Epilepsy Presentation

Learning to Swim

I often find that my greatest learning is done when I’m able to equate a new topic to a familiar experience. Recently I was introduced to the Allen Brain Atlas, BrainNavigator, and The Human Connectome Project. In many ways reading through articles and journal entries about the brain atlas and connectome is like learning to swim as a young child. When I began reading I felt intimidated, the impressive information that I found in front of me resembled a body of water before jumping in for the first time. As I continued to read I was overcome by a sense of comfort. The more I understood the new information about the Connectome, and became familiar with the Allen Brain Atlas the more I felt like I was competently stroking through water, learning to swim. What I hope to do in this entry is highlight how anyone can become familiar with the Allen brain Atlas, explain its importance, and describe why The Human Connectome Project will greatly benefit from its technology.

The Allen Brain Atlas and BrainNavigator software are stunning innovations that allow 3-D & 4-D brain navigation, the fourth dimension being time. The software makes it possible for users to manipulate, rotate, magnify, and highlight many structures within the mouse and human brain. Neuroscientists will be able to benefit from this because prior to 3-D brain navigation 2-D neurological photos were the most reliable navigation tools. Prior to 3-D once a neuroscientist completed the difficult task of navigating by way of 2-D pictures they still had no way of determining how deep within a structure they should go to reach a desired location. The Allen Brain Atlas and BrainNavigator not only improve upon outdated methods but they also provide the crucial addition of depth exploration. Before directly immersing yourself into 3-D brain navigation it’s probably best to begin by browsing a few websites to familiarize yourself with the types of structures you will be seeing.

The best place to start learning about these tools would most likely be the opposite of where I started, which was Google.

I found that the Harvard research website of the high-resolution mouse brain atlas is particularly user friendly and allows for a lot of simple clicking and observing. This is a great place to start familiarizing yourself with the types of images you’re going to see in 2-D before moving to more complex sites that may require a more in depth background to successfully navigate. The Harvard website is http://www.hms.harvard.edu/research/brain/3D_atlas_vDemo.html. Once you reach the website if you click on 2-D atlas you’ll be provided with many clearly labeled pictures of mouse brain cross-sections.

To navigate these websites no knowledge is required, but to gain maximum insight from the brain navigator software a basic understanding of neuroanatomy and the functions associated with the various lobes is helpful. Those who will benefit the most from brain navigation innovations are neuroscientists in an academic setting, and medical researchers working to cure neurological disorders. Currently a large amount of time and attention has been placed on The Human Connectome Project. The Human Connectome Project is a research project directed towards creating a functional map of the complete structural and neural connections in vivo within and across individuals (www.humanconnectomeproject.org).

The Human Connectome Project is the next crucial step in an attempt to understand human theory of mind. Often times it seems as if what dictates who we are as conscious individuals is left up to the notion that there is some intangible force controlling us. The idea that each person is born with a soul and how we express our thoughts, preferences, dislikes, and emotions is controlled by that soul. The Human Connectome Project could be the answer to the age-old question of “what makes us tick?” As we continue to discover new information neuroscientists can make use of the Allen Brain Atlas to precisely map exactly where connections are made using 3-D, and use 4-D to determine how early those connections can be seen during neural development.

There has been a lot of progress made since the time of Ramon Y Cajal, but just as Golgi staining was a revolutionary tool used to radically change neuroscience so are the Allen Brain Atlas, BrainNavigator, and Human Connectome Project. What we see today can very well be the stepping-stones to unimaginable discoveries in the field of neuroscience.

Brain Exploration of the Future: The Magic School Bus Goes Full Speed Ahead

If Ms. Frizzle were still teaching today, she would be thrilled with some of the newest projects and navigation tools for her Magic School Bus. For while she has navigated her students through the digestive system, circulatory system, immune system, and muscles, she has left the brain untouched. What if we could take her class on a ride into the brain; the complex system of neurons, axons, dendrites, and structures that make us who we are? Maybe in the 90’s this would have been unimaginable, but today, BrainNavigator and the Human Connectome Project (HCP) make this field trip a possibility.

