Proprioceptive recalibration following implicit visuomotor adaptation is preserved in Parkinson's disease.

Individuals with Parkinson's disease (PD) and healthy adults demonstrate similar levels of visuomotor adaptation provided that the distortion is small or introduced gradually, and hence, implicit processes are engaged. Recently, implicit processes underlying visuomotor adaptation in healthy individuals have been proposed to include proprioceptive recalibration (i.e., shifts in one's proprioceptive sense of felt hand position to match the visual estimate of their hand experienced during reaches with altered visual feedback of the hand). In the current study, we asked if proprioceptive recalibration is preserved in PD patients. PD patients tested during their "off" and "on" medication states and age-matched healthy controls reached to visual targets, while visual feedback of their unseen hand was gradually rotated 30° clockwise or translated 4 cm rightwards of their actual hand trajectory. As expected, PD patients and controls produced significant reach aftereffects, indicating visuomotor adaptation after reaching with the gradually introduced visuomotor distortions. More importantly, following visuomotor adaptation, both patients and controls showed recalibration in hand position estimates, and the magnitude of this recalibration was comparable between PD patients and controls. No differences for any measures assessed were observed across medication status (i.e., PD off vs PD on). Results reveal that patients are able to adjust their sensorimotor mappings and recalibrate proprioception following adaptation to a gradually introduced visuomotor distortion, and that dopaminergic intervention does not affect this proprioceptive recalibration. These results suggest that proprioceptive recalibration does not involve striatal dopaminergic pathways and may contribute to the preserved visuomotor adaptation that arises implicitly in PD patients.

The effects of unilateral versus bilateral subthalamic nucleus deep brain stimulation on prosaccades and antisaccades in Parkinson's disease.

Unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease improves skeletomotor function assessed clinically, and bilateral STN DBS improves motor function to a significantly greater extent. It is unknown whether unilateral STN DBS improves oculomotor function and whether bilateral STN DBS improves it to a greater extent. Further, it has also been shown that bilateral, but not unilateral, STN DBS is associated with some impaired cognitive-motor functions. The current study compared the effect of unilateral and bilateral STN DBS on sensorimotor and cognitive aspects of oculomotor control. Patients performed prosaccade and antisaccade tasks during no stimulation, unilateral stimulation, and bilateral stimulation. There were three sets of findings. First, for the prosaccade task, unilateral STN DBS had no effect on prosaccade latency and it reduced prosaccade gain; bilateral STN DBS reduced prosaccade latency and increased prosaccade gain. Second, for the antisaccade task, neither unilateral nor bilateral stimulation had an effect on antisaccade latency, unilateral STN DBS increased antisaccade gain, and bilateral STN DBS increased antisaccade gain to a greater extent. Third, bilateral STN DBS induced an increase in prosaccade errors in the antisaccade task. These findings suggest that while bilateral STN DBS benefits spatiotemporal aspects of oculomotor control, it may not be as beneficial for more complex cognitive aspects of oculomotor control. Our findings are discussed considering the strategic role the STN plays in modulating information in the basal ganglia oculomotor circuit.

Prospective Optimization with Limited Resources.

The future is uncertain because some forthcoming events are unpredictable and also because our ability to foresee the myriad consequences of our own actions is limited. Here we studied how humans select actions under such extrinsic and intrinsic uncertainty, in view of an exponentially expanding number of prospects on a branching multivalued visual stimulus. A triangular grid of disks of different sizes scrolled down a touchscreen at a variable speed. The larger disks represented larger rewards. The task was to maximize the cumulative reward by touching one disk at a time in a rapid sequence, forming an upward path across the grid, while every step along the path constrained the part of the grid accessible in the future. This task captured some of the complexity of natural behavior in the risky and dynamic world, where ongoing decisions alter the landscape of future rewards. By comparing human behavior with behavior of ideal actors, we identified the strategies used by humans in terms of how far into the future they looked (their "depth of computation") and how often they attempted to incorporate new information about the future rewards (their "recalculation period"). We found that, for a given task difficulty, humans traded off their depth of computation for the recalculation period. The form of this tradeoff was consistent with a complete, brute-force exploration of all possible paths up to a resource-limited finite depth. A step-by-step analysis of the human behavior revealed that participants took into account very fine distinctions between the future rewards and that they abstained from some simple heuristics in assessment of the alternative paths, such as seeking only the largest disks or avoiding the smaller disks. The participants preferred to reduce their depth of computation or increase the recalculation period rather than sacrifice the precision of computation.

