Publications by authors named "Zhenhao Shi"

32 Publications

Addicted to green: priming effect of menthol cigarette packaging on brain response to smoking cues.

Tob Control 2021 Oct 1. Epub 2021 Oct 1.

Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

Introduction: Mentholated tobacco cigarettes are believed to be more addictive than non-menthol ones. Packaging of most menthol cigarette brands includes distinctive green hues, which may act as conditioned stimuli (ie, cues) and promote menthol smoking. To examine the cue properties of menthol cigarette packaging, we used a priming paradigm to assess the effect of packaging on the neural substrates of smoking cue reactivity. We hypothesised that menthol packaging will exert a specific priming effect potentiating smoking cue reactivity in menthol compared with non-menthol smokers.

Methods: Forty-two menthol and 33 non-menthol smokers underwent functional MRI while viewing smoking and neutral cues. The cues were preceded (ie, primed) by briefly presented images of menthol or non-menthol cigarette packages. Participants reported craving for cigarettes in response to each cue.

Results: Menthol packaging induced greater frontostriatal and occipital smoking cue reactivity in menthol smokers than in non-menthol smokers. Menthol packaging also enhanced the mediation by neural activity of the relationship between cue exposure and cigarette craving in menthol but not non-menthol smokers. Dynamic causal modelling showed stronger frontostriatal-occipital connectivity in response to menthol packaging in menthol compared with non-menthol smokers. The effects of non-menthol packaging did not differ between categories of smokers.

Conclusions: Our findings demonstrate heightened motivational and perceptual salience of the green-hued menthol cigarette packaging that may exacerbate menthol smokers' susceptibility to smoking cues. These effects could contribute to the greater addiction severity among menthol smokers and could be considered in the development of science-based regulation and legal review of tobacco product marketing practices.
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http://dx.doi.org/10.1136/tobaccocontrol-2021-056639DOI Listing
October 2021

Multivariate pattern analysis links drug use severity to distributed cortical hypoactivity during emotional inhibitory control in opioid use disorder.

Neuroimage Clin 2021 Aug 29;32:102806. Epub 2021 Aug 29.

Center for Studies of Addiction, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, 3535 Market St Ste 500, Philadelphia, PA 19104, USA.

Opioid use disorder (OUD) is characterized by emotional and cognitive impairements that are associated with poor treatment outcomes. The present study investigated the neural mechanism underlying emotion evaluation and inhibitory control using an affective go/no-go (AGN) task and its association with drug use severity and craving in patients with OUD. Twenty-six recently detoxified patients with OUD underwent functional magnetic resonance imaging (fMRI) while performing the AGN task that required response to frequently presented appetitive stimuli ("go") and inhibition of response to infrequently presented aversive stimuli ("no-go"). The fMRI session was immediately followed by an injection of extended-release opioid antagonist naltrexone (XR-NTX). Participants' opioid craving was assessed immediately before fMRI and 10 ± 2 days after XR-NTX injection. Multivariate pattern analysis (MVPA) showed that drug use severity was associated with distributed brain hypoactivity in response to aversive no-go stimuli, with particularly large negative contributions from the cognitive control and dorsal attention brain networks. While drug use severity and its associated MVPA brain response pattern were both correlated with opioid craving at baseline, only the brain response pattern predicted craving during XR-NTX treatment. Our findings point to widespread functional hypoactivity in the brain networks underlying emotional inhibitory control in OUD. Such a distributed pattern is consistent with the multifaceted nature of OUD, which affects multiple brain networks. It also highlights the utility of the multivariate approach in uncovering large-scale cortical substrates associated with clinical severity in complex psychiatric disorders and in predicting treatment response.
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http://dx.doi.org/10.1016/j.nicl.2021.102806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436158PMC
August 2021

The role of withdrawal in mesocorticolimbic drug cue reactivity in opioid use disorder.

Addict Biol 2021 07 23;26(4):e12977. Epub 2020 Oct 23.

Center for Studies of Addiction, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

Opioid use disorder (OUD) is characterized by heightened cognitive, physiological, and neural responses to opioid-related cues that are mediated by mesocorticolimbic brain pathways. Craving and withdrawal are key symptoms of addiction that persist during physiological abstinence. The present study evaluated the relationship between the brain response to drug cues in OUD and baseline levels of craving and withdrawal. We used functional magnetic resonance imaging (fMRI) to examine brain responses to opioid-related pictures and control pictures in 29 OUD patients. Baseline measures of drug use severity, opioid craving, and withdrawal symptoms were assessed prior to cue exposure and correlated with subsequent brain responses to drug cues. Mediation analysis was conducted to test the indirect effect of drug use severity on brain cue reactivity through craving and withdrawal symptoms. We found that baseline drug use severity and opioid withdrawal symptoms, but not craving, were positively associated with the neural response to drug cues in the nucleus accumbens, orbitofrontal cortex, and amygdala. Withdrawal, but not craving, mediated the effect of drug use severity on the nucleus accumbens' response to drug cues. We did not find similar effects for the neural responses to stimuli unrelated to drugs. Our findings emphasize the central role of withdrawal symptoms as the mediator between the clinical severity of OUD and the brain correlates of sensitization to opioid-related cues. They suggest that in OUD, baseline withdrawal symptoms signal a high vulnerability to drug cues.
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http://dx.doi.org/10.1111/adb.12977DOI Listing
July 2021

Reduced cigarette smoking during injectable extended-release naltrexone treatment for opioid use disorder.

Am J Drug Alcohol Abuse 2020 07 7;46(4):472-477. Epub 2020 May 7.

Center for Studies of Addiction, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA, USA.

Background: The prevalence of tobacco cigarette smoking in the US has declined to approximately 15%, yet, it remains over 90% among individuals with opioid use disorder regardless of whether they are currently using opioids illicitly or as opioid substitution therapy. This disparity raises the question of whether opioids facilitate smoking among individuals with opioid use disorder and whether opioid antagonists may reduce it.

