Rehabilitation Robotics: Technology and Application

Italy

Rehabilitation Robotics: Technology and Applications

The last decades have seen major advances in interventions for neuromotor rehabilitation. Forms of treatment based on repetitive exercise of coordinated motor activities have been proved effective in improving gait and arm functions and ultimately the patients' quality of life. Exercise-based treatments constitute a significant burden for therapists and are heavy consumers of health-care resources. Technologies such as robotics and virtual reality can make them more affordable.

Rehabilitation robotics specifically focuses on systems—devices, exercise scenarios, and control strategies—aimed at facilitating the recovery of impaired sensory, motor, and cognitive skills. The field has a relatively long history, dating back to the early 1990s. Early attempts were part of the general trend toward automating heavy tasks by using intelligent machines, with minimal human intervention. The notion of artificial therapist was common in early scientific papers and patent applications. However, the most distinctive feature of these devices is not their ability to automate treatment but, rather, that of precisely quantifying sensorimotor performance during exercise, in terms of movement kinematics and exchanged forces. This resulted in a gradual shift toward more evidence-based and data-driven forms of treatment. Present-generation rehabilitation robots are designed as complements, rather than substitutes, of the therapist's work. They support the recovery of functions by efficiently exploiting structure and adaptive properties of the human sensorimotor systems and provide rich information on sensorimotor performance and their evolution. Their design, implementation, and modalities of intervention incorporate findings from behavioral studies on sensorimotor adaptation and motor skill learning and their neural substrates.

Rehabilitation robotics is therefore characterized by highly specific design approaches and technical solutions, with roots in both engineering and neurophysiology.

This book addresses both technology and application aspects of Rehabilitation Robotics. Part I focuses on the state of the art and representative advancements in the design, control, analysis, and implementation of rehabilitation robots and the underlying neurophysiological principles. Part II addresses the existing applications and the clinical validation of these systems, with a special emphasis on therapy robots, which support exercise-based treatments aimed at recovering sensorimotor or cognitive functions.

PART I: Background and Technology

Neurophysiology

Planning and execution of movements results from the coordinated activity of multiple interconnected sensory and motor areas in the cerebral cortex. When an area in this specialized motor network is damaged—for example, through a traumatic brain injury or an ischemic event—the activity of the motor networks can be disrupted, thus leading to functional deficits. How the surviving motor networks reorganize to compensate for the injury depends on the location and extent of the lesion but may be affected by sensorimotor exercise.

Chapter 1 summarizes how neuroplasticity modifies motor networks in response to injury, by focusing on the changes after a cerebrovascular accident in the primary motor cortex. Neuroanatomical and neurophysiological evidence in animal models and human stroke survivors is reviewed to demonstrate how injuries functionally impair motor networks, how motor networks compensate for the lesion to improve motor function, and how selected therapies may facilitate recovery.

Chapter 2 focuses on the hierarchical architecture and synergistic functioning of the motor system. These aspects are crucial for the development of successful robotics applications with rehabilitation purposes. The same framework is used to discuss the mechanisms underlying rehabilitation interventions with a potential to facilitate the recovery process.

Technology and Design Concepts

Devices for rehabilitation benefit from advances in robot technologies, including sensors and actuators, mechanical architectures, and the corresponding control architectures. These devices are characterized by a continuous interaction with the human body, which poses specific design constraints.

Chapter 3 summarizes the notion of biomechatronic design for systems for robot-mediated rehabilitation, encompassing robot structure, musculoskeletal biomechanics, and neural control. Robots for rehabilitation are typically conceived to constantly work in constrained motion with the human body, which represents a challenge for designers. This requires a top-down design approach, in which a model of the human agent guides a concurrent, iterative design cycle of the robot's mechanical, electronic, and multilayered control subsystems. Criteria for the identification of functional and technical specifications and the selection of key components of the robotic system are also derived. Two design case studies demonstrate how these design principles are translated into practice.

Chapter 4 addresses how actuators play a critical role in defining the characteristics of the robot-patient interaction. The different options for actuating and controlling a rehabilitation device are discussed, considering the complex flow of information between the user and the robot during a rehabilitation task. Strategies for both high- and low-level control are presented. Impedance and admittance control modalities are discussed as means of decoding human intention and/or modulating the assistive forces delivered by the robot. Mathematical tools for model-based compensation of nonlinear phenomena (backlash and friction) are also presented.

