Report on “directional phenomena” inconclusive

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An investigation published today in the Journal of the American Medical Association found that 40 people who worked at the U.S. Embassy in Havana experienced a loss in white brain matter.
Authors of the 12-page study, called “Neuroimaging Findings in US Government Personnel With Possible Exposure to Directional Phenomena in Cuba,” said the cause of the losses was unclear and “may require further study.”
The study concluded:

Among U.S. government personnel in Havana, Cuba, with potential exposure to directional phenomena, compared with healthy controls, advanced brain magnetic resonance imaging revealed significant differences in whole brain white matter volume, regional gray and white matter volumes, cerebellar tissue microstructural integrity, and functional connectivity in the auditory and visuospatial subnetworks but not in the executive control subnetwork. The clinical importance of these differences is uncertain and may require further study.

The main purpose of white brain matter “is to provide a pathway for connecting the different areas of the brain,” according to ThoughtCo.
The JAWA study compared the brain images of 40 embassy employees – 23 men and 17 women – with 48 control samples.
The embassy employees had an average of 27 percent less white brain matter mass, the study said.
Authors of the study could not explain why and wrote that their study had a number of limitations:

  1. First, the effort was not designed as a research study but was undertaken retrospectively, using clinically acquired data and measures of deficit assessment.
  2. Second, the ideal control cohort, composed of unaffected personnel who were identical to those deployed in Cuba, was not feasible to obtain. Although the controls recruited for the study were matched on age and sex, and generally matched on race/ethnicity, education, and multifunctional lifestyle of the patients, factors like blood pressure, bilingualism, and life experiences could not be matched. Race/ethnicity was not used as a covariate in the statistical analysis due to the small sample size. The race/ ethnicity characteristics of the patient cohort cannot be revealed because of privacy and anonymity. A second independent control cohort was used to further ensure reproducibility of the results and mitigate any sampling bias that may have affected control set 1.
  3. Third, the analysis involved a small sample with high heterogeneity, compounded by clinical (as opposed to research) neuroimaging acquisition. In the absence of a common clinical severity score due to varied symptomatology, the cohort cannot be subdivided. Therefore, the findings represent group-level statistical differences
    as opposed to individual changes that may be highly variable. Additionally, it cannot be determined whether the differences among the patients are due to individual differences between patients or differences in level and degree of exposure to an uncharacterized directional phenomenon.
  4. Fourth, because the patients have undergone neurological rehabilitation, the imaging findings may be representative of brain changes associated with the rehabilitation or compensatory changes in a recovering brain. Although this hampers future replication studies, complementary findings across various MRI measures, as undertaken in this study, are in themselves a form of replication in such a unique and small sample.
  5. Fifth, the tissue integrity measures of fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity are gross representations of tissue microstructure, to the extent that microstructural tissue properties can be captured by in vivo MRI protocols. However, these measures have been used for investigating various pathologies, as described above. Investigation of other microstructure measures, like axon diameter, requires advanced dMRI acquisition commonly acquired in dedicated research MRI acquisitions, and is therefore beyond the scope of the current clinical acquisition. In DTI, the macroresolution of acquisition means that the indexes are only a representation of the underlying microstructural changes and tissue integrity. The underlying mechanisms of axonal injury, myelin changes, or free water changes are challenging to disentangle in group-based statistical results.
  6. Sixth, image analysis methods have limitations. Segmentation methods quantify the volume of “gray- appearing” and “white-appearing” tissue. Although the former is known to correlate strongly with neuronal cell bodies and the latter to reflect axonal and myelin volumes, various pathological processes like axonal death, demyelination, and dehydration, among other processes, affect them.
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