Dose Response to Upper Extremity Stroke Rehabilitation Varies by Individual: Early Indicators of Treatment Response.

BACKGROUND: Dose response has remained a priority area in motor rehabilitation research for decades, prompting several large randomized trials and meta-analyses. These between-subjects comparisons have revealed equivocal relationships between the duration of motor practice and rehabilitation response. Prior reliance on time-consuming clinical assessments made it infeasible to capture within-subjects dose response, as tracking the dose-response trajectory of an individual requires dozens of repeated administrations. METHODS: This secondary observational cohort analysis of existing data from the gaming arms of the VIGoROUS multisite trial (Video Game Rehabilitation for Outpatient Stroke) describes the rehabilitation dose response of 80 participants with mild-moderate chronic stroke. The 3-dimensional joint position data were captured via the Kinect v2 optical sensor as participants completed a prescribed 15 hours of in-home unsupervised game-based motor practice. Kinematic dose response trajectories were fitted from hundreds to thousands of in-game repetitions for 4 separate upper extremity movements for each participant. RESULTS: Of 75 participants with sufficient data for dose-response analysis, 85% showed improved motor capacity for at least 1 movement. Dose response was bimodal; 42% required <5 hours of motor practice before reaching a plateau in movement kinematics, whereas 55% required >10 and 34% required >30 hours. We could predict with 93% accuracy whether or not an individual would ultimately respond to game-based motor practice within 5 hours of gameplay. CONCLUSIONS: Dose response varies considerably between individuals. About half of chronic stroke patients benefit from higher doses of motor practice than the current standard of care. Individualized dose-response data from motion capture rehabilitation gaming can guide clinical decision-making early on in treatment. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02631850.

Compliance With In-Home Self-Managed Rehabilitation Post-Stroke is Largely Independent of Scheduling Approach.

OBJECTIVE: To investigate how participants self-schedule their engagement with domestic rehabilitation gaming platform, and how their scheduling behavior in turn influence overall compliance. DESIGN: Cohort of individuals randomized to receive in-home rehabilitation gaming during a multi-site randomized controlled trial. SETTING: In-home self-managed rehabilitation. PARTICIPANTS: Eighty community-dwelling participants who were >6 months post-stroke and had mild to moderate upper extremity impairment (N=80). INTERVENTIONS: Participants were prescribed 15 hours of independent in-home self-scheduled game play for upper extremity mobility over 3 weeks. MAIN OUTCOME MEASURES: Total number of hours of active game play was objectively measured by the rehabilitation gaming system. Cluster analysis identified scheduling patterns from the following scheduling characteristics: total number of sessions, average session length, and consistency of play schedule. RESULTS: Four distinct scheduling profiles were revealed, 3 of which were associated with complete or near-complete compliance, while a fourth (inconsistent schedule of short, infrequent sessions) was associated with very poor compliance. Poor compliance could be predicted within the first 7 days of the program with 78% accuracy based on the same play pattern metrics used to identify player profiles. CONCLUSIONS: Our findings support client autonomy in selecting the home practice schedule that works best for them, as compliance can successfully be achieved through a variety of different scheduling patterns. The objective measurements of compliance provided through rehabilitation gaming can assist therapists to identify individuals early on who exhibit scheduling behavior that is predictive of poor compliance.

Effectiveness of Virtual Reality- and Gaming-Based Interventions for Upper Extremity Rehabilitation Poststroke: A Meta-analysis.

