From Tissue to Thought

by Shruthi Shivkumar

Across the fields of neuroscience, psychology and philosophy, one problem has constantly presented itself: what is the link between the human body and the mind? To better describe this complex relationship, some philosophers presented the idea of mind-body dualism, or that the two realms are completely distinct - meaning that humans are a composite between soul and body. For example, the French philosopher and scientist Rene Descartes believed that the body received information through the sensory organs, which transmitted information to the brain, where it was translated to the immaterial spirit. Others proposed the idea of monism, where the two realms are united. Various monists subscribe to different understandings of this general ideology. For example, some posit that mind gives rise to matter, or matter gives rise to mind. Yet others believe that a unified third natural substance branches off to yield both mind and the physical body.

In neuroscience, the problem of the relationship between mind and body is not relegated to the age-old debates of ponderous philosophy. Rather, it is a main focus of contemporary biomedical research. Connections between the mind and body can reveal how the two affect each other. For example, one clinical application pertains to the study of “psychosomatic” disorders –

a class of diseases which is viewed suspiciously in modern science, mainly because they are characterized by a lack of an identifiable origin. Patients can sense that they are suffering from pain or health issues, but physicians cannot identify any physical cause of their symptoms. Societal stigma leads to the doubt of psychosomatic disorders: they are seen as “fake” diseases. Discovering a neural basis to better determine the underlying pathology of these disorders that are “all in your head” could lead to possible treatment and reduce this stigma.

Another application of mind-body research involves the calming effects of physical activity like yoga or running. Could scientists possibly discover the physiological basis for how these various exercises can reduce stress? Or is it simply a placebo effect? At the University of Pittsburgh, neurobiologist Dr. Peter Strick and his team of researchers

delved into these questions through a new anatomical tracing method they pioneered. By injecting a neurotropic rabies virus into specific cortical areas of the brains of monkeys, they were able to map out neural pathways between different regions of the body and various cortical areas. The team immediately began to focus on studying the adrenal medulla, a gland which secretes important hormones, such as epinephrine and norepinephrine, and acts as a main effector in stress and the human “fight-or-flight” response. To their surprise, the team found many neural connections between the adrenal medulla and other brain regions along with other parts of the body.

Why are these findings regarding the adrenal medulla so critical? Humans experience more than a simple dichotomy between fight and flight, the sweaty palms and dilated eyes of an age-old process. As higher-order beings, we have what neuroscientists call “top-down control” over our stress responses. “Because we have a cortex, we have options,” said Strick. “If someone insults you, you don’t have to punch them or flee. You might have a more nuanced response and ignore the insult or make a witty comeback. These options are part of what the cerebral cortex provides.” Now, with his research, we have more insight into the neurological circuitry that allow humans to have these varieties of complex responses to a stimulus. Long chains of neurons connect to the adrenal medulla and provide input on stress reactions. One such expansive circuit uncovered by Strick connects the adrenal medulla to the motor cortex, a region of the brain that is involved in initiating and executing voluntary movements. A second, smaller pathway connected this adrenal gland to the cortical areas involved in higher-order thinking and cognition, such as regions of the anterior cingulate cortex. Given that pathways exist from the brain to glands such as the adrenal medulla, these findings provide insight into the underlying neural basis that links mental states to their physical manifestations.

As Strick said, “My sons have told me that I can have a bit of a stressful job...so they said to ‘deal with stress, you ought to try some yoga and core strengthening’. And I said, ‘I don’t see that there’s a neural substrate, a real reason why core strengthening would have any influence on stress. And of course playing games and doing something other than work can be a stress reliever- but what about core strengthening?’” Strick ended up finding a surprising answer to his own question. The motor cortex is said to be somatically organized – meaning that different parts of the brain region correspond to different parts of the body. When looking at this “motor map,” the team discovered that the axial body muscles – or core region – had a direct pathway to affect the adrenal medulla. Whenever the core region and other anatomical areas are used to maintain and proper alignment for exercise, the motor cortex of the brain directly connects and provides input to the adrenal medulla and reduces the activity of the hormones responsible for producing a stress reaction. Thus, there is a real neural basis for the connection between stress and movement-based activities like yoga and running.

The second neurological pathway connects the adrenal medulla to regions responsible for higher-order functions such as cognition and affect. One clinical application of this pathway relates to a potential explanation for Post-Traumatic Stress Disorder. “When we look at the regions of the brain that went to the adrenal medulla, some other areas are cortical regions that are within our cognitive control network: areas that light up when you appreciate that you’ve made an error, when you have a stressful decision to take, when you sense that there’s a conflict,” Strick explains. Whenever someone beats themselves up over a mistake, this connection inputs to the adrenal medulla and they experience just as much stress as when the actual conflict or event occurred. This might elucidate the mechanism behind PTSD, which causes people suffering from the disease to relive periods of high anxiety long after the events occurred.

Strick’s discovery of these two main pathways – the medulla to the motor cortex and the medulla to the medial prefrontal cortex – have incredible implications. His team has learned about the networks that connects movement, emotion, cognition and stress. Taken altogether, the results point to how all of these brain functions affect the human body as a whole. “This circuitry,” states Dr. Strick’s abstract, “may mediate the effects of internal states like chronic stress and depression on organ function.”

Psychosomatic illness often involves mental pathways affecting internal organ processes. However, until recently, the mechanisms by which emotions and mental states can have such a tangible physical impact have not been widely understood. Strick’s research on circuits leading through the adrenal medulla can be used to find specific neural connections between the brain and different parts of the body. Now, with neurological bases for psychosomatic symptoms, researchers can look to develop medication that targets specific areas in the brain in order to prevent physical symptoms instead of just treating them somatically, like any other illness. Through this mind-body research, Strick believes that his team may have discovered a neural basis for functional disorders such as irritable bowel syndrome, fibromyalgia and stress-related heart disease.

As one of ten recipients of the Transformative Research Awards – a five-year, 6 million dollar grant from the National Institutes of Health – Strick and his research team are currently leading a groundbreaking project to continue building a structural framework for the brain-body connection. Their overarching goal is to create a mental roadmap to chart out the neural pathways that allow regions of the brain to exert control over various body systems such as the cardiovascular, immune and digestive systems.

Overall, the team hopes to widen our view of how the physical body and mind interconnect, furthering potential for finding targets for treatment and shifting the paradigm on how two aspects of our humanity come together. While we may never find out if Descartes’ beliefs in dualism or the different branches of the monism were right, research teams like Dr. Strick’s have narrowed the gap between the physical body and the mind.