Language and developmental plasticity after perinatal stroke.

The mature human brain is lateralized for language, with the left hemisphere (LH) primarily responsible for sentence processing and the right hemisphere (RH) primarily responsible for processing suprasegmental aspects of language such as vocal emotion. However, it has long been hypothesized that in early life there is plasticity for language, allowing young children to acquire language in other cortical regions when LH areas are damaged. If true, what are the constraints on functional reorganization? Which areas of the brain can acquire language, and what happens to the functions these regions ordinarily perform? We address these questions by examining long-term outcomes in adolescents and young adults who, as infants, had a perinatal arterial ischemic stroke to the LH areas ordinarily subserving sentence processing. We compared them with their healthy age-matched siblings. All participants were tested on a battery of behavioral and functional imaging tasks. While stroke participants were impaired in some nonlinguistic cognitive abilities, their processing of sentences and of vocal emotion was normal and equal to that of their healthy siblings. In almost all, these abilities have both developed in the healthy RH. Our results provide insights into the remarkable ability of the young brain to reorganize language. Reorganization is highly constrained, with sentence processing almost always in the RH frontotemporal regions homotopic to their location in the healthy brain. This activation is somewhat segregated from RH emotion processing, suggesting that the two functions perform best when each has its own neural territory.

One right can make a left: sentence processing in the right hemisphere after perinatal stroke.

When brain regions that are critical for a cognitive function in adulthood are irreversibly damaged at birth, what patterns of plasticity support the successful development of that function in an alternative location? Here we investigate the consistency of language organization in the right hemisphere (RH) after a left hemisphere (LH) perinatal stroke. We analyzed fMRI data collected during an auditory sentence comprehension task on 14 people with large cortical LH perinatal arterial ischemic strokes (left hemisphere perinatal stroke (LHPS) participants) and 11 healthy sibling controls using a "top voxel" approach that allowed us to compare the same number of active voxels across each participant and in each hemisphere for controls. We found (1) LHPS participants consistently recruited the same RH areas that were a mirror-image of typical LH areas, and (2) the RH areas recruited in LHPS participants aligned better with the strongly activated LH areas of the typically developed brains of control participants (when flipped images were compared) than the weakly activated RH areas. Our findings suggest that the successful development of language processing in the RH after a LH perinatal stroke may in part depend on recruiting an arrangement of frontotemporal areas reflective of the typical dominant LH.

Critical Period After Stroke Study (CPASS): A phase II clinical trial testing an optimal time for motor recovery after stroke in humans.

Restoration of human brain function after injury is a signal challenge for translational neuroscience. Rodent stroke recovery studies identify an optimal or sensitive period for intensive motor training after stroke: near-full recovery is attained if task-specific motor training occurs during this sensitive window. We extended these findings to adult humans with stroke in a randomized controlled trial applying the essential elements of rodent motor training paradigms to humans. Stroke patients were adaptively randomized to begin 20 extra hours of self-selected, task-specific motor therapy at ≤30 d (acute), 2 to 3 mo (subacute), or ≥6 mo (chronic) after stroke, compared with controls receiving standard motor rehabilitation. Upper extremity (UE) impairment assessed by the Action Research Arm Test (ARAT) was measured at up to five time points. The primary outcome measure was ARAT recovery over 1 y after stroke. By 1 y we found significantly increased UE motor function in the subacute group compared with controls (ARAT difference = +6.87 ± 2.63, P = 0.009). The acute group compared with controls showed smaller but significant improvement (ARAT difference = +5.25 ± 2.59 points, P = 0.043). The chronic group showed no significant improvement compared with controls (ARAT = +2.41 ± 2.25, P = 0.29). Thus task-specific motor intervention was most effective within the first 2 to 3 mo after stroke. The similarity to rodent model treatment outcomes suggests that other rodent findings may be translatable to human brain recovery. These results provide empirical evidence of a sensitive period for motor recovery in humans.

The neural basis of language development: Changes in lateralization over age.

