Age-related Increase in Locus Coeruleus Activity and Connectivity with Prefrontal Cortex during Ambiguity Processing

Abstract

Interpreting ambiguous environmental cues, like facial expressions, becomes increasingly challenging with age, especially as cognitive resources decline. Managing these challenges requires adaptive neural mechanisms that are essential for maintaining mental well-being. The locus coeruleus (LC), the brain's main norepinephrine source, regulates attention, arousal, and stress response. With extensive cortical connections, the LC supports adapting to cognitive demands and resolving conflicting cues from environment, particularly in later life. Previous research suggests that the LC interacts with the prefrontal cortex during high-conflict tasks. However, whether LC activity and its connectivity with the PFC support emotional ambiguity processing and contributes to emotional well-being in healthy aging remains unclear. To address this gap, we used 7T-MRI to examine LC function in 75 younger (25.8 +/- 4.02 years, 35 females) and 69 older adults (71.3 +/- 4.1 years, 35 females) during facial emotion-recognition task morphed with varying ambiguity: anchor (unambiguous happy or fearful), intermediate-ambiguity (30% happy-70% fearful and 40% happy-60% fearful expressions, in either direction), and absolute-ambiguity (50% happy-fearful). Behaviorally, participants had longer response times and lower confidence in the absolute-ambiguity condition, while older adults perceived ambiguous faces as happy more frequently than younger adults. Neuroimaging results revealed older adults exhibited greater LC activity and enhanced connectivity with dorsolateral PFC (dlPFC) during absolute-ambiguity compared to younger adults. This heightened connectivity in older adults was linked to better emotional resilience and mental well-being. These findings suggest greater LC activity supports managing cognitively demanding tasks, while enhanced LC-dlPFC connectivity helps maintain emotional well-being, underscoring the importance of this neural pathway for healthy aging.