Resting-state connectivity of the bed nucleus of the stria terminalis and the central nucleus of the amygdala in clinical anxiety

Resting-state connectivity of the bed nucleus of the stria terminalis and the central nucleus of the amygdala in clinical anxiety

J Psychiatry Neurosci 2019;44(5):313-323 | PDF | Appendix

Salvatore Torrisi, PhD; Gabriella M. Alvarez, BA; Adam X. Gorka, PhD; Bari Fuchs, BA; Marilla Geraci, MSN; Christian Grillon, PhD*; Monique Ernst, MD, PhD*

Background: The central nucleus of the amygdala and bed nucleus of the stria terminalis are involved primarily in phasic and sustained aversive states. Although both structures have been implicated in pathological anxiety, few studies with a clinical population have specifically focused on them, partly because of their small size. Previous work in our group used high-resolution imaging to map the resting-state functional connectivity of the bed nucleus of the stria terminalis and the central nucleus of the amygdala in healthy subjects at 7 T, confirming and extending structural findings in humans and animals, while providing additional insight into cortical connectivity that is potentially unique to humans.

Methods: In the current follow-up study, we contrasted resting-state functional connectivity in the bed nucleus of the stria terminalis and central nucleus of the amygdala at 7 T between healthy volunteers (n = 30) and patients with generalized and/or social anxiety disorder (n = 30).

Results: Results revealed significant voxel-level group differences. Compared with healthy volunteers, patients showed stronger resting-state functional connectivity between the central nucleus of the amygdala and the lateral orbitofrontal cortex and superior temporal sulcus. They also showed weaker resting-state functional connectivity between the bed nucleus of the stria terminalis and the dorsolateral prefrontal cortex and occipital cortex.

Limitations: These findings depart from a previous report of resting-state functional connectivity in the central nucleus of the amygdala and bed nucleus of the stria terminalis under sustained threat of shock in healthy volunteers.

Conclusion: This study provides functional MRI proxies of the functional dissociation of the bed nucleus of the stria terminalis and central nucleus of the amygdala, and suggests that resting-state functional connectivity of key structures in the processing of defensive responses do not recapitulate changes related to induced state anxiety. Future work needs to replicate and further probe the clinical significance of these findings.


*These authors contributed equally to this work.

Submitted Sep. 2, 2018; Revised Dec. 11, 2018; Accepted Jan. 16, 2019; Published online Apr. 9, 2019

Acknowledgements: This research was supported (in part) by the Intramural Research Program of the National Institute of Mental Health. The authors thank Katherine O’Connell and Andrew Davis for assistance with data collection, Nicholas Balderston for manuscript commentary, and Gang Chen and Justin Rajendra for guidance with statistical imputation. This work used the computational resources of the National Institutes of Health HPC Biowulf cluster (http://hpc.nih.gov). This work was supported by the Intramural Research Program of the National Institute of Mental Health, project number ZIAMH002798 (clinical protocol 02-M-0321, NCT00047853) to C. Grillon.

Affiliations: From the Section on the Neurobiology of Fear and Anxiety, National Institute of Mental Health, Bethesda, MD, USA (Torrisi, Alvarez, Gorka, Fuchs, Geraci, Grillon, Ernst).

Competing interests: None declared.

Contributors: S. Torrisi, C. Grillon and M. Ernst designed the study. S. Torrisi, G. Alvarez, B. Fuchs and M. Geraci acquired the data, which S. Torrisi, G. Alvarez, A. Gorka, B. Fuchs, C. Grillon and M. Ernst analyzed. S. Torrisi, G. Alvarez, C. Grillon and M. Ernst wrote the article, which all authors reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.

DOI: 10.1503/cjs.180150

Correspondence to: S. Torrisi, Building 15K, Room 203, National Institute of Mental Health, Bethesda, MD, 20814; sam.torrisi@nih.gov