Desynchronization of autonomic response and central autonomic network connectivity in posttraumatic stress disorder

doi:10.1002/hbm.23340

. 2017 Jan;38(1):27-40.

doi: 10.1002/hbm.23340. Epub 2016 Sep 20.

Desynchronization of autonomic response and central autonomic network connectivity in posttraumatic stress disorder

Janine Thome¹, Maria Densmore², Paul A Frewen^{2

3

4}, Margaret C McKinnon⁵, Jean Théberge^{2

6}, Andrew A Nicholson⁴, Julian Koenig^{7

8}, Julian F Thayer⁷, Ruth A Lanius^{2

4}

Affiliations

¹ Medical Faculty Mannheim, Institute of Psychiatric and Psychosomatic Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Germany.
² Department of Psychiatry, University of Western Ontario, London, Ontario, Canada.
³ Department of Psychology, University of Western Ontario, London, Ontario, Canada.
⁴ Department of Neuroscience, University of Western Ontario, London, Ontario, Canada.
⁵ Department of Psychiatry and Behavioral Neurosciences, Mc Master University, Hamilton, Ontario, Canada.
⁶ Department of Medical Imaging, Lawson Health Research Institute, London, Ontario, Canada.
⁷ Department of Psychology, Ohio State University, Columbus, Ohio.
⁸ Section for Translational Psychobiology in Child and Adolescent Psychiatry, Department of Child and Adolescent Psychiatry, Centre for Psychosocial Medicine, University of Heidelberg, Heidelberg, Germany.

PMID: 27647521
PMCID: PMC6866719
DOI: 10.1002/hbm.23340

Desynchronization of autonomic response and central autonomic network connectivity in posttraumatic stress disorder

Janine Thome et al. Hum Brain Mapp. 2017 Jan.

. 2017 Jan;38(1):27-40.

doi: 10.1002/hbm.23340. Epub 2016 Sep 20.

Authors

Janine Thome¹, Maria Densmore², Paul A Frewen^{2

3

4}, Margaret C McKinnon⁵, Jean Théberge^{2

6}, Andrew A Nicholson⁴, Julian Koenig^{7

8}, Julian F Thayer⁷, Ruth A Lanius^{2

4}

Affiliations

¹ Medical Faculty Mannheim, Institute of Psychiatric and Psychosomatic Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Germany.
² Department of Psychiatry, University of Western Ontario, London, Ontario, Canada.
³ Department of Psychology, University of Western Ontario, London, Ontario, Canada.
⁴ Department of Neuroscience, University of Western Ontario, London, Ontario, Canada.
⁵ Department of Psychiatry and Behavioral Neurosciences, Mc Master University, Hamilton, Ontario, Canada.
⁶ Department of Medical Imaging, Lawson Health Research Institute, London, Ontario, Canada.
⁷ Department of Psychology, Ohio State University, Columbus, Ohio.
⁸ Section for Translational Psychobiology in Child and Adolescent Psychiatry, Department of Child and Adolescent Psychiatry, Centre for Psychosocial Medicine, University of Heidelberg, Heidelberg, Germany.

PMID: 27647521
PMCID: PMC6866719
DOI: 10.1002/hbm.23340

Abstract

Objectives: Although dysfunctional emotion regulatory capacities are increasingly recognized as contributing to posttraumatic stress disorder (PTSD), little work has sought to identify biological markers of this vulnerability. Heart rate variability (HRV) is a promising biomarker that, together with neuroimaging, may assist in gaining a deeper understanding of emotion dysregulation in PTSD. The objective of the present study was, therefore, to characterize autonomic response patterns, and their related neuronal patterns in individuals with PTSD at rest.

Methods: PTSD patients (N = 57) and healthy controls (N = 41) underwent resting-state fMRI. Connectivity patterns of key regions within the central autonomic network (CAN)-including the ventromedial prefrontal cortex (vmPFC), amygdala, and periaqueductal gray (PAG)-were examined using a seed-based approach. Observed connectivity patterns were then correlated to resting HRV.

Results: In contrast to controls, individuals with PTSD exhibited lower HRV. In addition, whereas controls engaged a localized connectivity pattern of CAN-related brain regions, in PTSD, key CAN regions were associated with widespread connectivity patterns in regions related to emotional reactivity (vmPFC and amygdala to insular cortex and lentiform nucleus; PAG to insula) and motor readiness (vmPFC and amygdala to precentral gyrus; PAG to precentral gyrus and cerebellum). Critically, whereas CAN connectivity in controls was strongly related to higher HRV (insula, mPFC, superior frontal cortex, thalamus), HRV covariation was absent in PTSD subjects.

Conclusions: This study provides the first evidence for a specific psychophysiological-neuronal profile in PTSD individuals characterized by lower resting HRV and a lack of HRV covariation with CAN-related brain connectivity. Hum Brain Mapp 38:27-40, 2017. © 2016 Wiley Periodicals, Inc.

Keywords: central autonomic network; fMRI; heart rate variability; periaqueductal gray; posttraumatic stress disorder; top-down modulation.

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Figures

**Figure 1**
Between group differences in HRV. Figure represents significant lower Mean Natural Log RMSSD, LF‐HRV, and HF‐HRV in PTSD as compared to the control group (all F _(1,96)'s > 4.14, all P's < 0.048). Statistical threshold P < 0.05. Abbreviations: PTSD = posttraumatic stress disorder group; HC = healthy control group; RMSSD = root‐mean square differences of successive R‐R intervals; LF‐HRV = low frequency heart rate variability, HF‐HRV = high frequency heart rate variability, ln = natural logarithm.

