Amygdala–frontal connectivity during emotion regulation

“This is broadly consistent with the role of these regions in cognitive inhibition/control and executive function (Cabeza and Nyberg, 2000; Miller and Cohen, 2001), processes that are relevant to reappraisal-based affect regulation.”

“Based on our experimental design (i.e., involving negatively valenced images) and to perform unbiased contrast analysis, we first performed a conjunction analysis with SPM2 (Price and Friston, 1997; Friston et al., 1999; Nichols et al., 2005) to identify amygdala activation that was present across both Maintain and Re…”

“For example, the ACC, VLPFC and DLPFC have been found to activate to response inhibition during the cognitive-emotion interference tasks (Whalen et al., 1998; Bush et al., 2000; Etkin et al., 2006).”

“…future studies driven by these findings and anatomical studies would develop an a priori mechanistic neural network model of how prefrontal cortex influences amygdala, and vice versa and pursue effective connectivity analyses in order to infer causal relationships (Friston et al., 2003).”

“Taken together, the data from animal and human studies point to a specific amygdala–frontal circuit of emotion generation and regulation (Davidson et al., 2000; Phan et al., 2002; Phillips et al., 2003a; Ochsner and Gross, 2005; Quirk and Beer, 2006).”

“This is broadly consistent with the role of these regions in cognitive inhibition/control and executive function (Cabeza and Nyberg, 2000; Miller and Cohen, 2001), processes that are relevant to reappraisal-based affect regulation.”

“…analysis identified that the left amygdala cluster (MNI coordinates of peak activation: [À22, 0, À22], 70 voxels, Z ¼ 2.37, P < 0.05, small-volume corrected) was active during both Maintain and Reappraise blocks, consistent with prior reports (Phan et al., 2002, 2005; Wager et al., 2003).”

“…PPIrelated amygdala coupling were identified with a threshold of P < 0.001 uncorrected (t > 3.85) with at least 10 contiguous voxels in the cluster (120 mm 3 ); the combination of the height-extent threshold effectively yields equivalent correction for multiple comparisons (Forman et al., 1995).”

“The mean (AEs.d.) valence and arousal values on a 9-point scale for the pictures were 2.03 AE 0.44 and 6.03 AE 0.72, respectively (1 ¼ most unpleasant/least arousing, 9 ¼ most pleasant/most arousing) based on normative ratings (Lang et al., 1993).”

“Using PPI analyses (Friston et al., 1997), we demonstrate amygdala–frontal coupling specifically during emotion regulation.”

“…in the amygdala during anticipation of negative emotion (Erk et al., 2006), and associated with monitoring and/or appraising one's own emotional state (Taylor et al., 2003; Ochsner et al., 2004a) and making self-referential judgments regarding emotionally salient stimuli (Gusnard et al., 2001).”

“…expression and experience of negative emotions as demonstrated by both animal and human lesion studies (Aggleton, 1993; Angrilli et al., 1996; Davis and Whalen, 2001; Adolphs, 2002; Amaral et al., 2003; Phelps, 2004), and human imaging studies (Phan et al., 2002; Murphy et al., 2003;…”

“…activation of prefrontal brain regions, including OFC and rostral ACC, as associated with attenuated amygdala reactivity during emotion regulation (Ochsner et al., 2002; Urry et al., 2006), consistent with the notion that frontal cortex exerts a top–down inhibitory influence on the amygdala.”

“…correlations in activation signal between or coactivation of amygdala and frontal cortex, specifically the OFC/ventral MPFC (Kim et al., 2004; Heinz et al., 2005; Schmitz and Johnson, 2006), dorsal MPFC (Williams et al., 2006) and ACC (Das et al., 2005; Pezawas et al., 2005; Williams et al., 2006).”

“…of negative emotions as demonstrated by both animal and human lesion studies (Aggleton, 1993; Angrilli et al., 1996; Davis and Whalen, 2001; Adolphs, 2002; Amaral et al., 2003; Phelps, 2004), and human imaging studies (Phan et al., 2002; Murphy et al., 2003; Phillips et al., 2003a; Wager…”

“Taken together, the data from animal and human studies point to a specific amygdala–frontal circuit of emotion generation and regulation (Davidson et al., 2000; Phan et al., 2002; Phillips et al., 2003a; Ochsner and Gross, 2005; Quirk and Beer, 2006).”

“…negatively valenced images) and to perform unbiased contrast analysis, we first performed a conjunction analysis with SPM2 (Price and Friston, 1997; Friston et al., 1999; Nichols et al., 2005) to identify amygdala activation that was present across both Maintain and Reappraise task blocks.”

