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| ID | Type | Description | Link |
|---|---|---|---|
| R21NS120274 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Casa Colina Hospital and Centers for Healthcare | OTHER |
| National Institute of Neurological Disorders and Stroke (NINDS) | NIH |
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Every year, almost 800,000 people experience a stroke in the United States, which lead to upper-limb impairments, making recovery of motor function a priority in stroke rehabilitation. 1) The primary objective of this study is to determine whether fast arm movement training on a tracking task ("Speed-training"), in chronic stroke survivors with mild to moderate paresis, will generalize to improve arm function better than dose-equivalent accuracy training on the same task. 2) study the effect of intensive arm training on the recovery of anticipatory feedforward control. 3) Determine the involvement of cerebellar-cortical circuits in the recovery of arm movements due to speed training.
About 65% of stroke survivors experience long-term limitations in upper extremity (UE) functions. In particular, limitations in arm reaching movements are prominent and correlate strongly with patients' impairment levels. Because activities of daily living often involve the UEs, retraining reach and grasp skills is critical for return to a full quality-of-life. Yet, the training parameters required for effective rehabilitation of UE function are not known. Recent evidence suggests that high-speed movements during training are effective at improving arm movements in individuals with chronic stroke. Hence, fast movements generating large errors, would promote the restoration of the feedforward controllers and therefore improves arm movements and UE functions in individuals with chronic stroke. Because the cerebellum is involved in learning feedforward controllers from motor errors, the improvements would be proportional to the integrity of the cerebellar-cortical networks.
A double-blind quasi-randomized controlled study will be carried out in chronic post-stroke survivors. Participants will be assigned to either the speed-bias training group or a dose equivalent accuracy-bias training group (control) and will receive 4 days of training over a 1week period by a trained Occupational or physical therapist. Behavioral, EMG, and MRI data will be acquired within two weeks before, 3 days post, and one month after intervention.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Speed-biased complex motor skill training | Active Comparator | Participants will perform 400 complex movements per day over 4 days over a one-week period. The task requires participants to navigate their hand through a "track" projected on the surface of a table with a width of 5cm. Participants receive adaptive score based on their movement time. . |
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| Accuracy-biased complex motor skill training | Other | The accuracy-biased group receives a dose equivalent intervention with a emphasize on accuracy. The width of the track projected on the table is narrower (less than 2cm) and the adaptive score received are based on their accuracy to say within the boundary of the track. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fast intervention | Behavioral | This intervention is based on recent body of evidence that high-speed movements during training are effective at improving arm movements in individuals with chronic stroke.Participants will be rewarded for movements performed within a short amount of time. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Arm Reaching Movement Time. | Average movement time for 30 planar reaching movements to targets arrayed on a planar workspace. Negative changes indicate that participants moved faster to the targets following the intervention. | Change from baseline (assessed during the week preceding the intervention) to 3 days post-intervention, representing an average interval of 12 days |
| Change in Movement Smoothness | Average movement smoothness for 30 planar reaching movements to target arrayed on a planar workspace. Smoothness is computed by number of peaks in hand tangential velocity profiles of arm-reaching movements. Negative changes indicate that participants had smoother movement to the targets following the intervention. | Change from baseline (assessed during the week preceding the intervention) to 3 days post-intervention, representing an average interval of 12 days |
| Change in Speed Accuracy Trade-off | The speed-accuracy trade-off of reaching movements was assessed as a linear relationship between movement time and the Index of Difficulty : log ratio of the movement distance to target size. Negative changes indicate that participants are less affected by the index of difficulty, reflecting a better speed-accuracy trade-off. | Change from baseline (assessed during the week preceding the intervention) to 3 days post-intervention, representing an average interval of 12 days |
| Change in Arm Reaching Movement Time. | Average movement time for 30 planar reaching movements to targets arrayed on a planar workspace. Negative changes indicate that participants moved faster to the targets following the intervention. | We evaluated the change from baseline (assessed during the week preceding the intervention) to one month post-intervention, representing an average interval of 40 days. |
