Brain mapping

How well did we map the human brain? Do we really know the real role of each brain part? The truth is pretty complex. We definitely know a lot of details. Like certain pieces of the puzzle that show the underlying image, but not all of it. Once in a while, there is huge progress in brain mapping. Recently something cool happened. More info here.

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How do we map a dead brain?

This question is actually more complex than it looks. The human brain is pretty complex. It is a non-trivial three-dimensional structure. The brain in autopsy can be sliced by a surgeon and the slices analyzed. The so-called limbic and reptilian brain has several parts that appear very different from each other to any trained surgeon. 

The neocortex is huge, and it looks very uniformly like a walnut. The human brain is nearly 60 percent fat, which is the white substance we often see. Lipids are especially focal to brain activity in structure and in function, helping to form nerve cell membranes, insulate neurons, and facilitate the signaling of electrical impulses throughout the brain. We’ve learned in recent years that fatty acids are among the most crucial molecules that determine your brain’s integrity and ability to perform. There are good and bad fats, and you need to include more good omega-3 based fat to protect your brain against the bad fat. From foods such as olive oil, nuts, or avocado and fish —perform best.

Functional mapping of a living brain

The functioning of the neocortex is very complex, and its functions are mapped on the relevant columns of the limbic brain. This makes the functional images so important. The engineering of fMRI scanners is pretty complex, but that should not really matter for most of us.  The result is pretty simple: people are asked to do some very controlled activity like a puzzle or coordination game or watch emotionally intense images and certain areas of the brain light up in the 3D brain model.

This sounds simple, but it is not. Brain structure is a bit different between individuals and brain areas with certain functions are in slightly different locations. Averaging these results over many people produces a very inconsistent smeared picture. So the basic idea is very accurate 4D registration with deformation of the brain areas for a single individual and then mapping the result on some idealized brain model – with different models for male and female brains, and also possibly per age group.

After the registration and correction of individual differences, suddenly the brain activations do not smear and scientists get high-resolution results. Clearly, the clinical and algorithmic parts need to be fine-tuned to produce consistent high-resolution output. So actually getting this high-resolution activation mapping is a big achievement.

Surgical mapping

Each activity performed by a subject generates a very complex map of fMRI activation. There are only so many activities a subject can perform and map in fMRI, and then it is difficult to understand how each area of the brain contributes to the activity.

Fortunately, there are unfortunate individuals, humans, and mice, with very selective brain injuries. Humans may suffer from some terrible accidents and survive. A Russian engineer’s brain was shot through with a particle accelerator leaving a permanent hole, yet the engineer is healthy except for occasional migraines. Mice can be surgically or pharmacologically altered, removing certain areas of the brain or flooding them with drugs that stimulate or suppress the area, or zapping the area with an electrical charge.

Certain areas of the brain are still unmapped because they are very difficult to alter selectively. Many areas of the brain have been mapped following the patients that suffered a stroke or war injury. Until the mid-20th century, there were common lobotomy procedures in mental patients, for example treating epilepsy by cutting the connection between the brain lobes. While very interesting, these procedures are no more practiced.

A brain of a mouse is surprisingly similar to the human brain: we just have a much larger neocortex. I am pretty sure that there are wrong theories that came to be from applying ideas of various mammals to the human brain, I just do not know which theories. The study of horses, for example, provides a complex and very different mammalian brain for comparison.

Transcranial stimulation

Some scientists use a controversial mapping technique. They stimulate various brain areas of a healthy person via low-intensity electric charge or magnetic stimulation and see what happens.

The vagal nerve, for example, is rather large and easy to activate and the resulting relaxation is also very easy to see.

There are activation maps that allow modifying various cognitive functions by small DC current. The device is cheap and simple. I occasionally use it for the extra 10% intellectual performance for 20 minutes…

This electro-magnetic stimulation is not very strong and not very selective. It can occasionally treat drug-resistant depression and migraines, improve focus and reading speed (pattern matching). But it is not very effective.

New complex tech

There are new methodologies of brain mapping introduced now and then. Some of these methods are rather complex and usually applied to mice.

Brain tissue is semi-transparent. Optical and ultrasonic methods of mapping work over several centimeters of brain tissue, by measuring certain blood qualities of the relevant brain area.

Direct brain implants. Computer interfaces with exposed cables can be spliced with the human neural system. This can provide vision, hearing, or activate prosthetic limbs for several years. Eventually, the nerve-metal junctions stop working and new operations need to be performed. Are several years of vision worth the operation for a blind? Are several years of walking worth it for a paralyzed person? There are significantly more applications to these experiments than doctors performing them can treat.

Capsules with the subsequent release. To damage very specific areas of mice brain, miniature capsules can be delivered via a very small syringe. The capsules then can be activated (for example, optically), generating several millimeters of damaged tissue. This allows mapping areas complex for surgical interventions.

All of these super-high-tech methods are rarely used in actual experiments. fMRI is still the leading methodology.

Just how smart are brain surgeons?

The actual work of brain surgery is very different from what most of us think. This article describes it vividly. I quote:

Because it is soft, the brain, it turns out, is a forgiving, flexible organ. In the large frontal lobes, tumors can grow to “impressive citrus fruit proportions” before patients even notice something amiss. Neurosurgeons learn early to recognize the sound that a drill makes as it passes through each layer of the skull. A senior neurologist, ignoring the ambiguous information coming from a computer guidance system in the operating room, locates a tumor by running his finger over the surface of the baby patient’s brain.

This is not what most people expect. As a person who occasionally develops medical equipment as his main job, I can say that some stories are much worse. Some brain surgeons are very smart, intuitive, quick, and effective. Others are lazy to treat strokes or double-check the fancy equipment readings, and the people involved suffer.

There is a story about a person performing an autopsy on Einstein, cutting and preserving his brain without his superiors’ permission, and then keeping the jars with brain slices in his room for years, occasionally performing selective measurements.

How much do we actually know?

The human brain is incredibly complex. Every now and then new things are discovered. There areas of the brain, new understanding about less known brain areas, new mechanisms involving neurotransmitters and gene expression. Huge revolutionary discoveries are reported two or three times every year.

It is very hard to understand the available information. I am not a medical doctor by training, and understanding the complex brain systems is hard for me: a lot of details with very complex research methodology. From what I know, somehow I do not think that the understanding comes easily to medical doctors either.

A cool case is a story of the serotonin 5-HT1C receptor. It used to exist in medical books for a while, but it was reclassified as the 5-HT2C receptor. 5-HT2C receptors mediate the release and increase of extracellular dopamine in response to many drugs, including caffeine, nicotine, amphetamine, morphine, cocaine, and others.  Its crystal structure is known since 2018 (this is not ancient history). Several generations of patients suffered from its misunderstanding. Activation of 5-HT2C by serotonin is responsible for many of the negative side effects of SSRI and SNRI medications, such as sertraline, paroxetine, venlafaxine, and others. Some of the initial anxiety caused by SSRIs is due to excessive signaling at 5-HT2C. Genetically, polymorphism of 5-HT2C may cause depression, OCD, and anxiety-related conditions, drug abuse, and obesity… And this monster used to be misclassified…

I suggest treating brain mapping information with a mix of enthusiastic interest and skeptic doubt. This is a very complex and not very exact science, with interesting discoveries in the recent past and near future…