Dysmenorrhea and the Body: More Research on Understudied Phenomenon

 

In their 2020 study “Dysmenorrhea Subtypes Exhibit Differential Quantitative Sensory Assessment Profiles” by Hellman et. al. researchers looked at the relationship between dysmenorrhea and provoked bladder pain, and sensory sensitivity. Dysmenorrhea is the medical term for menstruation pain. This study found widespread sensory sensitivity in women with dysmenorrhea and provoked bladder pain, and also called for more research into this extremely understudied area (Hellman 2020).

            Because this study was published so recently, there has not yet been time for the scientific community to respond these findings. However, there have been other studies that look more deeply at the mechanisms of dysmenorrhea and investigate why it caused the widespread sensory sensitivity found the Hellman study. One review paper by Barcikowska et. al. wanted to investigate cytokins and other proinflammatory factors and their role in primary dysmenorrhea (Barcikowska 2020). They found previous research that looked only at biochemical reactions between the endocrine, vascular, and immune systems lacking. Another study by Li et. al. looked at the association between dysmenorrhea and chronic pain, both pelvic pain (like the Hellman study) and nonpelvic pain. The team reported a positive association between the two factors (Li 2020).

            While the Hellman study was published too recently for there to be anything more recent in direct response to the questions it posed, there have been other studies and reviews that research the phenomenon of dysmenorrhea and its relationship other conditions of the body. Not only does this highlight the need for further research in this area, but it shows that future research needs to be done on the effects of dysmenorrhea as well as the cause of heightened severity in some women.

 

References:

Barcikowska, Z., Rajkowska-Labon, E., Grzybowska, M. E., Hansdorfer-Korzon, R., & Zorena, K. (2020). Inflammatory Markers in Dysmenorrhea and Therapeutic Options. International Journal of Environmental Research and Public Health, 17(4), 1191. https://doi.org/10.3390/ijerph17041191

Hellman, K. M., Roth, G. E., Dillane, K. E., Garrison, E. F., Oladosu, F. A., Clauw, D. J., & Tu, F. F. (2020). Dysmenorrhea subtypes exhibit differential quantitative sensory assessment profiles. Pain, 161(6), 1227–1236. https://doi.org/10.1097/j.pain.0000000000001826

Li, R., Li, B., Kreher, D. A., Benjamin, A. R., Gubbels, A., & Smith, S. M. (2020). Association between dysmenorrhea and chronic pain: a systematic review and meta-analysis of population-based studies. American Journal of Obstetrics and Gynecology, 223(3), 350–371. https://doi.org/10.1016/j.ajog.2020.03.002

 

 

Aromatic Associations

Aromatic Associations

Laura Shanahan’s article “Scents and Reminiscence: Olfactory Influences on Memory Consolidation in the Sleeping Human Brain'' provides a unique perspective into the extensive impact the olfactory system has with memory. The use of sensory cues, known as targeted memory reactivation, or TMR, is utilized in this study in order to find effective translational research uses to solidify and manipulate declarative and emotional memories. In a similar lens, a recent article was published by the University of Fukui “Smell you later: Exposure to smells in early infancy can modulate adult behavior” explored the phenomenon in which newborn mice “imprint” onto scents that ultimately affect their future social behaviors. With the knowledge that mammals such as mice and humans are both social animals, the long term impact found in the olfactory association is a topic that is necessary to understand due to its impact on social behavior. 

Dr. Shanahan’s research not only correlates memory to the olfactory system, but implements the use of such methods into the sleep cycle to find potential effects that would result from such exposure. Using both positively and negatively perceived aromas, subjects were trained, exposed in their sleep, and recorded once again once awoken to find detectable differences that would be a result of the sleep exposure. An interesting aspect that I found in the study was the fact that the use of TMR led to promising results in fear extinction when previously exposed to negative olfactory stimuli.