We have long known that language is lateralized to the left hemisphere (LH) in most neurologically healthy adults. In contrast, findings on lateralization of function during development are more complex. As in adults, anatomical, electrophysiological, and neuroimaging studies in infants and children indicate LH lateralization for language. However, in very young children, lesions to either hemisphere are equally likely to result in language deficits, suggesting that language is distributed symmetrically early in life. We address this apparent contradiction by examining patterns of functional MRI (fMRI) language activation in children (ages 4 through 13) and adults (ages 18 through 29). In contrast to previous studies, we focus not on lateralization per se but rather on patterns of left-hemisphere (LH) and right-hemisphere (RH) activation across individual participants over age. Our analyses show significant activation not only in the LH language network but also in their RH homologs in all of the youngest children (ages 4 through 6). The proportion of participants showing significant RH activation decreases over age, with over 60% of adults lacking any significant RH activation. A whole-brain correlation analysis revealed an age-related decrease in language activation only in the RH homolog of Broca's area. This correlation was independent of task difficulty. We conclude that, while language is left-lateralized throughout life, the RH contribution to language processing is also strong early in life and decreases through childhood. Importantly, this early RH language activation may represent a developmental mechanism for recovery following early LH injury.

Measurement of Functional Use in Upper Extremity Prosthetic Devices Using Wearable Sensors and Machine Learning.

Trials for therapies after an upper limb amputation (ULA) require a focus on the real-world use of the upper limb prosthesis. In this paper, we extend a novel method for identifying upper extremity functional and nonfunctional use to a new patient population: upper limb amputees. We videotaped five amputees and 10 controls performing a series of minimally structured activities while wearing sensors on both wrists that measured linear acceleration and angular velocity. The video data was annotated to provide ground truth for annotating the sensor data. Two different analysis methods were used: one that used fixed-size data chunks to create features to train a Random Forest classifier and one that used variable-size data chunks. For the amputees, the fixed-size data chunk method yielded good results, with 82.7% median accuracy (range of 79.3-85.8) on the 10-fold cross-validation intra-subject test and 69.8% in the leave-one-out inter-subject test (range of 61.4-72.8). The variable-size data method did not improve classifier accuracy compared to the fixed-size method. Our method shows promise for inexpensive and objective quantification of functional upper extremity (UE) use in amputees and furthers the case for use of this method in assessing the impact of UE rehabilitative treatments.

A trade-off between kinematic and dynamic control of bimanual reaching in virtual reality.

Bimanual coordination is an essential component of human movement. Cooperative bimanual reaching tasks are widely used to assess the optimal control of goal-directed reaching. However, little is known about the neuromuscular mechanisms governing these tasks. Twelve healthy, right-handed participants performed a bimanual reaching task in a three-dimensional virtual reality environment. They controlled a shared cursor, located at the midpoint between the hands, and reached targets located at 80% of full arm extension. Following a baseline of normal reaches, we placed a wrist weight on one arm and measured the change in coordination. Relative contribution (RC) was computed as the displacement of the right hand divided by the sum of displacements of both hands. We used surface electromyography placed over the anterior deltoid and biceps brachii to compute muscle contribution (MC) from root mean squared muscle activity data. We found RC was no different than 50% during baseline, indicating participants reached equal displacements when no weights were applied. Participants systematically altered limb coordination in response to altered limb dynamics. RC increased by 0.91% and MC decreased by 5.3% relative to baseline when the weight was applied to the left arm; RC decreased by 0.94% and MC increased by 6.3% when the weight was applied to the right arm. Participants adopted an optimal control strategy that attempted to minimize both kinematic and muscular asymmetries between limbs. What emerged was a trade-off between these two parameters, and we propose this trade-off as a potential neuromuscular mechanism of cooperative bimanual reaching.NEW & NOTEWORTHY This study is the first to propose a trade-off between kinematic and dynamic control parameters governing goal-directed reaching. We propose a straightforward tool to assess this trade-off without the need for computational modeling. The technologies and techniques developed in this study are discussed in the context of upper extremity rehabilitation.

Emotion recognition impairments and social well-being following right-hemisphere stroke.

