William H. Calvin and George A. Ojemann's CONVERSATIONS WITH NEIL'S BRAIN (bibliography and notes)
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Conversations with Neil’s Brain
The Neural Nature of Thought & Language
Copyright  1994 by William H. Calvin and George A. Ojemann.

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William H. Calvin, Ph.D., is a neurophysiologist on the faculty of the Department of Psychiatry and Behavioral Sciences, University of Washington.

George A. Ojemann, M.D., is a neurosurgeon and neurophysiologist on the faculty of the Department of Neurological Surgery, University of Washington.

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General References
1     A Window to the Brain 1
2.     Losing Consciousness 21
3.     Seeing the Brain Speak 41
4.     If Language Is Left, What's Right? 61
5.     The Problems with Paying Attention 77
6.     The Personality of the Lowly Neuron 91
7.     The What and Where of Memory 113
8.     How Are Memories Made? 125
9.     What's Up Front 139
10.     When Things Go Wrong with Thought and Mood 153
11.     Tuning Up the Brain by Pruning 169
12.     Acquiring and Reacquiring Language 183
13.     Taking Apart the Visual Image 195
14.     How the Brain Subdivides Language 211
15.     Why Can We Read So Well? 225
16.     Stringing Things Together in Novel Ways 235
17.     Deep in the Temporal Lobe, Just Across from the Brain Stem 245
18.     In Search of the Narrator

William H. Calvin, The Cerebral Symphony: Seashore Reflections on the Structure of Consciousness (Bantam 1989). [The 1996 book, The Cerebral Code, has much more on this topic.]

Jean-Pierre Changeux, Neuronal Man (Oxford University Press 1986; translation of L'Homme Neuronal, Fayard 1983).

Richard L. Gregory, The Oxford Companion to the Mind (Oxford University Press 1987).

Michael I. Posner, Marcus E. Raichle, Images of Mind (Freeman 1994).

Scientific American special issues on the brain, September 1979 and September 1992.


John E. Dowling, Neurons and Networks: An Introduction to Neuroscience (Harvard University Press 1992).

Daniel Gardner (ed.), The Neurobiology of Neural Networks (MIT Press 1993).

Eric R. Kandel, James H. Schwartz, Thomas M. Jessell, Principles of Neural Science, 3d edition (Elsevier 1991).

Stephen M. Kosslyn, Richard A. Andersen (eds.), Frontiers in Cognitive Neuroscience (MIT Press 1992). Collected articles on vision, audition, somatosensory system, attention, memory, language, and reasoning.

John G. Nicholls, A. Robert Martin, Bruce G. Wallace, From Neuron to Brain: A Cellular and Molecular Approach to the Function of the Nervous System, 3rd edition (Sinauer, Sunderland MA, 1992).

Lloyd D. Partridge, L. Donald Partridge, The Nervous System (MIT Press 1993).

Robert F. Schmidt, Gerhard Thews, Human Physiology, 2nd edition (Springer Verlag 1989, translation of Physiologie des Menschen, 1987).

Gordon M. Shepherd, The Synaptic Organization of the Brain, 3rd edition (Oxford University Press 1990).


Rather than citing the earliest observations in the research literature, we have attempted to cite recent articles in books and journals that are widely found in college and public libraries; most of our citations, unfortunately, will be found only in medical libraries.

Page numbers refer to the manuscript pages, not the hardcover and softcover editions from Addison-Wesley.

Chapter 1. A Window into the Brain

Some of the history of attempts to localize functions in the human brain can be found in Anne Harrington, "Beyond phrenology: localization theory in the modern era," in The Enchanted Loom: Chapters in the History of Neuroscience, edited by Pietro Corsi, pp. 207-239 (Oxford University Press 1991). See also Stanley Finger, Origins of Neuroscience: A History of Explorations into Brain Function (Oxford University Press 1994).

A. R. Luria, "The functional organization of the brain," Scientific American (March 1970).

14 The sensory strip figure is modified from the version found in Wilder Penfield, Theodore Rasmussen, The Cerebral Cortex of Man (Macmillan 1950).

14 Wilder Penfield, Herbert Jasper, Epilepsy and the Functional Aantomy of the Human Brain (Little Brown 1954). Although most cortical movements and sensation relate to the opposite side of the body, there are connections between primary motor and sensory cortices and ipsilateral body, especially for face and to a lesser extent leg. Only fine finger movement seems to be totally dependent on contralateral motor cortex. These ipsilateral connections are probably important in recovery from damage to primary motor and sensory areas. Only very rarely will electrical stimulation of primary motor or sensory cortex evoke ipsilateral responses. However, stimulation of some of the secondary motor or sensory maps will more often yield ipsilateral effects.

