Ventromedial Frontal Cortex Is Critical for Guiding Attention to Reward-Predictive Visual Features in Humans

“They were excluded if they scored 25 or less on the Montreal Cognitive Assessment (Nasreddine et al., 2005).”

“This sort of biased competition has been suggested as a mechanism by which PFC could influence selective attention (Desi- mone and Duncan, 1995) and decision-making (Miller and Cohen, 2001; Cisek and Kalaska, 2010; Cisek, 2012).”

“Additional neglect screening was performed with a classic Posner spatial cueing task (Posner, 1980), which was tested with a two-way mixedmeasures ANOVA, with a factor for group status and target location (left or right, or contralesional or ipsilesional).”

“…this theory, orbitofrontal lesions in rats reduce the sensitivity of dopaminergic neurons in the ventral tegmental area to prediction errors (Takahashi et al., 2011), which are considered a physiological correlate of the teaching signal described by animal learning theorists (Schultz et al., 1997).”

“This sort of biased competition has been suggested as a mechanism by which PFC could influence selective attention (Desi- mone and Duncan, 1995) and decision-making (Miller and Cohen, 2001; Cisek and Kalaska, 2010; Cisek, 2012).”

“Attentional bias to reward-associated stimuli is thought to reflect the activation of the behavioral approach system (Gray, 1991; Ikemoto and Panksepp, 1999) or a change in the incentive salience of previously neutral stimuli (Robinson and Berridge, 1993; Maunsell, 2004).”

“In this framework, attention is directed to features based on their predictive value, providing an additional layer of learning about the nature of the environment that adjusts the gain on prediction errors for individual stimulus features (Mackintosh, 1975; Pearce and Hall, 1980; Le Pelley, 2010a; Pearce and Mackinto…”

“In this framework, attention is directed to features based on their predictive value, providing an additional layer of learning about the nature of the environment that adjusts the gain on prediction errors for individual stimulus features (Mackintosh, 1975; Pearce and Hall, 1980; Le Pelley, 2010a; Pearce and Mackinto…”

“Schioppa and Assad, 2006; Kable and Glimcher, 2007; Boorman et al., 2009; Kennerley et al., 2011).”

“The amygdala and pulvinar nucleus of the thalamus could also mediate the influence of rewards on attention, similar to their proposed role in mediating attention to emotional stimuli (Pessoa and Adolphs, 2010).”

“This sort of biased competition has been suggested as a mechanism by which PFC could influence selective attention (Desi- mone and Duncan, 1995) and decision-making (Miller and Cohen, 2001; Cisek and Kalaska, 2010; Cisek, 2012).”

“Magnetoencephalography data indicate that the VMF and ventral visual regions communicate within a timeframe that could allow the VMF to directly influence selective attention processes underlying visual search (Luck et al., 2000; Bar et al., 2006).”

“VLSM is an analytic approach that overcomes this limitation, systematically testing the effect of damage at the voxel level (Bates et al., 2003; Rorden et al., 2007), although with greater power for detecting effects in regions with greater lesion overlap (Kimberg et al.”

“Attentional bias to reward-associated stimuli is thought to reflect the activation of the behavioral approach system (Gray, 1991; Ikemoto and Panksepp, 1999) or a change in the incentive salience of previously neutral stimuli (Robinson and Berridge, 1993; Maunsell, 2004).”

“VLSM is an analytic approach that overcomes this limitation, systematically testing the effect of damage at the voxel level (Bates et al., 2003; Rorden et al., 2007), although with greater power for detecting effects in regions with greater lesion overlap (Kimberg et al.”

“This region is connected robustly with subcortical regions involved in reward processing (Carmichael and Price, 1995a; Eblen and Graybiel, 1995; Cavada et al., 2000; Price, 2007) and has reciprocal connections with diverse sensory systems (Carmichael and Price, 1995b).”

“Magnetoencephalography data indicate that the VMF and ventral visual regions communicate within a timeframe that could allow the VMF to directly influence selective attention processes underlying visual search (Luck et al., 2000; Bar et al., 2006).”

“This task involved a priming of pop-out manipulation (Maljkovic and Nakayama, 1994), in which the color of the target and salient distractor would randomly remain the same, or switch, every trial.”

“Selective attention allows us to filter the external world and focus on what matters, such as cues that predict rewards (Della Libera and Chelazzi, 2006, 2009; Kiss et al., 2009; Hickey et al., 2010a,b; Kristjánsson et al., 2010; Anderson et al., 2011a,b).”

“This region is connected robustly with subcortical regions involved in reward processing (Carmichael and Price, 1995a; Eblen and Graybiel, 1995; Cavada et al., 2000; Price, 2007) and has reciprocal connections with diverse sensory systems (Carmichael and Price, 1995b).”

