Objective-Previous research has noted functional and structural temporal lobe abnormalities in schizophrenia that relate to symptoms such as auditory hallucinations and thought disorder. The goal of the study was to determine whether the functional abnormalities are present in schizophrenia at early stages of auditory processing.Method-Functional magnetic resonance imaging activity was examined during the presentation of the mismatch stimuli, which are deviant tones embedded in a series of standard tones. The mismatch stimuli are used to elicit the mismatch negativity, an early auditory event-related potential. Ten patients with schizophrenia and 10 comparison subjects were presented the mismatch stimuli condition and a control condition in which only one tone was presented repeatedly.Results-The superior temporal gyrus showed the most prevalent and consistent activation. The superior temporal gyrus showed less activation in the schizophrenic subjects than in the comparison subjects only during the mismatch stimuli condition.Conclusions-This result is consistent with those of mismatch negativity event-related potential studies and suggests that early auditory processing is abnormal in chronic schizophrenia.The mismatch negativity is a negative-going brain potential elicited between 150 and 250 msec after the presentation of a deviant stimulus within a repetitive pattern (1) and is usually measured by subtracting the level of activity elicited by the standard stimuli from the level of activity elicited by the deviant stimuli. Naatanen and Gaillard (2) proposed that the mismatch negativity was evoked preattentively and that it indexed an echoic memory comparison of a stimulus to the neural trace of previous stimuli (3,4). Thus, the mismatch negativity is the earliest identified cortical event-related potential that is elicited by deviant, infrequent auditory stimuli and that occurs independently of whether or not the stimuli are consciously attended (5).Our laboratory recently used high-density event-related potential recording during a mismatch negativity paradigm and found an event-related potential scalp topography abnormality in schizophrenic subjects that was localized to the parietotemporal junction (6) and that was slightly more pronounced on the left. Mismatch negativity amplitude also correlated with several measures of psychopathology in that study, including the severity of auditory hallucinations. In two studies, no mismatch negativity event-related potential abnormalities were found in patients with schizophrenia at their first hospitalization, indicating a functional abnormality that may develop with disease chronicity (7,8).The current study used functional magnetic resonance imaging (fMRI) to examine brain activity during presentation of the mismatch stimuli to schizophrenic and comparison subjects. Several fMRI studies involving schizophrenic subjects (9) have found abnormal activity in the temporal lobe (as well as other regions) (10-12). The mismatch stimuli and tone repetition condition...