21 The comparative neuroanatomist Irving Diamond argues that the "motor cortex" isn't restricted to the motor strip but is the fifth layer of the entire cerebral cortex. This is true because the fifth layer, no matter where it is, contains neurons that send their mass mailings down to the spinal cord, with copies to the brain stem, basal ganglia, and hypothalamus. Diamond likewise argues that the fourth layer everywhere is the "sensory cortex" and that second and third layers everywhere are the "association cortex." See "The subdivisions of neocortex: A proposal to revise the traditional view of sensory, motor, and association areas," in J. M. Sprague, A. N. Epstein (eds.), Progress in Psychobiology and Physiological Psychology, 8:1-43 (Academic Press 1979).

22 D. J. Felleman, David C. Van Essen, "Distributed hierarchical processing in the primate cerebral cortex," Cerebral Cortex 1:1-47 (1991).

Chapter 2. Losing Consciousness

For some general background on the EEG and its relation to chaos theory, see Walter J. Freeman, "The physiology of perception," Scientific American 264(2):78-85 (February 1991).

J. Allan Hobson, Sleep (Freeman 1989).

Rodolfo R. Llinás, D. Paré, "Of dreaming and wakefulness," Neuroscience 44:521-535 (1991).

26 J. Allan Hobson, The Dreaming Brain (Basic Books 1988), p.133.

28 Marvin Minsky, quoted by Clive Davidson, "I process therefore I am," New Scientist 1866:22-26 (27 March 1993).

33 Neurons are only one of the cell types in the brain. There are even more astrocytes, the glial cells that line every surface of the brain and surround the nonmyelinated parts of most neurons. They surround the blood vessels and contribute to the so-called blood-brain barrier that keeps many substances (such as antibiotics) from reaching further into the brain. The myelin wrapping on the axons inside the central nervous system is due to the oligodendrocytes (that in the peripheral nervous system is due to Schwann cells).

33 Serotonin neurons are concentrated in the raphe nuclei, which get their name from the Greek word rhaphe, which means "seam" and refers to the midline crease that can be seen along the top surface of the brain stem. Besides norepi and serotonin, there are also diffuse projecting systems for dopamine and acetylcholine. These four diffuse systems can be thought of as like a set of four underground sprinkler systems that spray out various mixes of short-acting fertilizer over broad areas of the brain.

34 The illustration of stages of sleep is modified from Nancy C. Andreasen, The Broken Brain (Harper & Row 1984).

34 Adam N. Mamelak, J. Allan Hobson, "Dream bizarreness as the cognitive correlate of altered neuronal behavior in REM sleep," Journal of Cognitive Neuroscience 1:201-222 (Summer 1989).

34 Jonathan Winson, "The meaning of dreams," Scientific American 263(5):86-96 (November 1990).

37 René Descartes, Meditations on First Philosophy (1641, various editions).

50 Suzanne Stensaas, D. Eddington, and W. Dobelle, "The topography and variability of the primary visual cortex in man," Journal of Neurosurgery 40:747 (1973).

50 Cortical surface area in various species, calculated from the figures in Jean-Pierre Changeux, Neuronal Man (1983, Random House translation from the French in 1985).

51 Nancy C. Andreasen et al., "Intelligence and brain structure in normal individuals," American Journal of Psychiatry 150:130-134 (January 1993).

51 Arthur R. Jensen, "Understanding g in terms of information processing," Educational Psychology Review 4:271-308 (1992).

Chapter 3. Seeing the Brain Speak

The blood flow studies of seeing words, hearing words, speaking and generating words are from the work of Marcus Raichle and his collaborators; the original color illustration can be readily found in Gerald D. Fischbach, "Mind and brain," Scientific American 267(3):48-57 (September 1992). For more on both reading and PET methods, see Julie A. Fiez, Steven E. Petersen, "PET as part of an interdisciplinary approach to understanding processes involved in reading," Psychological Science 4:287-293 (September 1993).

Wilder Penfield, Lamar Roberts, Speech and Brain Mechanisms (Princeton University Press 1959).

Albert M. Galaburda, "Asymmetries of cerebral neuroanatomy," Ciba Foundation Symposia 162:219-226 (1991). Two-thirds of human brains have a larger planum temporale on the left.

Antonio R. Damasio, Hanna Damasio, "Brain and language," Scientific American 267(3):63-71 (September 1992).

