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.”

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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.”

“…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.”

“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.”

“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).”

“…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…”

“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).”

“…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,…”

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

“…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).”

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

“…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).”

“…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…”

“…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).”

“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).”

“…(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;…”

“, 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).”

“…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.”

“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).”

“…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).”

“…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).”

“…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).”

“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).”

“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).”

“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…”

“…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).”

“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).”

“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).”

“This is accommodated by predictions about transitions over increasingly protracted time scales (Friston, 2008; Pezzulo, 2012).”

“Note that the PI is preferentially involved in interoception and the AI in emotion reactivity/generation and emotional awareness (Craig, 2009; Gu et al., 2013).”

“The somatic marker hypothesis further assumes that the representation of the body is necessary not only for emotions [56], but also for a broader core self-image, crucial for feelings to arise [4], which is in agreement with the notion that conscious experience cannot occur without feelings and interoception [57,58].”

“…to both the body and the physical and social world outside the body; this is for notational brevity only and not meant to disregard differences in how bodily, social and physical states can influence brain activity in general and the emergence of fatigue in particular; a topic we return to below.”

“This proposed role for the insula as a core module in the interoceptive hierarchy is a key motif appearing in a variety of related approaches (Barrett and Simmons 2015; Gu et al. 2013; Seth 2013).”

“However, we do not subscribe to the more extreme view that holds that the insula is necessary for interoceptive awareness (Craig 2002), self-awareness (Craig 2009), emotional awareness (Gu et al. 2013), and pain (Segerdahl et al. 2015).”

“assumes that attention increases the precision of PEs associated with the heartbeat, which are 284 then cascaded up through the hierarchy causing activity visible in the anterior insula under 285 fMRI (40).”

“The feeling of selfhood may arise from internal agency associated with accurate predictions about the inner physiological state of the body, while negative emotions such as anxiety may emerge from interoceptive prediction errors [92–94].”

“Right AI activation is absent in empathy for positive emotions and is present only in empathy for negative emotions such as pain, whereas the left AI is activated by all valence categories [52].”

“Initially, the insula became known for its involvement in affective processes (for meta-analyses, see Gu et al., 2013; Duerden et al., 2013).”

“The insula is also involved in emotional information processing, and is necessary for empathic pain perception and compassion, hence referring to hot EF, but also for the integration of emotional and cognitive processes, thus referring to cool EF (Gu et al. 2012, 2013; Lamm and Singer 2010).”

“, (Bartels and Zeki, 2004; Gu et al., 2013; Smith et al., 2015)], empathy (Lamm and Singer, 2010), as well as more complex perceptions, such as, the recognition of oneself in a mirror (Devue and Bredart, 2011) and other visual perceptual tasks (Salomon et al.”

“In this setting, negative emotions contextualise events that induce expectations of unpredictability, while positive emotions refer to events that resolve uncertainty and confer a feeling of control (Barrett & Satpute, 2013; Gu et al. 2013).”

“In the context of interoceptive and embodied predictive coding (Allen and Friston, 2018; Gu et al., 2013), previous studies hypothesized that interoceptive predictions are computed within a network of brain regions with the AIC as the key node (Allen et al.”

“However, the same inference challenge exists with regard to bodily states (interoception) (76 – 78).”

“This makes the mid-insula well placed to serve as an intermediary between the processing of sensory representation of bodily state in the posterior insula (31) and the abstract representation of affective state in the anterior insula (34), where the latter, as demonstrated empirically in our conjunction analysis, appe…”

“The physical adjacency of the salience network to the AMN in the cortex 21 , striatum 57 and red nucleus 134 hints at the possibility that its allostatic salience signals could bias adjacent action-mode processes and vice versa 162,163 .”

“G, STS, auditory association cortex: Ban et al. (1991) (Monkey), Hackett et al. (1998) kris and Pandya (2009) (Human), Saleem et al. (2008) (Monkey).”

“This will involve (among others) the insular, somatosensory, and anterior cingulate cortices (Adolphs et al., 2000; Barrett and Simmons, 2015; Craig, 2009; Gu et al., 2013), and should proceed similarly to processing within other cortical sensory systems.”

“…more importantly, altered signaling between the PIVC and anterior insula, which is thought to integrate bottom-up interoceptive signals with top-down predictions to generate a body-centered awareness state (Craig, 2009; Gu et al., 2013), may impair production of a stable sense of self-motion.”

“, 2012), social motivation of others (Schreuders, 2018) and emotional awareness (Gu et al., 2013).”

“The AIC compares the interoceptive feedback with the top-down predictions of interoceptive state, which it received from the DLPFC, in order to generate a current awareness state (Gu et al., 2013).”

“The anterior insula has been implicated in a wide range of behaviors and is proposed to have a pivotal role for the neuronal representation of interoception (Craig, 2009) by integrating stimulus-driven and topdown driven information (Gu et al., 2013).”

“aINS is therefore well-situated to contribute to emotional awareness by receiving ascending interoceptive inputs and communicating with structures encoding higher-order representations of goals, attention, and motor plans (namely, vlPFC and pACC; (Medford and Critchley, 2010; Gu et al., 2013).”

“Recent theoretical work suggests that alexithymia might be the result of impaired “interoception,” referring to one's sensitivity to the internal state of one's own body (Gu et al., 2013; Quattrocki and Friston, 2014; Seth, 2013).”

