the subjects to explore different and sometimes unusual movement combinations was beneficial for recovering distal arm functions and for increasing their overall mobility.

Modular organization of motor behavior in the frog's spinal cord.

The complex issue of translating the planning of arm movements into muscle forces is discussed in relation to the recent discovery of structures in the spinal cord. These structures contain circuitry that, when activated, produce precisely balanced contractions in groups of muscles. These synergistic contractions generate forces that direct the limb toward an equilibrium point in space. Remarkably, the force outputs, produced by activating different spinal-cord structures, sum vectorially. This vectorial combination of motor outputs might be a mechanism for producing a vast repertoire of motor behaviors in a simple manner.

Modular features of motor control and learning.

The study of complex motor behaviours has highlighted the role of modular representations both in the planning and in the execution of actions. Recent findings suggest the presence of functional modules within a variety of neural structures. Computational investigations are now addressing the issue of how these modules may act concurrently to generate a wide repertoire of behaviours.

Neural basis of motor control and its cognitive implications.

It has recently been demonstrated that human subjects and nonhuman primates adapt their arm movements when subjected to complex patterns of disturbing forces. The presence of aftereffects following the removal of the disturbing forces indicates that adaptation takes place through the development of an internal model of the disturbing force. The experimental evidence described in this paper has identified some important properties of this internal model: (1) it is limited to a region surrounding that part of the space where the disturbances had been experienced; (2) there is an enhancement of the internal model that depends only on the passage of time; and (3) there is a process of consolidation of the internal model, which takes a minimum of four hours. Anatomically, the substrate of the internal model is distributed; the motor cortex, basal ganglia, and cerebellum are interconnected structures that are active to different degrees during the acquisition of motor skills. Recent investigation of the spinal cord has suggested the existence of modules that organize the motor output in a discrete set of synergies. The outputs of these modules combine by addition, and might thus form the building blocks for the internal models represented by supraspinal structures.

A body-machine interface for training selective pelvis movements in stroke survivors: A pilot study.

The body-machine interfaces (BMIs) map the subjects' movements into the low dimensional control space of external devices to reach assistive and/or rehabilitative goals. This work is a first proof of concept of this kind of BMI as tool for rehabilitation after stroke. We designed an exercise to improve the control of selective movements of the pelvis in stroke survivors, increasing the ability to decouple the motion in the sagittal and frontal planes and decreasing compensatory adjustments at the shoulder girdle. A Kinect sensor recorded the movements of the subjects. Subjects played different games by controlling the vertical and horizontal motion of a cursor on a screen with respectively the lateral tilt and the ante/retroversion of their pelvis. We monitored also the degrees of freedom not directly involved in cursor control, thus subjects could complete the task only with a correct posture. Our preliminary results highlight significant improvement not only in cursor control, but also in the Trunk Impairment Scale (TIS) and in the Five Times Sit to Stand Test (5xSST).

Analysis of the antigen specific T cell repertoires in HIV infection.

In addition to HIV infection, several acquired immunodeficiencies lead to depletion of CD4 lymphocytes. These include immunosuppression resulting from high dose cancer chemotherapy or induced to control graft rejection, as well as in autoimmune diseases. The consequence of this depletion is an increased susceptibility to opportunistic infections or the inability to control primary infection in the case of HIV infection. In all instances a full or partial immunoreconstitution is desirable. In order to monitor the cellular immune state of a patient, rational information cannot be simply derived from phenotypic quantification of T lymphocytes. Instead loss or recovery of CD4 cells should be monitored by defining the specificity, the function and the clonality of the relevant cell population. Several methods are now available for this type of investigation. Here we describe an approach for the definition of clonal heterogeneity of antigen specific CD4 lymphocytes, a parameter that may help monitor loss or reconstitution in acquired immunodeficiencies. As examples of antigen specific CD4 T cell responses we focused on Pneumocystis carinii and on cytomegalovirus, as prototypic opportunistic pathogens which are responsible for severe infections in AIDS and in other immunosuppressive conditions which arise for instance following transplantation. Specific CD4 T cell lines were generated from normal controls and from seropositives in order to select antigen specific lymphocytes. The cells were subsequently analyzed for clonal diversity according to TCR BV gene family usage and according to TCR CDR3 size heterogeneity (spectratyping).

Do neurons in the motor cortex encode movement direction? An alternative hypothesis.

Previous investigations by Georgopoulos et al. of cell activities in the primate motor cortex during the execution of voluntary arm movements have shown that these cells are characterized by tuning properties related to the direction of hand trajectories. Here, it is demonstrated that these findings do not necessarily imply that cortical cells encode spatial features of hand movements and an alternative hypothesis is considered according to which cortical cells encode muscle state variables. It is shown that this hypothesis would lead both to the single-cell activities and to the population behaviors observed by Georgopoulos et al.

In vitro selection of HIV and CMV specific T-lymphocytes.

