Early brain changes in Lyme disease are associated with clinical outcomes

Lyme disease (LD) is a tick-borne infection due to the bacteria Borrelia burgdorferi . After antibiotic treatment, 10-20% of patients develop post-treatment Lyme disease (PTLD). Neurological symptoms are commonly reported in PTLD. This case-control study tested the hypothesis that brain changes occur in LD and are related to clinical outcomes.

A working memory task was administered during functional MRI (fMRI), in conjunction with cognitive assessments and health surveys, to examine brain function and clinical outcomes in people with acute LD disease (n=20; 55.0% male; mean age (range) = 52.3 (26-78)). Assessments were conducted a mean of 15.2 days (range: 1-51) after initial antibiotic treatment [i.e., “baseline”] and again 6 months later. A well-matched group of healthy controls (HC, n=19; 31.6% male; mean age (range) = 46.5 (19-60)) was also assessed 6 months apart. At the 6-month follow-up, the LD group was categorized into those who returned to health (RTH, n=11) and those reporting persistent symptoms (sPTLD, n=9) to determine if early brain changes predicted subsequent outcomes. FMRI data from both LD groups were compared to the HC group. Regions of interest (ROI) values were obtained from the fMRI results and correlated to cognitive performance and symptom survey scores.

At baseline, brain activity in the RTH group was significantly increased relative to that of HC. Notably, 64% of the RTH group’s activation clusters were in white matter, confirmed by segmentation analysis. ROIs created from the RTH vs. HC fMRI results, including white matter regions, significantly correlated with better self-reported clinical outcomes. At the 6-month follow-up, most of the RTH group’s activity had normalized relative to HC, and associations between ROI values and clinical outcomes were no longer observed. The sPTLD group showed few fMRI activation differences versus the HC group at either time point, and no significant associations were observed between ROI values and clinical outcomes. Instead, the sPTLD group’s ROI values negatively correlated with cognitive performance at the 6-month follow-up.

These results indicate that early brain changes in LD predict future RTH status. Increased brain activation during cognition, including in white matter, may reflect a healing response without which LD patients are more likely to develop PTLD. The observed increased activation in white matter suggests specific mechanisms, such as appropriate astrocyte reactivity, and require further investigation. Understanding how increased brain activity relates to RTH in LD will aid early identification of those vulnerable to developing PTLD and guide treatment.