Anterior insular cortex and emotional awareness

“…awareness Although several other brain regions such as ACC, amygdala, and ventromedial prefrontal cortex are commonly implicated (Lane et al., 1998; LeDoux, 2000; Cohen et al., 2001; Adolphs, 2002; Ochsner and Gross, 2005; Phelps, 2006; Duncan and Barrett, 2007; Lieberman, 2007), the insular…”

“According to a predictive coding account of the brain (Dayan et al., 1995; Friston, 2002, 2010), bottomup stimulus-driven projections convey prediction errors, and top-down pathways convey active predictions.”

“Although AIC and ACC are usually considered as one system with AIC as the input sensory region and ACC as the output control region (Seeley et al., 2007; Craig, 2009; Jones et al., 2010), the finding that ACC is usually activated by but not necessary for empathetic pain perception suggests the…”

“…the insular cortex is roughly divided into an anterior agranular portion (anterior insula, AIC), a middle dysgranular portion (middle insula), and a posterior granular portion (posterior insula) in both humans (Flynn et al., 1999; Butti and Hof, 2010; Bauernfeind et al., 2013;…”

“…cortex has been commonly associated with somatotopic representations of bodily states such as itch, pain and temperature, and touch (Damasio et al., 2000; Craig, 2002, 2009; Harrison et al., 2010), whereas AIC participates in a wide range of functions, including and beyond bodily representations.”

“Third, although we were not able to compare gender differences in the current meta-analysis, males and females have been shown to use different strategies in emotion paradigms (Baron-Cohen and Wheelwright, 2004; Singer et al., 2006; Schulte-Ruther et al., 2008).”

“…general emotional processing (Davidson and Irwin, 1999; Zaki et al., 2012), cognitive control (Eckert et al., 2009; Menon and Uddin, 2010), empathy (Singer et al., 2004; Gu and Han, 2007a; Gu et al., 2010, 2012, 2013; Lamm et al., 2010; Ebisch et al., 2011), intuition (Kuo et al., 2009),…”

“By incorporating ideas from theoretical neurobiology, it has recently been suggested that predictive coding of interoceptive information is important in awareness (Seth et al., 2011).”

“*CORRESPONDENCE TO: Xiaosi Gu, PhD, Wellcome Trust Centre for Neuroimaging, University College London, 12 Queen Square, London, United Kingdom WC1N 3BG. E-mail: xiaosi.gu@ucl.ac.uk”

“, 2007), interoceptive awareness (Critchley et al., 2004; Zaki et al., 2012), general emotional processing (Davidson and Irwin, 1999; Zaki et al.”

“*CORRESPONDENCE TO: Xiaosi Gu, PhD, Wellcome Trust Centre for Neuroimaging, University College London, 12 Queen Square, London, United Kingdom WC1N 3BG. E-mail: xiaosi.gu@ucl.ac.uk”

“This implies that emotion can be viewed as a form of interoceptive inference; that is, subjective feelings are based on the active interpretation of changes in the physiological conditions of the body (Seth et al., 2011).”

“…that the insular cortex works closely with a network of regions, including the ACC (Critchley, 2004; Critchley et al., 2004; Medford and Critchley, 2010; Fan et al., 2011; Denny et al., 2012; Lindquist et al., 2012), somatosensory cortex (Gu et al., 2013), and amygdala (Etkin and Wager, 2007).”

“…insular cortex has been commonly associated with somatotopic representations of bodily states such as itch, pain and temperature, and touch (Damasio et al., 2000; Craig, 2002, 2009; Harrison et al., 2010), whereas AIC participates in a wide range of functions, including and beyond bodily…”

“…of work on emotion involves visual stimuli depicting another person’s emotions (e.g., facial expressions; for reviews see Davidson and Irwin, 1999; Adolphs, 2002; Phelps, 2006; Pessoa and Adolphs, 2010) because of the advantage of allowing specific yet flexible experimental manipulations (e.g.,…”

“Another study showed that AIC is activated by not only prediction of risk but also the prediction error of risk (Preuschoff et al., 2008), which relates to unexpected uncertainty and state transition (Yu and Dayan, 2005).”

