Nov. 15, 2022 – People who have been treated for Lyme disease, but continue to have symptoms, have changes in their brains that confirm the memory and concentration problems many of them have reported, a new study has found.
Many people with what’s known as post-treatment Lyme disease – or PTLD – complain about problems with memory and concentration, which sometimes come with fatigue, muscle pain, insomnia, and depression.
To understand potential changes in brain function that might explain these cognitive difficulties, researchers used specialized imaging techniques to compare the brains of 12 adults with PTLD and 18 adults with no history of Lyme disease.
The researchers found changes in the white matter of the brains of those with PTLD. White matter is found in the deeper brain tissues and contains nerve fibers that are extensions of nerve cells.
"We found that ... white matter function increased while participants with PTLD were performing a cognitive task," says lead investigator Cheri Marvel, PhD, an associate professor of neurology and psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine in Baltimore.
"I think if patients heard this, they might feel validated that there is a biologic basis for their persistent symptoms, even if there is no good way to treat the cognitive difficulties yet," she says. This may be similar to what patients with long COVID experience, Marvel says.
The study was published online Oct. 26 in the journal PLOS One.
‘We Could Begin to Connect the Dots’
"Objective biologic measures" of PTLD symptoms "typically can’t be identified using regular MRIs, CT scans, or blood tests," senior author John Aucott, MD, director of the Johns Hopkins Lyme Disease Clinical Research Center, said in a news release.
Because of the number of people affected by this condition — 10%-20% of the nearly half a million Americans who contract the disease each year — the researchers felt they needed to "expand" the evaluation methods.
"We were motivated by the persistent complaints of cognitive difficulties by patients who have been treated for their Lyme disease, with a lack of data to explain the reason behind these symptoms," Marvel says.
It seemed logical "that if there were cognitive and neurological symptoms involved, then the brain may reveal something about this. Then we could begin to connect the dots between the patient experience and the underlying mechanisms driving them," she says.
To investigate, Marvel’s team used functional magnetic resonance (fMRI), an imaging technique that measures blood flow to areas of the brain, often while specific tasks are performed — in this case, short-term memory tasks that involved memorizing and recalling capital and lowercase letters as well as the alphabetical order of multiple letters.
Those with PTLD performed more slowly on some of the memory tasks, although their slower speed did not affect the accuracy of their performance.
The researchers found unusual activity in the white matter of the frontal lobe — an area of the brain involved in cognitive tasks, such as memory recall and concentration — in the PTLD group.
Typically, this type of tissue sees less blood flow, compared to gray matter in the brain, and is responsible for moving information around the brain and "delivering" it to the gray matter. The amount of activity they saw "is unusual to observe with the MRI methods we used, and we did not see such activity in the healthy control group," Marvel says.
Sign of Healing?
To confirm the finding, the investigators used a second imaging technique called diffusion tensor imaging in all 12 PTLD patients and 12 of the 18 people without PTLD. The imaging technique detects whether there is water moving within the brain tissue and what direction it goes.
In the patients with PTLD, the researchers found what’s called axon diffusion – or leakage – from the white matter was tied to better brain function. The water that was diffusing was found in the same white matter regions that the first imaging test had identified.
"This led us to speculate that the white matter changes are a healthy response to Lyme disease’s effect on the brain," Marvel says. She suggests that the increased white matter leakage "may be a marker of healing during PTLD and represent a healthier outcome."
In the meantime, the researchers want to work with other experts to answer their remaining questions, she says.
"It is important for clinicians to know that PTLD leads to real, quantifiable brain changes and that patients’ cognitive complaints may be a direct consequence of these brain changes, rather than a side effect of other symptoms, such as fatigue, for example," Marvel said.
Commenting on the study for this report, John Keilp, PhD, an associate professor of clinical psychology at Columbia University in New York City, says it is an "important, carefully executed study that expands upon earlier brain imaging studies of patients with PTLD" using "state-of-the-art brain imaging and analysis methods."
The researchers "have shown us a way forward to examine these patients and this disorder in greater detail as we attempt to unlock the uncertainties surrounding the physiological basis of these patients’ symptoms," says Keilp, who heads the neuropsychology laboratory in the division of Molecular Imaging and Neuropathology at the New York State Psychiatric Institute.