Two-Stage Processing of Sounds Explains Behavioral Performance Variations due to Changes in Stimulus Contrast and Selective Attention: An MEG Study Jaakko Kaurama¨ ki1*, Iiro P. Ja¨ a¨ skela¨ inen1, Jarno L. Ha¨ nninen 1 , Toni Auranen2,3, Aapo Nummenmaa4, Jouko Lampinen1, Mikko Sams1 1 Department of Biomedical Engineering and Computational Science (BECS), Brain and Mind Laboratory, Aalto University School of Science, Espoo, Finland, 2 Advanced Magnetic Imaging Centre, O.V. Lounasmaa Laboratory, Aalto University School of Science, Espoo, Finland, 3 Brain Research Unit, O.V. Lounasmaa Laboratory, Aalto University School of Science, Espoo, Finland, 4 Athinoula A. Martinos Center in Biomedical Imaging and Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America Abstract Selectively attending to task-relevant sounds whilst ignoring background noise is one of the most amazing feats performed by the human brain. Here, we studied the underlying neural mechanisms by recording magnetoencephalographic (MEG) responses of 14 healthy human subjects while they performed a near-threshold auditory discrimination task vs. a visual control task of similar difficulty. The auditory stimuli consisted of notch-filtered continuous noise masker sounds, and of 1020-Hz target tones occasionally (p~0:1) replacing 1000-Hz standard tones of 300-ms duration that were embedded at the center of the notches, the widths of which were parametrically varied. As a control for masker effects, tone-evoked responses were additionally recorded without masker sound. Selective attention to tones significantly increased the amplitude of the onset M100 response at *100 ms to the standard tones during presence of the masker sounds especially with notches narrower than the critical band. Further, attention modulated sustained response most clearly at 300–400 ms time range from sound onset, with narrower notches than in case of the M100, thus selectively reducing the masker- induced suppression of the tone-evoked response. Our results show evidence of a multiple-stage filtering mechanism of sensory input in the human auditory cortex: 1) one at early (*100 ms) latencies bilaterally in posterior parts of the secondary auditory areas, and 2) adaptive filtering of attended sounds from task-irrelevant background masker at longer latency (*300 ms) in more medial auditory cortical regions, predominantly in the left hemisphere, enhancing processing of near-threshold sounds. Citation: Kaurama¨ki J, Ja¨a¨skela¨inen IP, Ha¨nninen JL, Auranen T, Nummenmaa A, et al. (2012) Two-Stage Processing of Sounds Explains Behavioral Performance Variations due to Changes in Stimulus Contrast and Selective Attention: An MEG Study. PLoS ONE 7(10): e46872. doi:10.1371/journal.pone.0046872 Editor: Trevor Bruce Penney, National University of Singapore, Singapore Received December 29, 2011; Accepted September 10, 2012; Published October 11, 2012 Copyright: 2012 Kaurama¨ki et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was financially supported by the Finnish Graduate School of Neuroscience (JK), Emil Aaltonen Foundation (JK), Ella and Georg Ehrnrooth Foundation (JK) and by the Academy of Finland, grant nos. 127624 (AN), 129670 (IPJ and MS), 130412 (IJ). No additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: jaakko.kauramaki@aalto.fi Introduction Selective attention has been shown to increase the ‘‘gain’’ of neural responses (i.e., augment responses to attended and suppress responses to non-attended stimuli) both in auditory [1–4] and visual [5] modalities. Using adaptation paradigms, magnetoen- cephalography (MEG) [6,7] and functional magnetic resonance imaging (fMRI) [8] studies have extended these results by suggesting that, besides the ‘‘gain increase’’ [9], feature selectivity of sensory cortical neurons also increases when attending to sound features. Specifically, neuronal receptive fields are reshaped to match the relevant features of the to-be-attended stimuli. Furthermore, recent findings in electroencephalography EEG [10] and MEG [11] studies suggest that the mechanisms for attentional enhancement and inhibition are distinct. Together, these attentional mechanisms rapidly and task-specifically reorga- nize human auditory system function (for a review, see e.g. [12,13]). Sometimes the ‘‘gain’’ and ‘‘tuning’’ models of selective attention have been viewed as mutually exclusive, however, noise-normalization models of attention have been recently proposed for visual cortex neurons that combines these two views [14,15]. Specifically, the noise-normalization model proposes that the changes in receptive field shape occur when multiple objects fall within a single-neuron receptive field, or when a neuron’s preferred contrast does not match the presented stimulus. An auditory analogue of this is simultaneous occurrence of multiple sounds within the critical band of the attended sound frequency. In humans, auditory-evoked responses are suppressed in amplitude by masking [16,17]. The amplitude of the N100 response, peaking at around 100 ms after sound onset, increases as the distance in sound frequency increases between the masker and test sounds. Importantly, this effect has been used to derive estimates of underlying neuronal receptive field selectivity (i.e., ‘‘frequency tuning’’ of the neurons). Specifically, it is assumed that neurons with receptive fields that are sharply tuned to sound PLOS ONE | www.plosone.org 1 October 2012 | Volume 7 | Issue 10 | e46872