“This allowed us to test how attention is biased by reward independent of explicit task goals, shedding light on a potential mechanism underlying previous observations of impaired value-based learning and decision-making after VMF damage (Zald and Andreotti, 2010; Fellows, 2011).”

“Imaging and monkey electrophysiology studies support these findings, showing that VMF activity encodes the relative value of options (Thorpe et al., 1983; Padoa- Received April 25, 2015; revised July 3, 2015; accepted Aug. 9, 2015.”

“This region is connected robustly with subcortical regions involved in reward processing (Carmichael and Price, 1995a; Eblen and Graybiel, 1995; Cavada et al., 2000; Price, 2007) and has reciprocal connections with diverse sensory systems (Carmichael and Price, 1995b).”

“Schioppa and Assad, 2006; Kable and Glimcher, 2007; Boorman et al., 2009; Kennerley et al., 2011).”

“Selective attention allows us to filter the external world and focus on what matters, such as cues that predict rewards (Della Libera and Chelazzi, 2006, 2009; Kiss et al., 2009; Hickey et al., 2010a,b; Kristjánsson et al., 2010; Anderson et al., 2011a,b).”

“…have been observed after VMF or orbitofrontal damage in humans and nonhuman primates but only under specific conditions (Butter, 1968; Jones and Mishkin, 1972; Hornak et al., 2004; Noonan et al., 2010; Tsuchida et al., 2010; Walton et al., 2010; but see Jones et al., 2012; Rudebeck et al., 2013).”

“Premorbid intelligence quotient (IQ) was estimated using the American Nelson Reading Test (AMNART; Grober and Sliwinski, 1991).”

“Lesions to this region in patients and animal models impair learning about dynamic stimulus–reward associations (Berlin et al., 2004; Tsuchida et al., 2010; Walton et al., 2010).”

“Subjects are more efficient at detecting targets that appear in the same location compared with when the location changes and are less efficient when targets appear where a distractor appeared on the previous trial (Maljkovic and Nakayama, 1996; Kristjánsson et al., 2007).”

“Schioppa and Assad, 2006; Kable and Glimcher, 2007; Boorman et al., 2009; Kennerley et al., 2011).”

“Selective attention allows us to filter the external world and focus on what matters, such as cues that predict rewards (Della Libera and Chelazzi, 2006, 2009; Kiss et al., 2009; Hickey et al., 2010a,b; Kristjánsson et al., 2010; Anderson et al., 2011a,b).”

“Attentional bias to reward-associated stimuli is thought to reflect the activation of the behavioral approach system (Gray, 1991; Ikemoto and Panksepp, 1999) or a change in the incentive salience of previously neutral stimuli (Robinson and Berridge, 1993; Maunsell, 2004).”

“This region is connected robustly with subcortical regions involved in reward processing (Carmichael and Price, 1995a; Eblen and Graybiel, 1995; Cavada et al., 2000; Price, 2007) and has reciprocal connections with diverse sensory systems (Carmichael and Price, 1995b).”

“…learning impairments have been observed after VMF or orbitofrontal damage in humans and nonhuman primates but only under specific conditions (Butter, 1968; Jones and Mishkin, 1972; Hornak et al., 2004; Noonan et al., 2010; Tsuchida et al., 2010; Walton et al., 2010; but see Jones et al.,…”

“This region is connected robustly with subcortical regions involved in reward processing (Carmichael and Price, 1995a; Eblen and Graybiel, 1995; Cavada et al., 2000; Price, 2007) and has reciprocal connections with diverse sensory systems (Carmichael and Price, 1995b).”

“…have been observed after VMF or orbitofrontal damage in humans and nonhuman primates but only under specific conditions (Butter, 1968; Jones and Mishkin, 1972; Hornak et al., 2004; Noonan et al., 2010; Tsuchida et al., 2010; Walton et al., 2010; but see Jones et al., 2012; Rudebeck et al., 2013).”

“Selective attention allows us to filter the external world and focus on what matters, such as cues that predict rewards (Della Libera and Chelazzi, 2006, 2009; Kiss et al., 2009; Hickey et al., 2010a,b; Kristjánsson et al., 2010; Anderson et al., 2011a,b).”

“This ability would be particularly critical in complex environments in which options are defined by multiple features (Wilson and Niv, 2011; Niv et al., 2015).”

“Damage to this region does not affect learning about the reward value of stimuli in deterministic settings (Dias, Robbins, and Roberts, 1996; Fellows and Farah, 2003) or learning to associate probabilistic reward to actions (Rudebeck et al., 2008; Camille et al., 2011).”

