Myelin status is associated with change in functional mobility following slope walking in people with multiple sclerosis.

BACKGROUND: The level of myelin disruption in multiple sclerosis patients may impact the capacity for training-induced neuroplasticity and the magnitude of therapeutic response to rehabilitation interventions. Downslope walking has been shown to increase functional mobility in individuals with multiple sclerosis, but it is unclear if myelin status influences therapeutic response. OBJECTIVE: The current study aimed to examine the relationship between baseline myelin status and change in functional mobility after a walking intervention. METHODS: The Timed Up and Go test was used to measure functional mobility before and after completion of a repeated, six-session slope walking intervention in 16 participants with relapsing-remitting multiple sclerosis. Multi-component T2 relaxation imaging was used to index myelin water fraction of overall water content in brain tissue compartments. RESULTS: Results demonstrated that the ratio of the myelin water fraction in lesion to normal-appearing white matter (myelin water fraction ratio) significantly predicted 31% of the variance in change in Timed Up and Go score after the downslope walking intervention, where less myelin disruption was associated with greater intervention response. CONCLUSIONS: Myelin water content fraction ratio may offer a neural biomarker of myelin to identify potential responders to interventions targeting functional impairments in multiple sclerosis.

Validation of a short cognitive battery to screen for fitness-to-drive of people with multiple sclerosis.

BACKGROUND AND PURPOSE: Some symptoms of multiple sclerosis (MS) affect driving. In a recent study, performance on five cognitive tests predicted the on-road test performance of individuals with relapsing-remitting MS with 91% accuracy, 70% sensitivity and 97% specificity. However, the accuracy with which the battery will predict the driving performance of a different cohort that includes all types of MS is unknown. METHODS: Participants (n = 118; 48 ± 9 years of age; 97 females) performed a comprehensive off-road evaluation that lasted about 3 h and a standardized on-road test that lasted approximately 45 min over a 2-day period within the same week. Performance on the five cognitive tests was used to predict participants' performance on the standardized on-road test. RESULTS: Performance on the five tests together predicted outcome of the on-road test with 82% accuracy, 42% sensitivity and 90% specificity. CONCLUSIONS: The accuracy of predicting the on-road performance of a new MS cohort using performance on the battery of five cognitive tests remained very high (82%). The battery, which was administrable in <45 min and cost ~$150, was better at identifying those who actually passed the on-road test (90% specificity). The sensitivity (42%) of the battery indicated that it should not be used as the sole determinant of poor driving-related cognitive skills. A fail performance on the battery should only imply that more comprehensive testing is warranted.

United States (US) multi-center study to assess the validity and reliability of the Spinal Cord Independence Measure (SCIM III).

STUDY DESIGN: Multi-center, prospective, cohort study. OBJECTIVES: To assess the validity and reliability of the Spinal Cord Independence Measure (SCIM III) in measuring functional ability in persons with spinal cord injury (SCI). SETTING: Inpatient rehabilitation hospitals in the United States (US). METHODS: Functional ability was measured with the SCIM III during the first week of admittance into inpatient acute rehabilitation and within one week of discharge from the same rehabilitation program. Motor and sensory neurologic impairment was measured with the American Spinal Injury Association Impairment Scale. The Functional Independence Measure (FIM), the default functional measure currently used in most US hospitals, was used as a comparison standard for the SCIM III. Statistical analyses were used to test the validity and reliability of the SCIM III. RESULTS: Total agreement between raters was above 70% on most SCIM III tasks and all κ-coefficients were statistically significant (P<0.001). The coefficients of Pearson correlation between the paired raters were above 0.81 and intraclass correlation coefficients were above 0.81. Cronbach's-α was above 0.7, with the exception of the respiration task. The coefficient of Pearson correlation between the FIM and SCIM III was 0.8 (P<0.001). For the respiration and sphincter management subscale, the SCIM III was more responsive to change, than the FIM (P<0.0001). CONCLUSION: Overall, the SCIM III is a reliable and valid measure of functional change in SCI. However, improved scoring instructions and a few modifications to the scoring categories may reduce variability between raters and enhance clinical utility.