Since the second century, the brain has intrigued many different groups of people, but due to complications in navigating this intricate and messy organ, the brain has been uncharted for much of history. However, recent advances in technology have led to a revolutionary program, BrainNavigator, that gives us 3-D web access to virtually travel through the intricate structures of the brain. After updating her bus with this device (available for download at http://www.brainnav.com/nav3d), Ms. Frizzle can locate structures and rotate them in any plane to fully grasp the physical characteristics of the destination. Although the creators of this program may have used cutting-edge methods to create these 3-D models, anyone who can type in “hippocampus” (the structure most associated with memory), or any other structure of interest, can manipulate the images on the screen to gain a more comprehensive understanding of this brain structure.

With BrainNavigator, Ms. Frizzle could visualize the hippocampus and its location in the medial temporal lobe in 3-D, but how would she get her bus there? This is where the Human Connectome Project (HCP) comes into play (more information at http://www.humanconnectomeproject.org/). Using different neuroimaging techniques such as Diffusion Tensor Imaging and Brainbow (more about the techniques at http://www.scholarpedia.org/article/Connectome), the creators of this project are attempting to identify all of the 10¹⁴ synaptic connections in the brain and supply this information in a comprehensive on-line database. Mr. Frizzle’s students could learn not only about the structure of the hippocampus, but also track the highways and exits of white matter to reach this destination. Without this project, entering through the nostrils and driving through the catastrophe of white matter webs would be insurmountable, but we’re getting closer to a smoother, more direct ride.

While the HCP is yet to be complete and it may be a while before Ms. Frizzle’s students can steer through the brain, this large database allows for a broader scope of analysis and neuroscientists are beginning to formulate new questions as a consequence. For example, investigating the maze of proteins, changes in synapse length, enlargement of ventricles, and the buildup of plaque along the path to the hippocampus in a patient with Alzheimer’s disease could provide a better understanding of the defects in diseased individuals. The accessibility and the possibility of discovery make this an exciting program for all, from curious individuals such as Ms. Frizzle and her students to highly-trained neuroscientists.

So, as we wait for the completion of these programs, go ahead and start exploring. Plan a field trip into the brain; get ready for an extraordinary ride through the most complex and fascinating organ in our bodies.

Jenny Moyer

Connecting the Human Brain to the Mind

For almost a decade now, we have had the technology to map the entire DNA sequence of human beings. The price of having one’s own genome sequenced drops dramatically every year, and soon we will all have our genetic code deciphered. But even with the blueprint in hand, what can our DNA sequence tell us about who we are? Identical twins have the same genome, yet their personalities are unique.

Modern neuroscience tells us that our personalities emerge from our brains – that we are our brains. What in our brains determines who we are? We have the same anatomical structures and pathways, the same kinds of neurons. The distinctive feature is our brain’s organization. The neurons of the brain form thousands of connections with one another called synapses, through which they communicate information. These tiny and ubiquitous connections make two brains distinct.

This is why some neuroscientists aspire to map the connectome. A complete connectome would show the full set of synaptic connections in a human brain: the full biological organization that is a person’s mind. The brain’s fine structure is the reason rigid genomes can give rise to flexible people that are shaped by their experiences: our DNA gets our brain up and running and prepared to be molded by the world via synaptic changes. Scientists are hoping that access to the brain’s system of connections will help us discover how the peculiarities of being a person come from the peculiarities of our synapses.

Mapping the billions of connections in the human brain is too large a project right now, but neuroscientists are engaged in smaller tasks that can be stepping-stones toward the final goal. Researchers are currently building connectomes with coarser levels of detail than that of individual synaptic connections. A common design feature of the brain is that functionally related groups of neurons send their outputs collectively. A map of these major pathways would be like a roadmap: though containing only the highways, it still shows you most of what you need to know to navigate in the country.

At the fine-grained level, researchers are making connectomes of tiny regions of brain tissue. This requires making ultrathin brain slices, capturing images of the slices with electron microscopes, and analyzing the images to detect individual neurons. The shapes of neurons are traced from slice to slice in order to build 3-D models of the paths they take and the connections they make in the brain. These relatively slow methods will someday need to be replaced if we are to construct the human connectome in its entirety.