Accurately recognizing and responding to the emotions of others is essential for proper social communication and helps bind strong relationships that are particularly important for stroke survivors. Emotion recognition typically engages cortical areas that are predominantly right-lateralized including superior temporal and inferior frontal gyri - regions frequently impacted by right-hemisphere stroke. Since prior work already links right-hemisphere stroke to deficits in emotion recognition, this research aims to extend these findings to determine whether impaired emotion recognition after right-hemisphere stroke is associated with worse social well-being outcomes. Eighteen right-hemisphere stroke patients (≥6 months post-stroke) and 21 neurologically healthy controls completed a multimodal emotion recognition test (Geneva Emotion Recognition Test - Short) and reported engagement in social/non-social activities and levels of social support. Right-hemisphere stroke was associated with worse emotion recognition accuracy, though not all patients exhibited impairment. In line with hypotheses, emotion recognition impairments were associated with greater loss of social activities after stroke, an effect that could not be attributed to stroke severity or loss of non-social activities. Impairments were also linked to reduced patient-reported social support. Results implicate emotion recognition difficulties as a potential antecedent of social withdrawal after stroke and warrant future research to test emotion recognition training post-stroke.

Shoulder position and handedness differentially affect excitability and intracortical inhibition of hand muscles.

Individuals with stroke show distinct differences in hand function impairment when the shoulder is in adduction, within the workspace compared to when the shoulder is abducted, away from the body. To better understand how shoulder position affects hand control, we tested the corticomotor excitability and intracortical control of intrinsic and extrinsic hand muscles important for grasp in twelve healthy individuals. Motor evoked potentials (MEP) using single and paired-pulse transcranial magnetic stimulation were elicited in extensor digitorum communis (EDC), flexor digitorum superficialis (FDS), first dorsal interosseous (FDI), and abductor pollicis brevis (APB). The shoulder was fully supported in horizontal adduction (ADD) or abduction (ABD). Separate mixed-effect models were fit to the MEP parameters using shoulder position (or upper-extremity [UE] side) as fixed and participants as random effects. In the non-dominant UE, EDC showed significantly greater MEPs in shoulder ABD than ADD. In contrast, the dominant side EDC showed significantly greater MEPs in ADD compared to ABD; %facilitation of EDC on dominant side showed significant stimulus intensity x position interaction, EDC excitability was significantly greater in ADD at 150% of the resting threshold. Intrinsic hand muscles of the dominant UE received significantly more intracortical inhibition (SICI) when the shoulder was in ADD compared to ABD; there was no position-dependent modulation of SICI on the non-dominant side. Our findings suggest that these resting-state changes in hand muscle excitabilities reflect the natural statistics of UE movements, which in turn may arise from as well as shape the nature of shoulder-hand coupling underlying UE behaviors.

Inaccurate Use of the Upper Extremity Fugl-Meyer Negatively Affects Upper Extremity Rehabilitation Trial Design: Findings From the ICARE Randomized Controlled Trial.

OBJECTIVE: To determine the extent to which estimates of sample and effect size in stroke rehabilitation trials can be affected by simple summation of ordinal Upper Extremity Fugl-Meyer (UEFM) items compared with a Rasch-rescaled UEFM. DESIGN: Rasch analysis of Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE) phase III trial data, comparing 3 upper extremity (UE) motor treatments in stroke survivors enrolled 45.8±22.4 days poststroke. Participants underwent a structured UE motor training known as the Accelerated Skill Acquisition Program, usual and customary care, or dose-equivalent care. UEFM data from baseline, postintervention, and 6 and 12 months later were included for analysis. SETTING: Outpatient stroke rehabilitation. PARTICIPANTS: ICARE participants (N=361). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Item difficulties, person abilities, and sample size. RESULTS: Because of their ordinality, summed raw UEFM scores measured motor impairment inconsistently across different ranges of stroke severity relative to the rescaled UEFM. In the full ICARE sample, raw UEFM understated scores relative to the rescaled UEFM by 7.4 points for the most severely impaired, but overstated scores by up to 8.4 points toward the ceiling. As a result, 50.9% of all UEFM observations showed a residual error greater than 10% of the total UEFM score. Relative to the raw scores, the rescaled UEFM improved the effect size of change in motor impairment between baseline and 1 year (d=0.35). For a hypothetical 3-arm trial resembling ICARE, UEFM rescaling reduced the required sample size by 32% (n=108) compared with raw UEFM (n=159). CONCLUSIONS: In UE rehabilitation trials, a rescaled UEFM potentially decreases sample size by one-third, decreasing costs, duration, and the number of subjects exposed to experimental risks. This benefit is obtained through increased measurement efficiency. Reductions in ceiling effects are also possible. These findings apply to ICARE-like trials. Confirmatory validation in another phase III trial is needed.

