Functional reorganisation of lingual gyrus mediates cognitive impairment in COPD: a multimodal neuroimaging study

Background Chronic Obstructive Pulmonary Disease (COPD) is a systemic disorder associated with cognitive impairment and affective dysfunction. However, the underlying neurobiological mechanisms remain unclear. This study examines brain reorganisation in patients with COPD and investigates potential neural mediators of cognitive and affective deficits. Methods We enrolled 51 COPD patients and 50 age- and sex-matched healthy controls (HC). All participants underwent high-resolution structural MRI and resting-state functional MRI. Comprehensive neuropsychological assessments for cognitive function (Montreal Cognitive Assessment, MoCA) and affective symptoms (Beck Depression Inventory, BDI; State-Trait Anxiety Inventory, S-TAI). Voxel-wise analyses compared gray matter volume (GMV), fractional amplitude of low-frequency fluctuations (fALFF), and functional connectivity strength (FCS) between groups. Mediation analysis was performed to explore causal pathways linking COPD, brain alterations, and cognitive-affective dysfunction. Results COPD patients exhibited significant cognitive deficits (lower MoCA scores) and higher affective symptom burden (elevated BDI and S-TAI scores) compared to HC. Neuroimaging revealed no GMV differences but distinct functional abnormalities: increased fALFF in bilateral lingual gyri and decreased fALFF in the right inferior orbitofrontal and left middle occipital regions, alongside enhanced long-range FCS in right frontal and fusiform areas (cluster-level p<0.05, FWE-corrected). Functional connectivity between bilateral lingual gyri was strengthened in COPD and correlated with anxiety symptoms. Critically, mediation analysis demonstrated that increased fALFF in the left lingual gyrus and enhanced interhemispheric connectivity in the lingual region mediated COPD-related cognitive decline, suggesting compensatory mechanisms. Conclusions COPD is associated with functional brain reorganisation, particularly in cognitive and emotional regions, without overt structural changes. The lingual gyrus emerges as a key compensatory hub, where heightened activity and connectivity may mediate cognitive impairment. These findings illuminate neuroprotective pathways in COPD and propose the lingual gyrus as a potential target for interventions aimed at preserving cognitive function.