For example, Nutlin-3a cost in the olfactory domain, a hunting dog may require multiple sniffs to decide whether a fast-moving rabbit has darted left or right under a hedgerow; a human may take several sniffs to decide whether a carton of milk on the verge of spoiling is a wise

breakfast option. The implication is that the nervous system accumulates sensory information over time for efficient perceptual decision-making. Neuroscientific support for the integration of noisy perceptual evidence is principally based on single-unit studies in nonhuman animals (Gold and Shadlen, 2007; Newsome et al., 1989; Platt, 2002; Romo and Salinas, 2001; Schall and Thompson, 1999). In a widely studied visual perceptual paradigm (Cook and Maunsell, 2002; Hanes and Schall, 1996;

Newsome et al., 1989; Platt and Glimcher, 1999), responses in the lateral intraparietal area (LIP) show a ramp-like increase during a dot-motion discrimination task, such that animals make a decision when neuronal activity surpasses a bound (Roitman and Shadlen, 2002; Shadlen and Newsome, 2001). Such findings have helped inform and constrain models of perceptual decision-making. Human imaging studies have begun using simple two-choice tasks to explore the neural substrates of visual perceptual decision-making (Heekeren et al., 2004; Huettel et al., 2005; Ivanoff et al., 2008; Noppeney et al., 2010; Ploran et al., 2007; Tosoni et al., 2008). However, the direct integration of perceptual evidence over time and Obeticholic Acid clinical trial its modulation by the degree Histone demethylase of sensory noise are poorly understood. Resolving temporal integration using functional magnetic resonance imaging (fMRI) is difficult because

humans tend to solve perceptual tasks much faster than the minimum data-acquisition rate of functional MRI scanners—too few data points are obtained per trial to allow the characterization of signal integration during the decision process. Traditional wisdom thus holds that fMRI is too slow to capture sensory integration (Noppeney et al., 2010; Philiastides and Sajda, 2007). Here we took advantage of the fact that human olfactory perception evolves at a slow timescale, particularly for mixtures of odorants (Laing and Francis, 1989). This natural prolongation of response times implies that the olfactory system is ideally suited to characterize perceptual evidence integration with imaging techniques. In this study, we used fMRI to measure brain activity while subjects participated in a two-choice olfactory categorization task. Varying the relative proportion of components in a two-odorant mixture (Abraham et al., 2004; Boyle et al., 2009; Kepecs et al., 2008; Khan et al., 2008; Rinberg et al., 2006; Uchida and Mainen, 2003; Wesson et al., 2008) allowed us to manipulate odor mixture difficulty and to titrate the speed and accuracy of decision-making. With a combination of model-based fMRI approaches (O’Doherty et al., 2007), olfactory psychophysics, and deconvolution techniques (Glover, 1999; Zelano et al.