TY  - JOUR
PY  - 2018//
TI  - Identifying disease foci from static and dynamic effective connectivity networks: illustration in soldiers with trauma
JO  - Human brain mapping
A1  - Rangaprakash, D.
A1  - Dretsch, Michael N.
A1  - Venkataraman, Archana
A1  - Katz, Jeffrey S.
A1  - Denney, Thomas S.
A1  - Deshpande, Gopikrishna
SP  - 264
EP  - 287
VL  - 39
IS  - 1
N2  - Brain connectivity studies report group differences in pairwise connection strengths. While informative, such results are difficult to interpret since our understanding of the brain relies on region-based properties, rather than on connection information. Given that large disruptions in the brain are often caused by a few pivotal sources, we propose a novel framework to identify the sources of functional disruption from effective connectivity networks. Our approach integrates static and time-varying effective connectivity modeling in a probabilistic framework, to identify aberrant foci and the corresponding aberrant connectomics network. Using resting-state fMRI, we illustrate the utility of this novel approach in U.S. Army soldiers (N = 87) with posttraumatic stress disorder (PTSD), mild traumatic brain injury (mTBI) and combat controls. Additionally, we employed machine-learning classification to identify those significant connectivity features that possessed high predictive ability. We identified three disrupted foci (middle frontal gyrus [MFG], insula, hippocampus), and an aberrant prefrontal-subcortical-parietal network of information flow. We found the MFG to be the pivotal focus of network disruption, with aberrant strength and temporal-variability of effective connectivity to the insula, amygdala and hippocampus. These connectivities also possessed high predictive ability (giving a classification accuracy of 81%); and they exhibited significant associations with symptom severity and neurocognitive functioning. In summary, dysregulation originating in the MFG caused elevated and temporally less-variable connectivity in subcortical regions, followed by a similar effect on parietal memory-related regions. This mechanism likely contributes to the reduced control over traumatic memories leading to re-experiencing, hyperarousal and flashbacks observed in soldiers with PTSD and mTBI. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.<br><br>© 2017 Wiley Periodicals, Inc.<p />  <p>Language: en</p>
LA  - en
SN  - 1065-9471
UR  - http://dx.doi.org/10.1002/hbm.23841
ID  - ref1
ER  -