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P.4.007 Altered orbitofrontal network organization in veterans with PTSD: a graph theoretical analysis
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Neural and cellular networks in the brain, function and dysfunction
results suggest a functional disconnection in the social brain network of these patients. The disrupted connectivity of this circuitry may contribute to the behavioral and symptomatic outcome of the disorder and might be proposed as one of the possible neural biomarkers of treatment efficacy studies. Reference(s) [1] Das, P., Kemp, A.H., Flynn, G., Harris, A.W., Liddell, B.J., Whitford, T.J., Peduto, A., Gordon, E., & Williams, L.M. Functional disconnections in the direct and indirect amygdala pathways for fear processing in schizophrenia. Schizophr Res 2007;90:284−94. [2] Fakra, E., Salgado-Pineda, P., Delaveau, P., Hariri, A.R., & Blin, O. Neural bases of different cognitive strategies for facial affect processing in schizophrenia. Schizophr Res 2008;100:191–205. [3] Hariri, A.R., Mattay, V.S., Tessitore, A., Kolachana, B., Fera, F., Goldman, D., Egan, M.F., & Weinberger, D.R. Serotonin transporter genetic variation and the response of the human amygdala. Science 2002;297:400−3.
P.4.007 Altered orbitofrontal network organization in veterans with PTSD: a graph theoretical analysis M. Kennis1 ° , A.R. Rademaker2 , S.J.H. van Rooij1 , M.P. van den Heuvel1 , R.S. Kahn1 , E. Geuze2 . 1 Brain Center Rudolf Magnus, Psychiatry, Utrecht, The Netherlands; 2 Ministry of Defence, Research Centre − Military Mental Health, Utrecht, The Netherlands Post-traumatic stress disorder (PTSD) is an anxiety disorder that can develop after experiencing a traumatic event. Alterations in functional connectivity of brain regions, such as the amygdala and medial prefrontal cortex, have been reported in PTSD patients versus controls. In addition, studies have reported alterations of resting state functional connectivity of these brain regions in PTSD, mainly using a seed-based analysis. Quantifying topological properties of complex networks on the wholebrain scale is now possible because of advances in network analysis. Here, we investigate resting state functional brain network topology in PTSD using graph theoretical analysis [1]. Nine minutes of resting state functional magnetic resonance images were obtained for 51 male veterans with PTSD (mean age 36.1±9.7), and 54 male controls (mean age 35.8±9.7). Images were preprocessed in SPM5, including slice-timing correction, realignment, coregistration, normalization, and smoothing (8 FWHM).
In addition, detrending, band-pass filtering, correction for nuisance variables, and motion scrubbing were applied. Using the automated anatomical labeling (AAL) template, the mean time-series of 90 anatomical structures (nodes) were extracted and correlated with each other to create individual subject correlation matrices. Matrices were proportionally thresholded at 0.6 (preserving 60% of the strongest connections), and binarized. From these binary matrices the degree (number of connections of a node), clustering coefficient (number of connections of nearest neighbors of a node as a fraction of the maximum number of possible connections), and pathlength (the average minimum number of connections that must be crossed to go to another node) were calculated for each node specifically. Group differences in these network metrics were determined with independent samples t-tests (SPSS, p < 0.05 uncorrected). The degree of the left inferior orbitofrontal gyrus (OFG) was decreased in PTSD patients versus controls (p = 0.019). In particular, reduced functional connectivity of the left inferior OFG was found with the left rolandic operculum, right anterior cingulum, bilateral middle cingulum, left hippocampus, left parahippocampus, right amygdala, left middle occipital, left inferior occipital, and left precuneus. PTSD patients had more functional connectivity between the left inferior OFG and the right olfactory. A decreased node-specific clustering coefficient was found in PTSD patients versus controls in the right inferior OFG (p = 0.039), and the right medial OFG (p = 0.001). An increased node-specific clustering coefficient was found in PTSD patients versus controls in the right inferior occipital gyrus (p = 0.039). Thus, PTSD patients have reduced orbitofrontal-limbic synchronization and decreased orbitofrontal network integrity. The orbitofrontal OFG is involved in emotional regulation, and altered structure and function of the OFG has been previously reported in PTSD. The results are also in line with studies suggesting that PTSD patients suffer from dysfunctional control of frontal brain areas over emotional brain regions. Further exploration of network topology and integrity may potentially be helpful for predicting treatment response. Reference(s) [1] Bullmore, E., Sporns, O., 2009. Complex brain networks: graph theoretical analysis of structural and functional systems. Nat Rev Neurosci 10, 186–198.
