Connectome
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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.
[>] 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.
[>] 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.
[>] correcting the genetic defect: Ehninger et al. 2011; Guy et al. 2011.
7. Renewing Our Potential
[>] 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).
[>] “zero-to-three movement”: Bruer 1999.
[>] elderly as well as young adults: Draganski et al. 2004; Boyke et al. 2008.
[>] videos of these remarkable processes: Meyer and Smith 2006; Ruthazer, Li, and Cline 2006.
[>] 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.
[>] 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.
[>] between nearby neurons: Schüz et al. 2006.
[>] 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.
[>] 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.
[>] 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.
[>] when they read Braille: Sadato et al. 1996; Cohen et al. 1997.
[>] 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.
[>] 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.
[>] 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.
[>] took a tragic turn: Jones 1995.
[>] real sentence structure: Rymer 1994.
[>] 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.
[>] 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.
[>] Greenough and his colleagues: Greenough, Black, and Wallace 1987.
[>] George Stratton: Stratton 1897a, 1897b.
[>] their pointing arm: Bock and Kommerell 1986.
[>] This skewed behavior: Knudsen and Knudsen 1990.
[>] Kennard Principle: Schneider 197
9.
[>] 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.
[>] new branches can grow: Yamahachi et al. 2009.
[>] 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.
[>] Researchers have employed: Vetencourt et al. 2008; He et al. 2006; Sale et al. 2007.
[>] more optimistic message: Linkenhoker and Knudsen 2002.
[>] injury facilitates rewiring: Carmichael 2006.
[>] subtler kinds of rewiring: In the Knudsen experiments, rewiring could be seen relative to the map in the inferior colliculus. A similar strategy could work in sensory and motor areas of the cortex, which generally contain analogous maps. Many other areas are not organized according to such simple maps, however, so rewiring is more difficult to detect.In the Knudsen experiments, rewiring could be seen relative to the map in the inferior colliculus. A similar strategy could work in sensory and motor areas of the cortex, which generally contain analogous maps. Many other areas are not organized according to such simple maps, however, so rewiring is more difficult to detect.
[>] No new neurons: Rakic 1985 cemented the dogma.
[>] Elizabeth Gould: Gould et al. 1999.
[>] “most startling”: Blakeslee 2000.
[>] champion at self-repair: Taub 2004.
[>] prevailed in the neocortex: Most of the evidence comes from monkeys, but Bhardwaj et al. 2006 additionally studied the human brain.
[>] hippocampus and the olfactory bulb: Kornack and Rakic 1999, 2001. New neurons in these regions of the adult rat brain had previously been shown by Joseph Altman in the 1960s, but his pioneering discovery had been largely ignored by his colleagues.
[>] “gateway” to memory: Kempermann 2002.
[>] memories of smells: Lledo, Alonso, and Grubb 2006.
[>] fingers fused together: Flatt 2005.
[>] died as survived: Cowan et al. 1984.
[>] wasteful to create: Buss, Sun, and Oppenheim 2006.
[>] I’ll call regeneration: When neuroscientists use the term regeneration, they are usually referring to the regrowth of axons after they are severed, but I call this rewiring. My usage of regeneration is typical of biology, and refers to the creation and elimination of cells.
[>] since the 1960s: Gross 2000 reviews the history of such reports and speculates about why they were ignored.
[>] grain of truth: Kornack and Rakic 2001 charged that Gould had erroneously identified non-neuronal cells as neurons. There are many types of brain cells that are not neurons.
[>] foster learning and plasticity: On a related note, some critics say that the Rosenzweig experiments reveal the effects of deprivation, not enrichment. The fancy cages with toys and companions should not be regarded as “enriched,” as they only relieve the deprivation of the ordinary laboratory cage. The latter is a highly impoverished environment compared with the rats’ natural habitat.
[>] migrate into the zone: Carmichael 2006.
8. Seeing Is Believing
[>] and Francis Crick: Watson and Crick relied on the data of Rosalind Franklin, who was a crystallographer. She died prematurely and could not share their Nobel Prize.
[>] didn’t fully recognize its significance: Leeuwenhoek reported his observations of sperm in a letter to the president of the Royal Society of London. Embarrassed by the subject, he stressed that the specimen was the natural product of his marriage bed, and asked the president to suppress the letter if he found it offensive (Ruestow 1983).