Dr. Nobuko Inoue along with their team explored a question that also pertained to the use of smells in memory retention. Specifically, this correlation was discovered between newborn mice and the odors they are exposed to during a critical period. This critical period, only lasting a week, is a result of the interaction between Sema7A, a signaling molecule, and the receptor PlxnC1. During this time, scents that are detected are all positively correlated due to the release of oxytocin from this interaction. Although this appears to be a good system, difficulty arises when newborn mice are exposed to an aversive scent, the mice will now be conflicted for the rest of its life due to the positive correlation from imprinting and the negative correlation from their natural response. Although this exact pattern has not been seen in humans, it is important to note that this critical period may apply to other sensory inputs that can lead to long term effects to newborns. Ultimately, the importance of the olfactory system in animals such as mice and humans extends beyond its immediate use, and extends itself to the implementation of memories that may affect those exposed for their entire life.  Although much of the process in either studies are heavily unknown, the relation between potential fear extinction and its similarity to Dr. Nobuko Inoue’s research on the impact of negative olfactory stimuli during the critical period of newborn mice is interesting to see. 

Work Cited:

Shanahan, Laura K., and Jay A. Gottfried. “Scents and Reminiscence: Olfactory Influences on Memory Consolidation in the Sleeping Human Brain.” Cognitive Neuroscience of Memory Consolidation Studies in Neuroscience, Psychology and Behavioral Economics, 2017, pp. 335–346., doi:10.1007/978-3-319-45066-7_20.

“Smell You Later: Exposure to Smells in Early Infancy Can Modulate Adult Behavior.” ScienceDaily, ScienceDaily, 13 Apr. 2021, www.sciencedaily.com/releases/2021/04/210413110645.htm.

ERP Effects in Infant Brain

Infants social bonding is strongly supported by mother’s face and voice recognition. Though, other aspects of the external world play an important role in development. Prior studies suggested that odor, and more especially maternal odor, is a significant influence: it can produce a soothing effect on crying, reduce anxiety during medical procedures and impact perceptual and cognitive processing. However, little is known about the precise role of maternal odor in early development.

In the recent study “Maternal odor reduces the neural response to fearful faces in human infants” (2020), researchers investigated how infant brain responses and emotional expression may be impacted when exposed to maternal odor. The research was conducted by using electroencephalogram (EEG) on seven-month-old infants and comparing exposure to happy and scary faces. The chosen age of the objects of study was seven-months of age since during that stage of life infants are able to distinct emotional facial expressions. To analyze the impact of maternal odor, researchers used two controls:

* Control 1: exposure to either no specific odor or an odor different from the infant’s mother
* Control 2: exposure to their mother’s odor

The results showed that infants exposed to Control 1 expressed a fear response and the infants exposed to Control 2 did not, which suggested that maternal odor has a significant impact in infants’ social perception.

What I found most interesting about this study, is that researchers quantified the response to fear signals by measuring the amplitude of the Nc, an event-related potential (ERP) component. The Nc component of ERP is frequently studied during infancy because it is related to the attention control (Conte et al., 2020) and the amplitude is believed to increase in response to fearful faces (Jessen, 2020).

Likewise, Conte et al. also investigated infants’ ERP responses (in this case to faces and objects) in developing infants for their research study denominated “Face-sensitive brain responses in the first year of life” where their focus of study was mainly the amplitude variation and cortical localization, and the results suggested that the Nc component differs for faces and objects and is dependent on the attentional state.

Both of the mentioned studies highlight the importance of attention, perception and recognition and how ERPs responses are related to them. Sensory processing is critical for pathological diagnosis but may be even more important to detect certain mechanisms during infancy to prevent or improve cognitive disorders. At that point of life, brain is still developing, and events are not fully encoded; thus, much of the brain development depends on the stimuli exposure during early childhood. Since recording and analyzing ERPs seems to reveal wide information about the brain activity in infants, it is crucial to continue investigating their action mechanisms to design treatments that enhance mental engagement, sense development and stimulation.
 
References
 
Conte, S., Richards, J. E., Guy, M. W., Xie, W., & Roberts, J. E. (2020). Face-sensitive brain responses in the first year of life. NeuroImage, 211, 116602. https://doi.org/10.1016/j.neuroimage.2020.116602
Jessen S. (2020). Maternal odor reduces the neural response to fearful faces in human infants. Developmental cognitive neuroscience, 45, 100858. https://doi.org/10.1016/j.dcn.2020.100858

The Relationship Between Odor and Memory

 The Relationship Between Odor and Memory 

For many centuries, the connection between memory and odor has been studied through various means. A person’s sense of smell has been said to produce the most vivid forms of memory, more than visual imagery or sound. The sense of smell can have a powerful influence on the consolidation of associated memories and can clarify how sensory-rich memories are able to be stored in our brains. Studies have shown evidence for the sense of smell being highly connected to memory, in both slow-wave sleep and in Alzheimer’s Disease. 

