Altered resting-state amygdala functional connectivity in men with posttraumatic stress disorder

Altered resting-state amygdala functional connectivity in men with posttraumatic stress disorder


J Psychiatry Neurosci 2012;37(4):241-49

Rebecca K. Sripada, MS; Anthony P. King, PhD; Sarah N. Garfinkel, PhD; Xin Wang, MD; Chandra S. Sripada, MD; Robert C. Welsh, PhD; Israel Liberzon, MD

R.K. Sripada, Liberzon — Department of Psychology, University of Michigan, Ann Arbor, Mich.; R.K. Sripada, King, Wang, C.S. Sripada, Welsh, Liberzon — Department of Psychiatry, University of Michigan, Ann Arbor, Mich.; Garfinkel — Brighton and Sussex Medical School, Brighton, United Kingdom; Welsh — Department of Radiology, University of Michigan, Ann Arbor, Mich.


Background: Converging neuroimaging research suggests altered emotion neurocircuitry in individuals with posttraumatic stress disorder (PTSD). Emotion activation studies in these individuals have shown hyperactivation in emotion-related regions, including the amygdala and insula, and hypoactivation in emotion-regulation regions, including the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). However, few studies have examined patterns of connectivity at rest in individuals with PTSD, a potentially powerful method for illuminating brain network structure.

Methods: Using the amygdala as a seed region, we measured resting-state brain connectivity using 3 T functional magnetic resonance imaging in returning male veterans with PTSD and combat controls without PTSD.

Results: Fifteen veterans with PTSD and 14 combat controls enrolled in our study. Compared with controls, veterans with PTSD showed greater positive connectivity between the amygdala and insula, reduced positive connectivity between the amygdala and hippocampus, and reduced anticorrelation between the amygdala and dorsal ACC and rostral ACC.

Limitations: Only male veterans with combat exposure were tested, thus our findings cannot be generalized to women or to individuals with non–combat related PTSD.

Conclusion: These results demonstrate that studies of functional connectivity during resting state can discern aberrant patterns of coupling within emotion circuits and suggest a possible brain basis for emotion-processing and emotion-regulation deficits in individuals with PTSD.

Submitted July 8, 2011; Revised Oct. 21, 31, Nov. 15, 2011; Accepted Nov. 16, 2011.

Acknowledgements: The research reported in this article was supported by grants from the National Institute of Mental Health (R24 MH075999) to I. Liberzon, from the Telemedicine and Advanced Technology Research Center (W81XWH-08-2-0208) to I. Liberzon and A.P. King, from the Michigan Institute for Clinical & Health Research (U028028) to S.N. Garfinkel and from the University of Michigan Center for Computational Medicine and Bioinformatics Pilot Grant Program to A.P. King.

Competing interests: None declared for R.K. Sripada, X. Wang, C.S. Sripada and R.C. Welsh. As above for A.P. King, S.N. Garfinkel and I. Liberzon.

Contributors: R.K. Sripada, A.P. King and I. Liberzon designed the study. R.K. Sripada, A.P. King, S.N. Garfinkel, X. Wang, C.S. Sripada, R.C. Welsh and I. Liberzon acquired the data. R.K. Sripada, A.P. King, C.S. Sripada and R.C. Welsh analyzed the data. R.K. Sripada wrote the article. All authors reviewed the article and approved its publication.

DOI: 10.1503/jpn.110069

Correspondence to: R.K. Sripada, 4250 Plymouth Rd., 2702 Rachel Upjohn Bldg., Ann Arbor MI 48109;