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An amygdala-centered effective connectivity network in trait anxiety

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Abstract

Previous studies have established that the amygdala plays an important role in trait anxiety. However, there remains limited knowledge regarding the changes in amygdala-centered effective connectivity network associated with this trait. The current study employed the Granger Causal analysis to investigate the directional connectivity patterns involving the amygdala in relation to trait anxiety in a large cohort of young adults (N = 424). The results revealed a negative association between trait anxiety scores and the Granger causality from the left middle frontal gyrus and right superior frontal gyrus to the right amygdala. Conversely, higher trait anxiety levels were found to be associated with increased effective connectivity from the left amygdala to the left hippocampus. These results demonstrated the significance of the prefrontal cortex-amygdala-hippocampus neural circuitry in the neurobiological mechanisms underlying trait anxiety. Our findings advance the comprehension of this characteristic, holding promise for informing strategies in the prevention and treatment of related mental disorders.

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Data availability

Our data was obtained from a publicly accessible database. For specific details, please refer to this referenced literature (Liu et al., 2017).

Code availability

These data were analyzed by the following software applications available in the public domain: SPM8 (Wellcome Department of Imaging Neuroscience, University College London, U.K.), DPABI (http://rfmri.org/DPABI), the REST-GCA in the REST toolbox (http://www.restfmri.net), and the PROCESS macro Model 4 within SPSS 20.0.

References

  • Alexandra Kredlow, M., et al., (2022). Prefrontal cortex, amygdala, and threat processing: Implications for PTSD. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 47(1), 247–259.

    Article  CAS  PubMed  Google Scholar 

  • Alper, J., et al., (2023). Stress-related reduction of hippocampal subfield volumes in major depressive disorder: A 7-Tesla study. Frontiers in Psychiatry, 14, 1060770.

    Article  PubMed  PubMed Central  Google Scholar 

  • Amaral, D. G. (1992). Anatomical organization of the primate amygdaloid complex. The amygdala: Neurobiological aspects of emotion, memory, and mental dysfunction (pp. 1–66). New York, NY: Wiley-Liss.

  • Andrews, G. (1991). Anxiety, personality and anxiety disorders. International Review of Psychiatry, 3(2), 293–302.

    Article  Google Scholar 

  • Bannerman, D., et al., (2004). Regional dissociations within the hippocampus—memory and anxiety. Neuroscience Biobehavioral Reviews, 28(3), 273–283.

    Article  CAS  PubMed  Google Scholar 

  • Baur, V., et al., (2012). Volumetric associations between uncinate fasciculus, amygdala, and trait anxiety. BMC Neuroscience, 13(1), 1–8.

    Article  Google Scholar 

  • Bremner, J. D., et al., (2000). Hippocampal volume reduction in major depression. American Journal of Psychiatry, 157(1), 115–118.

    Article  CAS  PubMed  Google Scholar 

  • Burghy, C. A., et al., (2012). Developmental pathways to amygdala-prefrontal function and internalizing symptoms in adolescence. Nature Neuroscience, 15(12), 1736–1741.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cremers, H. R., et al., (2010). Neuroticism modulates amygdala—prefrontal connectivity in response to negative emotional facial expressions. NeuroImage, 49(1), 963–970.

    Article  PubMed  Google Scholar 

  • De Witte, N. A., & Mueller, S. C. (2017). White matter integrity in brain networks relevant to anxiety and depression: Evidence from the human connectome project dataset. Brain Imaging and Behavior, 11, 1604–1615.

    Article  PubMed  Google Scholar 

  • Deji, C., et al. (2022). The basolateral amygdala to ventral hippocampus circuit controls anxiety-like behaviors induced by morphine withdrawal. Frontiers in Cellular Neuroscience, 16, 894886.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dong, M., et al., (2019). A failed top-down control from the prefrontal cortex to the amygdala in generalized anxiety disorder: Evidence from resting-state fMRI with Granger causality analysis. Neuroscience Letters, 707, 134314.

    Article  CAS  PubMed  Google Scholar 

  • Etkin, A., et al., (2004). Individual differences in trait anxiety predict the response of the basolateral amygdala to unconsciously processed fearful faces. Neuron, 44(6), 1043–1055.