Connectomics may someday help us understand how the basic features of our everyday experience – thinking, remembering, feeling – reflect the organization of our brain and, importantly, effect changes in that organization. Whereas our genome is a finalized blueprint, our connectome is an unfinished draft, continuously working on itself. If you want to understand how your biology is linked to these changes, stay informed about progress in the human connectome project.

Wrapping Our Minds Around Our Minds

Neuroscientists on the cutting edge of research are often blindly probing into their subjects’ brains using only two-dimensional images as guides. This is all changing now with the progress of brain scanning technology and the international digital age. Scientists are combining advanced mapping techniques to create digital, interactive models of an animal’s brain, using the Internet to make it available to the entire world. Like the transition from maps to GPS systems, this has changed the way researchers visualize, think about, and navigate our most treasured organ.

There are many techniques used to image brains, and each has its unique strengths and weaknesses. The new atlas being offered on the Internet combines all of these scanning techniques to tell as much information as possible, while closing the gaps within individual techniques. These atlases even have the ability to trace gene expressions in the brain, combining the relatively young science of the genome with visualizations of the brain. This provides a concrete link between genes and how their expressions manifest within the brain, yielding a greater understanding of the genome and perhaps, in the future, having implications for gene therapies that treat neurological diseases.

In addition, researchers can combine the images from many healthy subjects of the same species and create an “averaged” brain. This would be the closest thing we have to a stereotypical, model brain of a particular species. By comparing diseased brains to these averaged atlases, we could potentially map the types of abnormalities that manifest in each disorder, making greater strides towards a complete understanding of every neurological disease and, hopefully, leading to treatments and cures.

Certain imaging techniques allow scientists to zoom into our brains, eventually getting down to the individual neurons. A human brain can have upwards of 10¹⁰ neurons with 10¹⁴ connections between them. The next step in visualizing the brain is creating a comprehensive connectome, a map of the neuronal connections. The essence of a brain is the electrical signals that relay across these connections and through the body, translating into movement, attention, memory, beliefs, our being. Stopping at a brain atlas without developing an understanding of the neurons and their interconnections would be like using a GPS to navigate through a town but having no idea of its people, politics, and culture. As there is more to a town than its roads, the brain is more than its gross structures. Many drugs that doctors prescribe work directly on neurotransmitters (a neuron’s signaling chemical) and synapses (points of neuronal communication), so a connectome could offer scientists a chance to reveal increasingly accurate mechanisms by which new drugs can work more efficiently to eradicate a disorder.

With the sheer number of neurons and connections, the completion of a comprehensive brain atlas is a daunting task, but it exemplifies the progress of science and technology. This atlas requires the accumulation of years’ worth of data, from both in vivo and post-mortem tests. The work of hundreds of scientists lives on in the current brain atlas, aiding research across the world.

Not only is this project a testament to science and technology, but it also carries on the spirit of digital progress. The brain atlas can be found on the web, available to anyone with an Internet connection. These developers even offer free versions for educational purposes. Perhaps scientists can take this to the next level, creating an open-source version of this software, so that when a problem arises with the commercial version, individuals around the world can come together to fix it. The power of international crowd sourcing has been proven with the problem of protein structure. Scientists offered a free game that required you to figure out the protein structure of amino acids. Using this game, the collective mind of hundreds of gamers made great strides in determining previously unknown protein structures. Maybe this type of open-sourced approach would be worth a try with the brain atlas endeavor, accelerating our journey towards wrapping our minds around our own minds.

-Ian Park

To explore the brain for yourself, check out BrainNavigator and the Allen Brain Atlas.

The Google Maps of the Human Brain!

It’s 2011. By now, most of us are very familiar with Google Maps. After all, it’s a pretty incredible resource. We can get driving directions, view street maps and satellite images, check traffic conditions, locate nearby businesses, and more. Essentially, we’re able to identify locations throughout the world, the connections between them, and the condition of those connections. Google Maps has made many of our lives easier and our travel more efficient. A project like Google Maps is ever evolving, but the effects of its development are quite obvious in today’s world. What if we could expand on the concept of mapping all of planet earth, and attempt to map other complex systems? Might it be possible to map the structures and connections of the human brain? Many neuroscientists believe so, and have, in recent years, undertaken a project akin to the much-discussed human genome project, known as the human connectome project. Simply put, the connectome project is an attempt to map each and every neural connection in the brain. It’s a gigantic task considering that the human brain’s one hundred billion or so neurons have the potential to form several hundred trillion synaptic connections. There are some neuroscientists who believe that the development of a complete connectome is nearly impossible, but many agree that the seemingly endless potential of the project makes attempting it a no-brainer.

