Back From Battle: The Conditioning of Fear in PTSD
Elsie McKendry
Illustrations by Katie Hieb
Everyone has felt afraid before. Maybe you have a fear of heights, spiders, or the dark. Fear keeps us safe when it warns us of danger. Now imagine if you frequently felt fear in harmless situations, such as every time you brushed your teeth or heard a plane. An overactive fear response would quickly become disruptive to your daily life. For many people with post-traumatic stress disorder, this imagined scenario is a reality. Post-traumatic stress disorder (PTSD) is a mental health condition that can arise after a person experiences a traumatic event [1]. A traumatic event can be defined as a frightening or dangerous experience that threatens an individual’s life or physical security [2]. What defines a trauma is complex, but traumatic events can include abuse, natural disasters, bullying, refugee and war experiences, and life-threatening illnesses [2]. Characteristic symptoms of PTSD include re-experiencing and avoidance of a trauma, heightened arousal, and mood disruptions [3]. PTSD is characterized by a heightened fear response in reaction to occurrences that remind an individual of a previous traumatic event, potentially resulting in impairments to well-being, cognition, memory, identity, and relationship formation [2]. Heightened fear responses become a source of dysfunction when they occur frequently enough to interfere with day-to-day life [4].
Classical Conditioning: How we Learn to Respond
Heightened fear responses can be triggered by both threatening and non-threatening stimuli that remind a person of traumatic events [5]. Trauma responses can be explained as a disorder of learning and memory processing, specifically through the lens of classical conditioning: a type of associative learning where two unrelated stimuli are paired, leading to the same response when either stimulus is encountered individually [5]. When most people think about classical conditioning, they recall the scientist Ivan Pavlov and his salivating dogs [6]. In Pavlov’s experiment, each time the dogs were fed, a bell was rung right before the delivery of food [7]. Dogs automatically salivate in anticipation of food; accordingly, food is an unconditioned stimulus that triggers an automatic response. Over time, the dogs began associating the bell sound with food, salivating at its tone [7]. Their salivation indicated that the sound of the bell had become a conditioned stimulus: a stimulus that did not previously evoke an automatic response, but one that the subject learns to react to in a particular manner [8]. We encounter classical conditioning in our everyday lives: hearing a school bell elicits excitement at the end of the school day while hearing a soda can open may elicit thirst.
How is Classical Conditioning Related to PTSD?
The concept of classical conditioning can be applied to fear responses caused by trauma-related cues [6]. Consider a hypothetical war veteran named Phil. Imagine that Phil spent a few years serving overseas and experienced significant violence firsthand. During combat, an enemy plane dropped a bomb close to Phil’s station, and he rushed to find shelter. His instinct to run away ended up saving his life. Throughout the remainder of his service, the sound of planes was frequent. Each time he heard an incoming plane, he feared that it was another enemy plane preparing to drop a bomb, and ran to find cover. After Phil’s initial traumatic experience, he used the sound of planes to predict the dropping of bombs. Phil’s learned response to the sound of planes is an example of classical conditioning [6]. The unconditioned stimulus is the bomb, since a fear response to a bombing is natural. Conversely, plane sounds are a conditioned stimulus for Phil, because they do not typically evoke fear. He began to associate the sound of planes with danger through repeated recall of his previous traumatic bombing experience each time a plane flew overhead. While his instinct to run from the sound of planes was initially life-saving, it became maladaptive after his service ended [9].