“Given that a number of psychiatric disorders are associated with affective instability and emotion dysregulation (Koenigsberg et al., 2002; Phillips et al., 2003b), paradigms and analyses such as the one presented here should be extended to studies of patients with anxiety, mood and personality…”

“For example, the ACC, DMPFC, DLPFC and/or OFC appear to be dysfunctional during cognitive-emotional tasks in patients with depression (Mayberg, 1997; Beauregard et al., 2006), anxiety (Shin et al., 2001; Lanius et al., 2004), impulsive aggression (Coccaro et al., in press) and personality disorders…”

“…as demonstrated by both animal and human lesion studies (Aggleton, 1993; Angrilli et al., 1996; Davis and Whalen, 2001; Adolphs, 2002; Amaral et al., 2003; Phelps, 2004), and human imaging studies (Phan et al., 2002; Murphy et al., 2003; Phillips et al., 2003a; Wager et al., 2003; Zald, 2003).”

“Although multiple strategies for conscious control of emotion exist (Lazarus, 1991; Gross, 1999b), extant neuroimaging research on the neural correlates of affect regulation has concentrated on two empirical approaches—suppression and reappraisal (Ochsner and Gross, 2005; Quirk and Beer, 2006).”

“In addition, based on similar approaches (Ochsner et al., 2002; Phan et al., 2005; Etkin et al., 2006), we were specifically interested in the relationship between withinsubject amygdala–cortical coupling with subject-specific behavioral measures.”

“Moreover, cognitive labeling (i.e., appraisal) of negative emotional stimuli similarly engages VLPFC, DLPFC and DMPFC (Hariri et al., 2000, 2003; Taylor et al., 2003).”

“…the cortex involved in feed-forward mechanisms , and terminate on inhibitory interneurons in the amygdala (Carmichael and Price, 1995; McDonald et al., 1996) providing some evidence for a top–down role for the prefrontal cortex on limbic regions (Carmichael and Price, 1995; McDonald et al., 1996).”

“…in press) and personality disorders (McCloskey et al., 2005; New et al., 2007); furthermore, these patients also exhibit exaggerated amygdala reactivity to emotionally negative stimuli (Coccaro et al., in press; Rauch et al., 2000; Herpertz et al., 2001; Sheline et al., 2001; Donegan et al., 2003).”

“Anatomical tracing studies have demonstrated strong reciprocal connections between the amygdala and the ACC, OFC, VLPFC and DMPFC (Amaral and Price, 1984; Ghashghaei and Barbas, 2002; Ghashghaei et al., 2007).”

“…analysis identified that the left amygdala cluster (MNI coordinates of peak activation: [À22, 0, À22], 70 voxels, Z ¼ 2.37, P < 0.05, small-volume corrected) was active during both Maintain and Reappraise blocks, consistent with prior reports (Phan et al., 2002, 2005; Wager et al., 2003).”

“…between the left amygdala time series and a block vector representing the tasks of interest (Reappraise vs Maintain) (Gitelman et al., 2003; Egner and Hirsch, 2005; Etkin et al., 2006); as such the activity within this left amygdala mask was regressed on a voxel-wise basis against the…”

“…as demonstrated by both animal and human lesion studies (Aggleton, 1993; Angrilli et al., 1996; Davis and Whalen, 2001; Adolphs, 2002; Amaral et al., 2003; Phelps, 2004), and human imaging studies (Phan et al., 2002; Murphy et al., 2003; Phillips et al., 2003a; Wager et al., 2003; Zald, 2003).”

“…in press) and personality disorders (McCloskey et al., 2005; New et al., 2007); furthermore, these patients also exhibit exaggerated amygdala reactivity to emotionally negative stimuli (Coccaro et al., in press; Rauch et al., 2000; Herpertz et al., 2001; Sheline et al., 2001; Donegan et al., 2003).”

“The parietal cortex is strongly anatomically interconnected with the prefrontal cortex (Petrides and Pandya, 1984), and functional connectivity has also been indicated between these regions (Chafee and Goldman- Rakic, 2000).”

“…negatively valenced images) and to perform unbiased contrast analysis, we first performed a conjunction analysis with SPM2 (Price and Friston, 1997; Friston et al., 1999; Nichols et al., 2005) to identify amygdala activation that was present across both Maintain and Reappraise task blocks.”

“…as demonstrated by both animal and human lesion studies (Aggleton, 1993; Angrilli et al., 1996; Davis and Whalen, 2001; Adolphs, 2002; Amaral et al., 2003; Phelps, 2004), and human imaging studies (Phan et al., 2002; Murphy et al., 2003; Phillips et al., 2003a; Wager et al., 2003; Zald, 2003).”