For a map of the human connectome to be useful, however, there must be a proper way to experience it. Relatively new software programs like the Allen Brain Atlas and Elsevier’s BrainNavigator utilize the latest technologies to digitalize the connectome and present the brain in an interactive way. Students, researchers, doctors, and curious minds alike all have the potential to benefit from the development of the latest brain mapping technologies and software programs because they will be able to save time and resources in more ways than one.

Neuroscientists use this software to evaluate the data they collect and pinpoint precise brain regions in the software that correspond to regions they’re studying. They are also able to eliminate their reliance on enormous and expensive print versions of brain atlases. Of course, software like BrainNavigator isn’t just for neuroscientists. High school students, college undergrads, or any inquiring individual can successfully operate the software and explore the brain in full. Anyone can register to use it online for free, making the availability of this software one of its most attractive qualities. The supply of authentic animal brains is small, and access to human brains is even more limited. Some universities have access, but many students may be forced to share one brain, or crowd around an instructor to identify miniscule structures and connections; a situation I have personally experienced on multiple occasions.

If the software’s unlimited access to brains isn’t enough to convince you how game-changing it really is, consider this: mouse, rat, and monkey brains are the most commonly studied brains throughout the scientific community. While their usefulness can’t be overstated, the fewer sentient beings sacrificed for research purposes, the better. The 2010 EU directive on the protection of animals in scientific research states, “the use of animals for scientific or educational purposes should only be considered where a non-animal alternative is unavailable.” BrainNavigator’s 3D imaging technology is so accurate and insightful that it might be possible to significantly reduce the number of animals sacrificed for brain research. The future holds the possibility of a connectome so intricate that anatomy, and even more in-depth experimental research, could be conducted solely through the use of software programs. Perhaps many of our small, furry friends will live long lives in the wild, and successfully avoid spending any time in a laboratory.

In just the way that Google Maps has become the default method of navigating planet earth, the creators of BrainNavigator and the Allen Brain Atlas hope that their software will become the default method for navigating through animal and human brains. You could be the first of your friends to familiarize yourself with the future of brain research! So, what are you waiting for? Check out BrainNavigator at http://www.brainnav.com/ and the Allen Brain Atlas at http://www.brain-map.org/. They’re free, easy to use, and quite possibly the coolest way to experience brain structures and the connectome!

The Tangible Soul

Many years ago, a friend’s parents were contemplating divorce. His father had rapidly changed from congenial and loving to angry and aggressive. It put enormous strain on the marriage. He had become a different person. They found out that the changes were due to a small brain tumor that shrunk with treatment, allowing him to become more like the man he once was. An alteration in the normal functioning of his neural networks had created a different personality. The behavior of neurons is precisely what controls how we act, remember, reason, and emote and an abnormality is enough to generate a noticeable change in personality. This has led me to think it possible that the entirety of human nature and personality can be found within the coils and folds of the brain.

Studies of the connectome, the complete structural connectivity of the nervous system, may shed new light on the origin and function of the human mind. There are an estimated 10 billion neurons making 100 trillion synapses in the human brain. If we are amazed at the computational and problem solving capabilities of some computers, it is no wonder we find so much of the transcendent and numinous in ourselves, as our brains comprise a much more complex and powerful network than that found in any computer. We correctly think of ourselves as the product of our experiences, recognizing the influence of our environments on the people we become. It may therefore be difficult to think of a rigid network of cellular wires and their connections as the root of our character. As it happens, that is precisely what the connectome is not. Rather, our neural networks have plasticity and are shaped and altered by experiences. Connections between neurons and networks can be added or subtracted, enhance or inhibit, and adjust sensitivity to information all depending on activity of cells. Almost any changes in activity, from thinking differently about something to experiencing a traumatic event, result in alterations of neural structure. The connectome grows and changes, not just correlating with changes in ourselves but driving those changes.

