Long-Term Effects of Repeated Blast Exposure in United States Special Operations Forces Personnel: A Pilot Study Protocol

Abstract

Emerging evidence suggests that repeated blast exposure (RBE) is associated with brain injury in military personnel. United States (U.S.) Special Operations Forces (SOF) personnel experience high rates of blast exposure during training and combat, but the effects of low-level RBE on brain structure and function in SOF have not been comprehensively characterized. Further, the pathophysiological link between RBE-related brain injuries and cognitive, behavioral, and physical symptoms has not been fully elucidated. We present a protocol for an observational pilot study, Long-Term Effects of Repeated Blast Exposure in U.S. SOF Personnel (ReBlast). In this exploratory study, 30 active-duty SOF personnel with RBE will participate in a comprehensive evaluation of: 1) brain network structure and function using Connectome magnetic resonance imaging (MRI) and 7 Tesla MRI; 2) neuroinflammation and tau deposition using positron emission tomography; 3) blood proteomics and metabolomics; 4) behavioral and physical symptoms using self-report measures; and 5) cognition using a battery of conventional and digitized assessments designed to detect subtle deficits in otherwise high-performing individuals. We will identify clinical, neuroimaging, and blood-based phenotypes that are associated with level of RBE, as measured by the Generalized Blast Exposure Value. Candidate biomarkers of RBE-related brain injury will inform the design of a subsequent study that will test a diagnostic assessment battery for detecting RBE-related brain injury. Ultimately, we anticipate that the ReBlast study will facilitate the development of interventions to optimize the brain health, quality of life, and battle readiness of U.S. SOF personnel.

Impact of repeated blast exposure on active-duty United States Special Operations Forces

“…The ReBlast (Long-term Effects of RBE in US SOF Personnel) study protocol was approved by the Mass General Brigham Institutional Review Board (2020P002695) and registered at ClinicalTrials.gov (NCT05183087). Data acquisition protocols and the prespecified statistical plan were previously described in detail ( 30 ).…”

“…In addition to standard paper-and-pencil cognitive assessments, we administered the computer-based Automated Neuropsychological Assessment Metrics (ANAM) ( 31 ) and the iPad-based Philips IntelliSpace Cognition ( 32 ) tests. In the week prior to and during the study visit, participants also completed self-report measures assessing psychological health and physical symptoms, as previously described ( 30 ). Scores on cognitive performance and self-report symptom measures were assessed for validity in one of two ways depending on the measure: 1) comparison to standard cutoffs on stand-alone measures [i.e., Mild Brain Injury Atypical Symptoms ( 33 ), Medical Symptom Validity Test ( 34 )]; or 2) automated evaluation of effort via metrics embedded in the assessment (i.e., ANAM, Philips IntelliSpace Cognition).…”

“…Participants were scanned with 7T MRI for functional connectivity analysis, 3T Connectome MRI for diffusion and volumetric analyses, [ 11 C]PBR28 TSPO PET-MRI for analysis of TSPO, a mitochondrial protein involved in neuroimmune function, and [ 18 F]MK6240 tau PET-MRI for analysis of neurofibrillary tangles. Acquisition parameters are described in SI Appendix and have been previously published ( 30 ).…”

Twenty Years of Blast-Induced Neurotrauma: Current State of Knowledge

“… 72 Recent investigations in special operations personnel, predominantly exposed to primary blast, are encouraging in this regard. 195 , 206–211 These studies suggest that repetitive, low BOP (range, 7–90 kPa 207–209 ) has the potential to cause neurological effects such as tinnitus, sleep imbalance, cognitive impairment, anxiety, insomnia, and headaches. 195 , 208–211 Additional investigations (including longitudinal) in humans with a large sample size are needed to understand the short- and long-term effects of BINT.…”

Study protocol: Identifying transcriptional regulatory alterations of chronic effects of blast and disturbed sleep in United States Veterans

“…The forementioned issues all change the risk profile associated within a given occupational specialty. While work is being done to better categorize and understand occupational blast exposure in the military [ 14 , 15 , 20 , 21 ], there remains no gold standard for classifying HROs across branches of the military.…”