By MingMing Yang
Have you ever wondered how this feeling is generated? Fear is an inevitable experience that everyone will go through at some point in life. As unpleasant as it feels sometimes, it is what keeps us away from danger, an important emotion to have for survival. Imagine an animal who does not run away when its predator is near; this does not sound like an evolutionary advantage. Fear is usually a healthy response. However, if it extends over a long period, or when the response is disproportionate with stress or danger, and negatively affects a person’s quality of life, it is classified as an anxiety disorder. Despite it being a natural response to danger some people try to purposefully seek this adrenaline rush from time to time, for instance by watching horror movies.
How our brain responds to external stimuli and generates fear is a complicated process involving several neural circuits and parts of the brain. The amygdala, a collection of nuclei that form an almond-like shape buried deep in the temporal lobe, is identified as the centre to these processes. According to research, the amygdala in humans has an important role in the recognition, expression, and experience of fear(Adolphs, Ralph, 2013). Among the most well-studied regions in the amygdala, the central nuclei (CeA) participate in a number of aspects of fear response including regulating the release of cortisol through the paraventricular nucleus of the hypothalamus, enhancing startle response via the midbrain, and modulating the autonomic nervous system through the lateral hypothalamus(Ressler, 2010). It was found in a study (LeDoux, 1992) that fear conditioned responses like fear-potentiated startle and freezing were eliminated in rodents with CeA lesions. Therefore, this region is thought to be the primary output of the amygdala in the generation of fear.
To further characterize the role of amygdala in fear induction, famous studies(Adolphs, R. et al., 1995; Feinstein et al., 2011) focused on a patient known as SM, a woman with bilateral amygdala damage due to Urbach-Wiethe disease, a rare genetic disorder that causes the amygdalae to harden and shrivel. SM has normal IQ, memory, language, and perception, but is found to be severely impaired in fear conditioning, recognizing fear in facial expressions, and in certain social behaviours linked to emotions related to fear. In this study where SM was being brought to an exotic pet store with snakes and spiders, and a haunted house, nearly no induction or experience of fear was detected in SM. It was thought that with bilateral amygdala damage, SM lost the concept of fear.
When we feel scared, the response produced by our body is called “fight or flight” or acute stress response. This process starts in the amygdala, where information from the external environment is being processed and directed to the hypothalamus, the “command centre” of our brain that controls the autonomic nervous system (ANS) via the hypothalamic pituitary adrenal (HPA) axis. The hypothalamus first sends a hormone called CRH (corticotropin-releasing hormone) to the pituitary gland, which signals the secretion of a hormone called ACTH (adrenocorticotropic hormone). ACTH reaches the adrenal glands located on top of the kidneys to prompt the release of another hormone called cortisol. Together with direct actions directed by the ANS, numerous changes occur within the body like a rise in blood pressure and breathing rate, preparing our muscles for violent actions(How The Fight or Flight Response Works: Return to Rest and Digest. ).
The hippocampus also helps manage the intensity of fear response by working alongside the prefrontal cortex, the area of the brain involved in high-level decision-making. Apart from sending signals to the pituitary gland and activating the ANS, the hippocampus also directs the information to the prefrontal cortex, where the stress response is being assessed. This helps to justify whether the fear response is accurate or exaggerated and will relay back to the amygdala to dampen its activity if the later appears to be true. This briefly explains why some people can enjoy watching horror movies without their stress response triggered, as their consciousness override the automated fear response during the process(Fear: What happens in the brain and body? 2018).
Although fear and anxiety are considered as normal and usually healthy response, they may require clinical attention once the symptoms become more sustained and are disproportionate with external stimuli that can trigger a fear response. According to the American Psychological Association(Anxiety. ), anxiety is an emotion characterized by feelings of tension, worried thoughts, and physical changes like increased blood pressure. If these symptoms become recurrent, anxiety disorder will arise. Anxiety disorders are characterized by excessive fear and anxiety or avoidance of perceived threats that are persistent and impairing due to dysfunction in brain circuits that respond to danger. For instance, a study found a disconnection between the amygdala and prefrontal cortex in phobia patients, areas in the brain essential for overriding or minimizing fear response(Ahs et al., 2009). Risk for anxiety disorders is complex, often influenced by both genetic and environmental factors, and their epigenetic relations(Penninx et al., 2021). Some more common forms include panic disorder characterized by brief or sudden attacks of intense terror and apprehension, and phobias, irrational fear and avoidance of a particular object or situation.
Currently, treatments for anxiety disorders are usually a combination of psychotherapy, behavioural therapy, and medication like antidepressants(Anxiety: Symptoms, types, causes, prevention, and treatment. 2020). With better understanding of the neural circuits underlying the generation of fear and anxiety, it provides a potential to develop more effective treatments targeting specific areas of the brain, where damage could lead to dysfunction in the production of fear and anxiety.
Anxiety: Symptoms, types, causes, prevention, and treatment. (2020) Available from: https://www.medicalnewstoday.com/articles/323454 [Accessed Jun 1, 2021].
Fear: What happens in the brain and body? (2018) Available from: https://www.medicalnewstoday.com/articles/323492 [Accessed Jun 1, 2021].
Anxiety. Available from: https://www.apa.org/topics/anxiety [Accessed Jun 1, 2021].
How The Fight or Flight Response Works: Return to Rest and Digest. Available from: https://www.anahana.com/wellness-resources/fight-or-flight [Accessed May 31, 2021].
Adolphs, R., Tranel, D., Damasio, H. & Damasio, A. R. (1995) Fear and the human amygdala. Journal of Neuroscience. 15 (9), 5879-5891. [Accessed May 31, 2021].
Adolphs, R. (2013) The Biology of Fear. Current Biology : CB. 23 (2), R79-R93. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595162/. Available from: doi: 10.1016/j.cub.2012.11.055. [Accessed Mar 20, 2021].
Ahs, F., Pissiota, A., Michelgård, A., Frans, O., Furmark, T., Appel, L. & Fredrikson, M. (2009) Disentangling the web of fear: amygdala reactivity and functional connectivity in spider and snake phobia. Psychiatry Research. 172 (2), 103-108. Available from: doi: 10.1016/j.pscychresns.2008.11.004. [Accessed Jun 1, 2021].
Feinstein, J. S., Adolphs, R., Damasio, A. & Tranel, D. (2011) The Human Amygdala and the Induction and Experience of Fear. Current Biology. 21 (1), 34-38. Available from: https://www.cell.com/current-biology/abstract/S0960-9822(10)01508-3. Available from: doi: 10.1016/j.cub.2010.11.042. [Accessed May 31, 2021].
LeDoux, J. E. (1992) Brain mechanisms of emotion and emotional learning. Current Opinion in Neurobiology. 2 (2), 191-197. Available from: doi: 10.1016/0959-4388(92)90011-9. [Accessed May 31, 2021].
Penninx, B. W., Pine, D. S., Holmes, E. A. & Reif, A. (2021) Anxiety disorders. The Lancet. 397 (10277), 914-927. Available from: https://www.sciencedirect.com/science/article/pii/S0140673621003597. Available from: doi: 10.1016/S0140-6736(21)00359-7. [Accessed Jun 1, 2021].
Ressler, K. J. (2010) Amygdala Activity, Fear, and Anxiety: Modulation by Stress. Biological Psychiatry. 67 (12), 1117-1119. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882379/. Available from: doi: 10.1016/j.biopsych.2010.04.027. [Accessed May 31, 2021].