Neuroimaging Evidence in Havana Syndrome: Diffusion Tensor Imaging and White Matter Microstructure

The Verma et al. (2019) Study: Core Findings

The landmark neuroimaging study by Verma and colleagues, published in JAMA in July 2019, enrolled 40 US government employees who had been evaluated at the University of Pennsylvania's Center for Brain Injury and Repair following service in Havana, Cuba. These individuals were compared with 48 healthy controls matched for age, sex, and handedness. All participants underwent multimodal MRI including structural imaging, diffusion tensor imaging (DTI), resting-state functional MRI, and neurite orientation dispersion and density imaging (NODDI).

The study found significant differences in white matter microstructure in the affected group, including lower mean diffusivity and higher fractional anisotropy in multiple white matter tracts. Affected individuals also showed differences in cerebellar tissue volume and altered functional connectivity in the visuospatial and auditory networks. The authors concluded that these findings were consistent with a diffuse process affecting white matter integrity, and that the pattern was distinct from that seen in mild traumatic brain injury, concussion, or other common neurological conditions.

"Compared with controls, [affected personnel] had significant differences in whole-brain white matter microstructure, functional connectivity in the auditory and visuospatial subnetworks, and cerebellar tissue volume."

DTI Methodology and Its Relevance to AHI

Diffusion tensor imaging measures the directional diffusion of water molecules in brain tissue. In healthy white matter, water diffuses preferentially along the length of axons — a property quantified as fractional anisotropy (FA). When axonal integrity is disrupted, water diffuses more freely in all directions, reducing FA and increasing mean diffusivity (MD). DTI is therefore sensitive to microstructural changes in white matter that are invisible on conventional T1 or T2 MRI sequences.

The relevance of DTI to AHI research stems from the proposed mechanisms. If directed RF energy or acoustic energy causes microstructural damage to axons or myelin sheaths — as the NASEM 2020 report considered plausible — this damage would be expected to manifest as DTI abnormalities before any gross structural changes become visible. DTI is therefore the most sensitive available tool for detecting the type of injury that the leading AHI mechanisms would be expected to produce.

Methodological Limitations and the Replication Challenge

The Verma et al. study has been subject to several methodological critiques. First, the absence of pre-exposure baseline neuroimaging for any of the affected participants makes it impossible to determine whether the observed differences represent acquired changes or pre-existing individual variation. Second, the healthy control group was not matched for occupational stress, international travel history, or other factors that might independently affect white matter microstructure. Third, the study's cross-sectional design cannot establish temporal precedence between the reported exposures and the neuroimaging findings.

A 2023 study by Hoffer and colleagues, which examined a larger cohort of AHI-affected personnel using a broader neurological assessment battery, found consistent vestibular and oculomotor abnormalities but did not specifically confirm the white matter DTI differences reported by Verma. The Hoffer study used different imaging protocols and a different comparison group, making direct comparison difficult. A 2022 study by Weisskopf and colleagues at Harvard found no significant neuroimaging differences in a separate cohort of affected State Department personnel, though this study has itself been criticized for methodological limitations.

Evidentiary Weight in the HSDI Framework

The HSDI Evidence Strength Dashboard classifies the neuroimaging evidence for AHI as Tier 2 — significant but not definitive — reflecting the genuine scientific uncertainty surrounding the Verma findings and the absence of independent replication. This classification is not a dismissal of the neuroimaging evidence; rather, it reflects the HSDI commitment to calibrated, source-traceable evidentiary assessment that accurately represents the state of the scientific record.

The Differential Diagnosis Engine incorporates DTI white matter findings as a supporting criterion for the AHI diagnosis pathway, weighted at 0.8 on a 0-to-1 scale. The criterion is flagged as requiring clinical imaging confirmation rather than self-report, consistent with the methodological requirements of the underlying studies. This approach ensures that the diagnostic tool accurately reflects the evidentiary basis of each criterion rather than overstating or understating the neuroimaging evidence.