Antonio R. Damasio, "Aphasia," New England Journal of Medicine 326:531-539 (20 February 1992).

George Ojemann, "Cortical organization of language," Journal of Neuroscience 11:2281-2287 (1991). See also Scientific American (to appear).

Alan S. Gevins, Judy Illes, "Neurocognitive networks of the human brain," Annals of the New York Academy of Sciences 620:22-44 (1991). Scalp-recorded EEG and evoked potentials.

56 There is a fascinating story concerning personality differences in the rats whose left brain is larger than the right: see Victor H. Dennenberg, "Hemispheric laterality in animals and the effects of early experience," Behavioral and Brain Sciences 4(1):1-50 (March 1981).

56 Norman Geschwind, "Specializations of the human brain," Scientific American (September 1979). Caution: the planum temporale is mislabeled in the next-to-last illustration of this article. The planum temporale asymmetry has recently been challenged on the grounds that infolding (within the sylvian infolding itself) is greater on the right, compensating for the differences in gross appearance: see William C. Loftus, Mark Jude Tramo, Catherine E. Thomas, Ronald L. Green, Robert A. Nordgren, Michael S. Gazzaniga, "Three-dimensional quantitative analysis of hemispheric asymmetry in the human superior temporal region," Cerebral Cortex 3:348-355 (July/August 1993).

57 The appearance of asymmetry in the planum temporale during human fetal development is described in J. Wada, R. Clarke, A. Hamm, "Cerebral hemispheric asymmetry in humans," Archives of Neurology 32:239-246 (1975). And see Albert M. Galaburda, "Anatomical asymmetries," in Cerebral Dominance, edited by Norman Geschwind, Albert M. Galaburda, pp. 11-25 (Harvard University Press 1984).

59 Harry Whitaker recently pointed out that Wernicke was not the first person to describe the pattern of aphasia with temporal lobe damage. There is an earlier case report by Theodore Meynert, an Austrian neurologist, of a patient with a left temporal lobe stroke, and the pattern of language changes we would now call "Wernicke's" aphasia, a case cited by Wernicke in his book.

66 E. Sue Savage-Rumbaugh, Jeannine Murphy, Rose A. Sevcik, Karen E. Brakke, Shelley L. Williams, and Duane Rumbaugh, Language Comprehension in Ape and Child (University of Chicago Press 1993). Monographs of the Society for Research on Child Development 58(3).

67 Derek Bickerton, Language and Species (University of Chicago Press 1990).

69 The illustration of mental rehearsal of finger movements is adapted from P. E. Roland, E. Skinhøj, N. A. Lassen, B. Larsen, "Different cortical areas in man in organization of voluntary movements in extrapersonal space," Journal of Neurophysiology 43:137-150 (1980).

71 Rodolfo Llinás, U. Ribary, "Coherent 40-Hz oscillation characterizes dream state in humans," Proceedings of the National Academy of Sciences (U.S.A.) 90:2078-2081 (1 March 1993).

73 J. W. Belliveau, D. N. Kennedy, Jr., R. C. McKinstry, B. R. Buchbinder, R. M. Weisskoff, M. S. Cohen, J. M. Vevea, T. J. Brady, B. R. Rosen, "Functional mapping of the human visual cortex by magnetic resonance imaging," Science 254:716-719 (1 November 1991).

75 Mapping by neural activity altering the reflectance of light from the brain's surface: while this may be, in part, a matter of blood flow changing the average color of the surface, it has been known since the 1940s that even isolated peripheral nerves change their reflectance when kept busy conducting impulses. Reflectance changes also occur in brain slices kept alive by an oxygenated bath without any blood supply, making it likely that reflectance changes are at least in part also a result of swelling of neurons and glia with activity. The first full report of reflectance changes in human cortex during movements and language is Michael M. Haglund, George A. Ojemann, Daryl Hochman, "Optical imaging of epileptiform and functional activity in human cerebral cortex," Nature 358:668-671 (20 August 1992).

75 A detailed analysis of the size and location of sites where stimulation altered naming in 117 patients is found in George Ojemann, Jeff Ojemann, Ettore Lettich, Mitchell Berger, "Cortical language localization in left, dominant hemisphere", Journal of Neurosurgery 71:316-326 (September 1989). This report also includes correlations between the location of sites related to naming by stimulation, and patient sex and verbal IQ.

Further evidence that a removal of brain that encroaches on sites where stimulation alters naming is likely to result in a postoperative language deficit is presented in George A. Ojemann, "Electrical stimulation and the neurobiology of language," Behavioral and Brain Science 6:221-226 (1983).

