Brain network functional connectivity changes in patients with anterior knee pain: a resting-state fMRI exploratory study

Background: This study investigates the functional brain connectivity in patients with anterior knee pain (AKP). While biomechanical models are frequently employed to investigate AKP, it is important to recognize that pain can manifest even in the absence of structural abnormalities. Leveraging the capabilities of functional magnetic resonance imaging (fMRI), this research aims to investigate the brain mechanisms present in AKP patients.

Methods: Forty-five female subjects (24 AKP patients, 21 controls) underwent resting-state fMRI and T1-weighted structural MRI. Functional brain connectivity patterns were analyzed, focusing on pain network areas, and the influence of catastrophizing thoughts was evaluated.

Results: Comparing patients and controls, several findings emerged. First, patients with AKP exhibited increased correlation between the right supplementary motor area and cerebellum I, as well as decreased correlation between the right insula and the left rostral prefrontal cortex and superior frontal gyrus. Second, in AKP patients with catastrophizing thoughts, there was increased correlation of the left lateral parietal cortex with two regions of the right cerebellum (II and VII) and the right pallidum, and decreased correlation between the left medial frontal gyrus and the right thalamus. Furthermore, the correlation between these regions showed promising results for discriminating AKP patients from controls, achieving a cross-validation accuracy of 80.5%.

Conclusions: Resting-state fMRI revealed correlation differences in AKP patients compared to controls and based on catastrophizing thoughts levels. These findings shed light on neural correlates of chronic pain in AKP, suggesting that functional brain connectivity alterations may be linked to pain experience in this population.

Relevance statement: Etiopathogenesis of pain in anterior knee pain patients might not be limited to the knee, but also to underlying alterations in the central nervous system: cortical changes might lead a perpetuation of pain.

Key points: • Anterior knee pain patients exhibit distinct functional brain connectivity compared to controls, and among catastrophizing subgroups. • Resting-state fMRI reveals potential for discriminating anterior knee pain patients with 80.5% accuracy. • Functional brain connectivity differences improve understanding of pain pathogenesis and objective anterior knee pain identification.