Connectome (47 page)

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growth cone acts like a dog:
Kolodkin and Tessier-Lavigne 2011.

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200 million axons:
The numerical estimate comes from Tomasch 1954 and Aboitiz et al. 1992.

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milder than in microcephaly:
Paul et al. 2007. “Split-brain” patients, with a corpus callosum severed by epilepsy surgery, also have relatively minor impairments.

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half a million per second:
The estimate of half a million comes from Huttenlocher 1990, Figure 1, which summarizes data from Huttenlocher et al. 1982.

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number of synapses has dropped:
Huttenlocher and Dabholkar 1997. Similar observations were made in the monkey cortex by Rakic 1986.

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a less than ideal way:
Earlier I mentioned channelopathies, defective ion channels that cause electrical signaling of individual neurons and synapses to malfunction. Because neural activity alters connectomes by mechanisms like Hebbian plasticity, a channelopathy is expected to lead to abnormal connectivity. This example shows that connectopathies may be associated with other types of neuropathology.

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autistic brain is slightly smaller:
Redcay and Courchesne 2005 is a meta-analysis, combining the results of many studies.

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schizophrenia, like autism:
Lewis and Levitt 2002; Rapoport et al. 2005.

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too
few
connections:
Courchesne and Pierce 2005; Geschwind and Levitt 2007.

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schizophrenia, too, be caused: Friston 1998. According to Kubicki et al. 2005, Carl Wernicke and the German psychiatrist Emil Kraepelin proposed the connectopathy theory of psychosis at the beginning of the twentieth century.
Friston 1998. According to Kubicki et al. 2005, Carl Wernicke and the German psychiatrist Emil Kraepelin proposed the connectopathy theory of psychosis at the beginning of the twentieth century.

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rapidly again in adolescence:
Huttenlocher and Dabholkar 1997.

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over the edge to psychosis:
Is the connectopathy theory consistent with the observed effects of schizophrenia medications? Psychotic symptoms are relieved by drugs interfering with synapses that secrete dopamine. The symptoms are induced in normal people by drugs interfering with synapses that secrete glutamate. (Examples are ketamine and phencyclidine or PCP, which temporarily turn recreational users into schizophrenics, as emergency room physicians can attest.) According to the traditional view, the connectivity of the schizophrenic brain is normal, but the synapses don't work properly. Synaptic malfunction is corrected by the antipsychotic drugs and induced by the psychosis-generating drugs. But another view would be that antipsychotic drugs cause changes in synaptic function that compensate for connectopathy in schizophrenics, while psychosis-generating drugs mimic the effects of connectopathy in normals. This is possible because changes in synaptic function and changes in connectivity may have similar effects. For example, drastically weakening a synapse may be indistinguishable from removing it altogether. There is an even more subtle possibility. It may be wrong to think of abnormal synaptic function and abnormal connectivity as two independent defects. Suppose that synapse elimination is driven by synaptic weakening, which in turn is dependent on activity. If abnormal synaptic function changes activity patterns, it could end up causing the brain's connectivity to develop abnormally. Any initial abnormality in connectivity might also lead to abnormal activity patterns, which could cause further development of abnormal connectivity. Connectopathy would accompany schizophrenia, but it would be difficult to say which is cause and which is effect.

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predicting the IQ of individuals:
Actually neo-phrenologists can predict mental retardation with certainty in the special case that the brain is extremely small, as in microcephaly.

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will develop HD:
Since there is no cure, and since the test does not predict when the symptoms will start, most people with a family history of HD choose not to take the test.

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genetics of autism and schizophrenia:
Given enough time, genomics researchers may eventually identify all the different genetic defects involved in autism. Then perhaps a large battery of genetic tests will make it possible to predict autism accurately. But even if all the relevant mutations are known, the complex interactions between genes may still make it difficult to predict autism accurately.

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correcting the genetic defect:
Ehninger et al. 2011; Guy et al. 2011.

 

7. Renewing Our Potential

 

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5 or 10 percent: The numbers depend on the exact definition of “long-term.” In a more recent book, Seligman says that 5 to 20 percent of dieters regain their lost weight (or more) within three years (Seligman 2011).
The numbers depend on the exact definition of “long-term.” In a more recent book, Seligman says that 5 to 20 percent of dieters regain their lost weight (or more) within three years (Seligman 2011).

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“zero-to-three movement”:
Bruer 1999.

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elderly as well as young adults:
Draganski et al. 2004; Boyke et al. 2008.

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videos of these remarkable processes:
Meyer and Smith 2006; Ruthazer, Li, and Cline 2006.

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wires themselves are fixed:
It's common to use the term
rewiring
to include reconnection as well, but I think it's more helpful to distinguish between them.

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brain into regions: Karl Lashley, the proponent of the principle of equipotentiality, was the most vigorous opponent of cortical localization. He had many ways of downplaying the existence of cortical areas. One of them was to deny or question whether localization had any significance for function: “The basis of localization of function within the nervous system is apparently the grouping of cells of similar function within brain regions. . . . What activities of the cells are favored by such an arrangement? What functions does it permit that could not be carried out if the cells were uniformly distributed throughout the system? Has localization or gross anatomic differentiation any functional significance whatever? . . . Increasing knowledge of the facts of cerebral localization has only emphasized ignorance of the real reason for any gross localization whatever.” Lashley's questions are answered in this chapter.
Karl Lashley, the proponent of the principle of equipotentiality, was the most vigorous opponent of cortical localization. He had many ways of downplaying the existence of cortical areas. One of them was to deny or question whether localization had any significance for function: “The basis of localization of function within the nervous system is apparently the grouping of cells of similar function within brain regions. . . . What activities of the cells are favored by such an arrangement? What functions does it permit that could not be carried out if the cells were uniformly distributed throughout the system? Has localization or gross anatomic differentiation any functional significance whatever? . . . Increasing knowledge of the facts of cerebral localization has only emphasized ignorance of the real reason for any gross localization whatever.” Lashley's questions are answered in this chapter.