Neural and cellular networks in the brain, function and dysfunction
results suggest a functional disconnection in the social brain network of these patients. The disrupted connectivity of this circuitry may contribute to the behavioral and symptomatic outcome of the disorder and might be proposed as one of the possible neural biomarkers of treatment efficacy studies. Reference(s) [1] Das, P., Kemp, A.H., Flynn, G., Harris, A.W., Liddell, B.J., Whitford, T.J., Peduto, A., Gordon, E., & Williams, L.M. Functional disconnections in the direct and indirect amygdala pathways for fear processing in schizophrenia. Schizophr Res 2007;90:284−94. [2] Fakra, E., Salgado-Pineda, P., Delaveau, P., Hariri, A.R., & Blin, O. Neural bases of different cognitive strategies for facial affect processing in schizophrenia. Schizophr Res 2008;100:191–205. [3] Hariri, A.R., Mattay, V.S., Tessitore, A., Kolachana, B., Fera, F., Goldman, D., Egan, M.F., & Weinberger, D.R. Serotonin transporter genetic variation and the response of the human amygdala. Science 2002;297:400−3.
P.4.007 Altered orbitofrontal network organization in veterans with PTSD: a graph theoretical analysis M. Kennis1 ° , A.R. Rademaker2 , S.J.H. van Rooij1 , M.P. van den Heuvel1 , R.S. Kahn1 , E. Geuze2 . 1 Brain Center Rudolf Magnus, Psychiatry, Utrecht, The Netherlands; 2 Ministry of Defence, Research Centre − Military Mental Health, Utrecht, The Netherlands Post-traumatic stress disorder (PTSD) is an anxiety disorder that can develop after experiencing a traumatic event. Alterations in functional connectivity of brain regions, such as the amygdala and medial prefrontal cortex, have been reported in PTSD patients versus controls. In addition, studies have reported alterations of resting state functional connectivity of these brain regions in PTSD, mainly using a seed-based analysis. Quantifying topological properties of complex networks on the wholebrain scale is now possible because of advances in network analysis. Here, we investigate resting state functional brain network topology in PTSD using graph theoretical analysis [1]. Nine minutes of resting state functional magnetic resonance images were obtained for 51 male veterans with PTSD (mean age 36.1±9.7), and 54 male controls (mean age 35.8±9.7). Images were preprocessed in SPM5, including slice-timing correction, realignment, coregistration, normalization, and smoothing (8 FWHM).
In addition, detrending, band-pass filtering, correction for nuisance variables, and motion scrubbing were applied. Using the automated anatomical labeling (AAL) template, the mean time-series of 90 anatomical structures (nodes) were extracted and correlated with each other to create individual subject correlation matrices. Matrices were proportionally thresholded at 0.6 (preserving 60% of the strongest connections), and binarized. From these binary matrices the degree (number of connections of a node), clustering coefficient (number of connections of nearest neighbors of a node as a fraction of the maximum number of possible connections), and pathlength (the average minimum number of connections that must be crossed to go to another node) were calculated for each node specifically. Group differences in these network metrics were determined with independent samples t-tests (SPSS, p < 0.05 uncorrected). The degree of the left inferior orbitofrontal gyrus (OFG) was decreased in PTSD patients versus controls (p = 0.019). In particular, reduced functional connectivity of the left inferior OFG was found with the left rolandic operculum, right anterior cingulum, bilateral middle cingulum, left hippocampus, left parahippocampus, right amygdala, left middle occipital, left inferior occipital, and left precuneus. PTSD patients had more functional connectivity between the left inferior OFG and the right olfactory. A decreased node-specific clustering coefficient was found in PTSD patients versus controls in the right inferior OFG (p = 0.039), and the right medial OFG (p = 0.001). An increased node-specific clustering coefficient was found in PTSD patients versus controls in the right inferior occipital gyrus (p = 0.039). Thus, PTSD patients have reduced orbitofrontal-limbic synchronization and decreased orbitofrontal network integrity. The orbitofrontal OFG is involved in emotional regulation, and altered structure and function of the OFG has been previously reported in PTSD. The results are also in line with studies suggesting that PTSD patients suffer from dysfunctional control of frontal brain areas over emotional brain regions. Further exploration of network topology and integrity may potentially be helpful for predicting treatment response. Reference(s) [1] Bullmore, E., Sporns, O., 2009. Complex brain networks: graph theoretical analysis of structural and functional systems. Nat Rev Neurosci 10, 186–198.