Neurocognitive stages of spatial cognitive mapping measured during free exploration of a large-scale virtual environment.

Using a novel, fully mobile virtual reality paradigm, we investigated the EEG correlates of spatial representations formed during unsupervised exploration. On day 1, subjects implicitly learned the location of 39 objects by exploring a room and popping bubbles that hid the objects. On day 2, they again popped bubbles in the same environment. In most cases, the objects hidden underneath the bubbles were in the same place as on day 1. However, a varying third of them were misplaced in each block. Subjects indicated their certainty that the object was in the same location as the day before. Compared with bubble pops revealing correctly placed objects, bubble pops revealing misplaced objects evoked a decreased negativity starting at 145 ms, with scalp topography consistent with generation in medial parietal cortex. There was also an increased negativity starting at 515 ms to misplaced objects, with scalp topography consistent with generation in inferior temporal cortex. Additionally, misplaced objects elicited an increase in frontal midline theta power. These findings suggest that the successive neurocognitive stages of processing allocentric space may include an initial template matching, integration of the object within its spatial cognitive map, and memory recall, analogous to the processing negativity N400 and theta that support verbal cognitive maps in humans.

Delay differential analysis of electroencephalographic data.

We propose a time-domain approach to detect frequencies, frequency couplings, and phases using nonlinear correlation functions. For frequency analysis, this approach is a multivariate extension of discrete Fourier transform, and for higher-order spectra, it is a linear and multivariate alternative to multidimensional fast Fourier transform of multidimensional correlations. This method can be applied to short and sparse time series and can be extended to cross-trial and cross-channel spectra (CTS) for electroencephalography data where multiple short data segments from multiple trials of the same experiment are available. There are two versions of CTS. The first one assumes some phase coherency across the trials, while the second one is independent of phase coherency. We demonstrate that the phase-dependent version is more consistent with event-related spectral perturbation analysis and traditional Morlet wavelet analysis. We show that CTS can be applied to short data windows and yields higher temporal resolution than traditional Morlet wavelet analysis. Furthermore, the CTS can be used to reconstruct the event-related potential using all linear components of the CTS.

Human cortical θ during free exploration encodes space and predicts subsequent memory.

Spatial representations and walking speed in rodents are consistently related to the phase, frequency, and/or amplitude of θ rhythms in hippocampal local field potentials. However, neuropsychological studies in humans have emphasized the importance of parietal cortex for spatial navigation, and efforts to identify the electrophysiological signs of spatial navigation in humans have been stymied by the difficulty of recording during free exploration of complex environments. We resolved the recording problem and experimentally probed brain activity of human participants who were fully ambulant. On each of 2 d, electroencephalography was synchronized with head and body movement in 13 subjects freely navigating an extended virtual environment containing numerous unique objects. θ phase and amplitude recorded over parietal cortex were consistent when subjects walked through a particular spatial separation at widely separated times. This spatial displacement θ autocorrelation (STAcc) was quantified and found to be significant from 2 to 8 Hz within the environment. Similar autocorrelation analyses performed on an electrooculographic channel, used to measure eye movements, showed no significant spatial autocorrelations, ruling out eye movements as the source of STAcc. Strikingly, the strength of an individual's STAcc maps from day 1 significantly predicted object location recall success on day 2. θ was also significantly correlated with walking speed; however, this correlation appeared unrelated to STAcc and did not predict memory performance. This is the first demonstration of memory-related, spatial maps in humans generated during active spatial exploration.

Spatiotemporal dynamics of online motor correction processing revealed by high-density electroencephalography.

The ability to control online motor corrections is key to dealing with unexpected changes arising in the environment with which we interact. How the CNS controls online motor corrections is poorly understood, but evidence has accumulated in favor of a submovement-based model in which apparently continuous movement is segmented into distinct submovements. Although most studies have focused on submovements' kinematic features, direct links with the underlying neural dynamics have not been extensively explored. This study sought to identify an electroencephalographic signature of submovements. We elicited kinematic submovements using a double-step displacement paradigm. Participants moved their wrist toward a target whose direction could shift mid-movement with a 50% probability. Movement kinematics and cortical activity were concurrently recorded with a low-friction robotic device and high-density electroencephalography. Analysis of spatiotemporal dynamics of brain activation and its correlation with movement kinematics showed that the production of each kinematic submovement was accompanied by (1) stereotyped topographic scalp maps and (2) frontoparietal ERPs time-locked to submovements. Positive ERP peaks from frontocentral areas contralateral to the moving wrist preceded kinematic submovement peaks by 220-250 msec and were followed by positive ERP peaks from contralateral parietal areas (140-250 msec latency, 0-80 msec before submovement peaks). Moreover, individual subject variability in the latency of frontoparietal ERP components following the target shift significantly predicted variability in the latency of the corrective submovement. Our results are in concordance with evidence for the intermittent nature of continuous movement and elucidate the timing and role of frontoparietal activations in the generation and control of corrective submovements.

