frequency are minimally affected by notched-noise masker sounds when the notch is wide enough to fall on the neuronal receptive fields. In this case the neurons are left unadapted and thus elicit robust response upon presentation of the test sound. However, as the notch width is narrowed down, the noise masker edges begin to fall on the receptive fields of the neurons that respond to the test sound. This results in adaptation of the neurons and diminution of the response that is generated when the test sound is presented (this is schematically illustrated in the upper panel of Figure 1). Selective attention effects on neuronal receptive fields can then be assessed by studying whether there are changes in the suppressive effects of maskers as a function of decreasing notch width of the maskers. Tone-in-noise experiments using continuous maskers have suggested a combination of attention-dependent gain and selec- tivity increase of neural responses using EEG [18] and MEG [7,19,20]. Kaurama¨ki and colleagues [18] showed a robust N100 enhancement in EEG while attending to sound compared to a passive silent movie baseline. However, the attentional enhance- ment was not constant with different masker notch widths, but rather the enhancement in the attend vs. ignore conditions was largest with some of the intermediate notch widths below the critical band, smaller with the widest notches (easiest-to-detect targets) as well as with the white noise masker (hardest-to-detect targets). Thus, these results could not be explained by a simple Figure 1. A schematic illustration of the paradigm. (A) During selective auditory attention (AttAud condition), subjects attempted to detect higher-frequency target tones. The background grey represents the noise masker, while the white area represents the frequency gaps in the noise. (B) During visual attention (AttVis condition), target stimuli with higher spatial frequency were to be detected. Auditory and visual stimuli were identical in both conditions. (C) Each masker type was presented for about 8 minutes, with AttAud and AttVis conditions alternating every 2 minutes, indicated by instructions on the screen during the condition start and change. doi:10.1371/journal.pone.0046872.g001 Two-Stage Processing of Sounds during Attention gain increase alone (i.e., multiplicative increase in the tuning function), but likely involved enhanced selectivity of the receptive fields of underlying neural populations as well. Unfortunately, the limited spatial resolution in this EEG study prevented estimation of the cortical loci of these selective attention effects. Here, we explored the attention-related frequency tuning changes in the auditory cortex with continuous notched-noise maskers (Fig. 1A). We specifically hypothesized that 1) the biggest attention effects would be seen at intermediate masker notches, 2) exploiting the spatial accuracy of MRI-constrained MEG [21,22] combined with an extensive selection of masker notches that the effects are localized in the auditory cortex, and 3) we further explored whether similar effects can be seen in the sustained response or whether the tuning effects are unique to M100 latency. Further, we designed the experiment so that possible arousal- related effects were controlled by a visual control task of similar difficulty (Fig. 1B) and so that the build-up of the selective attention effects as a function of time on the task could be assessed by using task switching (Fig. 1C) that requires high level of cognitive control. Results The main findings of the present study were the following: 1) The M100 response peak amplitudes increased and latencies shortened with increasing notch width. 2) Selective attention to sounds increased the M100 response amplitude in both hemi- spheres with all noise maskers. 3) Attention enhanced the sustained response, localized more medially than M100, selectively with narrow notches especially in the left hemisphere. Equivalent current dipole fitting results The equivalent current dipoles (ECDs), modeling the sensor- level N100m response and referred to as M100 response in the manuscript, were localized in left and right planum temporale, in superior temporal gyrus (STG) posterior to Heschl’s gyrus (HG). Mean dipole locations in stereotactic MNI space in AttAud condition were x = {59 mm, y = {23 mm, z = 9 mm for left, and x = 57 mm, y = {15 mm, z = 12 mm for right hemisphere (N = 10, subgroup of subjects with MRI images, see Materials and Methods). Dipole locations for AttVis condition did not differ significantly from those in the auditory condition. The activation foci at M100 latency are visualized using dynamic statistical parametric (dSPM) maps [23] with AttAud condition shown in Figure 2A. Sustained-response ECDs were localized in absolute terms slightly but statistically significantly more medially com- pared with the M100 (Fig. 3). Figure 2B displays the full time scales of left and right dipole sources. The M100 peak amplitude was clearly modulated as a function of masker notch width (F6,78~30:66, pv0:0001, e~0:50), ranging on average from 5.4 nAm (0 Hz masker) to 20.8 nAm (+500 Hz masker), thus showing nearly a four-fold increase (Fig. 4A). The source strengths were on average 18% (2.8 nAm) stronger during selective auditory attention (F1,13~21:99, p~0:00042). Despite failing to reach statistical significance in the interaction term of the ANOVA, attention effect was not constant in amplitude with different maskers, but showed a clear tendency of being largest with narrow notches (+150 Hz,+100 Hz, +50 Hz). There were no hemispheric effect (F1,13~0:58, p~0:46) nor significant interaction terms (e.g., MASKERTYPE|ATTENTION interaction: F6,78~1:42, p~0:22, e~0:83). The M100 peak latencies showed a significant dependency on the masker notch width (F6,78~138:56, pv0:0001, e~0:70), with mean range of 124–206 ms (Fig. 4B). PLOS ONE | www.plosone.org 2 October 2012 | Volume 7 | Issue 10 | e46872