Neural mechanisms of implicit cognitive reappraisal: Preceding descriptions alter emotional response to unpleasant images

Accepted Manuscript Neural mechanisms of implicit cognitive reappraisal: preceding descriptions alter emotional response to unpleasant images Hai-Yang Wang, Guo-Qing Xu, Ming-Fei Ni, Cui-Hong Zhang, Xiao-Pei Sun, Yi Chang, Bing-Wei Zhang PII: DOI: Reference:

S0306-4522(17)30067-2 http://dx.doi.org/10.1016/j.neuroscience.2017.01.047 NSC 17583

To appear in:

Neuroscience

Received Date: Accepted Date:

17 November 2016 27 January 2017

Please cite this article as: H-Y. Wang, G-Q. Xu, M-F. Ni, C-H. Zhang, X-P. Sun, Y. Chang, B-W. Zhang, Neural mechanisms of implicit cognitive reappraisal: preceding descriptions alter emotional response to unpleasant images, Neuroscience (2017), doi: http://dx.doi.org/10.1016/j.neuroscience.2017.01.047

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Neural mechanisms of implicit cognitive reappraisal: preceding descriptions alter emotional response to unpleasant images Hai-Yang Wang a 1, Guo-Qing Xu b 1, Ming-Fei Ni c, Cui-Hong Zhang a, Xiao-Pei Sun a, Yi Chang a, Bing-Wei Zhang a d *. a Department of Neurology and Psychiatry, First Affiliate Hospital of Dalian Medical University, Dalian, China. b Department of Psychology, Dalian Medical University, Dalian, China. c

Department of Radiology, First Affiliate Hospital of Dalian Medical University, Dalian, China. d

Center for Clinical Research on Neurological Diseases, Liaoning Province, China. Running Title: Functional MRI of implicit reappraisal Key words: implicit emotion regulation, cognitive reappraisal, fMRI, prefrontal cortex, orbitofrontal cortex, amygdala. Word count: 6701 Pages: 32 Number of table & figures: 1 table, 4 figures *Corresponding Author: Bing-Wei Zhang, Ph.D. and M.D. Department of Neurology and Psychiatry, First Affiliate Hospital of Dalian Medical University. No.222, Zhongshan Road, Dalian, Liaoning Province 116011, China. Tel: + 86 411 836 359 63 x3136 [email protected] 1 These authors contributed equally to this work.

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Abbreviations BOLD: blood-oxygen-level dependent dmPFC: dorsomedial prefrontal cortex dlPFC: dorsolateral prefrontal cortex ERP: event-related potential fMRI: functional magnetic resonance imaging GLM: generalized linear model IAPS: International Affective Picture System lOFC: lateral orbitofrontal cortex MNI: Montreal Neurological Institute NEG-DESC: unpleasant pictures preceded by negative descriptions NNEG-DESC: unpleasant pictures preceded by non-negative (neutral/positive) descriptions ROI: region of interest TPO: temporo-parietal-occipital vlPFC: ventrolateral prefrontal cortex

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Abstract The importance of reappraising negative events to reduce negative emotional responses has been widely acknowledged. However, most neuroimaging studies have explored the neural mechanisms of deliberate and intentional reappraisal, while little is known about the neural correlates of reappraisal that occurs outside of one's awareness. Electrophysiological studies suggest that precedent neutral descriptions could implicitly reduce neural responses to unpleasant images. To investigate the neural mechanism underlying implicit reappraisal, functional magnetic resonance imaging was conducted on 25 participants while they passively viewed unpleasant images that were previously neutrally/positively or negatively described. Increased activity in prefrontal areas including the dorsolateral and dorsomedial prefrontal cortices, lateral orbitofrontal cortex, and temporal cortex, and decreased activation in the amygdala was observed—similar to the pattern reported in deliberate emotion regulation—when unpleasant images were preceded by neutral/positive versus negative descriptions. Functional connectivity analysis revealed significant negative couplings between prefrontal regions and the amygdala. These findings suggest that implicit reappraisal recruits prefrontal regions to change semantic representations in the temporal cortex, in turn modulating the emotional response of the amygdala.

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Key words: implicit emotion regulation, cognitive reappraisal, fMRI, prefrontal cortex, orbitofrontal cortex, amygdala.