The Expansion of Fear Through Stimulus Generalization
Phil’s inability to process non threatening stimuli, even in a different context, contributed to his disrupted fear response. After his return home, Phil found himself having intense fear reactions to plane sounds and other harmless noises that sounded similar, such as lawnmowers and vacuums [9]. For instance, when Phil was awoken by the sound of an electric mixer on a Sunday morning, he immediately jumped out of bed and dove into his closet. After a sweet smell wafted through the closet door, Phil realized that his wife was using the kitchen mixer to make blueberry muffins, as she occasionally did on the weekends. Phil’s reaction is consistent with the finding that people with PTSD have difficulty differentiating between safety and danger cues [9, 10]. Even though Phil consciously knew he was safe in his home, he reacted to the sound as if he was in danger and found it difficult to calm himself [9, 11]. In classical conditioning, a tendency to respond to neutral stimuli that bear similarities to a conditioned stimulus is known as stimulus generalization [9]. Generalization typically serves as an adaptive process to help people respond to new situations based on prior experiences. However, it can become harmful when it occurs too frequently [9]. It’s possible that overgeneralization in those with PTSD may be attributed to deficiency in the dentate gyrus, a brain region involved in the encoding of similar events as distinct based on specific, oftentimes minute details that differ between the two events [12]. This process is known as pattern separation, and its impairment has been theorized to contribute to stimulus generalization [12]. In Phil’s case, he responded to the sound of the mixer similarly to how he would respond to the original conditioned stimulus — the sound of the plane [6, 9]. However, once Phil returned to civilian life, his learned reaction no longer protected him; instead, it caused him unnecessary distress [9, 10].
Fight or Flight: Our Fear Response
When learned fear becomes overwhelming and is no longer protective, it may be not only unhelpful, but harmful [9, 10]. As Phil hid in his bedroom closet, his hands shook, his lungs constricted, and his heart raced. Phil exhibited dilated pupils, slowed digestion, and an adrenaline rush [4, 13]. The sensations that Phil was experiencing are products of an active sympathetic nervous system: the part of the nervous system best known for its role in triggering the fight-or-flight response [14]. Notably, the sympathetic nervous system works alongside the hypothalamic-pituitary-adrenal (HPA) axis: a system responsible for releasing hormones that activate the fight or flight response [13, 14, 15]. One of these hormones, known as adrenaline, triggers physiological changes to help respond to frightening stimuli. Adrenaline release leads to increased blood flow that encourages muscle activation, while an increase in blood glucose concentration allows the body to make use of energy reserves [16]. Essentially, the sympathetic nervous system works to maximize survival in stressful or dangerous situations by activating bodily responses that improve our ability to react to threats [17]. However, when the sympathetic nervous system is chronically activated, such as in individuals with PTSD, health consequences that affect a person for the rest of their life may occur [2]. When the HPA axis becomes dysregulated in response to chronic stress, a person faces possible damage to these crucial systems. Cortisol, another hormone released during HPA activation, particularly contributes to the ‘wear and tear’ of these regulatory systems, which can lead to the impairment of cognitive functions such as memory and behavioral regulation [2]. Altogether, strain of the sympathetic nervous system due to fear responses in those with PTSD can impose an array of debilitating symptoms.
Memory Storage Gone Wrong: Why PTSD Flashbacks Feel So Real
In addition to physiological responses, those with PTSD often experience intrusive memories related to a traumatic event. Such flashbacks can occur even years after the traumatic event has passed [5]. When experiencing these memories, it can be difficult to differentiate between the past and present. Let’s return to Phil. When he first heard the sound of his wife’s electric mixer, he was reminded of the enemy planes that dropped bombs near his station. Even though that event took place overseas many years ago, Phil had difficulty remembering he was in the safety of his home and not at war, causing his flashback to feel real. Disruptions with contextualizing familiar stimuli in different environments is partly attributed to dysfunction of the hippocampus, which is a brain structure that regulates our learned fear responses, learning, and memory [5, 6]. The hippocampus — along with other brain regions — is involved in identifying whether a stimulus is safe or dangerous based on the context of the situation, and stores this information for later use [6, 18]. Although the mechanism by which the storing of information is debated, unpleasant emotional arousal — such as Phil’s experience during the bombing — disrupts hippocampal memory processing. Disrupted hippocampal functioning makes contextualizing information surrounding a stimulus difficult [19, 20]. If a person incorrectly associates a previous context with a stimulus, they can experience flashbacks and stimulus generalization similar to what Phil experienced [19].
