• Carlo Pierpaoli, Amritha Nayak, Rakibul Hafiz, M Okan Irfanoglu, Gang Chen, Paul Taylor, Mark Hallett, Michael Hoa, Dzung Pham, Yi-Yu Chou, Anita D Moses, André J van der Merwe, Sara M Lippa, Carmen C Brewer, Chris K Zalewski, Cris Zampieri, L Christine Turtzo, Pashtun Shahim, Leighton Chan, NIH AHI Intramural Research Program Team, Brian Moore, Lauren Stamps, Spencer Flynn, Julia Fontana, Swathi Tata, Jessica Lo, Mirella A Fernandez, Annie Lori-Joseph, Jesse Matsubara, Julie Goldberg, Thuy-Tien D Nguyen, Noa Sasson, Justine Lely, Bryan Smith, Kelly A King, Jennifer Chisholm, Julie Christensen, M Teresa Magone, Chantal Cousineau-Krieger, Louis M French, Simge Yonter, Sanaz Attaripour, and Chen Lai.
• Laboratory on Quantitative Medical Imaging, National Institute of Biomedical Imaging and Bioengineering, Bethesda, Maryland.
• JAMA. 2024 Apr 2; 331 (13): 112211341122-1134.

ImportanceUS government personnel stationed internationally have reported anomalous health incidents (AHIs), with some individuals experiencing persistent debilitating symptoms.ObjectiveTo assess the potential presence of magnetic resonance imaging (MRI)-detectable brain lesions in participants with AHIs, with respect to a well-matched control group.Design, Setting, And ParticipantsThis exploratory study was conducted at the National Institutes of Health (NIH) Clinical Center and the NIH MRI Research Facility between June 2018 and November 2022. Eighty-one participants with AHIs and 48 age- and sex-matched control participants, 29 of whom had similar employment as the AHI group, were assessed with clinical, volumetric, and functional MRI. A high-quality diffusion MRI scan and a second volumetric scan were also acquired during a different session. The structural MRI acquisition protocol was optimized to achieve high reproducibility. Forty-nine participants with AHIs had at least 1 additional imaging session approximately 6 to 12 months from the first visit.ExposureAHIs.Main Outcomes And MeasuresGroup-level quantitative metrics obtained from multiple modalities: (1) volumetric measurement, voxel-wise and region of interest (ROI)-wise; (2) diffusion MRI-derived metrics, voxel-wise and ROI-wise; and (3) ROI-wise within-network resting-state functional connectivity using functional MRI. Exploratory data analyses used both standard, nonparametric tests and bayesian multilevel modeling.ResultsAmong the 81 participants with AHIs, the mean (SD) age was 42 (9) years and 49% were female; among the 48 control participants, the mean (SD) age was 43 (11) years and 42% were female. Imaging scans were performed as early as 14 days after experiencing AHIs with a median delay period of 80 (IQR, 36-544) days. After adjustment for multiple comparisons, no significant differences between participants with AHIs and control participants were found for any MRI modality. At an unadjusted threshold (P < .05), compared with control participants, participants with AHIs had lower intranetwork connectivity in the salience networks, a larger corpus callosum, and diffusion MRI differences in the corpus callosum, superior longitudinal fasciculus, cingulum, inferior cerebellar peduncle, and amygdala. The structural MRI measurements were highly reproducible (median coefficient of variation <1% across all global volumetric ROIs and <1.5% for all white matter ROIs for diffusion metrics). Even individuals with large differences from control participants exhibited stable longitudinal results (typically, <±1% across visits), suggesting the absence of evolving lesions. The relationships between the imaging and clinical variables were weak (median Spearman ρ = 0.10). The study did not replicate the results of a previously published investigation of AHIs.Conclusions And RelevanceIn this exploratory neuroimaging study, there were no significant differences in imaging measures of brain structure or function between individuals reporting AHIs and matched control participants after adjustment for multiple comparisons.

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