    Article  CAS  PubMed  Google Scholar 

  • Felix-Ortiz, A. C., et al., (2013). BLA to vHPC inputs modulate anxiety-related behaviors. Neuron, 79(4), 658–664.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Felix-Ortiz, A. C., & Tye, K. M. (2014). Amygdala inputs to the ventral hippocampus bidirectionally modulate social behavior. Journal of Neuroscience, 34(2), 586–595.

    Article  CAS  PubMed  Google Scholar 

  • Friston, K., et al., (2013). Analysing connectivity with Granger causality and dynamic causal modelling. Current Opinion in Neurobiology, 23(2), 172–178.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ghasemi, M., et al., (2022). Anxiety and hippocampal neuronal activity: Relationship and potential mechanisms. Cognitive, affective. Behavioral Neuroscience, 22(3), 431–449.

    Google Scholar 

  • Ghashghaei, H., et al., (2007). Sequence of information processing for emotions based on the anatomic dialogue between prefrontal cortex and amygdala. NeuroImage, 34(3), 905–923.

    Article  CAS  PubMed  Google Scholar 

  • Gray, J. P., et al., (2020). Multimodal abnormalities of brain structure and function in major depressive disorder: A meta-analysis of neuroimaging studies. American Journal of Psychiatry, 177(5), 422–434.

    Article  PubMed  Google Scholar 

  • Grupe, D. W., & Nitschke, J. B. (2013). Uncertainty and anticipation in anxiety: An integrated neurobiological and psychological perspective. Nature Reviews Neuroscience, 14(7), 488–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Günther, V., et al., (2020). Individual differences in anxiety and automatic amygdala response to fearful faces: A replication and extension of Etkin et al.,(2004). NeuroImage. Clinical, 28, 102441.

    Google Scholar 

  • Han, Y., et al., (2020). Factor structure and gender invariance of Chinese version state-trait anxiety inventory (form Y) in university students. Frontiers in Psychology, 11, 2228.

    Article  PubMed  PubMed Central  Google Scholar 

  • Huo, H., et al., (2020). The effect of trait anxiety on risk-taking: Functional coupling between right hippocampus and left insula. Psychophysiology, 57(10), e13629.

    Article  PubMed  Google Scholar 

  • Hyde, L. W., et al., (2011). Perceived social support moderates the link between threat-related amygdala reactivity and trait anxiety. Neuropsychologia, 49(4), 651–656.

    Article  PubMed  Google Scholar 

  • Ironside, M., et al., (2019). Effect of prefrontal cortex stimulation on regulation of amygdala response to threat in individuals with trait anxiety: A randomized clinical trial. JAMA Psychiatry, 76(1), 71–78.

    Article  PubMed  Google Scholar 

  • Kamboureli, C., & Economou, A. (2023). Trait anxiety and interference in the emotional Stroop task in young and old adults. Current Psychology, 42(11), 8887–8896.

    Article  Google Scholar 

  • Kim, M. J., Gee, D. G., Loucks, R. A., Davis, F. C., Whalen, P. J., et al. (2011a). Anxiety dissociates dorsal and ventral medial prefrontal cortex functional connectivity with the amygdala at rest. Cerebral Cortex, 21(7), 1667–1673.

    Article  PubMed  Google Scholar 

  • Kim, M. J., Loucks, R. A., Palmer, A. L., Brown, A. C., Solomon, K. M., Marchante, A. N., Whalen, P. J., et al. (2011b). The structural and functional connectivity of the amygdala: From normal emotion to pathological anxiety. Behavioural Brain Research, 223(2), 403–410.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kim, M. J., & Whalen, P. J. (2009). The structural integrity of an amygdala–prefrontal pathway predicts trait anxiety. Journal of Neuroscience, 29(37), 11614–11618.

    Article  CAS  PubMed  Google Scholar 

  • Knowles, K. A., & Olatunji, B. O. (2020). Specificity of trait anxiety in anxiety and depression: Meta-analysis of the state-trait anxiety inventory. Clinical Psychology Review, 82, 101928.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lau, J. Y., et al., (2012). Neural responses to peer rejection in anxious adolescents: Contributions from the amygdala-hippocampal complex. International Journal of Behavioral Development, 36(1), 36–44.

