WASHINGTON — A group of U.S. government workers potentially exposed to unexplained phenomena in Cuba have less white matter in their brains and less connectivity in the areas that control vision and hearing than similar healthy people, doctors have found.

The findings from University of Pennsylvania researchers are the most specific to date about the neurological condition of the U.S. diplomats, spies and their families who reported strange sounds and sensations while serving in Havana between 2016 and 2018.

Yet while doctors found "significant differences" in their brains compared to a control group, they couldn't say whether they were caused by whatever may have happened in Cuba, nor whether those differences account for the Americans' symptoms.

Maps of white matter and gray matter tissue volume were created for each participant using T1-weighted images and registering them to a template. For panel A, axial views of the brain, and panel B, sagittal views of the cerebellum and cerebrum, locations of chosen slices are shown by red lines on the template brain (first image in each panel).

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The medical findings, revealed Tuesday in the Journal of the American Medical Association, come as U.S. national security officials tell NBC News that more than two years into the mystery, the government still has not determined who or what is responsible for what transpired in Havana.

The FBI, enlisted in 2017 to investigate what the U.S. has called "targeted attacks," paid multiple trips to Havana but has exhausted its leads in the case, individuals briefed on the investigation say. While the investigation hasn't been formally closed, no external energy source in Cuba has yet been identified that could have caused the injuries, they said. The FBI declined to comment.

Although the Trump administration has not retreated from its assertions that its workers in Cuba were attacked, officials at the FBI, the CIA and the State Department are also examining the possibility that mass psychogenic illness, or psychosomatic symptoms that spread through a community, may be to blame in at least some of the cases, officials said.

The Cuban Embassy in Washington didn't respond to a request for comment. But Dr. Mitchell Joseph Valdés-Sosa, the Cuban Neuroscience Center chief who has been investigating the U.S. claims, said there were major "causes for concern" in the study's methodology, including the makeup of the control group and assertions about brain changes that he said could have resulted from "many factors, including psychological states."

"The most worrisome aspect is the attempt to link these findings with an unspecified 'directional phenomenon,'" Valdés-Sosa said. "The research in this area has been cloaked in secrecy, and driven by cold war paranoia."

Twenty-six Americans who served in Cuba were "medically confirmed" by the State Department to have been affected. The Penn study included most of those workers, their relatives who lived with them and other U.S. workers referred to Penn for potential exposure, bringing the total to 40.

Using a battery of advanced MRIs, researchers created a detailed map of their brains, including the pathways and connections that let parts of the brain communicate with one another. It takes a computer more than 24 hours to process the data and create the maps, officials tell NBC News. The results from all individuals in the Cuba group were combined, then custom software was used to compare those results to a map made from MRIs of 48 individuals of similar age and ethnicity.

Doctors found that in measuring white matter — nerve fibers that form the brain's communications network — the Cuba patients had a mean volume that was 27 cubic centimeters smaller than the control patients. Overall, they had similar volumes of gray matter — rich with brain cells that process information — but in some regions of the brain, the Cuba patients had more gray matter.

Advanced neuroimaging that tracks how water molecules travel through the brain found decreased connectivity in the networks related to seeing and hearing, which tracks with many of the symptoms reported, but not in the networks that handle higher-level thinking processes. Still, doctors were unable to draw a clear connection between the findings and the patients' symptoms, which also included problems with balance, sleep and memory.

In 2018, similar incidents were reported among U.S. government workers serving in Guangzhou, China, and one American was "medically confirmed" by the State Department to have been affected. The Penn study was limited to Americans who were in Cuba, none of whom have been publicly identified.

NBC News Medical Correspondent Dr. John Torres said the small sample size and high sensitivity of the brain scans could have produced results that appear unusual but aren't clinically significant.

"Even though, as a group, these government personnel have changes to parts of their brains seen on MRI images, those changes cannot be tied directly to what they report happened in Cuba," Torres said.

Starting in late 2016, U.S. diplomats and intelligence officers in Cuba started reporting strange incidents that the Penn study describes as "potential exposure to uncharacterized directional phenomena" of unknown origins, "manifesting as pressure, vibration or sound." Some reported ear-piercing sounds in their homes at night that would suddenly disappear when they moved just a few feet away.

The mysterious noises initially led investigators to suspect a sonic weapon, but investigators ruled out the possibility sound waves could have caused the damage. Officials have explored other possibilities such as a microwave or other electromagnetic energy source, as well as potential environmental causes and psychosomatic illness.

Because of how much is still unknown about the brain's inner workings, it's difficult to say whether any of those theories could neatly explain the specific changes to brain matter volume and connectivity identified by the MRI study, medical experts said.

The bizarre saga has inflicted significant damage on a U.S.-Cuba relationship that was only beginning to warm in recent years following half a century of enmity.

After declaring that its diplomats had been attacked, the United States pulled most of its workers out of Cuba and warned all Americans not to travel there. Those ties have been further weakened by the Trump administration's crackdown on Cuba and re-imposition of sanctions and travel restrictions that had been eased during the Obama administration.

In addition to Penn's study, the National Institutes of Health is conducting its own "brain injury research study" involving the Cuba patients with help from Energy Department supercomputers and national laboratories capable of processing massive amounts of neurological data. The Defense Department has also been engaged to look into technologies that could have been used to harm the Americans, NBC News has reported.

The State Department said it was aware of the new study from Penn doctors 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," the State Department said in a statement.