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Introduction Humans experience unpleasant encounters daily. The ability to effectively regulate one’s negative emotional response to these encounters is of significance to one’s mental and physical health, work performance, and interpersonal relationships (John and Gross, 2004; Gross and Thompson, 2007). In Gross’s model of emotion regulation, the most commonly studied strategy is cognitive reappraisal, a form of antecedent-focused strategy that regulates emotions by altering one’s interpretation of the emotional situation (Ochsner et al., 2002; Zilverstand et al., 2016). Cognitive reappraisal strategy has been proven to be highly efficacious in regulating affect and physiological arousal (Gross, 1998), and provides enduring effects (Ochsner and Gross, 2005; Ochsner et al., 2012). Cognitive reappraisal is generally assumed to involve the deliberate transformation of negative stimuli into less distressing terms by reinterpreting, rationalizing, or objectifying them (Mauss et al., 2007; Zilverstand et al., 2016). Over the last 10 years, neuroimaging studies have shown that implementing cognitive reappraisal consistently activates cognitive control regions including the dorsolateral prefrontal cortex (dlPFC), dorsomedial prefrontal cortex (dmPFC), ventrolateral prefrontal cortex (vlPFC), parietal cortex, and temporal cortex, as well as the amygdala and insula (see Buhle et al., 2014 and Kohn et al., 2014 for review). These observations suggest that deliberate reappraisal recruits frontoparietal control regions to modulate the amygdalar response. 5

While most prior emotion regulation studies focused on conscious or deliberate strategies, also termed “explicit” emotion regulation (Gyurak et al., 2011), an increasing body of evidence suggests that more automatic or unintended processes of emotion regulation operate implicitly (Mauss et al., 2007; Gyurak et al., 2011; Koole and Rothermund, 2011; Gross, 2013). Although neuroimaging studies have been useful in confirming the neural mechanism of explicit reappraisal, they have thus far failed to investigate whether the same mechanism operates during reappraisal occurring outside of one’s awareness. Two recent behavioral and physiological studies reported that while implicit reappraisal was as effective as explicit reappraisal, it was less costly to one’s cognitive resources in decreasing the physiological consequences of negative emotion compared to explicit reappraisal (Williams et al., 2009; Yuan et al., 2014). Several neuroimaging studies have explored the mechanism of brain function associated with implicit emotion regulation (Lieberman et al., 2007; Berkman et al., 2009; Meyer et al., 2011; Payer et al., 2012; Burklund, 2014). For instance, in one such study, individuals verbally labeled the emotional content of affective stimuli or their emotion-related responses without the conscious intention of changing their emotional responses (Burklund, 2014). This task was associated with increased activation of the dmPFC, dlPFC, and vlPFC, accompanied by decreased activation of the amygdala, a pattern typically seen during deliberate emotion regulation. Similarly, another study 6

explored the neural mechanism of implicit emotion regulation in romantically committed participants (Meyer et al., 2011). The romantically involved participants viewed the attractiveness of alternative partners and showed implicit derogation of attractive alternatives. This effect was associated with increased activation of the vlPFC and dmPFC and a decreased ventral-striatal response. These studies demonstrated that brain regions associated with cognitive control, including the dlPFC, dmPFC, and vlPFC, might play an important role in implicit emotion regulation. However, direct research on the neural basis of implicit reappraisal is relatively sparse. To our knowledge, only one group used 1.5-Tesla functional magnetic resonance imaging (fMRI) to investigate the neural basis of implicit reappraisal (Mocaiber et al., 2011). They demonstrated that limbic responses to negative stimuli in the amygdala and insula were automatically reduced when participants were told that the forthcoming negative images were obtained from movie scenes rather than real life. However, they separately reported the comparison of negative versus neutral images within the “fictitious” and “real” contexts, and there were not enough prefrontal activation differences between the two contexts on clusters obtained during whole-brain analysis. Therefore, the prefrontal neural mechanisms of implicit reappraisal remain unclear and warrant a more rigorous investigation. To date, a few studies have adopted an incidental reappraisal strategy and analyze coincident event-related potential (ERP) to successfully reduce the 7

negativity of participants’ subjective experience and modulate the associated electrocortical response (late positive potential) (Foti and Hajcak, 2008; Mocaiber et al., 2010). In Foti and Hajcak’s task, participants received a brief description of the forthcoming image. Prior to a negative image, the description was either neutral or negative. During passive viewing of affective stimuli, the cognitive regulatory process was uninstructed, effortless, and outside of awareness. This paradigm is the embodiment of the incidental reappraisal, since every negative image has its specific description (Foti and Hajcak, 2008). In addition, the presentation time courses of the affective image in Foti and Hajcak’s study were longer than those in Mocaiber’s study, which could evoke more emotional responses. Several ERP studies subsequently employed this paradigm to investigate the influences of behavior and electrophysiology in both healthy individuals (Macnamara et al., 2009), and clinical samples (Strauss et al., 2013; Zhang et al., 2015). The present study aimed to investigate the prefrontal-limbic neural response model in healthy participants during an implicit cognitive reappraisal task. We recorded 3.0-Tesla fMRI data from healthy adult subjects during the passive viewing of negative affective images under two conditions: (a) unpleasant pictures preceded by negative descriptions, and (b) unpleasant pictures preceded by neutral/positive (non-negative) descriptions. Past studies have demonstrated that increasing recruitment of prefrontal areas during implicit emotion regulation is associated with a decreased response in the 8

amygdala (Meyer et al., 2011; Burklund, 2014). Accordingly, we hypothesized that negative images preceded by neutral/positive descriptions would recruit more prefrontal regions to modulate the emotional response of the amygdala, a region involved in the perception and encoding of affective stimuli (Ochsner et al., 2012), compared to negative images preceded by negative descriptions. Moreover, given psychological models suggesting that cognitive reappraisal changes affective stimuli’s emotional import by altering their semantic and perceptual representations (Ochsner and Gross, 2005, Ochsner et al., 2012), we hypothesized that neural activation in the temporal cortex would be observed during implicit reappraisal.

