Prefrontal-Subcortical Pathways Mediating Successful Emotion Regulation

“The MEPM analysis is based on a standard three-variable path model (Baron and Kenny, 1986) with a bootstrap test for the statistical significance of the product a*b (Efron and Tibshirani, 1993; Shrout and Bolger, 2002), as diagrammed in Figure 1.”

“The Mediation Effect Parametric Map (MEPM) analysis is based on a standard 3-variable path model (Baron and Kenny, 1986) with a bootstrap test for statistical significance (Efron and Tibshirani, 1993; Shrout and Bolger, 2002).”

“The MEPM analysis is based on a standard three-variable path model (Baron and Kenny, 1986) with a bootstrap test for the statistical significance of the product a*b (Efron and Tibshirani, 1993; Shrout and Bolger, 2002), as diagrammed in Figure 1.”

“…in the control and switching of attention among objects and object features (Barber and Carter, 2005; Wager et al., 2004a) and in monitoring of the internal environment and “self” (Cavanna and Trimble, 2006; Gusnard and Raichle, 2001) and episodic memory retrieval (Lundstrom et al., 2005).”

“However, as MacKinnon et al. (MacKinnon et al., 2000) describe in their re-analysis of these data, those who had greater reason to use steroids tended to enroll in the program, creating a positive link between reasons for using steroids and program enrollment.”

“…stimuli that do (e.g. a small child crying hysterically) and stimuli that do not (e.g. a fearful facial expression) generate negative emotional experiences, it is more consistently activated by the stimuli that do not elicit experience (Phan et al., 2002; Phan et al., 2004; Wager et al., in press).”

“The amygdala is the affect-related region most commonly modulated during reappraisal (Ochsner and Gross, 2005, 2008); it has been implicated in detecting, attending to, and encoding into memory affectively arousing and especially threatening stimuli (Holland and Gallagher, 1999; Phelps, 2006; Whalen, 1998), and it is…”

“This region has been called primary “interoceptive” cortex (Craig, 2003), though it appears to be activated by aversive social experiences as well (Sanfey et al., 2003).”

“environment and “self” (Cavanna and Trimble, 2006; Gusnard and Raichle, 2001) and episodic”

“Forty-eight aversive images were selected from the International Affective Picture Set (IAPS; Lang etal., 1993; mean normative valence = 2.24, mean norma-”

“For example, hypnosis (Faymonville et al., 2000; Rainville et al., 1997) and placebo treatments (Lieberman et al., 2004; Price et al., 2007; Wager et al., 2004b) that lead to reduced pain have consistently reduced rdACC activity.”

“Striatal activity has been reported in reappraisal studies, although its functional role has not been clarified (McRae et al., 2008a; Ochsner et al., 2002, 2004; van Reekum et al., 2007).”

“…which has recently been shown to play an important role in the modulation of depression and mood (Drevets, 2001; Johansen-Berg et al., 2007; Mayberg et al., 1999); high-resolution studies are needed to dissociate the contributions of NAC and subgenual cingulate to the pathways reported…”

“We think this unlikely, however, because the largest projections are from PFC to amygdala rather than vice versa (Pitkanen, 2000), and there is direct evidence that PFC plays an important role in modulating amygdala responses (Davis, 1992; Milad and Quirk, 2002), whereas we know of no direct evidence that supports the…”

“, and Poldrack, R.A. (2005). The cognitive neuroscience of response inhibition: relevance for genetic research in attention-deficit/hyperactivity disorder.”

“…be reliably collected in the scanner environment, provides clear valence information (unlike most autonomic measures), and has been shown to predict mental and physical health outcomes (Brosschot et al., 2006; Gross and Munoz, 1995; Moskowitz, 2003; Scheier and Carver, 1992; Tugade et al., 2004).”

“As described previously (Ochsner et al., 2002; Ochsner et al., 2004), this method is meant to capture the fact that in everyday no single type of reinterpretation is expected to be applicable to all life events – or here, all photos.”

“An alternative view is that PFC is involved in the appraisal process itself, with the type of appraisal (positive or negative) determined by the specific cognitions involved (Lazarus, 1991).”