“…activation of prefrontal brain regions, including OFC and rostral ACC, as associated with attenuated amygdala reactivity during emotion regulation (Ochsner et al., 2002; Urry et al., 2006), consistent with the notion that frontal cortex exerts a top–down inhibitory influence on the amygdala.”

“…it has been posited that conscious down-regulation of emotion appears to have a top–down inhibitory effect of prefrontal brain regions on the amygdala (Beauregard et al., 2001; Ochsner et al., 2002, 2004a; Levesque et al., 2003b, 2004; Phan et al., 2005; Ohira et al., 2006; Urry et al., 2006).”

“The ACC, VLPFC, DMPFC and OFC are engaged when subjects divert their attention from threat and/or painful stimuli (Bantick et al., 2002; Tracey et al., 2002; Bishop et al., 2004).”

“…it has been posited that conscious down-regulation of emotion appears to have a top–down inhibitory effect of prefrontal brain regions on the amygdala (Beauregard et al., 2001; Ochsner et al., 2002, 2004a; Levesque et al., 2003b, 2004; Phan et al., 2005; Ohira et al., 2006; Urry et al., 2006).”

“The ACC, VLPFC, DMPFC and OFC are engaged when subjects divert their attention from threat and/or painful stimuli (Bantick et al., 2002; Tracey et al., 2002; Bishop et al., 2004).”

“Moreover, recent studies using similar PPI-based analyses have shown increased coactivation between amygdala and MPFC (Erk et al., 2006; Schmitz and Johnson, 2006; Williams et al., 2006) and between amygdala and DLPFC (Siegle et al., 2007) during cognitive-emotional tasks.”

“…it has been posited that conscious down-regulation of emotion appears to have a top–down inhibitory effect of prefrontal brain regions on the amygdala (Beauregard et al., 2001; Ochsner et al., 2002, 2004a; Levesque et al., 2003b, 2004; Phan et al., 2005; Ohira et al., 2006; Urry et al., 2006).”

“Anatomical tracing studies have demonstrated strong reciprocal connections between the amygdala and the ACC, OFC, VLPFC and DMPFC (Amaral and Price, 1984; Ghashghaei and Barbas, 2002; Ghashghaei et al., 2007).”

“Based on our experimental design (i.e., involving negatively valenced images) and to perform unbiased contrast analysis, we first performed a conjunction analysis with SPM2 (Price and Friston, 1997; Friston et al., 1999; Nichols et al., 2005) to identify amygdala activation that was present across both Maintain and Re…”

“Moreover, cognitive labeling (i.e., appraisal) of negative emotional stimuli similarly engages VLPFC, DLPFC and DMPFC (Hariri et al., 2000, 2003; Taylor et al., 2003).”

“…term, as calculated between the left amygdala time series and a block vector representing the tasks of interest (Reappraise vs Maintain) (Gitelman et al., 2003; Egner and Hirsch, 2005; Etkin et al., 2006); as such the activity within this left amygdala mask was regressed on a voxel-wise…”

“Anatomical tracing studies have demonstrated strong reciprocal connections between the amygdala and the ACC, OFC, VLPFC and DMPFC (Amaral and Price, 1984; Ghashghaei and Barbas, 2002; Ghashghaei et al., 2007).”

“Taken together, the data from animal and human studies point to a specific amygdala–frontal circuit of emotion generation and regulation (Davidson et al., 2000; Phan et al., 2002; Phillips et al., 2003a; Ochsner and Gross, 2005; Quirk and Beer, 2006).”

“Urry et al. (2006) have recently observed that individual variation in OFC/ventral MPFC is related to successful regulation of negative affect, such that individuals with higher activity in this region during the reappraisal task also exhibited lower amygdala signal and more normative diurnal decline of the stress-rel…”

“…the cortex involved in feed-forward mechanisms , and terminate on inhibitory interneurons in the amygdala (Carmichael and Price, 1995; McDonald et al., 1996) providing some evidence for a top–down role for the prefrontal cortex on limbic regions (Carmichael and Price, 1995; McDonald et al., 1996).”

“…it has been posited that conscious down-regulation of emotion appears to have a top–down inhibitory effect of prefrontal brain regions on the amygdala (Beauregard et al., 2001; Ochsner et al., 2002, 2004a; Levesque et al., 2003b, 2004; Phan et al., 2005; Ohira et al., 2006; Urry et al., 2006).”

