Using whole-brain diffusion tensor analysis to evaluate white matter structural correlates of delayed visuospatial memory and one-week motor skill retention in nondemented older adults: A preliminary study.

Skill retention is important for motor rehabilitation outcomes. Recent work has demonstrated that delayed visuospatial memory performance may predict motor skill retention in older and neuropathological populations. White matter integrity between parietal and frontal cortices may explain variance in upper-extremity motor learning tasks and visuospatial processes. We performed a whole-brain analysis to determine the white matter correlates of delayed visuospatial memory and one-week motor skill retention in nondemented older adults. We hypothesized that better frontoparietal tract integrity would be positively related to better behavioral performance. Nineteen participants (age>58) completed diffusion-weighted imaging, then a clinical test of delayed visuospatial memory and 50 training trials of an upper-extremity motor task; participants were retested on the motor task one week later. Principal component analysis was used to create a composite score for each participant's behavioral data, i.e. shared variance between delayed visuospatial memory and motor skill retention, which was then entered into a voxel-based regression analysis. Behavioral results demonstrated that participants learned and retained their skill level after a week of no practice, and their delayed visuospatial memory score was positively related to the extent of skill retention. Consistent with previous work, neuroimaging results indicated that regions within bilateral anterior thalamic radiations, corticospinal tracts, and superior longitudinal fasciculi were related to better delayed visuospatial memory and skill retention. Results of this study suggest that the simple act of testing for specific cognitive impairments prior to therapy may identify older adults who will receive little to no benefit from the motor rehabilitation regimen, and that these neural regions may be potential targets for therapeutic intervention.

Low normal FMR1 genotype in older adult women: Psychological well-being and motor function.

The FMR1 gene plays a key role in adult neurogenesis and neuroplasticity, and thus may contribute to age-related health in the population. The current study focused on the "low normal" FMR1 genotype, defined by lower-than-typical numbers of FMR1 CGG repeats (<26), as a potential genetic determinant of age-related health. We characterized the effect of the low normal FMR1 genotype on psychological well-being and motor function in a racially diverse non-clinical sample of older adult women. Women with low CGG repeats were distinguished from those with CGGs falling within the mid-high end of the normal range by reduced performance on multimodal assessments of motor function and psychological well-being, with large effect sizes. Robust continuous associations were also detected between lower CGG repeat length and reduced psychological well-being, balance, and dexterity. Findings suggest that FMR1 may represent an important mediator of individual differences in age-related health; larger epidemiological studies are needed. Given that approximately 23-35% of females carry the low normal genotype, efforts to understand its clinical effects have relevance a broad swath of the aging population.

Observational Study of Neuroimaging Biomarkers of Severe Upper Limb Impairment After Stroke.

BACKGROUND AND OBJECTIVES: It is difficult to predict post-stroke outcome for people with severe motor impairment, as both clinical tests and corticospinal tract (CST) microstructure may not reliably indicate severe motor impairment. Here, we test whether imaging biomarkers beyond the CST relate to severe upper limb impairment post-stroke by evaluating white matter microstructure in the corpus callosum (CC). In an international, multisite hypothesis-generating observational study we determined if: a) CST asymmetry index can differentiate between individuals with mild-moderate and severe upper limb impairment; and b) CC biomarkers relate to upper limb impairment within individuals with severe impairment post-stroke. We hypothesised that CST asymmetry index would differentiate between mild-moderate and severe impairment, but CC microstructure would relate to motor outcome for individuals with severe upper limb impairment. METHODS: Seven cohorts with individual diffusion imaging and motor impairment (Fugl Meyer-Upper Limb) data were pooled. Hand-drawn regions-of-interest were used to seed probabilistic tractography for CST (ipsilesional/contralesional) and CC (prefrontal/premotor/motor/sensory/posterior) tracts. Our main imaging measure was mean fractional anisotropy. Linear mixed-effect regression explored relationships between candidate biomarkers and motor impairment, controlling for observations nested within cohorts, as well as age, sex, time post-stroke and lesion volume. RESULTS: Data from 110 individuals (30 mild-moderate, 80 with severe motor impairment) were included. In the full sample, greater CST asymmetry index (i.e., lower fractional anisotropy in the ipsilesional hemisphere, p<.001) and larger lesion volume (p=.139) were negatively related to impairment. In the severe subgroup, CST asymmetry index was not reliably associated with impairment across models. Instead, lesion volume and CC microstructure explained impairment in the severe group beyond CST asymmetry index (p's<.010). CONCLUSIONS: Within a large cohort of individuals with severe upper limb impairment, CC microstructure related to motor outcome post-stroke. Our findings demonstrate that CST microstructure does relate to upper limb outcome across the full range of motor impairment but was not reliably associated within the severe subgroup. Therefore, CC microstructure may provide a promising biomarker for severe upper limb outcome post-stroke, which may advance our ability to predict recovery in people with severe motor impairment after stroke.