Dopamine function and the efficiency of human movement.

To sustain successful behavior in dynamic environments, active organisms must be able to learn from the consequences of their actions and predict action outcomes. One of the most important discoveries in systems neuroscience over the last 15 years has been about the key role of the neurotransmitter dopamine in mediating such active behavior. Dopamine cell firing was found to encode differences between the expected and obtained outcomes of actions. Although activity of dopamine cells does not specify movements themselves, a recent study in humans has suggested that tonic levels of dopamine in the dorsal striatum may in part enable normal movement by encoding sensitivity to the energy cost of a movement, providing an implicit "motor motivational" signal for movement. We investigated the motivational hypothesis of dopamine by studying motor performance of patients with Parkinson disease who have marked dopamine depletion in the dorsal striatum and compared their performance with that of elderly healthy adults. All participants performed rapid sequential movements to visual targets associated with different risk and different energy costs, countered or assisted by gravity. In conditions of low energy cost, patients performed surprisingly well, similar to prescriptions of an ideal planner and healthy participants. As energy costs increased, however, performance of patients with Parkinson disease dropped markedly below the prescriptions for action by an ideal planner and below performance of healthy elderly participants. The results indicate that the ability for efficient planning depends on the energy cost of action and that the effect of energy cost on action is mediated by dopamine.

Scaling and coordination deficits during dynamic object manipulation in Parkinson's disease.

The ability to reach for and dynamically manipulate objects in a dexterous fashion requires scaling and coordination of arm, hand, and fingertip forces during reach and grasp components of this behavior. The neural substrates underlying dynamic object manipulation are not well understood. Insight into the role of basal ganglia-thalamocortical circuits in object manipulation can come from the study of patients with Parkinson's disease (PD). We hypothesized that scaling and coordination aspects of motor control are differentially affected by this disorder. We asked 20 PD patients and 23 age-matched control subjects to reach for, grasp, and lift virtual objects along prescribed paths. The movements were subdivided into two types, intensive (scaling) and coordinative, by detecting their underlying self-similarity. PD patients off medication were significantly impaired relative to control subjects for both aspects of movement. Intensive deficits, reduced peak speed and aperture, were seen during the reach. Coordinative deficits were observed during the reach, namely, the relative position along the trajectory at which peak speed and aperture were achieved, and during the lift, when objects tilted with respect to the gravitational axis. These results suggest that basal ganglia-thalamocortical circuits may play an important role in fine motor coordination. Dopaminergic therapy significantly improved intensive but not coordinative aspects of movements. These findings are consistent with a framework in which tonic levels of dopamine in the dorsal striatum encode the energetic cost of a movement, thereby improving intensive or scaling aspects of movement. However, repletion of brain dopamine levels does not restore finely coordinated movement.

Unconstrained reaching modulates eye-hand coupling.

Eye­hand coordination is a crucial element of goal-directed movements. However, few studies have looked at the extent to which unconstrained movements of the eyes and hand made to targets influence each other. We studied human participants who moved either their eyes or both their eyes and hand to one of three static or flashed targets presented in 3D space. The eyes were directed, and hand was located at a common start position on either the right or left side of the body. We found that the velocity and scatter of memory-guided saccades (flashed targets) differed significantly when produced in combination with a reaching movement than when produced alone. Specifically, when accompanied by a reach, peak saccadic velocities were lower than when the eye moved alone. Peak saccade velocities, as well as latencies, were also highly correlated with those for reaching movements, especially for the briefly flashed targets compared to the continuous visible target. The scatter of saccade endpoints was greater when the saccades were produced with the reaching movement than when produced without, and the size of the scatter for both saccades and reaches was weakly correlated. These findings suggest that the saccades and reaches made to 3D targets are weakly to moderately coupled both temporally and spatially and that this is partly the result of the arm movement influencing the eye movement. Taken together, this study provides further evidence that the oculomotor and arm motor systems interact above and beyond any common target representations shared by the two motor systems.

Prospective Optimization.

