Skip to main content
SpringerLink
Log in

Cerebellar Neural Circuits Involving Executive Control Network Predict Response to Group Cognitive Behavior Therapy in Social Anxiety Disorder

  • Original Paper
  • Published:
The Cerebellum Aims and scope Submit manuscript

Abstract

Some intrinsic connectivity networks including the default mode network (DMN) and executive control network (ECN) may underlie social anxiety disorder (SAD). Although the cerebellum has been implicated in the pathophysiology of SAD and several networks relevant to higher-order cognition, it remains unknown whether cerebellar areas involved in DMN and ECN exhibit altered resting-state functional connectivity (rsFC) with cortical networks in SAD. Forty-six patients with SAD and 64 healthy controls (HC) were included and submitted to the baseline resting-state functional magnetic resonance imaging (fMRI). Seventeen SAD patients who completed post-treatment clinical assessments were included after group cognitive behavior therapy (CBT). RsFC of three cerebellar subregions in both groups was assessed respectively in a voxel-wise way, and these rsFC maps were compared by two-sample t tests between groups. Whole-brain voxel-wise regression was performed to examine whether cerebellar connectivity networks can predict response to CBT. Lower rsFC circuits of cerebellar subregions compared with HC at baseline (p < 0.05, corrected by false discovery rate) were revealed. The left Crus I rsFC with dorsal medial prefrontal cortex was negatively correlated with symptom severity. The clinical assessments in SAD patients were significantly decreased after CBT. Higher pretreatment cerebellar rsFC with angular gyrus and dorsal lateral frontal cortex corresponded with greater symptom improvement following CBT. Cerebellar rsFC circuits involving DMN and ECN are possible neuropathologic mechanisms of SAD. Stronger pretreatment cerebellar rsFC circuits involving ECN suggest potential neural markers to predict CBT response.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Stein MB, Stein DJ. Social anxiety disorder. Lancet. 2008;371:1115–25.

    Article  PubMed  Google Scholar 

  2. Goldin PR, Manber T, Hakimi S, Canli T, Gross JJ. Neural bases of social anxiety disorder: emotional reactivity and cognitive regulation during social and physical threat. Arch Gen Psychiatry. 2009;66:170–80.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Bruhl AB, Delsignore A, Komossa K, Weidt S. Neuroimaging in social anxiety disorder—a meta-analytic review resulting in a new neurofunctional model. Neurosci Biobehav Rev. 2014;47C:260–80.

    Article  Google Scholar 

  4. Fox MD, Raichle ME. Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci. 2007;8:700–11.

    Article  CAS  PubMed  Google Scholar 

  5. Greicius MD, Krasnow B, Reiss AL, Menon V. Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc Natl Acad Sci U S A. 2003;100:253–8.

    Article  CAS  PubMed  Google Scholar 

  6. Beckmann CF, DeLuca M, Devlin JT, Smith SM. Investigations into resting-state connectivity using independent component analysis. Philos Trans R Soc Lond Ser B Biol Sci. 2005;360:1001–13.

    Article  Google Scholar 

  7. Mantini D, Vanduffel W. Emerging roles of the brain’s default network. Neuroscientist. 2013;19:76–87.

    Article  PubMed  Google Scholar 

  8. Seeley WW, Menon V, Schatzberg AF, Keller J, Glover GH, Kenna H, et al. Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci. 2007;27:2349–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Liao W, Chen H, Feng Y, Mantini D, Gentili C, Pan Z, et al. Selective aberrant functional connectivity of resting state networks in social anxiety disorder. NeuroImage. 2010;52:1549–58.

    Article  PubMed  Google Scholar 

  10. Liao W, Xu Q, Mantini D, Ding J, Machado-de-Sousa JP, Hallak JE, et al. Altered gray matter morphometry and resting-state functional and structural connectivity in social anxiety disorder. Brain Res. 2011;1388:167–77.

    Article  CAS  PubMed  Google Scholar 

  11. Gentili C, Ricciardi E, Gobbini MI, Santarelli MF, Haxby JV, Pietrini P, et al. Beyond amygdala: default mode network activity differs between patients with social phobia and healthy controls. Brain Res Bull. 2009;79:409–13.

