Anatomical and functional predictors of disorientation after first-ever brain damage

•Disorientation is frequent after acute brain lesions, confusional state and dementia.•The mechanisms and anatomical basis of disorientation are poorly understood.•We explored the mechanisms and anatomical basis in a cohort of unselected patients with first-ever brain damage.•Impaired reality filtering and deficient learning are the strongest predictors of disorientation.•Multivariate lesion-symptom mapping identified the orbitofrontal cortex and head of caudate.