The biology of fear

Abstract

Each of us has felt afraid, and we can all recognize fear in many animal species. Yet there is no consensus in the scientific study of fear. Some argue that 'fear' is a psychological construct rather than something discoverable through scientific investigation. Others argue that the term 'fear' cannot properly be applied to animals because we cannot know whether they feel afraid. Studies in rodents show that there are highly specific brain circuits for fear, whereas findings from human neuroimaging seem to make the opposite claim. Here, I review the field and urge three approaches that could reconcile the debates. For one, we need a broadly comparative approach that would identify core components of fear conserved across phylogeny. This also pushes us towards the second point of emphasis: an ecological theory of fear that is essentially functional. Finally, we should aim even to incorporate the conscious experience of being afraid, reinvigorating the study of feelings across species.

Figure 1. Neuroimaging of emotion in humans

(A,B) Examples suggesting that there is no focused neural network for fear, but that emotions are instead processed in a very distributed fashion. (A) Meta-analysis of activation in the amygdala. The y-axis plots the proportion of studies surveyed that showed significant activation within 10mm of the amygdala (inset), broken down in terms of studies looking at the perception (per) or experience (exp) of particular emotions. (B) Significant activations in specific brain regions (structures in boxes around the outside of the circle) as a function of specific processes (blue lines: left hemisphere, green lines: right hemisphere). The percentage plots from the origin denote the change in odds that an activation would be seen, from logistic regression of the meta-analysis. Modified from a meta-analysis of 91 neuroimaging studies [126]; see also [11]. Abbreviations: DLPFC=dorsolateral prefrontal cortex; ATL=anterior temporal lobe; VLPFC=ventrolateral prefrontal cortex; DMPFC=dorsomedial prefrontal cortex; aMCC=anterior middle cingulate cortex; sACC=subgenual anterior cingulate cortex; OFC=orbitofrontal cortex. (C) Example to the contrary, suggesting that there is a focused neural network for fear, prominently including the amygdala. Activation likelihood maps of fear are shown from another meta-analysis of 30 recent neuroimaging studies [8]; here hotter colors represent greater spatial overlap (consistency) among significant activations across multiple studies in the meta-analysis. The amygdala is prominently activated across studies of fear.

Figure 2. The amygdala

(A) Some of the main amygdala nuclei and their inputs and outputs, emphasizing the complex internal architecture of this structure. (B) Amygdala connectivity with other brain structures, emphasizing its participation in multiple networks that process fear, and its central location in mediating between parts of the prefrontal cortex and nuclei in the hypothalamus and brainstem. Modified from [69] and [120]. Abbreviations: MDm: dorsomedial thalamus, which mediates between amygdala and medial prefrontal cortex; Ca, Acc, P, VP: components of the basal ganglia (Caudate, Accumbens, Putamen, Ventral Pallidum); Ce, AB, B, L: nuclei of the amygdala (Central, Accessory Basal, Basal, Lateral); EC: entorhinal cortex.

Figure 3. Functional components of fear: stimuli, cognition, and behavior

(A) Stimuli and behaviors related to fear, schematized in terms of their complexity and the degree of an organism’s involvement and control (regulation). Fear can be caused by a wide range of stimuli, from basic unconditioned stimuli to complex symbolic knowledge; and it can in turn trigger core biological responses as well as be modulated volitionally, at least in humans. Very roughly, the components at the upper left are shared across a wider range of species, whereas the components at the bottom right may be unique to humans. (B) Schematic of some of the effects of a central state of fear on cognition and processing mode. Fear interfaces with nearly all other aspects of cognition.

Figure 4. Fear, the amygdala, and distance

Physical distance (proximity) is one of the most basic stimulus cues to trigger fear. (A) Different adaptive types of fear behaviors can be elicited as a function of distance, ranging from freezing to fleeing to defensive attack. Adapted from [74], see also [20] for a similar scheme. (B) Lesions of the human amygdala reduce interpersonal distance and the sense of invasion of personal space. At the top are schematized the mean interpersonal distances from an experimenter for healthy controls (left) and a patient with bilateral amygdala lesions (patient SM, right). At the bottom is a plot of the data showing mean distance that people felt comfortable standing from the experimenter (at the origin), patient SM is the red bar and the rest are healthy controls. From [91]. (C) Approach or retreat of a threatening stimulus (a tarantula) in a human fMRI study showed differential activation of the amygdala and bed nucleus of the striaterminalis. Participants lay inside the fMRI scanner while their foot was placed in compartments at varying distances from the tarantula, a procedure they observed through video (left panel). Subtraction of approach minus retreat (for the same distance, middle panel) resulted in the activation shown on the right panel. From [96].

Figure 5. Components of a central fear system

The schematic outlines some of the processing that contributes to fear, including sensory inputs, central structures, and effectors. From [31].