Researchers have investigated brain function in people with Lyme disease using a new method involving functional MRI scans.
In a study utilising specialised imaging techniques, researchers at Johns Hopkins Medicine reported on distinctive changes in the white matter, a condition affecting 10–20 per cent of the nearly half a million Americans diagnosed with Lyme disease each year.
The findings of the study, published in the journal PLOS ONE on 26 October, support and help to substantiate the view that the memory and other cognitive difficulties experienced in the long term by people with post-treatment Lyme disease are linked to functional and structural changes in the brain.
Lyme disease, whose early symptoms may include the characteristic bull’s-eye rash, flu-like aches and fever, joint pain and fatigue, can be treated with a rigorous course of antibiotics, which usually cures the disease. However, in those considered to be long-term sufferers, whose symptoms of Lyme disease persist even after the completion of antibiotic treatment, the condition becomes a chronic illness characterised by fatigue, muscle pain, insomnia, depression and cognitive difficulties, such as problems with concentration and memory. In these patients, there is generally no obvious clinical or laboratory evidence of ongoing problems.
Real-time monitoring of changes in the brain
Researchers from the departments of neurology, psychiatry and behavioural sciences at Johns Hopkins Medicine, in collaboration with the Lyme Disease Research Centre, have conducted functional MRI (fMRI) scans. fMRI shows changes in blood flow within the brain, enabling the identification of long-term changes in brain function that may cause certain persistent symptoms of Lyme disease. These scans enable researchers to monitor changes in the brain in real time.
“Objective biological markers of post-treatment Lyme symptoms cannot usually be identified using standard CT, MRI or blood tests” – says Dr John Aucott, director of the Johns Hopkins Clinical Research Centre for Lyme Disease and associate professor at the Johns Hopkins University School of Medicine. “We had to expand our assessment methods,” he adds.
Led by lead author Dr Cherie Marvel, the team recruited 12 men and women, patients with Lyme disease who had undergone antibiotic treatment, as well as 18 participants who did not have Lyme disease, to take part in fMRI scans whilst performing a short-term memory task.
The imaging scans revealed unusual activity in the frontal lobe, the area of the brain responsible for cognitive tasks such as memory recall and concentration. Participants were asked to memorise and recall upper- and lower-case letters, as well as the alphabetical order of several letters.
According to the researchers, it is noteworthy that the scans revealed differences in the activity of the frontal lobes between the two groups in the brain’s white matter, which is not usually visible in fMRI scans as this tissue functions with less blood flow than grey matter. White matter is vital for the transmission of information within the brain; it functions like railway tracks, helping to convey information to the railway station – that is, the grey matter.
Frontal lobe activity
“Certain areas of the frontal lobe were underactive, whilst others were overactive, which was somewhat to be expected,” says Cherie Marvel. “However, we did not see the same white matter activity in the group that did not have post-treatment Lyme disease.”
To corroborate this finding, the researchers used another form of imaging, diffusion tensor imaging (DTI), on all 12 participants with Lyme disease and on 12 of the 18 participants without Lyme disease. DTI detects the direction of water movement within brain tissue. This unique approach corroborated their fMRI findings and revealed new insights: Water diffused – that is, seeped – along the patients’ axons – the extensions of nerve cells that transmit electrical signals to other nerve cells – within the very same areas of white matter that had been identified during the fMRI scans.
Surprisingly, the researchers also found that axonal leakage in the white matter correlated with fewer cognitive deficits and better outcomes in the post-treatment condition of the Lyme disease patients they studied.
The researchers believe that the increased activity observed in the white matter in post-treatment Lyme disease patients may reflect a beneficial immune response, as this correlated with a better outcome of the disease. However, this finding was also associated with the fact that patients with Lyme disease who had undergone treatment took longer to complete the memory task. According to the researchers, this suggests that the white matter response may be adaptive, but that the physiology and function of the white matter have changed.
“It was by approaching the problem in collaboration with experts from various fields that we obtained these novel findings, and hopefully this will provide answers to our remaining questions, particularly regarding the role of axonal leakage and white matter activation in post-treatment Lyme disease,” says the researcher.
According to Marvel and Aucott, this research may help shed light on the underlying mechanisms of neurological Lyme disease and potential therapeutic targets. Their findings may also be relevant to other chronic diseases associated with infections.
Source: Lymedisease.org, Johns Hopkins Medicine
(C) Lyme Borreliosis Foundation
