text: Neural and Self report Measures of Sensitivity to Uncertainty as Predictors of COVID Related Negative Affect The COVID 19 pandemic has been a period of unprecedented uncertainty Research indicates individuals differ in their response to uncertainty and these differences are mediated by anterior insula aINS function Those most sensitive to uncertainty are likely vulnerable to negative affect in the context of the pandemic The current study was designed to directly test this question using both neural and self reported measures of sensitivity to uncertainty Fifty nine volunteers completed a task designed to probe neural response to anticipation of predictable P and unpredictable U threat of electric shock during functional magnetic resonance imaging and a self report measure of intolerance of uncertainty IU Approximately two years later during the peak of the pandemic participants reported their emotional reactions to the COVID 19 crisis Multilevel mixed models revealed that greater aINS activation to U threat and greater self reported IU were independent predictors of increased COVID related negative affect These findings were significant when adjusting for biological sex and depression and anxiety symptom severity The results add to a growing literature demonstrating that individual differences in response to uncertainty have a robust impact on mood and functioning Results also highlight that individuals highly sensitive to uncertainty may be at increased risk for poor mental health during the ongoing pandemic 