Connectome (42 page)

I am grateful to Scott Emmons and David Hall for information on
C. elegans,
Axel Borst on the fly brain, Kevin O'Hara on the California redwood, Misha Tsodyks and Haim Sompolinsky on associative memory models, Eric Knudsen and Stephen Smith on reconnection and rewiring, Carlos Lois and Fatih Yanik on regeneration, Mitya Chklovskii and Alex Koulakov on wiring economy, Kristen Harris on serial electron microscopy, Guyeon Wei on semiconductor electronics, Dick Masland and Josh Sanes on neuron types, Kathy Rockland and Almut Schüez on cortical anatomy, Harvey Karten and Jerry Schneider on brain evolution, Michale Fee on birdsong, Li-Huei Tsai and Pavel Osten on brain disorders, Vamsi Mootha on biology, Niko Schiff on neurology, Drazen and Danica Prelec on philosophy and psychology, and Michael Häusser and Arnd Roth on dendritic biophysics.

Mike Suh and John Shon assisted me with the initial proposal for the book. Along with Janet Choi and Julia Kuhl, they also commented on the final version. Scott Heftler suggested some fun comparisons. Fellow authors Sue Corkin, Mike Gazzaniga, Allan Hobson, and Lisa Randall advised me at critical junctures. The meticulous editing and impeccable logic of Katya Rice polished the prose, to my delight.

Several public speaking experiences attuned me to the zeitgeist. Ute Meta Bauer invited me to lecture for the Visual Arts Program at MIT, Susan Hockfield brought me to the World Economic Forum, and Sarah Caddick helped me spread the word through a 2010 TED talk.

Finally, I owe thanks to the Gatsby Charitable Foundation, the Howard Hughes Medical Institute, and the Human Frontiers Science Program for funding my research in connectomics.

Introduction

page

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“Let man contemplate Nature”:
Pensées 72.
“the eternal silence”:
Pensées 206.

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Figure 2:
The picture was taken by differential interference contrast (DIC) microscopy, and can be found at
wormatlas.org
, a wonderful database of information about the worm. The scale bar is 0.1 millimeter. The two ellipsoids are embryonic worms.

   
centralized in a single organ:
The majority of the worm's neurons and synapses are found in a structure called the nerve ring. (Actually this is true for hermaphroditic worms, but the nerve ring is less dominant in the much rarer male.) The nerve ring surrounds the worm's “throat” and is the closest thing to its “brain.” The human brain contains the overwhelming majority of neurons in the human nervous system. The rest are in the spinal cord and scattered in other parts of the body.

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Figure 3:
The first map of the entire
C. elegans
nervous system was published by White et al. 1986. Although their map is generally considered definitive, it is not actually complete. Varshney et al. 2011 updated it with data drawn from other sources but estimated that 10 percent of the worm's connections were still missing. The diagram shown in Figure 3, summarizing their work, can also be found at
wormatlas.org
.

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million pages long:
To browse the human genome, go to the NCBI Map Viewer (
www.ncbi.nlm.nih.gov/projects/mapview
). From there you can navigate to a page that displays all the chromosomes in the human genome (look for
Homo sapiens,
the official name for our species). Clicking on any chromosome will give you a more detailed map showing the locations of genes, and further clicking will display actual DNA sequences. Figure 4 shows the beginning of chromosome 11. To find the sequences of specific genes, you can search for the names of the proteins they encode.

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unique in a way that a worm is not:
Worm connectomes, although more similar to one another than human connectomes, are not identical. The topic is explored at greater length in Chapter 12.
   
fixed from the moment of conception:
It's an oversimplification to say that your genome is fixed. Each of your cells contains a copy of your genome. (There are exceptions, such as red blood cells, which lack DNA when mature.) The copies are almost identical, but there are slight differences. Some are caused by copying errors as your cells divide, and can lead to cancer. Some differences are important for function, as in certain cells of the immune system. DNA can also be modified in ways that do not change the sequence, which is part of a more general class of phenomena known as epigenetics.

