Altered amplitude of low-frequency fluctuations in herpes simplex encephalitis: a resting-state fMRI study and...

To investigate alterations in the amplitude of low-frequency fluctuations (ALFF) in herpes simplex encephalitis (HSE) patients using resting-state functional magnetic resonance imaging (rs-fMRI) and evaluate their associations with anxiety symptoms. In this single-center cohort study, 45 HSE patients and 46 healthy controls (HC) were recruited from the First Affiliated Hospital of Zhejiang University School of Medicine, China. HSE was confirmed by clinical features and positive herpes simplex virus (HSV) DNA in cerebrospinal fluid via polymerase chain reaction. Participants underwent rs-fMRI scans within one week of ICU admission. ALFF was calculated using REST software; group differences were assessed with voxel-wise two-sample t-tests (covariates: age, sex, education, framewise displacement; whole-brain voxel-wise FDR-corrected P < 0.05) and validated nonparametrically. Associations between ALFF and anxiety (Hamilton Anxiety Rating Scale, HAMA) were examined via general linear models, controlling for age, sex, hypertension, and education, with Spearman's correlations for robustness. Compared to HC, HSE patients exhibited increased ALFF in the left precuneus and right putamen, alongside decreased ALFF in the right angular gyrus and right caudate nucleus (whole-brain voxel-wise FDR-corrected P < 0.05). These changes correlated significantly with HAMA scores: positive associations in hyperactive regions (left precuneus: β = 0.558, 95% CI: 0.312 to 0.805, p < 0.001; right putamen: β = 0.511, 95% CI: 0.254 to 0.768, p < 0.001) and negative associations in hypoactive regions (right angular gyrus: β = -0.517, 95% CI: -0.773 to -0.261, p < 0.001; right caudate: β = -0.556, 95% CI: -0.804 to -0.307, p < 0.001). No significant correlations emerged with depression scores (Hamilton Depression Rating Scale). HSE induces region-specific ALFF disruptions, characterized by hyperactivity in the precuneus and putamen together with hypoactivity in the angular gyrus and caudate within limbic-paralimbic networks. These alterations show strong associations with anxiety severity, suggesting ALFF as a potential noninvasive biomarker for HSE-related functional and neuropsychiatric impairments. Larger longitudinal studies are warranted to elucidate underlying mechanisms and therapeutic implications.