Two rigorous government studies found no unusual pattern of injury or disease in the brains of people with the mysterious cluster of symptoms known as Havana syndrome.
The studies involved more than 80 government employees and family members who experienced "anomalous health incidents" while stationed in countries including Cuba, China, Austria, and the United States.
Many of the individuals had reported hearing odd sounds or sensing pressure before suddenly developing symptoms including vertigo, loss of balance, and ear pain.
Some U.S. government officials have suggested the symptoms were the result of attacks by other nations, perhaps using a weapon that directed electromagnetic energy at individuals.
But the studies, conducted at the National Institutes of Health, did not find evidence supporting that idea. Instead, it found that the brains of affected people were no different than the brains of similar people who hadn't reported symptoms. The results were published in JAMA, the journal of the American Medical Association.
"We didn't see differences in the structure of the brain or even in the functional connectivity of the brain," says Dr. Leighton Chan, chief of rehabilitation medicine at the NIH Clinical Center.
The findings are the latest to challenge the idea that hundreds of government workers and their families have been targeted and injured since 2016, when the first cases were reported by embassy staff in Havana.
In 2023, five U.S. intelligence agencies concluded it was "highly unlikely" that Havana syndrome was the result of a foreign attack, and found "no credible evidence" that a weapon capable of causing the symptoms even existed.
In 2022, a CIA report found that most of the symptoms attributed to Havana syndrome were from previously diagnosed illnesses or stress.
But neither those reports, nor the two new studies, rule out the possibility that some individuals have been attacked and injured, says Dr. David Relman, a professor of medicine and of microbiology and immunology at Stanford University who wrote an editorial accompanying the new research.
"There are multiple problems with both of the studies," says Relman, who was part of an assessment by the National Academies that concluded that "directed pulsed radio frequency energy" could have produced the signs and symptoms of Havana syndrome.
For example, he says, even the most sophisticated brain scans can miss a subtle brain injury, especially if the brain has had time to heal.
Another problem is that the studies lumped together a broad range of people, and studied their brains at different time points after symptoms first appeared, Relman says. A focus on certain individuals, all tested soon after the event, might have produced a different result, he says.
Brain scans and blood tests
One of the new studies used magnetic resonance imaging to compare the brains of 81 affected individuals with the brains of 48 people in similar jobs.
A smaller study at the University of Pennsylvania in 2019 had found some subtle differences in the brains of people with symptoms of Havana syndrome.
"We didn't," says Dr. Carlo Pierpaoli, chief of the NIH's laboratory on quantitative medical imaging.
The NIH study was larger, Pierpaoli says, and used a control group that was better matched — in terms of age, profession, and location — to the group being studied. It also was designed to produce highly consistent results.
The results should be "reassuring" to affected government workers and their families, Pierpaolo says. If there had been any progressive disease in the brains, he says, "we would have been able to measure it."
The other NIH study tested 86 participants' hearing, vision, and balance, and conducted blood tests that can indicate a traumatic brain injury. These tests showed no significant difference between the participants and 30 similar people without symptoms.
But psychosocial tests found that affected people were more likely to have symptoms of fatigue, post-traumatic stress, and depression.
"Some of these people are in distress," says Louis French, a neuropsychologist who has been treating Havana syndrome patients at Walter Reed National Military Medical Center. "So we are doing our best to address some of that distress that's associated with them feeling sick."
Proving a negative
The scientists studying Havana syndrome agree that it is all but impossible to prove that something doesn't exist or didn't happen. But they differ on what steps should be taken next.
"I would urge a more holistic, truly integrated assessment of all available data on individual cases," Relman says. "It's not going to be easy, but I believe it can be done."
Chan doubts that would settle the matter.
"Medical research may not be the answer to this," he says. If there really is something triggering Havana syndrome, "the answer is counterintelligence, somebody taking a photo of whatever it is."