Experimental Procedures Participants Twenty-five right-handed healthy adults (mean age = 35.2 ± 6.7 years; 13 male) were recruited from the First Affiliated Hospital of Dalian Medical University and the surrounding community. All participants were screened for lifetime mood, anxiety, psychotic, and substance dependence disorders by the Structured Clinical Interview for the Non-Patient (First et al., 2001). Pregnant women or individuals with metallic implants or other contraindications for MRI were excluded. Anxiety and depression symptoms were evaluated with the 14-item Hamilton Anxiety Rating Scale (2.32 ± 2.12) and 17-item Hamilton Depression Rating Scale (3.52 ± 1.83), respectively. Cognitive impairment was 9

screened with the Mini Mental State Examination (29.6 ± 0.82). In accordance with the Declaration of Helsinki, all procedures were carried out with the adequate understanding and written consent of the participants. Ethical approval was obtained from the Ethical Committee of Dalian Medical University. Stimuli The paradigm employed was modified from that described by Foti and Hajcak (Foti and Hajcak, 2008). Stimuli comprised 60 unpleasant images (2.80 ± 0.64 for valence, 5.71 ± 0.67 for arousal rating) selected from the International Affective Picture System (IAPS) (Lang et al., 2008), with a pixel-wise scrambled version of each image presented as a baseline for each trial. Of these, 50 images were used for the task and 10 for practice. Before viewing each image, a Chinese description of the forthcoming image was projected on a monitor. For the 50 negative images, 25 prior descriptions emphasized the negative aspects of images (unpleasant pictures preceded by negative descriptions condition, NEG-DESC), and other 25 descriptions introduced images in more neutral or positive way (unpleasant pictures preceded by non-negative descriptions condition, NNEG-DESC). The IAPS image numbers and corresponding descriptions are given in Supplementary Appendixes A. Procedure The task consisted of two runs that each included 25 trials. During each 16-s 10

trial, the negative image was presented for 4 s and was preceded and followed by the corresponding scrambled image (and black fixation cross) for a total of 12 s (Figure 1). Each run started with a 12-s scrambled image with a black fixation cross, and participants received either a neutral/positive or negative Chinese description of the forthcoming image that remained on the screen for 3 s. This was followed by the scrambled image and black fixation cross (1–3 s). The negative image was then displayed on the full screen for 4 s. After this period, participants saw the scrambled image and fixation cross and had 3 s to rate the emotional valence from 1 (not at all unpleasant) to 4 (very unpleasant) using a keypad. This was followed by continued presentation of scrambled image with a black fixation cross (3–5 s). The period of interest was the 4 s during which the participant was passively viewing the negative image. Each image was presented only once and was associated with only one of the two possible description types on any given viewing. As an example, participants read the following negative description text: unluckily, a woman died in the big fire. The same image’s non-negative description context was: the firefighters got this woman to safety just in time before the big fire. The goal of this manipulation was to investigate the prefrontal neural response of negative images during the NNEG-DESC condition compared to the NEG-DESC condition. All participants completed 50 trials, including 25 NEG-DESC and 25 NNEG-DESC stimuli. The order of trials and the description that preceded each negative image were randomly generated in 11

two runs for each participant. Prior to fMRI scanning, participants completed 10 practice trials to confirm understanding. Image acquisition Data were acquired on a 3.0-Tesla MRI scanner (SIGNA; GE Healthcare, Chicago, IL, USA) equipped with a standard radiofrequency coil at the MRI room of the First Affiliated Hospital of Dalian Medical University. Two 6-min-52-s blood-oxygen-level dependent (BOLD) fMRI runs were conducted, using T2*-weighted echo planar imaging sequence (TR = 2000 ms, TE = 30 ms, FOV = 220 × 220 mm3, flip angle = 90°, 64 × 64 matrix, 36 2.6-mm axial slices with a 1.4-mm gap). High-resolution three-dimensional BRAVO sequences were collected for each subject (TR = 8.8 ms, TE = 1 ms, FOV = 256 × 256 mm3, flip angle = 12°, 184 sagittally acquired slices with 1-mm thickness) for use in coregistration, spatial normalization, and the viewing of individual participant activation patterns. fMRI data analysis All functional and structural images were preprocessed using the Analysis of Functional NeuroImages software package (Cox, 1996). The first four scans conducted were excluded from data processing to minimize the transit effects of hemodynamic responses. The functional images were corrected for slice timing and head movement using a six-parameter rigid-body transformation, before each participant’s functional images were registered to corresponding high-resolution anatomical images. The corrected data were then spatially 12