Objectives: Determine whether injectable extended-release naltrexone (XR-NTX) treatment of opioid use disorder patients is associated with a spontaneous smoking reduction. We hypothesized that treatment with XR-NTX for would lead to a reduction in smoking in tobacco cigarette smokers with opioid use disorder.

Methods: We analyzed data from 64 tobacco cigarette smokers (38% female) with opioid use disorder who were induced on XR-NTX for prevention of relapse to opioids. The number of cigarettes smoked per day and opioid-related craving and withdrawal were assessed at baseline and during treatment.

Results: Smoking was reduced from 14.4 ± 1.0 to 9.8 ± 1.0(p < 0.001) cigarettes per day after one month and 8.6 ± 1.1 cigarettes per day after two months of treatment. Daily cigarette consumption was positively correlated with the pre-treatment frequency of opioid use and opioid-related craving during the XR-NTX treatment.

Conclusions: XR-NTX treatment in smokers with opioid use disorder was associated with a 29% decline in daily cigarette consumption. Together with prior evidence of increased smoking during opioid agonist therapy, our finding suggests a pharmacodynamic interaction between nicotine and opioid systems that could influence treatment choices in this population. Our findings merit confirmation in a prospective controlled study. (NCT02324725 and NCT01587196).
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http://dx.doi.org/10.1080/00952990.2020.1741001DOI Listing
July 2020

Connectivity between visual and auditory cortices mediates the influence of argument strength on the effectiveness of smoking-cessation videos among smokers low in sensation seeking.

Psychol Res Behav Manag 2019 18;12:531-542. Epub 2019 Jul 18.

Center for Studies of Addiction, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.

Purpose: Argument strength (AS) is a validated measure of persuasiveness that has been identified as one of the key variables determining the effectiveness of video ads. Smoking-cessation videos with high AS are more effective at reducing smoking behavior than videos with low AS. The neural processes that mediate the effects of AS on subsequent smoking have not been identified. In the present study, we tested whether the efficacy of high-AS smoking-cessation videos is determined by the level of integration of visual and auditory (ie, multisensory) processes. In addition, we tested differences in sensation seeking, which is repeatedly associated with smokers' sensitivity to cessation interventions.

Patients And Methods: Using functional magnetic resonance imaging (fMRI), we recorded the brain response of 66 smokers randomly assigned to view either 16 high-AS or 16 low-AS smoking-cessation videos. Multisensory processing was assessed by the functional connectivity between brain regions that encoded visual and auditory information in the videos. Smoking behavior was indexed by the urine level of cotinine, a nicotine metabolite, immediately before and approximately 30 days after the fMRI session.

Results: We found a significant moderated mediation effect, such that the connectivity between visual and auditory cortices mediated the effect of AS on subsequent smoking, but only for smokers lower in sensation seeking. The prediction performance of the model was confirmed by leave-one-out cross-validation.

Conclusion: Our study suggests that audiovisual integration underlies the greater efficacy of high- vs low-AS smoking-cessation videos for individuals lower in sensation seeking. High-sensation-seeking smokers may be responsive to other characteristics of smoking-cessation videos.
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http://dx.doi.org/10.2147/PRBM.S183394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6645608PMC
July 2019

Brain regions in response to character feedback associated with the state self-esteem.

Biol Psychol 2019 11 25;148:107734. Epub 2019 Jul 25.

Faculty of Psychology, Southwest University, Chongqing, China. Electronic address:

Research on the Sociometer theory of self-esteem have demonstrated that manipulations of interpersonal appraisal reliably influence an individual's state self-esteem and that state levels of self-esteem correlate very highly with perceived acceptance and rejection. However, how social feedback from different sources (e.g., appearance vs. character) affect the state self-esteem and its neural underpinnings have not been explored. To address this, participants underwent functional magnetic resonance imaging (fMRI) while viewing either appearance-related feedback words or character-related feedback words, and for each feedback word, they were asked to rate their state self-esteem. Results showed that participants reported a higher state self-esteem following character feedback, irrespective of valence, than that following appearance feedback. Moreover, fMRI results demonstrated that the left caudate tail was more activated in response to positive character feedback and the lateral prefrontal cortex (LPFC), dorsal anterior cingulate, posterior cingulate, and precuneus were more activated in response to negative character feedback than in response to appearance feedback. Moreover, activation of the left caudate tail was significantly correlated with the difference in participant's reported state self-esteem scores after receiving positive character feedback versus that after receiving positive appearance feedback. Further, activation of the LPFC was significantly correlated with a difference in participant's reported state self-esteem scores after receiving negative character feedback versus that after receiving negative appearance feedback. These findings suggest a reward-related mechanism when processing positive social feedback and a self-critical processing when processing the negative social feedback on an important aspect of self-concept (e.g., character-related).
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http://dx.doi.org/10.1016/j.biopsycho.2019.107734DOI Listing
November 2019

Behavioral and Accumbal Responses During an Affective Go/No-Go Task Predict Adherence to Injectable Naltrexone Treatment in Opioid Use Disorder.

Int J Neuropsychopharmacol 2019 03;22(3):180-185

Annenberg Public Policy Center, University of Pennsylvania, Philadelphia, PA.