Executive/life coaching for first year medical students: a prospective study.

BACKGROUND: Student physicians are particularly prone to high rates of poor mental and physical quality of life, including depression, anxiety, and fatigue. We prospectively tested whether a structured, theory-based executive/life coaching program tailored to first year medical students in the United States was feasible, tolerable, and would be recommended by participants. Secondary goals included impact on coaching goals, resilience, and perceived stress. METHODS: This single-arm intervention study evaluated a program of two group and two private coaching sessions during the first year, second semester of the Georgetown University School of Medicine Class of 2019. Survey data (global and tailored questions, Connor-Davidson resilience scale, Friedricksson-Larsson stress question) were collected from participants at baseline and post-intervention. RESULTS: 37/40 students completed the intervention; 32 completed the pre-post surveys. Most (32/37) were willing to recommend the program (16/37 were very willing) and 29/37 recommended inclusion in the curriculum. Responses to tailored questions showed significant increases in self-efficacy regarding stress management (p < 0.001); increased awareness of thoughts about stress and management of those thoughts (p = 0.05). Reported improvements in time management (p = 0.10) and energy for relationships and school (p = 0.089) did not achieve significance. Global resilience rating was not different (p = 0.186), but significant changes were seen in control (p = 0.029) and spiritual influence (p = 0.005) factors. Although the Friedricksson-Larsson item was not significantly different (p = 0.242), 40.6% of participants reported decreased stress and 40.6% reported unchanged stress during this most challenging preclinical semester. Substantial ceiling effects were seen in study measures. CONCLUSIONS: We showed that a tailored executive/life coaching program for first year medical students in the United States is feasible, tolerable, and safe; adherence was excellent. Global utility ratings and willingness to recommend coaching provide substantial support for efficacy. Better measures and larger-scale clinical trial designs are needed for formal proof.

Dose response of task-specific upper limb training in people at least 6 months poststroke: A phase II, single-blind, randomized, controlled trial.

OBJECTIVE: The objectives of this work were to (1) determine whether higher doses of motor therapy in chronic poststroke hemiparesis result in better outcomes, compared to lower doses, and (2) evaluate potential modifiers of the dose-response relationship. METHODS: Eighty-five adults with upper extremity paresis ≥6 months poststroke were randomized to one of four dose groups in this single-blind, parallel, randomized, control trial. The dosing parameter manipulated was amount of task-specific training, as indexed by the number of task repetitions. Groups received 3,200, 6,400, 9,600, or individualized maximum (IM) repetitions, during 1-hour sessions, 4 days/week for 8 weeks. The intervention was an individualized, progressive, task-specific upper-limb training program designed to improve upper-limb functional motor capacity. The primary outcome was the slope of the Action Research Arm Test (ARAT) during the intervention. Effects of dose and potential modifiers of the dose-response relationship were evaluated with hierarchical linear models. RESULTS: ARAT scores for the 3,200, 9,600, and IM groups improved over time as indicated by slopes (ΔARAT/week, mean ± standard errors) of 0.40 ± 0.15, 0.31 ± 0.16, and 0.66 ± 0.14, respectively (p < 0.05). The slope of the 6,400 group was smaller (-0.05 ± 0.15) and significantly different from the 3,200 and IM groups (p < 0.001). Initial motor capacity, neglect, and other tested characteristics did not modify the dose-response relationship. INTERPRETATION: Overall, treatment effects were small. There was no evidence of a dose-response effect of task-specific training on functional capacity in people with long-standing upper-limb paresis poststroke. Ann Neurol 2016;80:342-354.

