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 brains 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 LC interacts with the prefrontal cortex (PFC) 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 {+/-} 4.02years, 35females) and 69 older adults (71.3 {+/-} 4.1 years, 35females) 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), and absolute-ambiguity (50%happy-fearful). Behaviorally, participants had longer response times and lower confidence during 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 task-independent self-reported mental well-being questionnaires and greater emotional resilience scores derived from principal component analysis. Overall, these findings suggest that greater LC activity supports managing cognitively demanding tasks, while enhanced LC-dlPFC connectivity promotes emotional well-being, highlighting this neural pathways role in healthy aging. Significance StatementUnderstanding how the brain adapts to cognitive and emotional demands with age is key to promoting healthy aging. This study examined whether the locus coeruleus (LC), a brain region critical for regulating attention and arousal, undergoes adaptive changes with age, especially during emotional ambiguity task. Using ultra-high-field imaging, we explored younger and older adults recognize facial expressions with varying ambiguity levels. Our findings indicated that compared to young, older adults showed heightened LC activity and LC-dorsolateral prefrontal cortex (dlPFC) connectivity when processing absolute-ambiguous facial expressions, with enhanced connectivity linked to improved mental well-being. These results suggest higher LC activity supports cognitive demands of ambiguity processing with LC-dlPFC connectivity promoting emotional well-being and resilience, offering insights into mechanisms underlying healthy aging.