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1.  Behavioural and neural correlates of self-focused emotion regulation in social anxiety disorder 
Background
In healthy individuals, voluntary modification of self-relevance has proven effective in regulating subjective emotional experience as well as physiologic responses evoked by emotive stimuli. As social anxiety disorder (SAD) is characterized by both altered emotional and self-related processing, we tested if emotion regulation through self-focused reappraisal is effective in individuals with SAD.
Methods
While undergoing 3 T functional magnetic resonance imaging, individuals with SAD and matched healthy controls either passively viewed neutral and aversive pictures or actively increased or decreased their negative emotional experience through the modification of self-relevance or personal distance to aversive pictures. Participants rated all pictures with regard to the intensity of elicited emotions and self-relatedness.
Results
We included 21 individuals with SAD and 23 controls in our study. Individuals with SAD reported significantly stronger emotional intensity across conditions and showed a nonsignificant tendency to judge pictures as more self-related than controls. Compared with controls, individuals with SAD showed an overactivation in bilateral temporoparietal regions and in the posterior midcingulate cortex during the passive viewing of aversive compared with neutral pictures. During instructed emotion regulation, activation patterns normalized and no significant group differences were detected.
Limitations
As no positive pictures were presented, results might be limited to the regulation of negative emotion.
Conclusion
During passive viewing of aversive images, individuals with SAD showed evidence of neural hyperreactivity that may be interpreted as increased bodily self-consciousness and heightened perspective-taking. During voluntary increase and decrease of negative emotional intensity, group differences disappeared, suggesting self-focused reappraisal as a successful emotion regulation strategy for individuals with SAD.
doi:10.1503/jpn.130080
PMCID: PMC4074236  PMID: 24690369
2.  Neuroscience of human social interactions and adult attachment style 
Since its first description four decades ago, attachment theory (AT) has become one of the principal developmental psychological frameworks for describing the role of individual differences in the establishment and maintenance of social bonds between people. Yet, still little is known about the neurobiological underpinnings of attachment orientations and their well-established impact on a range of social and affective behaviors. In the present review, we summarize data from recent studies using cognitive and imaging approaches to characterize attachment styles and their effect on emotion and social cognition. We propose a functional neuroanatomical framework to integrate the key brain mechanisms involved in the perception and regulation of social emotional information, and their modulation by individual differences in terms of secure versus insecure (more specifically avoidant, anxious, or resolved versus unresolved) attachment traits. This framework describes how each individual's attachment style (built through interactions between personal relationship history and predispositions) may influence the encoding of approach versus aversion tendencies (safety versus threat) in social encounters, implicating the activation of a network of subcortical (amygdala, hippocampus, striatum) and cortical (insula, cingulate) limbic areas. These basic and automatic affective evaluation mechanisms are in turn modulated by more elaborate and voluntary cognitive control processes, subserving mental state attribution and emotion regulation capacities, implicating a distinct network in medial prefrontal cortex (mPFC), superior temporal sulcus (STS), and temporo-parietal junction (TPJ), among others. Recent neuroimaging data suggest that affective evaluation is decreased in avoidantly but increased in anxiously attached individuals. In turn, although data on cognitive control is still scarce, it points toward a possible enhancement of mental state representations associated with attachment insecurity and particularly anxiety. Emotion regulation strategies such as reappraisal or suppression of social emotions are also differentially modulated by attachment style. This research does not only help better understand the neural underpinnings of human social behavior, but also provides important insights on psychopathological conditions where attachment dysregulation is likely to play an important (causal) role.
doi:10.3389/fnhum.2012.00212
PMCID: PMC3398354  PMID: 22822396
adult attachment style; functional neuroanatomical framework; human social interactions; cognitive affective neuroscience; emotional versus cognitive mentalization
3.  The common and distinct neural bases of affect labeling and reappraisal in healthy adults 
Emotion regulation is commonly characterized as involving conscious and intentional attempts to change felt emotions, such as, for example, through reappraisal whereby one intentionally decreases the intensity of one's emotional response to a particular stimulus or situation by reinterpreting it in a less threatening way. However, there is growing evidence and appreciation that some types of emotion regulation are unintentional or incidental, meaning that affective modulation is a consequence but not an explicit goal. For example, affect labeling involves simply verbally labeling the emotional content of an external stimulus or one's own affective responses without an intentional goal of altering emotional responses, yet has been associated with reduced affective responses at the neural and experiential levels. Although both intentional and incidental emotional regulation strategies have been associated with diminished limbic responses and self-reported distress, little previous research has directly compared their underlying neural mechanisms. In this study, we examined the extent to which incidental and intentional emotion regulation, namely, affect labeling and reappraisal, produced common and divergent neural and self-report responses to aversive images relative to an observe-only control condition in a sample of healthy older adults (N = 39). Affect labeling and reappraisal produced common activations in several prefrontal regulatory regions, with affect labeling producing stronger responses in direct comparisons. Affect labeling and reappraisal were also associated with similar decreases in amygdala activity. Finally, affect labeling and reappraisal were associated with correlated reductions in self-reported distress. Together these results point to common neurocognitive mechanisms involved in affect labeling and reappraisal, supporting the idea that intentional and incidental emotion regulation may utilize overlapping neural processes.
doi:10.3389/fpsyg.2014.00221
PMCID: PMC3970015  PMID: 24715880
affect labeling; reappraisal; emotion regulation; fMRI; amygdala; prefrontal cortex
4.  Neural Correlates of the Use of Psychological Distancing to Regulate Responses to Negative Social Cues: A Study of Patients with Borderline Personality Disorder 
Biological psychiatry  2009;66(9):854.