We still do not and perhaps never will know how a personality comes to be but studying the connectome is sure to aid in our understanding. The synapses of the connectome dictate who we are. Learning, memory, and even brain tumors mold our neural responses, which, in turn, generate our thoughts and actions. These are the aspects of human nature that make up the core of what is labeled the soul and yet they have completely material foundations. Although advances in neuroimaging, immunohistochemistry, and diffusion tensor imaging have been helpful in creating elegant and complex 4D atlases of mammalian brains, we lack the technology to adequately map and analyze the 10¹⁴ connections in the human brain. At this point, we can only be excited by the prospect of knowing more about the blueprints of the mind and channel that curiosity and exhilaration into scientific thought and discovery. It is important to acknowledge that we do not have the answers but even more important to strive towards them, all the while appreciating how our brains give us the facility to do so. The connectome contains our memories, our experiences, our thoughts and emotions. It is the basis of our reason and logic and intermittent lack thereof. Perhaps knowing how neural structure differences between people and even changes throughout one person’s life correlate with the differences in personality we observe will show the ways in which the flesh and soul are one. Studying the structure of our neural networks will bring about a new way of understanding our faculties of thought, action, and emotion, allowing us to recognize the material, neurological basis for our remarkable nature. Perhaps then we might appreciate the novel concept of a tangible soul, one not imprisoned by the flesh but born from it. I believe it is essential to a good understanding of ourselves to begin thinking in this way. Anyone would do well to look into the progress of this study and consider a new self image or at least question the one they hold now and Sebastion Seung’s TED talk is a great starting point: http://www.ted.com/talks/sebastian_seung.html

The Map that Will Change the World

The central form of information transmission today is undoubtedly the internet; this bodiless network has the ability to create, strengthen, and destroy the connections that comprise it. This is not so different from our brains. Think of logging on to Google and typing in a search for brain. This single input elicits a response from many different web pages with a close match to the search term. At the top are the sites with stronger connections to the search “brain” and those at the bottom have the weaker connections. This order can be changed. As internet traffic increases to a certain site its position moves higher in the list. The brain performs a similar search after we hear a word. A “meter” might bring to mind a device for measurement, such as a parking meter or thermometer, or a unit of measure that equals 100 centimeters or even the rhythmic structure of poetry. Repeated exposure to a different term can lead to changes in what meaning the word is initially associated with due to increased neuronal activity and strengthening the relationship.

Another search for, say, “nervous system” may bring up some of the same web pages because the terms nervous system and brain are connected. These new pages will each respond to their own input and suddenly this simple network is complex. If we make a simple circuit of three neurons in which each have five connections there are a total of 15 synapses that can be arranged in any of 120 different connection patterns. A typical adult neuron makes about 7,500 synapses with any number of other neurons, yet in the adult brain there are billions of neurons to be analyzed. The formation of a collaboration named the Human Connectome Project (HCP) has set out to map every synapse in the human brain. This means that the location and number of connections between any two neurons will be identified. Many believe the big questions in neuroscience today (i.e. How do memories form?) can only be resolved through connectomic analysis, and while the project is currently in its formative stages new imaging techniques are being developed to speed up the process. The figure (below) shows a general map of the fiber tracts in the brain that has been generated, but the resolution power is not reliable enough to be considered 100% accurate. Even though completion is far off we don’t have to wait to make use of the findings. Websites such as Elsevier’s Brain Navigator (http://www.brainnav.com/home;jsessionid=E2CB717544FCA387D151968247BBEBD7) allow anyone to look at brain structures or view the whole brain in three dimensions. These tools are now an invaluable asset to many researchers due to the increased accuracy and functionality over printed atlases. New findings, such as, gene expression patterns, can be uploaded to these programs creating a growing database that has the ability to enlighten anyone from a high school student to a seasoned Neuroscientist.

