Connecting the Dots to Who You Are

The connectome, a term coined by Olaf Sporns, is a neural connectivity map for the entire brain. In 2010, the National Institutes of Health launched the Human Connectome Project, a $30 million initiative seeking to use advanced medical imaging techniques to map the structural and functional connectivity of the healthy human brain. The participating institutions were to be Washington University, St. Louis, the University of Minnesota, Twin Cities, Massachusetts General Hospital/Harvard University, Boston, and the University of California Los Angeles. "Better understanding of such connectivity promises improved diagnosis and treatment of brain disorders," said their news release. This post is about the recently released book Connectome: How the Brain's Wiring Makes Us Who We Are which happens to be quite an illuminating read on this cutting-edge topic. 

Book review: Connectome by Sebastian Seung

Author and MIT professor Sebastian Seung's assertion is that minds differ because connectomes differ as opposed to the hypothesis that minds differ because genomes differ. The slogan of the book is: 

You are more than your genes. You are your connectome.

While patterns of transient neural activity determine our rapidly changing self, our connectome represents our stable self that has to do with our unique personalities and memories and which changes slowly over time. Seung metaphorically describes these two selves as a stream and the bed lying underneath. While, in the short term, the groove in the earth directs the flow, over the long term, the stream erodes and shapes the bed. The latter is achieved by what Seung refers to as the four R's: reweighting, reconnection, rewiring, and regeneration. 

So what does the book cover? I would say it offers a scenic tour of the past, present, and future (as envisioned by the author) of this field. It begins with nineteenth century neuroscience when brain size was used as a basis for deductions (phrenology) and there were speculations regarding the modular nature of the brain (localizationalism). It provides a wonderful crash course on brain structure and how neurons and brain networks are known to work. It then elaborates on some exciting progress made over the last few decades, the technology we have at our disposal to acquire, understand, and utilize connectome data, and what possibly lies ahead of us. 

Why should you read this book? Well, for one, it is so beautifully written that chances are you will find it to be a delightful read irrespective of your background. I loved it for its structure, the lack of diffusion (which makes you want to retain every one of those little facts be they anecdotal or axiomatic), and of course those gorgeous metaphors. But the more compelling reason is that this book cleverly uses historical and philosophical tidbits to clearly define its context and presents a thorough outline of the state of the art and the directions of ongoing research. 

I would like to warn readers though that, while the groundwork is thorough, the actual connectomics content of this book is largely hypothetical. But that is unavoidable since the field is still in its infancy. The ultimate test of the "you are your connectome" hypothesis will be in mapping and "uploading" the entire connectome of a living human being, simulating his/her brain, and finally comparing the in vivo and in silico spiking patterns of the neurons. 

Although, my knowledge of this field is quite limited, I had a few critical comments. Currently there exist two broad classes of methods to extract the connectome. One of them (adopted by the Human Connectome Project) aims at using macroscopic in vivo imaging (MRI tractography and functional MRI) to map the regional connectome. The other approach (adopted by the BrainSTORM Consortium) seeks to maps the neural connectome by slicing up brain tissue and generating high resolution microscopic images. Seung himself hails from the latter club. He believes in spending time on neurons rather than regions and then eventually using neurons to find regional connectomes. This, however, is a low throughput and tedious approach and will depend largely on the emergence of faster technologies in the future. In light of that, I personally am more optimistic about the fate of the Human Connectome Project. 

The "you are your connectome" hypothesis rests largely on the notion that our experiences shape who we are in ways that cannot be defined by genes alone. There has certainly been compelling evidence (e.g. from studies on identical twins) in support of the fact that the genome alone is insufficient in explaining our traits (personalities, susceptibilities to diseases etc.). Seung therefore theorizes that neurodevelopmental disorders like autism or schizophrenia (that cannot be fully explained by genetics) are essentially connectopathies. Autism, he says, may arise when there are too many connections within the enlarged frontal cortex and too few between it and other regions. Schizophrenia, he thinks, may be due to abnormalities in synapse elimination (a natural process that a human undergoes while growing up). These may be great hypotheses. But, there is a possibility that some of these answers may lie in the epigenome and not the connectome. Yet, surprisingly, there is no mention of the former!

Toward the end of the book, Seung revises his favorite slogan:

You are your connectome plus models of the neuron types.

Now, this appears to me as no minor edit. The model of the neuron not only includes its shape and size, but also represents the unique chemical environment at its synapses. The model parameters will depends on much more than just the 4 R's determining the connectome.  This certainly sows a seed of doubt in my mind about the overall philosophy of the book. 

If you have got this far into this post, I would suggest you give this book a shot. If you are an expert, may be you can educate me further, and, if not, you may derive some amusement reading about the so-called "Jennifer Anniston neuron".