Why is Extinction Impaired in People with PTSD?
While dysregulated fear conditioning and stimulus generalization can cause major disruptions to a person’s life, it is possible to unlearn these harmful associations [5]. The suppression of a conditioned fear response is referred to as extinction. In classical conditioning, conditioned responses fade once the conditioned stimulus is no longer associated with the unconditioned stimulus that originally prompted a response. While extinction may resemble forgetting, extinction is more so a form of new, inhibitory learning that competes with the previously learned fear response. For instance, if Phil was continuously exposed to plane-like noises that were unaccompanied by bombs, he could eventually learn that those sounds do not predict danger and would stop having adverse reactions to the sound. If Phil’s conditioned fear of planes became extinct, he would no longer panic and jump into his closet at the sound of an electric mixer. In this instance, a stimulus that originally elicited fear would begin to elicit a new response as a new outcome is learned.
However, because the fear memory is not erased during the extinction process — but is overwritten during the extinction process instead — efforts to unlearn traumatic associations can be reversed in a process called reinstatement. In reinstatement, a fear response returns when the unconditioned stimulus reappears, such as in the event of another bombing [5]. In people with PTSD, fear extinction impairment may be attributed to decreased activation of the prefrontal cortex, a brain area involved in executive functions such as decision making and behavioral flexibility [21, 23]. A decrease in activation of the prefrontal cortex reduces its ability to regulate brain areas such as the amygdala, a brain region that plays a key role in reacting to danger and eliciting fear responses [6]. When the prefrontal cortex is inactive, its inhibitory power over the amygdala weakens, causing individuals with PTSD to experience an exaggerated fear response [6, 24]. The possibility of fear extinction impairment contributes to the persistent and debilitating nature of PTSD [5, 6, 24].
The Road to Recovery: an Array of PTSD Treatment Options
Though the difficulty of unlearning fear responses can result in persistent symptoms, new therapeutic techniques offer hope for people with PTSD [25]. Phil eventually sought out treatment for his PTSD and found a therapist that specializes in Eye Movement Desensitization and Reprocessing (EMDR). Phil’s therapist began by having him visualize the bombing he experienced, and then had him discuss his emotions and beliefs surrounding the event [26]. In the next phase of treatment, Phil was asked to focus on the traumatic event as he simultaneously tracked a bilaterally moving stimulus with his eyes. By working through these revisited memories with his therapist, he was able to positively reframe negative associations of his trauma and practice calming himself during moments of high arousal [27]. Though EMDR is effective, little is known about its underlying mechanisms [27]. Specific medications, such as selective serotonin inhibitors (SSRIs), can also be effective in treating PTSD; combining psychotherapy and medication can maximize the benefits of treatment [25]. Furthermore, there have been recent investigations into treatment plans involving the use of psychedelic drugs instead of SSRIs [28, 29]. For example, the clinical administration of MDMA in combination with psychotherapy is more effective in reducing PTSD symptoms than dual therapy-SSRI treatment plans. Fortunately, evolving treatments — such as those utilizing MDMA — show promise in reversing maladaptive fear triggers to non-threatening stimuli [28, 29]. As research progresses, PTSD treatment could continue to improve the quality of life for people with PTSD.
