. 2024 Aug:176:173-181.

doi: 10.1016/j.jpsychires.2024.06.009. Epub 2024 Jun 7.

Probing the neurocardiac circuit in trauma and posttraumatic stress

Antonia V Seligowski¹, Nathaniel G Harnett², Robyn A Ellis², Lana R Grasser³, Mubeena Hanif³, Charis Wiltshire³, Timothy D Ely⁴, Lauren A M Lebois², Sanne J H van Rooij⁴, Stacey L House⁵, Francesca L Beaudoin⁶, Xinming An⁷, Thomas C Neylan⁸, Gari D Clifford⁹, Sarah D Linnstaedt⁷, Laura T Germine¹⁰, Kenneth A Bollen¹¹, Scott L Rauch¹², John P Haran¹³, Alan B Storrow¹⁴, Christopher Lewandowski¹⁵, Paul I Musey Jr¹⁶, Phyllis L Hendry¹⁷, Sophia Sheikh¹⁷, Christopher W Jones¹⁸, Brittany E Punches¹⁹, Robert A Swor²⁰, Lauren A Hudak²¹, Jose L Pascual²², Mark J Seamon²³, Erica Harris²⁴, Claire Pearson²⁵, David A Peak²⁶, Roland C Merchant²⁷, Robert M Domeier²⁸, Niels K Rathlev²⁹, Brian J O'Neil³⁰, Paulina Sergot³¹, Leon D Sanchez³², Steven E Bruce³³, Steven E Harte³⁴, Karestan C Koenen³⁵, Ronald C Kessler³⁶, Samuel A McLean³⁷, Kerry J Ressler², Jennifer S Stevens⁴, Tanja Jovanovic³

Affiliations

¹ Massachusetts General Hospital, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA. Electronic address: aseligowski@mgh.harvard.edu.
² Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Division of Depression and Anxiety, McLean Hospital, Belmont, MA, USA.
³ Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, MI, USA.
⁴ Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
⁵ Department of Emergency Medicine, Washington University School of Medicine, St. Louis, MO, USA.
⁶ Department of Epidemiology, Brown University, Providence, RI, USA; Department of Emergency Medicine, Brown University, Providence, RI, USA.
⁷ Institute for Trauma Recovery, Department of Anesthesiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁸ Departments of Psychiatry and Neurology, University of California San Francisco, San Francisco, CA, USA.
⁹ Department of Biomedical Informatics, Emory University School of Medicine, Atlanta, GA, USA; Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
¹⁰ Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Institute for Technology in Psychiatry, McLean Hospital, Belmont, MA, USA; The Many Brains Project, Belmont, MA, USA.
¹¹ Department of Psychology and Neuroscience & Department of Sociology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹² Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Institute for Technology in Psychiatry, McLean Hospital, Belmont, MA, USA; Department of Psychiatry, McLean Hospital, Belmont, MA, USA.
¹³ Department of Emergency Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
¹⁴ Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁵ Department of Emergency Medicine, Henry Ford Health System, Detroit, MI, USA.
¹⁶ Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
¹⁷ Department of Emergency Medicine, University of Florida College of Medicine -Jacksonville, Jacksonville, FL, USA.
¹⁸ Department of Emergency Medicine, Cooper Medical School of Rowan University, Camden, NJ, USA.
¹⁹ Department of Emergency Medicine, Ohio State University College of Medicine, Columbus, OH, USA; Ohio State University College of Nursing, Columbus, OH, USA.
²⁰ Department of Emergency Medicine, Oakland University William Beaumont School of Medicine, Rochester, MI, USA.
²¹ Department of Emergency Medicine, Emory University School of Medicine, Atlanta, GA, USA.
²² Department of Surgery, Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
²³ Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Surgery, Division of Traumatology, Surgical Critical Care and Emergency Surgery, University of Pennsylvania, Philadelphia, PA, USA.
²⁴ Department of Emergency Medicine, Einstein Medical Center, Philadelphia, PA, USA.
²⁵ Department of Emergency Medicine, Wayne State University, Ascension St. John Hospital, Detroit, MI, USA.
²⁶ Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
²⁷ Department of Emergency Medicine, Brigham and Women's Hospital, Boston, MA, USA.
²⁸ Department of Emergency Medicine, Trinity Health-Ann Arbor, Ypsilanti, MI, USA.
²⁹ Department of Emergency Medicine, University of Massachusetts Medical School-Baystate, Springfield, MA, USA.
³⁰ Department of Emergency Medicine, Wayne State University, Detroit Receiving Hospital, Detroit, MI, USA.
³¹ Department of Emergency Medicine, McGovern Medical School at UTHealth, Houston, TX, USA.
³² Department of Emergency Medicine, Brigham and Women's Hospital, Boston, MA, USA; Department of Emergency Medicine, Harvard Medical School, Boston, MA, USA.
³³ Department of Psychological Sciences, University of Missouri - St. Louis, St. Louis, MO, USA.
³⁴ Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Internal Medicine-Rheumatology, University of Michigan Medical School, Ann Arbor, MI, USA.
³⁵ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
³⁶ Department of Health Care Policy, Harvard Medical School, Boston, MA, USA.
³⁷ Department of Emergency Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Institute for Trauma Recovery, Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

