Amygdala and Nucleus Accumbens Activation Predict Treatment Decisions in Knee Osteoarthritis: An fMRI Study Comparing TKR and Conservative Management

Background Pain in knee osteoarthritis (KOA) often shows a limited correlation with radiographic severity, complicating treatment decision-making and highlighting the need to understand central mechanisms of pain. Functional magnetic resonance imaging (fMRI) allows investigation of brain regions such as the amygdala and nucleus accumbens, which are increasingly recognized as key modulators of pain chronification and may influence therapeutic choices, including the decision to undergo total knee replacement (TKR). This study is part of the HOLOA Project (Clinical and virtual examination of patients for holistic and objective description of the osteoarthritis progression mechanisms). Methods We conducted a cross-sectional observational study nested within the HOLOA cohort. Thirty-one patients with KOA (20 managed conservatively [CM], 11 undergoing TKR) aged 60–70 years with Kellgren-Lawrence (KL) grades 2–3 were included. Participants underwent two fMRI paradigms with pressure stimulation (Knee Interline and Tibial Surface tests). Clinical assessment included WOMAC, Pain Catastrophizing Scale (PCS), Hospital Anxiety and Depression Scale (HAD), and Numeric Rating Scale (NRS). Group comparisons and correlation analyses were performed to explore associations between clinical variables and brain activation. Results Demographics were comparable between groups, although TKR patients had higher BMI (Body mass index) and more frequent KL grade 3. TKR patients scored higher on WOMAC (mean difference 19.3, p = 0.009) and PCS (mean difference 9.1, p = 0.022), reflecting greater functional impairment and catastrophizing. Across the whole cohort, painful stimulation evoked robust activation of classical pain-processing regions, but no significant amygdala or nucleus accumbens activation. However, nucleus accumbens activity correlated positively with PCS scores (p ≤ 0.004). In group comparisons, TKR patients exhibited significant bilateral amygdala activation during Tibial Surface stimulation, absent in the CM group, and reported higher post-test NRS scores (mean difference 2.0, p = 0.027). Conclusion Our findings suggest that heightened limbic activation and catastrophizing contribute to the decision to undergo TKR in KOA patients, independent of radiographic severity. The amygdala and nucleus accumbens appear central in linking affective–motivational processes with treatment choice. Our findings suggest that heightened limbic activation and catastrophizing are associated with the decision to undergo TKR in KOA patients, independent of radiographic severity.