Functional neuroanatomy of auditory mismatch processing: an event-related fMRI study of duration-deviant oddballs Ulrich Schall, a, * Patrick Johnston, a Juanita Todd, b Philip B. Ward, c and Patricia T. Michie b a Centre for Mental Health Studies, University of Newcastle, Australia b Functional Neuroimaging Laboratory, School of Behavioural Sciences, University of Newcastle, Australia c Neuroscience Institute of Schizophrenia and Allied Disorders, and School of Psychiatry, University of New South Wales, Australia Received 18 March 2003; revised 12 June 2003; accepted 30 June 2003 Abstract This study was designed to identify the neural networks underlying automatic auditory deviance detection in 10 healthy subjects using functional magnetic resonance imaging. We measured blood oxygenation level-dependent contrasts derived from the comparison of blocks of stimuli presented as a series of standard tones (50 ms duration) alone versus blocks that contained rare duration-deviant tones (100 ms) that were interspersed among a series of frequent standard tones while subjects were watching a silent movie. Possible effects of scanner noise were assessed by a “no tone” condition. In line with previous positron emission tomography and EEG source modeling studies, we found temporal lobe and prefrontal cortical activation that was associated with auditory duration mismatch processing. Data were also analyzed employing an event-related hemodynamic response model, which confirmed activation in response to duration-deviant tones bilaterally in the superior temporal gyrus and prefrontally in the right inferior and middle frontal gyri. In line with previous electrophys- iological reports, mismatch activation of these brain regions was significantly correlated with age. These findings suggest a close relationship of the event-related hemodynamic response pattern with the corresponding electrophysiological activity underlying the event-related “mismatch negativity” potential, a putative measure of auditory sensory memory. © 2003 Elsevier Inc. All rights reserved. Keywords: Auditory information processing; Mismatch negativity (MMN); Auditory sensory memory; Event-related functional magnetic resonance imaging; Temporal lobes; Frontal lobes; Prefrontal cortex; Schizophrenia; Dyslexia Introduction Since auditory information is of a transitory nature, in- tegration across time, extraction of relevant information, and decisions about where attention needs to be directed requires retention in auditory sensory memory for a short period of time (Cowan, 1984). Auditory sensory memory maintains a temporary, contextual history of the acoustic environment and provides the auditory system with a means of monitoring the correspondence between the stored model and the incoming sequence of auditory stimuli (Winkler et al., 1996). Deviations of the incoming sequence from the stored model result in the generation of mismatch negativity (MMN), an event-related potential (ERP) peaking approxi- mately 100 –250 ms after stimulus onset (Fig. 1). MMN therefore relies on a sensory memory trace (that is, the representation of repeated auditory events) and is elic- ited whenever a sound violates the properties encoded in this representation of the repeated sound sequence (Na ¨a ¨- ta ¨nen, 1990; Sams et al., 1993). This process is largely task-independent; hence physical features (i.e., loudness, duration, or pitch) are “automatically” analyzed, i.e., in the absence of attention (Na ¨a ¨ta ¨nen 2000). Largest MMN amplitudes are recorded over the fronto- central scalp areas. Source modeling of the ERP and of the magneto-encephalographic (MEG) counterpart of MMN suggests bilateral generators in the auditory cortices, thus resulting in summation of activity over the fronto-central * Corresponding author. Centre for Mental Health Studies, University of Newcastle, James Fletcher Hospital, Newcastle NSW 2300, Australia. Fax: +61-2-4924 6608. E-mail address: uschall@mail.newcastle.edu.au (U. Schall). NeuroImage 20 (2003) 729 –736 www.elsevier.com/locate/ynimg 1053-8119/$ – see front matter © 2003 Elsevier Inc. All rights reserved. doi:10.1016/S1053-8119(03)00398-7