PMID: 38875773
PMCID: PMC11283955
DOI: 10.1016/j.jpsychires.2024.06.009

Probing the neurocardiac circuit in trauma and posttraumatic stress

Antonia V Seligowski et al. J Psychiatr Res. 2024 Aug.

. 2024 Aug:176:173-181.

doi: 10.1016/j.jpsychires.2024.06.009. Epub 2024 Jun 7.

Authors

Affiliations

¹ Massachusetts General Hospital, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA. Electronic address: aseligowski@mgh.harvard.edu.
² Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Division of Depression and Anxiety, McLean Hospital, Belmont, MA, USA.
³ Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, MI, USA.
⁴ Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
⁵ Department of Emergency Medicine, Washington University School of Medicine, St. Louis, MO, USA.
⁶ Department of Epidemiology, Brown University, Providence, RI, USA; Department of Emergency Medicine, Brown University, Providence, RI, USA.
⁷ Institute for Trauma Recovery, Department of Anesthesiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁸ Departments of Psychiatry and Neurology, University of California San Francisco, San Francisco, CA, USA.
⁹ Department of Biomedical Informatics, Emory University School of Medicine, Atlanta, GA, USA; Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
¹⁰ Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Institute for Technology in Psychiatry, McLean Hospital, Belmont, MA, USA; The Many Brains Project, Belmont, MA, USA.
¹¹ Department of Psychology and Neuroscience & Department of Sociology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹² Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Institute for Technology in Psychiatry, McLean Hospital, Belmont, MA, USA; Department of Psychiatry, McLean Hospital, Belmont, MA, USA.
¹³ Department of Emergency Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
¹⁴ Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁵ Department of Emergency Medicine, Henry Ford Health System, Detroit, MI, USA.
¹⁶ Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
¹⁷ Department of Emergency Medicine, University of Florida College of Medicine -Jacksonville, Jacksonville, FL, USA.
¹⁸ Department of Emergency Medicine, Cooper Medical School of Rowan University, Camden, NJ, USA.
¹⁹ Department of Emergency Medicine, Ohio State University College of Medicine, Columbus, OH, USA; Ohio State University College of Nursing, Columbus, OH, USA.
²⁰ Department of Emergency Medicine, Oakland University William Beaumont School of Medicine, Rochester, MI, USA.
²¹ Department of Emergency Medicine, Emory University School of Medicine, Atlanta, GA, USA.
²² Department of Surgery, Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
²³ Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Surgery, Division of Traumatology, Surgical Critical Care and Emergency Surgery, University of Pennsylvania, Philadelphia, PA, USA.
²⁴ Department of Emergency Medicine, Einstein Medical Center, Philadelphia, PA, USA.
²⁵ Department of Emergency Medicine, Wayne State University, Ascension St. John Hospital, Detroit, MI, USA.
²⁶ Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
²⁷ Department of Emergency Medicine, Brigham and Women's Hospital, Boston, MA, USA.
²⁸ Department of Emergency Medicine, Trinity Health-Ann Arbor, Ypsilanti, MI, USA.
²⁹ Department of Emergency Medicine, University of Massachusetts Medical School-Baystate, Springfield, MA, USA.
³⁰ Department of Emergency Medicine, Wayne State University, Detroit Receiving Hospital, Detroit, MI, USA.
³¹ Department of Emergency Medicine, McGovern Medical School at UTHealth, Houston, TX, USA.
³² Department of Emergency Medicine, Brigham and Women's Hospital, Boston, MA, USA; Department of Emergency Medicine, Harvard Medical School, Boston, MA, USA.
³³ Department of Psychological Sciences, University of Missouri - St. Louis, St. Louis, MO, USA.
³⁴ Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Internal Medicine-Rheumatology, University of Michigan Medical School, Ann Arbor, MI, USA.
³⁵ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
³⁶ Department of Health Care Policy, Harvard Medical School, Boston, MA, USA.
³⁷ Department of Emergency Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Institute for Trauma Recovery, Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

