Victor W. Mark

Remodeling the Brain. Plastic Structural Brain Changes Produced by Different Motor Therapies After Stroke

Background and Purpose— Studies on adult stroke patients have demonstrated functional changes in cortical excitability, metabolic rate, or blood flow after motor therapy, measures that can fluctuate rapidly over time. This study evaluated whether evidence could also be found for structural brain changes during an efficacious rehabilitation program. Methods— Chronic stroke patients were randomly assigned to receive either constraint-induced movement therapy (n=16) or a comparison therapy (n=20). Longitudinal voxel-based morphometry was performed on structural MRI scans obtained immediately before and after patients received therapy. Results— The group receiving constraint-induced movement therapy exhibited far greater improvement in use of the more affected arm in the life situation than the comparison therapy group. Structural brain changes paralleled these improvements in spontaneous use of the more impaired arm for activities of daily living. There were profuse increases in gray matter in sensory and motor areas both contralateral and ipsilateral to the affected arm that were bilaterally symmetrical, as well as bilaterally in the hippocampus. In contrast, the comparison therapy group failed to show gray matter increases. Importantly, the magnitude of the observed gray matter increases was significantly correlated with amount of improvement in real-world arm use. Conclusions— These findings suggest that a previously overlooked type of brain plasticity, structural remodeling of the human brain, is harnessed by constraint-induced movement therapy for a condition once thought to be refractory to treatment: motor deficit in chronic stroke patients.

AutoCITE: Automated Delivery of CI Therapy With Reduced Effort by Therapists

Background and Purpose— To evaluate the effectiveness of a device that automates Constraint-Induced Movement therapy (CI therapy), termed AutoCITE, when only partially supervised by therapists. Methods— Twenty-seven participants with chronic stroke trained with AutoCITE for 3 hours per day for 10 consecutive weekdays. Participants were assigned to 1 of 3 groups in a fixed irregular order (ie, in alternating blocks): supervision from a therapist for 100%, 50%, or 25% of training time. Results— The effect sizes of the treatment gains for the 3 groups on the Motor Activity Log (MAL) were very large and for the Wolf Motor Function Test they were large (all P<0.001) but were not significantly different from one another. Gains were comparable to those previously reported for participants who received an equal amount of standard one-on-one CI therapy without the device. At 1-month and long-term follow-up, gains from pretreatment on the MAL were also significant (P<0.001). Conclusion— These results demonstrate that AutoCITE training with greatly reduced supervision from a therapist is as effective as standard one-on-one CI therapy.

Method for Enhancing Real-World Use of a More Affected Arm in Chronic Stroke Transfer Package of Constraint-Induced Movement Therapy

Background and Purpose— Constraint-induced movement therapy is a set of treatments for rehabilitating motor function after central nervous system damage. We assessed the roles of its 2 main components. Methods— A 2×2 factorial components analysis with random assignment was conducted. The 2 factors were type of training and presence/absence of a set of techniques to facilitate transfer of therapeutic gains from the laboratory to the life situation (Transfer Package; TP). Participants (N=40) were outpatients ≥1-year after stroke with hemiparesis. The different treatments, which in each case targeted the more affected arm, lasted 3.5 hours/d for 10 weekdays. Spontaneous use of the more affected arm in daily life and maximum motor capacity of that arm in the laboratory were assessed with the Motor Activity Log and the Wolf Motor Function Test, respectively. Results— Use of the TP, regardless of the type of training received, resulted in Motor Activity Log gains that were 2.4 times as large as the gains in its absence (P<0.01). These clinical results parallel previously reported effects of the TP on neuroplastic change. Both the TP and training by shaping enhanced gains on the Wolf Motor Function Test (P<0.05). The Motor Activity Log gains were retained without loss 1 year after treatment. An additional substudy (N=10) showed that a single component of the TP, weekly telephone contact with participants for 1 month after treatment, doubled Motor Activity Log scores at 6-month follow-up. Conclusions— The TP is a method for enhancing both spontaneous use of a more affected arm after chronic stroke and its maximum motor capacity. Shaping enhances the latter.

Neurological Principles and Rehabilitation of Action Disorders: Rehabilitation Interventions

This third chapter discusses the evidence for the rehabilitation of the most common movement disorders of the upper extremity. The authors also present a framework, building on the computation, anatomy, and physiology (CAP) model, for incorporating some of the principles discussed in the 2 previous chapters by Frey et al and Sathian et al in the practice of rehabilitation and for discussing potentially helpful interventions based on emergent neuroscience principles.

Atrophy of Spared Gray Matter Tissue Predicts Poorer Motor Recovery and Rehabilitation Response in Chronic Stroke

Background and Purpose— Although the motor deficit after stroke is clearly due to the structural brain damage that has been sustained, this relationship is attenuated from the acute to chronic phases. We investigated the possibility that motor impairment and response to constraint-induced movement therapy in patients with chronic stroke may relate more strongly to the structural integrity of brain structures remote from the lesion than to measures of overt tissue damage. Methods— Voxel-based morphometry analysis was performed on MRI scans from 80 patients with chronic stroke to investigate whether variations in gray matter density were correlated with extent of residual motor impairment or with constraint-induced movement therapy-induced motor recovery. Results— Decreased gray matter density in noninfarcted motor regions was significantly correlated with magnitude of residual motor deficit. In addition, reduced gray matter density in multiple remote brain regions predicted a lesser extent of motor improvement from constraint-induced movement therapy. Conclusions— Atrophy in seemingly healthy parts of the brain that are distant from the infarct accounts for at least a portion of the sustained motor deficit in chronic stroke.