    Article  PubMed  Google Scholar 

  12. Hahn A, Stein P, Windischberger C, Weissenbacher A, Spindelegger C, Moser E, et al. Reduced resting-state functional connectivity between amygdala and orbitofrontal cortex in social anxiety disorder. NeuroImage. 2011;56:881–9.

    Article  PubMed  Google Scholar 

  13. Geiger MJ, Domschke K, Ipser J, Hattingh C, Baldwin DS, Lochner C, et al. Altered executive control network resting-state connectivity in social anxiety disorder. World J Biol Psychiatry. 2016;17:47–57.

    Article  PubMed  Google Scholar 

  14. Bastian AJ. Learning to predict the future: the cerebellum adapts feedforward movement control. Curr Opin Neurobiol. 2006;16:645–9.

    Article  CAS  PubMed  Google Scholar 

  15. Ouchi Y, Okada H, Yoshikawa E, Nobezawa S, Futatsubashi M. Brain activation during maintenance of standing postures in humans. Brain. 1999;122(Pt 2):329–38.

    Article  PubMed  Google Scholar 

  16. Bostan AC, Dum RP, Strick PL. Cerebellar networks with the cerebral cortex and basal ganglia. Trends Cogn Sci. 2013;17:241–54.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Timmann D, Drepper J, Frings M, Maschke M, Richter S, Gerwig M, et al. The human cerebellum contributes to motor, emotional and cognitive associative learning. A review. Cortex. 2010;46:845–57.

    Article  CAS  PubMed  Google Scholar 

  18. Stoodley CJ. The cerebellum and cognition: evidence from functional imaging studies. Cerebellum. 2012;11:352–65.

    Article  PubMed  Google Scholar 

  19. Nakao T, Sanematsu H, Yoshiura T, Togao O, Murayama K, Tomita M, et al. fMRI of patients with social anxiety disorder during a social situation task. Neurosci Res. 2011;69:67–72.

    Article  PubMed  Google Scholar 

  20. Warwick JM, Carey P, Jordaan GP, Dupont P, Stein DJ. Resting brain perfusion in social anxiety disorder: a voxel-wise whole brain comparison with healthy control subjects. Prog Neuro-Psychopharmacol Biol Psychiatry. 2008;32:1251–6.

    Article  CAS  Google Scholar 

  21. Talati A, Pantazatos SP, Schneier FR, Weissman MM, Hirsch J. Gray matter abnormalities in social anxiety disorder: primary, replication, and specificity studies. Biol Psychiatry. 2013;73:75–84.

    Article  PubMed  Google Scholar 

  22. Tillfors M, Furmark T, Marteinsdottir I, Fredrikson M. Cerebral blood flow during anticipation of public speaking in social phobia: a PET study. Biol Psychiatry. 2002;52:1113–9.

    Article  PubMed  Google Scholar 

  23. Yuan ML, Ren ZJ, Zhu HR, Zhang Y, Meng YJ, Zhang W. Regional homogeneity changes in social anxiety disorder after cognitive behavioral therapy. J Sichuan Univ (Med Sci Edi). 2016;47:898–903.

    Google Scholar 

  24. Buckner RL, Krienen FM, Castellanos A, Diaz JC, Yeo BT. The organization of the human cerebellum estimated by intrinsic functional connectivity. J Neurophysiol. 2011;106:2322–45.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Habas C, Kamdar N, Nguyen D, Prater K, Beckmann CF, Menon V, et al. Distinct cerebellar contributions to intrinsic connectivity networks. J Neurosci. 2009;29:8586–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. O'Reilly JX, Beckmann CF, Tomassini V, Ramnani N, Johansen-Berg H. Distinct and overlapping functional zones in the cerebellum defined by resting state functional connectivity. Cereb Cortex. 2010;20:953–65.

    Article  PubMed  Google Scholar 

  27. Krienen FM, Buckner RL. Segregated fronto-cerebellar circuits revealed by intrinsic functional connectivity. Cereb Cortex. 2009;19:2485–97.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Sang L, Qin W, Liu Y, Han W, Zhang Y, Jiang T, et al. Resting-state functional connectivity of the vermal and hemispheric subregions of the cerebellum with both the cerebral cortical networks and subcortical structures. NeuroImage. 2012;61:1213–25.

