Canonical Microcircuits for Predictive Coding

“…by a single cortical cell receiving input from several ON 700 Neuron 76, November 21, 2012 ª2012 Elsevier Inc. center-OFF surround geniculate cells arranged along a particular orientation, thereby endowing it with a preference for bars oriented in a particular direction (Hubel and Wiesel, 1962).”

“Forward (driving) and backward (driving and modulatory) connections mediate the (linear) influence of prediction errors and the (linear and nonlinear) construction of predictions (Friston, 2008, 2010).”

“Encoding of conditional dependencies in terms of a graphical model (Mumford, 1992; Rao and Ballard, 1999; Friston, 2008).”

“, 1989; Singer, 1999), while others have emphasized inter-areal phase-synchronization or coherence (Varela et al., 2001; Fries, 2005; Fujisawa and Buzsáki, 2011).”

“, 1989; Singer, 1999), while others have emphasized inter-areal phase-synchronization or coherence (Varela et al., 2001; Fries, 2005; Fujisawa and Buzsáki, 2011).”

“anatomical segregation into parallel streams, the question naturally arises, how are these streams integrated? It has been previously suggested that integration occurs through the synchronized firing of multiple neurons that form a neural ensemble (Gray et al., 1989; Singer, 1999), while others have emphasized inter-a…”

“, 1995; Knill and Pouget, 2004) and many other compelling proposals about perceptual synthesis – including analysis by synthesis (Neisser, 1967; Yuille and Kersten, 2006) epistemological automata (MacKay, 1956), the principle of minimum redundancy (Attneave, 1954; Barlow, H.B., 1961; Dan et al., 1996), the Infomax pri…”

“We have previously discussed this in terms of attentional modulation, whichmay be intimately linked to the synchronization of presynaptic inputs and ensuing postsynaptic responses (Feldman and Friston, 2010; Fries et al., 2001).”

“…maximization of Bayesian model evidence provides an important link to the Bayesian brain hypothesis (Hinton and van Camp, 1993; Dayan et al., 1995; Knill and Pouget, 2004) and many other compelling proposals about perceptual synthesis, including analysis by synthesis (Neisser, 1967; Yuille and…”

“anatomical segregation into parallel streams, the question naturally arises, how are these streams integrated? It has been previously suggested that integration occurs through the synchronized firing of multiple neurons that form a neural ensemble (Gray et al., 1989; Singer, 1999), while others have emphasized inter-a…”

“A cortical column was classically defined as a vertical alignment of cells containing neurons with similar receptive field properties, such as orientation preference and ocular dominance in V1 or touch in somatosensory cortex (Mountcastle, 1957; Hubel and Wiesel, 1972).”

“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.”

“This section reviews laminar-specific connections that underlie the notion of a canonical microcircuit (Douglas et al., 1989; Douglas and Martin, 1991, 2004).”

“Hupé et al. (1998) cooled area V5/MT while recording from areas V1, V2, and V3 in the monkey.”

“Indeed, there is empirical evidence to support this notion in the visual (Lakatos et al., 2008; Meirovithz et al., 2012; Bosman et al., 2012) and motor (Gwin and Ferris, 2012) domain.”

“In addition, the thalamic reticular nucleus has been proposed to mediate the inhibition that might underlie cross-modal attention or top-down predictions (Yamaguchi and Knight, 1990; Crick, 1984; Wurtz et al., 2011).”

“are enhanced relative to predicted stimuli (Garrido et al., 2009).”

“…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, 2010).”

“This view has re-emerged in recent years, with the development of the requisite recording and analytic techniques for evaluating this proposal (Buzsáki, 2010; Canolty et al., 2010; Singer et al., 1997; Lopes-dos-Santos et al., 2011).”

“Indeed, this led Geoffrey Hinton and colleagues to propose that the brain is an inference (Helmholtz) machine (Hinton and Zemel, 1994; Dayan et al., 1995).”