Adherence is a major factor in the effectiveness of the injectable extended-release naltrexone as a relapse prevention treatment in opioid use disorder. We examined the value of a variant of the Go/No-go paradigm in predicting extended-release naltrexone adherence in 27 detoxified opioid use disorder patients who were offered up to 3 monthly extended-release naltrexone injections. Before extended-release naltrexone, participants performed a Go/No-go task that comprised positively valenced Go trials and negatively valenced No-go trials during a functional magnetic resonance imaging scan. Errors of commission and neural responses to the No-go vs Go trials were independent variables. Adherence, operationalized as the completion of all 3 extended-release naltrexone injections, was the outcome variable. Fewer errors of commission and greater left accumbal response during the No-go vs Go trials predicted better adherence. These findings support the clinical potential of the behavioral and neurophysiological correlates of response inhibition in the prediction of extended-release naltrexone treatment outcomes in opioid use disorder.
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http://dx.doi.org/10.1093/ijnp/pyz002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403086PMC
March 2019

Mitochondrion-Targeting Identification of a Fluorescent Apoptosis-Triggering Molecule by Mass Spectrometry Elucidates Drug Tracking.

Chembiochem 2019 03 1;20(6):778-784. Epub 2019 Feb 1.

State Key Laboratory for Chemistry and, Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, 541004, P.R. China.

The real-time tracking of localization and dynamics of small molecules in organelles helps to understand their function and identification of their potential targets at subcellular resolution. To identify the mitochondrion-targeting effects of small molecules (NA-17 and NA-2a) in cancer cells, we used mass spectrometry to study their distribution and accumulation in mitochondria and in the surrounding cytoplasm thus enabling tracing of action processes of therapeutic compounds. Colocalization analysis with the aid of imaging agents suggests that both NA-17 and NA-2a display mitochondrion-targeting effects. However, MS analysis reveals that only NA-2a displays both a mitochondrion-targeting effect and an accumulation effect, whereas NA-17 only distributes in the surrounding cytoplasm. A combination of mitochondrion imaging, immunoblotting, and MS analysis in mitochondria indicated that NA-17 neither has the ability to enter mitochondria directly nor displays any mitochondrion-targeting effect. Further studies revealed that NA-17 could not enter into mitochondria even when the mitochondrial permeability in cells changed after NA-17 treatment, as was evident from reactive oxygen species (ROS) generation and cytochrome c release. In the process of cellular metabolism, NA-17 itself is firmly restricted to the cytoplasm during the metabolic process, but its metabolites containing fluorophores could accumulate in mitochondria for cell imaging. Our studies have furnished new insights into the drug metabolism processes.
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http://dx.doi.org/10.1002/cbic.201800598DOI Listing
March 2019

Neural activation in response to the two sides of emotion.

Neurosci Lett 2018 09 7;684:140-144. Epub 2018 Jul 7.

School of Psychological and Cognitive Sciences, PKU-IDG/McGovern Institute for Brain Research, Beijing Key Laboratory of Behavior and Mental Health, Peking University, China. Electronic address:

Emotions are at the core of human cognition and behavior. Traditionally, emotions have been classified dichotomously as being either positive or negative. However, recent behavioral research (An et al., 2017) suggests that emotions contain both positivity and negativity. The current work investigated neural correlates of experiencing positive and negative emotions in response to happy and sad photos. Functional MRI revealed the precuneus and posterior cingulate cortex showed stronger activation when experiencing positivity compared to negativity of sadness, but not happiness, whereas the bilateral cerebellum showed greater response to positivity than negativity regardless of emotion. Results suggest that there are similarities and differences in the neural activation of positivity and negativity of happiness and sadness, consistent with previous findings (An et al., 2017). Emotion from both the neural and psychological perspectives were investigated. Further implications are discussed.
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http://dx.doi.org/10.1016/j.neulet.2018.07.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133757PMC
September 2018

Effects of extended-release naltrexone on the brain response to drug-related stimuli in patients with opioid use disorder.

J Psychiatry Neurosci 2018 07;43(4):254-261

From the Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa. (Shi, Wang, Jagannathan, Fairchild, O'Brien, Childress, Langleben); the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY (Wang); the Annenberg Public Policy Center, University of Pennsylvania, Philadelphia, Pa. (Langleben); and the Corporal Michael J. Crescenz Veterans Administration Medical Center, Philadelphia, Pa. (Langleben).

Background: Heightened response to drug-related cues is a hallmark of addiction. Extended-release naltrexone (XR-NTX) is a US Food and Drug Administration-approved pharmacotherapy for relapse prevention in patients with opioid use disorder (OUD). In these patients, XR-NTX has been shown to reduce brain responses to opioid-related visual stimuli. To assess the biomarker potential of this phenomenon, it is necessary to determine whether this effect is limited to opioid-related stimuli and whether it is associated with key OUD symptoms.

Methods: Using functional MRI (fMRI), we measured the brain responses to opioid-related and control (i.e., sexual and aversive) images in detoxified patients with OUD before, during and after XR-NTX treatment. Craving and withdrawal severity were evaluated using clinician- and self-administered instruments during each session.

Results: We included 24 patients with OUD in our analysis. During XR-NTX treatment, we found reduced responses to opioid-related stimuli in the nucleus accumbens (NAcc) and medial orbitofrontal cortex (mOFC). The reduction in mOFC response was specific to the opioid-related stimuli. The reduced NAcc and mOFC opioid cue reactivity was correlated with reduction in clinician-assessed and self-reported withdrawal symptoms, respectively.

Limitations: The study was not placebo-controlled owing to ethical, safety and feasibility concerns.

Conclusion: Extended-release naltrexone reduces the NAcc and mOFC cue reactivity in patients with OUD. This effect is specific to opioid-related stimuli in the mOFC only. The reduction in neural response to opioid-related stimuli is more robust in patients with greater decline in withdrawal severity. Our results support the clinical utility of mesocorticolimbic cue reactivity in monitoring the XR-NTX treatment outcomes and highlight the link between opioid withdrawal symptomatology and neural opioid cue reactivity.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019353PMC
July 2018

Activations of the dorsolateral prefrontal cortex and thalamus during agentic self-evaluation are negatively associated with trait self-esteem.

Brain Res 2018 08 16;1692:134-141. Epub 2018 May 16.

