Neural Mechanisms of Human Perceptual Learning: Electrophysiological Evidence for a Two-Stage Process Carlos M. Hamame´ 1,3,4,5*, Diego Cosmelli1,2,3, Rodrigo Henriquez1,3, Francisco Aboitiz1,3 1 Laboratorio de Neurociencia Cognitiva, Departamento de Psiquiatr´ıa, Escuela de Medicina, Pontificia Universidad Cato´ lica de Chile, Santiago, Chile, 2 Escuela de Psicolog´ıa, Pontificia Universidad Cato´ lica de Chile, Santiago, Chile, 3 Centro Interdisciplinario de Neurociencia, Pontificia Universidad Cato´ lica de Chile, Santiago, Chile, 4 Instituto de Ciencias Biome´dicas, Universidad de Chile, Santiago, Chile, 5 Lyon Neuroscience Center, INSERM U1028, CNRS UMR5292, Claude Bernard UL1, Lyon, France Abstract Background: Humans and other animals change the way they perceive the world due to experience. This process has been labeled as perceptual learning, and implies that adult nervous systems can adaptively modify the way in which they process sensory stimulation. However, the mechanisms by which the brain modifies this capacity have not been sufficiently analyzed. Methodology/Principal Findings: We studied the neural mechanisms of human perceptual learning by combining electroencephalographic (EEG) recordings of brain activity and the assessment of psychophysical performance during training in a visual search task. All participants improved their perceptual performance as reflected by an increase in sensitivity (d’) and a decrease in reaction time. The EEG signal was acquired throughout the entire experiment revealing amplitude increments, specific and unspecific to the trained stimulus, in event-related potential (ERP) components N2pc and P3 respectively. P3 unspecific modification can be related to context or task-based learning, while N2pc may be reflecting a more specific attentional-related boosting of target detection. Moreover, bell and U-shaped profiles of oscillatory brain activity in gamma (30–60 Hz) and alpha (8–14 Hz) frequency bands may suggest the existence of two phases for learning acquisition, which can be understood as distinctive optimization mechanisms in stimulus processing. Conclusions/Significance: We conclude that there are reorganizations in several neural processes that contribute differently to perceptual learning in a visual search task. We propose an integrative model of neural activity reorganization, whereby perceptual learning takes place as a two-stage phenomenon including perceptual, attentional and contextual processes. Citation: Hamame´ CM, Cosmelli D, Henriquez R, Aboitiz F (2011) Neural Mechanisms of Human Perceptual Learning: Electrophysiological Evidence for a Two- Stage Process. PLoS ONE 6(4): e19221. doi:10.1371/journal.pone.0019221 Editor: Michael H. Herzog, Ecole Polytechnique Federale de Lausanne, Switzerland Received October 18, 2010; Accepted March 30, 2011; Published April 26, 2011 Copyright: 2011 Hamame´ 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 research was supported by CONICYT doctoral grant to C.M.H. and by an ECOS-Sud/CONICYT grant C08S02 and FONDECYT 1090612 grant to D.C. and F.A. 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: carlos.hamame@inserm.fr Introduction The human brain can change its activity in order to learn novel sensory configurations thus ensuring adaptive behavior throughout life. This kind of experience-dependent modification in perception has been labeled perceptual learning [1], and its neural mechanisms have been the object of increasing interest and research. In the visual modality, one possible approach to study the neural basis of human perceptual learning is based on scalp recordings of event-related potentials (ERPs). For instance, training-dependent perceptual improvements during Vernier-like stimuli discrimination are accompanied by increases in scalp global field potential at different times after stimulus presentation [2]. Amplitude modulations have also been found in both early and late components of the visual ERP for different forms of perceptual training: for example, orientation discrimination of simple or complex stimuli yielded N1 and N2 decrements over posterior sites, together with P2 or P3 increments distributed more centro-parietally [3]. Although the absence of modifications in the P1 component is usually interpreted as a top-down modulation of stimulus processing at early stages of the neural pathway [4,5], a recent study carefully designed to obtain C1 -the earliest component of the visual ERP- after training in a texture discrimination, found stronger amplitude for trained when compared to not-trained subjects. This suggests reorganization of neural activity at the level of early visual cortices such as V1 [6]. Despite the wealth of knowledge such studies have produced, electrophysiological studies of human perceptual learning have usually focused on the difference in neural activity between trained and untrained conditions, or with how neural responses to stimuli change after a given practice period. As informative as this approach can be regarding the final consequences of expertise on brain activity, it cannot reveal how neural activity is dynamically reorganized to improve perceptual performance. In order to do so it is necessary to track changes in brain activity that follow improvement in perceptual performance throughout the entire training process. On the other hand, a rapidly growing approach is the spectral analysis of the EEG signal, by which oscillatory activity at different frequency bands can be described in terms of phase and amplitude. High frequency oscillatory activity in the gamma band (.40 Hz) has been found to be critical for the temporal PLoS ONE | www.plosone.org 1 April 2011 | Volume 6 | Issue 4 | e19221