Background
Emotional instability is a defining feature of borderline personality disorder (BPD), yet little is understood about its underlying neural correlates. One possible contributing factor to emotional instability is a failure to adequately employ adaptive cognitive regulatory strategies such as psychological distancing.
Method
To determine whether there are differences in neural dynamics underlying this control strategy, between BPD patients and healthy volunteers (HC’s), BOLD fMRI signals were acquired as 18 BPD and 16 HC subjects distanced from or simply looked at negative and neutral pictures depicting social interactions. Contrasts in signal between distance and look condition were compared between groups to identify commonalities and differences in regional activation.
Results
BPD patients show a different pattern of activation compared to HC subjects when looking at negative vs. neutral pictures. When distancing vs. looking at negative pictures, both groups showed decreased negative affect in rating and increased activation of the dorsolateral prefrontal cortex, areas near/along the intraparietal sulcus (IPS), ventrolateral prefrontal cortex and posterior cingulate/precuneus regions. However, the BPD group showed less BOLD signal change in dorsal anterior cingulate cortex and IPS, less deactivation in the amygdala and greater activation in the superior temporal sulcus and superior frontal gyrus.
Conclusion
BPD and HC subjects display different neural dynamics while passively viewing social emotional stimuli. In addition, BPD patients do not engage the cognitive control regions to the extent that HC’s do when employing a distancing strategy to regulate emotional reactions, which may be a factor contributing to the affective instability of BPD.
doi:10.1016/j.biopsych.2009.06.010
PMCID: PMC2821188  PMID: 19651401
Emotion; Cognitive Reappraisal; Social Cognitive Neuroscience; Psychological Distancing; Emotion Regulation; fMRI
5.  Emotion regulation reduces loss aversion and decreases amygdala responses to losses 
Emotion regulation strategies can alter behavioral and physiological responses to emotional stimuli and the neural correlates of those responses in regions such as the amygdala or striatum. The current study investigates the brain systems engaged when using an emotion regulation technique during financial decisions. In decision making, regulating emotion with reappraisal-focused strategies that encourage taking a different perspective has been shown to reduce loss aversion as observed both in choices and in the relative arousal responses to actual loss and gain outcomes. In the current study, we find using fMRI that behavioral loss aversion correlates with amygdala activity in response to losses relative to gains. Success in regulating loss aversion also correlates with the reduction in amygdala responses to losses but not to gains. Furthermore, across both decisions and outcomes, we find the reappraisal strategy increases baseline activity in dorsolateral and ventromedial prefrontal cortex and the striatum. The similarity of the neural circuitry observed to that seen in emotion regulation, despite divergent tasks, serves as further evidence for a role of emotion in decision making, and for the power of reappraisal to change assessments of value and thereby choices.
doi:10.1093/scan/nss002
PMCID: PMC3594725  PMID: 22275168
emotion; reappraisal; emotion regulation; decision making; loss aversion
6.  Individual Differences in Typical Reappraisal Use Predict Amygdala and Prefrontal Responses 
Biological psychiatry  2008;65(5):367-373.
Background
Participants who are instructed to use reappraisal to downregulate negative emotion show decreased amygdala responses and increased prefrontal responses. However, it is not known whether individual differences in the tendency to use reappraisal manifests in similar neural responses when individuals are spontaneously confronted with negative situations. Such spontaneous emotion regulation might play an important role in normal and pathological responses to the emotional challenges of everyday life.
Methods
Fifty-six healthy women completed a blood oxygenation-level dependent functional magnetic resonance imaging challenge paradigm involving the perceptual processing of emotionally negative facial expressions. Participants also completed measures of typical emotion regulation use, trait anxiety, and neuroticism.
Results
Greater use of reappraisal in everyday life was related to decreased amygdala activity and increased prefrontal and parietal activity during the processing of negative emotional facial expressions. These associations were not attributable to variation in trait anxiety, neuroticism, or the use of another common form of emotion regulation, namely suppression.