“For example, hypnosis (Faymonville et al., 2000; Rainville et al., 1997) and placebo treatments (Lieberman et al., 2004; Price et al., 2007; Wager et al., 2004b) that lead to reduced pain have consistently reduced rdACC activity.”

“In the worst of circumstances, regulatory failures take a severe toll and contribute to the genesis and symptomatology of many psychiatric disorders (Davidson et al., 2000; Phillips et al., 2003).”

“…was the pre-SMA, which has been implicated in multiple cognitive control processes (van Snellenberg and Wager, in press; Wager et al., 2004a; Wager and Smith, 2003) and in the energization of internally driven processes that lead to effective intentional response selection (Alexander et…”

“, to aversive versus appetitive stimuli), which have begun to be addressed in other papers (Eippert et al., 2007; Goldin et al., 2007; Johnstone et al., 2007; Kim and Hamann, 2007; Ochsner et al., 2004; van Reekum et al., 2007).”

“We think this unlikely, however, because the largest projections are from PFC to amygdala rather than vice versa (Pitkanen, 2000), and there is direct evidence that PFC plays an important role in modulating amygdala responses (Davis, 1992; Milad and Quirk, 2002), whereas we know of no direct evidence that supports the…”

“…first that although the amygdala has been broadly implicated in negative emotional responses, ranging from the acquisition of conditioned fear (Phelps, 2006) to hyperactivity in a range of anxiety disorders (Etkin and Wager, 2007), there has been reason to doubt that amygdala activation…”

“In the worst of circumstances, regulatory failures take a severe toll and contribute to the genesis and symptomatology of many psychiatric disorders (Davidson et al., 2000; Phillips et al., 2003).”

“…be reliably collected in the scanner environment, provides clear valence information (unlike most autonomic measures), and has been shown to predict mental and physical health outcomes (Brosschot et al., 2006; Gross and Munoz, 1995; Moskowitz, 2003; Scheier and Carver, 1992; Tugade et al., 2004).”

“…be reliably collected in the scanner environment, provides clear valence information (unlike most autonomic measures), and has been shown to predict mental and physical health outcomes (Brosschot et al., 2006; Gross and Munoz, 1995; Moskowitz, 2003; Scheier and Carver, 1992; Tugade et al., 2004).”

“This finding, and the individuals results on which it is based, have been taken to suggest that the amygdala may play a role in the perceptual detection and encoding of affectively relevant stimuli, which may or may not have a direct impact on affective experience (Anderson and Phelps, 2001, 2002; Barret et al., 2007;…”

“These regions have been consistently implicated in reward learning (McClure et al., 2003; Schultz, 2004), reward expectancies ( Breiter et al., 2001; Cromwell and Schultz, 2003), and paindiminishing placebo effects (Scott et al., 2007; Wager et al., 2007), as well as approach motivation more generally (Tindell et al.,…”

“, 2008), that it shows heightened activity in major depression (Drevets et al., 1992) that decreases with successful treatment (Brody et al.”

“The first region was the right lateral orbitofrontal cortex (lOFC), which has been associated with diverse forms of valenced affective experience (Berridge and Kringelbach, 2008; Wager et al., in press) and related motivational processes such as updating behavior on the basis of negative feedback…”

“We assessed the family-wise error rate (FWER) for the mediation search analyses in each ROI by using a permutation test ((Nichols and Hayasaka, 2003)), which provides estimates of the chances of obtaining a false positive result anywhere in the ROI, accounting for the observed correlations among…”

“These models have established the prefrontal cortex (PFC) as a key player in the cognitive regulation of emotion (Davidson, 2002; Ochsner and Gross, 2005).”

“Second, studies of reappraisal and other cognitivemeans of regulating affective responses (Cunningham and Zelazo, 2007; Lieberman et al., 2007) have consistently activated rvlPFC.”

“Implications of Network Analyses for Understanding Cognition-Emotion Interactions It has been increasingly recognized that higher-order cognitive processes like appraisal arise from information processing within large-scale distributed networks (Cole and Schneider, 2007; Kober et al., 2008; Schmitz and Johnson, 2007).”

