Large-scale brain network analysis reveals functional-structural dissynchrony in HIV-associated asymptomatic neurocognitive disorders: Functional disturbances precede structural changes

BackgroundIn the era following combined antiretroviral therapy (cART), asymptomatic neurocognitive impairment (ANI) has become the primary stage of HIV-associated neurocognitive disorder (HAND). As a potentially reversible phase, precise identification of ANI is crucial. Multimodal MRI, with its non-invasiveness and high sensitivity, can reveal potential changes in brain network function and structure, providing significant support for exploring biomarkers of HAND and optimizing intervention strategies.This study aims to explore the dynamic changes in the functional network, structural network, and functional-structural coupling in ANI patients using multimodal MRI combined with large-scale brain network analysis. MethodsA total of 95 participants were included, consisting of a healthy control group (HC, n=48) and an ANI patient group (n=47). Functional and structural connectivity matrices were constructed using resting-state fMRI (rs-fMRI) and diffusion tensor imaging (DTI), and graph theory analysis was used to evaluate global metrics, node characteristics, and functional-structural coupling changes. ResultsStructural Network: No significant changes were observed in the global or local topological properties of the structural network in ANI patients. Functional Network: Significant reorganization was observed in several key regions, including the visual network, executive control network, and default mode network. Functional-Structural Coupling: The functional-structural coupling in the occipital and frontal networks was significantly enhanced. Clinical Relevance: Changes in the functional network and functional-structural coupling were associated with the patients immune status, duration of infection, and cognitive performance. ConclusionThe reorganization of the functional network and enhancement of functional-structural coupling during the ANI phase may reflect early manifestations of microscopic pathological changes (such as synaptic and dendritic damage). These changes hold promise as early warning signals in the progression of HAND and provide sensitive biomarkers and important research perspectives for precise diagnosis and early intervention.