OBJECTIVE: To investigate the efficacy of virtual reality (VR)- and gaming-based interventions for improving upper extremity function poststroke, and to examine demographic and treatment-related factors that may moderate treatment response. DATA SOURCES: A comprehensive search was conducted within the PubMed, CINAHL/EBSCO, SCOPUS, Ovid MEDLINE, and EMBASE databases for articles published between 2005 and 2019. STUDY SELECTION: Articles investigating gaming and VR methods of treatment for upper extremity weakness were collected with the following study inclusion criteria: (1) participants aged 18 years or older with upper extremity deficits; (2) randomized controlled trials or prospective study design; (3) Downs-Black rating score of ≥18; and (4) outcome measure was the Wolf Motor Functioning Test, the Fugl-Meyer, or the Action Research Arm Test. DATA EXTRACTION: Thirty-eight articles met inclusion criteria. The primary outcome was proportional improvement on the Wolf Motor Functioning Test, Fugl-Meyer, or Action Research Arm Test. The following individual or treatment factors were extracted: VR or gaming dose, total treatment dose, chronicity (> or <6mo), severity of motor impairment, and presence of a gaming component. DATA ANALYSIS: Random effects meta-analysis models were utilized to quantify (1) the proportional recovery that occurs after VR or gaming; (2) the comparative treatment effect of VR or gaming vs conventional physiotherapy; and (3) whether the benefit of virtual reality differed based on participant characteristics or elements of the treatment. RESULTS: On average, VR or gaming interventions produced an improvement of 28.5% of the maximal possible improvement. Dose and severity of motor impairment did not significantly influence rehabilitation outcomes. Treatment gains were significantly larger overall (10.8%) when the computerized training involved a gaming component vs just visual feedback. VR or gaming interventions showed a significant treatment advantage (10.4%) over active control treatments. CONCLUSIONS: Overall, VR- or gaming-based upper extremity rehabilitation poststroke appears to be more effective than conventional methods. Further in-depth study of variables affecting improvement, such as individual motor presentation, treatment dose, and the relationship between them, are needed.

A Novel Methodology for Extracting and Evaluating Therapeutic Movements in Game-Based Motion Capture Rehabilitation Systems.

Virtual rehabilitation yields outcomes that are at least as good as traditional care for improving upper limb function and the capacity to carry out activities of daily living. Due to the advent of low-cost gaming systems and patient preference for game-based therapies, video game technology will likely be increasingly utilized in physical therapy practice in the coming years. Gaming systems that incorporate low-cost motion capture technology often generate large datasets of therapeutic movements performed over the course of rehabilitation. An infrastructure has yet to be established, however, to enable efficient processing of large quantities of movement data that are collected outside of a controlled laboratory setting. In this paper, a methodology is presented for extracting and evaluating therapeutic movements from game-based rehabilitation that occurs in uncontrolled and unmonitored settings. By overcoming these challenges, meaningful kinematic analysis of rehabilitation trajectory within an individual becomes feasible. Moreover, this methodological approach provides a vehicle for analyzing large datasets generated in uncontrolled clinical settings to enable better predictions of rehabilitation potential and dose-response relationships for personalized medicine.

Video Game Rehabilitation for Outpatient Stroke (VIGoROUS): protocol for a multi-center comparative effectiveness trial of in-home gamified constraint-induced movement therapy for rehabilitation of chronic upper extremity hemiparesis.

BACKGROUND: Constraint-Induced Movement therapy (CI therapy) is shown to reduce disability, increase use of the more affected arm/hand, and promote brain plasticity for individuals with upper extremity hemiparesis post-stroke. Randomized controlled trials consistently demonstrate that CI therapy is superior to other rehabilitation paradigms, yet it is available to only a small minority of the estimated 1.2 million chronic stroke survivors with upper extremity disability. The current study aims to establish the comparative effectiveness of a novel, patient-centered approach to rehabilitation utilizing newly developed, inexpensive, and commercially available gaming technology to disseminate CI therapy to underserved individuals. Video game delivery of CI therapy will be compared against traditional clinic-based CI therapy and standard upper extremity rehabilitation. Additionally, individual factors that differentially influence response to one treatment versus another will be examined. METHODS: This protocol outlines a multi-site, randomized controlled trial with parallel group design. Two hundred twenty four adults with chronic hemiparesis post-stroke will be recruited at four sites. Participants are randomized to one of four study groups: (1) traditional clinic-based CI therapy, (2) therapist-as-consultant video game CI therapy, (3) therapist-as-consultant video game CI therapy with additional therapist contact via telerehabilitation/video consultation, and (4) standard upper extremity rehabilitation. After 6-month follow-up, individuals assigned to the standard upper extremity rehabilitation condition crossover to stand-alone video game CI therapy preceded by a therapist consultation. All interventions are delivered over a period of three weeks. Primary outcome measures include motor improvement as measured by the Wolf Motor Function Test (WMFT), quality of arm use for daily activities as measured by Motor Activity Log (MAL), and quality of life as measured by the Quality of Life in Neurological Disorders (NeuroQOL). DISCUSSION: This multi-site RCT is designed to determine comparative effectiveness of in-home technology-based delivery of CI therapy versus standard upper extremity rehabilitation and in-clinic CI therapy. The study design also enables evaluation of the effect of therapist contact time on treatment outcomes within a therapist-as-consultant model of gaming and technology-based rehabilitation. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02631850 .