Conclusions
These findings suggest that, like instructed reappraisal, individual differences in reappraisal use are associated with decreased activation in ventral emotion generative regions and increased activation in prefrontal control regions in response to negative stimuli. Such individual differences in emotion regulation might predict successful coping with emotional challenges as well as the onset of affective disorders.
doi:10.1016/j.biopsych.2008.09.007
PMCID: PMC2855682  PMID: 18930182
Amygdala; cognitive control; emotion; fMRI; regulation; reappraisal
7.  The development of emotion regulation: an fMRI study of cognitive reappraisal in children, adolescents and young adults 
The ability to use cognitive reappraisal to regulate emotions is an adaptive skill in adulthood, but little is known about its development. Because reappraisal is thought to be supported by linearly developing prefrontal regions, one prediction is that reappraisal ability develops linearly. However, recent investigations into socio-emotional development suggest that there are non-linear patterns that uniquely affect adolescents. We compared older children (10–13), adolescents (14–17) and young adults (18–22) on a task that distinguishes negative emotional reactivity from reappraisal ability. Behaviorally, we observed no age differences in self-reported emotional reactivity, but linear and quadratic relationships between reappraisal ability and age. Neurally, we observed linear age-related increases in activation in the left ventrolateral prefrontal cortex, previously identified in adult reappraisal. We observed a quadratic pattern of activation with age in regions associated with social cognitive processes like mental state attribution (medial prefrontal cortex, posterior cingulate cortex, anterior temporal cortex). In these regions, we observed relatively lower reactivity-related activation in adolescents, but higher reappraisal-related activation. This suggests that (i) engagement of the cognitive control components of reappraisal increases linearly with age and (ii) adolescents may not normally recruit regions associated with mental state attribution, but (iii) this can be reversed with reappraisal instructions.
doi:10.1093/scan/nsr093
PMCID: PMC3252634  PMID: 22228751
reappraisal; emotion regulation; development; social; cognitive
8.  Neural bases of reappraisal regulatory effect on negative emotion in high reappraisers☆ 
Neural Regeneration Research  2012;7(32):2542-2547.
Previous studies have reported that individual differences in reappraisal use are associated with particular patterns of neural activity. We hypothesized that if ‘high reappraisers’ (individuals who use reappraisal well in a behavioral experiment) completed two training sessions, they would exhibit more reliable patterns of neural activity related to cognitive reappraisal. In the present study, 13 high reappraisers were selected from 27 healthy volunteers through an initial behavioral experiment (first training) followed by a functional MRI experiment (second training). Emotional images selected from the International Affective Picture System were used for both the behavioral and functional MRI sessions of the experiment. The behavioral results revealed that reappraisal reduced subjective unpleasantness. The functional MRI results revealed that the cognitive reappraisal used by high reappraisers decreased the activation of emotion-responsive regions, including the amygdala, insula, and cingulate gyrus, and increased the activation of regulation-related regions, including the inferior prefrontal cortex, orbital prefrontal cortex, and dorsal medial prefrontal cortex. These findings suggest the involvement of inferior orbital and dorsal medial prefrontal cortex in constructing reappraisal strategies that modulate activity in emotion-processing systems.
doi:10.3969/j.issn.1673-5374.2012.32.009
PMCID: PMC4200711  PMID: 25337107
cognitive reappraisal; negative emotion; amygdala; functional MRI; neural regeneration
9.  Impact of Cognitive-Behavioral Therapy for Social Anxiety Disorder on the Neural Dynamics of Cognitive Reappraisal of Negative Self-Beliefs 
JAMA psychiatry  2013;70(10):1048-1056.
Importance
Cognitive-Behavioral Therapy for social anxiety disorder is thought to enhance cognitive reappraisal in patients with social anxiety disorder. Such improvements should be evident in cognitive reappraisal-related prefrontal cortex responses.
Objective
To determine whether Cognitive-Behavioral Therapy for social anxiety disorder modifies cognitive reappraisal-related prefrontal cortex neural signal magnitude and timing when implementing cognitive reappraisal with negative self-beliefs.
Design
Randomized controlled trial of Cognitive-Behavioral Therapy for social anxiety disorder versus waitlist control group.
Setting
Psychology department.
Participants
Seventy-five patients with generalized social anxiety disorder randomly assigned to Cognitive-Behavioral Therapy or waitlist.
Intervention
Sixteen sessions of individual-Cognitive-Behavioral Therapy for social anxiety disorder during a study that enrolled patients from 2007 to 2010.
Main Outcome Measures
Negative emotion ratings and functional magnetic resonance blood oxygen-level dependent signal when reacting to and cognitively reappraising negative self-beliefs embedded in autobiographical social anxiety situations.
Results
During reactivity trials, compared to waitlist, Cognitive-Behavioral Therapy produced (a) greater reduction in negative emotion ratings and (b) greater blood oxygen-level dependent signal magnitude in medial prefrontal cortex. During cognitive reappraisal trials, compared to waitlist, Cognitive-Behavioral Therapy produced (c) greater reduction in negative emotion ratings, (d) greater blood oxygen-level dependent signal magnitude in dorsolateral and dorsomedial prefrontal cortex, (e) earlier temporal onset of dorsomedial prefrontal cortex activity, and (f) greater dorsomedial prefrontal cortex-amygdala inverse functional connectivity.
Conclusions and Relevance
Modulation of cognitive reappraisal-related brain responses, timing and functional connectivity may be important brain changes that contribute to the effectiveness of Cognitive-Behavioral Therapy for social anxiety.
