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000dosistently identified in prior neuroimaging research on the usecognitive strategies to regulate emotion. Consider, for exam-, research on depression, a mood disorder characterized byh levels of self-focused rumination (20,21). Although findingsarly indicate that subgenual anterior cingulate cortex (sgACC)ivity tracks closely with depressive symptoms (2230), re-rch on emotion regulation strategies thought to be relevant tonitive therapies for depression (e.g., reappraisal) rarely reportnges in activity in this region. This discrepancy suggests thate of the brain regions involved in regulating feelings associ-

d with emotional memories may be different than thoseolved in regulating responses to normatively negative stimuli.Here, we examined this issue by developing a novel func-nal magnetic resonance imaging (fMRI) paradigm in whichrticipants recalled a series of highly arousing negative auto-

buffer against rumination (3436). The third analyze strategydirected participants to objectively analyze the causes and rea-sons underlying their feelings and was designed as a memoryanalog of cognitive reappraisal strategies used in prior fMRIstudies (12,13,18,19).

Methods andMaterials

Twenty-four Columbia University affiliates (15 female sub-jects; M age 20.83, SD 3.27) provided informed consent.Prospective participants were screened to ensure they were notcurrently undergoing treatment from a mental health profes-sional, taking mental health-related medication (e.g., Prozac),were claustrophobic, or had metal in their bodies. The sampleconsisted of 60% European Americans, 24% Asians, 4% AfricanAmericans, and 12% other.

StimuliSimilar to prior studies that have used script-driven methods,

cue phrases were used to trigger the recall of negative autobio-graphical memories in the scanner. To obtain memory cues,participants were asked to describe in writing nine highlyarousing negative autobiographical experiences during a screen-ing session and then judge the extent to which thinking about

mtheDepartmentof Psychology (EK), University ofMichigan, AnnArbor,Michigan; and Psychology Department (MD, JW, KO), Columbia Univer-sity, New York, New York.dress reprint requests to Ethan Kross, Ph.D., University of Michigan, De-partment of Psychology, 530 Church Street, Ann Arbor, MI 48109-1043;E-mail: ekross@umich.edu.eived July 10, 2008; revisedOctober 6, 2008; acceptedOctober 13, 2008.

BIOL PSYCHIATRY 2009;65:3613666-3223/09/$36.00i:10.1016/j.biopsych.2008.10.019 2009 Society of Biological Psychiatryoping with Emotions Past:egulating Affect Associateutobiographical Memorieshan Kross, Matthew Davidson, Jochen Weber, and

ckground: Although the ability to adaptively reflect on negative aalth, to our knowledge no research has directly examined the neur

thods: Sixteen participants were scanned using functional magnphical memories using cognitive strategies designed to facilitatination.

sults: Two key findingswere obtained. First, consistentwith prior eivity was observed during the implementation of all three strategiecessing and emotion, including subgenual anterior cingulate cortategy and lowest for the accept strategy. This pattern of activationmh strategy.

nclusions: These findings shed light on the brain regions that distobiographical memories and offer a novel, ecologically valid route

y Words: Autobiographical memory, emotion regulation, fMRI,ppraisal, rumination, subgenual anterior cingulate cortex

he ability to adaptively cope with distressing life experi-ences is a key self-regulatory challenge. Failing to meetthis challenge can be costly, as intrusive and emotionally

rged thoughts about these experiences contribute to a varietyclinical disorders (1). Although an explosion of research hasmined the neural bases of consciously regulating negativeotions triggered in response to normatively aversive visual oraneous shock stimuli (219), no research has examined howse findings generalize to coping with such highly idiosyncraticgative emotional memories. This is important because somee Neural Bases ofith Negative

in Ochsner

iographical experiences without ruminating is critical to mentaltems underlying this process.

