Constraint-induced movement therapy (CIMT) is a physical rehabilitation regime that has been previously shown to improve motor function in chronic hemiparetic stroke patients. However, the neural mechanisms supporting rehabilitation-induced motor recovery are poorly understood. The goal of this study was to assess motor cortical reorganization after CIMT using functional magnetic resonance imaging (fMRI). In a repeated-measures design, 4 incompletely recovered chronic stroke patients treated with CIMT underwent motor function testing and fMRI. Five age-matched normal subjects were also imaged. A laterality index (LI) was determined from the fMRI data, reflecting the distribution of activation in motor cortices contralateral compared with ipsilateral to the moving hand. Pre-intervention fMRI showed a lower LI during affected hand movement of stroke patients (LI = 0.23+/-0.07) compared to controls (LI unaffected patient hand = 0.65+/-0.10; LI dominant normal hand = 0.65+/-0.11; LI nondominant normal hand = 0.69+/-0.11; P < 0.05) due to trends toward increased ipsilateral motor cortical activation. Motor function testing showed that patients made significant gains in functional use of the stroke-affected upper extremity (detected by the Motor Activity Log) and significant reductions in motor impairment (detected by the Fugl-Meyer Stroke Scale and the Wolf Motor Function Test) immediately after CIMT, and these effects persisted at 6-month follow-up. The behavioral effects of CIMT were associated with a trend toward a reduced LI from pre-intervention to immediately post-intervention (LI = -0.01+/-0.06, P = 0.077) and 6 months post-intervention (LI = -0.03+/-0.15). Stroke-affected hand movement was not accompanied by mirror movements during fMRI, and electromyographic measures of mirror recruitment under simulated fMRI conditions were not correlated with LI values. These data provide preliminary evidence that gains in motor function produced by CIMT in chronic stroke patients may be associated with a shift in laterality of motor cortical activation toward the undamaged hemisphere.

Quantitative oxygen extraction fraction (OEF) in cortical veins was studied in patients with multiple sclerosis (MS) and healthy subjects via magnetic resonance imaging (MRI) phase images at 7 Tesla (7 T). Flow-compensated, three-dimensional gradient-echo scans were acquired for absolute OEF quantification in 23 patients with MS and 14 age-matched controls. In patients, we collected T2*-weighted images for characterization of white matter, deep gray matter, and cortical lesions, and also assessed cognitive function. Variability of OEF across readers and scan sessions was evaluated in a subset of volunteers. OEF was averaged from 2 to 3 pial veins in the sensorimotor, parietal, and prefrontal cortical regions for each subject (total of ~10 vessels). We observed good reproducibility of mean OEF, with intraobserver coefficient of variation (COV)=2.1%, interobserver COV=5.2%, and scan-rescan COV=5.9%. Patients exhibited a 3.4% reduction in cortical OEF relative to controls (P=0.0025), which was not different across brain regions. Although oxygenation did not relate with measures of structural tissue damage, mean OEF correlated with a global measure of information processing speed. These findings suggest that cortical OEF from 7-T MRI phase is a reproducible metabolic biomarker that may be sensitive to different pathologic processes than structural MRI in patients with MS.