Altered effective connectivity within the hippocampal-prefrontal circuit in patients with non-small cell lung cancer after platinum chemotherapy.

Abstract

To investigate the effects of platinum-based chemotherapeutic drugs on the effective connectivity (EC) of hippocampal-prefrontal (HIP-PFC) circuit in non-small cell lung cancer (NSCLC) patients utilizing spectral dynamic causal model (sDCM), and to explore its correlation with cognitive deficits. A total of 109 patients diagnosed with NSCLC (57 without chemotherapy (CT-) and 52 with chemotherapy (CT+)) and 60 healthy controls (HCs) were enrolled. Longitudinal data pre- and post-chemotherapy were available for 30 patients. All participants underwent functional magnetic resonance imaging (fMRI) and cognitive assessments. Effective connectivity within the HIP-PFC circuit for all participants were analyzed using the sDCM approach. Relationships between abnormal connectivity strength and neuropsychological scores were evaluated. The results revealed ECs differences among three groups in the HIP-PFC circuit concentrated in the bilateral hippocampus and right frontal lobe. Analysis of paired groups identified more abnormalities across cerebral hemispheres, including excitatory connectivity from l-HIP to right lateral prefrontal cortex (LPFC). The reduced EC from the l-HIP to the medial prefrontal cortex (mPFC) was significantly negatively correlated with the MoCA scores (r = -0.315, p = 0.007), and the reduced EC from the r-HIP to the mPFC was significantly negatively correlated with the memory scores (r = -0.349, p = 0.006). These insights further bolstered the crucial role of the HIP-PFC circuit in the pathophysiology of cognitive impairment induced by platinum-based chemotherapeutic agents, highlighting its potential as a novel imaging biomarker and therapeutic target.