ERP study of pre-attentive auditory processing in treatment-refractory schizophrenia Denise L. Milovan, a, * Jacinthe Baribeau, b Robert M. Roth, c and Emmanuel Stip d a Department of Psychology, Concordia University, Centre de Recherche Fernand Seguin, Canada H3A 2B4 b D epartement de Psychologie, Universit e Laval, FAS1020, Centre de Recherche Fernand Seguin, Que., Canada G1K 7P4 c Neuropsychology and Neuroimaging Program, Dartmouth Medical School/DHMC, One Medical Center Drive, Lebanon, NH 03756-0001,USA d D epartement de Psychiatrie, Universit e de Montr eal, Centre de Recherche Fernand Seguin, 7331 Hochelaga, Montreal, Que., Canada H1N 3V2 Accepted 12 February 2004 Available online 9 April 2004 Abstract Event-related potential (ERP) studies have demonstrated impaired auditory sensory processing in patients with schizophrenia, as reflected in abnormal mismatch negativity (MMN). We sought to extend this finding by evaluating MMN in 13 treatment-refractory patients with schizophrenia, and 14 age- and gender-matched healthy controls. Subjects responded to infrequent visual stimulation while ignoring binaurally presented auditory tones. The amplitude and topographical pattern of the MMN were analyzed. The control group presented the expected reduction in the amplitude of the MMN from frontal to central and parietal locations. In comparison, the MMN amplitude was not reduced in the treatment-refractory patients, and was largest at the central-posterior electrode location. In addition, patients displayed larger negativities at left frontal, and left- and right-temporal electrode locations than the control subjects. These findings are consistent with pre-attentive abnormalities in treatment-refractory patients with schizophrenia. Ó 2004 Elsevier Inc. All rights reserved. 1. Introduction Approximately 20–30% of patients with schizophre- nia fail to show a significant reduction of positive or negative symptoms following treatment with neurolep- tics, despite adequate doses equivalent to a minimum of 1000 mg/day of chlorpromazine for at least three 6-week trials. Evidence suggests that treatment-refractory pa- tients differ from treatment-responsive individuals on several clinical characteristics that include a history of at minimum five years of moderately severe illness with persistent positive and negative psychotic symptoms, increased likelihood of aggression or other disruptive behaviors, greater and no period of adequate social functioning or ability to hold a job (Suppes et al., 1999). Few studies have investigated the possible neurobio- logical correlates of treatment-refractoriness in schizo- phrenia. Early descriptions of schizophrenia (Bleuler, 1908) considered attention deficits a central feature of the disorder. Behavioral and ERP studies have sug- gested that schizophrenia is associated with impaired pre-attentive (also called automatic) processing of in- formation (Baribeau, 1986; Cadenhead, Serper, & Braff, 1998). Pre-attentive processing is believed to occur without conscious awareness and without interfering with other ongoing cognitive operations. This contrasts with controlled processing which involve conscious al- location of attention to incoming sensory information. Over the past decade, event-related potentials have been increasingly applied to further evaluate pre-at- tentive processing in schizophrenia. In particular, research has focused on the mismatch negativity (MMN) component of the ERP. The MMN reflects pre-attentive processing of auditory information, and is typically elicited by low probability target stimuli embedded in a sequence of high probability stimuli. Studies of schizophrenia, at central electrode locations, * Corresponding author. Present address: Montreal Neurological Institute, Neuropsychology/Cognitive Neuroscience Unit, Room 276, 3801 University, Montreal, Que., Canada H3A 2B4. E-mail addresses: dmilovan@bic.mni.mcgill.ca (D.L. Milovan), jacinthe.baribeau@psy.ulaval.ca (J. Baribeau), Robert.M.Roth@ Dartmouth.EDU (R.M. Roth), stipe@medclin.umontreal.ca (E. Stip). 0278-2626/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.bandc.2004.02.045 Brain and Cognition 55 (2004) 355–357 www.elsevier.com/locate/b&c