| Change in Movement Smoothness |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Action Research Arm Test (ARAT) | The ARAT assesses specific changes in upper limb function among individuals who have sustained a stroke.The test consists of performing functional reaching tasks, with each sub-task scored on a scale from 0 to 3, where a score of 3 indicates the movement was performed normally. Scores range from 0 to 57, with higher scores indicating better performance. Positive changes reflect improvements in limb function. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nicolas Schweighofer, PhD | University of Southern California | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Casa Colina Hospital and Centers for Healthcare | Pomona | California | 91769 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27447365 | Background | Lang CE, Strube MJ, Bland MD, Waddell KJ, Cherry-Allen KM, Nudo RJ, Dromerick AW, Birkenmeier RL. Dose response of task-specific upper limb training in people at least 6 months poststroke: A phase II, single-blind, randomized, controlled trial. Ann Neurol. 2016 Sep;80(3):342-54. doi: 10.1002/ana.24734. Epub 2016 Aug 16. | |
| 31164067 | Background | Winstein C, Kim B, Kim S, Martinez C, Schweighofer N. Dosage Matters. Stroke. 2019 Jul;50(7):1831-1837. doi: 10.1161/STROKEAHA.118.023603. Epub 2019 Jun 5. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Speed-biased Complex Motor Skill Training | 21 participants performed 520 complex movements per day over 4 days over a one-week period. The task required participants to navigate their hand through a "track" projected on the surface of a table with a width of 5cm. Participants received adaptive score based on their movement time. Fast intervention: This intervention was based on recent body of evidence that high-speed movements during training were effective at improving arm movements in individuals with chronic stroke. Participants were rewarded for movements performed within a short amount of time. |
| FG001 | Accuracy-biased Complex Motor Skill Training | The accuracy-biased group (21 participants) received a dose equivalent intervention with a emphasize on accuracy. The width of the track projected on the table was narrower (1.25cm) and the adaptive scores received were based on their accuracy to stay within the boundary of the track. Active Monitoring: This is an observation-only group. The training received in this group will be dose equivalent to the active group. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Speed-biased Complex Motor Skill Training | 21 participants performed 520 complex movements per day over 4 days over a one-week period. The task required participants to navigate their hand through a "track" projected on the surface of a table with a width of 5cm. Participants received adaptive score based on their movement time. Fast intervention: This intervention was based on recent body of evidence that high-speed movements during training were effective at improving arm movements in individuals with chronic stroke. Participants were rewarded for movements performed within a short amount of time. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Arm Reaching Movement Time. | Average movement time for 30 planar reaching movements to targets arrayed on a planar workspace. Negative changes indicate that participants moved faster to the targets following the intervention. | Here, we compared 30 planar reaching movements performed by each of the 21 participants before and after the intervention, representing a total of 1,260 movements per group. | Posted | Least Squares Mean | Standard Error | seconds | Change from baseline (assessed during the week preceding the intervention) to 3 days post-intervention, representing an average interval of 12 days | Planar reaching movements | Planar reaching movements |
|
1 month
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Speed-biased Complex Motor Skill Training | 21 participants performed 520 complex movements per day over 4 days over a one-week period. The task required participants to navigate their hand through a "track" projected on the surface of a table with a width of 5cm. Participants received adaptive score based on their movement time. Fast intervention: This intervention was based on recent body of evidence that high-speed movements during training were effective at improving arm movements in individuals with chronic stroke. Participants were rewarded for movements performed within a short amount of time. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| nausea | General disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Nicolas Schweighofer | Division of Biokinesiology & Physical Therapy, University of Southern California | (323) 442-2900 | schweigh@usc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 10, 2020 | Apr 24, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 10, 2020 | Apr 24, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D020521 | Stroke |
| D010291 | Paresis |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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Assessments will be done by a blinded and standardized clinical researcher
|
| Active Monitoring | Behavioral | This is an observation-only group. The training received in this group will be dose equivalent to the active group. |
|
Average movement smoothness for 30 planar reaching movements to target arrayed on a planar workspace. Smoothness is computed by number of peaks in hand tangential velocity profiles of arm-reaching movements. Negative changes indicate that participants had smoother movement to the targets following the intervention. |
