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1.  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
2.  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
3.  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
4.  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
5.  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
6.  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
7.  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
8.  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
9.  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
10.  ‘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
11.  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
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.  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
14.  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
15.  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
16.  Impaired regulation of emotion: neural correlates of reappraisal and distraction in bipolar disorder and unaffected relatives 
Translational Psychiatry  2015;5(1):e497-.
Deficient emotion regulation has been proposed as a crucial pathological mechanism in bipolar disorder (BD). We therefore investigated emotion regulation impairments in BD, the related neural underpinnings and their etiological relevance for the disorder. Twenty-two euthymic patients with bipolar-I disorder and 17 unaffected first-degree relatives of BD-I patients, as well as two groups of healthy gender-, age- and education-matched controls (N=22/17, respectively) were included. Participants underwent functional magnetic resonance imaging while applying two different emotion regulation techniques, reappraisal and distraction, when presented with emotional images. BD patients and relatives showed impaired downregulation of amygdala activity during reappraisal, but not during distraction, when compared with controls. This deficit was correlated with the habitual use of reappraisal. The negative connectivity of amygdala and orbitofrontal cortex (OFC) observed during reappraisal in controls was reversed in BD patients and relatives. There were no significant differences between BD patients and relatives. As being observed in BD patients and unaffected relatives, deficits in emotion regulation through reappraisal may represent heritable neurobiological abnormalities underlying BD. The neural mechanisms include impaired control of amygdala reactivity to emotional stimuli and dysfunctional connectivity of the amygdala to regulatory control regions in the OFC. These are, thus, important aspects of the neurobiological basis of increased vulnerability for BD.
doi:10.1038/tp.2014.137
PMCID: PMC4312831  PMID: 25603413
17.  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
18.  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
19.  Detaching from the negative by reappraisal: the role of right superior frontal gyrus (BA9/32) 
The ability to reappraise the emotional impact of events is related to long-term mental health. Self-focused reappraisal (REAPPself), i.e., reducing the personal relevance of the negative events, has been previously associated with neural activity in regions near right medial prefrontal cortex, but rarely investigated among brain-damaged individuals. Thus, we aimed to examine the REAPPself ability of brain-damaged patients and healthy controls considering structural atrophies and gray matter intensities, respectively. Twenty patients with well-defined cortex lesions due to an acquired circumscribed tumor or cyst and 23 healthy controls performed a REAPPself task, in which they had to either observe negative stimuli or decrease emotional responding by REAPPself. Next, they rated the impact of negative arousal and valence. REAPPself ability scores were calculated by subtracting the negative picture ratings after applying REAPPself from the ratings of the observing condition. The scores of the patients were included in a voxel-based lesion-symptom mapping (VLSM) analysis to identify deficit related areas (ROI). Then, a ROI group-wise comparison was performed. Additionally, a whole-brain voxel-based-morphometry (VBM) analysis was run, in which healthy participant's REAPPself ability scores were correlated with gray matter intensities. Results showed that (1) regions in the right superior frontal gyrus (SFG), comprising the right dorsolateral prefrontal cortex (BA9) and the right dorsal anterior cingulate cortex (BA32), were associated with patient's impaired down-regulation of arousal, (2) a lesion in the depicted ROI occasioned significant REAPPself impairments, (3) REAPPself ability of controls was linked with increased gray matter intensities in the ROI regions. Our findings show for the first time that the neural integrity and the structural volume of right SFG regions (BA9/32) might be indispensable for REAPPself. Implications for neurofeedback research are discussed.
doi:10.3389/fnbeh.2014.00165
PMCID: PMC4023069  PMID: 24847230
emotion regulation; self-focused reappraisal; VLSM; VBM; right SFG
20.  Neural mechanisms of cognitive reappraisal in remitted major depressive disorder 
Journal of affective disorders  2013;151(1):171-177.
Background
Down-regulation of negative emotions by cognitive strategies relies on prefrontal cortical modulation of limbic brain regions, and impaired frontolimbic functioning during cognitive reappraisal has been observed in affective disorders. However, no study to date has examined cognitive reappraisal in unmedicated euthymic individuals with a history of major depressive disorder relative to symptom-matched controls. Given that a history of depression is a critical risk factor for future depressive episodes, investigating the neural mechanisms of emotion regulation in remitted major depressive disorder (rMDD) may yield novel insights into depression risk.