**Figure 2**
Between group differences in key CAN seed resting state functional connectivity, including vmPFC, amygdala, PAG. Illustration represents greater connectivity between key CAN seed regions, including the vmPFC, amygdala, and PAG with multiple cortical and subcortical regions in PTSD as compared to healthy controls. By contrast, HC individuals did not exhibit any significantly greater connectivity to any of the CAN seed regions as compared to PTSD individuals. Statistical threshold P < 0.001 corrected for whole brain FDR, k = 10 for all two‐sample t‐tests. Abbreviations: PTSD = posttraumatic stress disorder group; HC = healthy control group; vmPFC = ventromedial prefrontal cortex; PAG = periaqueductal gray; FDR = false discovery rate. [Color figure can be viewed at http://wileyonlinelibrary.com.]

**Figure 3**
HRV correlations related connectivity to key CAN seed regions within healthy control subjects, including vmPFC, amygdala, PAG. Illustration represents increased functional connectivity patterns to all CAN regions in controls, which is predicted by HRV. In PTSD, analyses did not reveal significant clusters; only healthy control subjects are, therefore, presented. Significance threshold P < 0.05, ROI FDR corrected, k = 10 voxels for all one‐sample t‐tests. Abbreviations: PTSD = posttraumatic stress disorder group; HC = healthy control group; vmPFC = ventromedial prefrontal cortex; PAG = periaqueductal gray; ROI = region of interest analysis. [Color figure can be viewed at http://wileyonlinelibrary.com.]

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References

1. Acheson DT, Geyer MA, Baker DG, Nievergelt CM, Yurgil K, Risbrough VB (2015): Conditioned fear and extinction learning performance and its association with psychiatric symptoms in active duty Marines. Psychoneuroendocrinology 51:495–505. - PMC - PubMed
1. Agorastos A, Boel JA, Heppner PS, Hager T, Moeller‐Bertram T, Haji U, Motazedi A, Yanagi MA, Baker DG, Stiedl O (2013): Diminished vagal activity and blunted diurnal variation of heart rate dynamics in posttraumatic stress disorder. Stress 16:300–310. - PubMed
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[1] Acheson DT, Geyer MA, Baker DG, Nievergelt CM, Yurgil K, Risbrough VB (2015): Conditioned fear and extinction learning performance and its association with psychiatric symptoms in active duty Marines. Psychoneuroendocrinology 51:495–505. - PMC - PubMed

[2] Acheson DT, Geyer MA, Baker DG, Nievergelt CM, Yurgil K, Risbrough VB (2015): Conditioned fear and extinction learning performance and its association with psychiatric symptoms in active duty Marines. Psychoneuroendocrinology 51:495–505. - PMC - PubMed

[3] Agorastos A, Boel JA, Heppner PS, Hager T, Moeller‐Bertram T, Haji U, Motazedi A, Yanagi MA, Baker DG, Stiedl O (2013): Diminished vagal activity and blunted diurnal variation of heart rate dynamics in posttraumatic stress disorder. Stress 16:300–310. - PubMed

[4] Agorastos A, Boel JA, Heppner PS, Hager T, Moeller‐Bertram T, Haji U, Motazedi A, Yanagi MA, Baker DG, Stiedl O (2013): Diminished vagal activity and blunted diurnal variation of heart rate dynamics in posttraumatic stress disorder. Stress 16:300–310. - PubMed

[5] Barkay G, Freedman N, Lester H, Louzoun Y, Sapoznikov D, Luckenbaugh D, Shalev AY, Chisin RG, Bonne O (2012): Brain activation and heart rate during script‐driven traumatic imagery in PTSD: Preliminary findings. Psychiatry Res 204:155–160. - PubMed

[6] Barkay G, Freedman N, Lester H, Louzoun Y, Sapoznikov D, Luckenbaugh D, Shalev AY, Chisin RG, Bonne O (2012): Brain activation and heart rate during script‐driven traumatic imagery in PTSD: Preliminary findings. Psychiatry Res 204:155–160. - PubMed

[7] Beck AT, Guth D, Steer RA, Ball R (1997): Screening for major depression disorders in medical inpatients with the Beck Depression Inventory for Primary Care. Behav Res Ther 35:785–791. - PubMed

[8] Beck AT, Guth D, Steer RA, Ball R (1997): Screening for major depression disorders in medical inpatients with the Beck Depression Inventory for Primary Care. Behav Res Ther 35:785–791. - PubMed

[9] Beissner F, Meissner K, Bar KJ, Napadow V (2013): The autonomic brain: An activation likelihood estimation meta‐analysis for central processing of autonomic function. J Neurosci 33:10503–10511. - PMC - PubMed

[10] Beissner F, Meissner K, Bar KJ, Napadow V (2013): The autonomic brain: An activation likelihood estimation meta‐analysis for central processing of autonomic function. J Neurosci 33:10503–10511. - PMC - PubMed

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Desynchronization of autonomic response and central autonomic network connectivity in posttraumatic stress disorder

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Desynchronization of autonomic response and central autonomic network connectivity in posttraumatic stress disorder

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