smoothed by an 8-mm full width at half maximum Gaussian kernel. Linear drift was eliminated for each voxel time series before the data were normalized to the mean signal value for each voxel. For the individual-level analysis, the approach of generalized linear model (GLM) was applied across the whole brain. Two regressors of interest (NNEG-DESC and NEG-DESC conditions), and another eight regressors of no interest (two for subject reading of the image descriptions, and six for head movement) were included. The predicted activation time course was modeled as a ‘gamma’ function convolved with the canonical hemodynamic response function. Individual contrast maps were normalized to Talairach stereotaxic space and resampled (voxel size = 3 × 3 × 3 mm). At the group level, paired t tests were performed, producing contrasts of NNEG-DESC condition versus NEG-DESC

condition,

NNEG-DESC

condition

versus

baseline,

and

NEG-DESC condition versus baseline. The contrast maps were then corrected for multiple comparisons at the whole-brain level, using the P < 0.05 level of statistical significance (60 contiguous voxels at a voxel level threshold of P < 0.001,

t

>

3.726)

by

AlphaSim

(http://afni.nimh.nih.gov/afni/doc/manual/AlphaSim) with 1000 Monte Carlo simulations and contrast-specific smoothness of residual errors. Due to strong evidence implicating that the amygdala is critically involved in the perception and encoding of aversive stimuli, and suggesting that successful downregulation of its response is related to increased cognitive 13

control of the PFC in implicit emotion regulation (Ochsner et al., 2012), we predetermined two 6-mm-radius spherical ROIs (regions of interest) in the amygdala. We selected previously published peak voxels of the bilateral amygdalae (Phan et al., 2005; Mcrae et al., 2008; Mocaiber et al., 2011; Ferri et al., 2012; Buhle et al., 2014) to avoid circular analysis (Kriegeskorte et al., 2009). The center coordinates in Talairach space reported were obtained by averaging the coordinates in previous studies (coordinates reported in MNI space were converted to Talairach space for further calculation), as follows: left amygdala (x = -16, y = -6, z = -10), right amygdala (x = 24, y = -3, z = -13). Next, the mean beta values of the NEG-DESC and NNEG-DESC conditions on individual activation maps were extracted and compared with paired t tests. Functional connectivity analysis was performed to assess functional connections between five spherical ROIs (6-mm-radius), including five activated clusters (bilateral dlPFC, left dmPFC, left lOFC, and right amygdala; see Table 1) that were selected from previous analysis, and are known to be significantly involved in emotion regulation. In particular, we examined brain regions capable of modulating the response of the amygdala, that is, regions showing increased activation during periods of decreased activity in the amygdala. Beta series correlation analysis approach (Rissman et al., 2004), which can be best model the inter-regional functional connectivity for an event-related fMRI data , was applied to investigate functional connectivity in 14

the NNEG-DESC condition of our study. Firstly, a design matrix including 25 separate trial-specific regressors of NNEG-DESC condition, was generated by the 3dDeconvolve function with -stim_times_IM parameter. Then , the matrix was fed into the 3dLSS function , resulting in a series of beta-value estimations at each voxel in each participant’s whole brain. Lastly, Pearson’s linear correlations between five selected ROIs were calculated by the average beta value series across voxels within each ROI for each participant. Correlation coefficients were converted into normally distributed Fisher’s z-values for averaging and further statistical testing. Several group level single-sample t tests were conducted to compare the mean z-values with zero.

Results Behavioral data A repeated measures ANOVA revealed less negative valence ratings in the NNEG-DESC condition compared to the NEG-DESC condition (1.89 ± 0.51 versus 2.49 ± 0.69, F1, 24 = 41.03, P < 0.001). BOLD fMRI Whole-brain analysis To identify brain areas associated with the processing of implicit reappraisal, voxel-wise whole-brain analysis for the simple effect of emotion (the NNEG-DESC condition greater than NEG-DESC condition) revealed clusters of BOLD signal increase in certain brain regions. In prefrontal areas, the 15

NNEG-DESC condition resulted in markedly greater activation in the bilateral dlPFC (BA9), left dmPFC (BA 8), and left lOFC (BA 11/47). There was also markedly greater activity in the bilateral lateral temporal cortex (BA 20/21) and bilateral temporo-parietal-occipital (TPO) junction (BA 39/19). All areas identified as significant in this contrast can be found in Table 1 and Figure 2 (all coordinates reported in Talairach space were converted to MNI space). Notably, the activated brain areas in the NNEG-DESC condition compared to the NEG-DESC condition are thought to be partly involved in deliberate emotion regulation (Buhle et al., 2014; Kohn et al., 2014). ROI analysis In order to explore the effects of emotion regulation strategy on the amygdala, ROI analyses were conducted to contrast the emotion-related response between the NNEG-DESC and NEG-DESC conditions. As shown in Figure 3, ROI analyses revealed less activation in the right amygdala during the NNEG-DESC condition compared to the NEG-DESC condition (t 24 = -2.31, corrected P = 0.03). In the case of the left amygdala, however, there was no significant difference in activity between the two conditions (t