Method
We assessed 37 individuals (18 rMDD, 19 controls) with functional magnetic resonance imaging (fMRI) during a task requiring cognitive reappraisal of sad images.
Results
Both groups demonstrated decreased self-reported negative affect after cognitive reappraisal and no group differences in the effects of cognitive reappraisal on mood were evident. Functional MRI results indicated greater paracingulate gyrus (rostral anterior cingulate cortex, Brodmann area 32) activation and decreased right midfrontal gyrus (Brodmann area 6) activation during the reappraisal of sad images.
Limitations
Trial-by-trial ratings of pre-regulation affect were not collected, limiting the interpretation of post-regulation negative affect scores.
Conclusions
Results suggest that activation of rostral anterior cingulate cortex, a region linked to the prediction of antidepressant treatment response, and of the right midfrontal gyrus, a region involved in cognitive control in the context of cognitive reappraisal, may represent endophenotypic markers of future depression risk. Future prospective studies will be needed to validate the predictive utility of these neural markers.
doi:10.1016/j.jad.2013.05.073
PMCID: PMC3769423  PMID: 23796796
Emotion regulation; remitted major depression; prefrontal cortex; rostral anterior cingulate cortex; fMRI
21.  Reappraising social emotions: the role of inferior frontal gyrus, temporo-parietal junction and insula in interpersonal emotion regulation 
Previous studies have reported the effect of emotion regulation (ER) strategies on both individual and social decision-making, however, the effect of regulation on socially driven emotions independent of decisions is still unclear. In the present study, we investigated the neural effects of using reappraisal to both up- and down-regulate socially driven emotions. Participants played the Dictator Game (DG) in the role of recipient while undergoing fMRI, and concurrently applied the strategies of either up-regulation (reappraising the proposer's intentions as more negative), down-regulation (reappraising the proposer's intentions as less negative), as well as a baseline “look” condition. Results showed that regions responding to the implementation of reappraisal (effect of strategy, that is, “regulating regions”) were the inferior and middle frontal gyrus, temporo parietal junction and insula bilaterally. Importantly, the middle frontal gyrus activation correlated with the frequency of regulatory strategies in daily life, with the insula activation correlating with the perceived ability to reappraise the emotions elicited by the social situation. Regions regulated by reappraisal (effect of regulation, that is, “regulated regions”) were the striatum, the posterior cingulate and the insula, showing increased activation for the up-regulation and reduced activation for down-regulation, both compared to the baseline condition. When analyzing the separate effects of partners' behavior, selfish behavior produced an activation of the insula, not observed when subjects were treated altruistically. Here we show for the first time that interpersonal ER strategies can strongly affect neural responses when experiencing socially driven emotions. Clinical implications of these findings are also discussed to understand how the way we interpret others' intentions may affect the way we emotionally react.
doi:10.3389/fnhum.2013.00523
PMCID: PMC3759791  PMID: 24027512
interpersonal emotion regulation; decision-making; social interactions; mentalizing
22.  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
23.  Serotonin transporter genotype modulates cognitive reappraisal of negative emotions: a functional magnetic resonance imaging study 
A functional polymorphism within the serotonin transporter gene (5-HTTLPR) has been reported to modulate emotionality and risk for affective disorders. The short (S) allele has less functional efficacy than the long (L) allele and has been associated with enhanced emotional reactivity. One possible contributing factor to the high emotionality in S carriers may be inefficient use of cognitive strategies such as reappraisal to regulate emotional responses. The aim of the present study was to test whether the 5-HTTLPR genotype modulates the neural correlates of emotion regulation. To determine neural differences between S and L allele carriers during reappraisal of negative emotions, 15 homozygous S (S′/S′) and 15 homozygous L (L′/L′) carriers underwent functional magnetic resonance imaging (fMRI), while performing an instructed emotion regulation task including downregulation, upregulation and passive viewing of negative emotional pictures. Compared to L′/L′ allele carriers, subjects who carry the S′/S′ allele responded with lower posterior insula and prefrontal brain activation during passive perception of negative emotional information but showed greater prefrontal activation and anterior insula activation during down- and upregulation of negative emotional responses. The current results support and extend previous findings of enhanced emotionality in S carriers by providing additional evidence of 5-HTTLPR modulation of volitional emotion regulation.
doi:10.1093/scan/nsr091
PMCID: PMC3594717  PMID: 22345383
cognitive reappraisal; emotion regulation; fMRI; serotonin transporter gene; 5-HTTLPR
24.  Neural Mechanisms of Cognitive Reappraisal of Negative Self-Beliefs in Social Anxiety Disorder 
Biological psychiatry  2009;66(12):1091-1099.