“Consider that bilateral vlPFC is activated by both positive and negative emotion-induction tasks (often in tandem with subcortical activation; Kober et al., 2008), that it shows heightened activity in major depression (Drevets et al., 1992) that decreases with successful treatment (Brody et al., 1999, 2001; Goldapple…”

“…in other reappraisal studies that use the amygdala as an outcome variable – but did not measure emotional experience (or any other behavioral index of emotional response) (Johnstone et al., 2007; Urry et al., 2006; van Reekum et al., 2007) – may in fact be relevant to shaping emotional experience.”

“…in other reappraisal studies that use the amygdala as an outcome variable – but did not measure emotional experience (or any other behavioral index of emotional response) (Johnstone et al., 2007; Urry et al., 2006; van Reekum et al., 2007) – may in fact be relevant to shaping emotional experience.”

“The use of mediation analysis to test relationships among variables has a long history (Baron and Kenny, 1986; Hyman, 1955; MacCorquodale and Meehl, 1948).”

“It is typically assumed that the beneficial effects of reappraisal are accomplished via interactions between PFC regions and subcortical networks related to emotional responding (Beauregard et al., 2001; Eippert et al., 2007; Goldin et al., 2007; Kalisch et al., 2006; Kim and Hamann, 2007; Ochsner et al., 2004; Phan e…”

“Though NAC/VS and amygdala activity are not expected to be pure markers of positive and negative emotion (Cromwell and Schultz, 2003; Jensen et al., 2003; Levita et al., 2002; Paton et al., 2006), recent meta-analyses suggest that activity in NAC/ VS and amygdala is biased toward positive and negative affective experi…”

“These regions have been consistently implicated in reward learning (McClure et al., 2003; Schultz, 2004), reward expectancies (Breiter et al.”

“Striatal activity has been reported in reappraisal studies, although its functional role has not been clarified ( McRae et al., 2008a; Ochsner et al., 2002, 2004; van Reekum et al., 2007).”

“The appraisal-process hypothesis also helps understand why few studies have reported correlations between the magnitudes of self-reported emotion and amygdala activity (Abercrombie et al., 1998; Ochsner et al., 2004; Phan et al., 2005; Schaefer et al., 2002).”

“Here we used non-metric multidimensional scaling (NMDS), which makes fewer assumptions than PCA, as the dissimilarities are not assumed to reflect distances in a Euclidean space (Shepard, 1980).”

“Finally, a third region encompassed the retrosplenial cingulate cortex and cingulate isthmus, which have been implicated in autobiographical memory (Maddock, 1999) and may provide an anatomical bridge from the precuneus to medial temporal lobe structures that have well-known roles in the formation…”

“For example, hypnosis (Faymonville et al., 2000; Rainville et al., 1997) and placebo treatments (Lieberman et al., 2004; Price et al., 2007; Wager et al., 2004b) that lead to reduced pain have consistently reduced rdACC activity.”

“, to aversive versus appetitive stimuli), which have begun to be addressed in other papers (Eippert et al., 2007; Goldin et al., 2007; Johnstone et al., 2007; Kim and Hamann, 2007; Ochsner et al., 2004; van Reekum et al., 2007).”

“The amygdala is the affect-related region most commonly modulated during reappraisal (Ochsner and Gross, 2005, 2008); it has been implicated in detecting, attending to, and encoding into memory affectively arousing and especially threatening stimuli (Holland and Gallagher, 1999; Phelps, 2006; Whalen, 1998), and it is…”

“The appraisal-process hypothesis also helps understand why few studies have reported correlations between the magnitudes of self-reported emotion and amygdala activity (Abercrombie et al., 1998; Ochsner et al., 2004; Phan et al., 2005; Schaefer et al., 2002).”

“First, vlPFC—and especially rvlPFC—is well known as a region critical for cognitive control in general, and response inhibition or the selection of information in particular (Aron and Poldrack, 2005; Badre and Wagner, 2005; Nee et al., 2007; Phillips et al., 2003).”

“, 2007), as well as approach motivation more generally (Tindell et al., 2006; Wager et al., 2007).”

