Box 3: Adaptive and maladaptive responses to threat uncertainty
To illustrate adaptive and maladaptive manifestations of processes highlighted in the uncertainty and anticipation model of anxiety (UAMA), consider the following vignette, in which each of the five UAMA processes are indicated.
Pete, home alone one night, hears rustling in the bushes and loud banging sounds outside his house. Pete immediately feels uncertain about whether these noises are benign (curious raccoons) or threatening (burglars). An adaptive response to this uncertainty begins with a rational assessment of the probability of threat (first process). Few burglaries occur in this neighbourhood, and similar noises have never turned out to be dangerous before. Pete turns down the television to give more attention to what may be outside, but this heightened vigilance (second process) is balanced by attention to cues that indicate safety (third process). Because Pete's security system is silent and the windows and doors are locked, he has reliable signs that nobody has entered his house. Nevertheless, Pete explores the situation to reduce nagging questions (fourth process). Heading downstairs, he sees trash strewn about the garbage cans and surmises the likely culprit was a raccoon. Despite some unresolved uncertainty, Pete can calm his racing heart (fifth process) and fall asleep knowing that all signs point towards safety.
Next door lives Paul, a chronic worrier diagnosed with generalized anxiety disorder, who hears the same noises and experiences similar feelings of uncertainty. Instead of objectively weighing the likelihood of alternative outcomes, Paul immediately imagines burglars entering his home (first process). Uncontrollable worries and cascading 'what if...' thoughts course through his head, and he generates increasingly elaborate scenarios of what evils may befall him. He becomes increasingly attuned to every movement in the branches or creak in the floorboards of his old house (second process). Owing to Paul's exclusive attention towards potential threat, he does not notice that his security system is silent (third process). Concerned for his safety, Paul locks his bedroom door instead of investigating (fourth process). Having avoided exploring the situation, Paul is left with greater unresolved uncertainty than Pete about the source of the noises. He tries to sleep but his racing heart and sweaty palms keep him from relaxing (fifth process). Not having learned that the situation was safe, Paul will be more likely to assume the worst the next time he hears a noise in the night.
Departments of Psychiatry and Psychology, Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin–Madison, 1500 Highland Avenue, Madison, Wisconsin 53705, USA.
- Dan W. Grupe &
- Jack B. Nitschke
Competing interests statement
The authors declare no competing interests.
Dan W. Grupe
Dan W. Grupe received his M.S. in 2009 from the University of Wisconsin–Madison, Wisconsin, USA, where he is currently pursuing his Ph.D. in psychology. His research uses functional and structural neuroimaging methods to investigate the neurobiology of clinical anxiety disorders, including post-traumatic stress disorder and generalized anxiety disorder, with a particular emphasis on aberrant cognitive and affective responses to uncertainty in anxiety.
Jack B. Nitschke
Jack B. Nitschke is Associate Professor of Psychiatry and Psychology at the University of Wisconsin–Madison Wisconsin, USA. He has been researching the neural basis of anxiety and its disorders for two decades using a range of brain measures in humans. His research the past decade has primarily used a range of functional and structural neuroimaging methods, with a primary focus on systematically evaluating the nature of anticipatory dysfunction in the brains of individuals with anxiety disorders. A prominent recent emphasis is on identifying pretreatment brain markers that have are useful for predicting treatment responses and that might ultimately guide treatment decisions.
The suite of anticipatory affective, cognitive and behavioural changes in response to uncertainty about a potential future threat.
- Ventromedial prefrontal cortex
(vmPFC). It encompasses the medial orbitofrontal cortex, posterior frontopolar cortex, subgenual anterior cingulate cortex (ACC) and inferior pregenual ACC, including Brodmann areas 11, 14 and 25, and portions of 10, 24 and 32.
- Orbitofrontal cortex
(OFC). Medial and lateral aspects of the orbital surface of the prefrontal cortex, including Brodmann areas 11, 13 and 14, and ventral portions of 10 and 47/12.
- Fear-potentiated startle
The enhanced response to a startling stimulus observed in negative arousing states, such as fear or anxiety.
A state of increased attention to a perceived threat in one's environment.
- Fear conditioning
The process by which a neutral conditioned stimulus (CS+) becomes associated with an aversive, unconditioned stimulus (US) through repeated contingent presentations of the CS+ and US, resulting in fear expression following presentation of the CS+ alone.
- Prediction error
The difference between predicted and actual outcomes, which results in a neural signal that leads to increasingly accurate future predictions.
- Rostral cingulate cortex
Encompasses the anterior cingulate cortex and anterior mid-cingulate cortex, including Brodmann areas 24, 25, 32 and 33.
The propensity of a stimulus to form associations with other stimuli in the environment; associability increases following surprising or unpredicted outcomes.
- Conditional discrimination tasks
A variant of fear-conditioning paradigms that allows for the independent investigation of safety learning and the inhibition of fear responses in the presence of learned safe cues.
- Fear extinction
An active learning process in which a conditioned stimulus (CS+) is repeatedly presented in the absence of a contingent unconditioned stimulus (US), leading to a new association between the CS+ and safety that competes with the original association between the CS+ and US.
- Diffusion tensor imaging
An MRI technique that assays the diffusion properties of water molecules, providing insight into the microstructural properties of white matter.
- Uncinate fasciculus
The primary white matter tract connecting ventral portions of the prefrontal cortex and anterior cingulate cortex with medial temporal lobe structures, including the amygdala.
- Exposure therapy
A therapeutic technique in which individuals are presented with feared objects, situations or memories in a safe setting, thus causing a reduction of fearful associations.
- Cognitive behavioural therapy
A diverse collection of therapies in which there is an emphasis on the correction or restructuring of inaccurate beliefs and maladaptive behaviours.
A widely used class of GABA receptor agonists for the treatment of anxiety disorders.
The perception of sensory events occurring within one's body.
A partial agonist of the NMDA glutamate receptor that has been shown to enhance learning.