How Does Lyme Disease Affect the Brain? New fMRI Study Reveals White Matter Changes

Researchers identified altered brain activity and white matter changes in PTLD
Patients completed memory tasks accurately but processed information more slowly
Early brain responses may help predict recovery after Lyme disease

Can Lyme disease affect the brain? Yes. Research using functional magnetic resonance imaging (fMRI) has identified altered brain activity and white matter changes in some individuals with post-treatment Lyme disease (PTLD). These findings may help explain why patients often report brain fog, slower thinking, difficulty concentrating, and memory problems even when routine brain imaging appears normal.

Marvel and colleagues administered working memory tests to 12 individuals with PTLD and 18 healthy controls while participants underwent functional magnetic resonance imaging. The investigators used multimodal neuroimaging techniques to better understand how Lyme disease may affect brain function. Unlike a conventional MRI, which primarily shows brain structure, an fMRI measures changes in blood flow associated with neural activity.

In their study, A multimodal neuroimaging study of brain abnormalities and clinical correlates in post treatment Lyme disease, the investigators found altered patterns of brain activation in patients with PTLD compared with healthy controls.¹

Patients processed information more slowly

Although individuals with PTLD completed the working memory tasks as accurately as healthy controls, they required more time to respond.

The authors reported that patients with PTLD “responded more slowly, but no less accurately, than did controls.” This finding suggests that cognitive processing speed may be affected even when memory accuracy remains intact.

What did the brain scans show?

Several brain regions demonstrated reduced activation in patients with PTLD during working memory testing. At the same time, other brain regions showed increased activity that was not observed in healthy controls.

The investigators concluded that these additional areas of activation likely represented compensatory mechanisms, allowing patients to maintain normal task performance despite slower processing speed.

“The PTLD group relied on compensatory mechanisms to complete the task, given that they performed as well as controls did.”

Why are white matter findings important?

One of the study’s most important observations involved the brain’s white matter.

White matter consists of bundles of nerve fibers that connect different regions of the brain, allowing information to travel efficiently between them. Injury or dysfunction involving white matter can affect processing speed, attention, executive function, and memory.

“Together, these results show that the brain is altered by PTLD, involving changes to white matter within the frontal lobe.”

The investigators also found that higher axial diffusivity within these white matter regions was associated with fewer neurologic and cognitive symptoms. They suggested these findings may represent white matter repair and healing over time rather than permanent injury.

“Higher axial diffusivity may reflect white matter repair and healing over time, rather than pathology.”

New research suggests early brain changes may predict recovery

Marvel and colleagues recently extended these observations by studying patients during early Lyme disease and following them for six months after treatment. Individuals who ultimately returned to health demonstrated stronger early brain activation, much of it involving white matter, than patients who later developed persistent symptoms.²

The investigators also found that greater early brain activation correlated with better health-related quality-of-life scores. These findings suggest that the brain’s early response to Lyme disease may influence long-term recovery and could eventually help identify patients at greater risk for persistent symptoms.

Does Lyme disease cause brain lesions?

Patients frequently ask whether Lyme disease causes brain lesions. Conventional MRI may occasionally demonstrate nonspecific white matter abnormalities, but these findings are neither sensitive nor specific enough to diagnose Lyme disease.

The advanced MRI techniques used in the Marvel studies evaluated brain function and white matter integrity rather than simply looking for structural lesions. These sophisticated imaging methods may provide important insights into cognitive symptoms that are not visible on routine MRI scans.

What do these findings mean?

The Marvel studies provide objective evidence that PTLD can be associated with measurable changes in brain function and white matter. These imaging findings help validate the cognitive complaints reported by many patients, including brain fog, slowed information processing, poor concentration, and mental fatigue.

However, the imaging studies do not identify the underlying cause of these abnormalities. Persistent Borrelia burgdorferi infection, ongoing tick-borne coinfections, immune dysregulation, neuroinflammation, altered neural activation, autonomic dysfunction, and other mechanisms remain active areas of investigation. These mechanisms are not mutually exclusive and may overlap in some patients.