The way robots are used to facilitate training is crucial for their application to therapy and has important implications for their mechanical and control design. Intensity and frequency of practice are major determinants of the recovery process, but different exercise modalities are possible. Robots may be used for haptic rendering in virtual environments, to provide forces that facilitate task performance or task completion, and/or to make a task more difficult and challenging.

Chapter 5 reviews the control strategies for robotic therapy devices and summarizes the techniques for implementing assistive strategies, including counterbalance techniques and adaptive controllers that modify control parameters based on the patient's ongoing performance.

Personalized treatment is becoming increasingly popular in neurorehabilitation. Two chapters discuss how new design techniques such as exoskeletons or wearable robots are applied to the design of modern therapy robots, for either upper or lower limb rehabilitation.

Chapter 6 specifically addresses the design of exoskeletons for upper-limb rehabilitation. After an introduction of the rationale behind the selection of this robot architecture and a review of the available solutions for actuation, the chapter discusses the state of the art and the most commonly adopted solutions. An overview of clinical evidences of upper-limb rehabilitation with exoskeletons is then provided, discussing evidences in favor of training with exoskeleton devices.

Chapter 7 reviews the current state and clinical effectiveness, safety, and usability of exoskeletons for gait rehabilitation. It provides an overview of the actuation technologies, including compliant and lightweight solutions. Control strategies aimed at guiding the patient according to his/her needs and encouraging his/her active participation are also discussed. Novel perspectives for symbiotic human-exoskeleton interaction based on interfaces with neural structures are also introduced.

Computational Neurorehabilitation

One important feature of therapy robots is that they integrate both therapeutic and measuring functionalities. Therapy robots have built-in technology and sensors that measure movement kinematics and kinetics, thus providing an accurate assessment of motor function by which it is possible to diagnose the patient state and to evaluate patient performance and their progress during treatment. The availability of quantitative information has triggered an entirely new paradigm for neurorehabilitation, unifying clinical assessment, and exercise. Computational neurorehabilitation is a new and emerging field, which uses modern data analysis and modeling techniques to understand the mechanisms of neural plasticity and motor learning, and incorporates this knowledge into personalized, data- and model-driven forms of treatment.

Chapter 8 reviews the quantitative measures—encompassing kinematic, kinetic, timing, sensory, and neuromechanical aspects of performance—which are most frequently used to describe motor behavior during robot-assisted rehabilitation of the upper limb. The chapter also analyzes how these indicators are used to monitor motor recovery during exercise, to understand the evolution of performance, and to precisely plan and, if necessary, modify the rehabilitation strategies. The relationship between robot-derived measures and their clinical counterparts is also discussed.

Chapter 9 addresses computational models for neuromotor recovery, with a focus on state-space models that describe the development of functional behaviors through exercise and the relation between neuromotor recovery and motor learning. The chapter first reviews models of the dynamics of sensorimotor adaptation and motor skill learning and then elaborates on similarities and differences with neuromotor recovery. Finally, it discusses how these models can be used to achieve a better understanding of the role of robots to promote recovery and to develop personalized forms of treatment.

Chapter 10 proposes a general framework to model the interaction between robot and patient during robot-assisted training. Human and robot are modeled as two agents, whose respective tasks are described by two cost functions. Optimal interaction strategies are then derived in terms of differential game theory. This approach allows to describe different forms of human-robot interaction. A specific prediction is that optimal interaction requires that the robot maintains a model of the behavior of its human partner. In this case, simulations and empirical studies exhibit more stable, reactive, and adaptive interaction. This form of symbiotic interaction is a step toward defining what it takes for robots to behave as optimal trainers.

Chapter 11 addresses the strategies implemented in rehabilitation robots to promote patient motivation, which is a major determinant of recovery through exercise. Motivation may be measured with self-report questionnaires or with indirect, more objective measures, such as exercise duration. Motivation may be promoted through interaction with virtual environments, which may consist of activities of daily living, which emphasize relatability, or games, which emphasize enjoyment. The design of these environments must take the hardware, the patients' characteristics, and goal-related feedback into account. Motivation during exercise must be maintained by regulating task difficulty, thus ensuring an appropriate challenge level.

