TY - JOUR
T1 - The bed nucleus of the stria terminalis and functionally linked neurocircuitry modulate emotion processing and HPA axis dysfunction in posttraumatic stress disorder
AU - Awasthi, Samir
AU - Pan, Hong
AU - LeDoux, Joseph E.
AU - Cloitre, Marylene
AU - Altemus, Margaret
AU - McEwen, Bruce
AU - Silbersweig, David
AU - Stern, Emily
N1 - Funding Information:
Dr. Emily Stern is the CEO and a Co-founder of Ceretype Neuromedicine, Inc., a spin out from Brigham and Women’s Hospital, Harvard Medical School (has received founders shares; not related). The submitted work was performed while she was the Director of the Functional Neuroimaging Laboratory and the Director of Functional and Molecular Neuroimaging at Brigham and Women’s Hospital. Dr. Stern has four patents submitted: System and Method for z-Shim Compensated Echo-Planar Magnetic Resonance Imaging, and Systems (issued), System and Methods for Generating Biomarkers Based on Multivariate Classification of Functional Imaging and Associated Data (issued), System and Method for a Multivariate, Automated, Systematic and/or Hierarchical Searching System for Biosignature Extraction and Biomarker Discovery via task-based fMRI Imaging Spacetime Data, and PhyNFI: System and Method for Physiological-Noise-Free Functional Magnetic Resonance Imaging. During the course of the past three years, she has served as Co-Editor of the International Journal of Imaging Systems and Technology – Neuroimaging and Brain Mapping and serves on the Editorial Board of the Journal of Neuroimaging. She has received funding for travel from the National Institutes of Health and the James S. McDonnell Foundation. She has received an honorarium from the American Academy of Physical Medicine and Rehabilitation and reimbursement for service from the National Institutes of Health. Dr. Stern has received research funding support from the DHHS Administration for Community Living, formerly the National Institute on Disability and Rehabilitation Research (NIDRR – 90DP0039-03-01), the Epilepsy Foundation, the NIH (NIMH – R01MH090291, co-investigator), Northeastern University and Blackthorn Therapeutics.
Funding Information:
Dr. Emily Stern is the CEO and a Co-founder of Ceretype Neuromedicine, Inc., a spin out from Brigham and Women's Hospital, Harvard Medical School (has received founders shares; not related). The submitted work was performed while she was the Director of the Functional Neuroimaging Laboratory and the Director of Functional and Molecular Neuroimaging at Brigham and Women's Hospital. Dr. Stern has four patents submitted: System and Method for z-Shim Compensated Echo-Planar Magnetic Resonance Imaging, and Systems (issued), System and Methods for Generating Biomarkers Based on Multivariate Classification of Functional Imaging and Associated Data (issued), System and Method for a Multivariate, Automated, Systematic and/or Hierarchical Searching System for Biosignature Extraction and Biomarker Discovery via task-based fMRI Imaging Spacetime Data, and PhyNFI: System and Method for Physiological-Noise-Free Functional Magnetic Resonance Imaging. During the course of the past three years, she has served as Co-Editor of the International Journal of Imaging Systems and Technology – Neuroimaging and Brain Mapping and serves on the Editorial Board of the Journal of Neuroimaging. She has received funding for travel from the National Institutes of Health and the James S. McDonnell Foundation. She has received an honorarium from the American Academy of Physical Medicine and Rehabilitation and reimbursement for service from the National Institutes of Health. Dr. Stern has received research funding support from the DHHS Administration for Community Living, formerly the National Institute on Disability and Rehabilitation Research (NIDRR – 90DP0039-03-01), the Epilepsy Foundation, the NIH (NIMH – R01MH090291, co-investigator), Northeastern University and Blackthorn Therapeutics.
Funding Information:
Funding for this study was provided by the NIMH Grant P50 MH58911-S1.