Because there is currently no laboratory test that reliably confirms whether Borrelia burgdorferi infection has been completely eradicated in an individual patient, careful clinical judgment remains essential when evaluating persistent neurologic symptoms. Clinicians must consider the patient’s history, physical examination, laboratory findings, response to previous treatment, possible coinfections, and alternative diagnoses when determining the most appropriate management strategy.

Future research combining advanced brain imaging with microbiologic, immunologic, and clinical studies may help determine which patients are most likely to benefit from different treatment strategies and further clarify the biological mechanisms responsible for persistent symptoms.

Note: The original neuroimaging study included a relatively small number of carefully selected participants. Larger studies will be needed before these findings can be generalized to all patients with PTLD.

Frequently Asked Questions

Can Lyme disease cause brain fog?

Yes. Brain fog is one of the most frequently reported cognitive symptoms in Lyme disease and PTLD. Patients commonly describe slower thinking, difficulty concentrating, memory problems, and mental fatigue. The Marvel studies identified measurable differences in brain activation that may help explain these symptoms.

Can an MRI detect Lyme disease?

A routine MRI is often normal in patients with Lyme disease. Advanced imaging techniques such as functional MRI (fMRI) and diffusion tensor imaging can detect subtle changes in brain function and white matter that are not visible on conventional MRI, but these tests are not currently used to diagnose Lyme disease in routine clinical practice.

Can brain fog improve after Lyme disease treatment?

Yes. Some patients experience gradual improvement in brain fog and cognitive function following treatment for Lyme disease, while others continue to have persistent symptoms. In my practice, some carefully selected patients have improved following retreatment, whereas others have required treatment directed at tick-borne coinfections, autonomic dysfunction, immune-mediated illness, sleep disorders, hormonal abnormalities, nutritional deficiencies, or other contributing conditions. Because no laboratory test can reliably determine whether infection has completely resolved, management must be individualized.

Clinical Takeaway

After nearly four decades of treating patients with Lyme disease, brain fog remains one of the most common and frustrating symptoms I encounter. Patients frequently describe slower thinking, poor concentration, difficulty finding words, and mental fatigue despite normal neurological examinations or routine MRI studies.

One of the greatest challenges is determining why these symptoms persist. Researchers continue to investigate several possible mechanisms, including persistent Borrelia burgdorferi infection, ongoing tick-borne coinfections, immune dysregulation, neuroinflammation, autonomic dysfunction, and combinations of these processes.

At present, clinicians do not have a reliable laboratory test that can determine whether a Borrelia burgdorferi infection has completely resolved after treatment. Likewise, no single test can reliably distinguish persistent infection from post-infectious immune or inflammatory mechanisms in an individual patient.

In my practice, I have cared for patients whose cognitive symptoms improved following carefully selected retreatment, suggesting that persistent Borrelia burgdorferi infection and/or ongoing tick-borne coinfections may contribute in some individuals. Other patients improve only after treatment directed at coinfections, autonomic dysfunction, immune-mediated illness, sleep disorders, hormonal abnormalities, nutritional deficiencies, or other contributing conditions.

These experiences reinforce the importance of individualized evaluation rather than assuming every patient has the same underlying mechanism for persistent cognitive symptoms.

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References:

1. Marvel CL, Alm KH, Bhattacharya D, Rebman AW, Bakker A, Morgan OP, et al. A multimodal neuroimaging study of brain abnormalities and clinical correlates in post treatment Lyme disease. PLoS One. 2022;17(10):e0271425.
2. Marvel CL, Rebman AW, Alm KH, Touradji P, Bakker A, et al. Early brain changes in Lyme disease are associated with clinical outcomes. Brain Behav Immun Health. 2025;50:101153.
3. Biniaz-Harris N, Kuvaldina M, Fallon BA. Neuropsychiatric Lyme Disease and Vagus Nerve Stimulation. Antibiotics (Basel). 2023;12(9):1347.
4. Coughlin JM, Yang T, Rebman AW, et al. Imaging glial activation in patients with post-treatment Lyme disease symptoms: a pilot study using PET. J Neuroinflammation. 2018;15:346.

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Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.

Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention