TY - JOUR
T1 - Default mode network abnormalities in posttraumatic stress disorder
T2 - A novel network-restricted topology approach
AU - Akiki, Teddy J.
AU - Averill, Christopher L.
AU - Wrocklage, Kristen M.
AU - Scott, J. Cobb
AU - Averill, Lynnette A.
AU - Schweinsburg, Brian
AU - Alexander-Bloch, Aaron
AU - Martini, Brenda
AU - Southwick, Steven M.
AU - Krystal, John H.
AU - Abdallah, Chadi G.
N1 - Publisher Copyright:
© 2018
PY - 2018/8/1
Y1 - 2018/8/1
N2 - Disruption in the default mode network (DMN) has been implicated in numerous neuropsychiatric disorders, including posttraumatic stress disorder (PTSD). However, studies have largely been limited to seed-based methods and involved inconsistent definitions of the DMN. Recent advances in neuroimaging and graph theory now permit the systematic exploration of intrinsic brain networks. In this study, we used resting-state functional magnetic resonance imaging (fMRI), diffusion MRI, and graph theoretical analyses to systematically examine the DMN connectivity and its relationship with PTSD symptom severity in a cohort of 65 combat-exposed US Veterans. We employed metrics that index overall connectivity strength, network integration (global efficiency), and network segregation (clustering coefficient). Then, we conducted a modularity and network-based statistical analysis to identify DMN regions of particular importance in PTSD. Finally, structural connectivity analyses were used to probe whether white matter abnormalities are associated with the identified functional DMN changes. We found decreased DMN functional connectivity strength to be associated with increased PTSD symptom severity. Further topological characterization suggests decreased functional integration and increased segregation in subjects with severe PTSD. Modularity analyses suggest a spared connectivity in the posterior DMN community (posterior cingulate, precuneus, angular gyrus) despite overall DMN weakened connections with increasing PTSD severity. Edge-wise network-based statistical analyses revealed a prefrontal dysconnectivity. Analysis of the diffusion networks revealed no alterations in overall strength or prefrontal structural connectivity. DMN abnormalities in patients with severe PTSD symptoms are characterized by decreased overall interconnections. On a finer scale, we found a pattern of prefrontal dysconnectivity, but increased cohesiveness in the posterior DMN community and relative sparing of connectivity in this region. The DMN measures established in this study may serve as a biomarker of disease severity and could have potential utility in developing circuit-based therapeutics.
AB - Disruption in the default mode network (DMN) has been implicated in numerous neuropsychiatric disorders, including posttraumatic stress disorder (PTSD). However, studies have largely been limited to seed-based methods and involved inconsistent definitions of the DMN. Recent advances in neuroimaging and graph theory now permit the systematic exploration of intrinsic brain networks. In this study, we used resting-state functional magnetic resonance imaging (fMRI), diffusion MRI, and graph theoretical analyses to systematically examine the DMN connectivity and its relationship with PTSD symptom severity in a cohort of 65 combat-exposed US Veterans. We employed metrics that index overall connectivity strength, network integration (global efficiency), and network segregation (clustering coefficient). Then, we conducted a modularity and network-based statistical analysis to identify DMN regions of particular importance in PTSD. Finally, structural connectivity analyses were used to probe whether white matter abnormalities are associated with the identified functional DMN changes. We found decreased DMN functional connectivity strength to be associated with increased PTSD symptom severity. Further topological characterization suggests decreased functional integration and increased segregation in subjects with severe PTSD. Modularity analyses suggest a spared connectivity in the posterior DMN community (posterior cingulate, precuneus, angular gyrus) despite overall DMN weakened connections with increasing PTSD severity. Edge-wise network-based statistical analyses revealed a prefrontal dysconnectivity. Analysis of the diffusion networks revealed no alterations in overall strength or prefrontal structural connectivity. DMN abnormalities in patients with severe PTSD symptoms are characterized by decreased overall interconnections. On a finer scale, we found a pattern of prefrontal dysconnectivity, but increased cohesiveness in the posterior DMN community and relative sparing of connectivity in this region. The DMN measures established in this study may serve as a biomarker of disease severity and could have potential utility in developing circuit-based therapeutics.
KW - Diffusion MRI
KW - Functional MRI
KW - Graph theory
KW - Intrinsic connectivity networks
KW - PTSD
KW - Veterans
UR - http://www.scopus.com/inward/record.url?scp=85046748862&partnerID=8YFLogxK
U2 - 10.1016/j.neuroimage.2018.05.005
DO - 10.1016/j.neuroimage.2018.05.005
M3 - Article
C2 - 29730491
AN - SCOPUS:85046748862
SN - 1053-8119
VL - 176
SP - 489
EP - 498
JO - NeuroImage
JF - NeuroImage
ER -