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“Third, although we were not able to compare gender differences in the current meta-analysis, males and females have been shown to use different strategies in emotion paradigms (Baron-Cohen and Wheelwright, 2004; Singer et al., 2006; Schulte-Ruther et al., 2008).”

“…1997; Wicker et al., 2003; Calder et al., 2007), interoceptive awareness (Critchley et al., 2004; Zaki et al., 2012), general emotional processing (Davidson and Irwin, 1999; Zaki et al., 2012), cognitive control (Eckert et al., 2009; Menon and Uddin, 2010), empathy (Singer et al., 2004; Gu and…”

“…imaging (fMRI) studies (see Table 1) that examined brain activations related to empathy in healthy adults using the coordinate-based meta-analysis (Salimi-Khorshidi et al., 2009) of activation likelihood estimation (ALE) approach (Turkeltaub et al., 2002; Laird et al., 2005; Eickhoff et al., 2009).”

“…recently, it has been proposed that reactivation of bodily and neural responses involved in lower-level sensorimotor processes contributes to subjective awareness (Thompson and Varela, 2001; Niedenthal, 2007; Harrison et al., 2010; Gray et al., 2012; Oosterwijk et al., 2012; Pollatos et al., 2012).”

“In rats, the insular cortex is interconnected with the autonomic system as well as limbic and frontal regions (Saper and Loewy, 1980; Saper, 1982; Allen et al., 1991) and has been shown to contain a viscerotopic map (Cechetto and Saper, 1987).”

“In rats, the insular cortex is interconnected with the autonomic system as well as limbic and frontal regions (Saper and Loewy, 1980; Saper, 1982; Allen et al., 1991) and has been shown to contain a viscerotopic map (Cechetto and Saper, 1987).”

“According to a predictive coding account of the brain (Dayan et al., 1995; Friston, 2002, 2010), bottomup stimulus-driven projections convey prediction errors, and top-down pathways convey active predictions.”

“VC 2013 Wiley Periodicals, Inc. INDEXING TERMS: anterior insular cortex; emotional awareness; empathy; fMRI; meta-analysis; top-down; bottomup; predictive coding”

“…demonstrated that AIC and ACC are coactivated in various experimental paradigms (Critchley, 2004; Dosenbach et al., 2006; Craig, 2009; Medford and Critchley, 2010; Fan et al., 2011) as well as in resting states (Seeley et al., 2007; Britz et al., 2010; Cauda et al., 2011; Fan et al., 2012).”

“In other words, we borrow from the classical view that ACC serves as a limbic motor region and the AIC as a limbic sensory structure (Craig, 2009; Medford and Critchley, 2010).”

“, 2012), thermosensory awareness (Craig et al., 2000), disgust (Phillips et al.”

“…2007; Lieberman, 2007), the insular cortex has been singled out as a critical neural substrate for interoceptive and emotional awareness (Craig, 2009, 2010, 2011; Singer et al., 3372 The Journal of Comparative Neurology |Research in Systems Neuroscience 2009; Jones et al., 2010; Seth et al., 2011).”

“…that the insular cortex works closely with a network of regions, including the ACC (Critchley, 2004; Critchley et al., 2004; Medford and Critchley, 2010; Fan et al., 2011; Denny et al., 2012; Lindquist et al., 2012), somatosensory cortex (Gu et al., 2013), and amygdala (Etkin and Wager, 2007).”

“For instance, focal lesions in this region impair disgust perception (Calder et al., 2000).”

“In rats, the insular cortex is interconnected with the autonomic system as well as limbic and frontal regions (Saper and Loewy, 1980; Saper, 1982; Allen et al., 1991) and has been shown to contain a viscerotopic map (Cechetto and Saper, 1987).”