resonance imaging (fMRI) as they focused on negative autobio-el strategy) versus undermine (analyze and accept strategies)

on regulation research using image-based stimuli, left prefrontalcond, activity in a network of regions involved in self-referentialnd medial prefrontal cortex, was highest in response to the feelred participants self-reports of negative affectwhen engaging in

ish adaptive versus maladaptive forms of reflecting on negativexploring the neural bases of emotion regulation using fMRI.

graphical memories and then focused on them using strate-s designed to facilitate versus undermine adaptive self-reflec-n. The first feel strategy directed individuals to focus on thecific feelings that naturally flowed through their mind as theyught about their recalled experiences. This strategy was usedcause prior research indicates that focusing concretely ongative feelings triggers the kind of negative affect infused,inative episodes that are the hallmark of dysfunctional

ping (3133). The second accept strategy directed individu-to recognize that the feelings they experienced duringollection were passing mental events that were psychologi-ly distant from the self and did not control them. Thetructions for this strategy were adapted from a form ofgnitive behavioral therapy that teaches people how to mind-

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second phase of the protocol, each cue was randomly presentedon screen and participants were instructed to press the space bar

regpri

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Table 1. Conjunction Analysis Identifying Regions Commonly Active inthe Feel, Analyze, and Accept Strategy Conditions Relative to an ActiveBas

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InfeCunCerMidLin

362 BIOL PSYCHIATRY 2009;65:361366 E. Kross et al.

wwh memory made them feel aroused (M 6.85; SD .65) andgative (M 6.94; SD .55) using a 7-point scale in whichher numbers corresponded to higher levels of arousal andgativity. Paired sample t tests comparing valence and arousalings for all memories revealed no significant differencesousal: ts 1.87, ps .08; valence: ts 1.07, ps .30).

iningUpon arrival at the fMRI scanner, participants were remindedthe negative autobiographical memories they generated dur-the screening session and taught how to quickly recall eachmory in response to specific cue words using a computerizedtocol. In the first part of the protocol, a cue phrase appearedscreen along with a description of the memory to which itresponded. Participants were given as much time as theyeded to pair the cue and memory so that they would be ablequickly recall each memory when presented with the cuene. This process repeated until participants saw a cue-mory description paring for all nine memories. During the

ure 1. Regions of lPFC active for each strategy relative to baseline. Bar graeline. Error bars represent SEM. AC, accept; AN, analyze; FE, feel; lPFC, left p

eline Task

ion of ActivationBrodmanns

Area t

TAL Coordinates

Voxelsx y z

rior Frontal Gyrus 46 4.46 51 29 16 218eus 19 4.46 12 88 31 94ebellum 4.11 24 70 38 29dle Occipital Gyrus 18 3.69 15 91 10 17gual Gyrus 18 3.89 6 73 2 16

TAL, Talairach.w.sobp.org/journalsoon as they were able to recall the specific negative autobio-phical experience it corresponded to. Reaction time data wereamined to ensure that participants recalled each memory ins than 10 seconds (i.e., the amount of time participants had toall their experiences during the experiment). Subsequently,rticipants received instructions regarding how to implementch strategy during scanning (see introduction for summary ofecific strategy instructions).

RI TaskParticipants viewed three repetitions each of three types ofulus blocks (feel, accept, or analyze) whose order was

unterbalanced. Each block was comprised of three 80-secondls. All trials began with a 10-second cue phrase indicating thatrticipants should recall the autobiographical memory indicatedthe cue. Subsequently, a strategy cue word appeared oneen directing them to engage in the feel, accept, or analyzeategy for 30 seconds. Next, participants indicated how arousedd negative they felt using a 5-point scale (1 not at allused/negative; 5 very aroused/negative). Each questionpeared on screen for 5 seconds. Finally, participants engageda 30-second spatial perception task in which they saw anow pointing left or right and were asked to indicate whichection the arrow was pointing. This task was used as aseline condition because pilot testing indicated that whenrticipants were asked to recollect memories naturally, theyded to spontaneously engage in the strategies. Therefore, weght an active baseline task that would not engage theulatory, memory, and emotional processes of interest, andor work suggests that this arrows task does not engage these

lustrate parameter estimates of signal intensity for each strategy versusntal cortex.asgraexlesrecpaeasp