Human performance approaches that of an ideal observer and optimal actor in some perceptual and motor tasks. These optimal abilities depend on the capacity of the cerebral cortex to store an immense amount of information and to flexibly make rapid decisions. However, behavior only approaches these limits after a long period of learning while the cerebral cortex interacts with the basal ganglia, an ancient part of the vertebrate brain that is responsible for learning sequences of actions directed toward achieving goals. Progress has been made in understanding the algorithms used by the brain during reinforcement learning, which is an online approximation of dynamic programming. Humans also make plans that depend on past experience by simulating different scenarios, which is called prospective optimization. The same brain structures in the cortex and basal ganglia that are active online during optimal behavior are also active offline during prospective optimization. The emergence of general principles and algorithms for goal-directed behavior has consequences for the development of autonomous devices in engineering applications.

Sign language aphasia from a neurodegenerative disease.

While Alois Alzheimer recognized the effects of the disease he described on speech and language in his original description of the disease in 1907, the effects of Alzheimer's disease (AD) on language in deaf signers has not previously been reported. We evaluated a 55-year-old right-handed congenitally deaf woman with a 2-year history of progressive memory loss and a deterioration of her ability to communicate in American Sign Language, which she learned at the age of eight. Examination revealed that she had impaired episodic memory as well as marked impairments in the production and comprehension of fingerspelling and grammatically complex sentences. She also had signs of anomia as well as an ideomotor apraxia and visual-spatial dysfunction. This report illustrates the challenges in evaluation of a patient for the presence of degenerative dementia when the person is deaf from birth, uses sign language, and has a late age of primary language acquisition. Although our patient could neither speak nor hear, in many respects her cognitive disorders mirror those of patients with AD who had normally learned to speak.

Impaired endogenously evoked automated reaching in Parkinson's disease.

Intended reaches triggered by exogenous targets often coexist with spontaneous, automated movements that are endogenously activated. It has been posited that Parkinson's disease (PD) primarily impairs automated movements, but it is unknown to what extent this may affect multijoint/limb control, particularly when patients are off their dopaminergic medications. Here we tested nine human patients with PD while off dopaminergic medication versus nine age-matched normal controls (NCs). Participants performed intentional reaches forward to a target in a dark room and then transitioned back to their initial posture. Upon target flash, three forms of guidance were used: (1) memory with eyes closed, (2) continuous target vision only, and (3) vision of their moving finger only. The trajectories of their arm joints were measured and their joint velocities decomposed into the (intended) task-relevant and the (spontaneous) task-incidental degrees of freedom (DOF). We also measured the balance between these two subsets of DOF as these movements unfolded. In PD patients we found that the incidental DOF values were abnormally variable during the retracting movements and prevailed over the task-relevant DOF values. By contrast, their forward intentional motions were abnormally dominated by the task-relevant components. Moreover, the patients abruptly transitioned between voluntary and automated modes of joint control, and, unlike NCs, the type of visual guidance differentially affected their postural trajectories. These findings lend support to an emerging view that there is a loss of automated control in PD patients that contributes to impairments in voluntary control, and that basal ganglia-cortical circuits are critical for the maintenance and balance of multijoint control.

Deep brain stimulation of the subthalamic nucleus alters the cortical profile of response inhibition in the beta frequency band: a scalp EEG study in Parkinson's disease.

Stopping an initiated response could be implemented by a fronto-basal-ganglia circuit, including the right inferior frontal cortex (rIFC) and the subthalamic nucleus (STN). Intracranial recording studies in humans reveal an increase in beta-band power (approximately 16-20 Hz) within the rIFC and STN when a response is stopped. This suggests that the beta-band could be important for communication in this network. If this is the case, then altering one region should affect the electrophysiological response at the other. We addressed this hypothesis by recording scalp EEG during a stop task while modulating STN activity with deep brain stimulation. We studied 15 human patients with Parkinson's disease and 15 matched healthy control subjects. Behaviorally, patients OFF stimulation were slower than controls to stop their response. Moreover, stopping speed was improved for ON compared to OFF stimulation. For scalp EEG, there was greater beta power, around the time of stopping, for patients ON compared to OFF stimulation. This effect was stronger over the right compared to left frontal cortex, consistent with the putative right lateralization of the stopping network. Thus, deep brain stimulation of the STN improved behavioral stopping performance and increased the beta-band response over the right frontal cortex. These results complement other evidence for a structurally connected functional circuit between right frontal cortex and the basal ganglia. The results also suggest that deep brain stimulation of the STN may improve task performance by increasing the fidelity of information transfer within a fronto-basal-ganglia circuit.