Perceived effort for reaching is associated with self-reported fatigue.

Perceived effort for goal-directed reaching may be impacted by the level of self-reported fatigue, however, the relationship between self-reported fatigue and perceived effort has not been examined. We examined how perceived effort changed under varied reach conditions and the relationship between fatigue, perceived effort and reach performance. Twenty-three young adults performed reach actions toward 9 different targets on a digitizing tablet. Perceived effort was measured using the Borg Rate of Perceived Exertion and Paas Mental Effort Rating Scale. Self-reported fatigue was quantified using the Fatigue Scales for Motor and Cognitive Functions. As reach conditions became more difficult, perceived effort increased significantly. Further, individuals who reported greater fatigue also reported greater perceived effort and showed greater endpoint error during reaching.

Scaling of Joint Motion and Muscle Activation for 3-Dimensional Control of Reach Extent.

This study investigated the scaling of upper arm kinematics, joint motion, and muscle activation for three-dimensional (3D) reaches to targets of increasing distance. Fifteen participants completed 108 total reaches to targets placed 7, 14, and 21 cm across midline. Peak velocity, acceleration, and time to peak velocity scaled to both target and movement distance. Shoulder and elbow excursion scaled to target distance and were highly coordinated. Anterior deltoid activation scaled to both target and movement distance in the early and late phases of reach control. Biceps and triceps activation scaled to movement distance primarily in the late phase. Scaling of these outcome variables provides a model for understanding the control of reach distance in a 3D environment.

Upper and Lower Limb Motor Function Correlates with Ipsilesional Corticospinal Tract and Red Nucleus Structural Integrity in Chronic Stroke: A Cross-Sectional, ROI-Based MRI Study.

BACKGROUND: Structural integrity of the ipsilesional corticospinal tract (CST) is important for upper limb motor recovery after stroke. However, additional neuromechanisms associated with motor function poststroke are less well understood, especially regarding the lower limb. OBJECTIVE: To investigate the neural basis of upper/lower limb motor deficits poststroke by correlating measures of motor function with diffusion tensor imaging-derived indices of white matter integrity (fractional anisotropy (FA), mean diffusivity (MD)) in primary and secondary motor tracts/structures. METHODS: Forty-three individuals with chronic stroke (time poststroke, 64.4 ± 58.8 months) underwent a comprehensive motor assessment and MRI scanning. Correlation and multiple regression analyses were performed to examine relationships between FA/MD in a priori motor tracts/structures and motor function. RESULTS: FA in the ipsilesional CST and red nucleus (RN) was positively correlated with motor function of both the affected upper and lower limb (r = 0.36-0.55, p ≤ 0.01), while only ipsilesional RN FA was associated with gait speed (r = 0.50). Ipsilesional CST FA explained 37.3% of the variance in grip strength (p < 0.001) and 31.5% of the variance in Arm Motricity Index (p = 0.004). Measures of MD were not predictors of motor performance. CONCLUSIONS: Microstructural integrity of the ipsilesional CST is associated with both upper and lower limb motor function poststroke, but appears less important for gait speed. Integrity of the ipsilesional RN was also associated with motor performance, suggesting increased contributions from secondary motor areas may play a role in supporting chronic motor function and could become a target for interventions.