The Answer Lies in the Connectome

            I had spent three hours—no, make that three and a half hours—trying to get Daniel to sing one line.  It had taken me about two minutes to learn it, but trying to translate the four lyrics and simple melody into Daniel’s brain was seeming like an impossible task, one that was not going to be accomplished in the mere four hours we spent together.  Frustrated, I closed up my big red binder, tried to ask him about his upcoming birthday party, and drifted off to my own daydreams.  In reality, I had given up.

            I started tutoring middle school children when I was sixteen.  While I enjoyed working with little kids, and always had, this job was different than most; these children had Asperger’s syndrome, a developmental disorder on the Autism spectrum.  In other classes I had worked in, kids talked and laughed and played with each other.  But in Daniel’s class, they didn’t, and I began to wonder why that was—why the term “Autism” correlated to these observable differences in social behaviors.  Such a question was the impetus for my study of neuroscience, and I now believe that the answer of what makes Daniel different lies in his brain—more specifically, in his connectome.

But what is a connectome?  Coined by Dr. Olaf Sporns as a play on the word “genome”, connectome refers to the complete mapping of all of the structural connections in the human brain (analogous to the genetic mapping of the genome).  The brain is made up of 10¹¹ cells called neurons, which form 10¹⁵ connections, or synapses, between them.  These seemingly infinite connections form higher, specialized regions in the brain, which communicate with one another to produce human cognition: for example, light hitting the sensory receptors of our eyes sends information down the optic nerve to the lateral geniculate nucleus, which then synapses, or makes a connection, with the occipital lobe in the brain.  The occipital lobe then communicates with more specialized regions, which altogether produce the ability to see.  In a way, we are our synapses—without the microscopic connections between neurons, we would be unable to process any sensory information from the outside world, encode memories, or gain knowledge—they are what make us who we are.  Using the connectome model and mapping the neuronal connections between large cortical areas on the human brain in 3D and 4D (with time, or brain development, as the fourth dimension), scientists may be able to fully understand the relationship between structure and function in the brain.

This is no small undertaking; brain networks can be defined at different scales, and there are many methods used to uncover the connections:  at the cellular scale, or neuron-by-neuron, scientists are utilizing a new technique called Brainbow, in which they use fluorescent proteins to stain tissue slices of the cortex.  This beautifully colorful labeling technique allows for distinct labeling of individual neurons, which they can then trace throughout the cortex.  On a larger scale, imaging methods such as diffusion tensor imaging (DTI) are being utilized, which uses radio-frequency and magnetic-field gradient pulses to track the movement of water molecules throughout the brain.  This allows researchers to map larger scale cortical connections.  These results are also becoming available to the public through websites such as Brain Navigator (www.brainnav.com), in which one can search through the multitude of cortical connections already uncovered in the human brain.

But why go through all of that trouble? If we are our synapses, the mapping the synaptic connections in our brain may open doors to understanding how we think, see, and remember; an understanding of structure may lead to one of function.  Which brings me back to my point: if scientist were able to map the connectome and see functional brain wiring, the potential for the understanding ‘miswring”, what is faulty in the brains children with Aspergers or Autism, is huge.  Recent research shows that neurons in an autistic brain have underdeveloped dendrites, the parts of the cell that form connections with other neurons.  Using the connectome as a comparison, scientists may fund underdeveloped neurons in regions such as the amygdala, which processes emotion, or in the cerebellum, which is responsible for fine motor movements---as many children with Aspergers jump or twitch regularly.  Of course, we will not know this without understand the structure of a healthy brain, or the connectome.

As I sat with Daniel years ago, frustrated over not being able to teach him that song, I remember wishing I understood why.  But with the recent advancements in understanding brain structure and function, the future of Aspergers may be very different.  Perhaps scientists will find a way to stimulate missing connections, or discover ways to make dendrites grow in certain regions of the cortex.  And when they do, we will have to thank the connectome.

Connecting the Dots in your Brain

A new era in neuroscience is upon us: you can now cut through a brain and expose its different parts without ever leaving your computer.  Online brain atlases are collections of many thin slices through brain tissue that are stained to show specific brain structures.  Atlases like BrainNavigator (available online at http://www.brainnav.com/home) and the Allen Brain Atlas (http://www.brain-map.org/) are organized primarily to be researcher-friendly, but they are straightforward enough for students to use.  Presently, there are brain atlases for human, rhesus monkey, mouse, and infant mouse brains.  Each brain atlas is organized by animal, brain structure, and areas that express related genes.  By combining these different functions, researchers can see where in the brain particular genes are expressed and relate them to each other in real, 3D space.