Size doesn't matter: cortical stroke lesion volume is not associated with upper extremity motor impairment and function in mild, chronic hemiparesis.

OBJECTIVES: To determine (1) the relationship between lesion volume and upper extremity (UE) motor impairment using the UE section of the Fugl-Meyer (FM) assessment; and (2) the relationship between lesion volume and UE functional outcomes using the Arm Motor Ability Test (AMAT) Functional Ability (FA) and Time scales. DESIGN: Secondary retrospective analysis of randomized controlled trial data. SETTING: Outpatient rehabilitation clinic. PARTICIPANTS: Subjects with chronic stroke (N=139, 83 men; mean age ± SD of all subjects, 56.7±11.2y; mean time ± SD since stroke onset, 59.6±65.6mo; 90 subjects with right hemiparesis) and stable, active, distal UE movement. INTERVENTION: Data were collected related to subjects' lesion volume and UE movement before their participation in a multicenter, randomized controlled trial. MAIN OUTCOME MEASURES: FM and AMAT. RESULTS: Neither age nor lesion volume was related to FM performance. The P value for the regression coefficient of lesion volume was .045 in the AMAT FA model and .016 in the AMAT Time model. Lesion volume accounted for only an additional 1.7% (AMAT FA) to 3.1% (AMAT Time) of the variability in motor function and was not clinically meaningful. CONCLUSIONS: Data suggest no relationship between lesion volume and UE impairment, and a small, clinically insignificant relationship between lesion volume and UE motor function. Stroke causes metabolic changes in intact regions and diffuse structural loss in anatomically remote regions from the infarction. These other factors may account for variance in motor outcomes after stroke.

Atrophy of spared gray matter tissue predicts poorer motor recovery and rehabilitation response in chronic stroke.

BACKGROUND AND PURPOSE: Although the motor deficit after stroke is clearly due to the structural brain damage that has been sustained, this relationship is attenuated from the acute to chronic phases. We investigated the possibility that motor impairment and response to constraint-induced movement therapy in patients with chronic stroke may relate more strongly to the structural integrity of brain structures remote from the lesion than to measures of overt tissue damage. METHODS: Voxel-based morphometry analysis was performed on MRI scans from 80 patients with chronic stroke to investigate whether variations in gray matter density were correlated with extent of residual motor impairment or with constraint-induced movement therapy-induced motor recovery. RESULTS: Decreased gray matter density in noninfarcted motor regions was significantly correlated with magnitude of residual motor deficit. In addition, reduced gray matter density in multiple remote brain regions predicted a lesser extent of motor improvement from constraint-induced movement therapy. CONCLUSIONS: Atrophy in seemingly healthy parts of the brain that are distant from the infarct accounts for at least a portion of the sustained motor deficit in chronic stroke.

Self-Supervised Learning for Electroencephalography.