An experimental analysis of factors underlying neglect in line bisection.

The finding that patients with neglect make larger errors when bisecting longer lines could be due to failure to disengage attention from a segment of the line on the ipsilesional side, or to a reduced ability to direct attention and/or action contralaterally. The findings are reported from a patient with left-sided neglect who set the midpoint further away from the right end of lines as their length increased, a finding consistent with the latter interpretation. His errors were significantly related to length and lateral extent of lines presented in left hemispace, but only to length of lines presented in right hemispace.

Biases in Attentional Orientation and Magnitude Estimation Explain Crossover: Neglect is a Disorder of Both

Crossover refers to a pattern of performance on the line bisection test in which short lines are bisected on the side opposite the true center of long lines. Although most patients with spatial neglect demonstrate crossover, contemporary theories of neglect cannot explain it. In contrast, we show that blending the psychophysical construct of magnitude estimation with neglect theory not only explains crossover, but also addresses a quantitative feature of neglect that is independent of spatial deficits. We report a prospective validation study of the orientation/estimation hypothesis of crossover. Forty subjects (17 patients with and without neglect following unilateral brain injury and 23 normal controls) completed four experiments that examined crossover using line bisection, line bisection with cueing, and reproducing line lengths from both memory and a standard. Replicating earlier findings, all except one subject group exhibited crossover on the standard line bisection test, all groups showed a spontaneous preference to orient attention to one end of the lines, and all groups overestimated the length of short lines and underestimated long lines. Biases in attentional orientation and magnitude estimation are exaggerated in patients with neglect. The truly novel finding of this study occurred when, after removing the line from the bisection task, the direction of crossover was completely reversed in all subject groups depending on where attention was oriented. These findings are consistent with our hypothesis of crossover: (1) crossover is a normal component of performance on line bisection; (2) crossover results from the interplay of biases in attentional orientation and magnitude estimation; and (3) attentional orientation predicts the direction of crossover, whereas a disorder of magnitude estimation, not previously emphasized in neglect, accounts for the quantitative changes in length estimation that make crossover more obvious in neglect subjects. Paradoxically, we observed that the traditional line bisection test is suboptimal for exploring crossover because lines elicit spontaneous orientation responses from subjects that confound experimental manipulations of attention. We conclude that attentional orientation and magnitude estimation are necessary and sufficient to explain crossover and that bias in magnitude estimation is a core component of neglect.

Improvement After Constraint-Induced Movement Therapy Is Independent of Infarct Location in Chronic Stroke Patients

Background and Purpose— Disruption of the corticospinal tract at various locations in the brain has been shown to predict worse spontaneous motor recovery after stroke. However, the anatomic specificity of previous findings was limited by the categorical classification of infarct locations. Here we used computational methods to more precisely determine the specific anatomic locations associated with impaired motor ability. More important, however, our study also used these techniques to evaluate whether infarct location could influence motor outcomes after Constraint-Induced Movement therapy (CI therapy), a specific and controlled form of physical therapy. Methods— Quantitative voxel-based analyses were used to determine whether infarct location could predict either initial motor ability or clinical improvement after CI therapy in chronic stroke patients. Results— Although corona radiata infarcts were associated with worse in-laboratory motor ability at pretreatment, infarct location did not predict improvement in either the laboratory or the life situation after CI therapy. Conclusions— The extent of improvement from CI therapy does not depend on the location of neurological damage, despite there being a pretreatment relationship between infarct location and in-laboratory motor ability. This dissociation could be explained by brain plasticity induced by CI therapy.

Bodily neglect and orientational biases in unilateral neglect syndrome and normal subjects

Patients with neglect erred toward the right when attempting to locate the intercepta of their midsagittal planes with a horizontal Une placed in front of them. When control subjects could not see their bodies, they also pointed to the right. While control subjects improved when they were able to see their bodies, neglect subjects did not. When the horizontal line was moved toward the right, both neglect and control subjects increased their rightward pointing errors. However, patients with neglect made greater errors than did controls. When the line was in far left hemispace, controls pointed accurately to their midsagittal planes. The neglect subjects, in contrast, erred toward the left. Our results suggest that patients with neglect from right hemisphere lesions are not only inattentive to their bodies, but are also distracted by extracorporeal stimuli, especially on the right. Our results also suggest that normal subjects have a propensity to orient to or be distracted by stimuli in right hemispace.

Diagonal spatial neglect

OBJECTIVE To determine whether stroke patients with diagonal neglect on cancellation may show diagonal neglect on line bisection, and hence to indicate whether diagonal neglect may be related solely to the type of test used or whether instead it may reflect a fundamental spatial disorder. METHODS Nine patients with subacute right hemispheric stroke who neglected targets primarily in the near left direction on line cancellation bisected diagonal lines of two opposing orientations: near left to far right and far left to near right. The errors were assessed to determine whether line orientation significantly affected bisection error. RESULTS Eight patients had significant bisection errors. One of these showed no effect of line orientation on error, consistent with lateral neglect. The remaining seven patients had a line orientation effect, indicating a net diagonal spatial bias. For the group, cancellation errors were significantly correlated with the line orientation effect on bisection errors. CONCLUSIONS A significant diagonal bias on two tests of spatial attention may appear in stroke patients, although the directions of the biases may differ within individual patients. None the less, diagonal neglect may be a fundamental spatial attentional disturbance of right hemispheric stroke. Greater severity of stroke deficit as indicated by cancellation error score may be associated with a greater degree of diagonal neglect on line bisection.