Introduction: ­­­­­­­­­­­­­­­ Blast exposure is a 21st century reality in warfare and has been called the signature injury of wars. In the military, mild traumatic brain injury (mTBI) is considered the most common brain injury caused by the exposure to low levels of blast from improvised explosive devices mainly referred to as mild blast TBI (mbTBI) but the least understood [1,2]. Increasing evidence suggests that a single traumatic brain injury can produce long-term structural and functional deficits. Various imaging modalities have been utilized in the clinical settings, revealing both structural and functional changes following blast injury. However, only a limited number of clinical studies included readouts at several post-injury timepoints in veterans [3]. In this work, we propose to apply a more data-driven approach using resting state functional connectivity MRI to investigate network changes induced by a single blast overpressure (BOP) event in breachers longitudinally. This will first allow us to examine the safety profile of BOP exposure in breachers undergoing training with emphasis on potential short-term (post blast) brain injury and second establish a signature pattern of blast injury in the brain. Methods: Subjects were recruited from in-service breachers who train with low-level explosives. We conducted a longitudinal study in well-experienced breachers with > 1 year post-blast (n=12 males). All subjects attended five separate MRI scans at 1 day prior to the blast event (Day0) and then 1, 3, 7, and 28 days following the blast. MRI data were collected using a 3T scanner (Siemens Trio, Germany). High-resolution anatomical data were acquired with an MPRAGE sequence with TR=1950 ms, TE=2.26ms, voxel size =1mm3 isotropic, FOV=256 x 256 and number of slices = 176. Resting state functional MRI data were acquired with a single-shot gradient echo EPI sequence with TR=2000 ms, TE=30ms, voxel size =4mm3 isotropic, and number of measurements = 89. Volumetric based analysis was done through the Freesurfer automated image analysis suite. Connectivity analysis of the functional data was performed with CPAC where functional data was slice time corrected, motion corrected, realigned and registered in the MRI space. Then centrality measure were computed on a voxel-by-voxel basis. A paired ttest was then applied between Day1, Day3, Day7, and Day28 versus Day0 respectively. Number of connections was extracted from main hubs such as the thalamus (Thal), visual cortex (VC), and motor cortex (MC). Results: Preliminary structural volumetric analysis showed minimal changes in whole and regional brain volumes at days 1, 3, 7, and 28 compared to Day0. No significant changes in the brain were seen on the susceptibility weighted and T2-weighted imaging suggesting no effect of a single blast event on brain structure. Exposure to a blast however, showed changes in functional connectivity hubs; a significant increase in the Thal connectivity was seen at Day1 only and then changed to pre-blast condition in the following days post-blast. The VC showed no change at Day1 but a significant increase in connectivity at Day3 which also regained pre-blast connectivity at Day7 and Day28. A significant reduction however was seen in the MC at day1 and day7 that was regained at day28 (Fig. 1). This is also depicted in the plots in Fig. 2. Discussion: Resting state functional connectivity MRI revealed marked significant increases in connectivity networks post-blast mainly in the Thal and VC being significantly greater at Day1 and Day3, respectively (p<0.01). These changes were recoverable and returned to pre-blast condition 7 days following the blast event. Interestingly, the Thal has been a region highly implicated in mbTBI. Indeed the Thal has already been demonstrated to be a highly vulnerable region to mTBI where significant decreases in diffusion has been shown compared to controls [4]. Decreases in diffusivity in thalamic nuclei has also been recently demonstrated in rats [5]. Deficits in the visual and motor cortices, consistent with our study, have also been demonstrated [6][7]. Therefore, using a data driven approach, we show that functional changes are induced by a single low level blast but these changes are reversible over the course of a month. Future work will include the investigation of the effect of multiple blasts on brain function and the assessment of the longitudinal effects of such events.