Hippocampal subfields volumes as biomarkers for early diagnosis of asymptomatic manganese overexposure

Chronic occupational manganese (Mn) overexposure is associated with motor and cognitive deficits, but its effects on hippocampal subfields remain underexplored. Although neurodegeneration is known to involve the hippocampus, subfield-specific structural abnormalities have received limited attention. This study aimed to assess the diagnostic power of hippocampal subfield volumes in discriminating asymptomatic Mn-exposed welders from healthy controls (HCs). Mn-exposed welders and age-matched HCs were recruited and underwent high-resolution T1-weighted MRI scans. Volumes across 19 hippocampal subfields of each subject were estimated from automated tissue segmentations and surface-based reconstruction using FreeSurfer. The laterality value was defined as: (Right-Left)/(Right+Left)*100. Between-group differences in subfield volumes and laterality were assessed using cross-sectional analysis. Three machine learning classifiers, including logistic regression, K-nearest neighbors and support vector machine (SVM), were applied to differentiate welders from HCs. Compared to HCs, Mn-exposed welders had reduced volumes mainly in the fimbria, subiculum, and presubiculum, while showing higher volumes in the cornu ammonis area 3 (CA3). The welders group demonstrated significant rightward laterality in CA1 and CA4, and leftward laterality in the presubiculum. Among the three classifiers, the SVM classifier achieved the best performance (AUC = 0.96) in distinguishing welders from HCs using subfield volumes. Additionally, the exposure duration was non-linearly associated with left fimbria volume. These results revealed distinct volumetric and asymmetric patterns in hippocampal subfields among Mn-exposed welders, indicating regional vulnerability and potential compensatory responses. Notably, our findings underscored that hippocampal subfield volumes might serve as imaging biomarkers for early diagnosis in individuals with asymptomatic Mn overexposure.