Dandekar S, Privitera C, Carney T, Klein SA. Neural saccadic response estimation during natural viewing. J Neurophysiol 107: 1776-1790, 2012. First published December 14, 2011 doi:10.1152/jn.00237.2011Studying neural activity during natural viewing conditions is not often attempted. Isolating the neural response of a single saccade is necessary to study neural activity during natural viewing; however, the close temporal spacing of saccades that occurs during natural viewing makes it difficult to determine the response to a single saccade. Herein, a general linear model (GLM) approach is applied to estimate the EEG neural saccadic response for different segments of the saccadic main sequence separately. It is determined that, in visual search conditions, neural responses estimated by conventional eventrelated averaging are significantly and systematically distorted relative to GLM estimates due to the close temporal spacing of saccades during visual search. Before the GLM is applied, analyses are applied that demonstrate that saccades during visual search with intersaccadic spacings as low as 100 -150 ms do not exhibit significant refractory effects. Therefore, saccades displaying different intersaccadic spacings during visual search can be modeled using the same regressor in a GLM. With the use of the GLM approach, neural responses were separately estimated for five different ranges of saccade amplitudes during visual search. Occipital responses time locked to the onsets of saccades during visual search were found to account for, on average, 79 percent of the variance of EEG activity in a window 90 -200 ms after the onsets of saccades for all five saccade amplitude ranges that spanned a range of 0.2-6.0 degrees. A GLM approach was also used to examine the lateralized ocular artifacts associated with saccades. Possible extensions of the methods presented here to account for the superposition of microsaccades in event-related EEG studies conducted in nominal fixation conditions are discussed. saccades; EEG; visual search; microsaccades; artifact removal EEG IS WELL SUITED FOR THE study of fast neural dynamics, and a variety of EEG studies have successfully explored saccadic planning (Everling et al. 1997;Richards 2003) and postsaccadic neural responses (Bellebaum et al. 2005;Ossandón et al. 2010). However, most EEG studies of saccadic eye movements are conducted with sparse synthetic visual targets and/or temporally well separated saccades in conditions that do not resemble those that are involved in natural viewing conditions. A variety of fMRI studies of saccadic eye movements, most of which were conducted in more controlled conditions than those associated with natural viewing, have identified various sites of neural activation likely involved in saccadic eye movements (Connolly et al. 2002;Corbetta et al. 1998). However, the low temporal resolution of fMRI makes the study of fast temporal neural dynamics during natural viewing conditions impractical. A general linear least squares or general linear model (GLM...