Choice modulates the neural dynamics of prediction error processing during rewarded learning.

Our ability to selectively engage with our environment enables us to guide our learning and to take advantage of its benefits. When facing multiple possible actions, our choices are a critical aspect of learning. In the case of learning from rewarding feedback, there has been substantial theoretical and empirical progress in elucidating the associated behavioral and neural processes, predominantly in terms of a reward prediction error, a measure of the discrepancy between actual versus expected reward. Nevertheless, the distinct influence of choice on prediction error processing and its neural dynamics remains relatively unexplored. In this study we used a novel paradigm to determine how choice influences prediction error processing and to examine whether there are correspondingly distinct neural dynamics. We recorded scalp electroencephalogram while healthy adults were administered a rewarded learning task in which choice trials were intermingled with control trials involving the same stimuli, motor responses, and probabilistic rewards. We used a temporal difference learning model of subjects' trial-by-trial choices to infer subjects' image valuations and corresponding prediction errors. As expected, choices were associated with lower overall prediction error magnitudes, most notably over the course of learning the stimulus-reward contingencies. Choices also induced a higher-amplitude relative positivity in the frontocentral event-related potential about 200 ms after reward signal onset that was negatively correlated with the differential effect of choice on the prediction error. Thus choice influences the neural dynamics associated with how reward signals are processed during learning. Behavioral, computational, and neurobiological models of rewarded learning should therefore accommodate a distinct influence for choice during rewarded learning.

Sensory-spatial transformations in the left posterior parietal cortex may contribute to reach timing.

The posterior parietal cortex (PPC) contains viewer-centered spatial maps important for reaching movements. It is known that spatial reaching deficits emerge when this region is damaged, yet less is known about temporal deficits that may also emerge because of a failure in sensory-spatial transformations. This work introduces a new geometric measure to quantify multimodal sensory transformation and integration deficits affecting the tempo of reaching trajectories that are induced by injury to the left PPC. Erratic rates of positional change involving faulty maps from rotational angular displacements to translational linear displacements contributed to temporal abnormalities in the reach. Such disruptions were quantified with a time-invariant geometric measure. This measure, paired with an experimental paradigm that manipulated the source of visual guidance for reaches, was used to compare the performance of normal controls to those from a patient (T.R.) who had a lesion in his left-PPC. For controls, the source of visual guidance significantly scaled the tempo of target-directed reaches but did not change the geometric measure. This was not the case in patient T.R., who altered this measure. With continuous, extrapersonal visual feedback of the target, however, these abnormalities improved. Vision of the target rather than vision of his moving hand also improved his arm-joint rotations for posture control. These results show that the left PPC is critically important for visuo-motor transformations that specifically rely on extrapersonal cues to align rotational-arm and linear-hand displacements and to continuously integrate their rates of change. The intactness of this system contributes to the fluidity of the reach's tempo.

Convergent evidence for abnormal striatal synaptic plasticity in dystonia.

Dystonia is a functionally disabling movement disorder characterized by abnormal movements and postures. Although substantial recent progress has been made in identifying genetic factors, the pathophysiology of the disease remains a mystery. A provocative suggestion gaining broader acceptance is that some aspect of neural plasticity may be abnormal. There is also evidence that, at least in some forms of dystonia, sensorimotor "use" may be a contributing factor. Most empirical evidence of abnormal plasticity in dystonia comes from measures of sensorimotor cortical organization and physiology. However, the basal ganglia also play a critical role in sensorimotor function. Furthermore, the basal ganglia are prominently implicated in traditional models of dystonia, are the primary targets of stereotactic neurosurgical interventions, and provide a neural substrate for sensorimotor learning influenced by neuromodulators. Our working hypothesis is that abnormal plasticity in the basal ganglia is a critical link between the etiology and pathophysiology of dystonia. In this review we set up the background for this hypothesis by integrating a large body of disparate indirect evidence that dystonia may involve abnormalities in synaptic plasticity in the striatum. After reviewing evidence implicating the striatum in dystonia, we focus on the influence of two neuromodulatory systems: dopamine and acetylcholine. For both of these neuromodulators, we first describe the evidence for abnormalities in dystonia and then the means by which it may influence striatal synaptic plasticity. Collectively, the evidence suggests that many different forms of dystonia may involve abnormal plasticity in the striatum. An improved understanding of these altered plastic processes would help inform our understanding of the pathophysiology of dystonia, and, given the role of the striatum in sensorimotor learning, provide a principled basis for designing therapies aimed at the dynamic processes linking etiology to pathophysiology of the disease.

