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Intrinsic Functional Connectivity and Cognition in PTSD


PTSD – dubbed a “signature injury” of the recent wars in Iraq and Afghanistan – has received unprecedented research and clinical focus because of its staggering prevalence rates among returning service members and Veterans. To compound the problem of prevalence, only two FDA-approved psychopharmacologic agents are available for PTSD (both SSRIs) and these require weeks or months to provide clinical benefit, offer limited efficacy, and do not target the cardinal cognitive symptoms of PTSD (e.g., impaired attention/concentration, memory, executive function). This last point is especially troubling as cognitive impairment in PTSD contributes significantly to overall morbidity and poor functional outcomes. Glutamate is responsible for many aspects of normal cognition and recent evidence suggests glutamatergic abnormalities in PTSD. Further, PTSD is associated with functional connectivity disturbances in multiple brain regions. Ketamine’s antagonism of the glutamatergic N-methyl-D-aspartate receptor appears to be the first step in a cascade of events that includes rapid increases in presynaptic glutamate release and improved signaling, enhanced regional activity in excitatory networks, and ultimately marked changes in synaptic plasticity and functional connectivity approximately 24-hours following a single sub-anesthetic dose (the peak time of ketamine’s antidepressant response). Considering the role of functional connectivity in cognitive function, there is strong support for using resting-state functional connectivity MRI (rs-fcMRI) to examine ketamine-induced neural system alterations that may have important implications for connectivity and cognition in PTSD, providing answers for ‘fast-tracked’ effects, both for overall symptom reduction and cognitive enhancement.

This study is an add-on trial to other studies in our research program. This means this study does not directly recruit – all participants in this study will be engaged in another study in our program (e.g., one of our ketamine trials).