Faculty of Psychology, Southwest University, Chongqing 400715, China. Electronic address:

Individual self-esteem is dominated more by agency than by communion. However, prior research has mainly focused on one's agentic/communal self-evaluation, while little is known about how one endorses others' agentic/communal evaluation of the self. The present study investigated the associations between trait self-esteem and fundamental dimensions of social cognition, i.e. agency vs. communion, during both self-evaluation and endorsement of others' evaluation of oneself. We also investigated the neural mechanisms underlying the relationship between trait self-esteem and agentic self-evaluation. Behavioral results revealed that self-esteem was positively correlated with the agentic ratings from self-evaluation and endorsement of others' evaluation of the self, and that the agentic self-evaluation was a significant full mediator between self-esteem and endorsement of others' agentic evaluation. Whole-brain regression analysis revealed that self-esteem was negatively correlated with right dorsolateral prefrontal and bilateral thalamic response to agentic self-evaluation. A possible interpretation is that low self-esteem people both hold a more self-critical attitude about the self and have less certainty or clarity of their self-concepts than high self-esteem people do. These findings have important implication for understanding the neural and cognitive mechanisms underlying self-esteem's effect on one's agentic self-evaluations.
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http://dx.doi.org/10.1016/j.brainres.2018.05.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5988258PMC
August 2018

Emotional salience of the image component facilitates recall of the text of cigarette warning labels.

Eur J Public Health 2019 02;29(1):153-158

Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Background: Graphic warning labels (GWLs) on cigarette packages, that combine textual warnings with emotionally salient images depicting the adverse health consequences of smoking, have been adopted in most European countries. In the US, the courts deemed the evidence justifying the inclusion of emotionally salient images in GWLs insufficient and put the implementation on hold. We conducted a controlled experimental study examining the effect of emotional salience of GWL's images on the recall of their text component.

Methods: Seventy-three non-treatment-seeking daily smokers received cigarette packs carrying GWLs for a period of 4 weeks. Participants were randomly assigned to receive packs with GWLs previously rated as eliciting high or low level of emotional reaction (ER). The two conditions differed in respect to images but used the same textual warning statements. Participants' recognition of GWL images and statements were tested separately at baseline and again after the 4-week repetitive exposure.

Results: Textual warning statements were recognized more accurately when paired with high ER images than when paired with low ER images, both at baseline and after daily exposure to GWLs over a 4-week period.

Conclusion: The results suggest that emotional salience of GWLs facilitates cognitive processing of the textual warnings, resulting in better remembering of the information about the health hazards of smoking. Thus, high emotional salience of the pictorial component of GWLs is essential for their overall effectiveness.
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http://dx.doi.org/10.1093/eurpub/cky059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345145PMC
February 2019

Effects of extended-release naltrexone on the brain response to drug-related stimuli in patients with opioid use disorder.

J Psychiatry Neurosci 2018 Feb 23;43(3):170036. Epub 2018 Feb 23.

From the Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa. (Shi, Wang, Jagannathan, Fairchild, O'Brien, Childress, Langleben); the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY (Wang); the Annenberg Public Policy Center, University of Pennsylvania, Philadelphia, Pa. (Langleben); and the Corporal Michael J. Crescenz Veterans Administration Medical Center, Philadelphia, Pa. (Langleben).

Background: Heightened response to drug-related cues is a hallmark of addiction. Extended-release naltrexone (XR-NTX) is a US Food and Drug Administration-approved pharmacotherapy for relapse prevention in patients with opioid use disorder (OUD). In these patients, XR-NTX has been shown to reduce brain responses to opioid-related visual stimuli. To assess the biomarker potential of this phenomenon, it is necessary to determine whether this effect is limited to opioid-related stimuli and whether it is associated with key OUD symptoms.

Methods: Using functional MRI (fMRI), we measured the brain responses to opioid-related and control (i.e., sexual and aversive) images in detoxified patients with OUD before, during and after XR-NTX treatment. Craving and withdrawal severity were evaluated using clinician- and self-administered instruments during each session.

Results: We included 24 patients with OUD in our analysis. During XR-NTX treatment, we found reduced responses to opioid-related stimuli in the nucleus accumbens (NAcc) and medial orbitofrontal cortex (mOFC). The reduction in mOFC response was specific to the opioid-related stimuli. The reduced NAcc and mOFC opioid cue reactivity was correlated with reduction in clinician-assessed and self-reported withdrawal symptoms, respectively.

Limitations: The study was not placebo-controlled owing to ethical, safety and feasibility concerns.

Conclusion: Extended-release naltrexone reduces the NAcc and mOFC cue reactivity in patients with OUD. This effect is specific to opioid-related stimuli in the mOFC only. The reduction in neural response to opioid-related stimuli is more robust in patients with greater decline in withdrawal severity. Our results support the clinical utility of mesocorticolimbic cue reactivity in monitoring the XR-NTX treatment outcomes and highlight the link between opioid withdrawal symptomatology and neural opioid cue reactivity.
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http://dx.doi.org/10.1503/jpn.170036DOI Listing
February 2018

Gender and neural substrates subserving implicit processing of death-related linguistic cues.

Cogn Process 2018 Feb 6;19(1):63-71. Epub 2018 Jan 6.

Department of Psychology, Peking University, Beijing, 100871, People's Republic of China.

Our recent functional magnetic resonance imaging study revealed decreased activities in the anterior cingulate cortex (ACC) and bilateral insula for women during the implicit processing of death-related linguistic cues. Current work tested whether aforementioned activities are common for women and men and explored potential gender differences. We scanned twenty males while they performed a color-naming task on death-related, negative-valence, and neutral-valence words. Whole-brain analysis showed increased left frontal activity and decreased activities in the ACC and bilateral insula to death-related versus negative-valence words for both men and women. However, relative to women, men showed greater increased activity in the left middle frontal cortex and decreased activity in the right cerebellum to death-related versus negative-valence words. The results suggest, while implicit processing of death-related words is characterized with weakened sense of oneself for both women and men, men may recruit stronger cognitive regulation of emotion than women.
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http://dx.doi.org/10.1007/s10339-017-0847-0DOI Listing
February 2018

Sustained opioid antagonism modulates striatal sensitivity to baby schema in opioid use disorder.