Software Environments for Rehabilitation Robotics

As a natural conclusion of this methodological section, Chapter 12 reviews the software development environments that can be used to implement the different levels of control of a modern rehabilitation robot. The robotic field suffers from a lack of standardization in programming environments. Hence, it is not surprising that even in the specific context of rehabilitation robotics, there is currently no consensus on specific software and hardware platforms. The chapter surveys different solutions used for combining robots (and, more in general, haptic interfaces) and virtual environments. Advantages and disadvantages of each of these environments are discussed, together with typical applications, with a focus on upper-limb rehabilitation.

PART II: Applications

The second part of the book addresses the application of rehabilitation robots in different pathologies for training of diverse districts (upper and lower limb) and using different training strategies.

High Intensity, Assist-As-Needed Therapy to Improve Motor Functions

Chapter 13 provides an overview of 28 + years of efforts at MIT's Newman Laboratory for Biomechanics and Human Rehabilitation for the developments of robotic tools to assist in the neurorecovery process. After a definition of the basic principles that are core for successful rehabilitation robotics technology, the chapter presents a snapshot of few of MIT's rehabilitation robots, discusses the results of metaanalyses for upper extremity robotics, and finally presents two exciting examples for acute and chronic stroke. Overall, the above material points out that robotic therapy for the upper extremity that involves an interactive high-intensity, intention-driven therapy based on motor learning principles and assist-as-needed leads to better outcomes than usual care in both acute/subacute and chronic stroke.

The above principles have been extended to training in a three-dimensional workspace, using robots with an exoskeleton structure. Chapter 14 describes the application of one of the first architectures developed with the purpose of mirroring the anatomical structure of the human arm and of enabling task-oriented training in the 3D space, mimicking activities of daily living.

Hand and finger functions are of critical importance for independence in everyday activities, but their recovery is often limited following neurological injury. This has motivated the development of novel therapeutic and assistive tools. Chapter 15 provides a comprehensive overview of robotic approaches for the rehabilitation of hand function and underlines their potential to complement conventional rehabilitation. First, the design concepts of existing hand exoskeletons and end-effector devices are presented. Then, clinical evidence that underlines the feasibility of robot-assisted rehabilitation of hand function is presented. Finally, promising research directions are discussed to further exploit the potential of robot-assisted rehabilitation of hand function in neurological patients.

Robot-assisted gait training typically involves body-weight support and physical guidance to move the legs into the correct pattern. Gait rehabilitation robots allow greater exercise duration and movement repetitions; improve patient safety and motivation; reduce the therapists' burden; and, eventually, improve the therapeutic outcome. Chapter 16 introduces the rationale for robot-assisted gait training. In particular, existing gait-rehabilitation robots and their control strategies are presented. The available clinical trials are also summarized, showing that training with robotic rehabilitation devices is at least as effective as conventional physiotherapy. Further clinical studies are required in order to define the most appropriate robotic technical features based on the task, patients' type, and degree of impairment.

Wearable systems open new perspectives for rehabilitation in individuals with disabilities, which can lead to difficulty in walking or making arm movements since they could be used to facilitate independent training in the clinic or at home. Wearable systems range from complex rigid exoskeleton structures for the assistance of joints or limbs to hybrid, soft, and interactive systems. The existing solutions are not yet widely used in clinical environments. The aim of Chapter 17 is to review the scientific challenges and the current developments of wearable systems and to discuss their clinical potential.

Robots Not Only for Stroke Rehabilitation

Although most applications of robot rehabilitation focus on stroke and traumatic brain injury, these devices may find application in the treatment of other pathologies.

Chapter 18 addresses robot-assisted rehabilitation in multiple sclerosis (MS). Robot-assisted training leads to improved movement quality on reaching tasks, but clinical effects on standard assessment have not been always observed after multiple-session training. An increasing number of studies report effects of a multiple-week training program, but the magnitude of the effect was often similar to conventional training programs. Overall, there is evidence supporting the beneficial effect of robot- and technology-supported training, but its superiority compared with other or conventional treatment programs is still debatable. Research investigating the impact of different technological settings and the motor learning strategies implemented in technology must be encouraged for MS patients.

