As scientists, it can be hard to find motivation and spirit in the quotidian work we perform. There are days when it is certainly difficult to execute qPCR or stereology studies without wondering what it will amount to. “What does it all mean? What is the point?” These are some of the questions that afflict us during trying times, or when the daily minutiae simply feels exhaustingly mundane. But of all the ways scientists can rejuvenate and refocus their research, I have found a duo to be particularly helpful: metacognition and contextual placement.
Metacognition often presents itself as a form of value judgment about one's thoughts, such as "My thinking is too narrow." Academic life is a difficult path, and these types of ruminations are not without reason. It is therefore essential to not just consider what you think, but how you think it. Contextual placement is a key concept associated with the psychological technique called cognitive reframing (or restructuring). Usually utilized as a therapeutic intervention for patients suffering from disorders such as depression and substance abuse, this method assists in changing a person's general mindset. The assumptions made in this framework are that we can be taught to think differently, with the objective of conforming our internal beliefs to reality. As researchers, we can greatly benefit by situating our work within the world—even if the connection between your work and the world is linked only by the basic human desire to gain knowledge.
Emotional connection to one's profession is not an obstacle—it can actually enable better work. A few years ago, I came across a video that put much of the emotional tug of the work I do into stark reality. This is a world almost out of some deluded version of a Stanley Kubrick film—shattered lives moving to the music of David Guetta. These scenes mark the greatest transition made by the Romanian orphans in the early 1990s, when they were not considered orphans as much as byproducts of Ceausescu’s forceful population-increase propaganda. Parents would give birth to more children than they could afford to support, eventually leaving them with state care. Most of the children living in these 600 Romanian orphanages underwent massive neglect, abuse, and ultimate separation from society.
One might wonder: Why should an early life experience in orphanages have such adverse effects on children? Advances in behavioral neuroscience are providing compelling evidence that such early life adversity can have powerful effects on the brain and body, lasting throughout one’s lifespan. Many of these early stress exposures produce long-lasting behavioral and pathophysiological problems, including onset of depression, substance abuse, and schizophrenia, as well as changes in brain structure, function, and volume. Studies have shown that children having experienced early institutionalization (more than 30 months) in Romanian orphanages have greatly reduced cognitive functionality, along with overall decreases in white matter, when compared to institutionalized children who were taken to foster homes (enriched environments) before 30 months. Apart from volumetric changes, psychological stress can lead to excessive secretion of the stress hormone cortisol and aberrant connections between brain regions. Recent data also suggests that early life stress can cause the brain and body to activate inflammatory responses, and trigger epigenetic modifications, which in turn impact gene regulation.
In our lab, we study the effects of negative early life experiences, such as emotional and/or physical abuse and neglect, on neurobiology and behavior. Adolescence is a period in which psychopathologies such as depression, anxiety, substance disorder, and schizophrenia often emerge due to such adversity. This is unsurprising, as adolescence is a time when major circuitry patterns between various brain regions begin to form. Since maternal care is essential for the proper growth and development of all mammals, we use a maternal-separation paradigm in a rodent model to assess these changes, using techniques including Western blotting, immunohistochemistry, laser capture microdissection, and neuroanatomical tract tracing. Our work focuses on the effects of early life stress on inflammatory responses in the brain, changes in connectivity between various brain regions (such as amygdala, hippocampus, and prefrontal cortex), the neuronal machinery alterations involved in such alterations, and the behavioral effects of the stress paradigm. But for people like us doing basic science research, it is easy to delve so deep into the nitty-gritty of our work that the big picture sometimes seems out of reach. Yet there is always a greater problem that our work tries to enlighten, even if in a minuscule way.
The work we do is modeled in rodents, and there is an issue with how translatable these results are in humans. That is the test of interdisciplinary work: getting from bench side to bedside. Ultimately, understanding the detrimental consequences of early adversity is not just a science problem; it is a human problem that needs understanding. Therefore, on days when the metacognitive judgments sway me toward ineptitude and desolation, I try to reframe my insecurities and remind myself of the contribution our research can bring to adolescents and adults alike—one small scientific discovery at a time. When I started graduate school, my advisor gave me a gift: Santiago Ramón y Cajal's Advice for a Young Investigator. His (perhaps a bit harsh) words of wisdom have always been of great comfort to me, and it is my sincerest hope that it shall ring true for you as well.
"The indescribable pleasure—which pales the rest of life's joys—is abundant compensation for the investigator who endures the painful and persevering analytical work that precedes the appearance of the new truth, like the pain of childbirth. It is true to say that nothing for the scientific scholar is comparable to the things that he has discovered. Indeed, it would be difficult to find an investigator willing to exchange the paternity of a scientific conquest for all the gold on earth. And if there are some who look to science as a way of acquiring gold instead of applause from the learned, and the personal satisfaction associated with the very act of discovery, they have chosen the wrong profession.”
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