24

= -1.29,

corrected P = 0.21). Functional connectivity analysis Functional connectivity analysis between several seed regions in PFC and right amygdala was conducted to further assess the neural network associated with implicit reappraisal. Therefore, the beta series correlation analysis was 16

only applied to the NNEG-DESC condition. The single-sample t tests comparing the mean of Fisher’s z values with zero were all significant (P < 0.05). These results showed that there were negative correlations between the right amygdala and each of the four prefrontal areas including the bilateral dlPFC, left dmPFC, and left lOFC, while positive correlations within each pairs of these prefrontal areas. The means of z values of the group were then converted to correlations by the Fisher transformation and illustrated in Figure 4. The results indicated that decreased activation in the right amygdala was coupled with increased activation in prefrontal areas, while the changes of activation within the prefrontal areas kept consistent with each other.

Discussion In the present study, we assessed self-report scale data and investigated the neural correlates of an implicit reappraisal strategy applied to the processing of unpleasant images. First, we found that non-negative descriptions reduced subjective negative experience at a behavioral level compared to negative descriptions, consistent with previous studies (Mocaiber et al., 2010; Zhang et al., 2015). Second, the decreased response observed in the right amygdala in the NNEG-DESC condition suggests that this strategy could modulate negative emotion at a neural level, as supported by a prior neuroimaging study (Mocaiber et al., 2011). Third, this modulation is subserved by activated prefrontal areas including the bilateral dlPFC, left dmPFC, and left lOFC. 17

Moreover, functional connectivity analysis confirmed the activation in prefrontal areas to be inversely correlated with activation in the amygdala, suggesting these areas play a key role in implicit reappraisal. Finally, we observed significant recruitment of the bilateral lateral temporal cortex by contrasting the two description conditions. These results seem to support an automatic top-down modulation by which the PFC might alter semantic and perceptual representations of stimuli via the lateral temporal cortex, and these altered representations attenuate activity in the amygdala. Increased dlPFC activation was more strongly associated with the NNEG-DESC condition than with the NEG-DESC condition. The dlPFC has been proposed to play a significant role in emotion regulation (Ochsner and Gross, 2005). This area is traditionally considered important in working memory, response selection, and reasoning, cognition in general (Buhle et al., 2014; Kohn et al., 2014). A recent study demonstrated that greater dlPFC activity was associated with the implicit attenuation of negative experiences (Woo et al., 2015). Activation in the dlPFC has also been implicated in threat-related vigilance, withdrawal-related negative emotion during an anticipatory task, a paradigm exploring automatic cognitive change (Nitschke et al., 2006; Rive et al., 2013). Similar findings were reported in an implicit emotional task (Groenewold et al., 2014) and non-emotional task (Egner and Hirsch, 2005; Egner et al., 2008) that both investigated automatic attentional and cognitive control. Therefore, it may be speculated that the dlPFC is 18

associated with automatic attentional and cognitive control, which shifts participants’ attitudes toward negative stimuli when negative images were viewed after receiving neutral/positive descriptions. Contrasting the NNEG-DESC and NEG-DESC conditions revealed clusters of activity in the dlPFC to extend also into the dmPFC. dmPFC activation has been related to drawing inferences about one’s emotional states (Paradiso et al., 1999; Gallagher et al., 2000), and self-related processing (Gusnard et al., 2001), and it may also reflect cognitive expectations of emotional experiences in anticipation (Ochsner and Gross, 2005). Moreover, the left dmPFC may be associated with semantic processing (Binder et al., 2009). Monitoring and evaluating the self-relevance of emotional stimuli could be essential for reappraisal (Scherer et al., 2001). Consequently, greater activation in the dmPFC could be required for monitoring and reflecting on the meaning of changing affective stimuli during implicit reappraisal. Because direct connections between the dlPFC and amygdala are relatively sparse, the dlPFC is likely to influence the amygdala indirectly by modulating activity in the lOFC, which is directly connected with the amygdala (Ochsner et al., 2002; Phillips et al., 2008). The lOFC is strongly implicated in response inhibition and selection, as well as in strategies employed to decrease negative affect (Hooker and Knight, 2006), and in particular reappraisal (Ochsner et al., 2004). Moreover, the literature supports our result that lOFC mediated top-down regulation and its activity was inversely 19