“…have been observed after VMF or orbitofrontal damage in humans and nonhuman primates but only under specific conditions (Butter, 1968; Jones and Mishkin, 1972; Hornak et al., 2004; Noonan et al., 2010; Tsuchida et al., 2010; Walton et al., 2010; but see Jones et al., 2012; Rudebeck et al., 2013).”

“VLSM may also be biased toward the region of maximal overlap in a given sample, affecting the anatomical precision of structure–function claims (Kimberg et al., 2007; Mah et al., 2014).”

“Selective attention allows us to filter the external world and focus on what matters, such as cues that predict rewards (Della Libera and Chelazzi, 2006, 2009; Kiss et al., 2009; Hickey et al., 2010a,b; Kristjánsson et al., 2010; Anderson et al., 2011a,b).”

“This sort of biased competition has been suggested as a mechanism by which PFC could influence selective attention (Desi- mone and Duncan, 1995) and decision-making (Miller and Cohen, 2001; Cisek and Kalaska, 2010; Cisek, 2012).”

“, 2007), although with greater power for detecting effects in regions with greater lesion overlap (Kimberg et al., 2007).”

“…with this theory, orbitofrontal lesions in rats reduce the sensitivity of dopaminergic neurons in the ventral tegmental area to prediction errors (Takahashi et al., 2011), which are considered a physiological correlate of the teaching signal described by animal learning theorists (Schultz et…”

“Selective attention allows us to filter the external world and focus on what matters, such as cues that predict rewards (Della Libera and Chelazzi, 2006, 2009; Kiss et al., 2009; Hickey et al., 2010a,b; Kristjánsson et al., 2010; Anderson et al., 2011a,b).”

“This sort of maladaptive priming could result from an impaired representation of the variance of rewards linked to the two colors, in line with electrophysiological evidence that orbitofrontal neurons encode this information (O’Neill and Schultz, 2010; Schultz et al., 2011).”

“Recent evidence points to a role for the lateral intraparietal area in representing the information value of cues for predicting future rewards (Peck et al., 2009; Foley et al., 2014).”

“Damage to this region does not affect learning about the reward value of stimuli in deterministic settings (Dias, Robbins, and Roberts, 1996; Fellows and Farah, 2003) or learning to associate probabilistic reward to actions (Rudebeck et al., 2008; Camille et al., 2011).”

“Previous work has found that reward expectations modify spatial attention, leading to prioritization of locations associated with greater likelihood of reward (Chelazzi et al., 2014; Hickey et al., 2014).”

“This rewardrelated attentional tuning might reflect an adaptive process, highlighting features based on their predictive value, which will in turn guide future learning (Mackintosh, 1975; Navalpakkam et al., 2010; Gottlieb, 2012; Wilson and Niv, 2011).”

“…have been observed after VMF or orbitofrontal damage in humans and nonhuman primates but only under specific conditions (Butter, 1968; Jones and Mishkin, 1972; Hornak et al., 2004; Noonan et al., 2010; Tsuchida et al., 2010; Walton et al., 2010; but see Jones et al., 2012; Rudebeck et al., 2013).”

“Orbitofrontal lesions in monkeys do not affect updating the value of primary rewards themselves but rather the ability to associate this value to a paired stimulus (Rudebeck and Murray, 2011).”

“This allowed us to test how attention is biased by reward independent of explicit task goals, shedding light on a potential mechanism underlying previous observations of impaired value-based learning and decision-making after VMF damage (Zald and Andreotti, 2010; Fellows, 2011).”

“Selective attention allows us to filter the external world and focus on what matters, such as cues that predict rewards (Della Libera and Chelazzi, 2006, 2009; Kiss et al., 2009; Hickey et al., 2010a,b; Kristjánsson et al., 2010; Anderson et al., 2011a,b).”

“This ability would be particularly critical in complex environments in which options are defined by multiple features (Wilson and Niv, 2011; Niv et al., 2015).”

“One possibility is that the VMF directly influences attention to reward associated stimuli through its connections with higher-order sensory regions (Carmichael and Price, 1995b; Barbas et al., 2011).”

“Recent work has shown that functional connectivity between the VMF and higher-order sensory regions is modulated dynamically as a function of the behavioral relevance of information processed in these areas (Philiastides et al., 2010; Lim et al., 2013).”

“Selective attention allows us to filter the external world and focus on what matters, such as cues that predict rewards (Della Libera and Chelazzi, 2006, 2009; Kiss et al., 2009; Hickey et al., 2010a,b; Kristjánsson et al., 2010; Anderson et al., 2011a,b).”

“This region might play a role in assigning attentional priority to stimulus attributes based on value associations encoded by VMF, as suggested recently by Hunt et al. (2014).”