J Subst Abuse Treat 2018 02 18;85:70-77. Epub 2017 Oct 18.

Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Behavioral Health Service, Veterans Administration Medical Center, Philadelphia, PA, USA.

Background: Chronic opioid misuse is associated with reduced sensitivity to natural rewards and social motivation deficits that include impaired caregiving. The neurobiological mechanisms underlying these deficits and their response to treatment are not well understood. Baby schema (Kindchenschema) is a set of juvenile physical features, which is perceived as "cute" and triggers motivation for caregiving. Recent studies suggest that the "baby schema effect" is mediated by the brain "reward" network. We studied the impact of opioid antagonist treatment on the baby schema response in patients with opioid use disorder.

Methods: Forty-seven (24 F) recently detoxified patients with opioid use disorder underwent functional magnetic resonance imaging (fMRI) while viewing infant portraits that were parametrically manipulated for baby schema content and rating them for cuteness, at baseline and during treatment with the injectable extended release opioid antagonist naltrexone (XRNTX). The study was not placebo-controlled.

Results: The behavioral effect of baby schema, indexed by "cuteness" ratings, was present and unaffected by XRNTX. The brain response to baby schema was absent at baseline, but present in the bilateral ventral striatum after two weeks of XRNTX treatment. The decline in self-reported craving for opioids was positively correlated with the brain fMRI response to baby schema in the bilateral ventral striatum.

Conclusions: Opioid antagonist treatment modulated the brain reward system response to a marker of caregiving motivation in patients with opioid use disorder. Neural response to baby schema may offer a novel probe of social motivation and affiliative behaviors in this population.
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http://dx.doi.org/10.1016/j.jsat.2017.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043353PMC
February 2018

Individual differences in the processing of smoking-cessation video messages: An imaging genetics study.

Biol Psychol 2017 09 28;128:125-131. Epub 2017 Jul 28.

Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Annenberg Public Policy Center, University of Pennsylvania, Philadelphia, PA 19104, United States; Corporal Michael J. Crescenz Veterans Administration Medical Center, Philadelphia, PA 19104, United States. Electronic address:

Studies testing the benefits of enriching smoking-cessation video ads with attention-grabbing sensory features have yielded variable results. Dopamine transporter gene (DAT1) has been implicated in attention deficits. We hypothesized that DAT1 polymorphism is partially responsible for this variability. Using functional magnetic resonance imaging, we examined brain responses to videos high or low in attention-grabbing features, indexed by "message sensation value" (MSV), in 53 smokers genotyped for DAT1. Compared to other smokers, 10/10 homozygotes showed greater neural response to High- vs. Low-MSV smoking-cessation videos in two a priori regions of interest: the right temporoparietal junction and the right ventrolateral prefrontal cortex. These regions are known to underlie stimulus-driven attentional processing. Exploratory analysis showed that the right temporoparietal response positively predicted follow-up smoking behavior indexed by urine cotinine. Our findings suggest that responses to attention-grabbing features in smoking-cessation messages is affected by the DAT1 genotype.
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http://dx.doi.org/10.1016/j.biopsycho.2017.07.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731475PMC
September 2017

Distinct effects of reminding mortality and physical pain on the default-mode activity and activity underlying self-reflection.

Soc Neurosci 2018 06 15;13(3):372-383. Epub 2017 May 15.

a School of Psychological and Cognitive Sciences, PKU-IDG/McGovern Institute for Brain Research, Beijing Key Laboratory of Behavior and Mental Health , Peking University , Beijing , China.

Behavioral research suggests that reminding both mortality and negative affect influences self-related thoughts. Using functional magnetic resonance imaging (MRI), we tested the hypothesis that reminders of mortality and physical pain decrease brain activity underlying self-related thoughts. Three groups of adults underwent priming procedures during which they answered questions pertaining to mortality, physical pain, or leisure time, respectively. Before and after priming, participants performed personality trait judgments on oneself or a celebrity, identified the font of words, or passively viewed a fixation. The default-mode activity and neural activity underlying self-reflection were identified by contrasting viewing a fixation vs. font judgment and trait judgments on oneself vs. a celebrity, respectively. The analyses of the pre-priming functional MRI (fMRI) data identified the default-mode activity in the posterior cingulate cortex (PCC), ventral medial prefrontal cortex (MPFC), and parahippocampal gyrus, and the activity underlying instructed self-reflection in both the ventral and dorsal regions of the MPFC. The analyses of the post-priming fMRI data revealed that, relative to leisure time priming, reminding mortality significantly reduced the default-mode PCC activity, and reminding physical pain significantly decreased the dorsal MPFC activity during instructed self-reflection. Our findings suggest distinct neural underpinnings of the effect of reminding morality and aversive emotion on default-mode and instructed self-reflection.
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http://dx.doi.org/10.1080/17470919.2017.1329165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5685934PMC
June 2018

Empathy for pain motivates actions without altruistic effects: evidence of motor dynamics and brain activity.

Soc Cogn Affect Neurosci 2017 06;12(6):893-901

School of Psychological and Cognitive Sciences, PKU-IDG/McGovern Institute for Brain Research, Beijing Key Laboratory of Behavior and Mental Health, Peking University, Beijing, China.

