There are certainly some emotional responses that I would rather do without. You have mostly likely encountered at some point the well-used horror movie scene in which the protagonist, cautiously tiptoeing down a dimly lit hallway, approaches a corner or doorway and suddenly…bam! Out leaps the villain/axe-murderer/monster, and you jump, feel your heart rate kick up a notch, and involuntarily grab whoever is sitting next to you in the theater. Or the situation in which you must venture into a dark basement or attic and find yourself sprinting back to the main floor, heart pounding, at a strange noise or the perceived movement of a shadow.
As useful as this stress response may be when danger is actually present, it is less appropriate in the usual safety of most basements and movie theaters. Nonetheless, even if you know that nothing good can happen at the end of that dark hallway on screen, the sympathetic branch of your body’s autonomic nervous system still presents a classic response. What enables you to feel that fear? Furthermore, what if that reflex were muted or lost?
Fortunately for science, there’s a rare, autosomal recessive genetic disorder to give insight into that question. Urbach-Wiethe disease, also called lipid proteinosis, is a gradual thickening and hardening of the body’s mucous membranes. The symptoms of the disorder are caused by the infiltration of the skin, brain, and mucous membranes by a substance similar to hyalin, a large, acidic, strongly adhesive protein that plays an important role in embryonic development. Symptoms include waxy papules on the face and around the eyelids from a buildup of hyaline material, vocal hoarseness, thickening of the tongue and impaired ability to heal from wounds. While generally not fatal, lipid proteinosis can become dangerous when it affects the respiratory system or brain. With respect to the respiratory system, enlargement of the tongue or hyaline deposits in the pharynx can obstruct breathing. With respect to the brain, the hardening of tissue in the medial temporal lobes can cause epilepsy and other neurological disorders.
One of the structures often damaged by the calcification caused by Urbach-Wiethe disease is of particular interest to neuroscience: the amygdalae. These two small, almond-shaped collections of nuclei are located deep within the brain’s temporal lobes and perform a variety of intriguing functions. Most notably in this case, they play a role in emotional memory, which brings us back to our opening horror movie scene. Lipid proteinosis patients with damaged amygdalae can have trouble identifying and relating to fear. One patient with almost completely destroyed amygdalae, known by her initials SM, seems fearless indeed. Haunted houses, disturbing movie footage, and even experiences such as being held at knifepoint induce in her not the slightest hint of panic or urgency. According to three scientists at the University of Iowa who have worked with her extensively, SM cannot tell what a fearful facial expression looks like or means, nor can she draw a fearful expression when asked, though she has no trouble identifying and illustrating other emotions.
Though cases of Urbach-Wiethe disease do not imply that the amygdala is the fear center of the brain, they do highlight its role in fear processing, likely as a stop that connects areas of the brain that sense the environment to parts of the brainstem that initiate fear and stress responses. While much remains to be studied about the enigmatic roles of the amygdala, in the meantime, you know what little almond-shaped structures play a big part in the next time you jump out of your skin in a movie theater.