Trial Registration
ClinicalTrials.gov identifier: NCT00380731; http://www.clinicaltrials.gov/ct2/show/NCT00380731?term=social+anxiety+cognitive+behavioral+therapy+Stanford&rank=1
doi:10.1001/jamapsychiatry.2013.234
PMCID: PMC4141477  PMID: 23945981
social anxiety; emotion regulation; CBT; fMRI; reappraisal; brain
10.  The Role of Dorsal Anterior Cingulate Cortex in the Regulation of Craving by Reappraisal in Smokers 
PLoS ONE  2012;7(8):e43598.
Rationale and Objective
Drug cues can induce craving for drugs of abuse. Dysfunctional regulation of emotion and motivation regarding rewarding objects appears to be an integral part of addiction. It has been found that cognitive strategies decreased the intensity of craving in addicts. Reappraisal strategy is a type of cognitive strategy that requires participants to reinterpret the meaning of an emotional situation. In addition, studies have found that activation of the dorsal anterior cingulate cortex (dACC) is associated with the selection and application of cognitive reappraisal. In present study, we sought to determine whether such cognitive regulation engages the dACC and improves inhibition of craving in smokers.
Methods
Sixteen smokers underwent functional magnetic resonance imaging (fMRI) during performance of a cigarette reward-conditioning procedure with cognitive reappraisal. We focused our analyses on the dACC as a key structure of cognitive control of craving. Cue induced craving under different conditions was obtained. Correlational analysis between the functional response in the dACC and the subjective craving was performed.
Results
We found that using a cognitive reappraisal was successful in decreasing the conditioned craving. Right dACC (BA 24/32) engaged in the cognitive reappraisal. In addition, the individual’s subjective craving was negatively correlated with the right dACC activation.
Conclusions
These findings suggest that the dACC are important substrates of Inhibition of cue induced craving in smokers. Cognitive regulation by cognitive reappraisal may help addicted individuals avoid the anticipated situations where they are exposed to conditioned cues.
doi:10.1371/journal.pone.0043598
PMCID: PMC3425483  PMID: 22928000
11.  An fMRI investigation of the cognitive reappraisal of negative memories 
Neuropsychologia  2013;51(12):2389-2400.
Episodic memory retrieval can be influenced by individuals’ current goals, including those that are emotional in nature. Participants underwent an fMRI scan while reappraising, or changing the way they thought about aversive images they had previously encoded, to down-regulate (i.e., decrease), up-regulate (i.e., increase), or maintain the emotional intensity associated with their recall. A conjunction analysis between down- and up-regulation during the entire 12-sec recall period revealed that both commonly activated reappraisal-related regions, particularly in the lateral and medial prefrontal cortex (PFC). However, when we analyzed a reappraisal instruction phase prior to recall and then divided the recall phase into the time when individuals were first searching for their memories and later elaborating on their details, we found that down- and up-regulation engaged greater neural activity at different time points. Up-regulation engaged greater PFC activity than down-regulation or maintenance during the reappraisal instruction phase. In contrast, down-regulation engaged greater lateral PFC activity as images were being searched for and retrieved. Maintaining the emotional intensity associated with the aversive images engaged similar regions to a greater extent than either reappraisal condition as participants elaborated on the details of the images they were holding in mind. Our findings suggest that down- and up-regulation engage similar neural regions during memory retrieval, but differ in the timing of this engagement.
doi:10.1016/j.neuropsychologia.2013.02.012
PMCID: PMC3723712  PMID: 23500898
episodic memory; retrieval; emotion; emotion regulation; cognitive reappraisal
12.  Neural Basis of Anticipatory Anxiety Reappraisals 
PLoS ONE  2014;9(7):e102836.
Reappraisal is a well-known emotion regulation strategy. Recent neuroimaging studies suggest that reappraisal recruits both medial and lateral prefrontal brain regions. However, few studies have investigated neural representation of reappraisals associated with anticipatory anxiety, and the specific nature of the brain activity underlying this process remains unclear. We used functional magnetic resonance imaging (fMRI) to investigate neural activity associated with reappraisals of transient anticipatory anxiety. Although transient anxiety activated mainly subcortical regions, reappraisals targeting the anxiety were associated with increased activity in the medial and lateral prefrontal regions (including the orbitofrontal and anterior cingulate cortices). Reappraisal decreased fear circuit activity (including the amygdala and thalamus). Correlational analysis demonstrated that reductions in subjective anxiety associated with reappraisal were correlated with orbitofrontal and anterior cingulate cortex activation. Reappraisal recruits medial and lateral prefrontal regions; particularly the orbitofrontal and anterior cingulate cortices are associated with successful use of this emotion regulation strategy.
doi:10.1371/journal.pone.0102836
PMCID: PMC4105563  PMID: 25048028
13.  Individual Differences in Some (But Not All) Medial Prefrontal Regions Reflect Cognitive Demand While Regulating Unpleasant Emotion 
NeuroImage  2009;47(3):852-863.