“…in press) and personality disorders (McCloskey et al., 2005; New et al., 2007); furthermore, these patients also exhibit exaggerated amygdala reactivity to emotionally negative stimuli (Coccaro et al., in press; Rauch et al., 2000; Herpertz et al., 2001; Sheline et al., 2001; Donegan et al., 2003).”

“For example, the ACC, VLPFC and DLPFC have been found to activate to response inhibition during the cognitive-emotion interference tasks (Whalen et al., 1998; Bush et al., 2000; Etkin et al., 2006).”

“…OFC appear to be dysfunctional during cognitive-emotional tasks in patients with depression (Mayberg, 1997; Beauregard et al., 2006), anxiety (Shin et al., 2001; Lanius et al., 2004), impulsive aggression (Coccaro et al., in press) and personality disorders (McCloskey et al., 2005; New et…”

“The ACC, VLPFC, DMPFC and OFC are engaged when subjects divert their attention from threat and/or painful stimuli (Bantick et al., 2002; Tracey et al., 2002; Bishop et al., 2004).”

“As above, these indirect forms of emotion modulation are also associated with attenuation of limbicamygdala responses (Hariri et al., 2000; Pessoa et al., 2002; Taylor et al., 2003; Etkin et al., 2006).”

“…in press) and personality disorders (McCloskey et al., 2005; New et al., 2007); furthermore, these patients also exhibit exaggerated amygdala reactivity to emotionally negative stimuli (Coccaro et al., in press; Rauch et al., 2000; Herpertz et al., 2001; Sheline et al., 2001; Donegan et al., 2003).”

“…is a region critical to the generation, expression and experience of negative emotions as demonstrated by both animal and human lesion studies (Aggleton, 1993; Angrilli et al., 1996; Davis and Whalen, 2001; Adolphs, 2002; Amaral et al., 2003; Phelps, 2004), and human imaging studies (Phan et…”

“The MPFC is consistently implicated in studies of emotional processing, including emotional arousal and personal salience (Phan et al., 2003, 2004) and has been linked to the integration of emotion–cognition interactions (Phan et al., 2002) and to processes that underlie cognitive reappraisal…”

“…shown positive temporal correlations in activation signal between or coactivation of amygdala and frontal cortex, specifically the OFC/ventral MPFC (Kim et al., 2004; Heinz et al., 2005; Schmitz and Johnson, 2006), dorsal MPFC (Williams et al., 2006) and ACC (Das et al., 2005; Pezawas et al.,…”

“Given that a number of psychiatric disorders are associated with affective instability and emotion dysregulation (Koenigsberg et al., 2002; Phillips et al., 2003b), paradigms and analyses such as the one presented here should be extended to studies of patients with anxiety, mood and personality…”

“…in the amygdala during anticipation of negative emotion (Erk et al., 2006), and associated with monitoring and/or appraising one's own emotional state (Taylor et al., 2003; Ochsner et al., 2004a) and making self-referential judgments regarding emotionally salient stimuli (Gusnard et al., 2001).”

“It has been posited that the prefrontal cortex has a top–down inhibitory effect on the amygdala (Pears et al., 2003; Rosenkranz et al., 2003; Izquierdo and Murray, 2005; Quirk and Beer, 2006).”

“…it has been posited that conscious down-regulation of emotion appears to have a top–down inhibitory effect of prefrontal brain regions on the amygdala (Beauregard et al., 2001; Ochsner et al., 2002, 2004a; Levesque et al., 2003b, 2004; Phan et al., 2005; Ohira et al., 2006; Urry et al., 2006).”

“Moreover, the recruitment of these frontal regions occurs when subjects engage in active selfregulation and is associated with modulation of amygdala reactivity (Beauregard et al., 2001; Ochsner et al., 2002; Schaefer et al., 2002; Phan et al., 2005; Urry et al., 2006).”

“This is further supported by the recent observation that metabolic rates in the amygdala are positively correlated with those in the OFC, DLPFC and ACC (New et al., 2007).”

“The amygdala is a region critical to the generation, expression and experience of negative emotions as demonstrated by both animal and human lesion studies (Aggleton, 1993; Angrilli et al., 1996; Davis and Whalen, 2001; Adolphs, 2002; Amaral et al., 2003; Phelps, 2004), and human imaging studies (Phan et al.”

