NATURE NEUROSCIENCE ADVANCE ONLINE PUBLICATION 1ARTICLESHierarchical and asymmetric temporal sensitivity in human auditory corticesAnthony Boemio1, Stephen Fromm2, Allen Braun2 & David Poeppel3Lateralization of function in auditory cortex has remained a persistent puzzle. Previous studies using signals with differing spectrotemporal characteristics support a model in which the left hemisphere is more sensitive to temporal and the right more sensitive to spectral stimulus attributes. Here we use single-trial sparse-acquisition fMRI and a stimulus with parametrically varying segmental structure affecting primarily temporal properties. We show that both left and right auditory cortices are remarkably sensitive to temporal structure. Crucially, beyond bilateral sensitivity to timing information, we uncover two functionally significant interactions. First, local spectrotemporal signal structure is differentially processed in the superior temporal gyrus. Second, lateralized responses emerge in the higher-order superior temporal sulcus, where more slowly modulated signals preferentially drive the right hemisphere. The data support a model in which sounds are analyzed on two distinct timescales, 25–50 ms and 200–300 ms.Structure, function and lateralization in human auditory cortex are the focus of much recent work1. One central issue concerns the origin and nature of lateralization. For example, there are subtle anatomic and physiological asymmetries in the afferent pathway, but compelling functional asymmetries attributable to cortical processing2,3. Where do such asymmetries originate? One hypothesis proposes that functional lateralization arises from differences in the early spectrotemporal computations performed in auditory cortices that transform sensory representations of signals into more abstract perceptual codes. A prevailing model is that temporal features are processed predominantly in the left hemisphere and spectral features in the right4. A second and different source of lateralization derives from the nature of the stored representations that the transformed sensory information must interface with for further processing—for example, lexical information in the left and affective prosodic information in the right hemisphere.Both explanations have led to the notion that speech—whether resulting from lateralization of stored lexical representations or from early auditory cortical specialization for processing temporal signal attributes—is preferentially processed within the left hemisphere5–7, whereas processing of dynamic pitch and prosody—whether resulting from lateralized representation of higher-order phrase-level intonation or specialized analysis of spectral information—is carried out in the right hemisphere8–10.We argue that both hemispheres together—including left and right non-primary auditory areas—participate in one critical intermediate com-putation, the analysis of the auditory signal on multiple timescales3,11,12, with the relevant scales being 25–50 ms and 200–300 ms (ref. 3). In addi-tion, we propose that functional lateralization emerges from differential connectivity patterns linking temporal cortices along the afferent path-way such that information processed on the longer timescales is routed predominantly to higher-order right hemisphere cortices, whereas information resulting from processing on the shorter timescale primar-ily projects to the left. To evaluate these hypotheses, we varied a single stimulus para-meter, the temporal structure, and looked for differential activation along the afferent pathway and between the two hemispheres. The present design controls for potential spectral confounds in a fashion that was not possible in previous studies in which stimuli varied both temporally and spectrally4,13.Fifteen participants listened passively to non-speech stimuli (Fig. 1) while we recorded the hemodynamic responses from the entire brain using a single-trial sparse acquisition fMRI design14,15. We cre-ated 9-s auditory signals by concatenating short-duration narrowband noise segments, spanning a range of segment transition rates from 3 to 83 segments per second, encompassing the syllabic to segmen-tal transition rates of speech16 (Fig. 1a,b; examples can be heard in Supplementary Audios 1–5 online). Each segment had a bandwidth of 125 Hz and a segment center frequency spanning a half-octave range from 1,000 Hz to 1,500 Hz. The bandwidth was chosen to be within the critical band at that frequency17 and interpretable in the context of the rate and bandwidth of speech formants16. Local spectrotem-poral variations were introduced by constructing two types of seg-ments. In one, the frequency remained constant throughout the signal 1Laboratory of Brain and Cognition, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. 2National Institute of Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA. 3Department of Linguistics and Department of Biology, University of Maryland, College Park, Maryland 20742, USA. Correspondence should be addressed to D.P. ([email protected]).Published online 20 February 2005; doi:10.1038/nn1409© 2005 Nature Publishing Group http://www.nature.com/natureneuroscience2 ADVANCE ONLINE PUBLICATION NATURE NEUROSCIENCEARTICLES(TN; Fig. 1b); in the other, frequency was swept linearly upward or downward randomly (FM; Fig. 1a). A control stimulus (CN; Fig. 1c) was constructed from a single 9-s TN segment with center frequency in the middle of the half-octave range.We show that early and higher-order auditory cortical areas are exqui-sitely sensitive to temporal structure bilaterally. In addition, local spectro-temporal structure is differentially processed within the superior temporal gyrus. Finally, in higher-order superior temporal sulcus, slowly modulated signals preferentially drive the right hemisphere. To account for these observations, we present a model involving cortical processing of audi-tory signals on short and long timescales, and a hypothesized differential connectivity pattern from lower- to higher-order auditory areas.RESULTSThe stimuli were effective at activating auditory cortex selectively and robustly (Fig. 2). Two independent analyses of the fMRI data were car-ried out, one at the cohort level, the second a region-of-interest (ROI) analysis at the level of individual