“…and feedback signaling may be mediated by distinct (high and low) frequencies (reviewed in Wang, 2010; see also Buschman and Miller, 2007), a proposal that has recently received experimental support, at least for the feedforward connections (Bosman et al., 2012; see also Gregoriou et al., 2009).”

“Some authors emphasize that even within a dendrite, there are all the necessary biophysical mechanisms for performing surprisingly advanced computations, such as direction selectivity, coincidence detection, or temporal integration (Häusser and Mel, 2003; London and Häusser, 2005).”

“Furthermore, the resulting scheme corresponds almost exactly to the computational architecture proposed by Mumford (1992).”

“Distinct (laminar-specific) extrinsic connections (Zeki and Shipp, 1988; Felleman and Van Essen, 1991; Barone et al., 2000; Vezoli et al., 2004; Markov et al., 2011).”

“Finally, Hubel and Wiesel defined a hypercolumn to be the unit of cortex necessary to traverse all possible values of a particular receptive field property, such as orientation or eye dominance, estimated to be between 0.5 and 1 mm wide (Hubel and Wiesel, 1974).”

“In terms of implementation, predictive coding is, arguably, the most plausible neurobiological candidate for making these inferences (Srinivasan et al., 1982; Mumford, 1992; Rao and Ballard, 1999).”

“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, computational considerations and recent experimental findings point to a potentially important role for higher-order thalamic nuclei in coordinating and synchronizing cortical responses (Vicente et al., 2008; Saalmann et al., 2012).”

“Forward (driving) and backward (driving and modulatory) connections mediate the (linear) influence of prediction errors and the (linear and nonlinear) construction of predictions (Friston, 2008, 2010).”

“A cortical column was classically defined as a vertical alignment of cells containing neurons with similar receptive field properties, such as orientation preference and ocular dominance in V1 or touch in somatosensory cortex (Mountcastle, 1957; Hubel and Wiesel, 1972).”

“prediction errors (deep pyramidal cells) (Mumford, 1992; Friston, 2008).”

“Recently, two studies have mapped the intrinsic connectivity of mouse sensory and motor cortices: Lefort et al. (2009) used multiple whole-cell recordings in mouse barrel cortex to determine the probability of monosynaptic connections and the corresponding connection strength.”

“When visual stimuli were presented in the classical receptive field (CRF), cooling of area V5/MT decreased unit activity in earlier areas, suggesting an excitatory effect of extrinsic feedback (Hupé et al., 1998).”

“P300 ERPs in response to novel stimuli—as if there were a failure to communicate top-down predictions to sensory cortex (Knight, 1984).”

“This notion builds on a long history of proposals that the brain uses internal or generative models to make inferences about the causes of its sensorium (Helmholtz, 1860; Gregory, 1968, 1980; Dayan et al., 1995).”

“Modulatory connections produce metabotropic and ionotropic responses when stimulated, evoke weak EPSPs, and show paired-pulse facilitation (Sherman and Guillery, 1998; 2011).”

“Distinct (laminar-specific) neuronal responses (Douglas et al., 1989; Douglas and Martin, 1991).”

“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).”

“In terms of the excitatory and modulatory effect of feedback connections, predictive input from higher cortical areas might have an important impact via the distal dendrites of pyramidal neurons (Larkum et al., 2009).”

“…one important route by which feedback connections could mediate selective inhibition is via their termination in L1 (Anderson and Martin, 2006; Shipp, 2007): layer 1 is sometimes referred to as acellular due to its pale appearance with Nissl staining (the classical method for separating…”

“These are more difficult to study, because inhibitory cells are less common than excitatory cells, and because there are at least seven distinct morphological classes (Salin and Bullier, 1995).”

“Minicolumns were originally proposed as elementary units of cortex by Lorente de No (1949) and appear to reflect the migration of cells from the ventricular zone to the cortical sheet during fetal development (reviewed in Horton and Adams, 2005).”

“Anatomical and functional data suggest that afferent input enters primarily into L4 and is conveyed to superficial layers L2/3 that are rich in pyramidal cells, which project forward to the next cortical area, forming a disynaptic route between thalamus and secondary cortical areas (Callaway, 1998).”