“…that the insular cortex works closely with a network of regions, including the ACC (Critchley, 2004; Critchley et al., 2004; Medford and Critchley, 2010; Fan et al., 2011; Denny et al., 2012; Lindquist et al., 2012), somatosensory cortex (Gu et al., 2013), and amygdala (Etkin and Wager, 2007).”

“In humans, the insula has bidirectional connections with the frontal, parietal, and temporal lobes; the cingulate gyrus; and subcortical structures such as the amygdala, brainstem, thalamus, and basal ganglia (Flynn et al., 1999).”

“…demonstrated that AIC and ACC are coactivated in various experimental paradigms (Critchley, 2004; Dosenbach et al., 2006; Craig, 2009; Medford and Critchley, 2010; Fan et al., 2011) as well as in resting states (Seeley et al., 2007; Britz et al., 2010; Cauda et al., 2011; Fan et al., 2012).”

“One previous study suggests that dorsolateral PFC is involved in cognition– emotion integration (Gray et al., 2002); however, cognitive and emotional information were spatially and temporally segregated in the design, so one can speak only to the existence of distinct yet partially shared…”

“Recent predictive coding formulations of motor control consider descending corticospinal signals from motor cortex to provide predictions or set-points for classical reflex arcs in the spinal cord (Adams et al., 2013).”

“…that the insular cortex works closely with a network of regions, including the ACC (Critchley, 2004; Critchley et al., 2004; Medford and Critchley, 2010; Fan et al., 2011; Denny et al., 2012; Lindquist et al., 2012), somatosensory cortex (Gu et al., 2013), and amygdala (Etkin and Wager, 2007).”

“Diminished ability to integrate information rapidly among spatially distinct regions may underlie functional deficits in these conditions and, ultimately, in the inability to make quick and intuitive judgments regarding uncertain and rapidly changing social contexts (Allman et al., 2005).”

“Among the popular tools to measure trait alexithymia is the 20-item Toronto Alexithymia Scale (TAS-20), which assesses three aspects of emotional deficits: difficulty in identifying emotions, difficulty in describing emotions, and externally oriented thinking style (Taylor et al., 2003).”

“Their ideas, usually mentioned together as the James-Lange theory, was challenged by the CannonBard theory (Bard, 1928; Cannon, 1932), which argues that bodily responses are the result, not the cause, of emotions and that a central nervous system is needed to generate emotional feelings.”

“Although much research has focused on the modulatory effect of one mental process on another (Ochsner and Gross, 2005; Blair et al., 2007), fMRI evidence supporting functional integration is limited.”

“…in the brain explains the involvement of AIC across low-level autonomic and sensorimotor (Craig et al., 2000; Sterzer and Kleinschmidt, 2010; Fan et al., 2012) to high-level cognitive and social (Montague and Lohrenz, 2007; King-Casas et al., 2008; Bossaerts, 2010; Kirk et al., 2011) domains.”

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“As assessed by TAS-20, the prevalence of alexithymia is approximately 10% in the general population (Kokkonen et al., 2001) and is remarkably high in patients with autism spectrum disorders (85%; Hill et al., 2004).”

“One study specifically showed that AIC encodes both prediction of pain and pain prediction error in the same task (Seymour et al., 2004), which directly supports the functional integration and predictive encoding account of AIC.”

“The following contrasts were identified as empathy for positive emotions: “overlap between sucrose–saliva and pleasant faces–neutral faces” (Jabbi et al., 2007) and “correlation of happy > neutral contrast with EQ” (Chakrabarti et al., 2006).”

“The insula has widespread connections with other parts of the brain (Saper, 2002).”

“Third, although we were not able to compare gender differences in the current meta-analysis, males and females have been shown to use different strategies in emotion paradigms (Baron-Cohen and Wheelwright, 2004; Singer et al., 2006; Schulte-Ruther et al., 2008).”

“In the current review, we simplify this definition as the conscious experience of emotions (the experiential or “feeling” domain of emotion); operationally, emotional awareness occurs during the supraliminal processing of affective stimuli (Pessoa, 2005).”