correlated with activation in the amygdala (Phan et al., 2005) and negative experiences (Ochsner et al., 2004). However, the lOFC is thought to be critically involved in the processing of implicit motivational value (Rothkirch et al., 2012) and implicit emotion regulatory processes (Mauss et al., 2007), a theory supported by a focal brain damage study (Beer et al., 2006). Therefore, the lOFC may mediate connections between higher-order dlPFC and subcortical limbic areas such as the amygdala during implicit reappraisal, and play a key role in the automatic process of identifying and inhibiting responses to emotionally valenced stimuli. However, significant activations of the dlPFC, dmPFC, and lOFC were observed in the NNEG-DESC condition compared to the NEG-DESC condition, regions typically engaged in deliberate cognitive emotion regulation (Kohn et al., 2014; Zilverstand et al., 2016). These findings may seem surprising given that implicit and explicit emotion regulation are two different processes at the experiential level. An alternative explanation is that implicit emotion regulation might activate at least part of the emotional network typically involved in deliberate emotion regulation (Meyer et al., 2011). Previous studies have reported that overlapping regions of the PFC are recruited to reduce the activation of the amygdala in implicit emotion regulation and explicit emotion regulation (Payer et al., 2012; Burklund, 2014). In some cases, deliberate cognitive reappraisal could be conducted more implicitly via repetitive training (Gyurak et al., 2011; Christouchampi et al., 2014). Thus, our results suggest 20

that increased activation in prefrontal areas generally associated with deliberate forms of emotion regulation, such as the dlPFC, dmPFC, and lOFC, are also partly engaged in implicit reappraisal. While our paradigm was operated implicitly, the brain regions activated in the NNEG-DESC condition activate brain areas typically implicated in deliberate emotion regulation. It is worthwhile to discuss whether the process of implicit reappraisal requires cognitive resources. Meyer et al. explored the neural basis of the derogation of attractive alternatives in romantic relationships (Meyer et al., 2011). They found that the increased activity observed in the right vlPFC of romantically involved participants rejecting attractive alternatives occurred only when cognitive resources were available, nevertheless they were not instructed to regulate their attraction and did not report being aware of doing so. These findings suggest that despite the fact that the derogation effect may occur outside of awareness (i.e., implicitly), it still demands cognitive resources. Additionally, some implicit emotion processing, including affect labeling (Lieberman et al., 2007) and inhibitory spillover (Berkman et al., 2009), is associated with increased activity in vlPFC coupled with decreased emotion-related responses in the amygdala, which also required relatively little cognitive resource. Therefore, we suppose that although participants in our study did not have a conscious intention to downregulate their negative experiences, they may have had an unconscious goal to adjust their emotional state to be in line with the prior neutral/positive 21

descriptions when viewing the unpleasant images. Effortful processes may be recruited in this activity to meet their goals, but these would never have risen to the conscious level. Involvement of the lateral temporal cortex and TPO junction was confirmed when we contrasted the two conditions. The TPO junction could also be related to semantic processing (Botzung et al., 2010). It could be supposed that the PFC modulates semantic representations in the temporal cortex, which in turn attenuates emotional responses in the amygdala. This view seems to be in accord with psychological models suggesting that cognitive reappraisal changes emotional import by altering semantic and perceptual representations of affective stimuli (Ochsner and Gross, 2005; Ochsner et al., 2012). A previous ERP study demonstrated that prior descriptions might modulate subsequent responses to stimuli by meaning-change, and this process may involve top-down cognition (Macnamara et al., 2009). Accordingly, our observation of lateral temporal cortex activation may reflect the region’s key role in automatically processing semantic changes and extracting meaning. As expected, decreased activation in the amygdala is consistent with the self-reported data in the NNEG-DESC condition. Functional connectivity analysis revealed significant negative couplings between the amygdala and prefrontal regions, and we observed positive correlations between the activities of these prefrontal areas independent of the amygdala. The 22

amygdala is a key area in responses to visual emotional stimuli involving fear and negative emotions (Ochsner et al., 2002). Our results seem to be in accord with the neurobiological theory of emotion regulation positing that prefrontal regions modulate emotional responses via their cognitive control of affective systems such as the amygdala (Ochsner et al., 2012), and indicate that the pattern of emotional responses in the amygdala can be implicitly modulated by incidental reappraisal. In Mocaiber’s study, the recruitment of prefrontal and temporal regions was not observed (Mocaiber et al., 2011). It is not surprising that the present study and that of Mocaiber et al., using distinct paradigms, produced inconsistent results. In the latter study, participants were told either that the upcoming images were obtained from movie scenes (fictitious context) or from real life (real context). Firstly, the fictitious or real descriptions were presented only once before each run, which included many target images; the relative simplicity and low frequency of the descriptions could have diminished their influence on affective image perception in Mocaiber’s study. In the present study, participants received different descriptions before each image. Every unpleasant image had a specific description rather than a context, so we posit that this design would produce a concrete reappraisal effect, and that the participants were less likely to suspect the intention of the task. Secondly, the presentation time (4000 ms) of the affective images in our paradigm was longer than that used in Mocaiber’s study (200 ms); the shorter duration may 23