To make a brain atlas, scientists averaged super-thin 2D slices of brains from many subjects and stacked them together to make a 3D model of a brain.  Since each individual brain is slightly different, some generalization has to be made when determining the level of detail of the brain. Apart from genetic differences, each person’s brain is slightly different just by having lived a different life and having different experiences.  Everyone’s brain has slightly different connections, or synapses, that represent differing memories, beliefs, and intelligence levels (Seung).  With the right stain, connections between neurons can be mapped, too.  Like dropping watercolor paint on a napkin traces the pattern on the paper, cell staining methods reveal patterns in the long projections between neurons.  Even though some slight differences exist, scientists assume that the major tracts of connections between brain structures that are responsible for thought and sensation are essentially the same in everyone.  By staining the interior of specific neurons or groups of neurons and seeing where the stain travels, scientists can show what brain regions interconnect, and how strongly they are coupled.  This principle forms the basis for building a connectome, which is a map of all the connections between brain cells.  Brain atlases are not detailed enough at this stage to show all the connections in the human brain yet.  Once the connectome is fully mapped, one great application of the brain atlases would be to overlay major connecting tracts of axons into the 3D brain atlases already available.  Scientists can then infer what might be responsible for mental deficits in people with brain damage (Toga et al.)

A brain atlas with major connections from the connectome would be supremely useful for scientists.  The ultimate goal of mapping the connectome is to superimpose the connections between neurons on the brain navigation maps already in use.  Since we can’t often cut open live human brains to access these deeper regions of the brain, the 3D Brain Navigator provides an ideal alternative for scientists and students to explore the impacts of various types of brain damage (Toga et al.).  When planning experiments, a standard brain atlas would be useful as well.  To measure electrical activity in live neurons, neuroscientists use tiny electrodes stuck in brain cells.  To reach deeper cells, though, the electrode must pass through several layers of cells on the surface.  By manipulating a 3D image of the brain in BrainNavigator, scientists can plan where to stick the electrode with minimal damage to other parts of the brain.  It is also difficult to judge electrode depth in a live brain.  With BrainNavigator, scientists can calculate the estimated depth of their target structure to eliminate a lot of guesswork when they are in the brain (Hamilton). 

It’s simple to look at 3D brain atlases.  Downloading the software takes about a minute, and the picture quality is good.  By selecting any number of specific structures, it’s easy to compare spatial relationships and relative sizes of parts of the brain. With the addition of connections between neurons, online brain atlases will give the best possible picture of brain anatomy to date.

Your own personal stream of water, the Human Connectome

Have you ever seen a stream flowing in nature? The flowing, always changing water of the stream is what seems to always catch the attention of the viewer. What most people fail to notice is the streambed through which the water flows. As Sebastian Seung stated in his TED talk, this essential indent in the earth shares many qualities with an area of growing interest in the field of neuroscience; the human connectome. The connectome is the bed of the stream floor that guides the neural activity of the human brain. Firstly, the connectome is about structure. This structure includes the links between the neural elements that comprise the human brain; the actual components of the flowing stream. Secondly, the connectome is a map of brain connections; a layout of the stream connections. You may think that this is the same as the first part but the connectivity of the brain goes much further than the structure of the brain. The structure labels the main building blocks of the brain (frontal lobe, parietal lobe, etc.), whereas the map of brain connections will show the connectivity between these brain regions. While it may seem extremely difficult to label all of the connections of the brain down to the smallest neurites, the goal of the connectome is to provide a description of the inner framework that forms the brain on different levels of organization. For example, a connectome shows the inner working of the frontal lobe, while also giving the connections between the frontal lobe and other parts of the brain.

It may be quite a while before one complete human connectome is described. The connectome has been found for the worm C. elegans which has 300 neurons and 7,000 synapses. This process took approximately 10 years from 1970 to 1980 because all of the work was done laboriously without computers. The human brain contains over 100 billion neurons so the number of synaptic connections far exceeds those of the worm.

