Background: This study focused on frontal dysfunction during a brief visual delayed matching-to-sample (DMS) task in patients with severe obstructive sleep apnea syndrome (OSAS). We also aimed to assess whether mismatch- or match-task would be more sensitive in the evaluation of OSAS frontal impairment and to determine the factors responsible for the association of the task performance and frontal activation. Methods: Nine severe OSAS patients and 9 age-matched healthy subjects were studied with an event-related functional magnetic resonance imaging (fMRI). The performance and activation of frontal region of interests (ROIs) were compared between the two groups. The ROls included anterior cingulate cortices (ACC), anterior prefrontal gyri (aPFG), middle frontal gyri (MFG) and inferior frontal gyri (IFG). The association of reaction time (RTs) and ROIs activation with severe nocturnal hypoxia (as measured by duration of time with oxygen desaturation SaO(2) below 80%) and arousals was estimated. Results: Patients with OSAS showed reduced frontal activation in ACCs, MFGs and IFGs and significantly increased activity in the right aPFG when being involved in mismatch tasks, when compared with healthy subjects. In addition, both the oxygen desaturation duration and arousal index were associated with the slower reaction times (RT) and greater reduction in the frontal activation in ROls for OSAS patients during mismatch information processing. Other OSAS variables, including apneic index (AI), hypopneic index (HI), desaturation index, and the Epworth Sleepiness Scale (ESS), were not associated with changes in ROI response to either mismatch or match tasks. Conclusions: Patients with severe OSAS showed decreased mismatch-related activation in frontal ROls when compared to healthy subjects during a brief visual DMS task. The association of arousal index and severe hypoxia with slow RTs and frontal mismatch-related activation suggests that both hypoxia and sleep fragmentation contributed to frontal dysfunction in OSAS patients. Moreover, the mismatch-related activity is more sensitive than match-related activity in the evaluation of OSAS frontal dysfunction during a brief visual DMS task. (C) 2011 Elsevier B.V. All rights reserved.