References
Duncan, L. E., Cooper, B. N., & Shen, H. (2018a). Robust findings from 25 years of PTSD genetics research. Current Psychiatry Reports, 20(12). doi:10.1007/s11920-018-0980-1
Laricchiuta, D., Panuccio, A., Picerni, E., Biondo, D., Genovesi, B., & Petrosini, L. (2023). The body keeps the score: The neurobiological profile of traumatized adolescents. Neuroscience & Biobehavioral Reviews, 145, 105033. doi:10.1016/j.neubiorev.2023.105033
National Institute of Mental Health (2023). Post-Traumatic Stress Disorder. Retrieved April 13, 2024 from https://www.nimh.nih.gov/health/topics/post-traumatic-stress-disorder-ptsd
American Psychiatric Association. (2013). [Trauma- and Stressor-Related Disorders]. In Diagnostic and statistical manual of mental disorders (5th ed.). doi:10.1176/appi.books.9780890425596
Careaga, M. B., Girardi, C. E., & Suchecki, D. (2016). Understanding posttraumatic stress disorder through fear conditioning, extinction and reconsolidation. Neuroscience & Biobehavioral Reviews, 71, 48–57. doi:10.1016/j.neubiorev.2016.08.023
VanElzakker, M. B., Kathryn Dahlgren, M., Caroline Davis, F., Dubois, S., & Shin, L. M. (2014). From Pavlov to PTSD: The extinction of conditioned fear in rodents, humans, and anxiety disorders. Neurobiology of Learning and Memory, 113, 3–18. doi:10.1016/j.nlm.2013.11.014
Pavlov P. I. (2010). Conditioned reflexes: An investigation of the physiological activity of the cerebral cortex. Annals of neurosciences, 17(3), 136–141. doi:10.5214/ans.0972-7531.1017309
Rehman, Ibraheem., Mahabadi, Navid., Sanvictores, Terrence., l. Rehman, Chaudhry. (2023). Classical Conditioning. In StatPearls. StatPearls Publishing. PMID:29262194
Lis, S., Thome, J., Kleindienst, N., Mueller-Engelmann, M., Steil, R., Priebe, K., Schmahl, C., Hermans, D., & Bohus, M. (2019). Generalization of fear in post-traumatic stress disorder. Psychophysiology, 57(1). doi:10.1111/psyp.13422
Dymond, S., Dunsmoor, J. E., Vervliet, B., Roche, B., & Hermans, D. (2014). Fear generalization in humans: Systematic review and implications for anxiety disorder research. Behavior Therapy, 46(5), 561-582. doi:10.1016/j.beth.2014.10.001
Besnard, A., & Sahay, A. (2016). Adult Hippocampal Neurogenesis, Fear Generalization, and Stress. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 41(1), 24–44. doi:10.1038/npp.2015.167
Hayes, J. P., Hayes, S., Miller, D. R., Lafleche, G., Logue, M. W., & Verfaellie, M. (2017). Automated measurement of hippocampal subfields in PTSD: Evidence for smaller dentate gyrus volume. Journal of Psychiatric Research, 95, 247–252. doi:10.1016/j.jpsychires.2017.09.007
Park, J., Marvar, P. J., Liao, P., Kankam, M. L., Norrholm, S. D., Downey, R. M., McCullough, S. A., Le, N. A., & Rothbaum, B. O. (2017). Baroreflex dysfunction and augmented sympathetic nerve responses during mental stress in veterans with post-traumatic stress disorder. The Journal of physiology, 595(14), 4893–4908. doi:10.1113/JP274269
Rotenberg, S., & McGrath, J. J. (2016). Inter-relation between autonomic and HPA axis activity in children and adolescents. Biological psychology, 117, 16–25. doi:10.1016/j.biopsycho.2016.01.015
Dunlop, B. W., & Wong, A. (2019). The hypothalamic-pituitary-adrenal axis in PTSD: Pathophysiology and treatment interventions. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 89, 361–379. doi:10.1016/j.pnpbp.2018.10.010