“Finally, the spiking activity of neurons in the superficial layers of visual cortex are more coherent with gamma-frequency oscillations in the local field potential, while neurons in deep layers are more coherent with alpha-frequency oscillations (Buffalo et al., 2011).”

“This issue is important as distinct neuronal dynamics in different cortical layers are becoming increasingly apparent (de Kock et al., 2007; Sakata and Harris, 2009; Maier et al., 2010; Bollimunta 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).”

“Suppression was also high in V1, around 80%–84% (Olsen et al., 2012).”

“Distinct (laminar-specific) neuronal responses (Douglas et al., 1989; Douglas and Martin, 1991).”

“The most popular scheme—for Bayesian filtering in neuronal circuits—is predictive coding (Srinivasan et al., 1982; Buchsbaum and Gottschalk, 1983; Rao and Ballard, 1999).”

“, 1989; Singer, 1999), while others have emphasized inter-areal phase-synchronization or coherence (Varela et al., 2001; Fries, 2005; Fujisawa and Buzsáki, 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).”

“, 1995; Knill and Pouget, 2004) and many other compelling proposals about perceptual synthesis – including analysis by synthesis (Neisser, 1967; Yuille and Kersten, 2006) epistemological automata (MacKay, 1956), the principle of minimum redundancy (Attneave, 1954; Barlow, H.B., 1961; Dan et al., 1996), the Infomax pri…”

“Feedback connections were typically seen when pyramidal cells in one layer targeted inhibitory cells in another (see Thomson and Bannister, 2003 for a review).”

“Distinct (laminar-specific) extrinsic connections (Zeki and Shipp, 1988; Felleman and Van Essen, 1991; Barone et al., 2000; Vezoli et al., 2004; Markov et al., 2011).”

“This issue is important as distinct neuronal dynamics in different cortical layers are becoming increasingly apparent (de Kock et al., 2007; Sakata and Harris, 2009; Maier et al., 2010; Bollimunta et al., 2011).”

“Furthermore, there is a specific type of GABAergic neuron that appears to control distal dendritic excitability, gating top-down excitatory signals differentially during behavior (Gentet et al., 2012).”

“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).”

“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).”

“The numbers denote connection strengths (mean amplitude of PSPs measured at soma in mV) and connection probabilities (in parentheses) according to Thomson et al. (2002).”

“More Neuron 76, November 21, 2012 ª2012 Elsevier Inc. 701 recently, George and Hawkins have suggested that the canonical microcircuit implements a form of Bayesian processing (George and Hawkins, 2009).”

“Columns, Connections, and Computations So is the cortical column the basic unit of cortical computation? Some authors emphasize that even within a dendrite, there are all the necessary biophysical mechanisms for performing surprisingly advanced computations, such as direction selectivity, coincidence detection, or tem…”

“Similarly, violating expectations of auditory repetition causes enhanced gamma-band responses in early auditory cortex (Todorovic et al., 2011).”

“For more information on inhibitory connections, see Yoshimura and Callaway (2005).”

“…(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).”

“The strongest evidence for this claim comes from the somatosensory system, where it was shown recently that the posterior medial nucleus of the thalamus (POm) – a higher-order thalamic nucleus that receives direct input from cortex – can relay information between S1 and S2 (Theyel et al., 2009).”

“Although it is generally thought that feedback connections are weak and modulatory (Crick and Koch, 1998; Sherman and Guillery, 1998), recent evidence suggests that feedback connections do more than modulate lower-level responses: Sherman and colleagues recorded cells in mouse areas V1/V2 and…”

“Finally, others have argued for an inhibitory effect of feedback based on the timing and spatial extent of surround suppression in monkey V1 – concluding that the far surround suppression effects were most likely mediated by feedback (Bair et al., 2003).”

“This issue is important as distinct neuronal dynamics in different cortical layers are becoming increasingly apparent (de Kock et al., 2007; Sakata and Harris, 2009; Maier et al., 2010; Bollimunta et al., 2011).”