Empathy has been supposed to be a proximate mechanism of altruistic behavior. We investigated whether empathy for pain drives actions without altruistic effects and how such actions modulate neural responses to others' pain. In two experiments, we asked healthy adults to press a button for no reason when viewing video clips showing faces with pain expressions receiving needle penetration or faces with neutral expressions receiving a cotton swab touch. Experiment 1 found that participants pressed a button with greater response force when watching painful than non-painful stimuli. Participants who reported greater unpleasant feelings pressed the button harder when viewing painful stimuli. Experiment 2 revealed that passively viewing painful vs non-painful stimuli increased blood-oxygen-level-dependent signals in the middle cingulate cortex, supplementary motor cortex, and bilateral second somatosensory and inferior frontal cortex, which, however, were reduced by the action of button press without altruistic effects. In addition, individuals who reported higher personal distress illustrated greater decrease of the second somatosensory activity induced by button press. Our results indicate that empathy for pain motivates simple actions without altruistic effects that in turn reduce neural responses to others' pain, suggesting a functional role of action execution in self distress relief when viewing others' suffering.
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http://dx.doi.org/10.1093/scan/nsx016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472110PMC
June 2017

The Importance of Relevant Emotional Arousal in the Efficacy of Pictorial Health Warnings for Cigarettes.

Nicotine Tob Res 2017 Jun;19(6):750-755

Annenberg Public Policy Center, University of Pennsylvania, Philadelphia, PA.

Introduction: Warning labels for cigarettes proposed by Food and Drug Administration (FDA) were rejected by the courts partly because they were thought to be emotionally evocative but have no educational value. To address this issue, we compared three types of smoking warnings: (1) FDA-proposed warnings with pictures illustrating the smoking hazards; (2) warnings with the same text information paired with equally aversive but smoking-irrelevant images; and (3) text-only warnings.

Methods: Smokers recruited through Amazon's Mechanical Turk were randomly assigned to one of the three conditions. They reported how many cigarettes they smoked per day (CPD) during the past week and then viewed eight different warnings. After viewing each warning, they rated its believability and perceived ability to motivate quitting. One week later, 62.3% of participants again reported CPD during the past week, rated how the warnings they viewed the week before changed their feeling about smoking, rated their intention to quit in the next 30 days, and recalled as much as they could about each of the warnings they viewed.

Results: Compared to the irrelevant image and text-only warnings, FDA warnings were seen as more believable and able to motivate quitting and at the follow-up, produced lower CPD, worse feeling about smoking, and more memory for warning information, controlling for age and baseline CPD.

Conclusions: Emotionally evocative warning images are not effective in communicating the risks of smoking, unless they pertain to smoking-related hazards. In future versions of warning labels, pictorial contents should be pretested for the ability to enhance the health-hazard message.

Implications: Our study shows that contrary to court opinions, FDA-proposed pictorial warnings for cigarettes are more effective in communicating smoking-related hazards than warnings that merely contain emotionally aversive but smoking-irrelevant images. The suggestion that FDA's proposed warnings employed emotionally arousing pictures with no information value was not supported. Pictures that illustrate the risk carry information that enhances the persuasiveness of the warning. The congruence between pictures and text should be a criterion for selecting warning images in the future.
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http://dx.doi.org/10.1093/ntr/ntw322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896506PMC
June 2017

Targeting modulates audiences' brain and behavioral responses to safe sex video ads.

Soc Cogn Affect Neurosci 2016 10 19;11(10):1650-7. Epub 2016 May 19.

Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Annenberg Public Policy Center, University of Pennsylvania, Philadelphia, PA, USA Behavioral Health Service, Veterans Administration Medical Center, Philadelphia, PA, USA.

Video ads promoting condom use are a key component of media campaigns to stem the HIV epidemic. Recent neuroimaging studies in the context of smoking cessation, point to personal relevance as one of the key variables that determine the effectiveness of public health messages. While minority men who have sex with men (MSM) are at the highest risk of HIV infection, most safe-sex ads feature predominantly Caucasian actors in heterosexual scenarios. We compared brain respons of 45 African American MSM to safe sex ads that were matched (i.e. 'Targeted') to participants' sexual orientation and race, and 'Untargeted' ads that were un matched for these characteristics. Ad recall, perceived 'convincingness' and attitudes towards condom use were also assessed. We found that Targeted ads were better remembered than the Untargeted ads but perceived as equally convincing. Targeted ads engaged brain regions involved in self-referential processing and memory, including the amygdala, hippocampus, temporal and medial prefrontal cortices (MPFC) and the precuneus. Connectivity between MPFC and precuneus and middle temporal gyrus was stronger when viewing Targeted ads. Our results suggest that targeting may increase cognitive processing of safe sex ads and justify further prospective studies linking brain response to media public health interventions and clinical outcomes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5040911PMC
http://dx.doi.org/10.1093/scan/nsw070DOI Listing
October 2016

Playing it safe: a video game probing the relationship between addiction, gender, and avoidance.

J Clin Psychiatry 2016 Mar;77(3):395-7

Annenberg Public Policy Center, University of Pennsylvania, Philadelphia.

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http://dx.doi.org/10.4088/JCP.16com10752DOI Listing
March 2016

Trait self-esteem and neural activities related to self-evaluation and social feedback.

Sci Rep 2016 Feb 4;6:20274. Epub 2016 Feb 4.

Department of Psychology, PKU-IDG/McGovern Institute for Brain Research, Beijing Key Laboratory of Behavior and Mental Health, Peking University, Beijing, 100871, China.

Self-esteem has been associated with neural responses to self-reflection and attitude toward social feedback but in different brain regions. The distinct associations might arise from different tasks or task-related attitudes in the previous studies. The current study aimed to clarify these by investigating the association between self-esteem and neural responses to evaluation of one's own personality traits and of others' opinion about one's own personality traits. We scanned 25 college students using functional MRI during evaluation of oneself or evaluation of social feedback. Trait self-esteem was measured using the Rosenberg self-esteem scale after scanning. Whole-brain regression analyses revealed that trait self-esteem was associated with the bilateral orbitofrontal activity during evaluation of one's own positive traits but with activities in the medial prefrontal cortex, posterior cingulate, and occipital cortices during evaluation of positive social feedback. Our findings suggest that trait self-esteem modulates the degree of both affective processes in the orbitofrontal cortex during self-reflection and cognitive processes in the medial prefrontal cortex during evaluation of social feedback.
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http://dx.doi.org/10.1038/srep20274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740758PMC
February 2016

Neural correlates of reflection on actual versus ideal self-discrepancy.

