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The thought-translation device (TTD) consists of a training device and spelling program for the completely paralyzed using slow-cortical brain potentials (SCP). During the training phase, the self-regulation of SCPs is learned through visual-auditory feedback and positive reinforcement of SCPs; during the spelling phase, patients select letters or words with their SCPs. A psychophysiological system for detection of cognitive functioning in completely paralyzed patients is an integral part of the TTD. The neurophysiological and anatomical basis of SCP-regulation was investigated by recording of BOLD-response in functional magnetic resonance imaging. Results showed involvement of basal ganglia and premotor cortex for required SCP positivity. The clinical outcome of 11 paralyzed patients using the TTD and quality of life of severely paralyzed patients is described. First attempts to improve learning of brain regulation with transcranial magnetic stimulation were successful.