organization of neural activity in terms of spike synchrony and cell assembly formation [7–9]. However, while its involvement in several cognitively relevant conditions such as visual grouping [10,11], object representation [12], attention [13], and short term memory [14], among others [15], is well documented, the role of neural oscillations in human perceptual learning remains unknown and unexplored. Here we undertake the study of the neural mechanisms of human perceptual learning during the actual training process of subjects practicing a visual search task (Figure 1). Although perceptual learning has been studied mainly by training subjects to discriminate basic features of fine-grained stimuli [16], a considerable number of investigations [4,5,17–27] have used visual search tasks. The increase in ecological validity and the potential for revealing interactions between different levels of hierarchical processing suggest that such paradigm is well suited for elucidating the mechanisms of perceptual learning in the human brain. In order to follow dynamical changes in brain activity, we combined psychophysical measures and electrophys- iological recordings (ERPs and oscillatory activity) during the entire processes. Our results indicate that there is stimulus (specific) and task (unspecific) related neural activity reorganization that can be observed in amplitude changes of the N2pc and P3 ERP components, which follow a similar temporal profile as perceptual performance. On the other hand, changes in the amplitude of oscillatory activity in the gamma and alpha bands of the EEG followed a ‘‘bell’’ and ‘‘U’’ shaped pattern respectively, suggesting that the acquisition process is composed by at least two phases with distinctive optimization mechanisms for stimulus processing. Neurophysiology of Human Perceptual Learning Materials and Methods Ethics Statement The Bioethical Committee of Research of the Pontificia Universidad Cato´ lica de Chile approved all experimental procedures. Research was conducted according to the principles expressed in the Declaration of Helsinki and the experiments were undertaken with the understanding and written consent of each participant. All experiments were performed at the Cognitive Neuroscience Laboratory of the Psychiatry Department of the University. Participants Ten healthy human subjects (four females, six males, age range 22–35) participated voluntarily in the study. All subjects were right-handed and had normal or corrected-to-normal vision. Participants were trained in a visual search task during five sessions in five consecutive days. Each training session was also an EEG recording session and was composed of eight blocks of 150 trials. Each block lasted approximately 8 minutes. There was a five minute resting period between each block and a longer one of 15 minutes between the fourth and fifth block. Each subject was therefore exposed to 6000 trials during a training period of five consecutive days. Task The visual search task used here is a modification of one used by Sigman and Gilbert [23]. All recording/training sessions took place in a dimly illuminated silent room. Stimuli were presented on a computer monitor with a 100 Hz refresh rate placed 57 cm Figure 1. Schematic presentation of the task and electrode coverage over the scalp. The left portion of the figure depicts the visual search task’s main sequence of events. At the beginning of each block a fixation cross was presented during 1000 ms, then S1 (target present) or S2 (target absent) are presented pseudo-randomly for 300 ms. Subjects then had 1200, 1500 or 1800 ms to respond by pressing either the left or right button of a mouse if the target was present or absent from the search array respectively. This was followed by a random duration ITI that could be 900, 1200 or 1500 ms long. The bottom left panel depicts an example of the target used during the control session. The right portion of the figure shows the electrode sites spanning frontal, central, temporal, parietal and occipital areas and the identified ROIs for ERPs and neural oscillatory activity analysis. doi:10.1371/journal.pone.0019221.g001 PLoS ONE | www.plosone.org 2 April 2011 | Volume 6 | Issue 4 | e19221