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between nearby neurons:
Schüz et al. 2006.

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touch, temperature, and pain:
The relevant brain regions belong to an important structure called the thalamus. As a rule, the most direct pathways from all the sense organs to the neocortex pass through the thalamus, which is sometimes called the “gateway to the neocortex.” The thalamus sits at the top of the brainstem, and is surrounded by the cerebrum. Some authorities include the thalamus as part of the brainstem, while others regard it as part of the diencephalon, also known as the interbrain.

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Gerald Schneider: A major pathway for auditory information travels from the ears to the brainstem to the inferior colliculus to the medial geniculate nucleus (MGN) of the thalamus to the primary auditory cortex (Brodmann areas 41 and 42). A major pathway for visual information travels from the retina to the superior colliculus (SC). Schneider 1973 and Kalil and Schneider 1975 damaged the SC as well as the axons traveling from the inferior colliculus to the MGN. This diverted retinal axons from growing into the SC, rerouting them toward the MGN to fill the “vacuum” that had been created there. In effect, the researchers wired the eyes to the nominal auditory system.
A major pathway for auditory information travels from the ears to the brainstem to the inferior colliculus to the medial geniculate nucleus (MGN) of the thalamus to the primary auditory cortex (Brodmann areas 41 and 42). A major pathway for visual information travels from the retina to the superior colliculus (SC). Schneider 1973 and Kalil and Schneider 1975 damaged the SC as well as the axons traveling from the inferior colliculus to the MGN. This diverted retinal axons from growing into the SC, rerouting them toward the MGN to fill the “vacuum” that had been created there. In effect, the researchers wired the eyes to the nominal auditory system.

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visual cortex was disabled:
Visual information travels not only to the SC but also along another pathway from the retina to the lateral geniculate nucleus (LGN) of the thalamus to the primary visual cortex (Brodmann area 17). The MGN and the LGN are analogous parts of the thalamus, serving hearing and vision respectively. Sur, Garraghty, and Roe 1988 disabled the visual cortex by damaging the LGN. Similar results were obtained in Schneider's hamsters by Frost et al. 2000.

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when they read Braille:
Sadato et al. 1996; Cohen et al. 1997.

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wiring between regions is selective:
This principle of “wiring economy” explains why most neural connections are between nearby neurons, and most areal connections between nearby areas. The principle can be formalized as the postulate that the connectome is realized using the minimum length of wires (axons and dendrites). Theorists have used it to explain why nearby neurons tend to have similar functions, and why this rule is sometimes violated by discontinuities in cortical maps. (See Chklovskii and Koulakov 2004.) Wiring economy is an important design principle for electrical engineers, too. One of their challenges is to arrange transistors on the surface of a silicon slab to minimize the length of wire required to establish a desired connectivity.

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constrain the potential: This echoes the earlier discussion of memory, which argued that neurons are sparsely connected because full connectivity would be wasteful of space and other resources. I theorized that sparse connectivity constrains the potential of neurons to store new associations, and reconnection renews this potential.
This echoes the earlier discussion of memory, which argued that neurons are sparsely connected because full connectivity would be wasteful of space and other resources. I theorized that sparse connectivity constrains the potential of neurons to store new associations, and reconnection renews this potential.

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feral children could not learn:
The critical period applies only to the learning of a first language. A second language, although much easier to learn before puberty, is not impossible in adulthood.

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took a tragic turn:
Jones 1995.

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real sentence structure:
Rymer 1994.

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Antonella Antonini and Michael Stryker:
Antonini and Stryker 1993, 1996. They studied the axons entering V1 from the LGN, a brain region described in an earlier note.

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deprivation was ended early:
Their results don't entirely explain the critical period for visual development. Binocular deprivation leads to an abnormal visual system, but LGN axons corresponding to both eyes remain normal, or even larger than normal. Perhaps some other kinds of connections are affected, but Antonini and Stryker were not able to see this.

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Greenough and his colleagues:
Greenough, Black, and Wallace 1987.

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George Stratton:
Stratton 1897a, 1897b.

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their pointing arm:
Bock and Kommerell 1986.

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This skewed behavior:
Knudsen and Knudsen 1990.

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Kennard Principle:
Schneider 1979.

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exceptions are well-known:
For example, if the brain damage is very early—just days after birth—the effects can be more severe later on (Kolb and Gibb 2007). A more conservative reformulation is: The earlier the damage, the greater the reorganization of the brain. The reorganization may succeed in restoring function, or it may not.

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new branches can grow:
Yamahachi et al. 2009.

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lifetime of stereo blindness:
Susan Barry had surgery to correct her strabismus at age two. If that surgery had happened later, it's not clear her special stereo training would have been as effective in adulthood.

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Researchers have employed:
Vetencourt et al. 2008; He et al. 2006; Sale et al. 2007.

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more optimistic message:
Linkenhoker and Knudsen 2002.

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injury facilitates rewiring:
Carmichael 2006.