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…”

“…with GM volume in the right hippocampus/ amygdala and the left OFC, all of which have been demonstrated as critical components within the neural circuitry of emotion regulation (Ochsner and Gross, 2005; Banks et al., 2007; Goldin et al., 2008; Wager et al., 2008; Hartley and Phelps, 2009).”

“[79], an additional limitation of using mediation analysis in fMRI is that models are made on the basis of naturally occurring variance over subjects, and thus conclusions are made with the assumption that inter-subject variability does not affect the coupling between dependent variables [79].”

“For example, mediation analyses showed that reappraisal-induced activation in the PFC was positively associated with activity in the NAC/VS, and successful regulation was related to increases in the NAC/VS pathway (Wager et al., 2008).”

“Hence, to test whether trial order may mediate any relationship between EEG activity and PSE, multilevel mixed-effects mediation analyses were carried out using the Mediation Toolbox (http://wagerlab.colorado.edu/tools (Wager et al., 2008; Woo et al., 2015)).”

“These results suggest an effect of CA on the WM tracts connecting limbic and prefrontal regions, previously found to play a role in emotion regulation (Roberts and Wallis 2000; Ghashghaei and Barbas 2002; Burgel et al. 2006; Wager et al. 2008; Thiebaut de Schotten et al. 2012).”

“This effect might partially deplete residual attention capacities that are not used for goal-directed behavior in the task (Bishop, 2007; Ochsner and Gross, 2005; Wager et al., 2008).”

“Although emotional states are mediated by limbic structures, most notably the ventral striatum for pleasure, approach and reward and the amygdala primarily for intense negative experiences, it is the human medial PFC (mPFC) and orbitofrontal cortex (OFC) that are associated with regulation of these emotional states (O…”

“37,38), but correlations did not stabilize to a 95% confidence interval of ±0.1 until n > 161 (ref.”

“The multilevel mediation analysis was implemented in a voxelwise analysis framework called mediation effect parametric mapping (Wager et al. 2008, 2009; Atlas et al. 2010, 2014) using the mediation toolbox (https://github.com/canlab/ MediationToolbox).”

“It is plausible that older adults needed more time to select out their preferred reappraisal tactic once they made the initial appraisal (Wager et al., 2008), or they might have had difficulty inhibiting prepotent negative affective responses when attempting to reappraise (Winecoff et al., 2011).”

“frontal cortex on reappraisal success (Wager et al., 2008), and”

“…of emotions by reappraisal strategies has been related to activation of the medial and lateral prefrontal areas (Ochsner et al. , 2002; Phan et al. , 2005; Kim et al. , 2007; Wager et al. , 2008), which prevent excessive experience of negative emotions (Urry et al. , 2009; Abler et al. , 2010).”

“VLPFC, can be recruited to modulate value representations in VMPFC, which may modulate downstream activity in the amygdala reflecting negative appraisals (for down-regulation), and/or activity in the ventral striatum, a key subcortical region in the brain’s reward circuitry that also plays a role in up-regulation of e…”

“In humans, high-order cognitive functions involve both the medial and lateral prefrontal cortex including integration of reward and sensory information, executive function, and emotion regulation (Alvarez and Emory 2006; O’Doherty 2004; Wager et al. 2008), and in turn, may contribute to sensitive parenting.”

“A large literature has indicated that lateral frontal regions, vmPFC, and SMA are associated with emotion regulation functions, including reappraisal of emotional stimuli (Johnstone et al., 2007; Kalisch, 2009; Kohn et al., 2014; New et al., 2009; Wager et al., 2008).”

“regions previously shown to be critical to ER success (Wager et al., 2008; Buhle et al., 2014).”

“…third-person perspective taking was predominantly found in the VLPFC. Activation in this region is consistent with other studies proposing the VLPFC as an important contributor to affective reappraisal processes within perceptional situations (Ochsner et al., 2004a,b; Wager et al., 2008).”