“Furthermore, computational considerations and recent experimental findings point to a potentially important role for higher-order thalamic nuclei in coordinating and synchronizing cortical responses (Vicente et al., 2008; Saalmann et al., 2012).”

“…anatomically interconnected, but mounting evidence suggests that they constitute functionally distinct processing streams: in an elegant experiment, Roopun et al. (2006) showed that L2/3 of rat somatomotor cortex shows prominent gamma oscillations that are coexpressed with beta oscillations in L5.”

“…while many studies have focused on extrinsic connections that project directly from one cortical area to the next, there is mounting evidence that feedforward driving connections (and perhaps feedback) in the cortex could be mediated by transthalamic pathways (Sherman and Guillery, 1998, 2011).”

“…view is that extrinsic corticocortical connections are exclusively excitatory (using glutamate as their excitatory neurotransmitter), although recent evidence suggests that inhibitory extrinsic connections exist andmay play an important role in synchronizing distant regions (Melzer et al., 2012).”

“Weiler and colleagues combined whole-cell recordings in mouse motor cortex with photostimulation to uncage Glutamate (Weiler et al., 2008).”

“Furthermore, neurons in monkey inferotemporal cortex respond significantly less to a predicted sequence of natural images, compared to an unpredicted sequence (Meyer and Olson, 2011).”

“However, one might speculate 706 Neuron 76, November 21, 2012 ª2012 Elsevier Inc. that the characteristic frequencies of canonical microcircuits have evolved to model and—through active inference—create the sensorium (Berkes et al., 2011; Engbert et al., 2011; Friston, 2010).”

“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).”

“This view has re-emerged in recent years, with the development of the requisite recording and analytic techniques for evaluating this proposal (Buzsáki, 2010; Canolty et al., 2010; Singer et al., 1997; Lopes-dos-Santos et al., 2011).”

“This view has re-emerged in recent years, with the development of the requisite recording and analytic techniques for evaluating this proposal (Buzsáki, 2010; Canolty et al., 2010; Singer et al., 1997; Lopes-dos-Santos et al., 2011).”

“Furthermore, simple cells project monosynaptically onto complex cells, where they exert a strong feedforward influence (Alonso and Martinez, 1998; Alonso, 2002).”

“Others suggest that this circuitry allows the cortex to organize and integrate bottom-up, lateral, and top-down information (Ullman, 1995; Raizada and Grossberg, 2003).”

“It should be noted that the suppression of responses to predictable stimuli can coexist with (top-down) attentional enhancement of signal 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, 2…”

“Others suggest that this circuitry allows the cortex to organize and integrate bottom-up, lateral, and top-down information (Ullman, 1995; Raizada and Grossberg, 2003).”

“of feline LGN cells: without feedback, LGN cells are disinhibited and show weaker surround suppression (Murphy and Sillito, 1987; Sillito et al., 1993; but see Alitto and Usrey, 2008).”

“…(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).”

“The laminar location highlighted by these studies—the bottom of L1 and the top of L2/3—has recently been shown to be a ‘‘hotspot’’ of inhibition in the column (Meyer et al., 2011).”

“, 1996), the Infomax principle (Linsker, 1990; Atick, 2011; Kay and Phillips, 2011), andperceptionashypothesis testing (Gregory,1968,1980).”

“Several conclusions can be drawn from this approach (Kätzel et al., 2011): first, L4 inhibitory connections are more restricted in their lateral extent, relative to other layers.”

“Andre M. Bastos,1,2,6 W. Martin Usrey,1,3,4 Rick A. Adams,8 George R. Mangun,2,3,5 Pascal Fries,6,7 and Karl J. Friston8,* 1Center for Neuroscience 2Center for Mind and Brain 3Department of Neurology 4Department of Neurobiology, Physiology and Behavior 5Department of Psychology University of California, Davis, Davis,…”

“The ensuing architecture bears a striking correspondence to the microcircuit in (Haeusler and Maass, 2007) in the left panel of Figure 5 – in the sense that nearly every connection required by the predictive coding scheme appears to be present in terms of quantitative measures of intrinsic connectivity.”

