Stroke
Conditions
Keywords
hemiparesis
Brief summary
This study investigates the effects of sub-maximal exercise to task-failure (e.g., fatigue) with the less involved, or so-called non-paretic hand, in people who have experienced a stroke. In previous work the investigators found that non-paretic hand exercise to task-failure increased excitability of the motor cortex in the more involved hemisphere and produced behavioral improvements in the unexercised paretic hand. Importantly, the magnitude of increased brain excitability is greater than what has been observed following brain stimulation with either repetitive transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) and lasts longer. This approach could be implemented in the clinical setting and could be accessible to a greater number of people than brain stimulation. The investigators' goals in the current study are to: repeat previous findings in a different group of participants and investigate the neural mechanisms that produce brain and behavioral facilitation in order to inform development of this approach for clinical implementation.
Detailed description
The long-term goal is to restore upper extremity (UE) motor function following stroke. The overall objective of this proposal is to improve the investigators' understanding of neural mechanisms contributing to inter-limb and inter-hemispheric transfer following non-paretic limb exercise to task failure. The investigators will use transcranial magnetic stimulation to probe acute adaptations in cortical excitability, intracortical and inter-hemispheric circuits that accompany behavioral facilitation of the paretic hand. The work proposed in this two year project will enable the investigators to obtain three data elements critical to complete the working hypothesis: 1. . Changes in intracortical and interhemispheric inhibition in both hemispheres following non-paretic limb exercise to task-failure. 2. . Behavioral effects using a motor task involving manipulation and dexterity. 3. . Determine the persistence and consistency of neural and behavioral facilitation.
Interventions
OTHERsubmaximal exercise (grip)
participants perform repeated gripping with visual feedback to task failure
Sponsors
VA Office of Research and Development
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Prospective, repeated measures
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* individuals at least 6 months post-stroke in the cortical or sub-cortical distribution with residual upper-extremity hemiparesis * Non-Veteran Participants are eligible
Exclusion criteria
* multiple strokes * strokes in both hemispheres * brainstem/medullary/cerebellar stroke * seizure disorder * metal implants in head or neck * pacemaker or other implanted device * inability to produce any measurable grip force
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Short Intracortical Inhibition (SICI) | baseline, post task-failure (minutes to an hour), every 45 min up to 3.5 hours post-task-failure (7 points total) | SICI is a neurophysiologic measure of intra-cortical inhibition, obtained using transcranial magnetic stimulation (TMS) measured here in the ipsilesional hemisphere (IH) at each point to determine how it is modulated in response to task-failure. SICI is quantified as a ratio where values \<1 reflect inhibition and \>1 disinhibition or relative excitation. In health, SICI is \ 0.5. Thus if SICI = 0.8, while \<1 it would indicate less inhibition than expected in health. Transient change in SICI from 0.8 to 1.1 over the course of this experimental paradigm would reflect a period of relative excitation in response to the exercise paradigm. |
| SICI Ratio | Baseline, pre-exercise of 8 repeated sessions | SICI is a neurophysiologic measure of intra-cortical inhibition, obtained using transcranial magnetic stimulation (TMS) measured here in the ipsilesional hemisphere (IH) at each point to determine how it is modulated in response to task-failure. SICI is quantified as a ratio where values \<1 reflect inhibition and \>1 disinhibition or relative excitation. In health, SICI is \ 0.5. Thus if SICI = 0.8, while \<1 it would indicate less inhibition than expected in health. Transient change in SICI from 0.8 to 1.1 over the course of this experimental paradigm would reflect a period of relative excitation in response to the exercise paradigm. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Box and Blocks Test (BBT) | baseline, post task-failure (requires variable timeline from minutes to an hour), every 45 min up to 3.5 hours post-task-failure (7 points total) | The BBT measures motor function/dexterity, scored as the number of blocks transferred in 1 minute. Here function of the paretic hand was measured at each time point: baseline, post-task failure, 45min post, 90min post, 135min post, 180min post, 225min post-task failure to determine the change in paretic hand BBT performance following exercise to task-failure. Scores are numeric ranging from 0 (no blocks transferred) to whatever the participant is able to achieve. Healthy age-matched adults without motor disability score in the range of 60 (+/- 10) blocks transferred in 1 minute. |
Countries
United States
Participant flow
Recruitment details
Participants identified by the VA Brain Rehabilitation Research Center (BRRC) screening and recruitment core enrolled between 2/1/2016 - 5/21/2018.
