Oct 14, 2019 / Neuroscience

The Where of the What: A Contemporary Reflection on a Legendary Neuroscience Case

Olivia Habern

Guest Author: Kasandra Burgos, 10x Genomics

The biological basis of psychological conditions have always intrigued me. As early as my first year in college, I remember learning about people who suffered brain damage that resulted in bizarre and altered experiences. For example, the complicated "neglect" syndromes: in these cases, due to stroke or other injury to the inferior parietal lobe, a person is only capable of recognizing half of their body as their own. These patients will protest vehemently that the unrecognized half belongs to another. Other examples of complex sensory damage resulting from even minor trauma, like the loss of smell as a consequence of a low speed car accident, seemed like pure fiction to me. While many of these lessons and case studies stuck with me, none stuck more vividly than the improbable story of the American railroad construction foreman, Phineas Gage.

Some of us have experienced a "light switch" moment – an event in one’s life from which stems an irreversible change. The birth of a child. The death of a loved one. Meeting the Dali Lama. For Mr. Gage, it was September 13, 1848, the day a 43-inch railroad spike "shot skyward" from the ground and through his cheek, penetrating his skull and brain. If you are familiar with this story, you know what happened next.  Astonishingly, he lived. For 12 years beyond the injury that destroyed much of his left frontal lobe, he lived with what folks who knew him best describe as a dramatically different personality. His friends and family reported that he was transformed from a once diligent and hard-working man to one who was lax and complacent. This is one of the first medical examples of personality being linked to a physical location in the body.

Beyond his survival and change in personality, what was even more intriguing, even antithetical to everything I’d ever learned about this kind of major brain injury, was that many of Gage’s original personality traits were restored, at least to some extent, over time. The timeframe in which these restorative changes occurred suggested brain region repair or perhaps even compensation from another area of the brain. While the scans of Gage’s injuries are informative, interesting, and sublimely terrifying, scientists at that time would likely have given anything to utilize the innovative tools we have today to study Gage’s post-mortem brain specimen.

Just imagine the questions they might have asked. What were the homeostatic cellular responses to the scarring around his brain injury? What was the effect of the particular immune response to the foreign object that shot through his head? Did neural stem cells from subventricular zones migrate toward the injury and integrate into the surviving neural networks? Were there compensatory increases in neural activity in surrounding areas? As I consider these questions, the latest tool from 10x Genomics comes to mind: the Visium Spatial Gene Expression Solution. With the Visium Solution, scientists can examine the microenvironment near the area of injury or pathology, capturing mRNA expression from intact tissue sections without target preselection, and enabling unbiased, discovery-level transcriptomics. Had it existed in 1848, the Visium Solution might have totally altered the course of study of the central nervous system. Of course, I’m bending time here and posing what would have been, for the scientists of 1848, unfathomable questions.

Call me a romantic, but I believe the Visium Spatial Gene Expression Solution is the type of genomics tool that neuroscientists have been waiting to use. In fact, it’s already impacting the work of our customers. At the Society for Neuroscience’s 49th annual conference, Neuroscience 2019, which runs October 19th-23rd in Chicago, the neuro community will have the opportunity to learn more about this tool and the ways our customers are using it to advance science. I can’t wait to hear what questions they’ll ask…and where they’ll find answers.