Two new studies on the mysterious 'Havana syndrome' found no physical cause, but they did suggest a possible link to mental health.

Since 2016, more than 1,000 US government personnel stationed internationally have reported hearing intrusive sounds and feeling pressure on their heads, followed by symptoms like intense headaches, dizziness, and cognitive dysfunction. Ever since federal employees stationed in Havana, Cuba, first reported these anomalous health incidents (AHIs), Havana syndrome has been the media's go-to term for the condition.

US researchers led by the National Institutes of Health (NIH) now report they have found no significant differences in brain scans or other biological tests between people with Havana syndrome and healthy controls.

Though the results provide little insight into a possible biological explanation for the symptoms, the authors emphasize there are multiple factors to consider when interpreting these findings.

"A lack of evidence for an MRI-detectable difference between individuals with AHIs and controls does not exclude that an adverse event impacting the brain occurred at the time of the AHI," says NIH neuroscientist Carlo Pierpaoli, first author of one of the studies.

"It is possible that individuals with an AHI may be experiencing the results of an event that led to their symptoms, but the injury did not produce the long-term neuroimaging changes that are typically observed after severe trauma or stroke.

"We hope these results will alleviate concerns about AHI being associated with severe neurodegenerative changes in the brain."

Researchers studied different types of MRI scans to measure brain volume, structure, and function in 81 participants who experienced AHIs and compared them with 48 healthy controls, 29 of whom had similar job assignments though no reported AHIs.

In a separate study, 86 participants with AHIs and 30 controls with similar job assignments underwent various tests including blood biomarker testing, and clinical, auditory, balance, visual, and neuropsychological assessments.

The researchers used multiple methods and models to examine the data. In analyzing a variety of observable traits that include a selection of biochemical characteristics, the team hoped to uncover significant clinical changes that might correlate with neuroimaging results.

"Our goal was to conduct thorough, objective and reproducible evaluations to see if we could identify structural brain or biological differences in people who reported AHIs," says Leighton Chan, a public health scientist and acting chief scientific officer at the NIH.

MRI scans were conducted approximately 80 days after symptom onset, with some participants scanned as early as 14 days post-reporting. Despite their thorough methods, the team didn't find consistent imaging abnormalities distinguishing those with AHIs from healthy controls.

Research published in 2019 comparing a smaller sample of people reporting AHIs with controls found significant differences in white matter volumes and reduced functional connectivity in auditory and visual brain regions.

While this latest research failed to support those findings, it did find that people with Havana syndrome self-reported more problems with balance and higher levels of fatigue, depression, and post-traumatic stress disorder compared to the control group.

"The post-traumatic stress and mood symptoms reported are not surprising given the ongoing concerns of many of the participants," says neuropsychologist Louis French from Walter Reed National Military Medical Center.

"Often these individuals have had significant disruption to their lives and continue to have concerns about their health and their future. This level of stress can have significant negative impacts on the recovery process."

In terms of reported symptoms, 41 percent of AHI-affected participants met the criteria for functional neurological disorders (FNDs) – conditions of weakness and sensory impediments stemming from abnormal brain function, often linked to stress, depression, and anxiety. Many of these participants also experienced symptoms like dizziness, vertigo, and unsteadiness.

The researchers suggest that if the Havana syndrome symptoms were caused by an external factor, it's possible they are no longer detectable with current tests and sample sizes.

"While we did not identify significant differences in participants with AHIs," Chan says, "it's important to acknowledge that these symptoms are very real, cause significant disruption in the lives of those affected and can be quite prolonged, disabling and difficult to treat."

The studies have been published in JAMA, here and here.