EDITORIAL: Our Squiggly Blob

Sal Iaquinta, MD

There are not many frontiers left to explore. The bottom of the ocean, Mars and deeper space all seem so inaccessible, and thus far they haven’t produced any discoveries that add significantly to our daily lives. Space exploration did popularize Velcro and astronaut food, but where are the big payoffs?

Perhaps we would be better served by exploring the frontier inside our heads: the human brain. Our understanding of the brain is rudimentary. We are building artificial hearts and cloning kidneys, but scientists don’t have a clue about how to raise my IQ.

An outside look at the human brain reveals almost nothing about how it works. You can look at a hand with its wonderful system of muscles and tendons acting together to coordinate a movement. But looking at a brain you see a squiggly blob. What does it do?

For centuries our understanding of the brain’s functions came from traumatic injuries. These are the findings taught in medical school. Left frontal lobe injury yields pseudo depression. Cerebellar injury causes loss of coordination. In essence, we have mapped the brain, but we don’t really understand it. I can open up my computer and map out the components, but that doesn’t mean I understand how they work.

Nonetheless, the last 20 years have produced major advances in brain science. Functional MRI has demonstrated that our brains are always active. Mental tasks increase energy consumption in the active parts by about 5%. This is not the same as the urban myth that we “only use 5% of our brain.” Many of us get by on far less.

Brain scientists recently discovered the glymphatic system. This glial lymphatic system, long thought impossible, appears to clear interstitial waste from the brain. A 2013 study found that glial lymph flow increased about 60% during sleep. It is hypothesized that the proteinopathies (ALS, Alzheimer’s, Parkinson’s and Huntington’s) might be related to a failure of the glymphatic system. A study of mice lacking a specific astrocyte water channel found that their clearance of amyloid-beta decreased by over 50%. Amyloid-beta plaques are found and implicated in Alzheimer’s.

The discovery of the glymphatic system and other brain mechanisms may be just in time, because our society is in for an epidemic. Census data show that seniors are the fastest growing population worldwide. One recent study found that 44% of American citizens between the ages of 75 to 84 have Alzheimer’s disease. As our ability to treat other diseases advances, we only increase the number of people who will suffer from brain disease. Should targeted inhibitors or immune-mediated treatments for cancer be even modestly successful, there will be many more people living into their 80s and beyond.

At the other end of the spectrum are the psychiatric diseases. Although they don’t only affect younger brains, it is true that 75% of all psychiatric disorders begin before age 25. Over the past few decades, the incidence of these disorders has been increasing. Some say it is just our ability to define and recognize more diseases that accounts for the growth in diagnoses. Either way, more diagnoses mean more patients needing help.

Our current medicinal treatment for psychiatric illness is based on known neurotransmitters. Perhaps the biggest breakthrough in this regard was the development of selective serotonin reuptake inhibitors. Their success has made antidepressants the most commonly prescribed medicines in the United States. But not all psychiatric illness benefits from such directed therapy. The best long-term medication for bipolar disorder is still lithium, yet after more than six decades of use, its exact mechanism is still not fully understood. In time, we will learn to identify more neurotransmitters and their receptors. With enough effort, there will be a drug that alleviates my arachnophobia.

Age-related brain disease and psychiatric illness have a huge impact on our quality of life. But so do headaches. Often enigmatic and astoundingly common, headaches plague the world. Nearly one-half of adults report having a headache during the last year. Recent studies have found genes associated with migraines, but the cause of cluster headaches remains a mystery. Joking with the inquisitive patient that their problem “is all in their head” might get a smile, but some real answers would be far more satisfying.

These mysteries are just a few of the many brain teasers to be found within our squiggly blob. For each one we straighten out, the squiggles get easier to follow, and soon what seemed like an inaccessible frontier will be in our rearview mirror.

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Dr. Iaquinta, an otolaryngologist at Kaiser San Rafael, serves on the MMS Editorial Board.
Email: salvatore.iaquinta@kp.org