    Article  PubMed  Google Scholar 

  • Liao, W., et al., (2010). Altered effective connectivity network of the amygdala in social anxiety disorder: A resting-state FMRI study. PLoS ONE, 5(12), e15238.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu, W. (2017). Longitudinal test-retest neuroimaging data from healthy young adults in southwest China. Scientific data, 4(1), 1–9.

    Article  Google Scholar 

  • MacMillan, S., et al., (2003). Increased amygdala: Hippocampal volume ratios associated with severity of anxiety in pediatric major depression. Journal of Child Adolescent Psychopharmacology, 13(1), 65–73.

    Article  PubMed  Google Scholar 

  • Mah, L., et al., (2016). Can anxiety damage the brain? Current Opinion in Psychiatry, 29(1), 56–63.

    Article  PubMed  Google Scholar 

  • McClure, E. B., et al., (2004). A developmental examination of gender differences in brain engagement during evaluation of threat. Biological Psychiatry, 55(11), 1047–1055.

    Article  PubMed  Google Scholar 

  • Modi, S., et al., (2013). Individual differences in trait anxiety are associated with white matter tract integrity in fornix and uncinate fasciculus: Preliminary evidence from a DTI based tractography study. Behavioural Brain Research, 238, 188–192.

    Article  PubMed  Google Scholar 

  • Modi, S., et al., (2015). Aberrant functional connectivity of resting state networks associated with trait anxiety. Psychiatry Research: Neuroimaging, 234(1), 25–34.

    Article  Google Scholar 

  • Montag, C., et al., (2012). Individual differences in trait anxiety are associated with white matter tract integrity in the left temporal lobe in healthy males but not females. Neuroscience, 217, 77–83.

    Article  CAS  PubMed  Google Scholar 

  • Phelps, E. A., & LeDoux, J. E. (2005). Contributions of the amygdala to emotion processing: From animal models to human behavior. Neuron, 48(2), 175–187.

    Article  CAS  PubMed  Google Scholar 

  • Phillips, R., & LeDoux, J. (1992). Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behavioral Neuroscience, 106(2), 274.

    Article  CAS  PubMed  Google Scholar 

  • Porta-Casteràs, D., et al., (2020). Prefrontal-amygdala connectivity in trait anxiety and generalized anxiety disorder: Testing the boundaries between healthy and pathological worries. Journal of Affective Disorders, 267, 211–219.

    Article  PubMed  Google Scholar 

  • Qiao, J., et al., (2017). Aberrant functional network connectivity as a biomarker of generalized anxiety disorder. Frontiers in Human Neuroscience, 11, 626.

    Article  PubMed  PubMed Central  Google Scholar 

  • Qin, S., et al., (2014). Amygdala subregional structure and intrinsic functional connectivity predicts individual differences in anxiety during early childhood. Biological Psychiatry, 75(11), 892–900.

    Article  PubMed  Google Scholar 

  • Satpute, A. B. (2012). Human anterior and posterior hippocampus respond distinctly to state and trait anxiety. Emotion, 12(1), 58.

    Article  PubMed  Google Scholar 

  • Saviola, F., et al., (2020). Trait and state anxiety are mapped differently in the human brain. Scientific Reports, 10(1), 1–11.

    Article  Google Scholar 

  • Schienle, A., et al., (2011). Localized gray matter volume abnormalities in generalized anxiety disorder. European Archives of Psychiatry and Clinical Neuroscience, 261, 303–307.

    Article  PubMed  Google Scholar 

  • Seth, A. K., et al., (2015). Granger causality analysis in neuroscience and neuroimaging. Journal of Neuroscience, 35(8), 3293–3297.

    Article  CAS  PubMed  Google Scholar 

  • Shan, X., et al., (2023). Abnormal causal connectivity of prefrontal-limbic circuit by structural deficits in drug-naive anxiety disorders. Journal of Psychiatric Research, 163, 14–23.