“The AIC is a critical cortical center in the interoceptive system which processes information from the body and exerts autonomic control [Craig, 2009; Craig, 2011; Critchley and Harrison, 2013; Gu et al., 2013a].”

“interoceptive and affective states [90] and emotional awareness [93].”

“The insular cortex is thought to be involved in consciousness, homeostatic regulation, motor control, emotion, and cognitive functioning (Gu et al., 2013).”

“This is an important point since several investigators have recently claimed that the anterior insula is the necessary substrate underlying all forms of emotional awareness (Craig 2009; Gu et al. 2013).”

“This convergence of cortical and interoceptive information upon the insular cortex has led to influential hypotheses concerning its potential roles in interoceptive prediction [14], information integration for awareness [20,21], emotional awareness [22], interoceptive inference and emotion [23,24] and error-based lear…”

“The anterior insula becomes actively engaged during emotional awareness, or conscious experience of emotion [50, 51].”

“This can be interpreted as a correlate of reduced alertness and hyperarousal with traumatic and other emotional stimuli after treatment (55).”

“The insula is critical for the representation of interoceptive information (Paulus and Stein, 2006; Gu et al., 2013).”

“, 2004), and re-represents the vast information to generate higher-level abstract and subjective information that are considered as “thoughts”, “feelings”, and “awareness” (Brass and Haggard, 2010; Craig, 2009, 2011; Gu et al., 2013; Nelson et al., 2010; Singer et al., 2009).”

“Physiological signals and feelings arising from the body are an essential part of cognition and decision-making (Damasio, 1996; Gu et al., 2013a; Gu and FitzGerald, 2014).”

“This result is interesting given that both amygdala and dorsal anterior insula serve as key hubs in the integration of interoceptive signals with emotional and cognitive aspects (Craig, 2009; Etkin and Wager, 2007; Gu et al., 2013; Neugebauer, 2015).”

“…variables, including social and contextual factors, and are less influenced by individual differences in introspection and self-report, which are likely mediated by other brain systems including insular cortices and the default network (Chang et al., 2013; Gu et al., 2013; Kleckner et al., 2017).”

“This network, and specifically the AIC, provides a salient representation of one’s own bodily states and has been suggested to be a correlate of one’s conscious experience of emotion [Gu et al., 2013].”

“Similarly, cortical maturational delays in insula, which has been described as critical for emotional awareness (Gu et al., 2013) may explain poor social competence described in VPT adolescents (Healy et al.”

“on the perception of bodily reactions to emotion-provoking objects and the cognitive interpretation of these interoceptive informations (Craig, 2009, 2010; Gu et al., 2013).”

“…the anterior insular cortex, a brain region involved in interoceptive awareness (Craig, 2002, 2009; Critchley et al., 2002; Pollatos et al., 2007; Gu et al., 2013), and with the medial prefrontal cortex, which is implicated in self-referential processing (Craik et al., 1999; Kelley et al., 2002;…”

“45 Emotional responses to stressful stimuli are partly mediated by the reciprocal connections of the amygdala, the thalamus, and the hippocampus.”

“To demonstrate the involvement of any brain region in the integration of multiple mental processes, two criteria need to be met: (1) participation in each process [Asplund et al., 2010; Shomstein, 2012]; and (2) an interaction effect between operations [Gray et al., 2002; Gu et al., 2013].”

“These AI-prefrontal circuits play a central role in emotional processing, particularly salience detection (Uddin, 2015) and emotional awareness (Gu et al., 2013), and promote flexible behavioral adaption, particularly via emotion regulation (Ochsner et al.”

“, 2014; Gogolla, 2017) and is reciprocally connected to the extended amygdala (Shi and Cassell, 1998), which may underlie its known role in human emotional recognition (Adolphs et al., 2003; Gu et al., 2013; Terasawa et al., 2015).”

“…cortex (AIC) receives afferent inputs from small diameter sensory fibers through the lamina I spinothalamocortical pathway, which carries fundamental information from all the tissues of the body (Craig, 2002, 2003, 2009; Gu et al., 2013; Gu and FitzGerald, 2014) creating interoceptive perceptions.”

“Specifically, the ventromedial prefrontal cortex, insula, and precuneus are key regions for socio-emotional processing [73-78], and prefrontal cortex is also associated with language processing [79, 80] and cognitive control [67, 81, 82]; the V1 and V4 areas belong to the visual system [83, 84]; and PMC is the primary…”

“Euphoric emotions have also been provoked by stimulation of the inferior temporal gyrus, temporal pole, amygdala, inferior frontal gyrus, anterior cingulate cortex, and supplementary motor area, with a predominance in the left hemisphere (Guillory and Bujarski, 2014).”

“Likewise, the AI has also been identified in a variety of tasks associated with cognition, emotion or the interaction between them [Gu et al., 2012, 2013a,b; Fan et al., 2011].”

“Anterior insular activation is also found when participants are aware of their internal bodily state (Evans et al., 2002; Critchley et al., 2004; Hamaguchi et al., 2004).”

“[45-49] Anatomical, physiological, and chemical-based vestibular projections exist to anterior insula, adjacent inferior frontal gyrus, and ACC, which has a regulatory role on interoceptive inputs necessary for physiology of emotions.[50-54]”