Participants by arm
| Arm | Count |
|---|---|
| Task-failure, Extended Session Exercise to fatigue followed by repeated monitoring of recovery until 3:45 after. | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | data not usable | 2 |
Baseline characteristics
| Characteristic | Task-failure, Extended Session |
|---|---|
| Age, Continuous Extended Session | 61.1 years STANDARD_DEVIATION 8.2 |
| Center for Epidemiologic Studies - Depression Scale | 9.0 units on a scale STANDARD_DEVIATION 9.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Fatigue Severity Scale | 3.95 units on a scale STANDARD_DEVIATION 1.58 |
| Montreal Cognitive Assessment | 27.0 units on a scale STANDARD_DEVIATION 1.96 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Region of Enrollment United States | 13 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 11 Participants |
| Upper-extremity Fugl-Meyer Motor Assessment | 54.6 units on a scale STANDARD_DEVIATION 13.2 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
Short Intracortical Inhibition (SICI)
SICI is a neurophysiologic measure of intra-cortical inhibition, obtained using transcranial magnetic stimulation (TMS) measured here in the ipsilesional hemisphere (IH) at each point to determine how it is modulated in response to task-failure. SICI is quantified as a ratio where values \<1 reflect inhibition and \>1 disinhibition or relative excitation. In health, SICI is \ 0.5. Thus if SICI = 0.8, while \<1 it would indicate less inhibition than expected in health. Transient change in SICI from 0.8 to 1.1 over the course of this experimental paradigm would reflect a period of relative excitation in response to the exercise paradigm.
Time frame: baseline, post task-failure (minutes to an hour), every 45 min up to 3.5 hours post-task-failure (7 points total)
Population: Only 13/15 data sets were usable for reasons explained elsewhere in the record. Thus, while 15 individuals were enrolled, we were able to analyze only 13 of these individuals' data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Task-Failure, Extended Session | Short Intracortical Inhibition (SICI) | Baseline | 0.83 SICI ratio | Standard Error 0.07 |
| Task-Failure, Extended Session | Short Intracortical Inhibition (SICI) | 0 min post-task-failure | 1.14 SICI ratio | Standard Error 0.15 |
| Task-Failure, Extended Session | Short Intracortical Inhibition (SICI) | 45 min post-task-failure | 0.89 SICI ratio | Standard Error 0.11 |
| Task-Failure, Extended Session | Short Intracortical Inhibition (SICI) | 90 min post-task-failure | 0.88 SICI ratio | Standard Error 0.05 |
| Task-Failure, Extended Session | Short Intracortical Inhibition (SICI) | 135 min post-task-failure | 0.82 SICI ratio | Standard Error 0.06 |
| Task-Failure, Extended Session | Short Intracortical Inhibition (SICI) | 180 min post-task-failure | 0.87 SICI ratio | Standard Error 0.06 |
| Task-Failure, Extended Session | Short Intracortical Inhibition (SICI) | 225 min post-task-failure | 0.81 SICI ratio | Standard Error 0.06 |
Comparison: We performed repeated measures analysis of variance (RM-ANOVA) to determine if intracortical inhibition, as measured by SICI, in the ipsilesional hemisphere was altered by less affected hand exercise to task-failure and to determine the time course and recovery of this effect.p-value: 0.15ANOVA
Primary
SICI Ratio
SICI is a neurophysiologic measure of intra-cortical inhibition, obtained using transcranial magnetic stimulation (TMS) measured here in the ipsilesional hemisphere (IH) at each point to determine how it is modulated in response to task-failure. SICI is quantified as a ratio where values \<1 reflect inhibition and \>1 disinhibition or relative excitation. In health, SICI is \ 0.5. Thus if SICI = 0.8, while \<1 it would indicate less inhibition than expected in health. Transient change in SICI from 0.8 to 1.1 over the course of this experimental paradigm would reflect a period of relative excitation in response to the exercise paradigm.