In the study “Scents and Reminiscence: Olfactory Influences on Memory Consolidation in the Sleeping Human Brain,” Laura K. Shanahan and Jay A. Gottfried reviewed human literature on the ability of sleep-borne odors to selectively target memories, which influences both declarative and emotional memory consolidation. Shanahan and Gottfried (2017) observed a study where subjects participated in a visuospatial learning task that was paired with a rose odor. After this task, the subjects were put to sleep, and either the same rose odor or an odor vehicle was presented to them in alternation. After waking up, the researchers found that subjects performed better on the memory post-test when they were presented with the rose odor during slow-wave sleep. This finding determined that memory enhancement was specific to slow-wave sleep, and illustrated how odors amplify the consolidation of associated declarative memories during sleep. The researchers also concluded that the hippocampus was activated to a greater level when presented with the rose odor during slow-wave sleep, indicating that the hippocampus may be receptive to olfactory sensory processing. 

An article published on ScienceDaily called “Scientists uncover new connection between smell and memory,” from the University of Toronto, explains the process underlying the strong connection between memory and odor, and the loss of smell in Alzheimer’s Disease. Similar to the article from Shanahan and Gottfried (2017), the authors here say that there is a strong connection between a sense of smell and memory, and examine the hippocampus as a structure important to memory representation. In this study, researchers looked at the function of the anterior olfactory nucleus (AON) in mice. The mice with a disconnected pathway between the AON and hippocampus returned to previously smelled odors to sniff them for longer time periods. This result illustrates how the degeneration of the AON indicates an inability to detect previously observed smells. Early detection of Alzheimer’s may be more feasible now due to smell tests, although further research still needs to be conducted to perfect this. In relation to the article from Shanahan and Gottfried (2017), the emphasis on the connection between sensory olfaction and memory is highlighted, showing two different experiments where this relationship is present. Furthermore, both articles point out the fact that further research needs to be done on each respective topic regarding the relationship between olfaction and memory, suggesting that this topic is still fairly new and much more can be done to explore this connection. 

Although much more work needs to be completed to fully understand the mechanisms underlying olfactory sensation and memory, the research from Shanahan and Gottfried (2017) and the neurobiologists from the University of Toronto provide strong evidence that a person’s sense of smell is the most powerful form of memory consolidation. Even though certain findings, like the hippocampus in slow wave sleep, and the AON in Alzheimer’s patients are not fully developed yet, improvements and new technological methods can help scientists understand further processes regarding connections between olfaction and memory.

Sources: 

Gottfried, J.A., Shanahan, L.K. (2017). Scents and Reminiscence: Olfactory Influences on Memory Consolidation in the Sleeping Human Brain. Cognitive Neuroscience of Memory Consolidation, 335-346. https://doi.org./10.1007/978331945066720

University of Toronto (2018). Scientists uncover new connection between smell and memory. ScienceDaily. www.sciencedaily.com/releases/2018/07/180723155726.htm

Modification of Emotional Connections

    Post-traumatic Stress Disorder (PTSD) and similar conditions such as depression and anxiety have a significant impact on people’s daily lives around the world.  PTSD, specifically, often is correlated with strong emotional connections to an event.  This connection can be extremely strong, and people often report total submersion into the memory of the event during an episode.  The root cause for the distress and cause of dysfunction in daily life is the emotional response when triggered back to the event.  The ability to remove these memories, or alter the emotional attachment to them, would be a significant step forward in the treatment of psychiatric disorders.

