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

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.

We enrolled 51 COPD patients and 50 age- and sex-matched healthy controls. All participants underwent high-resolution structural magnetic resonance imaging (MRI) and resting-state functional MRI. Comprehensive neuropsychological assessments for cognitive function (Montreal Cognitive Assessment (MoCA)) and affective symptoms (Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI)) were conducted. Voxel-wise analyses compared grey matter volume, fractional amplitude of low-frequency fluctuations (fALFF) and functional connectivity strength between groups. Mediation analysis was performed to explore causal pathways linking COPD, brain alterations and cognitive-affective dysfunction.

COPD patients exhibited significant cognitive deficits (lower MoCA scores) compared with healthy controls, and greater affective symptom burden (higher BDI and STAI scores). Neuroimaging revealed no grey matter volume 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 functional connectivity strength in the right frontal and fusiform areas (cluster-level p<0.05, family-wise error-corrected). Functional connectivity between bilateral lingual gyri was strengthened in those with 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.

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.