Crucially, because feedback connections convey predictions, which serve to explain and thereby reduce prediction errors in lower levels, their effective (polysynaptic) connectivity is generally assumed to be inhibitory. Cyclopamine research buy An overall inhibitory effect of feedback connections is consistent with in vivo studies. For example,

electrophysiological studies of the mismatch negativity suggest that neural responses to deviant stimuli, which violate sensory predictions established by a regular stimulus sequence, are enhanced relative to predicted stimuli (Garrido et al., 2009). Similarly, violating expectations of auditory repetition causes enhanced gamma-band responses in early auditory cortex (Todorovic et al., 2011). These enhanced responses are thought to reflect an inability of higher cortical areas to predict, and thereby

suppress, the activity of populations encoding prediction error (Garrido et al., 2007; Wacongne et al., 2011). The suppression of predictable responses can also be regarded as repetition suppression, observed in single-unit recordings from the inferior temporal cortex of macaque monkeys (Desimone, 1996). Furthermore, neurons in monkey inferotemporal cortex respond significantly less to a predicted sequence of natural Bleomycin images, compared to an unpredicted sequence (Meyer and Olson, 2011). The inhibitory effect of feedback connections is further supported by neuroimaging studies (Murray et al., 2002, 2006; Harrison et al., 2007; Summerfield et al.,

2008, 2011; Alink et al., 2010). These studies show that predictable stimuli evoke smaller responses in early cortical areas. Crucially, this suppression cannot be explained in terms of local adaptation, because the attributes of the stimuli that can be predicted are not represented in early sensory cortex (e.g., Harrison et al., 2007). It should be noted that the suppression of responses to predictable stimuli can coexist with (top-down) attentional enhancement of evoked processing (Wyart et al., 2012): in predictive coding, attention is mediated by increasing the gain of populations encoding prediction error (Spratling, 2008; Feldman and Friston, Rebamipide 2010). The resulting attentional modulation (e.g., Hopfinger et al., 2000) can interact with top-down predictions to override their suppressive influence, as demonstrated empirically (Kok et al., 2012). See Buschman and Miller (2007), Saalmann et al. (2007), Anderson et al. (2011), and Armstrong et al. (2012) for further discussion of top-down connections in attention. Further evidence for the inhibitory (suppressive) effect of feedback connections comes from neuropsychology: patients with damage to the prefrontal cortex (PFC) show disinhibition of event-related potential (ERP) responses to repeating stimuli (Knight et al., 1989; Yamaguchi and Knight, 1990; but see Barceló et al., 2000).