The present study investigated the premise that individual differences in autonomic physiology could be used to specify the nature and consequences of information processing taking place in medial prefrontal regions during cognitive reappraisal of unpleasant emotion. Neural (blood oxygenation level-dependent functional magnetic resonance imaging) and autonomic (electrodermal, pupil diameter, cardiac acceleration) signals were recorded simultaneously as twenty-six older people (ages 64-66 years) used reappraisal to increase, maintain, or decrease their responses to unpleasant pictures. EDA was higher when increasing and lower when decreasing compared to maintaining. This suggested modulation of emotional arousal by reappraisal. By contrast, pupil diameter and cardiac acceleration were higher when increasing and decreasing compared to maintaining. This suggested modulation of cognitive demand. Importantly, reappraisal-related activation (increase, decrease > maintain) in two medial prefrontal regions (dorsal medial frontal gyrus and dorsal cingulate cortex) was correlated with greater cardiac acceleration (increase, decrease > maintain) and monotonic changes in EDA (increase > maintain > decrease). These data indicate that these two medial prefrontal regions are involved in the allocation of cognitive resources to regulate unpleasant emotion, and that they modulate emotional arousal in accordance with the regulatory goal. The emotional arousal effects were mediated by the right amygdala. Reappraisal-related activation in a third medial prefrontal region (subgenual anterior cingulate cortex) was not associated with similar patterns of change in any of the autonomic measures, thus highlighting regional specificity in the degree to which cognitive demand is reflected in medial prefrontal activation during reappraisal.
doi:10.1016/j.neuroimage.2009.05.069
PMCID: PMC2766667  PMID: 19486944
emotion regulation; reappraisal; amygdala; medial prefrontal cortex; negative emotion; pupil dilation; autonomic physiology
14.  Emotion regulation in social anxiety disorder: behavioral and neural responses to three socio-emotional tasks 
Background
Social anxiety disorder (SAD) is thought to involve deficits in emotion regulation, and more specifically, deficits in cognitive reappraisal. However, evidence for such deficits is mixed.
Methods
Using functional magnetic resonance imaging (fMRI) of blood oxygen-level dependent (BOLD) signal, we examined reappraisal-related behavioral and neural responses in 27 participants with generalized SAD and 27 healthy controls (HC) during three socio-emotional tasks: (1) looming harsh faces (Faces); (2) videotaped actors delivering social criticism (Criticism); and (3) written autobiographical negative self-beliefs (Beliefs).
Results
Behaviorally, compared to HC, participants with SAD had lesser reappraisal-related reduction in negative emotion in the Beliefs task. Neurally, compared to HC, participants with SAD had lesser BOLD responses in reappraisal-related brain regions when reappraising faces, in visual and attention related regions when reappraising criticism, and in the left superior temporal gyrus when reappraising beliefs. Examination of the temporal dynamics of BOLD responses revealed late reappraisal-related increased responses in HC, compared to SAD. In addition, the dorsomedial prefrontal cortex (DMPFC), which showed reappraisal-related increased activity in both groups, had similar temporal dynamics in SAD and HC during the Faces and Criticism tasks, but greater late response increases in HC, compared to SAD, during the Beliefs task. Reappraisal-related greater late DMPFC responses were associated with greater percent reduction in negative emotion ratings in SAD patients.
Conclusions
These results suggest a dysfunction of cognitive reappraisal in SAD patients, with overall reduced late brain responses in prefrontal regions, particularly when reappraising faces. Decreased late activity in the DMPFC might be associated with deficient reappraisal and greater negative reactivity.
Trial registration
ClinicalTrials.gov identifier: NCT00380731
doi:10.1186/2045-5380-3-20
PMCID: PMC4029608  PMID: 24517388
Social anxiety; Emotion regulation; Reappraisal; fMRI; DMPFC; Temporal dynamics
15.  Individual differences in dispositional mindfulness and brain activity involved in reappraisal of emotion 
The regulation of negative emotion through reappraisal has been shown to induce increased prefrontal activity and decreased amygdala activity. Individual differences in dispositional mindfulness reflect differences in typical recognition, detachment and regulation of current experience, thought to also operate as top–down control mechanism. We sought to investigate whether such individual differences would be associated with brain activity elicited during reappraisal of negative emotion. Eighteen healthy participants completed a functional magnetic resonance imaging task that involved attending to or reappraising negative stimuli, and provided emotion experience ratings after each trial. Dispositional mindfulness was assessed with a self-report questionnaire. Reappraisal induced activity in a brain network involving predominantly dorsal portions of the prefrontal cortex, replicating previous studies. A voxelwise regression analysis showed that individual differences in the tendency to be mindful predicted activity in neural regions underlying reappraisal, with dorsomedial prefrontal cortex activation increasing with more mindfulness traits. Notably, this prefrontal activation was inversely correlated with the amygdala response to negative scenes, further supporting its role in down-regulating emotion-generation regions. These findings suggest that individual differences in dispositional mindfulness, which reflect the tendency to recognize and regulate current states, may modulate activity in neural systems involved in the effective cognitive control of negative emotion.