“A major effort in brain imaging research focuses on understanding the neuronal basis of emotional processing in the human brain (Barrett and Bar, 2009; Davidson et al., 2000; Fusar-Poli et al., 2009; Goldin et al., 2005; Kober et al., 2008; LeDoux, 2001; Lindquist and Barrett, 2012; Lindquist et al., 2012; Vytal and H…”

“Based on these findings, several models on emotion regulation evolved, supporting the idea that prefrontal regions, especially the DLPFC, downregulate activity in subcortical regions implicated in the processing of emotions, such as the amygdala (Ochsner and Gross, 2005; Quirk and Beer, 2006; Urry et al., 2006; Johnst…”

“P A A uthor M anuscript emotion regulation (Phan et al., 2005; Wager et al., 2008).”

“Of note, the ventrolateral pFC has been shown to play a crucial role in the instantiation of top – down control of both emotion (Wager, Davidson, Hughes, Lindquist, & Ochsner, 2008) and pain processing (Salomons, Johnstone, Backonja, Shackman, & Davidson, 2007).”

“The analyze strategy was designed as a memory analog of cognitive reappraisal strategies used in previous fMRI studies (Ochsner et al., 2002, 2004; Ray et al., 2005; Wager et al., 2008).”

“Furthermore, Wager et al. (2008) suggested a role for one particular region of the striatum, the NAcc, in cognitive regulation of negative affect, with vlPFC up-regulating the NAcc during reappraisal of negative affect.”

“A key factor regulating both sleep and emotion is amygdala activity (Goldstein-Piekarski et al., 2015; Wager et al., 2008).”

“Mediation effect parametric mapping as implemented in the M3 mediation toolbox (Wager et al., 2008) was used to investigate modality-specific and modality general pathways of emotion generation.”

“This relationship between VMPFC and negative affect differs from other research suggesting that VMPFC reduces negative affective responses during extinction, reversal, or reappraisal of negative cues (Schiller and Delgado, 2010; Wager et al., 2008).”

“The right VLPFC is involved in the reappraisal and cognitive control of emotions in healthy individuals (Lévesque et al., 2004; Johnstone et al., 2007; Wager et al., 2008 ).”

“An additional significant group-by-time interaction revealed abnormal intrinsic connectivity between the left vlPFC and the left anterior hippocampus ([32, 12, 218]; k = 22; Z = 23.”

“Activity in ventromedial prefrontal cortex during self-related processing: positive subjective value or personal significance?”

“Thus, both cost-benefit decision making, as studied here, and cognitive re-appraisal may depend upon the attentional control functions of the vlPFC for the re-interpretation of emotional stimuli (25).”

“, reappraisal) (Wager et al., 2008; Buhle et al., 2014) and have ignored control of emotional actions, an important component of emotion regulation concerned with conflict between the emotional value of stimulus and response (Frijda et al.”

“Specifically, prior work confirms involvement of the SMA (Etkin, Büchel, & Gross, 2015; Kohn et al., 2014; Wager et al., 2008) and precentral gyrus (Picó-Pérez, Radua,”

“Thus, mPFC stimulation may potentially provide the basis for noninvasive therapeutic interventions facilitating emotion regulation processes (86).”

“2015), and frontal pole (Wager et al. 2008) (see online Supplementary Fig.”

“…anuscript Overlap of activation Each self-control task activated areas previously reported in studies of the SST (Aron & Poldrack, 2006; Leung & Cai, 2007), emotion regulation (Kim & Hamann, 2007; Ochsner et al., 2004; Wager et al., 2008), and craving regulation (Kober et al., 2010), respectively.”

“Generally, these areas have implicated in emotion processing (insula) (Nitschke et al., 2006) and with cognitive regulation of emotions (VLPFC) (Wager et al., 2008).”

“The dorsolateral PFC appears to mediate successful regulation of negative emotional responses via interactions that engage the nucleus accumbens and suppress amygdala activation [ 60 , 61].”

“Finally, we wanted to test the ventrolateral prefrontal cortex (vlPFC), which has been implicated in threat reappraisal (Wager et al., 2008) and affective reflection processes (Lieberman et al., 2002b; Lieberman, 2003; Cunningham and Zelazo, 2007).”