Decades of research have shown machine learning superiority in discovering highly nonlinear patterns embedded in electroencephalography (EEG) records compared with conventional statistical techniques. However, even the most advanced machine learning techniques require relatively large, labeled EEG repositories. EEG data collection and labeling are costly. Moreover, combining available datasets to achieve a large data volume is usually infeasible due to inconsistent experimental paradigms across trials. Self-supervised learning (SSL) solves these challenges because it enables learning from EEG records across trials with variable experimental paradigms, even when the trials explore different phenomena. It aggregates multiple EEG repositories to increase accuracy, reduce bias, and mitigate overfitting in machine learning training. In addition, SSL could be employed in situations where there is limited labeled training data, and manual labeling is costly. This article: 1) provides a brief introduction to SSL; 2) describes some SSL techniques employed in recent studies, including EEG; 3) proposes current and potential SSL techniques for future investigations in EEG studies; 4) discusses the cons and pros of different SSL techniques; and 5) proposes holistic implementation tips and potential future directions for EEG SSL practices.

Video game rehabilitation for outpatient stroke (VIGoROUS): A multi-site randomized controlled trial of in-home, self-managed, upper-extremity therapy.

BACKGROUND: Integrating behavioral intervention into motor rehabilitation is essential for improving paretic arm use in daily life. Demands on therapist time limit adoption of behavioral programs like Constraint-Induced Movement (CI) therapy, however. Self-managed motor practice could free therapist time for behavioral intervention, but there remains insufficient evidence of efficacy for a self-management approach. METHODS: This completed, parallel, five-site, pragmatic, single-blind trial established the comparative effectiveness of using in-home gaming self-management as a vehicle to redirect valuable therapist time towards behavioral intervention. Community-dwelling adults with post-stroke (>6 months) mild/moderate upper extremity hemiparesis were randomized to receive one of 4 different interventions over a 3-week period: 5 h of behaviorally-focused intervention plus gaming self-management (Self-Gaming), the same with additional behaviorally-focused telerehabilitation (Tele-Gaming), 5 h of Traditional motor-focused rehabilitation, or 35 h of CI therapy. Primary outcomes assessed everyday arm use (Motor Activity Log Quality of Movement, MAL) and motor speed/function (Wolf Motor Function Test, WMFT) immediately before treatment, immediately after treatment, and 6 months later. Intent-to-treat analyses were implemented with linear mixed-effects models on data gathered from March 15, 2016 to November 21, 2019. ClinicalTrials.gov, NCT02631850. RESULTS: Of 193 enrolled participants, 167 began treatment and were analyzed, 150 (90%) completed treatment, and 115 (69%) completed follow-up. Tele-Gaming and Self-Gaming produced clinically meaningful MAL gains that were 1·0 points (95% CI 0·8 to 1·3) and 0·8 points (95% CI 0·5 to 1·0) larger than Traditional care, respectively. Self-Gaming was less effective than CI therapy (-0·4 points, 95% CI -0·6 to -0·2), whereas Tele-Gaming was not (-0·2 points, 95% CI -0·4 to 0·1). Six-month retention of MAL gains across all groups was 57%. All had similar clinically-meaningful WMFT gains; six-month retention of WMFT gains was 92%. INTERPRETATION: Self-managed motor-gaming with behavioral telehealth visits has outcomes similar to in-clinic CI therapy. It addresses most access barriers, requiring just one-fifth as much therapist time that is redirected towards behavioral interventions that enhance the paretic arm's involvement in daily life. FUNDING: PCORI, NIH.

Improvement after constraint-induced movement therapy is independent of infarct location in chronic stroke patients.

BACKGROUND AND PURPOSE: Disruption of the corticospinal tract at various locations in the brain has been shown to predict worse spontaneous motor recovery after stroke. However, the anatomic specificity of previous findings was limited by the categorical classification of infarct locations. Here we used computational methods to more precisely determine the specific anatomic locations associated with impaired motor ability. More important, however, our study also used these techniques to evaluate whether infarct location could influence motor outcomes after Constraint-Induced Movement therapy (CI therapy), a specific and controlled form of physical therapy. METHODS: Quantitative voxel-based analyses were used to determine whether infarct location could predict either initial motor ability or clinical improvement after CI therapy in chronic stroke patients. RESULTS: Although corona radiata infarcts were associated with worse in-laboratory motor ability at pretreatment, infarct location did not predict improvement in either the laboratory or the life situation after CI therapy. CONCLUSIONS: The extent of improvement from CI therapy does not depend on the location of neurological damage, despite there being a pretreatment relationship between infarct location and in-laboratory motor ability. This dissociation could be explained by brain plasticity induced by CI therapy.