Comparison of corticospinal tract integrity measures extracted from standard versus native space in chronic stroke.

BACKGROUND: Fractional anisotropy (FA) and mean diffusivity (MD) are measures derived from diffusion-weighted imaging that represent the integrity of the corticospinal tract (CST) after stroke. Some studies of the motor system after stroke extract FA and MD from native space while others extract from standard space making comparison across studies challenging. NEW METHOD: The purpose was to compare CST integrity measures extracted from standard versus native space in individuals with chronic stroke. Twenty-four individuals with stroke underwent diffusion-weighted imaging and motor impairment assessment. The spatial location of the CST was identified using four commonly utilized approaches; therefore, our results are applicable to a variety of approaches. RESULTS: FA extracted from standard space (FAstd) was significantly different from FA extracted from native space (FAnat) for all four approaches; FAstd was greater than FAnat for three approaches. The relationship between ipsilesional CST FA and UE FM was significant for all approaches and similar regardless of extraction space. MDstd was significantly different from MDnat for most approaches, however, the directionality of the differences was not consistent. COMPARISON WITH EXISTING METHOD(S): Our study shows that extraction space influences diffusion-based microstructural integrity values (FA and MD) of the CST in individuals with stroke, which is important when considering methods for aggregating CST integrity data across studies. The relationship between CST integrity and motor impairment appears to be robust to extraction space. CONCLUSIONS: The differences we identified are important for comparing FA and MD values across studies that use different extraction space. Our results provide context for future meta-analyses of diffusion-based metrics of CST integrity in individuals with stroke.

Feasibility of integrating survivors of stroke into cardiac rehabilitation: A mixed methods pilot study.

BACKGROUND: Survivors of stroke are often deconditioned and have limited opportunities for exercise post-rehabilitation. Cardiac Rehabilitation (CR), a structured exercise program offered post-cardiac event in the United States (U.S.), may provide an opportunity for continued exercise. The purpose of this study was to examine the feasibility of integrating survivors of stroke into an existing, hospital-based CR program through an assessment of (1) recruitment, uptake and retention, (2) adherence and fidelity, (3) acceptability and (4) safety. METHODS: A mixed methods design combined a single group, pre-post design, pilot feasibility study with an imbedded qualitative inquiry. Survivors of stroke were recruited into a standard 12-week, 36 visit CR program. RESULTS: Fifty-three survivors were referred, 29 started and 24 completed the program. Program uptake rate was 55% and completion rate was 83%. Eleven completers and one non-completer participated in the qualitative interviews. Program completers attended an average of 25.25 (SD 5.82) sessions with an average of 38.93 (SD 5.64) exercise minutes per session while reaching targeted rate of perceived exertion levels. Qualitative themes included perceived benefits of an individualized program in a group setting, positive interactions with qualified staff, opportunities for socialization, and regular monitoring and staff attentiveness promoting feelings of safety. CONCLUSIONS: Survivors of stroke were able to meet Medicare standard dosage (frequency and session duration) and rate of perceived intensity goals, and perceived the program as needed regardless of their mobility limitations or previous exercise experience. Primary challenges included managing referrals and uptake. Results support feasibility and benefit for survivors to integrate into U.S. CR programs.

Predictors of Daily Steps at 1-Year Poststroke: A Secondary Analysis of a Randomized Controlled Trial.

