Advanced brain scans found perplexing differences in U.S. diplomats who say they developed concussion-like symptoms after working in Cuba, a finding that only heightens the mystery of what may have happened to them, a new study says.

Extensive imaging tests showed the workers had less white matter than a comparison group of healthy people and other structural differences, researchers said.

While they had expected the cerebellum, near the brain stem, to be affected given the workers' reported symptoms — balance problems, sleep and thinking difficulties, headaches and other complaints — they found unique patterns in tissue connecting brain regions.

Ragini Verma, a University of Pennsylvania brain imaging specialist and the lead author, said the patterns were unlike anything she's seen from brain diseases or injuries.

"It is pretty strange. It's a true medical mystery," Verma said.

This image provided by the American Medical Association in July 2019 shows the amount of differences between brain scans of patients, U.S. diplomats who developed concussion-like symptoms after working in Cuba, and a control group. (American Medical Association via The Associated Press)

Cuba denies any kind of attack

Co-author Dr. Randel Swanson, a University of Pennsylvania specialist in brain injury rehabilitation, said "there's no question that something happened," but imaging tests can't determine what it was.

An outside expert, University of Edinburgh neurologist Jon Stone, said the study doesn't confirm that any brain injury occurred, nor that the brain differences resulted from the strange experiences the diplomats said happened in Cuba.

Cuba has denied any kind of attack, which has strained relations with the United States.

"The article published today doesn't change the situation," said Johana Tablada, Cuba's deputy head of U.S. affairs. "The article recognizes that the changes detected are minimal, that their conclusions are uncertain and that they can't identify the cause."

The results were published Tuesday in the Journal of the American Medical Association. A journal editorial says the study may improve understanding of the reported symptoms, but that the relevance of the brain differences is uncertain.

Deputy director for the United States division of the Cuban Ministry of Foreign Affairs, Johana Tablada, speaks to reporters in Havana, Cuba, on Tuesday, July 23, 2019. (Ramon Espinosa/The Associated Press)

Canadian diplomats also complained of health problems

In a statement, the U.S. State Department said it "is aware of the study and welcomes the medical community's discussion on this incredibly complex issue. The Department's top priority remains the safety, security, and well-being of its staff."

Between late 2016 and May 2018, several U.S. and Canadian diplomats in Havana complained of health problems from an unknown cause. One U.S. government count put the number of American personnel affected at 26.

Some reported hearing high-pitched sounds similar to crickets while at home or staying in hotels, leading to an early theory of a sonic attack. The Associated Press has reported that an interim FBI report found no evidence that sound waves could have caused the damage.

Dozens of U.S. diplomats, family members and other workers sought exams. The new study reports on 40 of them tested at the University of Pennsylvania. A group analysis of results from advanced MRI scans found brain differences in the diplomat group compared with 48 healthy people with similar ages and ethnic background.

Workers had MRI tests about six months after reporting problems, but because their brains were not scanned before their Cuba stints they can't know if anything changed in their brains, a drawback of the study that the researchers acknowledge.

'It's going to be harder and harder to figure out what really happened'

Dr. Douglas Smith, director of the Penn Center for Brain Injury and Repair at the University of Pennsylvania, also worked on the study. He said many people have tried to dismiss what the patients were dealing with and he hopes this provides some vindication.

"There have been many individuals who had their opinions reported in the press who had never examined this patient group and claimed it was a psychological issues," he told CBC Radio's All In A Day on Wednesday.

Unfortunately, they can't from this study pinpoint what caused the damage, because the damaged brains are unlike anything they have ever seen, he said.

"What we found is the changes were different in this group compared to a concussion or anything else we have ever seen."

The University of Edinburgh's Stone said the new study has several other limitations that weaken the results, including a comparison group that wasn't evenly matched to the patients.

"If you really want to suggest that something fundamentally different happened in Cuba ... then the best control group would be 40 individuals with the same symptoms who hadn't been to Cuba and had no history of head injury," Stone said.

The latest study builds on earlier preliminary reports involving 21 U.S. workers who got brain scans showing less detailed white matter changes. The new study includes 20 of those workers.

A previous study from the University of Miami found inner-ear damage in some workers who complained of strange noises and sensations, but it also lacked any pre-symptom medical records.

Although some workers have persistent symptoms, most have improved with physical and occupational therapy, are doing well and have returned to work, Swanson said.

As more time passes, he said, "It's going to be harder and harder to figure out what really happened."