Human fear neurobiology reimagined: Can brain-derived biotypes predict fear-based disorders after trauma?

Abstract

Human studies of fear neurobiology have established neural circuits that are activated to threatening stimuli, whether it be during Pavlovian fear conditioning or in response to naturally occurring threats. This circuitry involves the central and basolateral amygdala, as well as the bed nucleus of the stria terminalis, insula, hippocampus, and regulatory regions such as the anterior cingulate cortex and ventromedial prefrontal cortex. While research has found that fear-based disorders, such as anxiety and post-traumatic stress disorder, as associated with dysfunction in these circuits, there is substantial individual heterogeneity in the clinical presentation of symptoms. Recent work has used data-driven methods to derive brain biotypes that capitalize on the activity of the fear circuit and its interaction with other regions of the brain. These biotypes have great utility in both describing individual variation in psychopathology and in identifying individuals at greater risk for fear-based disorders after an environmental stressor, such as a traumatic event. The review discusses recent examples of how fear neurobiology studies can be leveraged to derive biotypes that may ultimately lead to improved treatment.

Keywords: Biotypes; Fear conditioning; Neuroimaging; Trauma.

Figure 1.. Schematic of different theoretical biotypes identified during fear learning.

A) The threat stimuli represented here is a reinforced conditioned stimulus (CS+) paired with an aversive shock. In the context of this threat, different patterns of neural interactions with the fear conditioning circuit (yellow) may emerge within groups. This example demonstrates three hypothetical functional profiles of brain activation or connectivity, or biotypes, defined by differing interactions with the ventral visual stream (green) or prefrontal regions (blue). Bidirectional arrows denote connectivity between regions. Brain-based biotypes may aid in characterizing heterogeneity in fear-based symptomology. B) Following trauma exposure, these brain-based biotypes can provide predictive value in determining mental health outcomes. This example demonstrates how hypothetical biotypes 1, 2, and 3 from panel A may aid in predicting different clinical symptom clusters, or subtypes, following trauma.