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fMRI Acquisition and AnalysisWhole-brain functional data were acquired on a GE 1.5 T

Fig ) Regcon stratecon edial

Table 2. Activations Revealed from aWithin-Subjects ANOVA Examiningthe Effect of Strategy (Feel vs. Accept vs. Analyze)

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AnMeCerCerMidSupCunCunInfe

E. Kross et al. BIOL PSYCHIATRY 2009;65:361366 363cesses (37). Postscan debriefings indicated that three partici-nts did not follow instructions. Their data were excluded fromsequent analyses.

ure 2. Effects of strategy condition on brain activity and negative affect. (Adition. Bar graphs illustrateparameter estimatesof signal intensity for eachdition. Error bars represent SEM. AC, accept; AN, analyze; FE, feel; mPFC, m

ion of ActivationBrodmanns

Area t

TALCoordinates

Voxelsx y z

terior Cingulate 25 11.67 0 14 5 55dial Frontal Gyrus 10 13.37 6 59 7 49ebellum 8.82 0 64 5 56ebellum/Lingual Gyrus 19 12.26 12 43 2 47dle Temporal Gyrus 39 10.06 45 70 25 38erior Frontal Gyrus 6 10.47 24 11 49 19eus 17 8.61 15 79 13 17eus 18 12.89 0 97 7 12rior Frontal Gyrus 47 8.45 30 23 17 12

ANOVA, analysis of variance; TAL, Talairach.nner (General Electric, Milwaukee, Wisconsin) in 24 contigu-s axial slices (4.5 mm thick, 1.5 1.5 mm in-plane resolution)rallel to the anterior commissure-posterior commissure (AC-) line with a T2*-weighted echo-planar imaging (EPI) se-ence (repetition time [TR] 2000, echo time [TE] 40, flipgle 60, field of view [FOV] 22) in three runs of 124lumes each (248 sec). Structural data were acquired with a-weighted spoiled gradient recalled echo (SPGR) scan (124es, 1.5 mm thick, in-plane resolution .86 .86 mm; 19, TE 5, flip angle 20, FOV 220).Functional scans were slice time and motion corrected usingford Centre for Functional MRI of the Brain (FMRIB; Oxford,ited Kingdom) Software Library (FSL) tools slicetimer andFLIRT and were normalized and smoothed with a Gaussianrnel of 8 mm full-width at half maximum (FWHM) using SPM2ellcome Department of Cognitive Neurology, Universityllege London, London, United Kingdom). Statistical analyses

ions of mPFC and sgACC displaying a significant linear effect of strategygyversusbaseline. (B)Self-report negative affect as a functionof strategyprefrontal cortex; sgACC, subgenual anterior cingulate cortex.scaoupaPCquanvoT1slicTR

OxUnMCke(WCowww.sobp.org/journal

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determine which strategies drove these activations, we extractedbeta values for each condition from each cluster. These analysesrevactbylinmirev24thipresermoHowiforme

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Table 3. Regions Showing a Positive Correlation Between Increases inSelf-Reported Negative Affect and Increases in Brain Activity

Reg

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364 BIOL PSYCHIATRY 2009;65:361366 E. Kross et al.

