Health Tech

Know Thyselves

By KIM BELLARD

With all the fuss about A.I. I was pleased to find some studies that illustrate that we don’t even fully understand the human brain yet. The ancient Greeks had a maxim “Know Thyself,” but the current research suggests they should have advised that we should “Know Thyselves.”

A new study from Stanford Medicine suggests that our brain is actually two separate organs: “…we postulate the brain is a composite organ emanating from two lineage-restricted progenitors; these dual progenitors may be evolutionarily conserved across 550 million years from hemichordates to mammals.”

Say what?

Now, let me make this clear: they’re not saying that the brain evolved from two separate organs into the brain we have today; they’re going a step further and saying there are still two separate organs, working together or in parallel. Freud must be feeling vindicated.

The press release says:

The new research finding shows that the human brain consists of two ancient nervous systems cleverly packaged together — a more primitive part that regulates our hearts’ beating, our breathing and other functions, and another that makes us distinctly human, capable of poetry, mathematics and wondering about our own origins.

“We’ve shown for the first time that the front of the brain arises from a totally different progenitor cell than the back of the brain,” said Kyle Loh, PhD, associate professor of developmental biology. “Our discovery means that we can now grow neurons from the back of the brain, the hindbrain, in a petri dish and study their functions.”

If you’re wondering why growing neurons from the hindbrain matters, it turns out that diseases that impact the brain stem, such as spinal muscular atrophy (also known as SMA) and amyotrophic lateral sclerosis (also known as ALS or Lou Gehrig’s disease), have been hard to study because of the difficulty of growing such neurons in the lab. The researchers discovered the hindbrain follows a separate developmental path, running in parallel to — rather than branching off from — the pathway that creates the forebrain and midbrain.

“Previous attempts to make hindbrain neurons likely tried to coax forebrain and midbrain progenitors into hindbrain cells, which our study shows is not possible,” co-first author Rayyan Jokhai said. He added: “Now we have a model to better understand these devastating diseases, and work toward regenerative therapies for them. This is a very exciting new frontier in brain research.”

The researchers looked at various organisms and found that the separate systems date back over 500 million years. “Our research suggests that evolution took two existing neural systems and pushed them together spatially,” Professor Loh said. “Having the brain as one organ would probably be more efficient, but we rely on this primordial way to make the brain as two separate pieces.”

“I was surprised at our findings because the word ‘brain’ implies a contiguous organ that likely has a singular origin,” Mr. Jokhai said. “But even 500 million years ago, there were these separate neural systems, which now almost operate as one, which is very cool.”

Very cool, indeed.

Meanwhile, up the road a few miles, researchers at UCSF and UC Berkeley have shown, in real time, the brain essentially arguing with itself. They studied patients who had electrodes implanted for surgical evaluation of epilepsy, and used those to watch the brain trying to decide to do something or not. They discovered – you guessed it — two neighboring patches of the brain that signal in opposite directions, one pushing toward “do it,” the other toward “don’t.”

“We’ve long suspected that this region was where the brain weighs reward against risk, but we’ve never been able to measure it while it is happening in the human brain in real time until now,” said Edward Chang, MD, Joan and Sanford I. Weill Chair of the Department of Neurological Surgery at UCSF and co-senior author of the study.

The researchers had participants play a video game where they had to navigate a maze with bomb-filled hallways, posing varying degrees of risk. As they reached decision points, the researchers identified two distinct areas of the brain firing; region near the middle of the eyebrow was connected to a risky choice, while a patch about two centimeters over, toward the side of the eyebrow, did the opposite.

“Most models of decision-making assume the brain gradually ramps up evidence until it crosses a threshold, like a dial slowly turning,” said Robert Knight, MD, professor of Psychology and Neuroscience at UC Berkeley and co-senior author. “What we saw instead was more like a switch flipping back and forth, oscillating between two extremes until one held.”

The researchers believe that their discovery could help conditions where people have an imbalance between risk-taking and caution, such as depression, OCD or gambling addiction. Co-author Clara Starkweather, MD, PhD, a neurosurgery chief resident at UCSF, who designed the video game, said: “Right now, psychiatry mostly relies on asking people how they feel, I want to give it something more objective: a real, measurable signature of how someone’s brain weighs risk, so treatment can target the specific circuit that’s off, in addition to a mood score.”

Last but not least, researchers at the Salk Institute discovered a part of the brain that seems to be responsible for long-lasting fear responses. The amygdala has long been associated with immediate fear responses, but they identified a tiny nearby area called the amygdalostriatal transition zone (ASt).

“The ASt is at a crossroads between the brain’s systems for emotional associations and action selection, but its function was largely unknown,” says co-corresponding author Fergil Mills, PhD. “When we started, we knew almost nothing about the ASt, and were truly exploring unknown territory in the brain. Now, we have a much deeper understanding of this structure and have found that the ASt is a ‘missing piece’ of the circuits for fear that was hiding in plain sight for decades.”

“The ASt and this circuit could be really relevant in developing therapies for panic attacks or phobias,” adds co-corresponding author Kay Tye, PhD, a professor and holder of the Wylie Vale Chair at Salk and Howard Hughes Medical Institute investigator. “Anxiety disorders affect hundreds of millions of people globally. Understanding what happens in the brain when it’s in high-alert danger mode is key to addressing those disorders.”

Admittedly, the research was done on mouse brains, so more research will be required, but it is both promising and more evidence that our brains still hold more mysteries than we realize.

With so much attention and funding focused on A.I., it’s gratifying to see that there is still startling research being done on what drives our own intelligence.

Kim is a former emarketing exec at a major Blues plan, editor of the late & lamented Tincture.io, and now regular THCB contributor

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