    Article  PubMed  Google Scholar 

  • Shek, D. T. (1988). Reliability and factorial structure of the Chinese version of the state-trait anxiety inventory. Journal of Psychopathology and Behavioral Assessment, 10, 303–317.

    Article  Google Scholar 

  • Song, X. W., et al., (2011). REST: A toolkit for resting-state functional magnetic resonance imaging data processing. PLoS ONE, 6(9), e25031.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Spielberger, C. D. (1983). State-trait anxiety inventory for adults. Consulting Psychologists Press: Palo Alto, CA.

  • Tian, X., et al., (2016). Assessment of trait anxiety and prediction of changes in state anxiety using functional brain imaging: A test–retest study. NeuroImage, 133, 408–416.

    Article  PubMed  Google Scholar 

  • Tovote, P., et al., (2015). Neuronal circuits for fear and anxiety. Nature Reviews Neuroscience, 16(6), 317–331.

    Article  CAS  PubMed  Google Scholar 

  • Tzourio-Mazoyer, N., et al., (2007). Neuroanatomy: Tool for functional localization, key to brain organization. NeuroImage, 37(4), 1059–1060.

    Article  CAS  PubMed  Google Scholar 

  • VanElzakker, M. B., et al., (2014). From Pavlov to PTSD: The extinction of conditioned fear in rodents, humans, and anxiety disorders. Neurobiology of Learning Memory, 113, 3–18.

    Article  PubMed  Google Scholar 

  • Xu, J., et al., (2019). Anxious brain networks: A coordinate-based activation likelihood estimation meta-analysis of resting-state functional connectivity studies in anxiety. Neuroscience Biobehavioral Reviews, 96, 21–30.

    Article  PubMed  Google Scholar 

  • Yan, C. G. (2016). DPABI: Data Processing and Analysis for (Resting-State) Brain Imaging. Neuroinformatics, 14(3), 339–351.

    Article  PubMed  Google Scholar 

  • Yang, X., et al., (2021). Global, regional and national burden of anxiety disorders from 1990 to 2019: Results from the global burden of Disease Study 2019. Epidemiology Psychiatric Sciences, 30, e36.

    Article  PubMed  PubMed Central  Google Scholar 

  • Yoo, C., et al. (2022). Structural connectome-based prediction of trait anxiety. Brain Imaging and Behavior, 16(6), 2467–2476.

    Article  PubMed  Google Scholar 

  • Young, K. S., et al., (2017). Treatment for social anxiety disorder alters functional connectivity in emotion regulation neural circuitry. Psychiatry Research: Neuroimaging, 261, 44–51.

    Article  PubMed  Google Scholar 

  • Zhang, J. Y., et al., (2019). Chronic stress remodels synapses in an amygdala circuit–specific manner. Biological Psychiatry, 85(3), 189–201.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, Q. (2022). The causal relationship of trait anxiety to positive and negative attentional bias in children: the moderation effect of gender. Current Psychology, 42(30), 26388–26397.

    Article  Google Scholar 

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Funding

This work was supported by the Natural Scientific Foundation of China (32100873) and the Fundamental Research Funds for the Central Universities (2072021132).

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Authors and Affiliations

  1. Institute of Psychology, School of Public Policy, Xiamen University, Xiamen, China

    Jingjing Chang

  2. Department of Neurology, Affiliated Hospital of Chengdu University, Chengdu, China

    Xin Liu

  3. School of Psychology, Nanjing Normal University, Nanjing, 210097, China

    Song Xue

  4. Faculty of Psychology, Key Laboratory of Cognition and Personality, Southwest University, Ministry of Education, Chongqing, China

    Song Xue & Jiang Qiu

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  1. Jingjing Chang
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  2. Xin Liu
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  4. Jiang Qiu
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Contributions

S.X. and J.Q. designed the study; J.J.C., X.L. and S.X. analyzed and interpreted the data; J.J.C., X.L. and S.X wrote the manuscript; All authors reviewed the manuscript.

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Correspondence to Song Xue.

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Chang, J., Liu, X., Xue, S. et al. An amygdala-centered effective connectivity network in trait anxiety. Brain Imaging and Behavior (2023). https://doi.org/10.1007/s11682-023-00837-8

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