    Article  PubMed  Google Scholar 

  29. Halko MA, Farzan F, Eldaief MC, Schmahmann JD, Pascual-Leone A. Intermittent theta-burst stimulation of the lateral cerebellum increases functional connectivity of the default network. J Neurosci. 2014;34:12049–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Caulfield MD, Zhu DC, McAuley JD, Servatius RJ. Individual differences in resting-state functional connectivity with the executive network: support for a cerebellar role in anxiety vulnerability. Brain Struct Funct. 2016;221:3081–93.

    Article  PubMed  Google Scholar 

  31. Whitfield-Gabrieli S, Ghosh SS, Nieto-Castanon A, Saygin Z, Doehrmann O, Chai XJ, et al. Brain connectomics predict response to treatment in social anxiety disorder. Mol Psychiatry. 2016;21:680–5.

    Article  CAS  PubMed  Google Scholar 

  32. Hofmann SG, Otto MW. Behavioral therapy for social anxiety disorder: evidence-based and disorder-specific treatment techniques. New York: Routledge; 2008.

    Google Scholar 

  33. Heimberg RG, Horner KJ, Juster HR, Safren SA, Brown EJ, Schneier FR, et al. Psychometric properties of the Liebowitz Social Anxiety Scale. Psychol Med. 1999;29:199–212.

    Article  CAS  PubMed  Google Scholar 

  34. Rytwinski NK, Fresco DM, Heimberg RG, Coles ME, Liebowitz MR, Cissell S, et al. Screening for social anxiety disorder with the self-report version of the Liebowitz Social Anxiety Scale. Depress Anxiety. 2009;26:34–8.

    Article  PubMed  Google Scholar 

  35. Spielberger CD, Gorsuch R, Lushene R, Vagg PR, Jacobs GA. Manual for the State-Trait Anxiety Inventory (Form Y). Palo Alto: Consulting Psychologists Press; 1983.

  36. Fox MD, Snyder AZ, Vincent JL, Corbetta M, Van Essen DC, Raichle ME. The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci U S A. 2005;102:9673–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Gotts SJ, Saad ZS, Jo HJ, Wallace GL, Cox RW, Martin A. The perils of global signal regression for group comparisons: a case study of autism spectrum disorders. Front Hum Neurosci. 2013;7:356.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Saad ZS, Gotts SJ, Murphy K, Chen G, Jo HJ, Martin A, et al. Trouble at rest: how correlation patterns and group differences become distorted after global signal regression. Brain Connect. 2012;2:25–32.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Diedrichsen J, Balsters JH, Flavell J, Cussans E, Ramnani N. A probabilistic MR atlas of the human cerebellum. NeuroImage. 2009;46:39–46.

    Article  PubMed  Google Scholar 

  40. Mennin DS, Fresco DM, Heimberg RG, Schneier FR, Davies SO, Liebowitz MR. Screening for social anxiety disorder in the clinical setting: using the Liebowitz Social Anxiety Scale. J Anxiety Disord. 2002;16:661–73.

    Article  PubMed  Google Scholar 

  41. Stoodley CJ, Schmahmann JD. Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing. Cortex. 2010;46:831–44.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Kelly RM, Strick PL. Cerebellar loops with motor cortex and prefrontal cortex of a nonhuman primate. J Neurosci. 2003;23:8432–44.

    CAS  PubMed  Google Scholar 

  43. Schmahmann JD, Pandya DN. The cerebrocerebellar system. Int Rev Neurobiol. 1997;41:31–60.

    Article  CAS  PubMed  Google Scholar 

  44. Buckner RL, Andrews-Hanna JR, Schacter DL. The brain’s default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci. 2008;1124:1–38.

    Article  PubMed  Google Scholar 

  45. Spreng RN, Mar RA, Kim AS. The common neural basis of autobiographical memory, prospection, navigation, theory of mind, and the default mode: a quantitative meta-analysis. J Cogn Neurosci. 2009;21:489–510.

    Article  PubMed  Google Scholar 

  46. Lemogne C, Delaveau P, Freton M, Guionnet S, Fossati P. Medial prefrontal cortex and the self in major depression. J Affect Disord. 2012;136:e1–e11.