“A host of brain imaging studies suggest that increased activation of the prefrontal cortex (PFC) is essential for ER (Beauregard et al., 2001; Ochsner and Gross, 2005; Wager et al., 2008).”

“…& DeWall, 2014; Chikazoe et al., 2009; Cohen et al., 2013; Ernst et al., 2002; Kim & Hamann, 2007; Lieberman et al., 2007; McClure et al., 2004; Wager et al., 2008; see also Boggio et al., 2016), only a few studies have used noninvasive brain stimulation techniques to study the role of the…”

“A previous study (Wager et al., 2008) reported greater right VLPFC activation when healthy participants were instructed to reduce their negative emotions.”

“More specifically, several brain imaging studies suggest that the rVLPFC might be directly involved in the regulation or suppression of negative emotions elicited by a wide array of stimuli (Berkman & Lieberman, 2009; Cohen, Berkman, & Lieberman, 2013; Lieberman et al., 2004; Ochsner & Gross, 2005; Wager et al., 2008).”

“…that generally subserves inhibition and top-down control of the amygdala and nucleus accumbens in the service of effective self-regulation (Berkman and Lieberman, 2009; Berkman et al., 2014; Cohen et al., 2012; Lieberman, 2011; Ochsner and Gross, 2005; Wager et al., 2008; Wagner et al., 2013).”

“(e.g., cognitive restructuring) may rely on functional integration within the same circuit (Wager et al., 2008).”

“…/scan/article-abstract/9/6/864/1668144 by guest on 16 M arch 2020 sadness and happiness) is reliably discernible using conventional approaches (e.g. Phan et al., 2002; Murphy et al., 2003; Pelletier et al., 2003; Wager et al., 2003, Habel et al., 2005, for discussion see Wager et al., 2008).”

“In this way mediation analyses, which are not new to neuroimaging [9], represent a specific statistically degenerate case of process models.”

“A single-level version of the mediation path model (Wager et al., 2008) was used to obtain further insights into the linkage between the various cortical responses (ERP, mu suppression) and the behavioral output (FPSR ratings).”

“It is also known that the VLPFC has a general role in the appraisal processes, and in the generation and regulation of emotions through subcortical pathways (Wager et al., 2008).”

“Australian & New Zealand Journal of Psychiatry, 53(6) PFC could also interact with regions involved in positive affect, such as the nearby ventral striatum (Wager et al., 2008).”

“…Peyron et al., 1999; Valet et al., 2004) and the cognitive reappraisal of stimulus meaning while self-detaching from its emotional qualities, which commonly involves right dorsolateral prefrontal activation (Kalisch et al., 2006; Levesque et al., 2003; Ochsner et al., 2004; Wager et al., 2008).”

“com/ canlab/MediationToolbox), which has been widely used in many neuroimaging studies [27-29].”

“In the literature, a, b, c and c’ were referred as path coefficients or simply paths (MacKinnon et al., 2007; Wager et al., 2008), and we followed this notation.”

“This framework is supported by functional magnetic resonance imaging (fMRI) studies showing that successful emotion regulation is associated with lower amygdala activity and greater vPFC activity (Hariri et al., 2000; Hartley and Phelps, 2010; Wager et al., 2008).”

“The trial strucure was similar to investigations of cognitive reappraisal onducted with older children and adults (Ochsner et al., 004; Perlman et al., 2012; Perlman and Pelphrey, 2011; itskel et al., 2011a; Wager et al., 2008), modified for use ith school-age children.”

“The ventral lateral prefrontal cortex (vlPFC), in particular, is thought to modulate emotion responses through an attentional biasing mechanism that acts on subcortical regions, such as the amygdala (Wager et al. 2008).”

“The VLPFC is activated during experimentally induced allodynia (Witting et al. 2001), and it is thought to be involved in both the generation and regulation of emotion in appraisal processes (Wager et al. 2008).”