Neuroimage 2016 Jan 12;124(Pt A):573-580. Epub 2015 Sep 12.

Department of Psychology, PKU-IDG/McGovern Institute for Brain Research, Beijing Key Laboratory of Behavior and Mental Health, Peking University, Beijing, China. Electronic address:

Subjective feelings of actual/ideal self-discrepancy vary across individuals and influence one's own affective states. However, the neural correlates of actual/ideal self-discrepancy and their genetic individual differences remain unknown. We investigated neural correlates of actual/ideal self-discrepancy and their associations with the serotonin transporter promoter polymorphism (5-HTTLPR) that moderates human affective states during self-reflection. We scanned short/short and long/long allele carriers of 5-HTTLPR, using functional MRI, during reflection on the distance between actual and ideal self in personality traits. We found that larger actual/ideal self-discrepancy was associated with activations in the ventral/dorsal striatum and dorsal medial and lateral prefrontal cortices. Moreover, these brain activities were stronger in short/short than long/long allele carriers and predicted self-report of life satisfaction in short/short carriers but trait depression in long/long carriers. Our findings revealed neural substrates of actual/ideal self-discrepancy and their associations with affective states that are sensitive to individuals' genetic makeup.
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http://dx.doi.org/10.1016/j.neuroimage.2015.08.077DOI Listing
January 2016

Equality bias impairs collective decision-making across cultures.

Proc Natl Acad Sci U S A 2015 Mar 9;112(12):3835-40. Epub 2015 Mar 9.

The Interacting Minds Centre, Aarhus University, 8000 Aarhus, Denmark; Institute of Cognitive Neuroscience, University College London, London WC1N 3AR, United Kingdom

We tend to think that everyone deserves an equal say in a debate. This seemingly innocuous assumption can be damaging when we make decisions together as part of a group. To make optimal decisions, group members should weight their differing opinions according to how competent they are relative to one another; whenever they differ in competence, an equal weighting is suboptimal. Here, we asked how people deal with individual differences in competence in the context of a collective perceptual decision-making task. We developed a metric for estimating how participants weight their partner's opinion relative to their own and compared this weighting to an optimal benchmark. Replicated across three countries (Denmark, Iran, and China), we show that participants assigned nearly equal weights to each other's opinions regardless of true differences in their competence-even when informed by explicit feedback about their competence gap or under monetary incentives to maximize collective accuracy. This equality bias, whereby people behave as if they are as good or as bad as their partner, is particularly costly for a group when a competence gap separates its members.
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http://dx.doi.org/10.1073/pnas.1421692112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378431PMC
March 2015

Interaction between oxytocin receptor polymorphism and interdependent culture values on human empathy.

Soc Cogn Affect Neurosci 2015 Sep 13;10(9):1273-81. Epub 2015 Feb 13.

Department of Psychology, PKU-IDG/McGovern Institute for Brain Research, and

Recent evidence suggests that the association between oxytocin receptor polymorphism (OXTR rs53576) and emotion-related behavioral/psychological tendencies differs between individuals from East Asian and Western cultures. What remains unresolved is which specific dimension of cultural orientations interacts with OXTR rs53576 to shape these tendencies and whether such gene × culture interactions occurs at both behavioral and neural level. This study investigated whether and how OXTR rs53576 interacts with interdependence-a key dimension of cultural orientations that distinguish between East Asian and Western cultures-to affect human empathy that underlies altruistic motivation and prosocial behavior. Experiment 1 measured interdependence, empathy trait and OXTR rs53576 genotypes of 1536 Chinese participants. Hierarchical regression analyses revealed a stronger association between interdependence and empathy trait in G allele carriers compared with A/A homozygotes of OXTR rs53576. Experiment 2 measured neural responses to others' suffering by scanning A/A and G/G homozygous of OXTR rs53576 using functional magnetic resonance imaging. Hierarchical regression analyses revealed stronger associations between interdependence and empathic neural responses in the insula, amygdala and superior temporal gyrus in G/G compared with A/A carriers. Our results provide the first evidence for gene × culture interactions on empathy at both behavioral tendency and underlying brain activity.
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http://dx.doi.org/10.1093/scan/nsv019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4560951PMC
September 2015

When "Your" reward is the same as "My" reward: self-construal priming shifts neural responses to own vs. friends' rewards.

Neuroimage 2014 Feb 31;87:164-9. Epub 2013 Oct 31.

Department of Psychology, Peking University, Beijing, China; PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China. Electronic address:

Is it possible for neural responses to others' rewards to be as strong as those for the self? Although prior fMRI studies have demonstrated that watching others get rewards can activate one's own reward centers, such vicarious reward activation has always been less strong than responses to rewards for oneself. In the present study we manipulated participants' self-construal (independent vs. interdependent) and found that, when an independent self-construal was primed, subjects showed greater activation in the bilateral ventral striatum in response to winning money for the self (vs. for a friend) during a gambling game. However, priming an interdependent self-construal resulted in comparable activation in these regions in response to winning money for the self and for a friend. Our findings suggest that interdependence may cause people to experience rewards for a close other as strongly as they experience rewards for the self.
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http://dx.doi.org/10.1016/j.neuroimage.2013.10.042DOI Listing
February 2014

Dynamic neural processing of linguistic cues related to death.

PLoS One 2013 28;8(6):e67905. Epub 2013 Jun 28.

