Abstract
BACKGROUND: Hemispheric lateralization of brain structure and function supports cognitive processing. However, its alterations across different cognitive impairment subtypes and severities remain unclear. METHODS: In this case-control study, 104 participants were enrolled, including 47 with amnestic mild cognitive impairment (aMCI), 27 with non-amnestic MCI (naMCI), and 30 healthy controls. Functional and white matter structural brain networks were constructed separately for the left and right hemispheres. Graph-theoretical metrics and structure-function coupling were computed to assess intergroup and interhemispheric differences. Correlation analyses examined associations between network alterations and cognitive performance. RESULTS: Functionally, both MCI groups showed a significant leftward reduction in small-world properties (p < 0.05), with aMCI patients exhibiting reduced clustering coefficient and local efficiency in the left hemisphere. Structurally, lateralization of left-hemispheric local efficiency was disrupted in patients. Altered structure-function coupling revealed loss of right-hemispheric dominance in patient groups. Abnormal interhemispheric parameters correlated with memory deficits in aMCI. Node-level analysis revealed aMCI abnormalities concentrated in limbic and multimodal networks, while naMCI displayed more diffuse alterations involving the executive control network. CONCLUSIONS: aMCI and naMCI exhibit distinct patterns of lateralization abnormalities, with aMCI patients being characterized by the disintegration of specific local functional networks in the left hemisphere. Therefore, ameliorating abnormal patterns of hemispheric lateralization could serve as a purpose of the intervention.