Early brain changes in Lyme disease are associated with clinical outcomes.

In Lyme disease (LD), 10-20 % of patients develop persistent symptoms following antibiotic treatment (i.e., post-treatment Lyme disease (PTLD)), which often includes neurological symptoms. This study tested the hypothesis that physiological brain changes occur early in LD and influence outcomes. Task-based functional MRI (fMRI) and health surveys were administered to patients with acute LD (n = 20) after treatment and six months later. Demographically matched healthy controls (HC; n = 19) were also assessed six months apart. The LD group was categorized at six months into those who had returned to health (RTH, n = 11) or reported persistent symptoms (sPTLD, n = 9). FMRI data from both LD subgroups were compared to each other and HC at both time points. FMRI-guided regions of interest (ROI) values were compared to health surveys. Baseline brain activity in RTH was elevated in fronto-parietal regions relative to sPTLD (p < .0025) and HC (p < .001). Notably, 64 % of activation clusters in RTH were in white matter, confirmed by segmentation analysis. FMRI-guided ROI values from RTH vs. HC correlated with higher health survey scores. At 6-months, few group differences remained. By contrast, sPTLD vs. HC fMRI comparisons yielded few activation differences at either time point or correlations with health survey scores. Robust brain activity in early LD was associated with future RTH. By contrast, the absence of early brain activity was associated with persistent symptoms, suggesting that failure to mount an early response contributes to PTLD. Understanding how brain activity relates to recovery in LD can aid prognosis and guide treatment.