Predicting Improved Daily Use of the More Affected Arm Poststroke Following Constraint-Induced Movement Therapy.

BACKGROUND: Constraint-induced movement therapy (CI therapy) produces, on average, large and clinically meaningful improvements in the daily use of a more affected upper extremity in individuals with hemiparesis. However, individual responses vary widely. OBJECTIVE: The study objective was to investigate the extent to which individual characteristics before treatment predict improved use of the more affected arm following CI therapy. DESIGN: This study was a retrospective analysis of 47 people who had chronic (> 6 months) mild to moderate upper extremity hemiparesis and were consecutively enrolled in 2 CI therapy randomized controlled trials. METHODS: An enhanced probabilistic neural network model predicted whether individuals showed a low, medium, or high response to CI therapy, as measured with the Motor Activity Log, on the basis of the following baseline assessments: Wolf Motor Function Test, Semmes-Weinstein Monofilament Test of touch threshold, Motor Activity Log, and Montreal Cognitive Assessment. Then, a neural dynamic classification algorithm was applied to improve prognostic accuracy using the most accurate combination obtained in the previous step. RESULTS: Motor ability and tactile sense predicted improvement in arm use for daily activities following intensive upper extremity rehabilitation with an accuracy of nearly 100%. Complex patterns of interaction among these predictors were observed. LIMITATIONS: The fact that this study was a retrospective analysis with a moderate sample size was a limitation. CONCLUSIONS: Advanced machine learning/classification algorithms produce more accurate personalized predictions of rehabilitation outcomes than commonly used general linear models.

Remodeling the brain: plastic structural brain changes produced by different motor therapies after stroke.

BACKGROUND AND PURPOSE: Studies on adult stroke patients have demonstrated functional changes in cortical excitability, metabolic rate, or blood flow after motor therapy, measures that can fluctuate rapidly over time. This study evaluated whether evidence could also be found for structural brain changes during an efficacious rehabilitation program. METHODS: Chronic stroke patients were randomly assigned to receive either constraint-induced movement therapy (n=16) or a comparison therapy (n=20). Longitudinal voxel-based morphometry was performed on structural MRI scans obtained immediately before and after patients received therapy. RESULTS: The group receiving constraint-induced movement therapy exhibited far greater improvement in use of the more affected arm in the life situation than the comparison therapy group. Structural brain changes paralleled these improvements in spontaneous use of the more impaired arm for activities of daily living. There were profuse increases in gray matter in sensory and motor areas both contralateral and ipsilateral to the affected arm that were bilaterally symmetrical, as well as bilaterally in the hippocampus. In contrast, the comparison therapy group failed to show gray matter increases. Importantly, the magnitude of the observed gray matter increases was significantly correlated with amount of improvement in real-world arm use. CONCLUSIONS: These findings suggest that a previously overlooked type of brain plasticity, structural remodeling of the human brain, is harnessed by constraint-induced movement therapy for a condition once thought to be refractory to treatment: motor deficit in chronic stroke patients.

Improved quality of life following constraint-induced movement therapy is associated with gains in arm use, but not motor improvement.

BACKGROUND: Constraint-induced movement therapy (CI therapy) is one of few treatments for upper extremity (UE) hemiparesis that has been shown to result in motor recovery and improved quality of life in chronic stroke. However, the extent to which treatment-induced improvements in motor function versus daily use of the more affected arm independently contribute to improved quality of life remains largely unexplored. OBJECTIVE: The objective of this study is to identify whether motor function or daily use of a hemiparetic arm has a greater influence on quality of life after CI therapy. METHODS: Two cohorts of participants with chronic stroke received either in-person CI therapy (n = 29) or video-game home-based CI therapy (n = 16). The two cohorts were combined and the motor-related outcomes (Wolf Motor Function Test, Action Research Arm Test, Motor Activity Log [MAL]) and quality of life (Stroke-Specific Quality of Life) were jointly modeled to assess the associations between outcomes. RESULTS: The only outcome associated with improved quality of life was the MAL. Improvements in quality of life were not restricted to motor domains, but generalized to psychosocial domains as well. CONCLUSIONS: Results suggest that improved arm use during everyday activities is integral to maximizing quality of life gains during motor rehabilitation for chronic post-stroke UE hemiparesis. In contrast, gains in motor function were not associated with increases in quality of life. These findings further support the need to implement techniques into clinical practice that promote arm use during daily life if improving quality of life is a main goal of treatment. ClinicalTrials.gov Registration Numbers: NCT01725919 and NCT03005457.

