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Neuroscience Letters 457 (2009) 101–106

Contents lists available at ScienceDirect

Neuroscience Letters

journa l homepage: www.e lsev ier .com/ locate /neule t

eural correlates of regulation of positive and negative emotions: An fMRI study

manda K.Y. Maka,b, Zhi-guo Huc, John X. Zhangd, Zhuang-wei Xiaoc, Tatia M.C. Leea,b,e,∗

Laboratory of Neuropsychology, The University of Hong Kong, Hong Kong, ChinaLaboratory of Cognitive Affective Neuroscience, The University of Hong Kong, Hong Kong, ChinaGuangdong Key Lab of Medical Molecular Imaging, The Medical College of Shantou University, ChinaDepartment of Psychiatry, The Chinese University of Hong Kong, Hong Kong, ChinaThe State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China

r t i c l e i n f o

rticle history:eceived 31 January 2009eceived in revised form 19 March 2009ccepted 25 March 2009

eywords:motion regulationrefrontal regionnterior cingulate cortex

a b s t r a c t

Regulation of emotion is important for adaptive social functioning and mental well-being. This functionalmagnetic resonance imaging study identified neural correlates of regulation of positive or negative emo-tion. Twelve healthy female Chinese participants performed the experimental task that required themto simply view emotional pictures or to regulate their emotions induced by these pictures while theirbrain activities were monitored by a 1.5 T MRI scanner. The neuroimaging findings indicate that the leftsuperior and lateral frontal regions (BA8/9) are common neural correlates of regulation of both emotions.For regulation of positive or negative emotion, changes of BOLD responses in the prefrontal regions andthe left insula are associated with regulation of positive emotion; whereas activity of the left orbitofrontal

nsulamygdala

APS

gyrus, the left superior frontal gyrus, and the anterior cingulate gyrus appears to be involved in regula-tion of negative emotion. According to the participants’ self-report, they appeared to be more effectivein regulating positive than negative emotions, which may relate to the distinct patterns of neural activityassociated with regulation of the specific emotion. As a conclusion, our findings suggest that there areshared as well as valence-specific neurocognitive mechanisms underlying regulation of positive and neg-ative emotions. Enhanced knowledge about the neural mechanisms of emotion regulation helps improve

plex

understanding of the com

ysregulation of emotion is associated with the inability to mod-late intense emotions that may precipitate affective disorders10,39]. Hence, understanding the neural mechanisms underlyingmotion regulation provides essential insights into the biologicalasis of mental health that facilitates socially appropriate behav-

or. Thus far research on emotion regulation has largely focusedn the neural activities underlying the regulation of negative emo-ions (e.g. [23,30,32,35]), although regulation of both positive andegative emotions are of equal importance.

Emotion regulation involves inhibiting or modulating the pri-ary emotion to produce contextually appropriate emotions and

ehaviors [38]. The regulatory process is underlined by the involve-ent of control-appraisal system dynamics between the prefrontal

ortex and other limbic-related regions [31]. The prefrontal cor-ex plays a central role in the cognitive control of behavior8,10,28,31,38,39], while the limbic-related regions, such as themygdala and insula, are implicated in appraisal of emotions

∗ Corresponding author at: K610, Laboratory of Neuropsychology, The Universityf Hong Kong, Pokfulam Road, Hong Kong, China. Tel.: +852 2857 8394;ax: +852 2540 8920.

E-mail address: tmclee@hkusua.hku.hk (T.M.C. Lee).

304-3940/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved.oi:10.1016/j.neulet.2009.03.094

interplay of emotion and cognition underlying human behaviors.© 2009 Elsevier Ireland Ltd. All rights reserved.

[36,38,39]. In prior studies that investigated the neural correlates ofthe regulation of negative emotions [23,30,32,35] by requiring thesubjects to view negative emotional pictures depicting emotion-laden scenes [6], increased activity in the prefrontal cortex and theanterior cingulate cortex, as well as decreased activity in the limbic-related regions were observed. It is unknown, however, whetherthe same neural system also underlies the regulation of positiveemotions.