CMV and HIV produce life-long infections. During CMV infection, cellular responses mediated by virus specific CD8 and CD4 lymphocytes are effective, while during HIV infection cellular responses are ineffective in the long run. In recent years, much work has been carried out to better characterize such responses by using different methodologies to define the fine epitope specificity, the frequency and the function of specific T-cells. These studies have diagnostic and therapeutic implications. In fact, monitoring of specific lymphocytes may help define the immune status of the patients for therapeutic interventions. Identification of CD8 and CD4 epitopes allows the use of relevant peptides for lymphocyte stimulation or for vaccine development. Enumeration of specific cells permits a quantitative estimate of the immune response. In vitro selection provides large numbers of virus specific T-cells for studies on clonal composition, on epitope mapping and on HLA restriction as well as for therapeutic immunoreconstitution with ex vivo expanded T-cells.

Effects of whole-body vibration on spinal reflexes in man.

Recent studies have described sensory-motor function alterations resulting from vibrations applied to various parts of the body. The present work describes the effects produced at the myotatic loop level by long-term vibration. Hoffmann and Tendon reflexes as well as tendon vibration response were substantially depressed by 18 Hz, +/- 0.25 G vibration applied to the whole body or to the legs of seated human subjects. The reflex inhibition lasted throughout the 15-min vibration period and persisted minutes after stimulus cessation. In contrast, vibration limited to the S's head and trunk showed much weaker effects. This suggests that the vibration acts mainly upon extero- and proprioceptive receptors rather than upon the vestibular organs. The results are discussed in relation to findings derived from experiments involving locally applied short-duration vibration.

Haptic perception of multi-joint hypertonia during simulated patient-therapist physical tele-interaction.

A potential solution to provide individualized physical therapy in remote areas is tele-interaction via robotic devices. To maintain stability during tele-interaction, transmission delay-compensation algorithms bound the impedance between the patient and the therapist. This can compromise the haptic perception of the patient being assessed, which can in turn lead to a bad diagnosis or intervention. We investigated how the perception of the severity of hypertonia (a common condition after neurological disorders) varied by modifying the connection impedance on a physical simulator. We found that assessing hypetonia using a low impedance connection may result in an overestimation of mild impairments.

Therapist recognition of impaired muscle groups in simulated multi-joint hypertonia.

It is common in today's clinical practice for a therapist to physically manipulate patients' limbs to assess hypertonic conditions (e.g. spasticity, rigidity, dystonia, among others). We present a study that evaluates the capabilities of expert therapists to correctly identify the location of a hypertonic impairment of an arm through standard manipulation. Therapists interacted with a hypertonic virtual arms rendered on a robotic device. Our results show that testing joints independently can cause misjudgment of the mechanical contributions of pluri-articular muscles to multi-joint impairment.

Haptic recognition of dystonia and spasticity in simulated multi-joint hypertonia.

This paper investigates the capability of naïve individuals to recognize dystonic- or spastic- like conditions through physical manipulation of a virtual arm. Subjects physically interact with a two-joint, six-muscle hypertonic arm model, rendered on a two degrees-of-freedom robotic manipulandum. This paradigm aims to identify the limitation of manual manipulation during diagnosis of hypertonia. Our results indicate that there are difficulties to discriminate between the two conditions at low to medium level of severity. We found that the sample entropy of the executed motion and the force experienced during physical manipulation, tended to be higher during incorrectly identified trials than in those correctly assessed.

Inhaled nitric oxide versus sodium nitroprusside for preoperative evaluation of pulmonary hypertension in heart transplant candidates.

OBJECTIVE: The development of pulmonary hypertension before heart transplantation increases the risk for postoperative right ventricular failure. Reversibility of pulmonary vascular resistance (PVR), which indicates the feasibility of heart transplantation, can be tested with the use of intravenous vasodilators, such as sodium nitroprusside (NaNTP) or prostacyclin. However, the drawback of these drugs is the development of systemic hypotension. The aim of this study was to evaluate the safely and feasibility of inhaled nitric oxide (iNO) compared with sodium nitroprusside to test PVR reversibility, while avoiding systemic hypotension. MATERIALS AND METHODS: We included all patients who were affected by end stage heart failure undergoing evaluation for heart transplantation if they showed elevated PVR > 2.5 Wood units and mean pulmonary arterial pressure (mPAP) >25 mm Hg. The hemodynamic parameters measured by right heart catheterization were: systolic blood pressure (SBP), mPAP, pulmonary capillary wedge pressure, and cardiac index (CI). The following variables were derived: transpulmonary gradient (TPG) and PVR. All patients were tested by both iNO (20-40 ppm) and intravenous NaNTP, at increasing dosages which were titrated based on systemic pressure. We randomly assigned the order of administration of iNO and NaNTP. RESULTS: The 9 male candidates has an average age of 56 ± 4 years. Seven of the 9 (71%) had postischemic cardiomyopathy, and 2 had idiopathic cardiomyopathy. We observed a reduction of mPAP (32% and 14%), PVR (41% and 32%), TPG (20% and 26%), and SBP (17% and 5%) and an increase of CI with administration of NaNTP and iNO, respectively. CONCLUSIONS: We observed a reduction in PVR and mPAP with administration of either iNO and NaNTP. A better effect of NaNTP was attributed to reducted post-load of the left ventricle. However, the main advantage of iNO was the absence of systemic hypotension and its selectivity for pulmonary vascular system, as underscored by TPG reduction.

