In addition, twenty-three healthy control participants (HC, 13 females, 29.8±10.1 years old) matched for age and gender with the MDD patients were recruited according to the criteria in Experiment 1; this sample of healthy subjects was different from the one reported in Experiments 1 and 2. Demographic and clinical data for the MDD (further separated into medicated and un-medicated) and the HC groups were listed in Table 1 (Part of the information was obtained after data screening).

For Experiment 3, twenty-three inpatients with MDD diagnosed according to DSM-IV by two professional psychiatrists were recruited (13 females, 31.8±9.8 years old). Only subjects with BDI-13 score>7 and HAMD-17>7 were included. All the participants were cooperative during the test without severe suicidal ideation. The average HAMD score was 19.6 (SD = 9.3). MDD patients with severe anxious symptoms (Self-rating Anxiety Scale (SAS)>60, 14-item version of Hamilton Rating Scale for Anxiety (HAMA-14)>29) and/or other neurologic, psychiatric or medical disorders were excluded from the study. MDD patients were either medicated or not (serotoninergic drugs; see Table 1 for details).

For Experiments 1 and 2, twenty healthy participants (13 females, 24.0±4.2 years old) were recruited according to following criteria: 13-term version of Beck Depression Inventory (BDI-13) ≤4; Self-rating Anxiety Scale (SAS)≤40; 17-term version of Hamilton Rating Scale for Depression (HAMD-17)≤7; 14-term version of Hamilton Rating Scale for Anxiety (HAMA-14)≤7; normal or corrected-to-normal vision (tested with international standard visual testing chart); no history of psychiatric or neurologic (or medial) disease; and no substance abuse. Both HAMD-17 and HAMA-14 have Chinese versions with good reliability and validity [24] .

All participants were recruited at Shanghai Mental Health Center. After a complete description of the study, written informed consent was obtained from each participant. The protocol of this study was approved by the Institute's Ethical Committees of both Shanghai Mental Health Center and Institute of Psychology, Chinese Academy of Sciences.

Stimuli and Procedure

Stimuli were programmed with the psychophysical toolbox [25]–[26] on MATLAB (The MathWorks, Natick, MA), and were presented on a 17-inch flat-panel monitor. Two square frames (10.7°×10.7°) were displayed side by side on the screen. Through a mirror stereoscope mounted on a chinrest, each eye of the participant could only see the frame on the same side, and the mirror stereoscope was adjusted so that the two frames were comfortably fused together for the participant. The viewing distance was 40 cm (see [27] for setup of the equipment).

The general experimental paradigm is shown in Figure 1. There were two separate sessions for invisible and visible stimuli, each containing 80 trials. At the beginning of each trial, a fixation cross (visual angle 0.8°×0.8°) was presented to each eye for one second. The following stimuli lasted for 800 ms in Experiments 1 and 3, and 200 ms in Experiment 2. The only difference between visible and invisible sessions was the content of the stimuli: In the invisible session, a pair of faces with different emotional expressions was presented to the participant's non-dominant eye (tested before experiment), while a pair of identical high contrast dynamic noise patches was presented to the dominant eye, so that the participant only perceived the identical noise patches due to the strong interocular suppression. For the visible session, a pair of faces with different emotional expressions was presented to both eyes and the participants could perceive the faces.

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larger image TIFF original image Download: Figure 1. Schematic representation of the experimental paradigm for the invisible and visible conditions. In the invisible condition, dynamic noise patches were presented to the dominant eye and faces with happy and sad emotional expressions were presented to the other eye. The duration of the face presentation was 800 ms for Experiments 1 and 3, and 200 ms for Experiment 2. After a 100-ms interval, participants were instructed to press one of two buttons as soon and accurate as possible to indicate the perceived orientation (clockwise or counter-clockwise) of a Gabor patch presented for 100 ms. In the visible condition, the dynamic noise patches were replaced by the same pair of faces presented to the other eye. https://doi.org/10.1371/journal.pone.0021881.g001

Each of the above face pairs was formed by grey-scale images of a positive and a negative emotional faces (4°×6° of visual angle), which were selected from happiness and sadness categories from three actors/actresses in Ekman and Friesen's [28] pictures of facial affect. The faces were masked using an ellipse so that the hair and background in the face images were excluded. The noise patches were masked in the same way to ensure their shape is the same as the face images. The distance between the centers of the two faces was around 5°. In half of the trials, the positive emotional faces were presented to the left, and the negative ones to the right side. For the other half trials, the positions were reversed.

The above stimuli were followed by a 100-ms fixation cross, and then identical small Gabor patches (2.5°×2.5°) were presented to both eyes for 100 ms. The positions of the Gabor patches were the centers of either the left or right previously presented faces. The Gabor patches were tilted one degree clockwise or counterclockwise (randomized), and the participant was instructed to press one of the two buttons (2-alternative force choice) to indicate their perception of the orientation of the Gabor patches, regardless of which side the Gabor patches were presented to. The fixation would not end until the participants made their choice. Among all 80 trials in each session, the presentation sides of the emotional faces and that of the Gabor patches were balanced so that there were 20 trials for each combination. The button-press and response time (RT) relative to the onset of the Gabor patch presentations was recorded.

Before the experiment, the participants were familiarized with the paradigm through a 50-trial training session. To ensure the participants were never explicitly aware of the invisible faces, they were instructed to press a different key to reject the trial if they detected grey-scale images during the invisible session. If more than two trials were rejected in the invisible session, the data for the corresponding participant were excluded from further analyses.