Measuring Functional Arm Movement after Stroke Using a Single Wrist-Worn Sensor and Machine Learning.

BACKGROUND AND PURPOSE: Trials of restorative therapies after stroke and clinical rehabilitation require relevant and objective efficacy end points; real-world upper extremity (UE) functional use is an attractive candidate. We present a novel, inexpensive, and feasible method for separating UE functional use from nonfunctional movement after stroke using a single wrist-worn accelerometer. METHODS: Ten controls and 10 individuals with stroke performed a series of minimally structured activities while simultaneously being videotaped and wearing a sensor on each wrist that captured the linear acceleration and angular velocity of their UEs. Video data provided ground truth to annotate sensor data as functional or nonfunctional limb use. Using the annotated sensor data, we trained a machine learning tool, a Random Forest model. We then assessed the accuracy of that classification. RESULTS: In intrasubject test trials, our method correctly classified sensor data with an average of 94.80% in controls and 88.38% in stroke subjects. In leave-one-out intersubject testing and training, correct classification averaged 91.53% for controls and 70.18% in stroke subjects. CONCLUSIONS: Our method shows promise for inexpensive and objective quantification of functional UE use in hemiparesis, and for assessing the impact of UE treatments. Training a classifier on raw sensor data is feasible, and determination of whether patients functionally use their UE can thus be done remotely. For the restorative treatment trial setting, an intrasubject test/train approach would be especially accurate. This method presents a potentially precise, cost-effective, and objective measurement of UE use outside the clinical or laboratory environment.

Dynamic motor tracking is sensitive to subacute mTBI.

Effective screening for mild traumatic brain injury (mTBI) is critical to accurate diagnosis, intervention, and improving outcomes. However, detecting mTBI using conventional clinical techniques is difficult, time intensive, and subject to observer bias. We examine the use of a simple visuomotor tracking task as a screening tool for mTBI. Thirty participants, 16 with clinically diagnosed mTBI (mean time since injury: 36.4 ± 20.9 days (95 % confidence interval); median = 20 days) were asked to squeeze a hand dynamometer and vary their grip force to match a visual, variable target force for 3 min. We found that controls outperformed individuals with mTBI; participants with mTBI moved with increased variability, as quantified by the standard deviation of the tracking error. We modeled participants' feedback response-how participants changed their grip force in response to errors in position and velocity-and used model parameters to classify mTBI with a sensitivity of 87 % and a specificity of 93 %, higher than several standard clinical scales. Our findings suggest that visuomotor tracking could be an effective supplement to conventional assessment tools to screen for mTBI and track mTBI symptoms during recovery.

Using Wearable Sensors and Machine Learning Models to Separate Functional Upper Extremity Use From Walking-Associated Arm Movements.

OBJECTIVE: To improve measurement of upper extremity (UE) use in the community by evaluating the feasibility of using body-worn sensor data and machine learning models to distinguish productive prehensile and bimanual UE activity use from extraneous movements associated with walking. DESIGN: Comparison of machine learning classification models with criterion standard of manually scored videos of performance in UE prosthesis users. SETTING: Rehabilitation hospital training apartment. PARTICIPANTS: Convenience sample of UE prosthesis users (n=5) and controls (n=13) similar in age and hand dominance (N=18). INTERVENTIONS: Participants were filmed executing a series of functional activities; a trained observer annotated each frame to indicate either UE movement directed at functional activity or walking. Synchronized data from an inertial sensor attached to the dominant wrist were similarly classified as indicating either a functional use or walking. These data were used to train 3 classification models to predict the functional versus walking state given the associated sensor information. Models were trained over 4 trials: on UE amputees and controls and both within subject and across subject. Model performance was also examined with and without preprocessing (centering) in the across-subject trials. MAIN OUTCOME MEASURE: Percent correct classification. RESULTS: With the exception of the amputee/across-subject trial, at least 1 model classified >95% of test data correctly for all trial types. The top performer in the amputee/across-subject trial classified 85% of test examples correctly. CONCLUSIONS: We have demonstrated that computationally lightweight classification models can use inertial data collected from wrist-worn sensors to reliably distinguish prosthetic UE movements during functional use from walking-associated movement. This approach has promise in objectively measuring real-world UE use of prosthetic limbs and may be helpful in clinical trials and in measuring response to treatment of other UE pathologies.

