Acute orexin antagonism selectively modulates anticipatory anxiety in humans: implications for addiction and anxiety.

Research indicates that heightened anticipatory anxiety underlies several forms of psychopathology. Anticipatory anxiety can be reliably and objectively measured in the laboratory using the No-Predictable-Unpredictable (NPU) threat paradigm. The NPU paradigm is an ideal research tool for the NIH 'Fast-Fail' approach of screening promising compounds and testing human target engagement.

Association between startle reactivity to uncertain threats and structural brain volume.

Sensitivity to uncertain threat (U-threat) is a clinically important individual difference factor in multiple psychopathologies. Recent studies have implicated a specific frontolimbic circuit as a key network involved in the anticipation of aversive stimuli. In particular, the insula, thalamus, and dorsal anterior cingulate cortex (dACC) have recently been found to be robustly activated by anticipation of U-threat.

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.