Orientation in space, time, and person is the essence of the behaving self, and the bedrock of neurological and psychiatric mental status examination. States of disorientation may be the hallmark manifestation of several neuropsychiatric disorders. Despite orientation’s central role in health and disease, orientation has almost never been a subject for neuroscientific research. Consequently, there is uncertainty as to the cognitive and clinical meaning of orientation, and its role in the psychopathology of several major neuropsychiatric disorders, such as dissociative disorders, misidentification syndromes, or Alzheimer’s disease and amnesia syndromes. Here we hypothesize that (1) orientation is a distinct cognitive function and that (2) orientations over the different domains and clinical conditions rely on shared psychological and neural mechanisms. We propose to investigate the ability of humans to orient themselves in time, space and person, based on a unified referential system. We will examine whether orientations in the different domains are placed on a common vectorial trajectory, using mental tasks, functional imaging (with new analyses methods as based on machine learning and networks research) and computational neuroscience in healthy individuals and those affected by disorders of disorientation. While presently we do not have any established definition of the role of orientation in central pathologies our results might therefore define the orientation system and its role in neuropsychiatric disorders in which orientation is disturbed. This may be important for the recent challenge of our orientation system by the cyber world, which changes our habitual relations to space, time, and people. Finally, the study results will be used in order to established neuroimaging based tools for diagnosis, monitoring and management of disorientation disorders such as Alzheimer’s disease and dissociative disorders.