have been insufficient to evoke emotional responses in participants viewing negative images. Besides, Mocaiber et al. only reported the contrasts of neutral versus unpleasant images within the “fictitious” and “real” conditions, separately, and no significant result was found when the two conditions were directly compared. We conducted whole-brain analyses by comparing two conditions (NNEG-DESC versus NEG-DESC). This is a more rigorous means of investigating the neural circuitry associated with implicit cognitive reappraisal. Several limitations should be noted in the present study. Firstly, although our findings suggest that the dlPFC, dmPFC, and lOFC associated with deliberate emotion regulation are also engaged in implicit reappraisal, we did not compare the underlying neural mechanisms between implicit and explicit reappraisal directly. Future work should seek to identify the similarities and differences between these two kinds of emotion regulation. Secondly, previous research has found that attending to a non-arousing portion of an unpleasant image successfully reduces activity in the amygdala and recruits frontal areas in attentional deployment (an antecedent-focused emotion regulation strategy) (Ferri et al., 2012). One possibility we failed to exclude is that attentional deployment is responsible for partial effect. For example, reappraisal may be automatically adjusted by varying the viewing location and time course. Future research may also benefit from the use of eye-tracking technology, allowing for participants’ focus on the presented images to be analyzed. Finally, due to the 24

lack of neutral image in the experimental paradigm, it is difficult to disentangle attenuation induced by non-negative description from the potentialization induced by the negative ones. A more rigorous design of experiments should be conducted to clarify the observed effects in implicit cognitive reappraisal.

Conclusion Taken together, the findings of the present study suggest that implicit reappraisal increases activity in prefrontal areas including the dlPFC, dmPFC, and lOFC, a phenomenon associated with reduced amygdala activation. Furthermore, our findings suggest the existence of an automatic top-down control mechanism in implicit reappraisal, one involving prefrontal modulation of semantic representations in the lateral temporal cortex that indirectly modulates emotional responses in the amygdala. This process of emotion regulation may require relatively few cognitive resources. Additionally, the structured practice of explicit reappraisal can facilitate automatic reappraisal to negative events (Christouchampi et al., 2014), while reinterpreting upcoming negative stimuli automatically enhances one’s ability to respond adaptively. Understanding the specific neural mechanisms of implicit reappraisal may be important to elucidating the processes underlying emotion regulation, and could also be helpful in explaining the neurological basis of affective disorders.

Acknowledgements 25

This work was supported by the National Natural Science Foundation of China (grants No. 81401486 and 81101113).

Conflicts of interest The authors declare that they have no conflict of interest.

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Figure Captions Figure 1. Task Design. The paradigm involves an antecedent-focused and implicit cognitive reappraisal manipulation. Each run started with a 12-s scrambled image with a black fixation cross. Participants received either a neutral or negative Chinese description of the forthcoming image that remained on the screen for 3 s. This was followed by the scrambled image and black fixation cross (1–3 s). The negative image was then displayed on the full screen for 4 s. After this period, participants saw the scrambled image and fixation cross and had 3 s to rate the emotional valence from 1 (not at all unpleasant) to 4 (very unpleasant) using a keypad. This was followed by continued presentation of scrambled image with a black fixation cross (3–5 s). Each trial was 16-s long, and there were 50 trials (25 non-negative and 25 negative descriptions) randomly presented in two runs, with all images shown only once.

Figure 2. Significant changes in BOLD response for the contrast of NNEG-DESC versus NEG-DESC. Activations were thresholded at P < 0.05, corrected (cluster size > 60 voxels).

Figure 3. Results of ROI analysis for the contrast of NNEG-DESC versus NEG-DESC. Reduced activity in the right amygdala. * P < 0.05 for corrected. Figure 4. Functional connections between the brain regions involved in the NNEG-DESC condition, revealed negative couplings between the prefrontal areas (right dlPFC, left dlPFC, left dmPFC and left lOFC) and the right amygdala, and positive couplings between these prefrontal areas. All P < 0.05. RAmyg = right amygdala.

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Appendix A. IAPS numbers and corresponding descriptions for unpleasant pictures (Presented in Chinese during the task).

IAPS #

Negative Description

Non-negative Description

1050

This poisonous snake is about to attack

This snake is harmless and is in a zoo exhibit

1201

A poisonous tarantula is biting this man

This is a harmless pet tarantula sitting on his owner’s shoulder

1302

This is an angry attack dog is about to bite people

This is a dog that has been trained to show its teeth on command

1930

This is a shark that killed a diver just now

This is the mechanical shark from the movie ‘‘Jaws.’’

2120

This is a violent and angry man

This man has just held his breath for 2 minutes

9530

Two children lost their families in the fire.

Two children were saved from the fire.

2141

This woman has just found her mother dead

These are actresses a scene in a movie called ‘‘The Funeral.’’

2205

This man has just lost his wife to cancer

This man’s wife was ill but is fully recovering

2399

This woman suffers from intense migraine headaches

This is an actress posing for an aspirin commercial

2661

This premature baby may not live more than a couple of days of days

Thanks to early care, this baby develops into a healthy toddler

2683

This is a bloody clash between soldiers and protestors

These are actors in a movie about tension in the Middle East

2688

The poacher want to shooting the bear

A vet is tranquilizing this bear to give him medicine

2691

There were 50 people died during a riot

There are hard actresses during a film of riot

2700

These women are mourning the loss of their relatives

Funny scene let everybody can't help bursting into laugh

2710

A drug user was dead because of an overdose

This is an actor from the film called ‘‘Drug Smuggle’’

2716

This man is addicted to heroin

An actor is acting in scene of addiction.