“Third, activation measures in vlPFC have been shown to be abnormal in emotional disorders (Drevets et al., 1992; Lawrence et al., 2004).”

“These regions have been consistently implicated in reward learning (McClure et al., 2003; Schultz, 2004), reward expectancies (Breiter et al.”

“as defined in ( Struyf et al., 1996 ): MEDIATED PFC-EMOTION PATHWAYS IN REAPPRAISAL 22”

“Though NAC/VS and amygdala activity are not expected to be pure markers of positive and negative emotion (Cromwell and Schultz, 2003; Jensen et al., 2003; Levita et al., 2002; Paton et al., 2006), recent meta-analyses suggest that activity in NAC/ VS and amygdala is biased toward positive and negative affective experi…”

“To accomplish this, a partial trial design was employed (Ollinger et al., 2001; Stern et al., 2007).”

“and negative (aversive) prediction errors (Seymour et al., 2005).”

“We applied nonmetric multidimensional scaling (NMDS) analysis to the resulting dissimilarity matrix using stress as the error metric (details in (Wager et al., 2007b)), retaining four dimensions.”

“…stimuli that do (e.g. a small child crying hysterically) and stimuli that do not (e.g. a fearful facial expression) generate negative emotional experiences, it is more consistently activated by the stimuli that do not elicit experience (Phan et al., 2002; Phan et al., 2004; Wager et al., in press).”

“…and Wager, in press; Wager et al., 2004a; Wager and Smith, 2003) and in the energization of internally driven processes that lead to effective intentional response selection (Alexander et al., 2007; Cunnington et al., 2005; Isoda and Hikosaka, 2007; Sumner et al., 2007) (Lau et al., 2004).”

“These regions have been consistently implicated in reward learning (McClure et al., 2003; Schultz, 2004), reward expectancies (Breiter et al., 2001; Cromwell and Schultz, 2003 ), and paindiminishing placebo effects (Scott et al., 2007; Wager et al., 2007), as well as approach motivation more generally (Tindell et al.,…”

“…in the control and switching of attention among objects and object features (Barber and Carter, 2005; Wager et al., 2004a) and in monitoring of the internal environment and “self” (Cavanna and Trimble, 2006; Gusnard and Raichle, 2001) and episodic memory retrieval (Lundstrom et al., 2005).”

“The results of some prior studies are consistent with the mediation hypothesis, but none have tested the complete mediation pathway and instead have examined only separate portions of it. For example, prefrontal correlates of reappraisal success (Ochsner et al., 2002, 2004; Ohira et al., 2006; Phan et al., 2005; Urry…”

“The appraisal-process hypothesis also helps understand why few studies have reported correlations between the magnitudes of self-reported emotion and amygdala activity (Abercrombie et al., 1998; Ochsner et al., 2004; Phan et al., 2005; Schaefer et al., 2002).”

“By contrast, prior reappraisal instructions have either given equal emphasis to positive-generation and negative-blunting appraisals ( Johnstone et al., 2007; Ochsner et al., 2002, 2004; Phan et al., 2005; Urry et al., 2006) or have emphasized distancing and detachment (Eippert et al., 2007; Kalisch et al., 2005).”

“, 1997) and placebo treatments (Lieberman et al., 2004; Price et al., 2007; Wager et al., 2004b) that lead to reduced pain have consistently reduced rdACC activity.”

“…be reliably collected in the scanner environment, provides clear valence information (unlike most autonomic measures), and has been shown to predict mental and physical health outcomes (Brosschot et al., 2006; Gross and Munoz, 1995; Moskowitz, 2003; Scheier and Carver, 1992; Tugade et al., 2004).”

“ysis ( Wager et al., 2005 ) to localize regions activated during reappraisal and regions in which activity correlated with reappraisal success.”

“Kim et al., for example, found amygdala increases when participants increased positive emotional responses (Kim and Hamann, 2007), and studies of autobiographical memory retrieval have found co-activation of amygdala and vlPFC (Greenberg et al., 2005; Maguire and Frith, 2003).”