Department of Psychology, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, PR China.

Behavioral studies suggest that humans evolve the capacity to cope with anxiety induced by the awareness of death's inevitability. However, the neurocognitive processes that underlie online death-related thoughts remain unclear. Our recent functional MRI study found that the processing of linguistic cues related to death was characterized by decreased neural activity in human insular cortex. The current study further investigated the time course of neural processing of death-related linguistic cues. We recorded event-related potentials (ERP) to death-related, life-related, negative-valence, and neutral-valence words in a modified Stroop task that required color naming of words. We found that the amplitude of an early frontal/central negativity at 84-120 ms (N1) decreased to death-related words but increased to life-related words relative to neutral-valence words. The N1 effect associated with death-related and life-related words was correlated respectively with individuals' pessimistic and optimistic attitudes toward life. Death-related words also increased the amplitude of a frontal/central positivity at 124-300 ms (P2) and of a frontal/central positivity at 300-500 ms (P3). However, the P2 and P3 modulations were observed for both death-related and negative-valence words but not for life-related words. The ERP results suggest an early inverse coding of linguistic cues related to life and death, which is followed by negative emotional responses to death-related information.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0067905PLOS
April 2014

5-HTTLPR polymorphism modulates neural mechanisms of negative self-reflection.

Cereb Cortex 2014 Sep 15;24(9):2421-9. Epub 2013 Apr 15.

Department of Psychology, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.

Cognitive distortion in depression is characterized by enhanced negative thoughts about both environment and oneself. Carriers of a risk allele for depression, that is, the short (s) allele of the serotonin transporter promoter polymorphism (5-HTTLPR), exhibit amygdala hyperresponsiveness to negative environmental stimuli relative to homozygous long variant (l/l). However, the neural correlates of negative self-schema in s allele carriers remain unknown. Using functional MRI, we scanned individuals with s/s or l/l genotype of the 5-HTTLPR during reflection on their own personality traits or a friend's personality traits. We found that relative to l/l carriers, s/s carriers showed stronger distressed feelings and greater activity in the dorsal anterior cingulate (dACC)/dorsal medial prefrontal cortex (dmPFC) and the right anterior insula (AI) during negative self-reflection. The 5-HTTLPR effect on the distressed feelings was mediated by the AI/inferior frontal (IF) activity during negative self-reflection. The dACC/dmPFC activity explained 20% of the variation in harm-avoidance tendency in s/s but not l/l carriers. The genotype effects on distress and brain activity were not observed during reflection on a friend's negative traits. Our findings reveal that 5-HTTLPR polymorphism modulates distressed feelings and brain activities associated with negative self-schema and suggest a potential neurogenetic susceptibility mechanism for depression.
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http://dx.doi.org/10.1093/cercor/bht099DOI Listing
September 2014

Reminders of mortality decrease midcingulate activity in response to others' suffering.

Soc Cogn Affect Neurosci 2014 Apr 17;9(4):477-86. Epub 2013 Jan 17.

Department of Psychology, Peking University, 5 Yiheyuan Road, Beijing 100871, P. R. China.

Reminders of mortality influence human social cognition, but whether and how reminders of mortality affect brain activity underlying social cognition remains unclear. To test whether increasing mortality salience modulates neural responses to others' suffering, we scanned healthy adults who viewed video clips showing others in pain using functional magnetic resonance imaging. One group of participants were primed to increase mortality salience and another group were primed with negative affect in terms of fear/anxiety. We found that perceiving painful vs non-painful stimuli in the pre-priming session activated the midcingulate/dorsal medial prefrontal cortex (MCC/dMPFC), bilateral anterior insula/inferior frontal cortex, bilateral secondary somatosensory cortex and left middle temporal gyrus. However, MCC/dMPFC activity in response to perceived pain in others was significantly decreased in the post-priming session by the mortality salience priming, but was not influenced by the negative affect priming. Moreover, subjective fear of death induced by the priming procedures mediated the change in MCC/dMPFC activity across the priming procedures. Subjective fear of death also moderated the co-variation of MCC/dMPFC and left insular activity during perception of others in pain. Our findings indicate that reminders of mortality decrease neural responses to others' suffering and this effect is mediated by the subjective fear of death.
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http://dx.doi.org/10.1093/scan/nst010DOI Listing
April 2014

Transient and sustained neural responses to death-related linguistic cues.

Soc Cogn Affect Neurosci 2013 Jun 14;8(5):573-8. Epub 2012 Mar 14.

Department of Psychology, Peking University, 5 Yiheyuan Road, Beijing 100871, People's Republic of China.

Recent research showed that perception of death-related vs death-unrelated linguistic cues produced increased frontoparietal activity but decreased insular activity. This study investigated (i) whether the increased frontoparietal and decreased insular activities are, respectively, associated with transient trial-specific processes of death-related linguistic cues and sustained death-related thought during death-relevance judgments on linguistic cues and (ii) whether the neural activity underlying death-related thought can predict individuals' dispositional death anxiety. Participants were presented with death-related/unrelated words, life-related/unrelated words, and negative-valence/neutral words in separate sessions. Participants were scanned using functional magnetic resonance imaging while performing death-relevance, life-relevance, and valence judgments on the words, respectively. The contrast of death-related vs death-unrelated words during death-relevance judgments revealed transient increased activity in the left inferior parietal lobule, the right frontal eye field, and the right superior parietal lobule. The contrast of death-relevance judgments vs life-relevance/valence judgments showed decreased activity in the bilateral insula. The sustained insular activity was correlated with dispositional death anxiety, but only in those with weak transient frontoparietal responses to death-related words. Our results dissociate the transient and sustained neural responses to death-related linguistic cues and suggest that the combination of the transient and sustained neural activities can predict dispositional death anxiety.
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http://dx.doi.org/10.1093/scan/nss034DOI Listing
June 2013
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