[>] called them “animalcules”: Actually animalcules seem like an afterthought in the letter, because they are mentioned only in the last paragraph (Leeuwenhoek 1674).
[>] three clergyman, a lawyer, and a physician: Dobell 1960 describes Leeuwenhoek’s life and career, and collects many of his letters.
[>] single, very powerful lens: Ford 1985 describes the history of the single-lens microscope and argues that Leeuwenhoek made his best lenses by letting molten glass solidify into small globules. Ruestow 1996 notes that Leeuwenhoek also made some lenses by the more standard method of grinding glass, as he claimed in his writings.
[>] individual neurons: Figure 26 depicts Golgi-stained neurons from the cortex (superior temporal sulcus) of the adult rhesus monkey. The image extends from the white matter at the bottom to layer 3 of the cortex at the top, a distance of roughly 1.5 millimeters.
[>] single dark strand: Those of you who are observant may notice that the pasta shown in Figure 27 is actually bucatini, which is thicker than spaghetti and has a hole running down the center. (It has a wonderful chewy texture, and I recommend it highly.) If every strand of the bucatini were stained with a unique color, it might be possible to trace the paths of all the strands, even in a somewhat blurry image. Researchers have actually implemented this strategy by genetically engineering mouse neurons to fluoresce in random colors, a method that Jeff Lichtman wittily named “Brainbow” (Livet 2007; Lichtman 2008). However, the number of distinguishable colors is limited, so Brainbow may be insufficient for tracing a large number of densely entangled neurites. It may be possible to improve the situation by combining Brainbow with sharper images, like those produced by recently invented methods of light microscopy that beat the diffraction limit (Hell 2007). In another approach, Tony Zador has proposed genetically engineering each neuron to contain a random RNA or DNA sequence. The sequence could be unique for every neuron, because the number of possibilities is so large—much larger than the number of distinguishable colors. Other molecular tricks and genomic technologies would be used to find the sequences for every pair of connected neurons, yielding the connectome. We don’t yet know whether these directions of research will provide alternatives to electron microscopy, the standard method of finding connectomes. I mention them only to make clear that connectomics is going through an exciting period of innovation.
[>] why Golgi’s stain: From a solution of potassium dichromate and silver nitrate, silver chromate precipitates in a small fraction of neurons, for some unknown reason.
[>] Golgi looked in his microscope: Guillery 2005. Cajal’s view was called the “neuron doctrine” and Golgi’s the “reticular theory.”
[>] as Golgi envisioned: Have you ever heard the joke “Economics is the only field in which two people can share a Nobel Prize for saying opposing things”? The quip probably dates from 1974, when the prize was shared by the economists Gunnar Myrdal and Friedrich Hayek, who were shocked to find themselves honored at the same event, given that their views were so diametrically opposed. At his banquet speech Hayek suggested that a prize for economics was a bit dangerous. Myrdal even wrote a paper calling for the abolition of the prize (Myrdal 1977). He argued that economics was a “soft” science, so its prize, established in 1968, did not belong with the “real” Nobel prizes in the “hard” sciences, which were originally established by the will of Alfred Nobel in 1895. According to Lindbeck 1985, this was ironic coming from Myrdal, who had lobbied strongly for the creation of the economics prize in the first place. Based on the 1906 Nobel Prize to Golgi and Cajal, should we also regard neuroscience as a “soft” science? Perhaps neuroscience is somewhere in between economics and physics. It’s true that Golgi and Cajal had opposing views, but no one called for the abolition of the Nobel Prize for Physiology and Medicine, as far as I know. And they both turned out to be correct, so the Nobel committee did the right thing.
[>] new stains: These are based on big and heavy atoms like osmium, uranium, and lead, which reflect electrons well.
[>] Figure 28: This transmission electron microscope image comes from the rat hippocampus. It can be found along with many ot
her interesting images of neurons and synapses at synapse-web.org.
[>] the diffraction limit: Recently physicists have realized that it’s possible to beat the diffraction limit using fluorescence microscopy, which was not available to Golgi (Hell 2007).
[>] in a light microscope: The blurred version of the image is due to Winfried Denk, who simulated the point-spread function of a 1.4 numerical aperture (NA) microscope objective assuming a wavelength of 500 nanometers.
[>] edge of a saw is blunt: As a hybrid of saw and knife, serrated knives are one of those irritating intermediate cases that are the bane of the classifier. We will ignore them.