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Low-resolution brain electromagnetic tomography (LORETA) was one of the first attempts to solve both the inverse problem and the reference electrode problem. It is able to localize deep sources as well by minimizing the squared three-dimensional (3D) spatial Laplacian operator to determine the unique solution. In 2001, the authors published the first study that applied LORETA to sleep electroencephalogram (EEG) data. They selected artifact-free epochs with sleep spindles and determined LORETA power in the frequency domain via the EEG cross-spectral matrix. LORETA revealed cortical spindle sources predominantly medially in the frontal and parietal lobe. The cortical generators localized for delta waves in slow-wave sleep (SWS) showed considerable overlap with the spindle generators. LORETA was applied to reveal changes in brain activity due to chronic hypoxia in patients with obstructive sleep apnea syndrome (OSAS).