05, one tailed t test) and significantly smaller signal-to-noise ratios across all three experiments (Figure 3D; p < 0.05, one tailed t test). Two complementary analyses revealed that larger variability in autism was evident only in cortical stimulus-evoked responses and not in ongoing activity fluctuations (Figure 4). In the first analysis, we selected 40 nonresponding cortical ROIs (e.g., anterior cingulate, superior frontal gyrus, and precuneus) separately in each subject,

using an automated anatomical procedure (see Experimental Procedures). For Bosutinib in vivo each of these ROIs, we performed an identical analysis to that presented above for the sensory ROIs; assessing their mean response amplitude, trial-by-trial response variability,

and HA-1077 mouse signal-to-noise ratios according to the stimulus presentations (Figures 4A–4C). Since none of these ROIs exhibited evoked responses to any of the stimuli, computing the trial-by-trial standard deviations offers a way of assessing the variability of background ongoing activity, which always fluctuates randomly. The standard deviation values from each ROI were averaged across the 40 ROIs and compared across groups, separately for each of the sensory experiments. All measures were statistically indistinguishable across groups. In a second analysis we assessed cortical activity in the three sensory ROIs during a resting-state experiment, which did not contain any stimulus or task (Figures 4D–4F). Applying the same logic, we computed mean response amplitudes, trial-by-trial standard deviation, and signal-to-noise ratios in each sensory ROI according to the almost trial sequences from the sensory experiments. Since no stimuli

were presented in this resting-state experiment, there were no evoked responses in any of the sensory ROIs, and trial-by-trial standard deviations were used to assess the variability of the ongoing activity fluctuations. In agreement with the first analysis, all measures were statistically indistinguishable across groups. In both analyses, we first removed the global mean time course by orthogonal projection, so as to assess only local variance, but results were also statistically indistinguishable across groups when omitting this step. Subjects who exhibited a low signal-to-noise ratio in one sensory modality tended to exhibit a low signal-to-noise ratio in the other two modalities as well (Figure 5, top). We computed the correlation between signal-to-noise ratios across pairs of modalities in each group separately as well as across all subjects from both groups. All correlations were positive and most were statistically significant as assessed by randomization tests (see Experimental Procedures).