[en] H(2)(15)O-PET was used to investigate changes in regional cerebral blood flow in response to auditory stimulation in patients in the vegetative state. Five patients in a vegetative state of hypoxic origin were compared with 18 age-matched controls. In addition, the cerebral metabolism of these patients and 53 age-matched controls was studied using [(18)F]fluorodeoxyglucose. In control subjects, auditory click stimuli activated bilateral auditory cortices [Brodmann areas (BA) 41 and 42] and the contralateral auditory association cortices (BA 22). In the patients, although resting metabolism was decreased to 61% of normal values, bilateral auditory areas 41 and 42 showed activation as seen in the controls, but the temporoparietal junction cortex (BA 22) failed to be activated. Moreover, the auditory association cortex was functionally disconnected from the posterior parietal association area (BA 40), the anterior cingulate cortex (BA 24) and the hippocampus, as revealed by psychophysiological interaction analysis. Thus, despite altered resting metabolism, the auditory primary cortices were still activated during external stimulation, whereas hierarchically higher-order multi- modal association areas were not. Such a cascade of functional disconnections along the auditory cortical pathways, from the primary auditory areas to multimodal and limbic areas, suggests that the residual cortical processing observed in the vegetative state cannot lead to the integrative processes that are thought to be necessary for the attainment of the normal level of awareness.