Localization of Primary Auditory Cortex in Humans by Magnetoencephalography B. Lu ¨ tkenho ¨ner,* K. Krumbholz,* C. Lammertmann,* A. Seither-Preisler,* O. Steinstra ¨ ter,* and R. D. Patterson† *Institute of Experimental Audiology, University Clinic Mu ¨ nster, 48129 Mu ¨ nster, Germany; and †Center for the Neural Basis of Hearing, Department of Physiology, University of Cambridge, Cambridge, United Kingdom Received May 3, 2002 Brief auditory stimuli activate the primary auditory cortex (PAC) earlier than any other cortical area so, within a certain latency range, the PAC is the only cortical source contributing to the auditory evoked field (AEF). Nevertheless, there is no AEF component specific to PAC that can be reliably detected in all individuals. The present study suggests that a peak in the first temporal derivative of the magnetic field at about 20 ms (dP20m) is a genuine correlate of PAC activity. AEFs in response to clicks presented to the right ear were recorded with a 37-channel axial gradi- ometer system positioned over the left hemisphere in nine normal-hearing subjects. More than 8500 stimuli were presented in each of two independent sessions at a rate of approximately 3/s. The dipole coordinates for the dP20m derived from the two sessions typically differed by only a few millimeters. Coregistration of the dipoles with structural magnetic resonance im- ages suggests that dP20m arises from an area close to the retroinsular origin of Heschl’s gyrus. Although the dP20m is simply the point of steepest slope on the well-known middle-latency peak, P30m or Pam, it would appear that dP20m and P30m do not have the same cortical origin. Evidence is provided that P30m receives major contributions from at least two distinct cortical areas, only one of which is PAC. © 2002 Elsevier Science (USA) INTRODUCTION In humans, the primary auditory cortex (PAC) is generally identified with Brodmann (1909) area 41, which is located in the depth of the Sylvian fissure where it occupies a substan- tial part of Heschl’s gyrus. However, recent studies suggest that there is not a strict correspondence between micro- and macroanatomic parcellation in auditory cortex; macroana- tomic landmarks for PAC, like gyral and sulcal borders, do not consistently match areal borders defined cytoarchitec- tonically (Morosan et al., 2001; Rademacher et al., 2001). This finding is of considerable importance for the interpreta- tion of functional investigations of the auditory cortex, since it questions the use of macroanatomic landmarks for assign- ing function to structure. Population maps (Roland and Zilles, 1998) that specify the probability that a certain posi- tion in stereotaxic space is associated with a specific cytoar- chitectonic area represent one approach to this problem. But by their nature, such maps preclude precise conclusions con- cerning individual subjects. In this article, we explore the feasibility of noninvasive labeling of PAC by means of magnetoencephalography (MEG). The primary auditory cortex and the secondary au- ditory projection areas are situated on the superior surface of the temporal lobe, and currents perpendicular to the cortical surface have a more or less tangential orientation with re- spect to the inner surface of the skull. This is fortunate because MEG is most sensitive to currents oriented tangen- tially to the surrounding volume conductor (Ha ¨ma ¨la ¨ inen et al., 1993). Thus, in principle, it should be relatively easy to record the auditory evoked field (AEF) arising from the PAC and thereby determine its location. Experience has shown, however, that the AEF generally exhibits a complicated spa- tiotemporal pattern indicating the presence of several dis- tinct sources. This means that, in practice, the critical tech- nical problem is to identify a component of the AEF that is dominated by activity in PAC and which has minimal contri- butions from other sources. As PAC is activated earlier than any other structure in auditory cortex, the first component of the AEF of cortical origin is the focus of investigation. The latency of the compo- nent can be inferred from intracortical electrical recordings in candidates for surgical treatment of epilepsy. Recordings from the posteromedial part of Heschl’s gyrus (Liegeois- Chauvel et al., 1991) have shown a triphasic response to clicks; the components are labeled according to their polari- ties and peak latencies (in milliseconds) as N13, P17, and N26. The onset of the response varied between 8 and 10 ms. It has been suggested (Steinschneider et al., 1992) that the intracortical N13 represents the initial segment of the earli- est scalp-recorded electrical response of auditory cortex, de- noted N19 or Na. The N19 is a negative deflection with a latency between 16 and 20 ms (Picton et al., 1974; O ¨ zdamar and Kraus, 1983; Scherg and von Cramon, 1986; Deiber et al., 1988). While Pellizone et al. (1987) were unable to identify a NeuroImage 18, 58 – 66 (2003) doi:10.1006/nimg.2002.1325 58 1053-8119/02 $35.00 © 2002 Elsevier Science (USA) All rights reserved.