Persons with cognitive deficits are a completely different target population that can be addressed by therapy robots. Cognitive rehabilitation therapy (CRT) is a set of interventions designed to enhance cognitive performance. Ideally, CRT engages the participant in a learning activity to enhance neurocognitive skills relevant to the overall recovery goals. There is ongoing research to identify the determinants of a positive response to treatment. Chapter 19 addresses the use of rehabilitation robots, socially interactive robots (SIR), and socially assistive robots (SAR), both virtual and embodied, to enhance, restore, or prevent early deterioration of cognitive abilities related to neurodegenerative disease or injury.

Integrating Robot Therapy With Neuro- and Psychophysiological Techniques

All the techniques and devices described until now use robot technology alone. Integration of different approaches and different technologies may improve the outcome, for instance, by training and restoring different functions within the same training session or by using physiological signals to monitor and/or control the recovery process. The following chapters focus on the use of neuro- and psychophysiological signals to enhance or complement robot-assisted therapy.

Chapter 20 presents hybrid FES-robot devices for training of activities of daily living aiming at the parallel restoration of functions by the external activation of paralyzed muscles and external mechanical support of postural functions. The combination of two modalities within the same treatment may multiply their individual effects as the external activation of muscles eliminates the need for large mechanical actuators and reduces the number of degrees of freedom to a controllable domain and, on the other hand, robot guidance removes the need for prolonged, fatiguing stimulation of muscles.

In spite of the acknowledged importance of proprioception for motor control and neuromotor rehabilitation, no effective method for assessment and rehabilitation of proprioceptive deficits has emerged in clinical practice. While there are many clinical scales for assessing proprioception, they all have insufficient psychometric properties and cannot be used in closed-loop treatment paradigms wherein treatment parameters are monitored and adjusted online or with a trial-by-trial frequency. Chapter 21 discusses how robots can simultaneously address two interrelated needs: to provide sensitive and repeatable assessments of proprioceptive integrity and to automate repetitive training procedures designed to enhance proprioception and its contributions to functional movement.

The outcome of a training program can be conditioned not only by the patient's physical conditions but also by his/her psychophysiological state during the whole course of the rehabilitation program. Chapter 22 reviews psychophysiological response modalities that, together with task performance parameters and biomechanical measurements, may be used in a biocooperative approach to rehabilitation. The chapter focuses in particular on electrocardiogram, skin conductance, respiration signal, and peripheral skin temperature. Each signal is described in terms of acquisition modalities, signal processing, and features extraction. The psychophysiological responses in the case of multimodal challenge and physical activity are also examined, with reference to the differentiation of arousal and valence.

Understanding the mechanisms underlying muscle coordination during daily motor activities is a fascinating challenge in neuroscience and may provide important information pertaining to the recovery strategies of the neuromuscular system. Muscle synergies have been hypothesized as a neural strategy to simplify the control of the redundant motor actuators leading human movement and as a method to study motor coordination in healthy and neurological subjects. Chapter 23 presents the theoretical framework for the extraction and the description of muscle synergies. Moreover, it summarizes how neuropathologies impact on muscle synergies and their potential for neurorehabilitation. Finally, it discusses how muscle synergies can be used to assess the effectiveness of robot-aided rehabilitation and the design of innovative control strategies.

Robots and Information Technologies Advances Toward Long-Term Intervention

As the world's population ages, the management of chronic diseases will become more important. This shift will put pressure on health-care systems that often focus on providing effective care while reducing costs. The use of technological advancements to augment health-care services provides a method to meet these demands. Telerehabilitation robotics, addressed in Chapter 24, combines established features of robot-assisted rehabilitation and tele-health care to provide distance rehabilitation services. While there is a growing market of robotic devices used in traditional rehabilitation settings, home-based implementations provide a unique set of challenges (e.g., remote monitoring, deployment constraints, and data management) that has limited the number of successful solutions. Clinical and kinematic outcomes show promising results and support further investigation. Cost analyses have demonstrated that telerehabilitation robotics is a cost-effective alternative compared with clinic-based therapy. While telerehabilitation robotics is a promising addition to conventional care, numerous barriers that limit practical integration will need to be addressed to allow a more widespread acceptance and use of this approach in rehabilitation.