wwre conducted using the general linear model (GLM) frame-rk implemented in Brain Voyager (Maastricht, The Nether-ds). Boxcar regressors, convolved with the canonical hemo-namic response function (HRF), modeled periods for thesec recall epoch and 30-sec strategy epoch. The arrow taskoch was used as the baseline. Voxelwise statistical parametricps (SPM) summarizing differences between trial types wereculated for each subject and then entered into random effectsup analyses with statistical maps thresholded at p .005corrected for multiple comparisons, with an extent threshold12 voxels. These parameters were chosen because theyresponded to an overall alpha level of p .05 corrected forltiple comparisons as calculated by the Monte Carlo simula-n method implemented in Analysis of Functional Neuroimagestp://afni.nimh.nih.gov/afni), which is widely used in fMRIearch (5,1517,3840). This technique controls for the fami-ise error rate (FWE) by simulating null data sets with the sametial autocorrelation found in the residual images and creates aquency distribution of different cluster sizes. Clusters largern the minimum size corresponding to the a priori chosen FWEthen retained for additional analysis. This technique offers anrnative to simple FWE-only voxel-based correction. Prelimi-ry analyses indicated that participants valence and arousalings were highly correlated (r .68, p .001). They wererefore averaged to form a single index of negative affect thats used for subsequent analyses. Data from three participantsre excluded because of technical difficulties. In addition, 3rticipants were excluded for excessive motion, leaving a total16 participants.

sults

We first examined regions commonly active across all threetegies by performing a conjunction analysis on regions activeeach strategy versus the baseline task. This analysis revealedreased activity in occipital regions implicated in visualizingollected events as well as left lateral prefrontal regionsviously implicated in studies of cognitive reappraisal usingual stimuli (Table 1; Figure 1).Next, we used an analysis of variance (ANOVA) with strategythe within-subjects factor to examine regions whose activitys modulated by the strategy participants implemented. Thisalysis revealed activations in regions involved in self-referen-processing, emotion, and autobiographical memory recall,luding right rostral medial and ventrolateral prefrontal cortexC), cuneus, and most notably sgACC (Table 2; Figure 2A). To

ion of ActivationBrodmanns

Area t

TAL Coordinates

Voxelsx y z

l Acceptiddle Frontal Gyrus 10 5.30 21 56 19 36nterior Cingulate/Rectal Gyrus

25/11 4.54 9 14 17 25

nferior FrontalGyrus

47 3.46 39 23 17 12

l Analyzeone

alyze Acceptnsula 13 4.07 39 16 5 12

TAL, Talairach.w.sobp.org/journalealed highlxy significant linear effects in 8 of 9 clusters, withivations in each cluster greatest for the feel strategy followedthe analyze strategy and then the accept strategy (Fs for allear effects 17.08, all ps .001). This pattern directlyrrored participants self-reported negative affect ratings, whichealed the same highly significant linear relationship [F(1,15) .12, p .001; Figure 2B]. The only cluster that did not displays pattern was a small region of activity in right ventrolateralfrontal cortex (rVLPFC). Consistent with the activations ob-ved in the other clusters, the feel strategy led to significantlyre activity in this region than the other two strategies.wever, analyze led to lower levels of activation comparedth accept, although this difference was not significant (p .26;strategy vs. strategy comparisons see Table 1 in Supple-nt 1).To more directly examine the relationship between neuralivity and self-reported negative affect, we next performed aies of simple regression analyses that examined whetherf-reported increases in negative affect across strategy condi-ns (e.g., feel - accept affect difference score; feel - analyzeect difference score; analyze - accept affect difference score)rrelated with brain activity identified by the correspondingategy versus strategy contrast (Supplement 1). We first com-red activity on accept and feel trials because these were thenditions that were maximally different on both self-reportedgative affect and neural activity identified in the ANOVAscribed above. These analyses revealed significant positiveociations between increases in self-reported negative affectd activity in sgACC and medial PFC (Table 3). Decreases ingative affect on accept versus feel trials were significantlysitively correlated with activity in caudate, superior parietalule, and medial frontal gyrus, suggesting that these regionsre involved in downregulating participants affective re-nses (Table 4). The only region correlating with increasedels of negative affect on analyze versus accept trails was theula (Table 4). No regions correlated with decreases in negativeect on accept versus analyze trials or with increases or decreasesnegative affect on feel versus analyze and analyze versus feells, respectively.

scussion

To our knowledge, this study is the first to directly examineneural systems underlying the ability to regulate emotion by

le 4. Regions Showing a Positive Correlation Between Decreases inf-Reported Negative Affect and Increases in Brain Activity

ion of ActivationBrodmanns

Area t

TALCoordinates

Voxelsx y z

ept Feelaudate 5.08 18 11 22 37edial Frontal Gyrus 4 3.93 18 22 58 23uperior Parietal Lobule 7 3.84 21 49 58 14alyze Feeloneept Analyzeone

TAL, Talairach.

adaptively reflecting on negative autobiographical experienceswithout ruminating. Two key findings were obtained.

