17 GENERAL INTRODUCTION, AIMS & OUTLINE 1 A properties. About every 1-3 seconds, a functional image is captured, which covers the entire brain (see Figure 3A, row 2-3), and measures the blood-oxygen level dependent (BOLD) signal. Varying intensity of the BOLD-signal indirectly quantifies cerebral activity. With task-based fMRI, a participant performs a task while functional images are obtained. This can provide insight into how the brain functions during a particular task. In order to discern activity related to a specific aspect of a task, and to prevent unwanted influence of unrelated factors and noise, conditions are usually repeated many times and contrasted against each other. Activity is typically quantified as the intensity of the BOLD signal of one condition relative to that of another condition (e.g. a left vs. a right button press). The resulting activation maps show what brain areas were more active during condition A vs. condition B (see Figure 3A, row 4). Functional images have considerably lower spatial resolution than the structural image. It is therefore common practice to also obtain a structural image, which can be used to localize the activity to specific brain areas. Activation maps of each individual subject will be registered to a standard space, after which they can be used for group level analyses: to identify shared activity (see Figure 3C), or to compare brain function between groups or time points. Specific multidisciplinary out-patient rehabilitation Despite the high incidence of NA, 3 and the fact that many patients suffer from debilitating residual symptoms, 8 there were no randomized controlled trials investigating rehabilitation treatments when we started the work described in this thesis. 6 Experts at the Radboud University Medical Center (Radboudumc) have developed a specific multidisciplinary out-patient rehabilitation program for NA patients with residual motor dysfunction. This approach has rendered promising results in the Radboudumc’ expert clinic, and was able to improve functional capability of the upper extremity, as measured with the Shoulder Rating Questionnaire – Dutch Language Version (SRQ-DLV) 34 and the Disabilities of Arm Shoulder and Hand (DASH) questionnaire35 in 8 patients in a pilot study. 1, 36 The program starts with a visit to the out-patient Plexus Clinic, where the patient is examined by a neurologist, a physical therapist, an occupational therapist, and a rehabilitation physician. At the end of this visit, the multidisciplinary expert team shares their diagnosis and personalized treatment advice with the patient. This treatment advice will be implemented over the following 16 weeks in 8 two-hour sessions (one hour of physical therapy, one hour of occupational therapy each). The treatment advice and subsequent treatment cover the different components in the model depicted in Figure 4. 1, 6 Although the coverage of the different components depends on the individual patient’s needs, there are two central elements. First, occupational therapy focusses on increasing self-management (e.g. through energy conservation strategies) to improve activities of daily life. 37 Second, physical therapy focusses on improving scapular stability and coordination through relearning motor control. 38, 39 We hypothesize that this motor relearning approach might be targeting cerebral sensorimotor processes that may play a role in persistent motor dysfunction after peripheral nerve injury in NA.