Time frame: Baseline, pre-exercise of 8 repeated sessions
Population: Only 10/12 data sets analyzed because it was possible to induce SICI in only 10 individuals.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Task-Failure, Extended Session | SICI Ratio | Session1 | 0.89 SICI ratio | Standard Deviation 0.25 |
| Task-Failure, Extended Session | SICI Ratio | Session2 | 0.85 SICI ratio | Standard Deviation 0.14 |
| Task-Failure, Extended Session | SICI Ratio | Session3 | 0.93 SICI ratio | Standard Deviation 0.29 |
| Task-Failure, Extended Session | SICI Ratio | Session4 | 0.80 SICI ratio | Standard Deviation 0.29 |
| Task-Failure, Extended Session | SICI Ratio | Session5 | 0.78 SICI ratio | Standard Deviation 0.28 |
| Task-Failure, Extended Session | SICI Ratio | Session6 | 0.77 SICI ratio | Standard Deviation 0.37 |
| Task-Failure, Extended Session | SICI Ratio | Session7 | 0.88 SICI ratio | Standard Deviation 0.25 |
| Task-Failure, Extended Session | SICI Ratio | Session8 | 0.83 SICI ratio | Standard Deviation 0.31 |
Comparison: We performed repeated measures analysis of variance (RM-ANOVA) to determine if intracortical inhibition, as measured by SICI, in the ipsilesional hemisphere was altered by repeated sessions of less affected hand exercise to task-failure. Pre-exercise SICI was compared between Session1 and Session8.p-value: 0.83ANOVA
Other Pre-specified
Box and Blocks Test (BBT)
The BBT measures motor function/dexterity, scored as the number of blocks transferred in 1 minute. Here function of the paretic hand was measured at each time point: baseline, post-task failure, 45min post, 90min post, 135min post, 180min post, 225min post-task failure to determine the change in paretic hand BBT performance following exercise to task-failure. Scores are numeric ranging from 0 (no blocks transferred) to whatever the participant is able to achieve. Healthy age-matched adults without motor disability score in the range of 60 (+/- 10) blocks transferred in 1 minute.
Time frame: baseline, post task-failure (requires variable timeline from minutes to an hour), every 45 min up to 3.5 hours post-task-failure (7 points total)
Population: The Box and Blocks test (BBT) is an accepted measure of motor function/dexterity. Score reflect the number of 1 blocks moved from one half of a divided box to the other in 1 minute. Higher numbers indicate better performance.~Only 13/15 data sets were analyzed because other data sets were not usable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Task-Failure, Extended Session | Box and Blocks Test (BBT) | Baseline | 25.4 blocks | Standard Error 3.6 |
| Task-Failure, Extended Session | Box and Blocks Test (BBT) | 0 min post-task-failure | 25.5 blocks | Standard Error 3.2 |
| Task-Failure, Extended Session | Box and Blocks Test (BBT) | 45 min post-task-failure | 25.0 blocks | Standard Error 3.3 |
| Task-Failure, Extended Session | Box and Blocks Test (BBT) | 90 min post-task-failure | 26.1 blocks | Standard Error 3.4 |
| Task-Failure, Extended Session | Box and Blocks Test (BBT) | 135 min post-task-failure | 26.7 blocks | Standard Error 3.6 |
| Task-Failure, Extended Session | Box and Blocks Test (BBT) | 180 min post-task-failure | 25.7 blocks | Standard Error 3.6 |
| Task-Failure, Extended Session | Box and Blocks Test (BBT) | 225 min post-task-failure | 26.9 blocks | Standard Error 3.7 |
Comparison: RM-ANOVAp-value: 0.204ANOVA
Other Pre-specified
Box and Blocks Test (BBT)
The BBT measures motor function/dexterity, scored as the number of blocks transferred in 1 minute. Here function of the paretic hand was measured prior to exercise at each of 8 repeated sessions conducted twice weekly for 4 weeks to determine the change in paretic hand BBT performance following repeated sessions of exercise to task-failure. Scores are numeric ranging from 0 (no blocks transferred) to whatever the participant is able to achieve. Healthy age-matched adults without motor disability score in the range of 60 (+/- 10) blocks transferred in 1 minute.
Time frame: baseline, pre-exercise of 8 repeated sessions
Population: BBT data were obtained in all 12 individuals at each of 8 sessions.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Task-Failure, Extended Session | Box and Blocks Test (BBT) | Session1 | 23.2 blocks | Standard Deviation 12.8 |
| Task-Failure, Extended Session | Box and Blocks Test (BBT) | Session2 | 23.5 blocks | Standard Deviation 13.2 |
| Task-Failure, Extended Session | Box and Blocks Test (BBT) | Session3 | 26.8 blocks | Standard Deviation 11.5 |
| Task-Failure, Extended Session | Box and Blocks Test (BBT) | Session4 | 28.5 blocks | Standard Deviation 11.9 |
| Task-Failure, Extended Session | Box and Blocks Test (BBT) | Session5 | 27.4 blocks | Standard Deviation 12.7 |
| Task-Failure, Extended Session | Box and Blocks Test (BBT) | Session6 | 29.8 blocks | Standard Deviation 10.9 |
| Task-Failure, Extended Session | Box and Blocks Test (BBT) | Session7 | 29.7 blocks | Standard Deviation 11.8 |
| Task-Failure, Extended Session | Box and Blocks Test (BBT) | Session8 | 29.3 blocks | Standard Deviation 11.9 |
Comparison: We performed repeated measures analysis of variance (RM-ANOVA) to determine if motor dexterity, as measured by the BBT, was improved by repeated sessions of non-paretic hand exercise to task-failure. BBT performance was compared between Session1 and Session8.p-value: 0.004ANOVA