In this study, we investigated the neural activities associatedwith regulating positive and negative emotions using functionalmagnetic resonance imaging (fMRI) methodology. We tested thenull hypothesis that there was no difference in the neural activi-ties associated with the regulation of positive or negative emotions.It was hypothesized that regulation of negative emotion wouldbe associated with increased neural activity in the prefrontal andthe anterior cingulate regions, and decreased neural activity in thelimbic-related regions.

Twelve female Chinese subjects (age range = 20–27, mean

age = 24, S.D. = 1.78 years) participated in this study. Our prior study[22] showed a significant gender-related effect on processing emo-tional stimuli. Therefore, in order to control for gender-inducedsignal variation, only female subjects were recruited for this study.All subjects were undergraduate or postgraduate students at the

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02 A.K.Y. Mak et al. / Neurosci

hantou University. They were all right-handed with no historyf medical or psychiatric illnesses. Subjects were assessed usinghe Chinese version of the Beck Depression Inventory-II (BDI-II) [7]o exclude people with depression according to the recommendedlinical cut-off score [3]. The study was approved by a local Instituteeview Board. Written informed consent was obtained from eachubject and the experimental protocol was explained.

We extracted 294 emotional pictures from the Internationalmotion Picture System (IAPS) [21] and from the popular media asotential stimuli for this study. We then tailored a stimulus set forach subject according to the rating of these 294 emotional stimuli.timuli selection was completed prior to scanning. The protocolf this study contained 48 negative, 48 positive, and 24 neutralictures selected according to the subject’s individual ratings.

We adopted a block design for this study, with each block con-aining four components. All visual stimuli were projected via theoggles. First, an arrow was displayed in the center of the screenor three seconds, the direction of which cued the subjects as tohether they should reduce their negative emotions (up arrow

↑”) or positive emotions (down arrow “↓”), or simply view the pic-ures (equal sign “=”). For the regulate condition, the subjects werenstructed to reduce their negative/positive emotions induced byhe emotional pictures by strategies of the subjects’ own choices.uring the practice trial, they were asked to get familiarize with

he experiment and also to arrive at a strategy that would employn the regulate condition. For the view condition, the subjects werenstructed to simply look at the picture but perform no regulation.

Second, four pictures for each emotion condition (positive, neg-tive, or neutral) appeared in succession for 24 s (6 s per picture).ubjects then responded to the pictures according to the cuednstruction followed by their rating of the perceived valence on a-point Likert scale (1 = very unpleasant, 5 = neutral, 9 = very pleas-nt) by pressing a button (9 s). A 21-second break followed beforehe next block commenced.

We examined the mood states (sadness, happiness, and tired-ess) of the subjects immediately before scanning using the Visualnalog Mood Scales (VAMS) [29]. After scanning, the participantsompleted a post-experiment questionnaire that consisted of open-nded questions. They were first asked to elaborate on the strategysed for regulating either the positive or negative emotions. Theyere then asked to illustrate to the experimenter the way they reg-lated their emotions when viewing three of the emotional picturesxtracted from the experimental stimuli. They were also required toate the effectiveness in regulation that they perceived. Finally, theyere requested to indicate the relative difficulty with regulating theegative and positive emotions.

Imaging was conducted on a 1.5 Tesla Philips scanner with atandard head coil. Twenty-two axial slices covering the wholerain were acquired using a T2*-weighted gradient echo pla-ar imaging (EPI) pulse sequence (TR = 3000 ms, TE = 45 ms, flipngle = 90◦) for the functional scans (acquisition matrix = 64 × 64,OV = 230 × 230 mm, slice thickness = 6, no gap). Co-planar anatom-cal images (acquisition matrix = 256 × 256) were acquired using a1-weighted spin-echo pulse sequence (TR = 450 ms, TE = 14 ms).

