Background and Purpose-An investigational trial examined safety and efficacy of targeted subthreshold cortical stimulation in patients with chronic stroke. The anatomical location for the target, hand motor area, varies across subjects, and so was localized with functional MRI (fMRI). This report describes the experience of incorporating standardized fMRI into a multisite stroke trial. Methods-At 3 enrollment centers, patients moved (0.25 Hz) the affected hand during fMRI. Hand motor function was localized at a fourth center guiding intervention for those randomized to stimulation. Results-The fMRI results were available within 24 hours. Across 12 patients, activation site variability was substantial (12, 23, and 11 mm in x, y, and z directions), exceeding stimulating electrode dimensions. Localizing functional areas underlies the effectiveness of some approaches to stroke therapy. Reports in rodents, 1 primates, 2 and humans 3 have described motor gains after introducing such targeted stimulation after stroke. A recent clinical trial examined safety and motor effects of epidural motor cortex stimulation in chronic stroke patients (Lutsep et al, submitted data, 2004).The underlying hypothesis of that trial was that stimulation of hand area of motor cortex, identified using functional MRI (fMRI), would increase physical therapy-derived motor gains. However, published fMRI data acquisition methods vary substantially. To address the hypothesis in the context of a multicenter study, therefore, implementation of a standardized fMRI protocol was necessary. The current report describes the approach and feasibility of this goal. In addition, fMRI examined effects of cortical stimulation on motor system function. To our knowledge, this is the first use of functional neuroimaging to guide decision-making in a stroke trial. Materials and MethodsAt each of 3 medical centers, patients with chronic ischemic stroke and arm paresis underwent fMRI scanning followed by randomization to 3 weeks physical therapy with/without epidural motor cortex stimulation with an investigational device, followed by repeat fMRI. A full report of trial clinical/safety outcomes is reported elsewhere (Lutsep et al, submitted data, 2004).At each site, patients underwent fMRI alternating 20 seconds rest and 20 seconds 0.25-Hz paretic index finger tapping, or, if this task could not be performed, wrist extension. These cycles were repeated for a total of 280 to 300 volumes. Each site used 1.5-T MRI (2ϭGE, 1ϭSiemens), repetition timeϭ2000 ms, echo timeϭ50 ms, in-plane resolution 3.75ϫ3.75 mm, and field of view that included cerebral vertex to Sylvian fissure via 5-mm axial slices (interslice gap 0 to 1 mm).Scans were digitally transmitted to a central laboratory where 2 investigators (R.R.B., V.C.B.) processed the images. Motion correction and in-plane spatial smoothing (6-mm full-width halfmaximum, SPM99) were followed by linear detrending and generation of statistical maps contrasting movement with rest . Within 24 hours, images were reviewed by a si...

Some treatments under development to improve motor outcome after stroke require information about organization of individual subject's brain. The current study aimed to characterize normal inter-subject differences in localization of motor functions, and to consider these findings in relation to a potential treatment of motor deficits after stroke. Functional MRI (fMRI) scanning in 14 subjects examined right index finger tapping, shoulder rotation, or facial movement. The largest activation cluster in left sensorimotor cortex was identified for each task, and its center expressed in Talairach stereotaxic coordinates. Across subjects, each task showed considerable variability in activation site coordinates. For example, during finger tapping, the range for center of activation was 7 mm in the x-axis, 19 mm in the y-axis, and 11 mm in the z-axis. The mean value for center of activation was significantly different for all three coordinates for all pairwise task comparisons. However, the distribution of activation site centers for the finger task overlapped with the other two tasks in the x- and y-axes, and with the shoulder task in the z-axis. On average, the center of activation for the three motor tasks were spatially separated and somatotopically distributed. However, across the population, there was considerable overlap in the center of activation site, especially for finger and shoulder movements. Restorative therapies that aim to target specific body segments, such as the hand, in the post-stroke motor system may need to map the individual brain rather than rely on population averages. Initial details are presented of a study using this approach to evaluate such a therapy.