2750

This is a homeless man who lives under a bridge in London

This performer is acting a role of beggar

33

2810

This boy is very angry

This boy is yelling ‘‘Ready or not, here I come’’

3168

This man suffers from a number of deformities from birth

The costume worn in this horror film won an Academy Award in 1982

3220

This man is dying in a hospital

This man is recovering upper limb from illness in a hospital

3301

This child was severely injured in a car accident

This child was injured but makes a full recovery

6020

This is an electric chair used to execute prisoners on death row

This is a prop from a movie about a man who is on death row

6190

This woman is about to pull the trigger on her husband

This is a picture from a training video on gun safety

6212

This solider is about to shoot and kill a boy

This solider notices the child and does not shoot

6250

This is a serial killer who has murdered 6 people

This is a poster for an upcoming action movie

6312

This woman is being abducted by a rapist

This is an actress in a self-defense training video

6313

This woman is being abducted by a rapist

6570.1

This man is about to commit suicide

This man ends up not committing suicide

6571

This man is having his car grabbed by a scoundrel

This is a scene from a movie about an undercover cop

6830

This man is preparing to rob a bank

This actor is preparing prop from a movie about bank robbery

6831

This is a police officer investigating the scene of a murder

Tow performers are acting in the scene of crime of murder

8230

This boxer been bitted in dripping with blood

This is a scene from the movie about boxing

9042

This man has been punished by his tribe

This tradition is a rite of passage and is actually not painful

9050

The plane crash leaded to more then one hundred of people died

This plane veered off the runway, luckily no one was seriously hurt

9250

These volunteers have found a dying victim

These volunteers have saved the victim in time

9400

This solider was killed by enemy

The director is posing to the performers who act sacrifice solider

9421

This solider has just lost his best friend in an attack

This solider is on his way to receive medical attention

Two performers are acting in the scene of violence abduction

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9425

This man has just been taken hostage by terrorists

This is a scene from a movie called ‘‘The Terrorists’’

9470

This building was bombed and 6 people were killed

This building was condemned and is being demolished

9490

This man was burned alive in an explosion

This is a prop from a monster film

9520

These abandoned children are near a nuclear reactor

This is a scene from a film called ‘‘Resident Evil’’

9584

This man is undergoing painful dental surgery

The man is having a routine dental dispose

9600

This ship sinks and no one survives

This scene of ship sinking from a movie is very reality

9611

Dozens of families were killed in this plane crash

This scene of ship sinking is forged by a film

9635.1

This man was burned alive

These actor from circus are rehearsing stunt

9800

The people of notorious German Nazi

This is an actor plays a part of Nazis in a movie

9901

The trouble-causing Driver died in time in this accident

This car was collapsed under the weight, luckily no one was in it

9911

The driver in this accident was killed before help could arrive

9920

Two people died in this horrendous car crash

This is contrived scene from an educational film about drunk driving. No one was seriously injured in this car accident

9921

Unluckily a woman died in the big fire

The firefighters get this woman to safety just in time in the big fire

9530

Two children lost their families in the fire.

Two children were saved from the fire.

35

36

37

38

Table 1. Regions demonstrated significant difference in two conditions ( NNEG-DES > NEG-DES).

Brain regions

BA

Side

Cluster size (voxels)

MNI coordinates x

y

z

t-value

Dorsolateral Prefrontal Cortex

9

L

236

–36

21

48

6.46

Dorsomedial Prefrontal Cortex

8

L

106

–24

24

51

6.57

11/47

L

104

–43

43

–22

5.61

Dorsolateral Prefrontal Cortex

9

R

260

40

29

37

7.02

Precentral Gyrus

4

L

82

–36

–23

58

7.26

Postcentral Gyrus

3

L

156

–40

–26

58

8.54

Middle Temporal Gyrus

21

R

298

66

–50

–9

8.87

Inferior Temporal Gyrus

20

L

91

–59

–35

–24

5.51

Middle Temporal Gyrus / Angular Gyrus/ Inferior Parietal Lobule

39

L

194

–43

–63

30

6.76

Angular Gyrus / Inferior Parietal Lobule / Precuneus

39/19

R

192

40

–68

40

5.74

R

202

18

–83

–37

5.24

Lateral Orbitofrontal Cortex

Cerebelum

All regions thresholded P < 0.001, P < 0.05 for corrected; BA, Brodmann area; L, left; R, right; x y z = MNI coordinates of the peak active voxel.

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Highlights


To investigate the neural basis of implicit reappraisal in healthy participants.




Activity in prefrontal and temporal areas increased during implicit reappraisal.




Activity in amygdala decreased during implicit reappraisal.




Negative coupling between prefrontal regions and the amygdala.

42