Mismatch negativity to pitch change: varied stimulus proportions in controlling effects of neural refractoriness on human auditory event- related brain potentials Thomas Jacobsen a, * , Erich Schro ¨ger a , Thorsten Horenkamp a , Istva ´n Winkler b a Institut fu ¨r Allgemeine Psychologie, Universita ¨t Leipzig, Seeburgstrasse 14-20, 04103 Leipzig, Germany b Institute for Psychology, Hungarian Academy of Sciences, P.O. Box 398, Szondi u. 83-85, H-1394 Budapest, Hungary Received 27 December 2002; received in revised form 23 March 2003; accepted 25 March 2003 Abstract Based on a memory-comparison process, changes in the pitch of repetitive sounds are pre-attentively detected, reflected by the mismatch negativity (MMN) event-related brain potential (ERP). In such oddball sequences, ERP responses are also affected by differential refractory states of frequency-specific afferent cortical neurons. This contamination of MMN can be controlled using an additional blocked sequence of equiprobable tones. The present study investigated effects of varying the in-sequence probabilities of these control tones from 10 to 45%, respectively. Results showed that an equal distribution of all control-sequence tones is not necessary for efficiently removing neural refractoriness effects on the ERPs. The genuine memory-comparison-based frequency-change MMN can be estimated using sequences, within which the number of equiprobable control tones varies between three and nine. q 2003 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Event-related brain potentials; Mismatch negativity; Change-detection; Auditory sensory memory; Neural refractory states; Cognitive electrophysiology The aim of the present study was to further develop a method for measuring memory-based detection of pitch deviants. When sequentially presented auditory stimuli have a uniform pitch, deviations from the constant pitch are pre- attentively detected, as reflected by the mismatch negativity (MMN) component of the event-related brain potential (ERP) [6]. Typically, frequency-change MMN is investi- gated by comparing the ERP elicited by the frequent (standard) and the infrequent (deviant) stimuli presented in an oddball sequence. For a wide range of stimuli, there is evidence that MMN is elicited when some discrepancy is detected between the incoming stimulus and the represen- tation of the regularities of the recent stimulation [10], reflecting the operation of a memory-based comparison mechanism [4,9]. An alternative hypothesis regarding the generation of the frequency-change MMN also deserves discussion. Stimulus repetition leads to repeated activation of a given pattern of activity of the frequency-specific neurons [11], the intensity of which decreases as a function of the repetition rate [2,8, 12]. This response decrement is caused by increasing refractoriness of the frequency-specific neurons [1]. Thus, in the traditional oddball protocol of frequency deviation, the frequency-specific neural activation elicited by the standard stimuli is weaker than that by the deviant stimuli, leading to different ERP responses to standard and deviant stimuli on the basis of differential states of neural refractoriness. Consequently, the commonly used deviant minus standard ERP difference might overestimate the ERP effects of memory-based processes, because of the refractoriness contribution [5,14]. Genuine MMN to pitch change can be estimated using a controlled protocol [3]. An additional blocked control sequence comprised of equiprobable tones (one of them identical to the deviant) which have the same probability of occurrence as the deviant in the oddball sequence is employed. Then, MMN is assessed by comparing the deviant to a physically identical tone with 0304-3940/03/$ - see front matter q 2003 Elsevier Science Ireland Ltd. All rights reserved. doi:10.1016/S0304-3940(03)00408-7 Neuroscience Letters 344 (2003) 79–82 www.elsevier.com/locate/neulet * Corresponding author. BioCog – Cognitive & Biological Psychology, Institut fu ¨r Allgemeine Psychologie, Universita ¨t Leipzig, Seeburgstrasse 14-20, 04103 Leipzig, Germany. Tel.: þ 49-341-97-35-907; fax: þ 49-341- 97-35-969. E-mail address: jacobsen@uni-leipzig.de (T. Jacobsen).