“…be dysfunctional during cognitive-emotional tasks in patients with depression (Mayberg, 1997; Beauregard et al., 2006), anxiety (Shin et al., 2001; Lanius et al., 2004), impulsive aggression (Coccaro et al., in press) and personality disorders (McCloskey et al., 2005; New et al., 2007);…”

“For example, the ACC, DMPFC, DLPFC and/or OFC appear to be dysfunctional during cognitive-emotional tasks in patients with depression (Mayberg, 1997; Beauregard et al., 2006), anxiety (Shin et al., 2001; Lanius et al., 2004), impulsive aggression (Coccaro et al., in press) and personality disorders…”

“…correlations in activation signal between or coactivation of amygdala and frontal cortex, specifically the OFC/ventral MPFC (Kim et al., 2004; Heinz et al., 2005; Schmitz and Johnson, 2006), dorsal MPFC (Williams et al., 2006) and ACC (Das et al., 2005; Pezawas et al., 2005; Williams et al., 2006).”

“The MPFC is consistently implicated in studies of emotional processing, including emotional arousal and personal salience (Phan et al., 2003, 2004) and has been linked to the integration of emotion–cognition interactions (Phan et al., 2002) and to processes that underlie cognitive reappraisal…”

“…it has been posited that conscious down-regulation of emotion appears to have a top–down inhibitory effect of prefrontal brain regions on the amygdala (Beauregard et al., 2001; Ochsner et al., 2002, 2004a; Levesque et al., 2003b, 2004; Phan et al., 2005; Ohira et al., 2006; Urry et al., 2006).”

“…correlations in activation signal between or coactivation of amygdala and frontal cortex, specifically the OFC/ventral MPFC (Kim et al., 2004; Heinz et al., 2005; Schmitz and Johnson, 2006), dorsal MPFC (Williams et al., 2006) and ACC (Das et al., 2005; Pezawas et al., 2005; Williams et al., 2006).”

“…emotions as demonstrated by both animal and human lesion studies (Aggleton, 1993; Angrilli et al., 1996; Davis and Whalen, 2001; Adolphs, 2002; Amaral et al., 2003; Phelps, 2004), and human imaging studies (Phan et al., 2002; Murphy et al., 2003; Phillips et al., 2003a; Wager et al., 2003;…”

“It has been posited that the prefrontal cortex has a top–down inhibitory effect on the amygdala (Pears et al., 2003; Rosenkranz et al., 2003; Izquierdo and Murray, 2005; Quirk and Beer, 2006).”

“Of note, a significant PPI does not inform us about the directional nature of the regression slope under each condition individually, it only shows the direction of the change in covariation (increase or decrease) between the tasks (Friston et al., 1997; Friston, 1998).”

“…correlations in activation signal between or coactivation of amygdala and frontal cortex, specifically the OFC/ventral MPFC (Kim et al., 2004; Heinz et al., 2005; Schmitz and Johnson, 2006), dorsal MPFC (Williams et al., 2006) and ACC (Das et al., 2005; Pezawas et al., 2005; Williams et al., 2006).”

“It has been posited that the prefrontal cortex has a top–down inhibitory effect on the amygdala (Pears et al., 2003; Rosenkranz et al., 2003; Izquierdo and Murray, 2005; Quirk and Beer, 2006).”

“In both animal and human studies, lesions to these areas result in emotion dysregulation (Williams and Mateer, 1992; Damasio, 1994; Izquierdo and Murray, 2005; ).”

“Moreover, recent studies using similar PPI-based analyses have shown increased coactivation between amygdala and MPFC (Erk et al., 2006; Schmitz and Johnson, 2006; Williams et al., 2006) and between amygdala and DLPFC (Siegle et al., 2007) during cognitive-emotional tasks.”

“…et al., 2006), anxiety (Shin et al., 2001; Lanius et al., 2004), impulsive aggression (Coccaro et al., in press) and personality disorders (McCloskey et al., 2005; New et al., 2007); furthermore, these patients also exhibit exaggerated amygdala reactivity to emotionally negative stimuli…”

“When individuals regulate their emotions, the amygdala is thought to be down-regulated by the vmPFC and hippocampus (Banks et al., 2007; Davidson et al., 2000; Milad, Rauch, Pitman, & Quirk, 2006), both of which have extensive connections with the amygdala.”

“…1 Anger R3 C1 39 42 0.74 0.66 Ayduk et al. (2002) 1 Negative affect R3 Cont1 88 100 0.44 Ayduk et al. (2002) 1 Negative affect C1 Cont1 85 100 0.02 Banks et al. (2007) 1 Negative affect R2 Cont5 14 1.83 Bates (2007) 1 Negative affect S4 Cont1 19 20 0.16 Bates (2007) 1 Negative affect D2 Cont1 19…”

“Banks and colleagues (58) found that the reduced amygdala coupling with the orbitofrontal cortex and the dorsal medial prefrontal cortex predicts the extent of attenuation of negative affect following reappraisal.”