Chu, Brianna., Marwaha, Komal., Sanvictores, Terrence., Ayers, Derek. (2022). Physiology, stress reaction. In StatPearls. StatPearls Publishing. PMID:31082164
Beutler, S., Mertens, Y. L., Ladner, L., Schellong, J., Croy, I., & Daniels, J. K. (2022). Trauma-related dissociation and the autonomic nervous system: A systematic literature review of psychophysiological correlates of dissociative experiencing in PTSD patients. European Journal of Psychotraumatology, 13(2). doi:10.1080/20008066.2022.2132599
Sangha, S., Diehl, M. M., Bergstrom, H. C., & Drew, M. R. (2020). Know safety, no fear. Neuroscience & Biobehavioral Reviews, 108, 218–230. doi: 10.1016/j.neubiorev.2019.11.006
Damis, L. F. (2022). The role of implicit memory in the development and recovery from trauma-related disorders. NeuroSci, 3(1), 63–88. doi:10.3390/neurosci3010005
van Rooij, S. J. H., Stevens, J. S., Ely, T. D., Hinrichs, R., Michopoulos, V., Winters, S. J., Ogbonmwan, Y. E., Shin, J., Nugent, N. R., Hudak, L. A., Rothbaum, B. O., Ressler, K. J., & Jovanovic, T. (2018). The role of the hippocampus in predicting future posttraumatic stress disorder symptoms in recently traumatized civilians. Biological Psychiatry, 84(2), 106–115. doi:10.1016/j.biopsych.2017.09.005
Joshi, S. A., Duval, E. R., Kubat, B., Liberzon, I. (2020). A review of hippocampal activation in post-traumatic stress disorder. Psychophysiology, 57. doi:10.1111/psyp.13357
Hathaway, W. R., Newton, B. W. (2023). Neuroanatomy, prefrontal cortex. In StatPearls. StatPearls Publishing. PMID:29763094
Jiao, X., Beck, K. D., Myers, C. E., Servatius, R. J., & Pang, K. C. H. (2015). Altered activity of the medial prefrontal cortex and amygdala during acquisition and extinction of an active avoidance task. Frontiers in Behavioral Neuroscience, 9. doi:10.3389/fnbeh.2015.00249
Schrader, C., & Ross, A. (2021). A review of PTSD and current treatment strategies. Missouri Medicine, 118(6), 546–551. PMID:34924624
Gainer, D., Alam, S., Alam, H., & Redding, H. (2020). A FLASH OF HOPE: Eye Movement Desensitization and Reprocessing (EMDR) Therapy. Innovations in clinical neuroscience, 17(7-9), 12–20. PMID:33520399
Landin-Romero, R., Moreno-Alcazar, A., Pagani, M., & Amann, B. L. (2018). How does eye movement desensitization and reprocessing therapy work? A systematic review on suggested mechanisms of action. Frontiers in Psychology, 9. doi:10.3389/fpsyg.2018.01395
Mitchell, J.M., Bogenschutz, M., Lilienstein, A., Harrison, C., Kleiman, S., Parker-Guilbert, K., Ot’alora G., M., Garas, W., Paleos, C., Gorman, I., Nicholas, C., Mithoefer, M., Carlin, S., Poulter, B., Mithoefer, A., Quevedo, S., Wells G., Klaire, S.S., van der Kolk, B., Tzarfaty, K., Amiaz, R., Worthy, R., Shannon, S., Woolley, J.D., Marta, C., Gelfand, Y., Hapke, E., Amar, S., Wallach, Y., Brown, R., Hamilton, S., Wang, J.B., Coker, A., Matthews, R., de Boer, A., Yazar-Klosinski, B., Emerson, A., & Doblin, R. (2021). MDMA-assisted therapy for severe PTSD: A randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine, 27, 1025-1033. doi:10.1038/s41591-021-01336-3
Mithoefer, M. C., Mithoefer, A. T., Feduccia, A. A., Jerome, L., Wagner, M., Wymer, J., Holland, J., Hamilton, S., Yazar-Klosinski, B., Emerson, A., & Doblin, R. (2018) 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: A randomised, double-blind, dose-response, phase 2 clinical trial. Lancet Psychiatry, 5(6), 486-497. doi:10.1016/S2215-0366(18)30135-4