Effect of a Task-Oriented Rehabilitation Program on Upper Extremity Recovery Following Motor Stroke: The ICARE Randomized Clinical Trial.

IMPORTANCE: Clinical trials suggest that higher doses of task-oriented training are superior to current clinical practice for patients with stroke with upper extremity motor deficits. OBJECTIVE: To compare the efficacy of a structured, task-oriented motor training program vs usual and customary occupational therapy (UCC) during stroke rehabilitation. DESIGN, SETTING, AND PARTICIPANTS: Phase 3, pragmatic, single-blind randomized trial among 361 participants with moderate motor impairment recruited from 7 US hospitals over 44 months, treated in the outpatient setting from June 2009 to March 2014. INTERVENTIONS: Structured, task-oriented upper extremity training (Accelerated Skill Acquisition Program [ASAP]; n = 119); dose-equivalent occupational therapy (DEUCC; n = 120); or monitoring-only occupational therapy (UCC; n = 122). The DEUCC group was prescribed 30 one-hour sessions over 10 weeks; the UCC group was only monitored, without specification of dose. MAIN OUTCOMES AND MEASURES: The primary outcome was 12-month change in log-transformed Wolf Motor Function Test time score (WMFT, consisting of a mean of 15 timed arm movements and hand dexterity tasks). Secondary outcomes were change in WMFT time score (minimal clinically important difference [MCID] = 19 seconds) and proportion of patients improving ≥25 points on the Stroke Impact Scale (SIS) hand function score (MCID = 17.8 points). RESULTS: Among the 361 randomized patients (mean age, 60.7 years; 56% men; 42% African American; mean time since stroke onset, 46 days), 304 (84%) completed the 12-month primary outcome assessment; in intention-to-treat analysis, mean group change scores (log WMFT, baseline to 12 months) were, for the ASAP group, 2.2 to 1.4 (difference, 0.82); DEUCC group, 2.0 to 1.2 (difference, 0.84); and UCC group, 2.1 to 1.4 (difference, 0.75), with no significant between-group differences (ASAP vs DEUCC: 0.14; 95% CI, -0.05 to 0.33; P = .16; ASAP vs UCC: -0.01; 95% CI, -0.22 to 0.21; P = .94; and DEUCC vs UCC: -0.14; 95% CI, -0.32 to 0.05; P = .15). Secondary outcomes for the ASAP group were WMFT change score, -8.8 seconds, and improved SIS, 73%; DEUCC group, WMFT, -8.1 seconds, and SIS, 72%; and UCC group, WMFT, -7.2 seconds, and SIS, 69%, with no significant pairwise between-group differences (ASAP vs DEUCC: WMFT, 1.8 seconds; 95% CI, -0.8 to 4.5 seconds; P = .18; improved SIS, 1%; 95% CI, -12% to 13%; P = .54; ASAP vs UCC: WMFT, -0.6 seconds, 95% CI, -3.8 to 2.6 seconds; P = .72; improved SIS, 4%; 95% CI, -9% to 16%; P = .48; and DEUCC vs UCC: WMFT, -2.1 seconds; 95% CI, -4.5 to 0.3 seconds; P = .08; improved SIS, 3%; 95% CI, -9% to 15%; P = .22). A total of 168 serious adverse events occurred in 109 participants, resulting in 8 patients withdrawing from the study. CONCLUSIONS AND RELEVANCE: Among patients with motor stroke and primarily moderate upper extremity impairment, use of a structured, task-oriented rehabilitation program did not significantly improve motor function or recovery beyond either an equivalent or a lower dose of UCC upper extremity rehabilitation. These findings do not support superiority of this program among patients with motor stroke and primarily moderate upper extremity impairment. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00871715.