“In all cases—when V1 is reversibly inactivated through cooling— single-cell activity in target areas is strongly suppressed (Girard and Bullier, 1989; Girard et al., 1991a, 1991b, 1992).”

“When visual stimuli were presented in the classical receptive field (CRF), cooling of area V5/MT decreased unit activity in earlier areas, suggesting an excitatory effect of extrinsic feedback (Hupé et al., 1998).”

“This finding is consistent with an earlier study by Livingstone (1996) showing that 50%of cells in L2/3 of squirrel monkey V1 expressed gamma oscillations, compared to less than 20% of cells in L4C and infragranular layers.”

“While these studies provide convincing evidence that cortical feedback to the LGN is inhibitory, the evidence is more complicated for corticocortical feedback connections (Sandell and Schiller, 1982; Johnson and Burkhalter, 1996, 1997).”

“Indeed, there is empirical evidence to support this notion in the visual (Lakatos et al., 2008; Meirovithz et al., 2012; Bosman et al., 2012) and motor (Gwin and Ferris, 2012) domain.”

“In all cases – when V1 is reversibly inactivated through cooling – single-cell activity in target areas is strongly suppressed (Girard and Bullier, 1989; Girard et al., 1991a, 1991b, 1992).”

“These L1 cells are almost all inhibitory and interconnect strongly with each other, via electrical connections and chemical synapses (Chu et al., 2003).”

“Feedback extrinsic connections are (driving and) modulatory (Mignard and Malpeli, 1991; Bullier et al., 1996; Sherman and Guillery, 1998; Covic and Sherman, 2011; De Pasquale and Sherman, 2011).”

“…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, 2010).”

“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., 2…”

“…contributions to length tuning in the LGN, showing that cortical feedback contributes to the surround suppression of feline LGN cells: without feedback, LGN cells are disinhibited and show weaker surround suppression (Murphy and Sillito, 1987; Sillito et al., 1993; but see Alitto and Usrey, 2008).”

“…smoothing—inherent in Bayesian filtering—leads to an asymmetry in frequency content of superficial and deep cells: for example, superficial cells should express more gamma relative to beta, and deep cells should express more beta relative to gamma (Roopun et al., 2006, 2008; Maier et al., 2010).”

“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).”

“However, one might speculate 706 Neuron 76, November 21, 2012 ª2012 Elsevier Inc. that the characteristic frequencies of canonical microcircuits have evolved to model and—through active inference—create the sensorium (Berkes et al., 2011; Engbert et al., 2011; Friston, 2010).”

“The corticogeniculate feedback pathway from L6 maintains this segregation, as upper L6 cells preferentially synapse onto parvocellular cells in the LGN, while lower L6 cells target the magnocellular LGN layers (Fitzpatrick et al., 1994; Briggs and Usrey, 2009).”

“This evidence is in line with classical studies of corticogeniculate contributions to length tuning in the LGN, showing that cortical feedback contributes to the surround suppression of feline LGN cells: without feedback, LGN cells are disinhibited and show weaker surround suppression (Murphy and Sillito, 1987; Sillit…”

“Dynamic causal modeling enables one to compare different connectivity models, using empirical electrophysiological responses (David et al., 2006; Moran et al., 2008, 2011).”

“The corticogeniculate feedback pathway from L6 maintains this segregation, as upper L6 cells preferentially synapse onto parvocellular cells in the LGN, while lower L6 cells target the magnocellular LGN layers (Fitzpatrick et al., 1994; Briggs and Usrey, 2009).”

“Feedback extrinsic connections are inhibitory (Murphy and Sillito, 1987; Sillito et al., 1993; Chu et al., 2003; Olsen et al., 2012; Meyer et al., 2011; Wozny and Williams, 2011).”

“In addition, the thalamic reticular nucleus has been proposed to mediate the inhibition that might underlie crossmodal attention or top-down predictions (Yamaguchi and Knight, 1990; Crick, 1984; Wurtz et al., 2011).”