| We evaluated the change from baseline (assessed during the week preceding the intervention) to one month post-intervention, representing an average interval of 40 days. |
| Change in Speed Accuracy Trade-off | The speed-accuracy trade-off of reaching movements was assessed as a linear relationship between movement time and the Index of Difficulty : log ratio of the movement distance to target size. Negative changes indicate that participants are less affected by the index of difficulty, reflecting a better speed-accuracy trade-off. | We evaluated the change from baseline (assessed during the week preceding the intervention) to one month post-intervention, representing an average interval of 40 days. |
| Change from baseline (assessed during the week preceding the intervention) to 3 days post-intervention, representing an average interval of 12 days |
| Change in Upper Extremity Fugl-Meyer (UEFM) | The UEFM is a test used to assess sensorimotor impairments in the upper extremity most affected by stroke. The test consists of performing specific upper extremity movements, with each sub-task scored on a scale from 0 to 2, where a score of 2 indicates normal performance. Scores range from 0 to 66, with higher scores indicating better performance. Positive changes reflect improvements in motor function. | Change from baseline (assessed during the week preceding the intervention) to 3 days post-intervention, representing an average interval of 12 days |
| Change in Box and Block Test Score (BBT) | The Box and Block Test (BBT) measures unilateral gross manual dexterity. The test involves moving, one by one, as many blocks as possible from one compartment of a box to an adjacent, identical compartment within 60 seconds. Scores range from 0 to 150, with higher scores indicating better performance. Positive changes reflect improvements in upper limb function. | Change from baseline (assessed during the week preceding the intervention) to 3 days post-intervention, representing an average interval of 12 days |
| Change in Action Research Arm Test (ARAT) | The ARAT assesses specific changes in upper limb function among individuals who have sustained a stroke. The test consists of performing functional reaching tasks, with each sub-task scored on a scale from 0 to 3, where a score of 3 indicates the movement was performed normally. Scores range from 0 to 57, with higher scores indicating better performance. Positive changes reflect improvements in limb function. | We evaluated the change from baseline (assessed during the week preceding the intervention) to one month post-intervention, representing an average interval of 40 days. |
| Change in Upper Extremity Fugl-Meyer (UEFM) | The UEFM is a test used to assess sensorimotor impairments in the upper extremity most affected by stroke. The test consists of performing specific upper extremity movements, with each sub-task scored on a scale from 0 to 2, where a score of 2 indicates normal performance. Scores range from 0 to 66, with higher scores indicating better performance. Positive changes reflect improvements in motor function. | We evaluated the change from baseline (assessed during the week preceding the intervention) to one month post-intervention, representing an average interval of 40 days. |
| Change in Box and Block Test Score (BBT) | The Box and Block Test (BBT) measures unilateral gross manual dexterity. | We evaluated the change from baseline (assessed during the week preceding the intervention) to one month post-intervention, representing an average interval of 40 days. |
| 26405046 | Background | Park H, Kim S, Winstein CJ, Gordon J, Schweighofer N. Short-Duration and Intensive Training Improves Long-Term Reaching Performance in Individuals With Chronic Stroke. Neurorehabil Neural Repair. 2016 Jul;30(6):551-61. doi: 10.1177/1545968315606990. Epub 2015 Sep 24. |
| 29127826 | Background | Kantak S, McGrath R, Zahedi N, Luchmee D. Behavioral and neurophysiological mechanisms underlying motor skill learning in patients with post-stroke hemiparesis. Clin Neurophysiol. 2018 Jan;129(1):1-12. doi: 10.1016/j.clinph.2017.10.010. Epub 2017 Nov 8. |
| 3488093 | Background | Pantano P, Baron JC, Samson Y, Bousser MG, Derouesne C, Comar D. Crossed cerebellar diaschisis. Further studies. Brain. 1986 Aug;109 ( Pt 4):677-94. doi: 10.1093/brain/109.4.677. |
| 1486143 | Background | Kawato M, Gomi H. A computational model of four regions of the cerebellum based on feedback-error learning. Biol Cybern. 1992;68(2):95-103. doi: 10.1007/BF00201431. |
| 10561408 | Background | Gribble PL, Ostry DJ. Compensation for interaction torques during single- and multijoint limb movement. J Neurophysiol. 1999 Nov;82(5):2310-26. doi: 10.1152/jn.1999.82.5.2310. |
| 30355628 | Background | Maeda RS, Cluff T, Gribble PL, Pruszynski JA. Feedforward and Feedback Control Share an Internal Model of the Arm's Dynamics. J Neurosci. 2018 Dec 5;38(49):10505-10514. doi: 10.1523/JNEUROSCI.1709-18.2018. Epub 2018 Oct 24. |
| 40346836 | Derived | Darmon Y, Kantak S, Cone H, Fullmer N, Ouellette D, Winstein C, Rosario ER, Schweighofer N. Speed-Biased Training Temporarily Improves Motor Performance of the Paretic Arm Compared to Accuracy-Biased Training in Chronic Stroke Survivors: The Phase 1 FAST Randomized Clinical Trial. Neurorehabil Neural Repair. 2025 Jul;39(7):542-554. doi: 10.1177/15459683251331582. Epub 2025 May 10. |
| BG001 | Accuracy-biased Complex Motor Skill Training | The accuracy-biased group (21 participants) received a dose equivalent intervention with a emphasize on accuracy. The width of the track projected on the table was narrower (1.25cm) and the adaptive scores received were based on their accuracy to stay within the boundary of the track. Active Monitoring: This is an observation-only group. The training received in this group will be dose equivalent to the active group. |