As a final remark, robot rehabilitation involving an interactive high-intensity, intention-driven therapy based on motor learning principles and assist-as-needed leads to better outcomes than usual care in acute/subacute, chronic stroke and other pathologies. For this reason, clinical guidelines recommend the application of these technologies for the recovery of the lost functions.

This book highlights the most important technical aspects and strategies for the design, development, and application of robot technologies for rehabilitation purposes. With their ability to adapt exercise parameters based on physiological signals, objective and sensitive metrics reflecting the state and performance of a patient, the unique possibility to combine motor and somatosensory training, and the perspective of simple and wearable tools for home rehabilitation, robot devices promise further potential for the rehabilitation of neurological patients aiming at an improved motor function, a reduction of their disability, and overall an improved quality of life.

Chapter 1

Physiological basis of neuromotor recovery

Kevin C. Elliott; David T. Bundy; David J. Guggenmos; Randolph J. Nudo    University of Kansas Medical Center, Kansas City, KS, United States

Abstract

Planning and execution of movement require coordinated activity from several interconnected cortical motor areas. When an area in this specialized motor network is damaged (e.g., through traumatic brain injury or ischemic event), motor network activity can be disrupted, leading to functional deficits. How the surviving motor network reorganizes to compensate for the injury and functional deficits can vary as a pathological consequence of the location and extent of the brain injury. The current chapter summarizes how neuroplasticity modifies motor networks in response to injury by focusing on the changes after an ischemic event in the primary motor cortex. Neuroanatomical and neurophysiological evidence in animal models and human stroke survivors is reviewed to demonstrate how injuries functionally impair motor networks, how motor networks compensate for injury to improve motor function, and how select therapies help facilitate recovery. Further research into these neuroplasticity mechanisms may one day help to develop more effective rehabilitation strategies.

Keywords

Stroke; Motor cortex; Neuronal plasticity; Animal models; Infarction; Synapses; Primates; Hand; Movement

Introduction

Each year in the United States, an estimated 795,000 people experience an acute, localized deprivation of oxygen and nutrient-rich blood that impairs the long-term structure and function of the brain: a phenomenon known as a stroke [1]. While a subset of strokes result from a blood vessel hemorrhage, the overwhelming majority (~ 87%) of stroke incidences are ischemic, resulting from a partial or complete blockage of a main arterial branch in the brain. Ischemic strokes typically involve the middle cerebral artery, a major arterial branch that supplies blood to the frontal, temporal, and parietal cortices and striatal and capsular subcortical areas. Approximately 51% of strokes occur in the cortex as a result of middle cerebral artery occlusion [2], and overall, there is a large variability in stroke type, injury location, severity, and subsequent cell death or infarction that induces a wide range of sensory, motor, and/or cognitive impairments among stroke survivors. As such, this chapter will focus on the effects of ischemic strokes on motor activity in normal and impaired cortices and further elaborate on potential therapeutic options to restore normal motor function after a stroke.

The emphasis of this chapter is on motor function, both in normal and impaired cortex, and the neurophysiological basis of neuromotor recovery following stroke. This chapter will (1) review the functional connectivity and activity within the motor network that underlies movement generation, (2) describe the phenomenon of infarction and explain how it alters motor network function, and (3) discuss the influence of rehabilitation on motor recovery following stroke.

The Functional Organization of the Motor Network

Neural processes, such as those that underlie the generation of arm movement, are thought to rely on distributed networks throughout cortical and subcortical brain areas. Though many of the pathways involved in the generation of simple and complex movements require extensive activity from these subcortical areas, the focus here is on the cortex. Studies in humans largely confirm the broad connections between primary motor cortex, M1 (see Table 1 for all anatomical abbreviations), and other cortical motor areas by the extensive white matter connections measured with diffusion tensor imaging and the strong functional interactions observed as part of resting state functional connectivity MRI networks [3]. For a more comprehensive description of connections between motor areas, see Fig. 1.