    Researchers are working on such an ability with the development of optogenetics.  This invasive medical procedure allows for extremely targeted modifications in synaptic strength.  Previously, researchers have been able to implant false memories into mice by tagging neurons of memory-engram regions in the mice’s hippocampus that were activated during a fear context.  They then later activated these neurons in a different context and elicited a fear response from the mice.  Perhaps more interestingly, researchers were also able to deactivate and then later reactivate memories.  This was done through optogenetic stimulation in the lateral amygdala.  The memory was deactivated via long-term depression which had disturbed the associative memory created earlier.  Researchers were then able to recover the memory via long-term potentiation the following day.  Impressively, researchers have been able to do repeat these results with well-established memories in mice by inhibiting CA1 hippocampal neurons when exposing the mice to a cue established over four weeks prior.  Similarly to the research done prior, these effects were temporary and reversible via stimulating the neurons in the CA1 hippocampus.  There are more possibilities with optogenetics than simply turning memories on and off, they can be manipulated as well.  We are capable of making valence modifications to memory, such as turning a sad one to a happy one.  This does not alter the memory itself but alters our emotion connected with it.  When we recall a memory engram, which is encoded in the hippocampus by the dentate gyrus, the valence of an elicited response could be altered through reassociation with a new unconditioned stimulus of an opposite valence.

    Emotional responses to stimuli studied by Dr. Foci, in his work “Differentiating neural responses to emotional pictures: Evidence from temporal-spatial PCA”, may have a unique connection to the future of optogenetic studies.  We consistently have emotional responses to the stimuli around us, and this may become highly taxing on those in high-stress work environments such as doctors and soldiers.  By targeting and flagging specific neurons, we may someday be able to turn on and off the emotional component of our connection to the world around us.  This may be highly beneficial for those who suffer from PTSD and similar anxiety disorders who may suddenly become overrun with emotion due to a triggering event.  Optogenetics may play a helpful role in psychiatric treatment through memory modification and through valence modifications in order to preserve memories but reverse negative emotional aspects of them.

https://link.springer.com/article/10.1007/s11569-020-00377-1

Think with your nose!

 Think with your nose!

The term memory can be defined as something remembered from the past, a recollection of sorts. However, we have come to know that memory is more than just a collection of the past. Sure, that is a part of it, but numerous studies and experiments throughout the fields of neuroscience and psychology has taught us that there are many variants of memory. We can begin with three basic levels of memory: sensory memory, short-term (working) memory, and long-term memory. When we think about the word memory, most often people immediately refer to long-term memory, which was defined earlier as collection of the past. What do these collections entail? Our brain is an amazing work of biological machinery with the ability to sort these memories and code them into different groups, or types of memories. It is not often that we randomly think about our past memories, yet there is always something to trigger a set of memories which allows us to remember our past experiences. 

In the article “Scents and Reminiscence: Olfactory Influences on Memory Consolidation in the Sleeping Human Brain”, researchers Shanahan and Gottfried analyze how certain memory can be consolidated through the use of olfactory cues. Now most of us would think that we tend to recall something after seeing a picture we can recognize of hearing a familiar voice, but most of us wouldn’t think right away that memories can be triggered via olfactory stimulation. Their research focused on how smells could improve memory. The researchers asked participants to complete a set of tasks. The experiment group was given certain odors while completing the task and while they would sleep. The research showed that showed that when participants completed tasks with a certain odor and were then presented with the same odor during their sleep, they demonstrated better performances overall when compared to the control group which didn’t receive the olfactory stimulation during their sleep. These results indicate that olfactory stimulation can play a role in improving memory consolidation, a theory that has been previously studied and agreed upon. 

Not only do olfactory cues help with memory consolidation in humans, it can also help improve working memory in other species as well. A research study conducted by Ka Ho and Roberts showed that certain odors improved the episodic memory of dogs. Episodic memory is the long-term memory for remembering events and experiences. When the dogs were tested with odor stimuli, they were able to show an improvement in memory in terms of what, when, and where they remembered certain things. Although it was difficult to address whether or not they showed improvement in the what, where, and why separately, it showed there was improvement in their memory regardless of whether they were grouped together or not. 

It is fascinating to see how far research and experiment has taken us to see what the brain is capable of and how much the brain is capable of doing. We still have yet to see understand the entirety of the brain, but what we have learned so far is quite exemplary. There are so many neuronal connections that we wouldn’t expect to make ourselves. For example, in this case, the temporal lobe contains the olfactory cortex and the hippocampus (responsible for memory), both of which can be related as we have discussed in this article. Not only can we see these associations in humans, but many other animals as well. It is interesting to see how unique the human brain is, but also very much similar to the brains of other species. More importantly, it will be exciting to discover more about the brain in future studies.  