“Dynamic causal modeling enables one to compare different connectivity models, using empirical electrophysiological responses (David et al., 2006; Moran et al., 2008, 2011).”

“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.”

“Feedback extrinsic connections are (driving and) modulatory (Mignard and Malpeli, 1991; Bullier et al., 1996; Sherman and Guillery, 1998; Covic and Sherman, 2011; De Pasquale and Sherman, 2011).”

“%) do not project outside the cortical column (Callaway and Wiser, 1996; Briggs and Callaway, 2005). d Second, we know that the superficial and deep pyramidal cells provide feedforward and feedback connections, respectively.”

“Similar effects were observed when area V2was cooled and neurons weremeasured in V1: when stimuli were presented only to the CRF, cooling V2 decreased V1 spiking activity; however, when stimuli were present in the CRF and the surround, cooling V2 increased V1 activity (Bullier et al., 1996).”

“While these studies provide convincing evidence that cortical feedback to the LGN is inhibitory, the evidence is more complicated for corticocortical feedback connections (Sandell and Schiller, 1982; Johnson and Burkhalter, 1996, 1997).”

“In all cases—when V1 is reversibly inactivated through cooling— single-cell activity in target areas is strongly suppressed (Girard and Bullier, 1989; Girard et al., 1991a, 1991b, 1992).”

“…supported these predictions, showing that input layers 4Ca and 4Cb contained the largest proportion of cells receiving monosynaptic geniculate input, while superficial and deep layer cells contain a larger number of cells receiving disynaptic or polysynaptic input (Bullier and Henry, 1980).”

“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).”

“This view has re-emerged in recent years, with the development of the requisite recording and analytic techniques for evaluating this proposal (Buzsáki, 2010; Canolty et al., 2010; Singer et al., 1997; Lopes-dos-Santos et al., 2011).”

“…automata (MacKay, 1956), the principle of minimum redun- 702 Neuron 76, November 21, 2012 ª2012 Elsevier Inc. dancy (Attneave, 1954; Barlow, 1961; Dan et al., 1996), the Infomax principle (Linsker, 1990; Atick, 2011; Kay and Phillips, 2011), andperceptionashypothesis testing (Gregory,1968,1980).”

“While these studies provide convincing evidence that cortical feedback to the LGN is inhibitory, the evidence is more complicated for corticocortical feedback connections (Sandell and Schiller, 1982; Johnson and Burkhalter, 1996, 1997).”

“In all cases—when V1 is reversibly inactivated through cooling— single-cell activity in target areas is strongly suppressed (Girard and Bullier, 1989; Girard et al., 1991a, 1991b, 1992).”

“However, one important route by which feedback connections could mediate selective inhibition is via their termination in L1 (Anderson and Martin, 2006; Shipp, 2007): layer 1 is sometimes referred to as acellular due to its pale appearance with Nissl staining (the classical method for separating…”

“%) do not project outside the cortical column (Callaway and Wiser, 1996; Briggs and Callaway, 2005). d Second, we know that the superficial and deep pyramidal cells provide feedforward and feedback connections, respectively.”

“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).”

“Indeed, a study of rat barrel cortex, which stimulated (and inactivated) L1, showed that it exerts a powerful inhibitory effect on whisker-evoked responses (Shlosberg et al., 2006).”

“Indeed, there is empirical evidence to support this notion in the visual (Lakatos et al., 2008; Meirovithz et al., 2012; Bosman et al., 2012) and motor (Gwin and Ferris, 2012) domain.”

“Furthermore, simple cells project monosynaptically onto complex cells, where they exert a strong feedforward influence (Alonso and Martinez, 1998; Alonso, 2002).”

“Others argue that single neurons can process their inputs at the dendrite, soma, and initial segment, such that the output spike trains of just two interconnected cells could mediate computations like independent components analysis (Klampfl et al., 2009).”

“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.”

“A simplified canonical microcircuit (36) includes intrinsic connectivity (inhibitory and excitatory) and extrinsic forward and backward connectivity.”