doi:10.1093/scan/nsq006
PMCID: PMC2999757  PMID: 20147457
emotion regulation; fMRI; individual differences; mindfulness; prefrontal cortex
16.  Emotion regulation in spider phobia: role of the medial prefrontal cortex 
Phobic responses are strong emotional reactions towards phobic objects, which can be described as a deficit in the automatic regulation of emotions. Difficulties in the voluntary cognitive control of these emotions suggest a further phobia-specific deficit in effortful emotion regulation mechanisms. The actual study is based on this emotion regulation conceptualization of specific phobias. The aim is to investigate the neural correlates of these two emotion regulation deficits in spider phobics. Sixteen spider phobic females participated in a functional magnetic resonance imaging (fMRI) study in which they were asked to voluntarily up- and down-regulate their emotions elicited by spider and generally aversive pictures with a reappraisal strategy. In line with the hypothesis concerning an automatic emotion regulation deficit, increased activity in the insula and reduced activity in the ventromedial prefrontal cortex was observed. Furthermore, phobia-specific effortful regulation within phobics was associated with altered activity in medial prefrontal cortex areas. Altogether, these results suggest that spider phobic subjects are indeed characterized by a deficit in the automatic as well as the effortful regulation of emotions elicited by phobic compared with aversive stimuli. These two forms of phobic emotion regulation deficits are associated with altered activity in different medial prefrontal cortex subregions.
doi:10.1093/scan/nsp013
PMCID: PMC2728632  PMID: 19398537
phobia; emotion regulation; medial prefrontal cortex; cognitive control; fMRI
17.  Serotonin Transporter Genotype Modulates Subgenual Response to Fearful Faces Using an Incidental Task 
Journal of cognitive neuroscience  2011;23(11):3681-3693.
This study assessed the impact of serotonin transporter genotype (5-HTTLPR) on regional responses to emotional faces in the amygdala and subgenual cingulate cortex (sgACC), while subjects performed a gender discrimination task. Although we found no evidence for greater amygdala reactivity or reduced amygdala–sgACC coupling in short variant 5-HTTLPR homozygotes (s/s), we observed an interaction between genotype and emotion in sgACC. Only long variant homozygotes (la/la) exhibited subgenual deactivation to fearful versus neutral faces, whereas the effect in s/s subjects was in the other direction. This absence of subgenual deactivation in s/s subjects parallels a recent finding in depressed subjects [Grimm, S., Boesiger, P., Beck, J., Schuepbach, D., Bermpohl, F., Walter, M., et al. Altered negative BOLD responses in the default-mode network during emotion processing in depressed subjects. Neuropsychopharmacology, 34, 932–943, 2009]. Taken together, the findings suggest that subgenual cingulate activity may play an important role in regulating the impact of aversive stimuli, potentially conferring greater resilience to the effects of aversive stimuli in la/la subjects. Using dynamic causal modeling of functional magnetic resonance imaging data, we explored the effects of genotype on effective connectivity and emotion-specific changes in coupling across a network of regions implicated in social processing. Viewing fearful faces enhanced bidirectional excitatory coupling between the amygdala and the fusiform gyrus, and increased the inhibitory influence of the amygdala over the sgACC, although this modulation of coupling did not differ between the genotype groups. The findings are discussed in relation to the role of sgACC and serotonin in moderating responses to aversive stimuli [Dayan, P., & Huys, Q. J., Serotonin, inhibition, and negative mood. PLoS Comput Biol, 4, e4, 2008; Mayberg, H. S., Liotti, M., Brannan, S. K., McGinnis, S., Mahurin, R. K., Jerabek, P. A., et al. Reciprocal limbic–cortical function and negative mood: Converging PET findings in depression and normal sadness. Am J Psychiatry, 156, 675–682, 1999].
doi:10.1162/jocn_a_00055
PMCID: PMC3435845  PMID: 21568644
18.  Representation of Cognitive Reappraisal Goals in Frontal Gamma Oscillations 
PLoS ONE  2014;9(11):e113375.
Recently, numerous efforts have been made to understand the neural mechanisms underlying cognitive regulation of emotion, such as cognitive reappraisal. Many studies have reported that cognitive control of emotion induces increases in neural activity of the control system, including the prefrontal cortex and the dorsal anterior cingulate cortex, and increases or decreases (depending upon the regulation goal) in neural activity of the appraisal system, including the amygdala and the insula. It has been hypothesized that information about regulation goals needs to be processed through interactions between the control and appraisal systems in order to support cognitive reappraisal. However, how this information is represented in the dynamics of cortical activity remains largely unknown. To address this, we investigated temporal changes in gamma band activity (35–55 Hz) in human electroencephalograms during a cognitive reappraisal task that was comprised of three reappraisal goals: to decease, maintain, or increase emotional responses modulated by affect-laden pictures. We examined how the characteristics of gamma oscillations, such as spectral power and large-scale phase synchronization, represented cognitive reappraisal goals. We found that left frontal gamma power decreased, was sustained, or increased when the participants suppressed, maintained, or amplified their emotions, respectively. This change in left frontal gamma power appeared during an interval of 1926 to 2453 ms after stimulus onset. We also found that the number of phase-synchronized pairs of gamma oscillations over the entire brain increased when participants regulated their emotions compared to when they maintained their emotions. These results suggest that left frontal gamma power may reflect cortical representation of emotional states modulated by cognitive reappraisal goals and gamma phase synchronization across whole brain regions may reflect emotional regulatory efforts to achieve these goals. Our study may provide the basis for an electroencephalogram-based neurofeedback system for the cognitive regulation of emotion.
doi:10.1371/journal.pone.0113375
PMCID: PMC4234654  PMID: 25401328
19.  The Neural Bases of Distraction and Reappraisal 
Journal of cognitive neuroscience  2010;22(2):248-262.