| BG002 | Total | Total of all reporting groups |
| Participants |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Upper Extremity Fugl-Meyer (UEFM) | standardized clinical score used to quantify motor impairment; Upper extremity score range: 0-66 | Mean | Standard Deviation | Scores on a scale |
|
| OG001 | Accuracy-biased Complex Motor Skill Training | The accuracy-biased group (21 participants) received a dose equivalent intervention with a emphasize on accuracy. The width of the track projected on the table was narrower (1.25cm) and the adaptive scores received were based on their accuracy to stay within the boundary of the track. Active Monitoring: This is an observation-only group. The training received in this group will be dose equivalent to the active group. |
|
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| Primary | Change in Movement Smoothness | Average movement smoothness for 30 planar reaching movements to target arrayed on a planar workspace. Smoothness is computed by number of peaks in hand tangential velocity profiles of arm-reaching movements. Negative changes indicate that participants had smoother movement to the targets following the intervention. | Here, we compared 30 planar reaching movements performed by each of the 21 participants before and after the intervention, representing a total of 1,260 movements per group. | Posted | Least Squares Mean | Standard Error | number of peaks | Change from baseline (assessed during the week preceding the intervention) to 3 days post-intervention, representing an average interval of 12 days | Planar reaching movements | Planar reaching movements |
|
|
|
| Primary | Change in Speed Accuracy Trade-off | The speed-accuracy trade-off of reaching movements was assessed as a linear relationship between movement time and the Index of Difficulty : log ratio of the movement distance to target size. Negative changes indicate that participants are less affected by the index of difficulty, reflecting a better speed-accuracy trade-off. | Participants performed planar reaching movements to targets positioned at the midline, varying in distance (10, 20, and 25 cm) and diameter (2, 4, and 8 cm), resulting in nine unique target combinations. Each target was presented six times, totaling 54 reaching movements per participant per session. This yielded 2,268 movements in total. We assessed changes in the speed-accuracy trade-off following the intervention. | Posted | Least Squares Mean | Standard Error | Fitts' slope (sec/index of difficulty) | Change from baseline (assessed during the week preceding the intervention) to 3 days post-intervention, representing an average interval of 12 days | planar reaching movements | planar reaching movements |
|
|
|
| Primary | Change in Arm Reaching Movement Time. | Average movement time for 30 planar reaching movements to targets arrayed on a planar workspace. Negative changes indicate that participants moved faster to the targets following the intervention. | Posted | Least Squares Mean | Standard Error | seconds | We evaluated the change from baseline (assessed during the week preceding the intervention) to one month post-intervention, representing an average interval of 40 days. | Planar reaching movements | Planar reaching movements |
|
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|
| Primary | Change in Movement Smoothness | Average movement smoothness for 30 planar reaching movements to target arrayed on a planar workspace. Smoothness is computed by number of peaks in hand tangential velocity profiles of arm-reaching movements. Negative changes indicate that participants had smoother movement to the targets following the intervention. | Here, we compared 30 planar reaching movements performed by each of the 21 participants before and after the intervention, representing a total of 1,260 movements per group. | Posted | Least Squares Mean | Standard Error | number of peaks | We evaluated the change from baseline (assessed during the week preceding the intervention) to one month post-intervention, representing an average interval of 40 days. | planar reaching movements | planar reaching movements |
|
|
|
| Primary | Change in Speed Accuracy Trade-off | The speed-accuracy trade-off of reaching movements was assessed as a linear relationship between movement time and the Index of Difficulty : log ratio of the movement distance to target size. Negative changes indicate that participants are less affected by the index of difficulty, reflecting a better speed-accuracy trade-off. | Participants performed planar reaching movements to targets positioned at the midline, varying in distance (10, 20, and 25 cm) and diameter (2, 4, and 8 cm), resulting in nine unique target combinations. Each target was presented six times, totaling 54 reaching movements per participant per session. This yielded 2,268 movements in total. We assessed changes in the speed-accuracy trade-off following the intervention. | Posted | Least Squares Mean | Standard Error | Fitts' slope (sec/index of difficulty) | We evaluated the change from baseline (assessed during the week preceding the intervention) to one month post-intervention, representing an average interval of 40 days. | planar reaching movements | planar reaching movements |
