Mental mapping: Deep brain science points to better mental health

Published on
December 1, 2016

Medical science has created a strong toolkit of preventive, medicinal, and surgical solutions for cardiovascular disorders. As a result, death rates from things like heart disease and stroke have fallen since 1990.

When it comes to addressing disorders of the brain, though, the medical toolkit is weak. Depression remains a widespread problem that is often misdiagnosed and poorly managed. Treatments for anxiety come with so many side effects that some people can feel worse off while taking the drugs. And, as we extend lifespans by improving survival rates from other diseases, it becomes more likely that people will get Alzheimer’s or another neurodegenerative disorder with no real hope for mitigating the damage.

Brain researchers are trying to change that. Big money has been poured into places like the Max Planck Institute for Brain Research in Frankfurt and the centers within the Massachusetts Institute of Technology’s Brain and Cognitive Sciences Complex in Boston. One of the most intriguing efforts is happening where I live, in Seattle, at the Allen Institute for Brain Science. Researchers at the Allen Institute are creating a publicly available, open access map of the functions that make our brains work.

Although these have to be considered early science — years away from new preventive measures or treatments — they are making discoveries about the way our brains work at a rapid pace. I happen to live in Seattle and drive by the Institute most days on the way to my office. I’ve never been inside, but I have become increasingly curious about the work they’re doing to create gene expression maps for human and mouse brains. Over a few posts, I’m going to highlight what brain mapping efforts there — and elsewhere — are starting to tell us about where the mental health field may be going.

So, how do brain mappers do it?

It starts with the ultimate act of generosity: People deciding to donate their brains – or their loved ones’ brains — for research.

The donated brains are preserved, shipped to the Allen Institute, and stored. Researchers scan these brains using MRIs and diffusion tensor imaging (DTI). They also take samples from the brains to zero in on specific areas. They also use histology techniques to study the cells and cellular structures that make up the brain. Going deeper still, they examine DNA sequences to create a map of DNA, antibodies, and proteins that together give a detailed view of the way genes are expressing themselves in different brains. Lydia Ng, the Institute’s director of technology, described the steps involved in a 2013 presentation.

The mapping of genes and how they are expressed in different parts of the brain and as part of different biological functions is critical for creating a better toolkit. 

The National Institute of Neurological Disorders and Stroke has been funding and collecting research on the brain since its creation in 1950. It notes that very few neurological disorders are fully understood at the genetic level. There are rare neurological disorders, including Huntington’s disease, that can be traced back to mutations in one gene. But most of the disorders that are causing widespread health loss — like strokes or Alzheimer’s — are the result of many different genes playing out in many different ways. As NINDS puts it:

First, for most people, a complex interplay between genes and environment influences the risk of developing these diseases. Second, where specific gene variations such as SNPs [single-nucleotide polymorphisms] are known to affect disease risk, the impact of any single variation is usually very small. In other words, most people affected by stroke or Alzheimer's disease have experienced an unfortunate combination of many ‘hits’ in the genome and in the environment. Finally, beyond changes in the DNA sequence, changes in gene regulation … can play a key role in the disease.

Researchers creating these brain maps are also gathering medical data and psychological histories from the people who donated their brains. All of these inputs become building blocks for a three-dimensional “biochemical architecture of the brain,” as Wikipedia so nicely puts it.

To gather the needed data, scientists at the Allen Institute use various techniques. One technique scans donated brains to discover where in the brain genes are turned on and off. Another technique, called in situ hybridization, requires painstaking work to isolate DNA and RNA within brain tissues and is used to create images of the gene expression.

In future posts, I will write about how researchers are using atlases like this to teach us about how our brains work — and when they don’t work.