In-Home Delivery of Constraint-Induced Movement Therapy via Virtual Reality Gaming.

PURPOSE: People with chronic hemiparesis are frequently dissatisfied with the recovery of their hand and arm, yet many lack access to effective treatments. Constraint-induced movement therapy (CI therapy) effectively increases arm function and spontaneous use in persons with chronic hemiparesis. The purpose of this study was to determine the feasibility and measure safety and outcomes of an in-home model of delivering CI therapy using a custom, avatar-based virtual reality game. METHODS: Seventeen individuals with chronic hemiparesis participated in this pretest/posttest quasi-experimental design study. The 10-day intervention had three components: 1) high-repetition motor practice using virtual reality gaming; 2) constraint of the stronger arm via a padded restraint mitt; and 3) a transfer package to reinforce arm use. Feasibility of the intervention was evaluated through comparison to traditional CI therapy and through participants' subjective responses. The primary outcome measures were the Wolf Motor Function Test (WMFT) and the Motor Activity Log quality of movement scale (MAL-QOM). RESULTS: On average, participants completed 17.2 ± 8 hours and 19,436 repetitions of motor practice. No adverse events were reported. Of 7 feasibility criteria, 4 were met. WMFT rate and MAL-QOM increased, with effect size (Cohen's d) of 1.5 and 1.1, respectively. CONCLUSIONS: This model of delivering CI therapy using a custom, avatar-based virtual reality game was feasible, well received, and showed preliminary evidence of being a safe intervention to use in the home for persons with chronic hemiparesis.

Gross motor ability predicts response to upper extremity rehabilitation in chronic stroke.

The majority of rehabilitation research focuses on the comparative effectiveness of different interventions in groups of patients, while much less is currently known regarding individual factors that predict response to rehabilitation. In a recent article, the authors presented a prognostic model to identify the sensorimotor characteristics predictive of the extent of motor recovery after Constraint-Induced Movement (CI) therapy amongst individuals with chronic mild-to-moderate motor deficit using the enhanced probabilistic neural network (EPNN). This follow-up paper examines which participant characteristics are robust predictors of rehabilitation response irrespective of the training modality. To accomplish this, EPNN was first applied to predict treatment response amongst individuals who received a virtual-reality gaming intervention (utilizing the same enrollment criteria as the prior study). The combinations of predictors that yield high predictive validity for both therapies, using their respective datasets, were then identified. High predictive classification accuracy was achieved for both the gaming (94.7%) and combined datasets (94.5%). Though CI therapy employed primarily fine-motor training tasks and the gaming intervention emphasized gross-motor practice, larger improvements in gross motor function were observed within both datasets. Poorer gross motor ability at pre-treatment predicted better rehabilitation response in both the gaming and combined datasets. The conclusion of this research is that for individuals with chronic mild-to-moderate upper extremity hemiparesis, residual deficits in gross motor function are highly responsive to motor restorative interventions, irrespective of the modality of training.

Motor recovery from constraint induced movement therapy is not constrained by extent of tissue damage following stroke.