“Recent work has shown that functional connectivity between the VMF and higher-order sensory regions is modulated dynamically as a function of the behavioral relevance of information processed in these areas (Philiastides et al., 2010; Lim et al., 2013).”

“…an increase in RT for trials in which colors switch compared with when they stay the same, which is thought to arise from an experience-dependent priming of search for the features discriminating the target from distractors in previous trials (Kristjánsson and Campana, 2010; Becker et al., 2013).”

“We applied this method in a secondary analysis, including all voxels in which at least three patients had damage (Coulthard et al., 2008; Haramati et al., 2008; Tsuchida et al., 2010).”

“Previous work has found that reward expectations modify spatial attention, leading to prioritization of locations associated with greater likelihood of reward (Chelazzi et al., 2014; Hickey et al., 2014).”

“Recent evidence points to a role for the lateral intraparietal area in representing the information value of cues for predicting future rewards (Peck et al., 2009; Foley et al., 2014).”

“This sort of maladaptive priming could result from an impaired representation of the variance of rewards linked to the two colors, in line with electrophysiological evidence that orbitofrontal neurons encode this information (O’Neill and Schultz, 2010; Schultz et al., 2011).”

“We also thank Joseph Kable for facilitating access to patients at the University of Pennsylvania and Anjan Chatterjee for providing lesion tracings for these patients.”

“…as the basal ganglia, more specifically, the rostral and caudal regions of the caudate nucleus in the striatum, and the VMPFC, which directly receives input from the basal ganglia (e.g., Anderson, Kuwabara, et al., 2016, 2017; Hickey & Peelen, 2015; Hikosaka et al., 2014; Vaidya & Fellows, 2015).”

“…by attention-dependent mOFC/vmPFC value signals (Lim et al., 2011) and by findings that lesions abolish the normal attentional advantage of reward-associated stimuli (Vaidya and Fellows, 2015) and diminish the influence of currently relevant stimulus dimensions on choice (Vaidya and Fellows, 2016).”

“Eventually, Vaidya and Fellows (2015) recently demonstrated a specific role of the ventromedial frontal (VMF) cortex for guiding attention in reward-predictive visual features.”

“…prefrontal cortex (vmPFC) and ventral striatum (VS; Hare et al., 2009; Rushworth et al., 2011; Jimura et al., 2013; FitzGerald et al., 2014; Vaidya and Fellows, 2015; Bissonette and Roesch, 2016), biasing choices away from immediate rewards (DelParigi et al., 2007; Hare et al., 2009; Kober…”

“First of all, lesions to the vmPFC lead to various decrements in decision making abilities, including learning from reward and punishment [42], making transitive choices [43], making future-oriented decisions [44], or directing attention towards reward-predicting information [45].”

“Thus, MFC represents internal focus, expressed in the choice (Lim et al., 2011; Vaidya and Fellows, 2015) as to which cue should be assigned credit for an outcome.”

“In a variety of different paradigms, VMF damage reduces sensitivity to reward cues (Aridan, Pelletier, Fellows, & Schonberg, 2019; Manohar & Husain, 2016; Pujara, Philippi, Motzkin, Baskaya, & Koenigs, 2016; Vaidya & Fellows, 2015b).”

“VmPFC value signals measured with fMRI are sensitive to the behavioral relevance of option dimensions during choice (Lim et al., 2013; Hunt et al., 2014), and the VMF is critical for attentional priming of rewarded stimulus features (Vaidya and Fellows, 2015).”

“We recently found evidence that another, more dorsal region within DMF [pre-supplementary motor area (preSMA)] is necessary for maintaining the value of the unattended option in a simple, two-choice value-based preference task (that did not involve learning) (Vaidya and Fellows 2015a).”

“This finding agrees with prior studies that point to other important structures and pathways that modulate visual perception [2,5,6,13,18,21].”

“…effects may be largely independent of HC and vmPFC systems when constructing and assimilating details into narratives is not required (Kwan et al., 2012, 2013; Mok et al., 2021) and in the absence of reward contingencies (Peters & D’Esposito, 2016; Vaidya et al., 2018; Vaidya & Fellows, 2015).”

“…(e.g. Paton et al., 2006 ), the ventral striatum ( Kable and Glimcher, 2009 ; Lim et al., 2011 ), and the ventromedial frontal lobe (VMF), including both the orbitofrontal and ventromedial prefrontal cortices ( Padoa-Schioppa and Assad, 2006 ; Rich and Wallis, 2016 ; Vaidya and Fellows, 2015 ).”

“The MedFC is located in the ventromedial frontal lobe, which is considered to play a role in guiding attention to stimulus features associated with the current task (Vaidya and Fellows, 2015).”