New types of brain viewing software make it easier for neuroscientists to navigate through a virtual brain, further increasing their knowledge of the connections in the brain. These new 3D maps of the brain will aid in finding more connections between different brain structures in a way that older 2D maps could not. It took 3 years to map the connections of a cube of mouse brain 6 microns on each side. Perhaps this new technology will help decrease the time spent locating these connections. Elsevier’s BrainNavigator 3.0 and the Allen Brain Atlas are two examples of software that is helping pave the way for the connectome. It allows for positioning of a probe or electrode to record activity in any part of the brain, allowing the user to locate the exact path the probe will take. With this software, the task of comparing gene expression data and anatomical information is made very easy. The results can be presented on the screen simultaneously, allowing for visualization of the different brain areas where the genes are expressed. Target genes and 3D views of gene expression are possible as well as the annotation of the slices by scientists for their past experiments. This is a very useful tool in a laboratory because the experimenter can study a 3D layout of the desired slice of the brain before the actual experiment takes place.

To be able to use these online tools requires simple computer skills. To take a trip down your personal stream and find out more about these tools, visit the website of both the BrainNavigator and the Allen Brain Atlas at https://www.brainnav.com/home and http://mouse.brain-map.org/welcome.do respectively.

The Connectome or How I Learned to Stop Worrying and Love the Worm.

A popular aphorism from ancient Greece states: knows thyself and for a few thousand years humans could be satisfied in this by pondering the nature of self and mind. However, with the advent of modern neuroscience, we as a species have been given a chance to achieve an unprecedented new level of self-knowledge: the connectome. When fully realized, the connectome will be a representation of the human brain so detailed that it will include every neuron and every synapse between neurons. Like the human genome, the overall distribution of structures in the human brain above the synaptic level is mostly conserved, thus the complete connectome would provide incredible new insight into every niche of neuroscience.

However, creating the connectome is a task that is anything but easy. To understand the epic magnitude of this map, consider the Human Genome Project. The effort to sequence the approximately 20,000 genes that we humans call our own began in 1990 and was completed a little over a decade later. Not too shabby: that’s a rate of 2000 genes a year. Now consider the scope of the connectome: a human brain contains an estimated 100 billion (10¹¹) neurons and 1 quadrillion (10¹⁵) synaptic connections. These numbers are unbelievably daunting and current technology could hardly hope to accomplish this task, yet the magnitude of scientific progress that the connectome will make possible is motivation enough to attempt this feat.

Of course, neuroscientists would logically start by mapping specific parts of the brain to scale their work. Little by little a complete connectome will be built. This work has already begun and in fact another species’ connectome was already fully mapped more than two decades ago. Before the term connectome was even coined, the humble roundworm, C. elegans, had its entire nervous system exhaustively described.

C. elegans, like mice, fruit flies, and monkeys, has long been a popular model organism for the study of nervous systems. While this nematode cannot lay claim to a brain per se, it does have neurons and neurotransmitters that function in much the same way that ours do, making it a simple and predictable organism to study. In the mid 1980s at Cambridge, John White and colleagues published what is now considered the first connectome, describing all 302 neurons and the approximately 7000 connections between them. While scientists still do not understand how C. elegans thinks, it has become more clear how certain behaviors, like feeding for instance, are driven by specific neural activity, such as the release of the neurotransmitter dopamine at certain synapses. The precise understanding of this tiny organism’s neural mapping has been a watershed in the field of neurophysiology and a necessary predecessor of the human connectome.

White’s seminal work was the first step towards understanding the nervous systems as a sum of their parts and connections. Perhaps one day, a human connectome will help us better understand how our patterns of neural activity are manifested in the experience of consciousness. Our emotions, memories, and thoughts as well as the symptoms and signs of disease and trauma, like Alzheimer’s and stroke, will be given a new, unprecedented clarity of perspective. If you’re lucky enough to be alive when that day comes, remember that we owe much to the worms.

If you’d like to learn more about the Human Connectome Project, visit their website at http://www.humanconnectomeproject.org/