Distraction and reappraisal are two commonly used forms of cognitive emotion regulation. Functional neuroimaging studies have shown that each one depends upon interactions between prefrontal cortex, interpreted as implementing cognitive control, and limbic regions, interpreted as mediating emotional responses. However, no study has directly compared distraction with reappraisal, and it thus remains unclear whether they draw upon different neural mechanisms and have different emotional consequences. The present fMRI study compared distraction and reappraisal, and found both similarities and differences between the two forms of emotion regulation. Both resulted in decreased negative affect, decreased activation in the amygdala, and increased activation in prefrontal and cingulate regions. Relative to distraction, reappraisal led to greater decreases in negative affect, and greater increases in a network of regions associated with processing affective meaning (medial prefrontal and anterior temporal cortices). Relative to reappraisal, distraction led to greater decreases in amygdala activation, and greater increases in activation in prefrontal and parietal regions. Taken together, these data suggest that distraction and reappraisal differentially engage neural systems involved in attentional deployment and cognitive reframing, and have different emotional consequences.
doi:10.1162/jocn.2009.21243
PMCID: PMC4136451  PMID: 19400679
20.  The Neural Correlates of Cognitive Reappraisal during Emotional Autobiographical Memory Recall 
We used fMRI to investigate the neural processes engaged as individuals down- and up-regulated the emotions associated with negative autobiographical memories (AMs) using cognitive reappraisal strategies. Our analyses examined neural activity during 3 separate phases, as participants: (a) viewed a reappraisal instruction (i.e., Decrease, Increase, Maintain), (b) searched for an AM referenced by a self-generated cue, and (c) elaborated upon the details of the AM being held in mind. Decreasing emotional intensity primarily engaged activity in regions previously implicated in cognitive control (e.g., dorsal and ventral lateral prefrontal cortex), emotion generation and processing (e.g., amygdala, insula), and visual imagery (e.g., precuneus) as participants searched for and retrieved events. In contrast, increasing emotional intensity engaged similar regions during the instruction phase (i.e., before a memory cue was presented) and again as individuals later elaborated upon the details of the events they had recalled. These findings confirm that reappraisal can modulate neural activity during the recall of personally-relevant events, though the time course of this modulation appears to depend on whether individuals are attempting to down- or up-regulate their emotions.
doi:10.1162/jocn_a_00289
PMCID: PMC3631011  PMID: 22905826
21.  Overlapping Neural Substrates between Intentional and Incidental Down-regulation of Negative Emotions 
Emotion (Washington, D.C.)  2012;12(2):229-235.
Emotion regulation can be achieved in various ways, but few studies have evaluated the extent to which the neurocognitive substrates of these distinct operations overlap. In the study reported here, functional magnetic resonance imaging (fMRI) was used to measure activity in the amygdala and prefrontal cortex of ten participants who completed two independent tasks of emotion regulation – reappraisal, measuring intentional emotion regulation, and affect labeling, measuring incidental emotion regulation – with the objective of identifying potential overlap in the neural substrates underlying each task. Analyses focused on a priori regions of interest in the amygdala and inferior frontal gyrus (IFG).For both tasks, fMRI showed decreased amygdala activation during “emotion regulation” compared to “emotion” conditions. During reappraisal, this decrease in amygdala activation was accompanied by a proportional decrease in emotional intensity ratings; during affect labeling, the decrease in amygdala activation correlated with self-reported aggression. Importantly, across participants, the magnitude of decrease in amygdala activation during reappraisal correlated with the magnitude of decrease during affect labeling, even though the tasks were administered on separate days, and values indexing amygdala activation during each task were extracted independently of one another. In addition, IFG-amygdala connectivity, assessed via psychophysiological interaction analysis, overlapped between tasks in two regions within the right IFG. The results suggest that the two tasks recruit overlapping regions of prefrontal cortex, resulting in similar reductions in amygdala activation, regardless of the strategy employed. Intentional and incidental forms of emotion regulation, despite their phenomenological differences, may therefore converge on a common neurocognitive pathway.
doi:10.1037/a0027421
PMCID: PMC4111128  PMID: 22468617
Emotion regulation; cognitive reappraisal; affect labeling; amygdala; prefrontal cortex; inferior frontal gyrus
22.  Evidence of successful modulation of brain activation and subjective experience during reappraisal of negative emotion in unmedicated depression 
Psychiatry research  2013;212(2):99-107.
