Russell T Toll1, Wei Wu1, Sharon Naparstek1, Yu Zhang1, Manjari Narayan1, Brian Patenaude1, Carlo De Los Angeles1, Kasra Sarhadi1, Nicole Anicetti1, Parker Longwell1, Emmanuel Shpigel1, Rachael Wright1, Jennifer Newman1, Bryan Gonzalez1, Roland Hart1, Silas Mann1, Duna Abu-Amara1, Kamron Sarhadi1, Carena Cornelssen1, Charles Marmar1, Amit Etkin1. 1. Department of Bioengineering (Toll), Department of Psychiatry and Behavioral Sciences (Toll, Naparstek, Zhang, Narayan, Patenaude, De Los Angeles, Kasra Sarhadi, Anicetti, Longwell, Shpigel, Wright, Kamron Sarhadi, Cornelssen, Etkin), and the Wu Tsai Neurosciences Institute (Toll, Wu, Naparstek, Zhang, Narayan, Patenaude, De Los Angeles, Kasra Sarhadi, Anicetti, Longwell, Shpigel, Wright, Kamron Sarhadi, Cornelssen, Etkin), Stanford University, Stanford, Calif.; Veterans Affairs Palo Alto Health Care System, and the Sierra Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Palo Alto, Calif. (Toll, Wu, Naparstek, Zhang, Patenaude, De Los Angeles, Kasra Sarhadi, Anicetti, Longwell, Shpigel, Wright, Kamron Sarhadi, Cornelssen, Etkin); Steven and Alexandra Cohen Veterans Center for Posttraumatic Stress and Traumatic Brain Injury, New York University Langone School of Medicine, New York (Wu, Naparstek, Narayan, Patenaude, De Los Angeles, Longwell, Shpigel, Newman, Gonzalez, Hart, Mann, Abu-Amara, Cornelssen, Marmar, Etkin); School of Automation Science and Engineering, South China University of Technology, Guangzhou, China (Wu); and Department of Psychiatry, New York University Langone School of Medicine, New York (Newman, Gonzalez, Hart, Mann, Abu-Amara, Marmar).
Abstract
OBJECTIVE: The authors sought to identify brain regions whose frequency-specific, orthogonalized resting-state EEG power envelope connectivity differs between combat veterans with posttraumatic stress disorder (PTSD) and healthy combat-exposed veterans, and to determine the behavioral correlates of connectomic differences. METHODS: The authors first conducted a connectivity method validation study in healthy control subjects (N=36). They then conducted a two-site case-control study of veterans with and without PTSD who were deployed to Iraq and/or Afghanistan. Healthy individuals (N=95) and those meeting full or subthreshold criteria for PTSD (N=106) underwent 64-channel resting EEG (eyes open and closed), which was then source-localized and orthogonalized to mitigate effects of volume conduction. Correlation coefficients between band-limited source-space power envelopes of different regions of interest were then calculated and corrected for multiple comparisons. Post hoc correlations of connectomic abnormalities with clinical features and performance on cognitive tasks were conducted to investigate the relevance of the dysconnectivity findings. RESULTS: Seventy-four brain region connections were significantly reduced in PTSD (all in the eyes-open condition and predominantly using the theta carrier frequency). Underconnectivity of the orbital and anterior middle frontal gyri were most prominent. Performance differences in the digit span task mapped onto connectivity between 25 of the 74 brain region pairs, including within-network connections in the dorsal attention, frontoparietal control, and ventral attention networks. CONCLUSIONS: Robust PTSD-related abnormalities were evident in theta-band source-space orthogonalized power envelope connectivity, which furthermore related to cognitive deficits in these patients. These findings establish a clinically relevant connectomic profile of PTSD using a tool that facilitates the lower-cost clinical translation of network connectivity research.
OBJECTIVE: The authors sought to identify brain regions whose frequency-specific, orthogonalized resting-state EEG power envelope connectivity differs between combat veterans with posttraumatic stress disorder (PTSD) and healthy combat-exposed veterans, and to determine the behavioral correlates of connectomic differences. METHODS: The authors first conducted a connectivity method validation study in healthy control subjects (N=36). They then conducted a two-site case-control study of veterans with and without PTSD who were deployed to Iraq and/or Afghanistan. Healthy individuals (N=95) and those meeting full or subthreshold criteria for PTSD (N=106) underwent 64-channel resting EEG (eyes open and closed), which was then source-localized and orthogonalized to mitigate effects of volume conduction. Correlation coefficients between band-limited source-space power envelopes of different regions of interest were then calculated and corrected for multiple comparisons. Post hoc correlations of connectomic abnormalities with clinical features and performance on cognitive tasks were conducted to investigate the relevance of the dysconnectivity findings. RESULTS: Seventy-four brain region connections were significantly reduced in PTSD (all in the eyes-open condition and predominantly using the theta carrier frequency). Underconnectivity of the orbital and anterior middle frontal gyri were most prominent. Performance differences in the digit span task mapped onto connectivity between 25 of the 74 brain region pairs, including within-network connections in the dorsal attention, frontoparietal control, and ventral attention networks. CONCLUSIONS: Robust PTSD-related abnormalities were evident in theta-band source-space orthogonalized power envelope connectivity, which furthermore related to cognitive deficits in these patients. These findings establish a clinically relevant connectomic profile of PTSD using a tool that facilitates the lower-cost clinical translation of network connectivity research.
Authors: Yu Zhang; Wei Wu; Russell T Toll; Sharon Naparstek; Adi Maron-Katz; Mallissa Watts; Joseph Gordon; Jisoo Jeong; Laura Astolfi; Emmanuel Shpigel; Parker Longwell; Kamron Sarhadi; Dawlat El-Said; Yuanqing Li; Crystal Cooper; Cherise Chin-Fatt; Martijn Arns; Madeleine S Goodkind; Madhukar H Trivedi; Charles R Marmar; Amit Etkin Journal: Nat Biomed Eng Date: 2020-10-19 Impact factor: 25.671