Functional brain reorganization for hand movement in patients with multiple sclerosis: defining distinct effects of injury and disability

Abstract

Previous work has demonstrated potentially adaptive cortical plasticity that increases with brain injury in patients with multiple sclerosis. However, animal studies showing use-dependent changes in motor cortex organization suggest that functional changes also may occur in response to disability. We therefore wished to test whether brain injury and disability lead to distinguishable patterns of activation with hand movement in patients with multiple sclerosis. By employing a passive as well as an active movement task, we also wished to test whether these changes were independent of voluntary recruitment and thus more likely to reflect true functional reorganization. Fourteen patients [Extended Disability Status Score (EDSS) 0-7.5] with relapsing-remitting multiple sclerosis were selected on the basis of pathology load and hand functional impairment for three study groups: group 1, low diffuse central brain injury (DCBI) as assessed from relative N-acetylaspartate concentration (a marker of axonal integrity) and normal hand function (n = 6); group 2, greater DCBI and normal hand function (n = 4); and group 3, greater DCBI and impaired hand function (n = 4). Functional MRI (fMRI) was used to map brain activation with a four-finger and both one-finger passive and active flexion-extension movement tasks for the three groups. Considering all the patients, we found increased activity in ipsilateral premotor and ipsilateral motor cortex (IMC) and in the ipsilateral inferior parietal lobule with increasing global disability (as assessed from the EDSS score). These changes appear to define true functional reorganization, as fMRI activations in IMC (r = 0.87, P < 0.001) and in the contralateral motor cortex (r = 0.67, P < 0.007) were highly correlated between active and passive single finger movements. We attempted to disambiguate any distinct effects of disability and brain injury by direct contrasts between patients differing predominantly in one or the other. To make these contrasts as powerful as possible, we used impairment of finger tapping as a measure of disability specific to the hand tested. A direct contrast of patients matched for DCBI, but differing in hand disability (group 3 - group 2) showed greater bilateral primary and secondary somatosensory cortex activation with greater disability alone. A contrast matched for hand disability, but differing in DCBI (group 2 - group 1) showed a different pattern of changes with relative ipsilateral premotor cortex and bilateral supplementary motor area activity. We conclude that the pattern of brain activity with finger movements changes both with increasing DCBI and with hand disability in patients with multiple sclerosis, and that these changes are distinct. Those related directly to disability may reflect responses to altered patterns of use. As injury- and disability-related activation changes are found even with passive finger movements, they may reflect true brain reorganization.

Sensorimotor Cortex Gamma-Aminobutyric Acid Concentration Correlates with Impaired Performance in Patients with MS

“…5 Cortical reorganization or adaptation has been found to take place in patients with MS as a compensatory mechanism for functioning. 10,[12][13][14] This reorganization/adaptation is manifested by increased activation, as measured by fMRI, involving a broader range of cortical regions in these patients versus controls. Reddy et al 10 reported increased activation in the ipsilateral sensorimotor cortex with simple hand movements in patients with MS.…”

“…Damage to both GM and WM components of the motor system has been reported in patients with MS. 10,11 Functional imaging studies have suggested that adaptive and/or compensatory mechanisms are involved in the attempt to maintain motor function during disease progression. 10,[12][13][14] These studies generally have demonstrated an increase in the extent of functional cortical activation in patients with MS versus controls during performance of specific tasks; this increased brain activation has been interpreted as cortical reorganization and/or adaptation. Given the role of GABA in other disease processes, we hypothesized that identifying a change in [GABA] within the sensorimotor cortex of patients with MS would provide us with additional information about the ongoing disease process and these compensatory mechanisms.…”

Ankle dorsiflexion as an fMRI paradigm to assay motor control for walking during rehabilitation

“…Future studies of passive ankle dorsiflexion will determine if this paradigm can substitute for voluntary movement in subjects who cannot dorsiflex the ankle. Passive movement has shown some potential in several other neuroimaging studies (Loubinoux et al, 2003;Reddy et al, 2002) with significant correlations between dynamic sensorimotor activations for hand function in bilateral inferior BA 40 and continued gains.…”

Neurorehabilitation in Multiple Sclerosis – Resilience in Practice

“…24,25 Various other MRI studies in MS have indicated recruitment of related brain regions after damage has occurred at a specific lesion. These changes in brain connectivity affect various functions including motor function, cognition and memory.…”