Background
Social anxiety disorder (SAD) is characterized by distorted negative self-beliefs (NSBs) which are thought to enhance emotional reactivity, interfere with emotion regulation, and undermine social functioning. Cognitive reappraisal is a type of emotion regulation used to alter NSBs, with the goal of modulating emotional reactivity. Despite its relevance, little is known about the neural bases and temporal features of cognitive reappraisal in patients with SAD.
Methods
Twenty-seven patients with SAD and 27 healthy controls (HC) were trained to react and to implement cognitive reappraisal in order to down-regulate negative emotional reactivity to NSBs while undergoing functional magnetic resonance imaging and providing ratings of negative emotion experience.
Results
Behaviorally, compared with HC, patients with SAD reported greater negative emotion both while reacting to and reappraising NSBs. However, when cued, participants in both groups were able to use cognitive reappraisal to decrease emotion. Neurally, reacting to NSBs resulted in early amygdala response in both groups. Reappraising NSBs resulted in greater early cognitive control, language, and visual processing in HC, but greater late cognitive control, visceral, and visual processing in patients with SAD. Functional connectivity analysis during reappraisal identified more regulatory regions inversely related to left amygdala in HCs than in patients with SAD. Reappraisal-related brain regions that differentiated patients and controls were associated with negative emotion ratings and cognitive reappraisal self-efficacy.
Conclusions
Findings regarding cognitive reappraisal suggest neural timing, connectivity, and brain-behavioral associations specific to patients with SAD, and elucidate neural mechanisms that might serve as biomarkers of interventions for SAD.
doi:10.1016/j.biopsych.2009.07.014
PMCID: PMC2788040  PMID: 19717138
brain; emotion; emotion regulation; social anxiety; fMRI; neuroimaging
25.  UNCINATE FASCICULUS FRACTIONAL ANISOTROPY CORRELATES WITH TYPICAL USE OF REAPPRAISAL IN WOMEN BUT NOT MEN 
Emotion (Washington, D.C.)  2013;13(3):385-390.
Emotion regulation refers to strategies through which individuals influence their experience and expression of emotions. Two typical strategies are reappraisal, a cognitive strategy for reframing the context of an emotional experience, and suppression, a behavioral strategy for inhibiting emotional responses. Functional neuroimaging studies have revealed that regions of the prefrontal cortex modulate amygdala reactivity during both strategies, but relatively greater down-regulation of the amygdala occurs during reappraisal. Moreover, these studies demonstrated that engagement of this modulatory circuitry varies as a function of gender. The uncinate fasciculus is a major structural pathway connecting regions of the anterior temporal lobe, including the amygdala, to inferior frontal regions, especially the orbitofrontal cortex. The objective of the current study was to map variability in the structural integrity of the uncinate fasciculus onto individual differences in self-reported typical use of reappraisal and suppression. Diffusion tensor imaging was used in 194 young adults to derive regional fractional anisotropy values for the right and left uncinate fasciculus. All participants also completed the Emotion Regulation Questionnaire. In women but not men, self-reported typical reappraisal use was positively correlated with fractional anisotropy values in a region of the left uncinate fasciculus within the orbitofrontal cortex. In contrast, typical use of suppression was not significantly correlated with fractional anisotropy in any region of the uncinate fasciculus in either men or women. Our data suggest that in women typical reappraisal use is specifically related to the integrity of white matter pathways linking the amygdala and prefrontal cortex.
doi:10.1037/a0031163
PMCID: PMC4094171  PMID: 23398586
emotional regulation; uncinate fasciculus; amygdala; orbitofrontal cortex; fractional anisotropy

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