A noninvasive imaging approach to understanding speech changes following deep brain stimulation in Parkinson's disease.

PURPOSE: To explore the use of noninvasive functional imaging and "virtual" lesion techniques to study the neural mechanisms underlying motor speech disorders in Parkinson's disease. Here, we report the use of positron emission tomography (PET) and transcranial magnetic stimulation (TMS) to explain exacerbated speech impairment following subthalamic nucleus deep brain stimulation (STN-DBS) in a patient with Parkinson's disease. METHOD: Perceptual and acoustic speech measures, as well as cerebral blood flow during speech as measured by PET, were obtained with STN-DBS on and off. TMS was applied to a region in the speech motor network found to be abnormally active during DBS. Speech disruption by TMS was compared both perceptually and acoustically with speech produced with DBS on. RESULTS: Speech production was perceptually inferior and acoustically less contrastive during left STN stimulation compared to no stimulation. Increased neural activity in left dorsal premotor cortex (PMd) was observed during DBS on. "Virtual" lesioning of this region resulted in speech characterized by decreased speech segment duration, increased pause duration, and decreased intelligibility. CONCLUSIONS: This case report provides evidence that impaired speech production accompanying STN-DBS may result from unintended activation of PMd. Clinical application of functional imaging and TMS may lead to optimizing the delivery of STN-DBS to improve outcomes for speech production as well as general motor abilities.

EEG-Based Quantification of Cortical Current Density and Dynamic Causal Connectivity Generalized across Subjects Performing BCI-Monitored Cognitive Tasks.

Quantification of dynamic causal interactions among brain regions constitutes an important component of conducting research and developing applications in experimental and translational neuroscience. Furthermore, cortical networks with dynamic causal connectivity in brain-computer interface (BCI) applications offer a more comprehensive view of brain states implicated in behavior than do individual brain regions. However, models of cortical network dynamics are difficult to generalize across subjects because current electroencephalography (EEG) signal analysis techniques are limited in their ability to reliably localize sources across subjects. We propose an algorithmic and computational framework for identifying cortical networks across subjects in which dynamic causal connectivity is modeled among user-selected cortical regions of interest (ROIs). We demonstrate the strength of the proposed framework using a "reach/saccade to spatial target" cognitive task performed by 10 right-handed individuals. Modeling of causal cortical interactions was accomplished through measurement of cortical activity using (EEG), application of independent component clustering to identify cortical ROIs as network nodes, estimation of cortical current density using cortically constrained low resolution electromagnetic brain tomography (cLORETA), multivariate autoregressive (MVAR) modeling of representative cortical activity signals from each ROI, and quantification of the dynamic causal interaction among the identified ROIs using the Short-time direct Directed Transfer function (SdDTF). The resulting cortical network and the computed causal dynamics among its nodes exhibited physiologically plausible behavior, consistent with past results reported in the literature. This physiological plausibility of the results strengthens the framework's applicability in reliably capturing complex brain functionality, which is required by applications, such as diagnostics and BCI.

Sensorimotor training in a virtual reality environment: does it improve functional recovery poststroke?

OBJECTIVE: To investigate the effectiveness of computerized virtual reality (VR) training of the hemiparetic hand of patients poststroke using a system that provides repetitive motor reeducation and skill reacquisition. METHODS: Eight subjects in the chronic phase poststroke participated in a 3-week program using their hemiparetic hand in a series of interactive computer games for 13 days of training, weekend breaks, and pretests and posttests. Each subject trained for about 2 to 2.5 h per day. Outcome measures consisted of changes in the computerized measures of thumb and finger range of motion, thumb and finger velocity, fractionation (the ability to move fingers independently), thumb and finger strength, the Jebsen Test of Hand Function, and a Kinematic reach to grasp test. RESULTS: Subjects as a group improved in fractionation of the fingers, thumb and finger range of motion, and thumb and finger speed, retaining those gains at the 1-week retention test. Transfer of these improvements was demonstrated through changes in the Jebsen Test of Hand Function and a decrease after the therapy in the overall time from hand peak velocity to the moment when an object was lifted from the table. CONCLUSIONS: It is difficult in current service delivery models to provide the intensity of practice that appears to be needed to effect neural reorganization and functional changes poststroke. Computerized exercise systems may be a way to maximize both the patients' and the clinicians' time. The data in this study add support to the proposal to explore novel technologies for incorporation into current practice.