Fig. 1 Neuroanatomical studies in the motor areas of nonhuman primates reveal extensive connectivity between M1, premotor, supplementary, and other association motor areas within each hemisphere. As motor areas are bilaterally symmetrical, the medial view of one hemisphere and lateral view of the other hemisphere are used to show all relevant areas. The smaller, whole brain diagram shows the motor areas with reference to the brain in gray. Medial (MCA), anterior (ACA), and posterior (PCA) arteries are shown in black. The larger diagram shows the connectivity between motor areas. Arrows represent bidirectional connectivity between corresponding motor areas. M1 interconnects with PMd and PMv, SMA, S1, posterior parietal cortex, cingulate cortex, and contralateral M1. PMd and PMv—regions that input extensively to M1—interconnect with SMA, prefrontal cortex, orbitoprefrontal cortex, S1, and CMA. Like premotor areas, SMA and anterior pre-SMA similarly interconnect with M1, PMd/PMv, and CMA.

Table 1

The M1, premotor, and supplementary motor areas contain a subset of neurons that target spinal motoneurons, and though these corticospinal (CS) neurons are distributed throughout the cortex, about half reside in M1 [4]. Compared with other mammals, primate CS neurons monosynaptically target a greater number of motoneurons that drive distal forelimb musculature, and an overwhelming 80% of these CS neurons originate directly from the caudal half of M1 [4,5]. A subset of CS neurons that target single motoneurons, referred to as corticomotoneuronal cells, functionally encode specific criteria, such that a single corticomotoneuronal cell may fire to activate, rigidly lock, or brake a specific muscle movement, but are unlikely to be involved in all three actions [6]. The functional significance of this organization is that M1 is uniquely specialized to drive fine motor control such as digit manipulation or complex forelimb movements and many other parameters associated with movement. It follows that M1 injury severely impairs these capabilities relative to other motor regions.

Motor Network Activity and Movement

To better understand the movement parameters encoded by M1, the activity of single CS neurons has been studied for several decades. Early work decoding the activity of individual M1 CS neurons showed that CS activity precedes muscle contraction of small groups of muscles, and the rate of firing of these neurons is related to the force exerted by distal forelimb movements. This suggests that individual CS neurons can encode kinetic-based parameters, where specific neurons correlate to the contraction of muscle groups involved in functional movement execution, such as arm flexion or extension [7]. While CS activity initiates gross muscle movements, the subset of CS neurons that project directly to spinal motoneurons (corticomotoneuronal cells) are recruited during precision movements that require finer muscle control [8]. Subsequent studies analyzed the population codes of M1 neuronal ensembles to demonstrate that most M1 neurons are tuned broadly to movement direction, with increases or decreases in firing rate during limb movements aimed toward or away from the neuron's preferred direction, respectively. These results suggest that in addition to simple muscle-/kinetic-based parameters, M1 encodes extrinsic movement kinematics that includes related features of direction, velocity, position, orientation, and specific muscle activations related to the completion of movement [9]. Thus, M1 contains neuronal populations that encode both simple kinetic activity and more complex kinematics [9].

In addition to recording neuronal activity during movement, stimulation of the motor areas noninvasively either via transcranial magnetic stimulation at the cortical surface (electrocortical stimulation mapping) or via intracortical microstimulation (ICMS) at the motor output layers can elicit movements that denote the area's functional representation. ICMS techniques have revealed that M1 contains prominent proximal (e.g., elbow/shoulder) and distal (e.g., digit) forelimb and hind limb representations for the contralateral side of the body [10]. These generated movement representations are not static, and even short-term behavioral experience is sufficient to reorganize the ICMS-defined borders of each representation [11], suggesting that functional organization—and neurophysiological activity generally—may be sensitive to the perturbations by a stroke within the motor network or subsequent recovery and rehabilitation.