Functional magnetic resonance imaging (fMRI) was used to examine cognitive regulation of negative emotion in unmedicated Major Depressive Disorder (MDD). Twenty-four controls and 12 depressed adults used reappraisal to increase (real condition) and reduce (photo condition) the personal relevance of negative and neutral pictures during fMRI as valence ratings were collected; passive viewing (look condition) served as a baseline. Reappraisal was not strongly affected by MDD. Ratings indicated that both groups successfully reappraised negative emotional experience. Both groups also showed better memory for negative vs. neutral pictures two weeks later. Across groups, increased brain activation was observed on negative/real vs. negative/look and negative/photo trials in left dorsolateral prefrontal cortex (DLPFC), rostral anterior cingulate, left parietal cortex, caudate, and right amygdala. Depressive severity was inversely correlated with activation modulation in the left DLPFC, right amygdala, and right cerebellum during negative reappraisal. The lack of group differences suggests that depressed adults can modulate the brain activation and subjective experience elicited by negative pictures when given clear instructions. However, the negative relationship between depression severity and effects of reappraisal on brain activation indicates that group differences may be detectable in larger samples of more severely depressed participants.
doi:10.1016/j.pscychresns.2013.01.001
PMCID: PMC3640775  PMID: 23570916
emotion regulation; major depressive disorder; default mode network; memory; fMRI
23.  ‘Put on your poker face’: neural systems supporting the anticipation for expressive suppression and cognitive reappraisal 
It is a unique human ability to regulate negative thoughts and feelings. Two well-investigated emotion-regulation strategies (ERSs), cognitive reappraisal and expressive suppression, are associated with overlapping prefrontal neural correlates, but differ temporally during the emotion-generation process. Although functional imaging studies have mainly investigated these ERS as a reaction to an emotion-inducing event, the intention to regulate upcoming negative emotions might already be associated with differences in neural activity. Hence, event-related functional magnetic resonance imaging was recorded in 42 participants while they completed an emotion-regulation paradigm. During this task, participants were instructed to proactively prepare to use a specific ERS knowing that a negative, high-arousing image would appear after the preparation period. As expected, the results demonstrated prefrontal and parietal activation while participants were suppressing or reappraising their emotions (family-wise error (FWE)-corrected). The intention to suppress emotions was associated with increased activation in the right inferior frontal gyrus, bilateral putamen, pre-supplementary motor area and right supramarginal gyrus (FWE-corrected). This enhanced proactive inhibitory control: (i) predicted decreased motoric activity during the actual suppression of emotional expressions and (2) trended toward a significant association with how successfully participants suppressed their emotions. However, neural correlates of preparatory control for cognitive reappraisal were not observed, possibly because contextual cues about the upcoming emotional stimulus are necessary to proactively start to cognitively reinterpret the situation.
doi:10.1093/scan/nss090
PMCID: PMC3831557  PMID: 22956675
emotion regulation; cognitive reappraisal; expressive suppression; proactive and reactive control
24.  Neural mechanisms of emotion regulation: Evidence for two independent prefrontal-subcortical pathways 
Neuron  2008;59(6):1037-1050.
Although prefrontal cortex has been implicated in the cognitive regulation of emotion, the cortical-subcortical interactions that mediate this ability remain poorly understood. To address this issue, we identified a right ventrolateral prefrontal region (vlPFC) whose activity correlated with reduced negative emotional experience during cognitive reappraisal of aversive images. We then applied a novel pathway-mapping analysis on subcortical regions to locate mediators of the association between vlPFC activity and reappraisal success (i.e. reductions in reported emotion). Results identified two separable pathways that together explained ~50% of the reported variance in self-reported emotion: 1) a path through nucleus accumbens that predicted greater reappraisal success, and 2) a path through ventral amygdala that predicted reduced reappraisal success (i.e., more negative emotion). These results provide direct evidence that vlPFC is involved in both the generation and regulation of emotion through different subcortical pathways, suggesting a general role for this region in appraisal processes.
doi:10.1016/j.neuron.2008.09.006
PMCID: PMC2742320  PMID: 18817740
25.  Social stimulation and corticolimbic reactivity in premenstrual dysphoric disorder: a preliminary study 
Background
Premenstrual dysphoric disorder (PMDD), characterized by luteal phase-induced negative affect and loss of impulse control, often results in compromised social interactions. Although amygdala activation is generally linked to negative affect, increased amygdala reactivity to aversive stimuli in the luteal phase has not been consistently reported in PMDD. We tested the hypothesis that amygdala hyper-reactivity in PMDD is symptom specific, rather than generalized, and linked to socially relevant stimuli. Blood oxygenation level dependent signal changes during exposure to negative images with social and non-social content were evaluated in the mid-follicular and late luteal phase of the menstrual cycle. Fourteen women with PMDD and 13 healthy controls participated.
Results
When compared with healthy controls, women with PMDD in the luteal phase had enhanced reactivity to social stimuli compared to non-social stimuli in the amygdala and insula, but attenuated reactivity in the anterior cingulate cortex. Functional couplings between emotion processing and controlling areas were significantly different, being positive in women with PMDD and negative in healthy controls. Changes in progesterone levels in women with PMDD correlated positively with altered amygdala reactivity.
Conclusions
Socially relevant aversive stimulation elicited enhanced activity in affective processing brain regions that were functionally coupled to compromised activity in cognitive control areas. Because increased reactivity correlated positively with alterations in ovarian steroid levels, data preliminary support the hypothesis that enhanced progesterone sensitivity in PMDD affects corticolimbic processing of social emotions.
doi:10.1186/2045-5380-4-3
PMCID: PMC4015856  PMID: 24572042

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