An electrophysiological index of stimulus unfamiliarity KIRK R. DAFFNER, a M. MARSEL MESULAM, b LEONARD F. M. SCINTO, a VIVIAN CALVO, a ROBERT FAUST, a and PHILLIP J. HOLCOMB c a Brigham Behavioral Neurology Group and Laboratory of Higher Cortical Functions, Division of Cognitive and Behavioral Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA b Center for Behavioral and Cognitive Neurology, Northwestern University Medical School, Chicago, Illinois, USA c Department of Psychology, Tufts University, Medford, Massachusetts, USA Abstract This study investigated the functional significance of the N2 response to novel stimuli. In one condition, background, target, and deviant stimuli were simple geometric figures. In a second condition, all stimulus types were unfamiliar 0 unusual figures. In a third condition, background and target stimuli were unusual figures and deviant stimuli were simple shapes. Unusual figures, whether they were deviant, target, or background stimuli, evoked larger N2 responses than their simple, familiar counterparts. N2 elicited by an unusual background stimulus was larger than that evoked by simple, deviant stimuli, a pattern opposite that exhibited by the subsequent P3. Deviance from immediate context had limited influence over N2 amplitude. The results suggest that novelty N2 and novelty P3 reflect the processing of different aspects of “novel” visual stimuli. The novelty P3 is particularly sensitive to deviation from immediate context. In contrast, the novelty N2 is sensitive to deviation from long-term context that renders a stimulus unfamiliar and difficult to encode. Descriptors: ERPs, Novelty processing, Stimulus unfamiliarity, Stimulus deviance, N2, P3 The mammalian brain has evolved to meet the formidable chal- lenge of being able to rapidly process different aspects of novelty. Something can be novel with respect to deviation from a person’s recent experience ~e.g., within the context of an experiment! or total experience ~e.g., determined by events prior to the experi- ment!. The existence of distinct electrophysiological markers of the processing of these various aspects of novelty has yet to be determined. The most commonly studied event-related brain potential ~ ERP! response to novel stimuli is the “novelty P3.” The novelty P3 ~sometimes designated as the P3a! is evoked in all three of the primary sensory modalities in response to infrequent, “novel” stim- uli that deviate from background ~Courchesne, Hillyard, & Galam- bos, 1975; Knight, 1984, 1997; Knight & Nakada, 1998; Knight & Scabini, 1998; Yamaguchi & Knight, 1991!. It has been distin- guished from the target P3 ~ P3b!, which tends to have a more posterior scalp distribution, longer latency, and a sensitivity to stimuli that a subject must detect and either respond to or count ~ Hillyard & Picton, 1987; Picton, 1992; Squires, Squires, & Hill- yard, 1975!. Typically, the novelty P3 is preceded by a large, anteriorly distributed negative wave in the 180–325 ms temporal window that is presumed to be part of the “family” of wave forms designated as the N2. The current study investigated the functional significance of the N2 ~or N200! response to novel visual stimuli, the primary emphasis being on how this component differs from the subsequent novelty P3. Like the P3, the N2 has not been viewed typically as a unitary brain potential, but instead has been characterized as representing various subcomponents, with different functions and underlying cerebral sources ~ Naatanen & Picton, 1986; Pritchard, Shappell, & Brandt, 1991!. For example, in the auditory modality, the N2a ~or mismatch negativity! is elicited automatically, without conscious perception of the evoking stimuli and tends to have a frontocentral maximum, whereas in the visual modality, the N2a is described as “semiautomatic,” evoked by task-irrelevant stimuli in an attended channel, and tends to have a lateral-posterior distribution ~ Ford, Roth, & Kopell, 1976; Naatanen & Gaillard, 1983; Naatanen & Picton, 1986; Naatanen, Simpson, & Loveless, 1982; Ritter, Sim- son, & Vaughan, 1983; Squires et al., 1975!. The N2a is extremely sensitive to stimuli that deviate physically from the immediately preceding context ~Sams, Alho, & Naatanen, 1983, 1984; Ulls- perger, Gille, & Pietschmann, 1985!. The N2b, on the other hand, requires conscious perception of the stimulus and is particularly sensitive to low stimulus probability ~ Naatanen & Gaillard, 1983; Naatanen et al., 1982; Sams et al., 1984; Squires et al., 1975!. The N2b tends to be centered around Cz in both the auditory and visual modalities ~ Ford et al., 1976; Sams et al., 1983; Simson, Vaughan, & Ritter, 1976; Squires et al., 1975!. The N2c also requires con- scious perception of the stimulus and in addition requires that the This research was supported by NIMH grant MH01378. We thank Drs. S. M. Kosslyn, J. F. Kroll, and M. C. Potter for the use of their stimulus sets. We acknowledge Lise Bliss and Barbara Vericker for their expert secretarial and administrative assistance. Address reprint requests to: Kirk R. Daffner, Division of Cognitive and Behavioral Neurology, Brigham and Women’s Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA. E-mail: kdaffner@ partners.org. Psychophysiology, 37 ~2000!, 737–747. Cambridge University Press. Printed in the USA. Copyright © 2000 Society for Psychophysiological Research 737