PMID: 38875773
PMCID: PMC11283955
DOI: 10.1016/j.jpsychires.2024.06.009

Abstract

The neurocardiac circuit is integral to physiological regulation of threat and trauma-related responses. However, few direct investigations of brain-behavior associations with replicable physiological markers of PTSD have been conducted. The current study probed the neurocardiac circuit by examining associations among its core regions in the brain (e.g., insula, hypothalamus) and the periphery (heart rate [HR], high frequency heart rate variability [HF-HRV], and blood pressure [BP]). We sought to characterize these associations and to determine whether there were differences by PTSD status. Participants were N = 315 (64.1 % female) trauma-exposed adults enrolled from emergency departments as part of the prospective AURORA study. Participants completed a deep phenotyping session (e.g., fear conditioning, magnetic resonance imaging) two weeks after emergency department admission. Voxelwise analyses revealed several significant interactions between PTSD severity 8-weeks posttrauma and psychophysiological recordings on hypothalamic connectivity to the prefrontal cortex (PFC), insula, superior temporal sulcus, and temporoparietaloccipital junction. Among those with PTSD, diastolic BP was directly correlated with right insula-hypothalamic connectivity, whereas the reverse was found for those without PTSD. PTSD status moderated the association between systolic BP, HR, and HF-HRV and hypothalamic connectivity in the same direction. While preliminary, our findings may suggest that individuals with higher PTSD severity exhibit compensatory neural mechanisms to down-regulate autonomic imbalance. Additional study is warranted to determine how underlying mechanisms (e.g., inflammation) may disrupt the neurocardiac circuit and increase cardiometabolic disease risk in PTSD.

Keywords: Autonomic; Cardiovascular; Connectivity; Imaging; PTSD; Trauma.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest Dr. Neylan reports consultation for Jazz Pharmaceuticals; Dr. Rauch reports royalties from Oxford University Press, the American Psychiatric Publishing Inc., and Springer Publishing royalties; Dr. McLean reports consultation for Walter Reed Army Institute for Research and for Arbor Medical Innovations; Dr. Kessler reports consultation for Cambridge Health Alliance, Canandaigua VA Medical Center, Holmusk, Partners Healthcare, INC Mirah, PYM, and Roga Sciences; Dr. Koenen reports royalties from Guilford Press and Oxford University Press; Dr. Ressler reports consultation for Bioxcel, Bionomics, Acer, and Jazz Pharma; All other authors report no biomedical financial interests or potential conflicts of interest.

Figures

**Figure 1.. PTSD moderates the association between diastolic BP and hypothalamic connectivity.**
*Note*. A) PTSD status significantly moderated the association between diastolic BP and hypothalamus connectivity to several brain regions including the insula (dark blue). B) Simple slopes analyses revealed participants with PTSD (cyan) showed a positive association between Diastolic BP and connectivity whereas participants without PTSD (red) showed an inverse relationship. BP = blood pressure.

**Figure 2.. PTSD moderates the association between systolic BP and hypothalamic connectivity.**
*Note*. A) PTSD status significantly moderated the association between diastolic BP and hypothalamus connectivity to several brain regions including the MTG (green). B) Simple slopes analyses revealed participants with PTSD (cyan) showed a positive association between Systolic BP and connectivity whereas participants without PTSD (red) showed an orthogonal relationship. BP = blood pressure; MTG = middle temporal gyrus.

**Figure 3.. PTSD moderates the association between HR and hypothalamic connectivity.**
*Note*. A) PTSD status significantly moderated the association between HR during acquisition (red) and extinction (blue) of conditioned fear and hypothalamus connectivity to the PFC (overlap shown in purple). B) Simple slopes analyses revealed participants with PTSD (cyan) showed a positive association between HR (acquisition and extinction) and connectivity whereas participants without PTSD (red) showed an inverse relationship. HR = heart rate; PFC = prefrontal cortex.

**Figure 4.. PTSD moderates the association between HRV and hypothalamic connectivity.**
*Note*. A) PTSD status significantly moderated the association between HRV during extinction of conditioned fear and hypothalamus connectivity to the STS (dark blue). B) Simple slopes analyses revealed participants with PTSD (cyan) showed a negative association between HRV and connectivity whereas participants without PTSD (red) showed an orthogonal relationship. HRV = heart rate variability; STS = superior temporal sulcus.

See this image and copyright information in PMC

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Probing the neurocardiac circuit in trauma and posttraumatic stress

Affiliations

Probing the neurocardiac circuit in trauma and posttraumatic stress

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

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MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

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