Background and Purpose: Walking has the potential to improve endurance and community participation after stroke. Obtaining ≥6000 daily steps can decrease subsequent stroke risk. Early identification of those prone to low daily steps could facilitate interventions that lead to increased walking and improved health. The purpose of this study was to (1) determine which factors at 2 months poststroke can predict daily step counts at 1 year and (2) determine what step count at 2 months corresponds to obtaining ≥6000 daily steps at 1-year poststroke. Methods: This was a secondary analysis of data from the Locomotor Experience Applied Post Stroke trial, which enrolled participants with walking speeds <0.80 m/second at 2 months poststroke. Daily steps were assessed at 2 months and 1-year poststroke. Linear regression was used to predict daily step counts at 1 year based on factors including age, sex, race and/or ethnicity, stroke severity, walking speed, endurance, fitness, motor function, balance, and balance confidence. A receiver operating characteristic curve determined which step count corresponded to reaching ≥6000 steps at 1 year. Results: Data from 206 participants, mean age=63 (13) years, 43% female, mean baseline daily step count=2922 (2749) steps, were analyzed. The final model to predict daily steps at 1 year poststroke contained daily steps at 2 months and balance (Berg Balance Scale score); these factors explained 38% of the variability in daily steps at 1 year (P≤0.001). Participants obtaining ≥1632 daily steps at 2 months were 1.86 (95% CI, 1.52­2.27) times more likely to reach ≥6000 daily steps at 1-year poststroke. Conclusions: Daily steps and balance at 2 months poststroke were the strongest predictors of future daily steps. Improving daily physical activity and targeting balance early after stroke may be necessary to increase physical activity at 1-year poststroke.

Integrating Survivors of Stroke Into Exercise-Based Cardiac Rehabilitation Improves Endurance and Functional Strength.

Background Cardiac rehabilitation (CR) is a structured exercise program prevalent in the United States for people with cardiovascular disease that has been shown to increase cardiovascular endurance and improve quality of life. Despite similar cardiovascular risk factors, stroke is not among the covered diagnoses for CR. The purpose of this study was to examine the participant impact of integrating survivors of stroke into the exercise portion of an existing hospital-based CR program through measures of physical function and other health impacts and through qualitative evaluation of participant perception. Methods and Results Subacute and chronic survivors of stroke were integrated into a standard 12-week, 3 sessions per week, exercise-based CR program. A total of 29 began the program, 24 completed the program, and 18 were available for 6-month follow-up. Quantitative measures were compared preprogram with postprogram with t-test or equivalent, and preprogram with postprogram to 6-month follow-up with ANOVA or equivalent. Semistructured interviews were completed with 11 participants postprogram. Exercise-based CR had significant impacts on cardiovascular endurance preprogram to postprogram, with maintenance at 6-month follow-up. The participants improved on the 6-minute walk test on average by 61.92 m(95% CI, 33.99-89.84 m), and maximum metabolic equivalents improved by a median of 3.6 (interquartile range, 2.35). Five times sit to stand (functional strength) improved preprogram to postprogram by a median of 2.85 s (interquartile range, 4.03 s). Qualitative findings highlight additional health improvements. Most participants (83% [15/18]) reported continued exercise at follow-up. Conclusions Exercise-based CR has the potential to improve cardiovascular endurance, health status, and quality of life for survivors of stroke. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03706105.

Test-retest reliability and minimal detectable change of corticospinal tract integrity in chronic stroke.

Diffusion tensor imaging (DTI) can be used to index white matter integrity of the corticospinal tract (CST) after stroke; however, the psychometric properties of DTI-based measures of white matter integrity are unknown. The purpose of this study was to examine test-retest reliability as determined by intraclass correlation coefficients (ICC) and calculate minimal detectable change (MDC) of DTI-based measures of CST integrity using three different approaches: a Cerebral Peduncle approach, a Probabilistic Tract approach, and a Tract Template approach. Eighteen participants with chronic stroke underwent DTI on the same magnetic resonance imaging scanner 4 days apart. For the Cerebral Peduncle approach, a researcher hand drew masks at the cerebral peduncle. For the Probabilistic Tract approach, tractography was seeded in motor areas of the cortex to the cerebral peduncle. For the Tract Template approach, a standard CST template was transformed into native space. For all approaches, the researcher performing analyses was blind to participant number and day of data collection. All three approaches had good to excellent test-retest reliability for fractional anisotropy (FA; ICCs >0.786). Mean diffusivity, axial diffusivity, and radial diffusivity were less reliable than FA. The ICC values were highest and MDC values were the smallest for the most automated approach (Tract Template), followed by the combined manual/automated approach (Probabilistic Tract) then the manual approach (Cerebral Peduncle). The results of this study may have implications for how DTI-based measures of CST integrity are used to define impairment, predict outcomes, and interpret change after stroke.