While the preceding understanding of motor activity has been largely based on animal models, several human studies have examined motor physiology using noninvasive electrophysiological recordings and functional imaging techniques. Electroencephalography (EEG) recordings reveal a decrease in mu (9–12 Hz) and beta (12–20 Hz) band spectral power, termed event-related desynchronization, starting in the contralateral M1 and propagating bilaterally just before the onset of voluntary movement. This decrease subsequently rebounds in spectral power, termed event-related synchronization, following movement [12]. Furthermore, studies using electrocorticography electrodes on the cortical surface have found a more focal increase in high-frequency spectral power [13]. Similar studies utilizing functional imaging methods such as positron-emission tomography and functional magnetic resonance imaging have demonstrated increases in activity in M1, supplementary motor, and premotor areas, with activations strongest in the cortical hemisphere contralateral to a moving limb but occurring bilaterally in each of these motor areas [14,15]. Unilateral movement recruits motor areas from both hemispheres and suggests that infarction in one unilateral motor area impairs bilateral motor network function that drives movement.

The Physiology of Ischemic Infarctions

Arterial occlusion may not induce ischemic infarction immediately. Whether temporary occlusions of blood vessels are relatively minor and go completely unnoticed or more severe and readily apparent, they are considered only a transient ischemia in the absence of tissue infarction. In the minutes that follow ischemia, a gradual and dynamic degradation of cortical tissue develops and is related to both the severity and extent of reduced cerebral blood flow. Reductions in flow rate can negatively impact local neuronal electrical activity, ion channel function, and metabolism within the 5–10 min that follow cerebral artery occlusion [16,17]. It is possible for the arterial occlusion to break apart naturally over several minutes, restoring normal blood flow and rapidly reversing both the onset of stroke-like symptoms and the likelihood of permanent damage. However, there is evidence that when arteries are occluded for longer than 1 h or when blood flow is reduced to below 10 mL/100 g/min, irreversible tissue damage can occur [17]. Prolonged periods of decreased blood flow will eventually lead to tissue infarction of not only the initial ischemic site but also the surrounding area or penumbra. Reinstatement of normal blood flow following occlusion can reperfuse the brain, rescue the tissue within the penumbra, and attenuate both the extent of infarction and severity of impairments [18]. Reperfusion of cortical tissue is not without risk, however, as it may cause an inflammatory response, increase cerebral edema, and exacerbate tissue infarction.

Motor Deficits Following Stroke

Generally, a unilateral infarct in M1 will produce severe muscular weakness in the upper and/or lower limbs and/or the contralateral face muscles and several sensory or motor impairments such as vertigo, ataxia (loss of movement control), hemiparesis (paralysis of one side of the body), aphasia (loss of ability to express or understand speech), or hemispatial neglect (inattention to one side of the body). Studies in both human and nonhuman primates show that infarcts can also produce significant reductions in upper and lower limb strength, grip force, and precision [19,20]. While this effect is most prominent in the contralateral side of the body, the stroke survivor may also experience less severe movement-related deficits in the limbs ipsilateral to the infarct [21]. Location and infarct size can also lead to specific sensorimotor deficits, such that similarly sized infarcts that vary by location within the same motor area can produce different deficits. For example, as demonstrated in a nonhuman primate model, infarcts in rostral M1 can impair proprioceptive feedback, resulting in aiming errors; conversely, caudal M1 infarcts can impair manual motor skill and cutaneous sensation [22].

Across the population of stroke survivors, 15%–30% are left with long-term disability. In one study, approximately 50% of the survivors continued to experience hemiparesis 6 months poststroke [1,23]. While some movement recovery occurs spontaneously, targeted therapies can improve motor function in both clinical populations [24] and experimental stroke models [25]. There is a growing consensus that the amount of neurorehabilitation therapy correlates to the level of functional improvement [26]. Additionally, the timing of therapy is important, as functional recovery is thought to plateau by 3 months poststroke [27], and therapy in the acute (< 1 week) and subacute (< 3 weeks) phases of recovery is thought to improve recovery. However, there is also evidence that introducing rehabilitation therapy too early in the subacute phase may be detrimental [28]. This information suggests an optimal window of time where therapies most benefit movement recovery. Additional clinical trials are needed to develop an understanding of the underlying changes in the damaged motor area and the interconnected motor network involved in movement control following a stroke. This clarity will contribute to subsequent recovery strategies and appropriate rehabilitation