“frontal regions (Saper and Loewy, 1980; Saper, 1982; Allen et al., 1991) and has been shown to contain a viscerotopic map (Cechetto and Saper, 1987).”

“To date, VENs have been found to exist only in humans and great apes (Nimchinsky et al., 1995, 1999; Allman et al., 2010), macaque monkeys (Evrard et al., 2012), cetaceans and a number of their related terrestrial herbivore species (Hof and Van der Gucht, 2007; Butti et al., 2009, 2013; Butti and…”

“It is tempting to speculate that VENs of the AIC (which are located in layer V) play this role, as suggested by several investigators (Allman et al., 2005; Seeley et al., 2006; Butti and Hof, 2010; Evrard et al., 2012).”

“…intuition (Kuo et al., 2009), unfairness (Sanfey et al., 2003; Kirk et al., 2011), risk and uncertainty (Preuschoff et al., 2008; Bossaerts, 2010; Ullsperger et al., 2010; Bach and Dolan, 2012), trust and cooperation (King-Casas et al., 2008), and norm violations (Montague and Lohrenz, 2007;…”

“, 2012), general emotional processing (Davidson and Irwin, 1999; Zaki et al., 2012), cognitive”

“been found to exist only in humans and great apes (Nimchinsky et al., 1995, 1999; Allman et al., 2010), macaque monkeys (Evrard et al.”

“…(Critchley et al., 2004; Zaki et al., 2012), general emotional processing (Davidson and Irwin, 1999; Zaki et al., 2012), cognitive control (Eckert et al., 2009; Menon and Uddin, 2010), empathy (Singer et al., 2004; Gu and Han, 2007a; Gu et al., 2010, 2012, 2013; Lamm et al., 2010; Ebisch…”

“First, although the insular lesions in the two patients “Roger” (Khalsa et al., 2009; Philippi et al., 2012) and “M” (Damasio et al., 2013) are bilateral, there are still residual tissues in the insula that might convey some interoceptive information (Craig, 2011).”

“variant frontotemporal dementia (Seeley et al., 2006; Seeley, 2010; Kim et al., 2012), callosal agenesis (Kaufman et al.”

“…posterior-to-anterior gradient in the insular cortex has been proposed, in which physical features of interoception are processed in the posterior insula and the integration of interoception with cognitive and motivational information in the AIC, and the right AIC serves a more dominant role than…”

“…studies consistently show that AIC activation is associated with cardiovascular functions (King et al., 1999; Henderson et al., 2002), respiration (Banzett et al., 2000; Henderson et al., 2002), pain (Treede et al., 1999; Wager et al., 2004), touch (Keysers et al., 2004; Lindgren et al., 2012),…”

“…insula) in both humans (Flynn et al., 1999; Butti and Hof, 2010; Bauernfeind et al., 2013; Butti et al., 2013) and macaque monkeys (Mesulam and Mufson, 1982a), although more subdivisions have been revealed in monkeys recently (Gallay et al., 2012; Evrard H, Logothetis NK, Craig AD, in press).”

“Diminished ability to integrate information rapidly among spatially distinct regions may underlie functional deficits in these conditions and, ultimately, in the inability to make quick and intuitive judgments regarding uncertain and rapidly changing social contexts (Allman et al., 2005).”

“First, although the insular lesions in the two patients “Roger” (Khalsa et al., 2009; Philippi et al., 2012) and “M” (Damasio et al., 2013) are bilateral, there are still residual tissues in the insula that might convey some interoceptive information (Craig, 2011).”