The six-minute walk test as a fall risk screening tool in community programs for persons with stroke: a cross-sectional analysis.

Background and Purpose: Persons with stroke have increased risk for recurrent stroke. Group exercise programs like cardiac rehabilitation might reduce this risk. These programs commonly use the six-minute walk test to measure aerobic capacity. However, failure to assess fall risk may compromise safety for persons with stroke. The study aim was to determine the association between the six-minute walk test and fall risk in persons with stroke.Methods: Cross-sectional analysis measured the association between the six-minute walk test and fall risk in 66 persons with stroke with a mean age of 66 years (SD 12) and median stroke chronicity of 60.9 months (range 6.0-272.1). The six-minute walk test was evaluated using logistic regression. The best fit model was used in Receiver Operating Characteristic analysis. Likelihood ratios and post-test probabilities were calculated.Results: Lower six-minute walk test distance was associated with increased fall risk in logistic regression (p = .002). The area under the curve for the univariate six-minute walk test model (best fit) was 0.701 (p = .006). The cutoff for increased fall risk was six-minute walk test <331.65 m. The post-test probability of fall risk increased to 74.3% from a pre-test probability of 59.1%.Discussion: The moderate association between fall risk and six-minute walk test suggests that in addition to assessing capacity, the six-minute walk test provides insight into fall risk/balance confidence.Conclusion: Using the six-minute walk test cutoff to screen fall risk in community exercise programs may enhance safety for persons with stroke without additional testing required.

Poststroke Fatigue Is Related to Motor and Cognitive Performance: A Secondary Analysis.

BACKGROUND AND PURPOSE: Poststroke fatigue (PSF) is a common debilitating and persistent symptom after stroke. The relationship between PSF and motor and cognitive function remains inconclusive partly due to lack of control for effects of depression and use of insensitive measures. We examined the relationship between PSF and motor and cognitive performance using a comprehensive set of behavioral measures and excluding individuals with depression. METHODS: Fifty-three individuals poststroke (16 female) were included (median age: 63 years, median months poststroke: 20 months). Poststroke fatigue was quantified using the Fatigue Severity Scale (FSS) and cognitive performance was measured with the Montreal Cognitive Assessment, simple and choice reaction time (SRT and CRT) tasks. Lower extremity motor performance included Fugl-Meyer Motor Assessment, 5 times sit-to-stand test (5 × STS), Berg Balance Scale, Functional Ambulation Category, and gait speed. Upper extremity motor performance was indexed with Fugl-Meyer, grip strength, and Box and Block test. Spearman correlation and stepwise linear regression analyses were performed to examine relationships. RESULTS: Two motor performance measures, Berg Balance Scale and Functional Ambulation Category, were significantly correlated with FSS (ρ = -0.31 and -0.27, respectively) while all cognitive measures were significantly correlated with FSS (ρ = -0.28 for Montreal Cognitive Assessment, 0.29 for SRT, and 0.29 for CRT). Regression analysis showed that Berg Balance Scale was the only significant determinant for FSS (R = 0.11). DISCUSSION AND CONCLUSIONS: Functional gait, balance, and cognitive performance are associated with PSF. Fatigue should be considered when planning and delivering interventions for individuals with stroke. Future studies are needed to explore the potential efficacy of balance and cognitive training in PSF management.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A287).

The Neurological Exercise Training (NExT) program: A pilot study of a community exercise program for survivors of stroke.

