Academic journal article South African Journal of Psychiatry

The Functional Neuro-Anatomy of the Human Response to Fear: A Brief Review

Academic journal article South African Journal of Psychiatry

The Functional Neuro-Anatomy of the Human Response to Fear: A Brief Review

Article excerpt

Being exposed to fear signals makes us feel threatened and prompts us to prepare an adaptive response. Fear perception and appropriate behavioural responses are crucial for environmental adaptation and survival of species. Sympathetic activation after fear perception triggers the fight or flight (or freeze) reaction, which allows an attempt to meet the stressful situation in an adaptive manner. Furthermore, the transmission or sharing of fear within social groups may represent a defensive mechanism for many species.

The neurobiology of the detection of threats and fear has long been studied using animal models. Sensory input signalling danger may gain rapid access to the amygdala through both bottom-up and top-down mechanisms, involving the thalamus and sensory cortices, respectively. The subcortical pathway activating the amygdala passes through the superior colliculi and the pulvinar of the thalamus before accessing it. This pathway operates at low spatial frequency information. (1)

The amygdala appears to play a role in both threat assessment and fear conditioning, as well as in other associative forms of learning, such as responding to potentially threatening stimuli. (2,3) It also mediates significant autonomic responses to threat through its descending projections to brainstem nuclei. (4,5) Furthermore, its projections to several layers of the visual cortex probably support sensory processing modulation. (6) The response of the amygdala to threatening stimuli is probably modulated by a network involving the infralimbic prefrontal cortex, which inhibits the activation of the amygdala, (7,8) and the hippocampus, which is involved in learning about safe versus dangerous contexts. (9) It has been speculated that similar brain mechanisms may underlie contextual fear conditioning across species. (10)

Modern neuro-imaging techniques have significantly fostered the identification of anatomical structures and networks involved in fear perception and response. The aim of this paper is briefly to review recent literature on functional imaging that focuses on the detection of threat and human fear.


We searched Medline and PsycInfo databases using the terms 'fear', 'fear response', 'fear conditioning', 'fear extinction', 'threat detection', 'magnetic resonance imaging', 'functional', 'positron emission tomography' and 'single photon emission computerized tomography'. More papers, which did not appear in this search, were found in the reference lists of retrieved papers. Papers were considered for inclusion only if they were published in peer-reviewed journals.

Papers were included if they satisfied standards for adequate methodology and inclusion criteria. Studies with inadequate methodology (method unspecified and/or inadequately described) were excluded. We also excluded papers that did not include a healthy control group in their analyses. Most of these studies were published in the last 10 years.

Fear perception and modulation

Several functional imaging studies focused on areas activated in healthy people after fearful stimuli. The basic forms of associative learning, i.e. fear conditioning and extinction, are becoming increasingly important paradigms. They have pathophysiological and therapeutic implications, since they increase our understanding of the anxiety disorders, facilitate their appropriate classification, and allow us to gauge the effects of their treatment, (11) both pharmacological and psychotherapeutic. These forms of learning have been exploited by creating paradigms of conditioning/ extinction resulting in a reduction of fear; this has been used in functional neuro-imaging studies focusing on the shift from fear to safety. (12)

Fear perception

Functional imaging studies showed increased activation of the amygdalae after fear stimuli in healthy volunteers. (13,14) Garrett and Maddock, (15) using functional magnetic resonance imaging (fMRI) with a fear-provocation paradigm, showed that the amygdala, rather than responding to a specifically defined fear stimulus, is set to initially respond to a general threat potential of the stimulus in question. …

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