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than your genome has letters:
This comparison is based on a figure of one quadrillion (10
¹⁵
) synapses, which was obtained by multiplying 100 billion neurons in the brain with an estimated 10,000 synapses per neuron. This is likely an overestimate, and its exact value should not be taken too seriously. A more reliable enumeration has been performed for a brain structure called the neocortex, and yielded 0.16 quadrillion synapses (Tang et al. 2001).

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and phallic graffiti everywhere:
Beard 2008.
   
notions of the self:
I'm indebted to Ken Hayworth for clarifying this point to me.
   
contains 100 billion neurons:
A recent study places the average number at 86 billion (Azevedo et al. 2009).

1. Genius and Madness

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Ivan Turgenev:
The brains of Turgenev and other famous Russians are described in Vein and Maat-Schieman 2008.

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Sir Arthur Keith:
Keith 1927. Unfortunately for Keith and his reputation, he is remembered less for his scientific discoveries than for his endorsement of the Piltdown Man. These skull fragments, purported to be a “missing link” in the evolution of man from ape, were eventually exposed as fake. Piltdown Man became one of the most famous hoaxes in the history of science.

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French theoretical physicist: Keith resolved his conundrum in a similar way, writing that “a detailed study of Anatole France's life, so far as it is known, shows us that he was in many senses a primitive man.” He wrapped up his essay by reaffirming his belief that brain size and intelligence are actually related: “In the long run I expect it will be found that there is a close correspondence between brain mass and the degree of function subserved by that organ.”
Keith resolved his conundrum in a similar way, writing that “a detailed study of Anatole France's life, so far as it is known, shows us that he was in many senses a primitive man.” He wrapped up his essay by reaffirming his belief that brain size and intelligence are actually related: “In the long run I expect it will be found that there is a close correspondence between brain mass and the degree of function subserved by that organ.”

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average head size:
Galton 1889.

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people with bigger brains:
McDaniel 2005.

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with high accuracy:
If the correlation coefficient of two variables is
r,
then knowing one variable reduces the typical prediction error of the other by a factor of √1–
r
²
.

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correlation between IQ and brain volume:
McDaniel 2005.

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“Beauty Map”:
Galton recounts the story in the last chapter of his memoirs, about “Race Improvement, or Eugenics” (Galton 1908). In a three-volume hagiography, Karl Pearson reminisced about his mentor: “Galton, influenced by his own motto . . . , seldom went for a walk or attended a meeting or lecture without counting something. If it was not yawns or fidgets, it was the colour of hair, of eyes, or of skins” (Pearson 1924, p. 340).
Galton.org
pays tribute to the man.

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imbecile:
Pearson 1906. While Pearson confirmed Galton's finding that head size and school grades were statistically related, he also noted that head size was a poor predictor of school grades for any particular individual. Even handwriting quality was a better predictor than head size.

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cerebrum, the cerebellum, and the brainstem:
Swanson 2000 divides the brain more finely into the cerebral cortex, basal ganglia, thalamus, hypothalamus, tectum, tegmentum, cerebellum, pons, and medulla. Swanson argues that all of the many proposed schemes for coarsely dividing the brain can be regarded as different groupings of these nine basic parts. For example, in the tripartite scheme of Figure 7, the cerebrum is defined as the cortex plus the basal ganglia, and the brainstem as the rest of the parts minus the cerebellum. A book-length exposition of his views can be found in Swanson 2012. Note that some authorities exclude the thalamus and hypothalamus from the brainstem, so its definition is ambiguous.

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spares mental abilities:
Although introductory textbooks usually don't mention it, cerebellar damage does have some effects on emotion and cognition (Strick, Dum, and Fiez 2009; Schmahmann 2010).