“…2012), cognitive control (Eckert et al., 2009; Menon and Uddin, 2010), empathy (Singer et al., 2004; Gu and Han, 2007a; Gu et al., 2010, 2012, 2013; Lamm et al., 2010; Ebisch et al., 2011), intuition (Kuo et al., 2009), unfairness (Sanfey et al., 2003; Kirk et al., 2011), risk and uncertainty…”

“…that the insular cortex works closely with a network of regions, including the ACC (Critchley, 2004; Critchley et al., 2004; Medford and Critchley, 2010; Fan et al., 2011; Denny et al., 2012; Lindquist et al., 2012), somatosensory cortex (Gu et al., 2013), and amygdala (Etkin and Wager, 2007).”

“…cortex has been commonly associated with somatotopic representations of bodily states such as itch, pain and temperature, and touch (Damasio et al., 2000; Craig, 2002, 2009; Harrison et al., 2010), whereas AIC participates in a wide range of functions, including and beyond bodily representations.”

“…2) did not report results in Talairach or Montreal Neurological Institute (MNI) space; 3) used tasks unrelated to empathetic processes and with no measurement of trait empathy; 4) were based on structural analyses only; 5) were based on region of interest (ROI) analysis (e.g., using…”

“As assessed by TAS-20, the prevalence of alexithymia is approximately 10% in the general population (Kokkonen et al., 2001) and is remarkably high in patients with autism spectrum disorders (85%; Hill et al., 2004).”

“However, it has been suggested that only coarse affective properties can be registered without awareness (Pessoa, 2005) and that the capacity to experience emotions fully significantly increases the likelihood of one to make an appropriate action or decision (Lane and Schwartz, 1987).”

“most abundant in humans and are found primarily in layer Vb in the anterior cingulate cortex (ACC; Nimchinsky et al., 1995) and in the junction of the posterior orbitofrontal cor-”

“For example, the following contrasts were identified as empathy for pain: “main effect of pain: pain>no pain” (Akitsuki and Decety, 2009) and “other’s pain>self pain” (Ochsner et al.”

“Diminished ability to integrate information rapidly among spatially distinct regions may underlie functional deficits in these conditions and, ultimately, in the inability to make quick and intuitive judgments regarding uncertain and rapidly changing social contexts (Allman et al., 2005).”

“, 2012), somatosensory cortex (Gu et al., 2013), and amygdala (Etkin and Wager, 2007).”

“…part of hierarchical predictive coding in the brain explains the involvement of AIC across low-level autonomic and sensorimotor (Craig et al., 2000; Sterzer and Kleinschmidt, 2010; Fan et al., 2012) to high-level cognitive and social (Montague and Lohrenz, 2007; King-Casas et al., 2008; Bossaerts,…”

“…and Han, 2007a; Gu et al., 2010, 2012, 2013; Lamm et al., 2010; Ebisch et al., 2011), intuition (Kuo et al., 2009), unfairness (Sanfey et al., 2003; Kirk et al., 2011), risk and uncertainty (Preuschoff et al., 2008; Bossaerts, 2010; Ullsperger et al., 2010; Bach and Dolan, 2012), trust and…”

“…recently, it has been proposed that reactivation of bodily and neural responses involved in lower-level sensorimotor processes contributes to subjective awareness (Thompson and Varela, 2001; Niedenthal, 2007; Harrison et al., 2010; Gray et al., 2012; Oosterwijk et al., 2012; Pollatos et al., 2012).”

“…analysis, or functional or effective connectivity analysis only; 6) were based on special populations (e.g., children, aging adults, psychiatric patients, medical physicians, Buddhist meditators); and 7) focused on the cognitive aspects of understanding others’ mental states (i.e., theory of mind).”

“…humans and great apes (Nimchinsky et al., 1995, 1999; Allman et al., 2010), macaque monkeys (Evrard et al., 2012), cetaceans and a number of their related terrestrial herbivore species (Hof and Van der Gucht, 2007; Butti et al., 2009, 2013; Butti and Hof, 2010), and elephants (Hakeem et al., 2009).”

“The following contrasts were identified as empathy for positive emotions: “overlap between sucrose–saliva and pleasant faces–neutral faces” (Jabbi et al., 2007) and “correlation of happy > neutral contrast with EQ” (Chakrabarti et al., 2006).”