“…in other reappraisal studies that use the amygdala as an outcome variable – but did not measure emotional experience (or any other behavioral index of emotional response) (Johnstone et al., 2007; Urry et al., 2006; van Reekum et al., 2007) – may in fact be relevant to shaping emotional experience.”

“For example, hypnosis (Faymonville et al., 2000; Rainville et al., 1997) and placebo treatments (Lieberman et al., 2004; Price et al., 2007; Wager et al., 2004b) that lead to reduced pain have consistently reduced rdACC activity.”

“These regions have been consistently implicated in reward learning (McClure et al., 2003; Schultz, 2004), reward expectancies (Breiter et al., 2001; Cromwell and Schultz, 2003), and paindiminishing placebo effects (Scott et al., 2007; Wager et al., 2007), as well as approach motivation more generally ( Tindell et al.,…”

“…2006) to hyperactivity in a range of anxiety disorders (Etkin and Wager, 2007), there has been reason to doubt that amygdala activation reflects experiential changes in all situations in which it has been activated (Anderson and Phelps, 2002; Barrett and Wager, 2006; Wager et al., in press).”

“A second region was the precuneus, which has been implicated in the control and switching of attention among objects and object features (Barber and Carter, 2005; Wager et al., 2004a) and in monitoring of the internal environment and “self” (Cavanna and Trimble, 2006; Gusnard and Raichle, 2001) and…”

“Kim et al., for example, found amygdala increases when participants increased positive emotional responses (Kim and Hamann, 2007), and studies of autobiographical memory retrieval have found co-activation of amygdala and vlPFC (Greenberg et al., 2005; Maguire and Frith, 2003).”

“It is typically assumed that the beneficial effects of reappraisal are accomplished via interactions between PFC regions and subcortical networks related to emotional responding (Beauregard et al., 2001; Eippert et al., 2007; Goldin et al., 2007; Kalisch et al., 2006; Kim and Hamann, 2007; Ochsner et al., 2004; Phan e…”

“…and Wager, in press; Wager et al., 2004a; Wager and Smith, 2003) and in the energization of internally driven processes that lead to effective intentional response selection (Alexander et al., 2007; Cunnington et al., 2005; Isoda and Hikosaka, 2007; Sumner et al., 2007) (Lau et al., 2004).”

“…and Wager, in press; Wager et al., 2004a; Wager and Smith, 2003) and in the energization of internally driven processes that lead to effective intentional response selection (Alexander et al., 2007; Cunnington et al., 2005; Isoda and Hikosaka, 2007; Sumner et al., 2007) (Lau et al., 2004).”

“The positive association of vlPFC with activity in this network suggests that the selection of reappraisal-appropriate information from memory may be used to construct a positive construal of the situations depicted in negative images (Ochsner, 2004), and that this can mediate reappraisal success.”

“This hypothesis suggests that reappraisal—as a form of cognitive reinterpretation—primarily impacts cortical systems involved either in cognitive appraisals (Barrett et al., 2007; Ochsner and Barrett, 2001; Scherer, 2001) or in assessing changes in one’s subjective emotional state ( McRae et al., 2008b ).”

“Though NAC/VS and amygdala activity are not expected to be pure markers of positive and negative emotion (Cromwell and Schultz, 2003; Jensen et al., 2003; Levita et al., 2002; Paton et al., 2006), recent meta-analyses suggest that activity in NAC/ VS and amygdala is biased toward positive and negative affective experi…”

“Neuron, volume 59 Supplemental Data”

“…forms of valenced affective experience (Berridge and Kringelbach, 2008; Wager et al., in press) and related motivational processes such as updating behavior on the basis of negative feedback (O'Doherty, 2003; O'Doherty et al., 2003) and negative (aversive) prediction errors (Seymour et al., 2005).”

“To accomplish this, a partial trial design was employed (Ollinger et al., 2001; Stern et al., 2007).”

“Consider that bilateral vlPFC is activated by both positive and negative emotion-induction tasks (often in tandem with subcortical activation; Kober et al., 2008), that it shows heightened activity in major depression (Drevets et al., 1992) that decreases with successful treatment ( Brody et al., 1999, 2001; Goldapple…”