Statistical parametric mapping (SPM2; Wellcome Depart-ent of Cognitive Neurology, London, UK; http://www.fil.ion.ucl.

c.uk/spm/) was used for fMRI image analysis. For each participant,unctional images were motion corrected and co-registered to theo-planar anatomical images. The T1 images were normalized to thetandard SPM template, and the resulting transformation matrixas applied to the co-registered functional images. Such normal-

zed functional images were interpolated to 4 mm isotropic voxelsnd were spatially smoothed with a Gaussian filter of 8-mm kernel.

There were five conditions in this study, namely, regulationf negative emotion, regulation of positive emotion, viewing ofegative emotion, viewing of positive emotion, and viewing of

etters 457 (2009) 101–106

neutral emotion. The viewing conditions were the control condi-tions. In the first level of analysis, we averaged these functionalimages to create a single image of mean activation per conditionand subject. We then performed contrasts identifying brain regionswith increased or decreased activation while regulating negative orpositive emotions. We used the functional images in the second-level random-effects analysis, entering the contrast images into aone-sample t-test across the 12 subjects. This produced statisti-cal parametric maps of the t statistic at each voxel, which weresubsequently transformed to the Z distribution. We performed con-junction analysis of the “regulate-view” contrasts to identify thebrain regions commonly involved in regulating positive and nega-tive emotions.

With reference to the threshold adopted in previous studies[4,35], for all the contrasts and regression analyses, we combined avoxel-wise intensity threshold (p < 0.005, uncorrected) and a spatialextent threshold (cluster size greater than 18 voxels, i < 0.01 uncor-rected) to control for multiple comparisons in the generation of thet-maps. Maxima were reported in the coordinates of the MontrealNeurological Institute (MNI) reference brain as in the SPM2.

We first conducted whole-brain analyses and then regionsof interest (ROI) analyses to prefrontal regions showing signif-icant BOLD responses. The peak voxels activation in selectedROI defined from clusters of significant activation in the con-trast analyses were extracted by using the MarsBaR software(http://marsbar.sourceforge.net/). We then used repeated mea-sures ANOVAs with the factors of emotion (negative, positive) andtask (view, regulate) to identify the interaction effect of these ROI.We also performed correlation analysis between the ROI and thechange in subjective mood ratings between the “regulate” and“view” conditions in each emotion to indicate the strength of emo-tion regulation.

A significant interaction effect (F(1,11) = 9.72, p = .01, partial�2 = .469) between emotion (negative, positive) and task (regulate,view) was shown. The change in subjective emotion rating wassignificantly larger when regulating positive emotions than nega-tive ones. Planned comparisons demonstrated that when regulatingnegative emotions, subjects reported significantly less negativeaffect [M = 4.68, t(11) = 7.4, p < .001, Cohen’s d = 2.474] than in theview condition [M = 2.67]; when regulating positive emotions, theyreported significantly less positive affect [M = 4.26, t(11) = 9.7, p < .01,Cohen’s d = 3.641] than in the view condition [M = 7.78].

With positive emotions (see Table 1A), we found increased acti-vation in the left superior medial frontal (BA8), which extended tothe dorsolateral prefrontal gyrus (BA9), and decreased activationin the left insula, the right rolandic operculum (BA6), as well asthe lingual gyri (BA18). With negative emotions (see Table 1B), weidentified increased brain activation in the left inferior orbitofrontal(BA11), the left superior medial frontal gyrus (BA8), the anterior cin-gulate gyrus (BA32), the left middle occipital gyrus (BA19), and theright precuneus (BA30), and decreased brain activation in the rightprecentral gyrus (BA6) and bilateral parietal gyrus (R:BA2; L:BA40).

We performed a conjunction analysis (see Table 1C) and identi-fied significantly stronger activation in the left superior and lateralprefrontal gyri (BA8/9).