“This notion is supported by the functional connectivity between ACC and lateral prefrontal, primary, and supplementary motor areas during conflict processing (Fan et al., 2008).”

“, 2010), macaque monkeys (Evrard et al., 2012), cetaceans and a num-”

“…2007; Lieberman, 2007), the insular cortex has been singled out as a critical neural substrate for interoceptive and emotional awareness (Craig, 2009, 2010, 2011; Singer et al., 3372 The Journal of Comparative Neurology |Research in Systems Neuroscience 2009; Jones et al., 2010; Seth et al., 2011).”

“…(Keysers et al., 2004; Lindgren et al., 2012), thermosensory awareness (Craig et al., 2000), disgust (Phillips et al., 1997; Wicker et al., 2003; Calder et al., 2007), interoceptive awareness (Critchley et al., 2004; Zaki et al., 2012), general emotional processing (Davidson and Irwin, 1999;…”

“…in the brain explains the involvement of AIC across low-level autonomic and sensorimotor (Craig et al., 2000; Sterzer and Kleinschmidt, 2010; Fan et al., 2012) to high-level cognitive and social (Montague and Lohrenz, 2007; King-Casas et al., 2008; Bossaerts, 2010; Kirk et al., 2011) domains.”

“, 2011), intuition (Kuo et al., 2009), unfairness (Sanfey et al.”

“In the current review, we simplify this definition as the conscious experience of emotions (the experiential or “feeling” domain of emotion); operationally, emotional awareness occurs during the supraliminal processing of affective stimuli (Pessoa, 2005).”

“…humans and great apes (Nimchinsky et al., 1995, 1999; Allman et al., 2010), macaque monkeys (Evrard et al., 2012), cetaceans and a number of their related terrestrial herbivore species (Hof and Van der Gucht, 2007; Butti et al., 2009, 2013; Butti and Hof, 2010), and elephants (Hakeem et al., 2009).”

“For example, the following contrasts were identified as empathy for pain: “main effect of pain: pain>no pain” (Akitsuki and Decety, 2009) and “other’s pain>self pain” (Ochsner et al., 2008).”

“…associated with neuropathological degeneration of the VENs and functional deficits of the AIC, such as behavioral variant frontotemporal dementia (Seeley et al., 2006; Seeley, 2010; Kim et al., 2012), callosal agenesis (Kaufman et al., 2008), and autism (Santos et al., 2011; Butti et al., 2013).”

“…al., 2002), respiration (Banzett et al., 2000; Henderson et al., 2002), pain (Treede et al., 1999; Wager et al., 2004), touch (Keysers et al., 2004; Lindgren et al., 2012), thermosensory awareness (Craig et al., 2000), disgust (Phillips et al., 1997; Wicker et al., 2003; Calder et al., 2007),…”

“The insula, and especially the agranular AIC, is also among the most differentially expanded neocortical regions in humans compared with other primate species (Bauernfeind et al., 2013).”

“…dysgranular portion (middle insula), and a posterior granular portion (posterior insula) in both humans (Flynn et al., 1999; Butti and Hof, 2010; Bauernfeind et al., 2013; Butti et al., 2013) and macaque monkeys (Mesulam and Mufson, 1982a), although more subdivisions have been revealed in…”

“…Neurology | Research in Systems Neuroscience 3379 in generating awareness, yet it might receive input from AIC and convey the “feeling” information to other brain networks that serve voluntary control functions (Posner and Rothbart, 1998; Craig, 2009; Medford and Critchley, 2010; Valentini, 2010).”

“This implies that emotion can be viewed as a form of interoceptive inference; that is, subjective feelings are based on the active interpretation of changes in the physiological conditions of the body (Seth et al., 2011).”

“Another distinguishing feature of AIC is that it contains a special group of large, bipolar, spindle-shaped neurons referred to as von Economo neurons (VENs; von Economo, 1926; Seeley et al., 2012).”