Publisher Copyright:
© 2020
PY - 2020/1
Y1 - 2020/1
N2 - Background: The bed nucleus of the stria terminalis (BNST) plays an important role in rodent posttraumatic stress disorder (PTSD), but evidence to support its relevance to human PTSD is limited. We sought to understand the role of the BNST in human PTSD via fMRI, behavioral, and physiological measurements. Methods: 29 patients with PTSD (childhood sexual abuse) and 23 healthy controls (HC) underwent BOLD imaging with an emotional word paradigm. Symptom severity was assessed using the Clinician-Administered PTSD Scale and HPA-axis dysfunction was assessed by measuring the diurnal cortisol amplitude index (DCAI). A data-driven multivariate analysis was used to determine BNST task-based functional co-occurrence (tbFC) across individuals. Results: In the trauma-versus-neutral word contrast, patients showed increased activation compared to HC in the BNST, medial prefrontal cortex (mPFC), posterior cingulate gyrus (PCG), caudate heads, and midbrain, and decreased activation in dorsolateral prefrontal cortex (DLPFC). Symptom severity positively correlated with activity in the BNST, caudate head, amygdala, hippocampus, dorsal anterior cingulate gyrus (dACG), and PCG, and negatively with activity in the medial orbiotofrontal cortex (mOFC) and DLPFC. Patients and HC showed marked differences in the relationship between the DCAI and BOLD activity in the BNST, septal nuclei, dACG, and PCG. Patients showed stronger tbFC between the BNST and closely linked limbic and subcortical regions, and a loss of negative tbFC between the BNST and DLPFC. Conclusions: Based upon novel data, we present a new model of dysexecutive emotion processing and HPA-axis dysfunction in human PTSD that incorporates the role of the BNST and functionally linked neurocircuitry.
AB - Background: The bed nucleus of the stria terminalis (BNST) plays an important role in rodent posttraumatic stress disorder (PTSD), but evidence to support its relevance to human PTSD is limited. We sought to understand the role of the BNST in human PTSD via fMRI, behavioral, and physiological measurements. Methods: 29 patients with PTSD (childhood sexual abuse) and 23 healthy controls (HC) underwent BOLD imaging with an emotional word paradigm. Symptom severity was assessed using the Clinician-Administered PTSD Scale and HPA-axis dysfunction was assessed by measuring the diurnal cortisol amplitude index (DCAI). A data-driven multivariate analysis was used to determine BNST task-based functional co-occurrence (tbFC) across individuals. Results: In the trauma-versus-neutral word contrast, patients showed increased activation compared to HC in the BNST, medial prefrontal cortex (mPFC), posterior cingulate gyrus (PCG), caudate heads, and midbrain, and decreased activation in dorsolateral prefrontal cortex (DLPFC). Symptom severity positively correlated with activity in the BNST, caudate head, amygdala, hippocampus, dorsal anterior cingulate gyrus (dACG), and PCG, and negatively with activity in the medial orbiotofrontal cortex (mOFC) and DLPFC. Patients and HC showed marked differences in the relationship between the DCAI and BOLD activity in the BNST, septal nuclei, dACG, and PCG. Patients showed stronger tbFC between the BNST and closely linked limbic and subcortical regions, and a loss of negative tbFC between the BNST and DLPFC. Conclusions: Based upon novel data, we present a new model of dysexecutive emotion processing and HPA-axis dysfunction in human PTSD that incorporates the role of the BNST and functionally linked neurocircuitry.
KW - Bed nucleus of the stria terminalis
KW - Functional connectivity
KW - Hypothalamic pituitary adrenal (HPA) axis
KW - PTSD
KW - Subcortical brain networks
KW - fMRI
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U2 - 10.1016/j.nicl.2020.102442
DO - 10.1016/j.nicl.2020.102442
M3 - Article
C2 - 33070099
AN - SCOPUS:85092497094
SN - 2213-1582
VL - 28
JO - NeuroImage: Clinical
JF - NeuroImage: Clinical
M1 - 102442
ER -