Works Cited

Lo, Ka Ho, and William A. Roberts. “Dogs (Canis Familiaris) Use Odor Cues to Show Episodic-like Memory for What, Where, and When.” Journal of Comparative Psychology, vol. 133, no. 4, Nov. 2019, pp. 428–441., doi:10.1037/com0000174. 

Shanahan, Laura K., and Jay A. Gottfried. “Scents and Reminiscence: Olfactory Influences on Memory Consolidation in the Sleeping Human Brain.” Cognitive Neuroscience of Memory Consolidation, 2017, pp. 335–346., doi:10.1007/978-3-319-45066-7_20. 

SSRIs for Comorbidity of Chronic Pelvic Pain and GAD in Women?

According to Anxiety & Depression Association of America, Generalized Anxiety Disorder (GAD) “is characterized by persistent and excessive worry about a number of different things” and is diagnose “when a person finds it difficult to control worry on more days than not for at least six months” and exhibits at least three associated symptoms, like having an increased heart rate or having trouble sleeping.  People who have GAD struggle to control their worry which may hinder other areas of their social, educational, or occupational lives.  Based on data from the National Institute of Health of the United States, an estimated 5.7% U.S. adults experience GAD at some point in their life.  In adults, women experience GAD at almost twice the rate that men do, at 3.4% and 1.9%, respectively.  

In “Dysmenorrhea subtypes exhibit differential quantitative sensory assessment profiles” Hellman et al. examined menstrual pain in reproductive aged women.  Although they were not directly studying anxiety, their data showed that “anxiety and somatic symptoms were significantly greater in all symptomatic groups”.  This means that the groups of women they studied who had another pelvic pain condition also showed a greater comorbidity rate of anxiety compared to healthy controls.  

Practical Pain Management, an all-in-one journalistic website about pain and pain management, published an article in 2021 titled “The Complex Intersection of Pelvic Pain and Mental Health in Women” written by Dr. Kathryn A. Witzeman.  There is limited research in this field (also acknowledged by Hellman et al. in their study) but Dr. Witzeman states that based on the existing research that there is a strong association between pelvic pain disorders and mood disorders, including anxiety.  She hypothesizes that “this increased comorbidity between persistent pelvic pain and mood disorders, as well as with other pain disorders of disparate body regions, may be influenced by disruptions in the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system, which contribute to the regulation of stress and influence the perception of pain”.  Serotonin is a neurotransmitter that has many roles, including mood regulation and the perception of pain.  The HPA and serotonin directly impact each other, although how they do so has not been well-defined.  What if there was a treatment that could help both conditions?

For women suffering from pelvic pain and anxiety, looking at a type of antidepressant could be an option for managing symptoms of both issues.  Selective Serotonin Reuptake Inhibitors (SSRIs) are a type of antidepressant that increase the serotonin levels within the brain.  They are a much more safer option compared to addictive opioids and typically cause fewer side effects compared to other classes of antidepressants.  There is very little current research that exists on SSRIs and pain management.  This could be a new avenue for researchers to look into to help women suffering from pelvic pain and GAD.  

References:

Chronic Pain. Chronic Pain | Anxiety and Depression Association of America, ADAA. (n.d.). https://adaa.org/understanding-anxiety/related-illnesses/other-related-conditions/chronic-pain. 

Kathryn A. Witzeman, M. D. (n.d.). Pelvic Pain and Mental Health Disorders in Women: Which Comes First? Practical Pain Management. https://www.practicalpainmanagement.com/complex-intersection-pelvic-pain-mental-health-women. 

Hellman, K. M., Roth, G. E., Dillane, K. E., Garrison, E. F., Oladosu, F. A., Clauw, D. J., & Tu, F. F. (2020). Dysmenorrhea subtypes exhibit differential quantitative sensory assessment profiles. Pain, 161(6), 1227–1236. https://doi.org/10.1097/j.pain.0000000000001826 

Complex-intersection-pelvic-pain-mental-health-women