PURPOSE: The purpose of this study was to delineate the relationship between several types of T1-weighted MRI pathology and motor rehabilitation potential following Constraint Induced Movement therapy (CI therapy) in chronic stroke. METHODS: Stepwise regression was employed (n = 80) to identify predictors of motor recovery (prior to therapy) and of response to Constraint-Induced Movement therapy [measured via the Wolf Motor Function Test (WMFT) and Motor Activity Log (MAL)] from among the following: age, side of motor deficit, chronicity, gender, lesion volume, peri-infarct damage volume, white matter hypointensity volume, ventricular asymmetry, and lesion location. RESULTS: Although extent of total stroke damage weakly correlated with poorer performance on the WMFT prior to therapy, this relationship was mediated by the location of the damage. No metric of tissue damage examined here was associated with real-world arm use at baseline (MAL at pre-treatment) or with CI therapy-induced improvement in either best motor performance upon request (WMFT) or spontaneous arm use for daily activities (MAL). CONCLUSIONS: In sum, the extent of brain tissue damage of any type examined here poorly predicted motor function and response to rehabilitation in chronic stroke.

Structural neuroplastic change after constraint-induced movement therapy in children with cerebral palsy.

Research from the present laboratory with adult stroke patients showed that structural neuroplastic changes are correlated with clinical improvements due to constraint-induced movement (CI) therapy. This pilot study evaluated whether comparable changes occur in children receiving CI therapy. Ten children (6 boys) with congenital hemiparesis (mean age: 3 years, 3 months) underwent MRI scans 3 weeks before, immediately before, and immediately after receiving 3 weeks of CI therapy. Longitudinal voxel-based morphometry was performed on MRI scans to determine gray matter change. In addition, the Pediatric Motor Activity Log-Revised was administered at these time points to assess arm use in daily life before and after treatment. Children exhibited large improvements after CI therapy in spontaneous use of the more-affected arm (P < .001, d' = 3.24). A significant increase in gray matter volume occurred in the sensorimotor cortex contralateral to the more-affected arm (P = .04); there was a trend for these changes to be correlated with motor improvement (r = 0.63, P = .063). Trends were also observed for increases in gray matter volume in the ipsilateral motor cortex (P = .055) and contralateral hippocampus (P = .1). No significant gray matter change was seen during the 3 weeks before treatment. These findings suggest that CI therapy produces gray matter increases in the developing nervous system and provide additional evidence that CI therapy is associated with structural remodeling of the human brain while producing motor improvement in patients with disabling central nervous system diseases.

Oscillatory correlates of the primacy effect in episodic memory.

Both intracranial and scalp EEG studies have demonstrated that oscillatory activity, especially in the gamma band (28 to 100 Hz), can differentiate successful and unsuccessful episodic encoding [Sederberg, P.B., Kahana, M.J., Howard, M.W., Donner, E.J., Madsen, J.R., 2003. Theta and gamma oscillations during encoding predict subsequent recall. Journal of Neuroscience, 23(34), 10809-10814; Fell, J., Klaver, P., Lehnertz, K., Grunwald, T., Schaller, C., Elger, C.E., Fernandez, G., 2001. Human memory formation is accompanied by rhinal-hippocampal coupling and decoupling. Nature Neuroscience, 4 (12), 1259-1264; Gruber, T., Tsivilis, D., Montaldi, D., and Müller, M. (2004). Induced gamma band responses: An early marker of memory encoding and retrieval. Neuroreport, 15, 1837-1841; Summerfield, C., Mangels, J.A., in press. Dissociable neural mechanisms for encoding predictable and unpredictable events. Journal of Cognitive Neuroscience]. Although the probability of recalling an item varies as a function of where it appeared in the list, the relation between the oscillatory dynamics of successful encoding and serial position remains unexplored. We recorded scalp EEG as participants studied lists of common nouns in a delayed free-recall task. Because early list items were recalled better than items from later serial positions (the primacy effect), we analyzed encoding-related changes in 2 to 100 Hz oscillatory power as a function of serial position. Increases in gamma power in posterior regions predicted successful encoding at early serial positions; widespread low-frequency (4-14 Hz) power decreases predicted successful memory formation for later serial positions. These results suggest that items in early serial positions receive an encoding boost due to focused encoding without having to divide resources among numerous list items. Later in the list, as memory load increases, encoding is divided between multiple items.