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largest of the three parts:
The cerebrum is largest by volume, but the cerebellum has the most neurons, with an estimated 70 billion (Azevedo et al. 2009) or 100 billion (Andersen, Korbo, and Pakkenberg 1992). Almost all of these are the so-called granule cells. Because these are very small, the cerebellum takes up only 10 percent of the brain's volume (Rilling and Insel 1998). The neocortex, the dominant part of the cerebrum, is estimated to contain 20 billion neurons (Pakkenberg and Gundersen 1997).

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into four lobes:
The borders of the occipital lobe are defined with additional landmarks but are somewhat arbitrary. The four lobes are named for the four bones of the skull that overlie them. Some authorities define a fifth, limbic lobe. This is visible on the faces of the hemispheres exposed by cutting the cerebrum in half along the longitudinal fissure. Buried inside the Sylvian fissure is a part of the cortex known as the insula, which is large enough that some regard it as another lobe.

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prisons and mental asylums:
Micale 1985.

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not confining them in chains:
Harris 2003.

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Figure 10:
The lesion is centered in the inferior frontal gyrus (fold) of the left cerebral hemisphere. The story of the patient Leborgne, nicknamed Tan, is told in Finger 2005 and Schiller 1963, 1992.

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hemispheres looked so similar:
Researchers have also found slight structural asymmetries between the right and left hemispheres, but it's been difficult to tell whether these have anything to do with lateralization of function (Keller et al. 2009).

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dominant for language:
Rasmussen and Milner 1977. In a minority of left-handers and ambidextrous people, the right hemisphere is dominant for language, or both hemispheres are involved.

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Harvey sent specimens:
Abraham 2002; Paterniti 2000.

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Sandra Witelson:
Witelson, Kigar, and Harvey 1999.

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brains of luminaries:
Burrell 2004.

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his 1819 treatise:
Gall 1835.

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IQ is correlated: Jung and Haier 2007.
Jung and Haier 2007.

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London taxi drivers:
Maguire et al. 2000.

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In musicians:
Hutchinson et al. 2003; Gaser and Schlaug 2003. My statement “thicker cortex” is a bit glib, because the measurements rely on a method called voxel-based morphometry, which can't distinguish between thickening and other structural changes. Thickening is just one possible interpretation.

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Bilinguals: Mechelli et al. 2004.
Mechelli et al. 2004.

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severe mental disorder:
Kessler et al. 2005.

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symptoms of autism:
Frith 2008.

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unable to function:
There are also milder forms of autism, which involve some but not all of the symptoms. For example, Asperger's syndrome is defined by social impairment and repetitive behaviors but not linguistic difficulties. The term
autism spectrum disorders
has been introduced to include the entire range, from mild to severe forms of autism. Fombonne 2009 estimated the incidence of full-blown autism as two per 1,000 people, and that of the autism spectrum disorders as several times higher.

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“beautiful child”:
Frith 1993.

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defined the syndrome:
The Viennese pediatrician Hans Asperger is also credited with having defined autism a few years earlier.

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large heads:
Kanner 1943.

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heads and brains:
Redcay and Courchesne 2005. Interestingly, autism provides counterevidence to the maxim that bigger is better. Phrenologists might respond by pointing to autistic “savants,” who exhibit impressive displays of memory, numerical calculation, or other mental abilities like the fictional character in the movie
Rain Man
(Treffert 2009). Perhaps these enhanced mental abilities could be explained by the enlargement of autistic brains. But most autistic children are not savants, and even savants have disabilities. Perhaps it's fairer to conclude that the phrenological approach of studying brain size is an oversimplification.

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frontal lobe:
Carper et al. 2002.

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first-person account:
BGW 2002.

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less effective for the negative symptoms:
Second-generation, or “atypical,” antipsychotic drugs were marketed as superior for negative symptoms, but this claim is now being questioned. For more on this controversy, see Murphy et al. 2006 and Leucht et al. 2009. The atypicals are less likely to produce movement disorders as side effects, which were common with first-generation, or “typical,” antipsychotics.