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E. Kross et al. BIOL PSYCHIATRY 2009;65:361366 365First, consistent with prior research using image-based stimuli19,41), left PFC was observed during the implementation ofthree strategies. In the context of prior work, this suggests thatt PFC implements reappraisal operations regardless of stimuluse or the specific type of cognitive strategy one employs.Second, activity in a network of regions involved in self-erential processing, autobiographical memory recall, andotionincluding sgACC and medial prefrontal cortexPFC)was highest in response to the feel strategy and lowestthe accept strategy, and this pattern of activation mirrored

rticipants self-reports of negative affect. Moreover, activity inse regions correlated positively with increases in negativeect on feel versus accept trials, indicating that they wereectly related to participants subjective emotional responses.These findings have important implications for understandingy depressed individuals, who are known to ruminate (1920),w activity at rest in a similar set of regions, including sgACC,42). They suggest that depressed individuals may spontane-sly engage in the same type of self-focused ruminationgered by the feel strategy. Importantly, the present findingsmonstrate that this activity can be brought under their cogni-e control when the appropriate type of self-regulatory strategyimplemented. More broadly, these findings provide neuralroboration for behavioral research showing that focusingcretely on negative feelings facilitates rumination, whereasusing on negative feelings as mental events that are psycho-ically distanced from the self undermines it (3133).These findings also suggest that attempts to objectively ana-e ones feelings may be a less successful form of reducinggative affect than acceptance when memories are the source ofgative feelings rather than standardized visual stimuli. In thisn, it is noteworthy that although both the accept and analyzetegies led to significant group average drops in self-reportedect relative to the feel strategy, these drops correlated withnges in sgACC and mPFC activity only for the feel versusept contrast. The failure to observe a similar correlation foranalyze versus feel contrast could be attributable to the

aller overall magnitude of regulatory success and the relativelytricted variability in this comparison (Figure 2). However, ity also have to do with the kind of variability: 4 of 16rticipants displayed no reduction in negative affect in thealyze versus feel contrast. By comparison, only two partici-nts did not show a drop in negative affect in the accept versusl contrast. To explore this issue, we reran the correlationalyses leaving out the four nonregulators on the analyze versusl contrast. This analysis revealed significant positive correla-ns between increases in self-reported affect and mPFC (x 6,56, z 1; r .80, p .001) and sgACC (x 1, y 5,6; r .60, p .02) activity. Although exploratory, whensidered in the context of the similar correlations found for thel versus accept comparison, this finding is consistent with thea that successful regulation diminishes activity in these re-ns.

nclusionThe present results raise a number of new questions for futureearch. To what extent do the neural processes involved inalling negative autobiographical memories differ from thoseolved in reflecting on them to enhance or diminish emotionalponses? And most important for translational research, howclinical versus normal populations differ in their ability toal emotional memories? Given the pervasive role that think-about such experiences plays in eliciting distress and dys-ction in everyday life, a key need for future research is todress these questions to refine our understanding of the neuraltems that characterize these different forms of self-reflectiond their emotional consequences.

Completion of this research was supported by National Insti-es of Health (NIH) Grant MH076137.We thank Nick Weiler for helping with the administration ofs experiment and Tor Wager for methodological feedback.The authors reported no biomedical financial interests ortential conflicts of interest.

Supplementary material cited in this article is availableline.

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Coping with Emotions Past: The Neural Bases of Regulating Affect Associated with Negative Autobiographical MemoriesMethods and MaterialsStimuliTrainingfMRI TaskfMRI Acquisition and Analysis

ResultsDiscussionConclusion

AcknowledgmentReferences