Wednesday, December 15, 2021

The Olfactory System and Fear Memory Recall: Implications for Odor-Mediated PTSD Therapy


One neurological phenomenon that many people have experienced is the recall of a strong emotional memory triggered by specific smells. Things like the smell of certain foods or plants like pine trees and gingerbread may cause you to have a vivid flashback to Christmas during your childhood. Images of family, pictures with a mall Santa, and the joy of opening presents are just a few of these memories that seem to come to life in your mind as you take in those smells. This phenomenon is known as ecphory, or the activation of a memory by some sort of sensory trigger or cue, which in this case is an odor. However, this memory reactivation is not always pleasant. Post Traumatic Stress Disorder is a neurological condition that is notorious for returning patients to states of anxiety and stress due to the reactivation of extremely unpleasant memories. It has been observed clinically that odors are particularly unique in their ability to trigger this memory reactivation. This paper discusses prior and ongoing research in relation to Dr. Grella’s paper regarding the reorganization of fear memory storage, offering evidence as to why olfactory stimuli seem to elicit strong emotional memories as well as possible odor-based solutions to PTSD therapy.

In her paper, Dr. Stephanie Grella discusses the reorganization of fear memories under the context of the Systems Consolidation Theory. This theory suggests that memories are initially stored in the Hippocampus but then reorganize to rely more on Prefrontal Cortex structures as they become older. Dr. Grella’s research suggests that odor stimuli may trigger a reversal of this reorganization, bringing distant memories in the Prefrontal Cortex back to the Hippocampus and once again making them highly contextualized and vivid. While Dr. Grella’s model utilizes fear-conditioned mice, her paper and seminar presentation made me particularly curious about the neural correlates of PTSD in humans and why olfactory stimuli seem to have such a unique ability to trigger the recall of strong emotional memories. 

Prior research has shown that regions such as the amygdala, hippocampus, and orbitofrontal cortex have been heavily implicated in the consolidation of the olfactory and emotional context of memories. For example, there is an abundance of research that has highlighted that the Amygdala is an essential region in the processing of fear, and exists at a high level of sensory integration for odor stimuli (Daniels and Vermetten). In the case of the Hippocampus, this structure is essential for processes associated with learning and memory and operates in conjunction with the Amygdala in controlling physiological responses to various stimuli (Daniels and Vermetten). Finally, the Orbitofrontal Cortex, a sub-region of the Prefrontal Cortex, is directly connected to regions of the Olfactory Cortex and is the only Prefrontal Cortex region that has a strong connection to the Amygdala (Daniels and Vermetten). Knowing that there is a strong relationship between these particular brain regions definitely justifies and supports the focuses of Dr. Grella’s research article. As mentioned above, Dr. Grella highlighted the Systems Consolidation Theory, which outlines the relationship between memory storage and two brain regions: the Hippocampus and the Prefrontal Cortex. As it turns out, these two regions are also heavily correlated with the processing of emotionally contextualized odor memories. Furthermore, the strong correlation between fear memory storage in the Amygdala and the olfactory system also supports Dr. Grella’s observation that a unique relationship seems to exist between traumatic memory recall and olfactory triggers. In fact, studies of veterans have shown that strong activation of many of the cortical regions mentioned above are associated with odor-cued recall of traumatic memories. For example, by using PET scanning and measuring cerebral blood flow (rCBF), researchers were able to show that exposure to an odor stimulus, like diesel, resulted in noticeably increased rCBF in regions including the amygdala and medial prefrontal cortex (Daniels and Vermetten). Research experiments such as these further support the strong association between olfactory systems and emotional memory recall. 

Finally, Dr. Grella’s research also reminded me of another research experiment that utilized odor stimuli to modulate memories of human subjects during sleep and led me to consider whether or not any research has been conducted to test the ability of odors to modulate traumatic memories. The research article that I had recalled used odor reexposure to reactivate brain regions stimulated during learning while human subjects were experiencing slow-wave sleep (Rasche et al). This astonishingly led to a statistically significant improvement in a memory task, suggesting that reactivation of hippocampus-dependent memories via an odor can actually modulate the memory consolidation process (Rasche et al). To many researchers, these findings seemed to suggest that memory is almost modifiable during a certain phase of sleep and that this plasticity may allow them to target emotional or traumatic memories, altering them through therapy and reducing the sensitivity of fear memory processing regions to reactivation (Daniels and Vermetten). One study used a fear conditioning model to show that fear extinction can actually be achieved by reexposing subjects to odors associated with fear memories during sleep. This experiment first required the subjects to undergo face-shock fear conditioning while under the context of a certain odor (Daniels and Vermetten). Then, while the participants slept, the researchers reintroduced them to the contextual odor without being exposed to the fear-conditioned face stimulus (Daniels and Vermetten). This experiment surprisingly led to a decrease in activation of the Hippocampus and Amygdala when the subjects were once again exposed to the fear-conditioned stimulus (Daniels and Vermetten). One caveat to translating this paradigm to PTSD therapy, however, is that the process would only be effective if reintroduction of a fear-conditioned odor stimulus avoids inducing nightmares in the patients (Daniels and Vermetten). 

Ultimately, there are a lot of questions to be answered in the realm of PTSD therapy and the actual neural correlates behind the development of PTSD and the symptoms that persist in PTSD patients. Animal research, such as the work done by Dr. Grella, has helped us gain a better understanding of how the complex storage and recall of emotional memories are modulated by the olfactory system. Furthermore, her work adds to the already complex puzzle of understanding how various sensory processing systems interact with numerous regions of the brain to create and consolidate contextually vivid memories. Finally, studies of the olfactory system have allowed us to better understand how these different brain regions can be manipulated to alter the strength of these memories, leaving us with the potential to help those suffering from neurological disorders such as PTSD. Although Dr. Grella’s work and all of the work discussed in this paper emphasize how little we know about the brain and its abilities, the amazing progress that the neuroscience field has made in such research can truly inspire those in need that the key to unlocking the secrets of the brain is being desperately pursued by researchers around the world. 


Sources:

Daniels, Judith K. & Vermetten, Eric. “Odor-induced recall of emotional memories in PTSD–Review and new paradigm for research.” Experimental Neurology, vo. 284 part B, 2016, pp. 168-180. Science Direct, https://www.sciencedirect.com/science/article/pii/S001448861630231X 


Grella, Stephanie et al. "Odor modulates the temporal dynamics of fear memory consolidation." Learning & Memory (Cold Spring Harbor, N.Y.). 27. 150-163. 10.1101/lm.050680.


Rasch et al. "Odor cues during slow-wave sleep prompt declarative memory consolidation." Science. 2007 Mar 9;314(5817):1426-9. doi: 10.1126/science.1138581. PMID: 17347444




No comments:

Post a Comment