Uncertainty and anticipation in anxiety: an integrated neurobiological and psychological perspective

In order to anticipate and prepare effectively for future experiences, the brain must cope with the inherent uncertainty of future events. In this Review, Grupe and Nitschke show how alterations in the processes by which the brain deals with future uncertainty may contribute to the development of pathological anxiety. Uncertainty about a possible future threat disrupts our ability to avoid it or to mitigate its negative impact and thus results in anxiety. Here, we focus the broad literature on the neurobiology of anxiety through the lens of uncertainty. We identify five processes that are essential for adaptive anticipatory responses to future threat uncertainty and propose that alterations in the neural instantiation of these processes result in maladaptive responses to uncertainty in pathological anxiety. This framework has the potential to advance the classification, diagnosis and treatment of clinical anxiety.