“Coactivation of AIC and ACC: a meta-analysis on empathy To overcome the heterogeneity in experimental methods and achieve an unbiased quantification of neural substrates underlying empathy, we first conducted a quantitative meta-analysis on 47 functional magnetic resonance imaging (fMRI) studies…”

“Another distinguishing feature of AIC is that it contains a special group of large, bipolar, spindle-shaped neurons referred to as von Economo neurons (VENs; von Economo, 1926; Seeley et al., 2012).”

“…show that AIC activation is associated with cardiovascular functions (King et al., 1999; Henderson et al., 2002), respiration (Banzett et al., 2000; Henderson et al., 2002), pain (Treede et al., 1999; Wager et al., 2004), touch (Keysers et al., 2004; Lindgren et al., 2012), thermosensory awareness…”

“…coding in the brain explains the involvement of AIC across low-level autonomic and sensorimotor (Craig et al., 2000; Sterzer and Kleinschmidt, 2010; Fan et al., 2012) to high-level cognitive and social (Montague and Lohrenz, 2007; King-Casas et al., 2008; Bossaerts, 2010; Kirk et al., 2011)…”

“Diminished ability to integrate information rapidly among spatially distinct regions may underlie functional deficits in these conditions and, ultimately, in the inability to make quick and intuitive judgments regarding uncertain and rapidly changing social contexts (Allman et al., 2005).”

“…several other brain regions such as ACC, amygdala, and ventromedial prefrontal cortex are commonly implicated (Lane et al., 1998; LeDoux, 2000; Cohen et al., 2001; Adolphs, 2002; Ochsner and Gross, 2005; Phelps, 2006; Duncan and Barrett, 2007; Lieberman, 2007), the insular cortex has been…”

“The following contrasts were identified as empathy for negative emotions: “compassionate–sad>zcompassionate–neutral” (Kim et al., 2009), and “overlap between observing and feeling disgust” (Wicker et al., 2003).”

“…associated with neuropathological degeneration of the VENs and functional deficits of the AIC, such as behavioral variant frontotemporal dementia (Seeley et al., 2006; Seeley, 2010; Kim et al., 2012), callosal agenesis (Kaufman et al., 2008), and autism (Santos et al., 2011; Butti et al., 2013).”

“…that the insular cortex works closely with a network of regions, including the ACC (Critchley, 2004; Critchley et al., 2004; Medford and Critchley, 2010; Fan et al., 2011; Denny et al., 2012; Lindquist et al., 2012), somatosensory cortex (Gu et al., 2013), and amygdala (Etkin and Wager, 2007).”

“Diminished ability to integrate information rapidly among spatially distinct regions may underlie functional deficits in these conditions and, ultimately, in the inability to make quick and intuitive judgments regarding uncertain and rapidly changing social contexts (Allman et al., 2005).”

“…insula) in both humans (Flynn et al., 1999; Butti and Hof, 2010; Bauernfeind et al., 2013; Butti et al., 2013) and macaque monkeys (Mesulam and Mufson, 1982a), although more subdivisions have been revealed in monkeys recently (Gallay et al., 2012; Evrard H, Logothetis NK, Craig AD, in press).”

“Corepresentation of the cognitive evaluation and the stimulus valence of pain in AIC have been shown in previous studies (Salomons et al., 2004; Wager et al., 2004; Gu and Han, 2007a,b).”

“Even in the absence of psychiatric or neurological disorders, alexithymia is very common among elderly people (34%; Joukamaa et al., 1996).”

“For each trial, an accuracy score was derived: 1 − (|nbeatsreal − nbeatsreported|)/((nbeatsreal + nbeatsreported)/2): Resulting accuracy scores were averaged over the 6 trials, yielding an average value for each participant (Hart et al., 2013).”

“If this explanation is right, then it provides a clear pointer to abnormalities of (precision) gain control in cortical systems mediating interoceptive inference such as the anterior insular and cingulate cortex (84, 85).”