Tonotopic organization of human auditory cortexIntroductionMethodsSubjectsStimuliProcedureResultsDiscussionAcknowledgmentsReferencesTonotopic organization of human auditory cortexColin Humphries⁎, Einat Liebenthal, Jeffrey R. BinderDepartment of Neurology, Medical College of Wisconsin, Functional Imaging Research Center, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USAabstractarticle infoArticle history:Received 29 July 2009Revised 11 January 2010Accepted 14 January 2010Available online 22 January 2010The organization of tonotopic fields in human auditory cortex was investigated using functional magneticresonance imaging. Subjects were presented with stochastically alternating multi-tone sequences in sixdifferent frequency bands, centered at 200, 400, 800, 1600, 3200, and 6400 Hz. Two mirror-symmetricfrequency gradients were found extending along an anterior–posterior axis from a zone on the lateral aspectof Heschl's gyrus (HG), which responds preferentially to lower frequencies, toward zones posterior andanterior to HG that are sensitive to higher frequencies. The orientation of these two principal gradients isthus roughly perpendicular to HG, rather than parallel as previously assumed. A third, smaller gradient wasobserved in the lateral posterior aspect of the superior temporal gyrus. The results suggest close homologiesbetween the tonotopic organization of human and nonhuman primate auditory cortex.© 2010 Elsevier Inc. All rights reserved.IntroductionNeurons at various levels in the auditory pathway are topograph-ically arranged by their response to different frequencies. Thisorganization, referred to as tonotopy or cochleotopy, mirrors thedistribution of receptors in the cochlea, with a gradient extendingbetween neurons that preferentially respond to high frequencies andthose that respond best to low frequencies. Many distinct functionalareas in the auditory system show a tonotopic response gradient. Inthe auditory cortex of nonhuman primates, each of the three divisionsof primary “core” cortex—A1, R and RT—exhibit tonotopic gradientsthat are mirror symmetric to each other (see Fig. 1)(Bendor andWang, 2008; Kaas and Hackett, 2000; Kosaki et al., 1997; Merzenichand Brugge, 1973; Morel et al., 1993). Tonotopic gradients have alsobeen demonstrated in lateral and medial “belt” cortex surroundingthe core (Kaas and Hackett, 2000; Kosaki et al., 1997; Kusmierek andRauschecker, 2009; Petkov et al., 2006; Rauschecker et al., 1995;Rauschecker and Tian, 2004). In contrast to the visual cortex, whereretinotopic gradients reverse direction at the boundary betweenprimary and secondary cortices, the receptive field gradients inauditory cortex run parallel to the primary/secondary (i.e., core/belt)boundary, such that the two mirror symmetric gradients observed inA1 and R extend laterally to belt areas ML and AL (Rauschecker et al.,1995) as well as medially to areas MM and RM (Kusmierek andRauschecker, 2009)(Fig. 1). An exception to this is the posteriorlateral gradient in secondary belt area CL, which does not appear toextend into primary cortex (Rauschecker and Tian, 2004).Tonotopic organization has been identified in human auditorycortex using a variety of imaging techniques. The majority of earlystudies used only two different stimulus frequencies (Bilecen et al.,1998; Lauter et al., 1985; Lockwood et al., 1999; Talavage et al., 2000;Wessinger et al., 1997). These studies suggested a general pattern inwhich high frequencies activated medial auditory cortex and lowfrequencies activated more anterolateral regions in the superiortemporal plane. This pattern has usually been interpreted as a singlelow-to-high frequency gradient oriented along Heschl's gyrus (HG).Later functional magnetic resonance imaging (fMRI) studies improvedon this design by adding intermediate frequencies, allowing theidentification of frequency gradients (Formisano et al., 2003; Langerset al., 2007; Petkov et al., 2006; Schonwiesner et al., 2002; Talavage etal., 2004; Woods et al., 2009). Results and interpretations from thesestudies have varied considerably. For example, one study reported asingle high-to-low gradient extending from posterior medial toanterior lateral auditory areas, similar to earlier studies (Langers etal., 2007). A second study, however, described two mirror-symmetricfrequency gradients (high–low–high) extending approximately alongthe axis of HG (Formisano et al., 2003). In a third study, threeconsistent gradients were reported, none of which clearly follow thelong axis of HG (Talavage et al., 2004). Finally, the authors of a fourthstudy found differences in activation between anterior and posteriorHG as well as medial and lateral differences, but concluded that theobserved activation profile did not represent frequency gradients butinstead different func tional regi ons within the auditory cortex(Schonwiesner et al., 2002).Although these imaging studies differed on numerous methodo-logical factors, another potential source of variability is the interpre-tation given to the observed gradients. Many authors have conceivedof these gradients as extending along a narrow line between high andlow poles. A consideration of the data from non-human primateNeuroImage 50 (2010) 1202–1211⁎ Corresponding author. Fax: +1 414 456 6562.E-mail address: [email protected] (C. Humphries).1053-8119/$ – see front matter © 2010 Elsevier Inc. All rights reserved.doi:10.1016/j.neuroimage.2010.01.046Contents lists available at ScienceDirectNeuroImagejournal homepage: www.elsevier.com/locate/ynimgstudies, however, suggests instead a topography composed of alter-nating high and low frequency bands, each of which extends acrosscontiguous core and belt regions (Fig. 1). Woods et al. (2009) recentlyreported such a pattern and interpreted the data in terms of a non-human primate model, though the anterior high-frequency region didnot form a continuous band as predicted by the primate data.Given the variety of results and differences in interpretationsamong previous imaging studies of human tonotopy, we sought tocharacterize the tonotopic maps in auditory cortex in more detailusing fMRI. In particular, we were interested in addressing severalopen questions that have not been completely resolved, such as thenumber of frequency gradients, the orientation of the gradientsrelative to HG, and the variability of the gradients across subjects.MethodsSubjectsFMRI data were collected from eight