BACKGROUND: Many survivors of stroke face chronic disability and increased risk for recurrent stroke. Regular physical activity can reduce these risk factors and improve cardiovascular fitness. Most survivors of stroke face barriers to exercise, including lack of access to programs; as a result, most are sedentary. OBJECTIVE: Pilot the Neurological Exercise Training (NExT) program or survivors of stroke for attendance, safety, and effectiveness. METHODS: The NExT program was designed to promote self-directed exercise in a safe, accessible environment. Six participants attended as desired during open gym hours over two exercise periods per week totalling 19 weeks. After, participants were encouraged to continue exercise away from the gym for 20 weeks. Practicability of the program was assessed through safety, attendance, exercise intensity, and perception of the program. Pilot effectiveness measures were performed at five time points and effect sizes were generated. RESULTS: Attendance averaged 76% (SD12%) of possible sessions with an average duration of 62 (SD 11.3) minutes. Effectiveness measures had positive effect sizes after 19 weeks of the NExT program, but these benefits were lost after 20-weeks (cohen's d, mobility = 0.67 to -0.22, balance = 0.57 to -1.22, strength = 0.41 to -0.30, endurance = 0.09 to -0.19 and fatigue = 1.02 to -0.57). CONCLUSION: Results demonstrate that a community-based gym that is accessible for survivors of stroke will be well attended and perceived as beneficial. Pilot data suggests positive changes in multiple health domains regardless of the type of exercise self-selected by participants. Offering the gym on a continual basis may maintain gains.

Cortical disconnection of the ipsilesional primary motor cortex is associated with gait speed and upper extremity motor impairment in chronic left hemispheric stroke.

Advances in neuroimaging have enabled the mapping of white matter connections across the entire brain, allowing for a more thorough examination of the extent of white matter disconnection after stroke. To assess how cortical disconnection contributes to motor impairments, we examined the relationship between structural brain connectivity and upper and lower extremity motor function in individuals with chronic stroke. Forty-three participants [mean age: 59.7 (±11.2) years; time poststroke: 64.4 (±58.8) months] underwent clinical motor assessments and MRI scanning. Nonparametric correlation analyses were performed to examine the relationship between structural connectivity amid a subsection of the motor network and upper/lower extremity motor function. Standard multiple linear regression analyses were performed to examine the relationship between cortical necrosis and disconnection of three main cortical areas of motor control [primary motor cortex (M1), premotor cortex (PMC), and supplementary motor area (SMA)] and motor function. Anatomical connectivity between ipsilesional M1/SMA and the (1) cerebral peduncle, (2) thalamus, and (3) red nucleus were significantly correlated with upper and lower extremity motor performance (P ≤ 0.003). M1-M1 interhemispheric connectivity was also significantly correlated with gross manual dexterity of the affected upper extremity (P = 0.001). Regression models with M1 lesion load and M1 disconnection (adjusted for time poststroke) explained a significant amount of variance in upper extremity motor performance (R2  = 0.36-0.46) and gait speed (R2  = 0.46), with M1 disconnection an independent predictor of motor performance. Cortical disconnection, especially of ipsilesional M1, could significantly contribute to variability seen in locomotor and upper extremity motor function and recovery in chronic stroke. Hum Brain Mapp 39:120-132, 2018. © 2017 Wiley Periodicals, Inc.

Within-Session Practice Effects in the Jebsen Hand Function Test (JHFT).

The Jebsen Hand Function Test (JHFT) is a standardized assessment that has been used as a clinical outcome measure. To appropriately interpret the effects of an intervention on hand function (as measured by the JHFT), the extent to which this instrument shows significant practice effects must be quantified. The purpose of this study was to determine whether the JHFT is susceptible to within-session practice effects. The results showed that the dominant and nondominant hands significantly improved on the JHFT and many of its subtests over six consecutive trials. Although practice effects might complicate the interpretation of change due to intervention, we briefly relate our findings to emerging neuropsychological evidence that practice effects may indicate a person's motor learning potential or treatment responsiveness.