Our journey towards bridging the gap between physical and mental health continues this week as we do a deep dive into the body’s systems. Researchers have long been interested in understanding a direct pathway between our organ systems and our brain. The hope is that we can develop a better understanding of how our body works and how our brain communicates with it. Through our previous learning, we determined that our body and brain are communicating synonymously, responding appropriately to changes in our environment in order to establish a baseline. This is a natural process referred to as homeostasis. Think of the human body as a machine, and each of the organ systems are the cogs that help it run properly. If one of the cogs is not functioning smoothly, the machine can still work, but it will be less effective. Naturally, our bodies want to maintain a comfortable state that is optimal for all of its “cogs” to rotate together like a well oiled machine. In short, if something feels wrong, our body recognizes, our brain interprets, and they both work together to fix it. The process of homeostasis is innate and illustrates how intertwined our systems truly are.

Let’s zoom in and, more specifically, take a look at the neural connection between the adrenal glands (located superior to the kidney) and different areas of the brain. A study completed by Richard P. Dum et al., “The mind-body problem: Circuits that link the cerebral cortex to the adrenal medulla”, focuses on this exact connection. The adrenal glands are part of the endocrine system and are unique because they secrete stress hormones when they receive the proper signals from the brain. In turn, these hormones activate a sympathetic response. If this sounds familiar, it should! Think, “fight or flight.” Again, this exemplifies the beautiful mutualistic relationship between our body and brain. Our body recognizes a change in our environment, our brain interprets this change and sends signals to the adrenal glands to secrete stress hormones into our blood. Action!

Furthermore, the adrenal glands are sequestered into different sections including the adrenal cortex which releases cortisol (a prevalent stress hormone), and the adrenal medulla which releases norepinephrine and epinephrine (i.e. adrenaline – our primary “fight or flight” hormones). Conceptually, if we could map out the path between the adrenal medulla and specific regions of the brain, we could assess other functions that those particular regions are responsible for. Having this understanding may allow us to further explore complex relationships between our brain, body, and mediation of its response to stress. In other words, when our body responds to stress (positively or negatively), our brain lights up in specific regions. What else makes those same regions glow? Could knowing the answer give us clues to help us effectively manage stress? Let’s see what the research suggests.

In this study, the researchers used radioactively tagged rabies virus (RV). RV is unique in a couple different ways which make it the perfect conduit for this test. First of all, RV specifically attacks the nervous system which is extremely helpful for neural mapping. In addition, RV is able to travel in a retrograde (reverse) fashion, backwards through the nervous system from its site of infection to the spinal cord, and eventually, the brain. By injecting primate subjects with RV directly into the adrenal medulla (responsible for secreting norepinephrine and epinephrine – i.e stress hormones), researchers were able to successfully map out the path back to the brain.

What the researchers discovered was pretty cool! The virus lit up the brain in regions that control very distinct functions. First, the prefrontal motor and motor cortex of the brain was affected specifically in regions that pertain to activating the muscles of the core. This suggests that there is a potential connection between the “fight or flight” response of the primate when they engage muscles of their core. Whether that relationship represents up-regulation (“turning up”) or down-regulation (“turning down”) of this response is unknown and not within the means of this specific study. However, recognizing that the relationship may exist is a great place to start.

Next, the pgACC region, which is activated during mindfulness based activities such as meditation, also lit up. This part of the brain plays a role in emotional processing and regulation. Potentially, this could provide an explanation as to why these techniques can help somebody toggle into a more relaxed state of mind and reduce symptoms of stress. The pgACC also has innervations to the vagus nerve (which we discussed last week) suggesting a possible relationship to the parasympathetic (“rest and digest”) nervous system as well.

Lastly, the sgACC region, responsible for emotional regulation, showed a connection to the adrenal medulla. This part of the brain is interesting and can be referred to as the “depression connectome.” It has been a subject of study regarding mood disorders and their effect on the autonomic nervous system. In general, the sgACC shows activation when one experiences negative emotions. However, deep stimulation of this part of the brain and the areas around it have shown to alleviate treatment failed symptoms of depression. Another interesting connection can be derived from mice studies. Research has shown that lesions to this part of the brain and its surroundings have increased the “fight or flight” response suggesting a direct correlation to the adrenal glands in mice. If all of this research can be applied to humans, it is very possible to assume that the sgACC both regulates emotions while also affecting the response of the autonomic nervous system (“fight or flight”). Since we have the general knowledge that exercise can mediate symptoms of depression, this could be a relatively untapped connection between the two. It remains unknown how exercise would directly manipulate this part of the brain for a positive outcome, but as mentioned, it is worth exploring the idea.

According to the study, it appears that the same regions of the brain that control these various functions also have a neural relationship to the adrenal medulla. Making the connection is great, but the next step is figuring out how these functions affect the nervous system. At this point, within the means of the study, it is unknown whether engaging the muscles of the core, meditating, or practicing other mindfulness based activities up-regulate or down-regulate the autonomic nervous system (although other research suggests down-regulation unanimously). However, knowing that there is a direct connection may be enough to further pursue this idea.

You’re probably thinking something along the lines of, “Yeah, that’s great, but how does this apply to my exercise routine on a daily basis?” If this crossed your mind at some point throughout your reading, I would not hold it against you, but rather, let me offer you a couple viable connections. Movements such as yoga and pilates that incorporate engagement of the core, aerobic exercise, and mindfulness may be a strong indicator as to how one can connect with their autonomic nervous system. As we continue to progress through more mindfulness prescriptions, we will learn of ways to become intentionally mindful before, during, and after exercise, all of which may assist with activating parts of the brain that regulate stress. If these methods hold true, it is possible that one could manipulate their response to stress through physical activity, and this is exactly the point that I intend for you to take forward.

Disclaimer: Of course, primate studies are the closest we can come to human studies, but there is no “one size fits all” neural networking map that can describe how an individual’s nervous system functions. Humans are complex and have developed their own ways of modulating stress through analyzing their surroundings, developing complex emotional responses, and more. We are all different, but hopefully some of these general trends can be applied with some legitimacy.

Images sourced:

https://www.hopkinsmedicine.org/health/conditions-and-diseases/adrenal-glands

https://isabellahasrabbies.weebly.com/the-science-of-rabies.html

https://pubmed.ncbi.nlm.nih.gov/31871146/#&gid=article-figures&pid=fig-3-uid-2

https://www.news-medical.net/health/Using-Brain-Maps-to-Predict-Behaviors.aspx

Primary sources:

Dum, Richard P, et al. “The Mind–Body Problem: Circuits That Link the Cerebral Cortex to the Adrenal Medulla.” PNAS, National Academy of Science, 23 Dec. 2019, www.pnas.org/doi/10.1073/pnas.1902297116.

Drevets, Wayne C, et al. “The Subgenual Anterior Cingulate Cortex in Mood Disorders.” CNS Spectrums, U.S. National Library of Medicine, Aug. 2008, www.ncbi.nlm.nih.gov/pmc/articles/PMC2729429/.