Target-, limb-, and context-dependent neural activity in the cingulate and supplementary motor areas of the monkey.

Very little is known about the role of the cingulate motor area (CMA) in visually guided reaching compared to other cortical motor areas. To investigate the hierarchical role of the caudal CMA (CMAc) during reaching we recorded the activity of neurons in CMAc in comparison to the supplementary motor area proper (SMA) while a monkey performed an instructed delay task that required it to position a cursor over visual targets on a computer screen using two-dimensional (2D) joystick movements. The direction of the monkey's arm movement was dissociated from the direction of the visual target by periodically reversing the relationship between the direction of movement of the joystick and that of the cursor. Neurons that responded maximally with a particular limb movement direction regardless of target location were classified as limb-dependent, whereas neurons that responded maximally to a particular target direction regardless of the direction of limb movement were classified as target-dependent. Neurons whose activity was directional in one of the two visuomotor mapping conditions and non-directional or inactive in the other were categorized as context-dependent. Limb-dependent activity was observed more frequently than target-dependent activity in both CMAc and SMA proper during both the delay period (preparatory activity; CMAc, 17%; SMA, 31%) and during movement execution (CMAc, 49%, SMA, 48%). A modest percentage of neurons with preparatory activity were target-dependent in both CMAc (11%) and SMA proper (8%) and a similar percentage of neurons in both areas demonstrated target-dependent, movement activity (CMAc, 8%; SMA, 10%). The surprising finding was that a very large percentage of neurons in both areas displayed context-dependent activity either during the preparatory (CMAc, 72%; SMA, 61%) or movement (CMAc, 43%, SMA 42%) epochs of the task. These results show that neural activity in both CMAc and SMA can directly represent movement direction in either limb-centered or target-centered coordinates. The presence of target-dependent activity in CMAc, as well as SMA, suggests that both are involved in the transformation of visual target information into appropriate motor commands. Target-dependent activity has been found in the putamen, SMA, CMAc, dorsal and ventral premotor cortex, as well as primary motor cortex. This indicates that the visuomotor transformations required for visually guided reaching are carried out by a distributed network of interconnected motor areas. The large proportion of neurons with context-dependent activity suggests, however, that while both CMAc and SMA may play a role in the visuomotor transformation of target information into movement parameters, their activity is not solely coding parameters of movement, since their involvement in this process is highly condition-dependent.

Neural activity correlated with the preparation and execution of visually guided arm movements in the cingulate motor area of the monkey.

Recent anatomical and physiological studies have suggested that parts of the cingulate cortex are involved in the control of movement. These areas have been collectively termed the cingulate motor area (CMA). Currently almost nothing is known, however, about how neurons in the CMA actually participate in the control of movement. Therefore, we investigated the role of cells in the dorsal and ventral banks of the CMA (CMAd and CMAv, respectively) in the preparation and execution of visually guided arm movements. We recorded the activity of neurons while a monkey performed a visually guided, two-dimensional instructed delay task. A monkey was required to operate a joystick that moved a cursor from a centrally located hold target to one of four peripheral targets. Neurons were classified as exhibiting preparatory activity if the neural discharge during the postinstruction delay period was significantly higher than the preinstruction activity. Neurons were classified as exhibiting movement activity if the neural discharge was significantly elevated around the time of the movement. Of the 115 task-related neurons studied, 18 (16%) exhibited only preparatory activity, 48 (42%) exhibited only movement activity, and 49 (43%) exhibited both preparatory and movement activity. Neurons were further classified in terms of their directional tuning. For 51% of neurons with preparatory activity, that activity was directional. A significantly larger proportion of movement-related activity was directional (78%). For neurons with both directional preparatory and movement activity, the preferred directions were highly correlated (r=0.83). The median onset of movement activity was 10 ms before the beginning of movement (range -200 to 200 ms). The patterns and directionality of task-related activity of CMA neurons observed in this study are similar to those previously reported for other cortical motor areas. Together, these data provide preliminary evidence that neurons in CMAd and CMAv play a role in both the preparation and execution of visually guided arm movements.