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| Secondary | Change in Action Research Arm Test (ARAT) | The ARAT assesses specific changes in upper limb function among individuals who have sustained a stroke.The test consists of performing functional reaching tasks, with each sub-task scored on a scale from 0 to 3, where a score of 3 indicates the movement was performed normally. Scores range from 0 to 57, with higher scores indicating better performance. Positive changes reflect improvements in limb function. | Here, we compared ARAT scores obtained by each of the 21 participants before and after the intervention, representing a total of 42 assessments per group. | Posted | Least Squares Mean | Standard Error | Scores on a scale | Change from baseline (assessed during the week preceding the intervention) to 3 days post-intervention, representing an average interval of 12 days | ARAT test | ARAT test |
|
|
|
| Secondary | Change in Upper Extremity Fugl-Meyer (UEFM) | The UEFM is a test used to assess sensorimotor impairments in the upper extremity most affected by stroke. The test consists of performing specific upper extremity movements, with each sub-task scored on a scale from 0 to 2, where a score of 2 indicates normal performance. Scores range from 0 to 66, with higher scores indicating better performance. Positive changes reflect improvements in motor function. | Here, we compared UEFM scores obtained by each of the 21 participants before and after the intervention, for a total of 42 assessments per group. | Posted | Least Squares Mean | Standard Error | Scores on a scale | Change from baseline (assessed during the week preceding the intervention) to 3 days post-intervention, representing an average interval of 12 days | UEFM test | UEFM test |
|
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|
| Secondary | Change in Box and Block Test Score (BBT) | The Box and Block Test (BBT) measures unilateral gross manual dexterity. The test involves moving, one by one, as many blocks as possible from one compartment of a box to an adjacent, identical compartment within 60 seconds. Scores range from 0 to 150, with higher scores indicating better performance. Positive changes reflect improvements in upper limb function. | Here, we compared BBT scores obtained by each of the 21 participants before and after the intervention, for a total of 42 assessments per group. | Posted | Least Squares Mean | Standard Error | Number of blocks | Change from baseline (assessed during the week preceding the intervention) to 3 days post-intervention, representing an average interval of 12 days | BBT test | BBT test |
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| Secondary | Change in Action Research Arm Test (ARAT) | The ARAT assesses specific changes in upper limb function among individuals who have sustained a stroke. The test consists of performing functional reaching tasks, with each sub-task scored on a scale from 0 to 3, where a score of 3 indicates the movement was performed normally. Scores range from 0 to 57, with higher scores indicating better performance. Positive changes reflect improvements in limb function. | Here, we compared ARAT scores obtained by each of the 21 participants before and after the intervention, representing a total of 42 assessments per group. | Posted | Least Squares Mean | Standard Error | Scores on a scale | We evaluated the change from baseline (assessed during the week preceding the intervention) to one month post-intervention, representing an average interval of 40 days. | ARAT test | ARAT test |
|
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| Secondary | Change in Upper Extremity Fugl-Meyer (UEFM) | The UEFM is a test used to assess sensorimotor impairments in the upper extremity most affected by stroke. The test consists of performing specific upper extremity movements, with each sub-task scored on a scale from 0 to 2, where a score of 2 indicates normal performance. Scores range from 0 to 66, with higher scores indicating better performance. Positive changes reflect improvements in motor function. | Here, we compared UEFM scores obtained by each of the 21 participants before and after the intervention, for a total of 42 assessments. | Posted | Least Squares Mean | Standard Error | Scores on a scale | We evaluated the change from baseline (assessed during the week preceding the intervention) to one month post-intervention, representing an average interval of 40 days. | UEFM test | UEFM test |
|
|
|
| Secondary | Change in Box and Block Test Score (BBT) | The Box and Block Test (BBT) measures unilateral gross manual dexterity. | Here, we compared BBT scores obtained by each of the 21 participants before and after the intervention, for a total of 42 assessments per group. | Posted | Least Squares Mean | Standard Error | Number of blocks | We evaluated the change from baseline (assessed during the week preceding the intervention) to one month post-intervention, representing an average interval of 40 days. | BBT test | BBT test |
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| 0 |
| 21 |
| 0 |
| 21 |
| 1 |
| 21 |
| EG001 | Accuracy-biased Complex Motor Skill Training | The accuracy-biased group (21 participants) received a dose equivalent intervention with a emphasize on accuracy. The width of the track projected on the table was narrower (1.25cm) and the adaptive scores received were based on their accuracy to stay within the boundary of the track. Active Monitoring: This is an observation-only group. The training received in this group will be dose equivalent to the active group. | 0 | 21 | 0 | 21 | 0 | 21 |
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| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |