The Symphony Inside Your Brain

Ever wonder what is it that makes you, you? Depending on whom you ask, there are a lot of different answers, but these days some of the world’s top neuroscientists might say: “You are your connectome.”

Grid of major pathways in human brain’s left hemisphere. Using diffusion spectrum imaging, which tracks movement of water through nerve fibers, researchers can trace groups of neurons as they cross from one region of the brain to another in living individuals. Credit: Van Wedeen, Massachusetts General/Harvard Medical School

The connectome refers to the exquisitely interconnected network of neurons (nerve cells) in your brain. Like the genome, the microbiome, and other exciting “ome” fields, the effort to map the connectome and decipher the electrical signals that zap through it to generate your thoughts, feelings, and behaviors has become possible through development of powerful new tools and technologies.

For some time, neuroscientists have been able to infer loosely the main functions of certain brain regions by studying patients with head injuries, brain tumors, and neurological diseases—or by measuring levels of oxygen or glucose consumption in healthy people’s brains during particular activities. But all along it’s been rather clear that these inferences were overly simplistic.  Now, new advances in computer science, math, and imaging and data visualization are empowering us to study the human brain as an entire organ, and at a level of detail not previously imagined possible in a living person.

Some have likened this new ability to the difference between listening to the string section (evaluating an isolated part of the brain) versus listening to an entire orchestra (the whole organ). If you listen only to the string or percussion section, you’ll gain a pretty good understanding of how that particular group of instruments sounds. However, that experience would not compare to the experience of listening to the whole orchestra and chorus perform Beethoven’s Symphony No. 9, the Ode to Joy.

Today, I’d like to tell you about an NIH-supported effort that’s aimed at revealing the “symphony” that’s happening at the speed of thought within our brains every second of every day. This effort, called the Human Connectome Project, has set out to map the brain’s neural connections in their entirety. Given that a typical human brain contains 100 billion neurons, each with about 10,000 connections, this sounds like an impossible task. But it’s been done already, albeit for a much simpler creature: a roundworm called C. elegans. It took researchers a little more than decade to produce a “circuit diagram” of the C. elegans’ nervous system, which contains roughly 300 neurons that make a total of about 7,000 connections.

Clearly, mapping the human brain is vastly more complicated. To meet this challenge, the Connectome Project has enlisted a diverse entourage—biologists, physicians, computer scientists and physicists—at many different institutions all across the nation. Some are scanning the brains of 1,200 healthy adults to generate a high-resolution map of the brain, while others are layering on genetic and behavioral data to build a more complete picture of the brain’s neural architecture.

With a detailed connectome map of a normal human brain, I believe we will gain a better understanding of the roots of human neurological disorders, including schizophrenia, autism spectrum disorders, and other baffling conditions that may arise from abnormal “wiring” during brain development. This knowledge should yield new and better ways to detect, treat, and, ultimately, prevent the brain disorders that currently disrupt and devastate so many lives.

The connectome will also give us a new tool to explore how genes influence the brain’s connections—and how behavioral and environmental factors act to sculpt those connections, affecting everything from our ability to solve crossword puzzles to our risk for addiction.

While the Connectome Project is very much a work in progress, I’m pleased to tell you that it’s already yielding some exciting results. A recent study by connectome researchers, published in the journal Science, revealed that the brain’s neurons are not the haphazard tangle that some had thought, but are arranged in a tidy grid that resembles a city street map. Pretty cool work, and I’m betting there’ll be even more impressive findings in the near future. So, stay tuned—this is one of the most exciting areas of rapid progress in biomedical research.

6 thoughts on “The Symphony Inside Your Brain

  1. According to Dr. Francis Collins’ blog, “the Human Connectome Project, has set out to map the brain’s neural connections in their ENTIRETY.” This sounds like a program that is rather akin to sequencing the “human genome”, but is in fact several orders of magnitude more challenging. While there are about 2.9 billion base pairs in the “human genome,” the number of neural connections in the adult human brain are in the order of 100 to 500 trillion. It is becoming apparent that individual human genomes may differ with more than 50 million single nucleotide polymorphisms and mutations. The variation in the connectivity of nervous system is highly likely to be vastly more extensive as the environment has a huge impact on brain development and fine structure. As a very plastic organ, whole regions of the brain can wane and expand depending on the sensory inputs, nutrition and exposure to toxic substances.

    While I do not criticize, but rather applaud the efforts of scientists to carefully investigate the architecture of the brain down to the level of intercellular connections and deeper, I do think that better care needs to be taken by very public officials such as Dr. Collins about the fruits and challenges associated with these kind of programs. Expectations need to be realistic.

    It is intriguing that with the sequencing of the first human genome over a decade ago, led by in large part by Dr. Collins, the functions of about 40% of the genes encoded by less than 3% of the DNA in the genome were unknown. More than 10 years later, the roles and regulation of most of the proteins specified by these “dark” genes still remain obscure. Yet there are now wild claims widely propagated by at least some members of the ENCODE Project that as much as 80% of the entire human genome sequence is important and functional.

    It seems to me that the objective of deducing the connections of all of the neuronal connections is like identifying all of the types and placements of trees, shrubs and plants in a vast forest. There are clearly underlying principles at work that influence the general composition and arrangement of the vegetation in a forest and how it functions as an ecosystem. However, when you view many forests over the surface of the planet, it is clear that no two forests are the same despite their initial similarities when viewed from 30,000 feet above. Such an analogy applies to our understanding of the human brain where clearly there are significant differences in cognitive abilities amongst even the general population.

  2. The discipline of Neural Networks (also called Neural Nets) a paradigm shift from AI to a class of algorithms that we created by 1990 could be helpful to interpret the “many-to-many” massively parallel systems. While the structure is in the initial focus both in Neuroscience and Genomics, the functional consequences make an impact in physiology and medicine.

  3. The Mouse Brain Architecture project aims to map the meso-scale connectivity map of the entire mouse brain by systematically tracing neuronal projections to and from a grid of locations covering the brain. Data from the project are now available at http://mouse.brainarchitecture.org

    For example, this video

    shows a reconstruction of projections from Primary Motor Cortex: in green are cortico-cortical projections (labelled by a tracer injection to superficial layers of cortex), and in red are projections to subcortical structures and the cortico-spinal tract (labelled by a tracer injection to deep layers of cortex).

    • Thanks for sharing this information and remarkable video, Partha! I’m very excited to see the progress being made by you and your collaborators. For all of the readers of this blog, I’m also happy to report that much of this pioneering work on the Connectome has been supported by NIH. In fact, just a few years ago, Dr. Mitra received a Transformative R01 Award from the NIH Common Fund for his project, The Missing Circuit: The First Brainwide Connectivity Map for Mouse. Really cool science!

      • Thank you Francis! We have been very grateful for the NIH support that has enabled the Mouse Brain Architecture project and other whole brain projects.

        We are excited about the scientific possibilities opened up by the current generation of whole-brain digital neuroanatomy, that will allow us to get a holistic, system level view of nervous system structure and function in an unprecedented manner (your analogy with the symphony is apt – neuroscientist Charles Sherrington referred to the Integrative Action of the Nervous System, which we can only comprehensively study if we can measure the nervous system as a whole).

        The mouse brain with a volume of 1cc is ~1 Teravoxels at light microscope resolution, giving rise to ~1 Terabyte of data, which in 1990 would have cost ~1 million dollars to store. In 2012 we can store and process that same amount of information with ease using consumer technologies. The human brain digitized at that same resolution is ~1 Petavoxels, and is just coming within our reach. This is indeed a transformative time for neuroscience!

  4. While a lot of interest lies in remedial efforts towards neurological disease, I’m looking forward to the normal function of the brain – how it processes and symbolizes the environment, processes language, math and reasoning, and manages patterns and memory. Perhaps we will advance science and society to the level where neuro-education occurs by managing the integration of neural networks consistent with the developmental processes of our neurological system for learning and enhancing these basic cognitive skills. Education would be programmed into the development of the brain as areas known to support speech, math, music, art, and symbolic processing (among others) mature. Such a society would have no need for central authority but would evolve through networked nodes of creative interest. Universities will be virtual networks of creative interests. Laws would be replaced by flexible rules for exchange and consent based on the network locality and consequences for network integration. We will be able to share our memories and experiences socially through this network. Insects use pheromes to create a swarm intelligence; what will the human species create to integrate intelligence with the biosphere?

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