    Article  PubMed  Google Scholar 

  47. Sylvester CM, Corbetta M, Raichle ME, Rodebaugh TL, Schlaggar BL, Sheline YI, et al. Functional network dysfunction in anxiety and anxiety disorders. Trends Neurosci. 2012;35:527–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Duncan J, Owen AM. Common regions of the human frontal lobe recruited by diverse cognitive demands. Trends Neurosci. 2000;23:475–83.

    Article  CAS  PubMed  Google Scholar 

  49. Ochsner KN, Gross JJ. The cognitive control of emotion. Trends Cogn Sci. 2005;9:242–9.

    Article  PubMed  Google Scholar 

  50. Hofmann SG. Cognitive factors that maintain social anxiety disorder: a comprehensive model and its treatment implications. Cogn Behav Ther. 2007;36:193–209.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Salmi J, Pallesen KJ, Neuvonen T, Brattico E, Korvenoja A, Salonen O, et al. Cognitive and motor loops of the human cerebro-cerebellar system. J Cogn Neurosci. 2010;22:2663–76.

    Article  PubMed  Google Scholar 

  52. Bruhl AB, Rufer M, Delsignore A, Kaffenberger T, Jancke L, Herwig U. Neural correlates of altered general emotion processing in social anxiety disorder. Brain Res. 2011;1378:72–83.

    Article  PubMed  Google Scholar 

  53. Meng Y, Lui S, Qiu C, Qiu L, Lama S, Huang X, et al. Neuroanatomical deficits in drug-naive adult patients with generalized social anxiety disorder: a voxel-based morphometry study. Psychiatry Res. 2013;214:9–15.

    Article  PubMed  Google Scholar 

  54. Levisohn L, Cronin-Golomb A, Schmahmann JD. Neuropsychological consequences of cerebellar tumour resection in children. Brain. 2000;123:1041–50.

    Article  PubMed  Google Scholar 

  55. Mathew SJ, Coplan JD, Gorman JM. Neurobiological mechanisms of social anxiety disorder. Am J Psychiatry. 2001;158:1558–67.

    Article  CAS  PubMed  Google Scholar 

  56. Hambrick JP, Turk CL, Heimberg RG, Schneier FR, Liebowitz MR. The experience of disability and quality of life in social anxiety disorder. Depress Anxiety. 2003;18:46–50.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge the contributions of Hehan Tang, Cui Yuan, and Meng Gao.

Author information

Authors and Affiliations

  1. Mental Health Center, West China Hospital of Sichuan University, No. 37 GuoXue Xiang, Chengdu, 610041, China

    MinlanYuan, Yajing Meng, Yan Zhang, Xiaojing Nie, Zhengjia Ren, Hongru Zhu, Yuchen Li, Changjian Qiu & Wei Zhang

  2. State Key Laboratory of Biotherapy, Psychiatric Laboratory, West China Hospital of Sichuan University, Chengdu, Sichuan, China

    Yajing Meng, Hongru Zhu & Wei Zhang

  3. Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China

    Su Lui & Qiyong Gong

  4. Radiology Department of the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China

    Su Lui

Authors
  1. MinlanYuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yajing Meng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaojing Nie
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhengjia Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hongru Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yuchen Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Su Lui
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Qiyong Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Changjian Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Wei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Changjian Qiu or Wei Zhang.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Role of Funding Source

This work was supported by the National Natural Science Foundation of China (grant nos. 81371484, 81222018, 81030027, 81227002, and 81220108013), National Key Technologies R&D Program (program no. 2012BAI01B03), the 863 Program (grant no. 2008AA02Z408), the 973 Project (grant no. 2008CB517407), and the Support Plan of Sichuan (grant nos. 2011SZ0292, 2014GZ0143). This research received no specific grant from any funding agency, commercial, or not-for-profit sectors.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Additional information

Minlan Yuan and Yajing Meng contributed equally to this study.

Electronic Supplementary Material

ESM 1

(DOCX 23 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

MinlanYuan, Meng, Y., Zhang, Y. et al. Cerebellar Neural Circuits Involving Executive Control Network Predict Response to Group Cognitive Behavior Therapy in Social Anxiety Disorder. Cerebellum 16, 673–682 (2017). https://doi.org/10.1007/s12311-017-0845-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12311-017-0845-x

Keywords

Search

Navigation