Background and Purpose-Stroke is a leading cause of long-term motor disability among adults. Present rehabilitative interventions are largely unsuccessful in improving the most severe cases of motor impairment, particularly in relation to hand function. Here we tested the hypothesis that patients experiencing hand plegia as a result of a single, unilateral subcortical, cortical or mixed stroke occurring at least 1 year previously, could be trained to operate a mechanical hand orthosis through a brain-computer interface (BCI). Methods-Eight patients with chronic hand plegia resulting from stroke (residual finger extension function rated on the Medical Research Council scaleϭ0/5) were recruited from the Stroke Neurorehabilitation Clinic, Human Cortical Physiology Section of the National Institute for Neurological Disorders and Stroke (NINDS) (nϭ5) and the Clinic of Neurology of the University of Tübingen (nϭ3). Diagnostic MRIs revealed single, unilateral subcortical, cortical or mixed lesions in all patients. A magnetoencephalography-based BCI system was used for this study. Patients participated in between 13 to 22 training sessions geared to volitionally modulate rhythm amplitude originating in sensorimotor areas of the cortex, which in turn raised or lowered a screen cursor in the direction of a target displayed on the screen through the BCI interface. Performance feedback was provided visually in real-time. Successful trials (in which the cursor made contact with the target) resulted in opening/closing of an orthosis attached to the paralyzed hand. Results-Training resulted in successful BCI control in 6 of 8 patients. This control was associated with increased range and specificity of rhythm modulation as recorded from sensors overlying central ipsilesional (4 patients) or contralesional (2 patients) regions of the array. Clinical scales used to rate hand function showed no significant improvement after training. Conclusions-These results suggest that volitional control of neuromagnetic activity features recorded over central scalp regions can be achieved with BCI training after stroke, and used to control grasping actions through a mechanical hand orthosis. (Stroke. 2008;39:910-917.)

Imagining motor acts is a cognitive task that engages parts of the executive motor system. While motor imagery has been intensively studied using neuroimaging techniques, most studies lack behavioral observations. Here, we used functional MRI to compare the functional neuroanatomy of motor execution and imagery using a task that objectively assesses imagery performance. With surface electromyographic monitoring within a scanner, 10 healthy subjects performed sequential finger-tapping movements according to visually presented number stimuli in either a movement or an imagery mode of performance. We also examined effects of varied and fixed stimulus types that differ in stimulus dependency of the task. Statistical parametric mapping revealed movement-predominant activity, imagery-predominant activity, and activity common to both movement and imagery modes of performance (movement-and-imagery activity). The movement-predominant activity included the primary sensory and motor areas, parietal operculum, and anterior cerebellum that had little imagery-related activity (-0.1 ~ 0.1%), and the caudal premotor areas and area 5 that had mild-to-moderate imagery-related activity (0.2 ~ 0.7%). Many frontoparietal areas and posterior cerebellum demonstrated movement-and-imagery activity. Imagery-predominant areas included the precentral sulcus at the level of middle frontal gyrus and the posterior superior parietal cortex/precuneus. Moreover, activity of the superior precentral sulcus and intraparietal sulcus areas, predominantly on the left, was associated with accuracy of the imagery task performance. Activity of the inferior precentral sulcus (area 6/44) showed stimulus-type effect particularly for the imagery mode. A time-course analysis of activity suggested a functional gradient, which was characterized by a more "executive" or more "imaginative" property in many areas related to movement and/or imagery. The results from the present study provide new insights into the functional neuroanatomy of motor imagery, including the effects of imagery performance and stimulus-dependency on brain activity.

Transcranial magnetic stimulation (TMS) was initially used to evaluate the integrity of the corticospinal tract in humans non-invasively. Since these early studies, the development of paired-pulse and repetitive TMS protocols allowed investigators to explore inhibitory and excitatory interactions of various motor and non-motor cortical regions within and across cerebral hemispheres. These applications have provided insight into the intracortical physiological processes underlying the functional role of different brain regions in various cognitive processes, motor control in health and disease and neuroplastic changes during recovery of function after brain lesions. Used in combination with neuroimaging tools, TMS provides valuable information on functional connectivity between different brain regions, and on the relationship between physiological processes and the anatomical configuration of specific brain areas and connected pathways. More recently, there has been increasing interest in the extent to which these physiological processes are modulated depending on the behavioural setting. The purpose of this paper is (a) to present an up-to-date review of the available electrophysiological data and the impact on our understanding of human motor behaviour and (b) to discuss some of the gaps in our present knowledge as well as future directions of research in a format accessible to new students and/or investigators. Finally, areas of uncertainty and limitations in the interpretation of TMS studies are discussed in some detail.

Approximately one-third of patients with stroke exhibit persistent disability after the initial cerebrovascular episode, with motor impairments accounting for most poststroke disability. Exercise and training have long been used to restore motor function after stroke. Better training strategies and therapies to enhance the effects of these rehabilitative protocols are currently being developed for poststroke disability. The advancement of our understanding of the neuroplastic changes associated with poststroke motor impairment and the innate mechanisms of repair is crucial to this endeavor. Pharmaceutical, biological and electrophysiological treatments that augment neuroplasticity are being explored to further extend the boundaries of poststroke rehabilitation. Potential motor rehabilitation therapies, such as stem cell therapy, exogenous tissue engineering and brain–computer interface technologies, could be integral in helping patients with stroke regain motor control. As the methods for providing motor rehabilitation change, the primary goals of poststroke rehabilitation will be driven by the activity and quality of life needs of individual patients. This Review aims to provide a focused overview of neuroplasticity associated with poststroke motor impairment, and the latest experimental interventions being developed to manipulate neuroplasticity to enhance motor rehabilitation.