Internal models of upper limb prosthesis users when grasping and lifting a fragile object with their prosthetic limb.

Internal models allow unimpaired individuals to appropriately scale grip force when grasping and lifting familiar objects. In prosthesis users, the internal model must adapt to the characteristics of the prosthetic devices and reduced sensory feedback. We studied the internal models of 11 amputees and eight unimpaired controls when grasping and lifting a fragile object. When the object was modified from a rigid to fragile state, both subject groups adapted appropriately by significantly reducing grasp force on the first trial with the fragile object compared to the rigid object (p < 0.020). There was a wide range of performance skill illustrated by amputee subjects when lifting the fragile object in 10 repeated trials. One subject, using a voluntary close device, never broke the object, four subjects broke the fragile device on every attempt and seven others failed on their initial attempts, but improved over the repeated trials. Amputees decreased their grip forces 51 ± 7 % from the first to the last trial (p < 0.001), indicating a practice effect. However, amputees used much higher levels of force than controls throughout the testing (p < 0.015). Amputees with better performance on the Box and Blocks test used lower grip force levels (p = 0.006) and had more successful lifts of the fragile object (p = 0.002). In summary, amputees do employ internal models when picking up objects; however, the accuracy of these models is poor and grip force modulation is significantly impaired. Further studies could examine the alternative sensory modalities and training parameters that best promote internal model formation.

Motor rehabilitation in stroke and traumatic brain injury: stimulating and intense.

PURPOSE OF REVIEW: The purpose of this review is to provide an update on the latest neurorehabilitation literature for motor recovery in stroke and traumatic brain injury to assist clinical decision making and assessing future research directions. RECENT FINDINGS: The emerging approach to motor restoration is now multimodal. It engages the traditional multidisciplinary rehabilitation team, but incorporates highly structured activity-based therapies, pharmacology, brain stimulation and robotics. Clinical trial data support selective serotonin reuptake inhibitors and amantadine to assist motor recovery poststroke and traumatic brain injury, respectively. Similarly, there is continued support for intensity as a key factor in activity-based therapies, across skilled and nonskilled interventions. Aerobic training appears to have multiple benefits; increasing the capacity to meet the demands of hemiparetic gait improves endurance for activities of daily living while promoting cognition and mood. At this time, the primary benefit of robotic therapy lies in the delivery of highly intense and repetitive motor practice. Both transcranial direct current and magnetic stimulation therapies are in early stages, but have promise in motor and language restoration. SUMMARY: Advancements in neurorehabilitation have shifted treatment away from nonspecific activity regimens and amphetamines. As the body of knowledge grows, evidence-based practice using interventions targeted at specific subgroups becomes progressively more feasible.

Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE): a randomized controlled trial protocol.

BACKGROUND: Residual disability after stroke is substantial; 65% of patients at 6 months are unable to incorporate the impaired upper extremity into daily activities. Task-oriented training programs are rapidly being adopted into clinical practice. In the absence of any consensus on the essential elements or dose of task-specific training, an urgent need exists for a well-designed trial to determine the effectiveness of a specific multidimensional task-based program governed by a comprehensive set of evidence-based principles. The Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE) Stroke Initiative is a parallel group, three-arm, single blind, superiority randomized controlled trial of a theoretically-defensible, upper extremity rehabilitation program provided in the outpatient setting.The primary objective of ICARE is to determine if there is a greater improvement in arm and hand recovery one year after randomization in participants receiving a structured training program termed Accelerated Skill Acquisition Program (ASAP), compared to participants receiving usual and customary therapy of an equivalent dose (DEUCC). Two secondary objectives are to compare ASAP to a true (active monitoring only) usual and customary (UCC) therapy group and to compare DEUCC and UCC. METHODS/DESIGN: Following baseline assessment, participants are randomized by site, stratified for stroke duration and motor severity. 360 adults will be randomized, 14 to 106 days following ischemic or hemorrhagic stroke onset, with mild to moderate upper extremity impairment, recruited at sites in Atlanta, Los Angeles and Washington, D.C. The Wolf Motor Function Test (WMFT) time score is the primary outcome at 1 year post-randomization. The Stroke Impact Scale (SIS) hand domain is a secondary outcome measure.The design includes concealed allocation during recruitment, screening and baseline, blinded outcome assessment and intention to treat analyses. Our primary hypothesis is that the improvement in log-transformed WMFT time will be greater for the ASAP than the DEUCC group. This pre-planned hypothesis will be tested at a significance level of 0.05. DISCUSSION: ICARE will test whether ASAP is superior to the same number of hours of usual therapy. Pre-specified secondary analyses will test whether 30 hours of usual therapy is superior to current usual and customary therapy not controlled for dose. TRIAL REGISTRATION: www.ClinicalTrials.gov Identifier: NCT00871715