We extracted the percent signal changes of the peak voxel in eachsignificantly activated prefrontal regions in the contrast analysis(see Table 1). We found significant interaction effects (see Table 2)in the left orbitofrontal gyrus (partial �2 = 0.480), the left superiormedial frontal gyrus (partial �2 = 0.520), and the left lateral frontalgyrus (partial �2 = 0.53). Further planned t-tests (see Fig. 1A–C)

showed that the left orbitofrontal gyrus (t = 5.768, p = 0.000) wasselectively recruited during the regulation of negative emotions,while the left superior medial frontal gyrus (t = 6.125, p = 0.000) andthe left lateral frontal gyrus (t = 6.163, p = 0.000) were selectivelyrecruited during the regulation of positive emotions.

A.K.Y. Mak et al. / Neuroscience Letters 457 (2009) 101–106 103

Fig. 1. Means and standard deviations of percent signal changes and results of ANOVAs and post hoc t-test in the (A) inferior orbitofrontal gyrus, (B) superior medial prefrontalgyrus and (C) lateral prefrontal gyrus which had significant interaction effects between valences and conditions. Results of correlational analyses and scatter plots duringthe regulation of positive emotion (D) and negative emotion (E). The x, y, and z coordinates are in the MNI coordinates. BA = approximate Brodmann’s areas; L = left; R = right.*p < 0.05, **p < 0.01.

104 A.K.Y. Mak et al. / Neuroscience Letters 457 (2009) 101–106

Table 1Significant regional brain activity during regulation of positive (A) and negative (B) emotions.

Region of activation Side BA Coordinates T-value Z-score Volume

x y z

A. Regulation of positive emotionRegulate > View

Superior medial frontal gyrus L 8 −4 40 40 6.25 4 13120Middle frontal gyrus L 9 −36 12 40 5.97 3.91

View > RegulateRolandic operculum gyrus R 6 52 4 12 4.97 3.52 5568Lingual gyrus L 18 −12 −72 4 5.56 3.76 4288Insula L −48 4 4 4.66 3.39 2880

B. Regulation of negative emotionRegulate > View

Inferior orbitofrontal gyrus L 11 −20 24 −20 5.82 3.86 1984Anterior cingulate gyrus L 32 −12 44 20 4.81 3.46 1152Superior frontal gyrus L 8 −24 20 52 4.46 3.3 1216Middle occipital gyrus L 19 −40 −80 8 5.11 3.58 2112Precuneus gyrus R 30 4 −52 12 7 4.24 2752

View > RegulatePrecentral gyrus R 6 56 4 28 4.68 3.4 1088Inferior parietal gyrus R 2 52 −36 52 4.72 3.42 5184

L 40 −36 −52 48 3.96 3.06 1280

C. Significant regional brain activity during conjunction analysisIncreased activation

Superior frontal gyrus L 8 −20 20 52 3.66 3.2 640

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Significant main effects (see Table 2) were found in the left supe-ior frontal gyrus (partial �2 = 0.647) and the left anterior cingulateyrus (partial �2 = 0.443). Further planned t-tests showed that thenhanced activation in the left superior frontal gyrus was significantn regulating negative emotions (t = 4.506, p = 0.001) and partiallyignificant in regulating positive emotions (t = 2.094, p = 0.060), buthe enhanced activation in the anterior cingulate gyrus was signif-cant only for regulating negative (t = 4.77, p = 0.001), not positivet = 1.589, p = 0.140) emotions.

We performed correlation analysis (see Fig. 1D and E) to iden-ify regions that were correlated with the strength of regulatingegative or positive emotions. With positive emotions, the left mid-le frontal gyrus (BA9: −24 28 40) showed a significant positiveorrelation (r = .714, p = 0.009) with the magnitude of change inhe subjective emotion ratings, while with negative emotions, theeft amygdala (−32 −8 −12) was negatively correlated (r = −.703,= 0.011) with the magnitude of change in the same ratings. This

hows that increasing the strength of regulating negative emotionsodulated the neural activity in the amygdala.Our findings indicate that both shared and distinct neural

egions are involved in regulating positive and negative emo-ions. The regulation of positive and negative emotions commonlynvolved the left superior and lateral frontal regions (BA8/9). Theuperior frontal region (BA8) is involved in the ability to makenferences about another’s mental state [44]. Hence activity of thisegion may facilitate regulation by altering the mental state of theeople in the emotional pictures. The dorsal lateral frontal regionBA9), which has been implicated in working memory and responseelection [28,43] may aid in generating and maintaining regulatorytrategies.