Perception and Action in Teleoperated Needle Insertion.

We studied the effect of delay on perception and action in contact with a force field that emulates elastic soft tissue with a rigid nonlinear boundary. Such a field is similar to forces exerted on a needle during teleoperated needle insertion. We found that delay causes motor underestimation of the stiffness of this nonlinear soft tissue, without perceptual change. These experimental results are supported by simulation of a simplified mechanical model of the arm and neural controller, and a model for perception of stiffness, which is based on regression in the force-position space. In addition, we show that changing the gain of the teleoperation channel cancels the motor effect of delay without adding perceptual distortion. We conclude that it is possible to achieve perceptual and motor transparency in virtual one-dimensional remote needle insertion task.

Multijoint arm stiffness during movements following stroke: implications for robot therapy.

Impaired arm movements in stroke appear as a set of stereotypical kinematic patterns, characterized by abnormal joint coupling, which have a direct consequence on arm mechanics and can be quantified by the net arm stiffness at the hand. The current available measures of arm stiffness during functional tasks have limited clinical use, since they require several repetitions of the same test movement in many directions. Such procedure is difficult to obtain in stroke survivors who have lower fatigue threshold and increased variability compared to unimpaired individuals. The present study proposes a novel, fast quantitative measure of arm stiffness during movements by means of a Time-Frequency technique and the use of a reassigned spectrogram, applied on a trial-by-trial basis with a single perturbation. We tested the technique feasibility during robot mediated therapy, where a robot helped stroke survivors to regain arm mobility by providing assistive forces during a hitting task to 13 targets covering the entire reachable workspace. The endpoint stiffness of the paretic arm was estimated at the end of each hitting movements by suddenly switching of the assistive forces and observing the ensuing recoil movements. In addition, we considered how assistive forces influence stiffness. This method will provide therapists with improved tools to target the treatment to the individual's specific impairment and to verify the effects of the proposed exercises.

Body machine interface: remapping motor skills after spinal cord injury.

The goal of a body-machine interface (BMI) is to map the residual motor skills of the users into efficient patterns of control. The interface is subject to two processes of learning: while users practice controlling the assistive device, the interface modifies itself based on the user's residual abilities and preferences. In this study, we combined virtual reality and movement capture technologies to investigate the reorganization of movements that occurs when individuals with spinal cord injury (SCI) are allowed to use a broad spectrum of body motions to perform different tasks. Subjects, over multiple sessions, used their upper body movements to engage in exercises that required different operational functions such as controlling a keyboard for playing a videogame, driving a simulated wheelchair in a virtual reality (VR) environment, and piloting a cursor on a screen for reaching targets. In particular, we investigated the possibility of reducing the dimensionality of the control signals by finding repeatable and stable correlations of movement signals, established both by the presence of biomechanical constraints and by learned patterns of coordination. The outcomes of these investigations will provide guidance for further studies of efficient remapping of motor coordination for the control of assistive devices and are a basis for a new training paradigm in which the burden of learning is significantly removed from the impaired subjects and shifted to the devices.

The remapping of space in motor learning and human-machine interfaces.

Studies of motor adaptation to patterns of deterministic forces have revealed the ability of the motor control system to form and use predictive representations of the environment. One of the most fundamental elements of our environment is space itself. This article focuses on the notion of Euclidean space as it applies to common sensory motor experiences. Starting from the assumption that we interact with the world through a system of neural signals, we observe that these signals are not inherently endowed with metric properties of the ordinary Euclidean space. The ability of the nervous system to represent these properties depends on adaptive mechanisms that reconstruct the Euclidean metric from signals that are not Euclidean. Gaining access to these mechanisms will reveal the process by which the nervous system handles novel sophisticated coordinate transformation tasks, thus highlighting possible avenues to create functional human-machine interfaces that can make that task much easier. A set of experiments is presented that demonstrate the ability of the sensory-motor system to reorganize coordination in novel geometrical environments. In these environments multiple degrees of freedom of body motions are used to control the coordinates of a point in a two-dimensional Euclidean space. We discuss how practice leads to the acquisition of the metric properties of the controlled space. Methods of machine learning based on the reduction of reaching errors are tested as a means to facilitate learning by adaptively changing he map from body motions to controlled device. We discuss the relevance of the results to the development of adaptive human-machine interfaces and optimal control.