Remodeling the brain: plastic structural brain changes produced by different motor therapies after stroke

Abstract

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.

Figure 1

Structural brain changes parallel changes in real-world arm use. The change in real-world arm use (a), as measured by the Quality of Movement scale of the MAL, was significantly greater in the CI therapy group compared to the comparison group (F_(1,32)=26.0; P<0.0001). Data shown are mean changes for the group receiving CI therapy (n=16) and the comparison group (n=20) with standard error bars. Similarly, the CI therapy group (b) showed larger increases in gray matter in contralateral sensory motor (SM) areas (P_FWE<0.002), ipsilateral SM areas (P_FWE=0.023), and bilateral hippocampus (P_{FWE ipsilateral}=0.033 and P_{FWE contralateral}<0.005). Data shown are mean changes for each region of interest with standard error bars.

Figure 2

Cortical surface-rendered images of gray matter change. Gray matter increases displayed on a standard brain for the (a) CI therapy group and for the (b) comparison group. Surface rendering was performed with a depth of 20 mm. Color bar values indicate t statistics ranging from 2.2 to 6.7.

Figure 3

Relationship between the magnitude of gray matter increase and the amount of change in real world arm use. The increase in gray matter in the (a) contralateral sensory and motor areas, (b) ipsilateral sensory and motor areas, and (c) hippocampus is significantly correlated with improvements on the Quality of Movement scale of the MAL (rs≥0.45, P≤0.024). CI therapy patients are represented with an “O” (n=12, 15, and 16, respectively) and comparison patients with an “X” (n=13, 20, and 20, respectively).