Regulation of positive emotion was associated with activity in

he dorsal and lateral frontal regions. This observation is consistentith that reported in previous imaging studies showing that pro-

essing of emotionally positive but not negative or neutral stimulis associated with increased neural activity of the dorsolateral pre-rontal cortex (DLPFC). Activity of the DLPFC is positively related

28 44 2.96 2.96

ma meet a t threshold of 3.11 (p < 0.005, uncorrected) are reported. The x, y, and zte Brodmann’s areas; L = left; R = right.

to performance in cognitively demanding tasks [16,34]. There-fore, positive affect, within normal limits, may enhance dopamineturnover in the DLPFC, resulting in increased working memory-related activity [2].

Regulation of negative emotions involved increased activa-tion in the left orbitofrontal gyrus, the left anterior cingulategyrus, and the left superior frontal gyrus, as well as modulat-ing activation in the left amygdala. These findings align wellwith the results of prior similar studies [23,30,32,33,35]. Theleft orbitofrontal gyrus (BA11) was distinctively recruited dur-ing the regulation of negative emotion. Indeed, lesions in thisregion seem to relate to the degree of severity of depression[25]. Negative emotional stimuli may evoke more autonomicand peripheral physiological responses than do positive emo-tional or neutral stimuli [14,33], and some previous studies havereported that the orbitofrontal gyrus was associated with vol-untary suppression of negative emotion as well as top-downregulation of autonomic or peripheral physiological responses ofemotional experiences [33,38]. Some studies have also suggestedthat the involvement of the orbitofrontal region in reversal learn-ing [13,17,20,40] as well as emotional perspective-taking [18]. Theseobservations may suggest that emotion regulation could be accom-plished by updating and altering the affective value of a stimulus[30].

The involvement of the anterior cingulate gyrus (BA32) was rel-atively stronger during the regulation of negative emotion. Previousstudies have shown this region was associated more with negativethan positive emotional stimuli [12,42] as well as with depression[9,27]. This region has also been implicated in detecting and eval-uating conflicts, indicating when cognitive control has to be morestrongly engaged during the regulation of negative emotion [24]. In

the post-scan questionnaires, 8 of the 12 subjects reported havinggreater difficulty regulating negative emotions relative to positiveemotions. Thus, the regulatory process might engage more cogni-tive control and employ the anterior cingulate gyrus more stronglyfor negative than positive emotion.

A.K.Y. Mak et al. / Neuroscience L

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etters 457 (2009) 101–106 105

This study confirms that common as well as distinct neural sys-tems are involved in regulating positive and negative emotions.Some studies did not show any valence-specific pattern of brainactivation in emotion regulation (e.g. [33]). Other studies reporteddistinct patterns of cortical activation with the processing of differ-ent valences of emotion [1,11,15,19,26,37,41,42]. Our findings appearto be in line with these observations that both shared as well as dis-tinct neural systems are involved in processing different emotions.

Subjective mood ratings are not the most valid measuresfor reflecting emotional experience. Inclusion of physiologicalresponses to emotions can provide a more reliable index [34].Besides, strategies for emotion regulation may have a cross-culturalbias, i.e. strategies that Asian employed might be quite differentfrom that employed by Caucasian or other ethnic groups [5]. Thebias may then be translated into different patterns of brain acti-vation. Hence, interpretation of the findings obtained from anycross-cultural replication of the present study must take the bias asdiscussed into consideration. We should also note that the resultscannot be generalized to male subjects because this study recruitedonly female samples. Investigating gender differences in the neuralcorrelates of emotion regulation might be a promising avenue forfurther studies.

Financial disclosures

None declared.

Acknowledgements

This project was supported by the Research Output Prize and theCRCG seed grant of The University of Hong Kong and Research Grantof the National Natural Science Foundation of China (#30828012).

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