The Critical Period After Stroke Study (CPASS) Upper Extremity Treatment Protocol.

Objective: To present the development of a novel upper extremity (UE) treatment and assess how it was delivered in the Critical Periods After Stroke Study (CPASS), a phase II randomized controlled trial (RCT). Design: Secondary analysis of data from the RCT. Setting: Inpatient and outpatient settings the first year after stroke. Participants: Of the 72 participants enrolled in CPASS (N=72), 53 were in the study groups eligible to receive the treatment initiated at ≤30 days (acute), 2-3 months (subacute), or ≥6 months (chronic) poststroke. Individuals were 65.1±10.5 years of age, 55% were women, and had mild to moderate UE motor capacity (Action Research Arm Test=17.2±14.3) at baseline. Intervention: The additional 20 hours of treatment began using the Activity Card Sort (ACS), a standardized assessment of activities and participation after stroke, to identify UE treatment goals selected by the participants that were meaningful to them. Treatment activities were broken down into smaller components from a standardized protocol and process that operationalized the treatments essential elements. Main Outcome Measures: Feasibility of performing the treatment in a variety of clinical settings in an RCT and contextual factors that influenced adherence. Results: A total of 49/53 participants fully adhered to the CPASS treatment. The duration and location of the treatment sessions and the UE activities practiced during therapy are presented for the total sample (n=49) and per study group as an assessment of feasibility and the contextual factors that influenced adherence. Conclusions: The CPASS treatment and therapy goals were explicitly based on the meaningful activities identified by the participants using the ACS as a treatment planning tool. This approach provided flexibility to customize UE motor therapy without sacrificing standardization or quantification of the data regardless of the location and UE impairments of participants within the first year poststroke.

Expansion of plasma MicroRNAs over the first month following human stroke.

Few have characterized miRNA expression during the transition from injury to neural repair and secondary neurodegeneration following stroke in humans. We compared expression of 754 miRNAs from plasma samples collected 5, 15, and 30 days post-ischemic stroke from a discovery cohort (n = 55) and 15-days post-ischemic stroke from a validation cohort (n = 48) to healthy control samples (n = 55 and 48 respectively) matched for age, sex, race and cardiovascular comorbidities using qRT-PCR. Eight miRNAs remained significantly altered across all time points in both cohorts including many described in acute stroke. The number of significantly dysregulated miRNAs more than doubled from post-stroke day 5 (19 miRNAs) to days 15 (50 miRNAs) and 30 (57 miRNAs). Twelve brain-enriched miRNAs were significantly altered at one or more time points (decreased expression, stroke versus controls: miR-107; increased expression: miR-99-5p, miR-127-3p, miR-128-3p, miR-181a-3p, miR-181a-5p, miR-382-5p, miR-433-3p, miR-491-5p, miR-495-3p, miR-874-3p, and miR-941). Many brain-enriched miRNAs were associated with apoptosis over the first month post-stroke whereas other miRNAs suggested a transition to synapse regulation and neuronal protection by day 30. These findings suggest that a program of decreased cellular proliferation may last at least 30 days post-stroke, and points to specific miRNAs that could contribute to neural repair in humans.