78 The illustration of how male and female brains are organized for language and hand movements is adapted (with the percentages recalculated) from Doreen Kimura, "Sex differences in the brain," Scientific American 267(3):118-125 (September 1992). Further evidence of differences in language organization in males and females, derived from stimulation mapping, is reported in Catherine Mateer, Samuel Polen, George Ojemann, "Sexual variation in cortical localization of naming as determined by stimulation mapping," Behavioral and Brain Science 5:310-311 (1982), and in the 117 patient series above.

Chapter 4. If Language Is Left, What's Right?

Any of the textbooks on human neuropsychology is a good starting place to read more, e.g., Bryan Kolb, Ian Q. Whishaw, Fundamentals of Human Neuropsychology, 3d edition (Freeman 1990). For a somewhat skeptical view of the left-right overemphasis, see Robert Efron, The Decline and Fall of Hemispheric Specialization (Erlbaum 1990) and William H. Calvin, The Throwing Madonna, Chapter 10 (Bantam 1991).

E. D. Ross, "The aprosodias: Functional-anatomical organization of the affective components of language in the right hemisphere," Archives of Neurology 38:561-569 (1981).

Richard B. Ivry, Paul C. Lebby, "Hemispheric differences in auditory perception are similar to those found in visual perception," Psychological Science 4(1):41-45 (January 1993).

Robert J. Zatorre, Alan C. Evans, Ernst Meyer, Albert Gjedde, "Lateralization of phonemic and pitch discrimination in speech processing," Science 256:846-849 (8 May 1992).

81 Juhn Wada actually invented the intracarotid amobarbital test in 1949 to test for language dominance. It was about a decade later when its primary use became one of pre-operative testing for memory function in the two hemispheres, following the report on H.M. by W. B. Scoville, Brenda Milner, "Loss of recent memory after bilateral hippocampal lesions," Journal of Neurology, Neurosurgery, and Psychiatry 20:11-21 (1957).

83 Edwin A. Weinstein, Woodrow Wilson: A Medical and Psychological Biography (Princeton University Press 1981).

84 The Justice Douglas story is in Howard Gardner, Hiram H. Brownell, Wendy Wapner, Diane Michelow, "Missing the point: the role of the right hemisphere in the processing of complex linguistic materials," in Cognitive Processing in the Right Hemisphere, pp. 169-191 (Academic Press 1983). For the press release, see p. 361 of Bob Woodward, Scott Armstrong, The Brethren (Simon and Schuster 1979).

88 Some of the implications for presidential disability under the 25th Amendment to the U.S. Constitution are discussed, along with Woodrow Wilson's stroke, by William H. Calvin, The Throwing Madonna: Essays on the Brain (McGraw-Hill 1983).

88 The series of self-portraits by Anton Räderscheidt, covering the period from before his right-hemisphere stroke through his partial recovery, is illustrated in Howard Gardner, The Shattered Mind: The Person After Brain Damage (Knopf 1975), pp. 330-331.

91 The data on proportions of left- or right-brain lesions producing aphasias, constructional apraxias, or dressing apraxias was derived from R. J. Joynt, M. N. Goldstein, "Minor cerebral hemisphere," Advances in Neurology 7:147-183 (1975).

92 Peter F. MacNeilage, Michael G. Studdert-Kennedy, Bjorn Lindblom, "Hand signals: Right side, left brain and the origin of language," The Sciences 33(1):32-37 (January-February 1993). This contains a good summary of the animal lateralization literature. See also the letter by William H. Calvin in the November-December 1993 issue.

92 When visual-spatial functions and language are crammed into one hemisphere (as in a child who has had one side of the brain removed in infancy for Sturge-Weber disease), language may be nearly normal, but visual-spatial functions are poorly developed. That suggests that one hemisphere isn't adequate to house both major groups of cortical functions.

It has long been known that left-handedness is much more common in those who stutter than in the overall population. Evidence of an unusually high incidence of bilateral language representation in stutterers, using the dichotic technique, has been reported by J. P. Brady, J. Berson, "Stuttering, dichotic listening, and cerebral dominance," Archives of General Psychiatry 32:1449-1452 (1975). Cases in which damage to one side of the brain, in what would ordinarily be language areas on the left side, have cured lifelong stuttering are collected in R. K. Jones, "Observations on stammering after localized cerebral injury," Journal of Neurology, Neurosurgery, and Psychiatry 29:192-195 (1966).

J. Mondlock, L. Caplan, "Behavioral abnormalities after right hemisphere stroke," Neurology 33:337-344 (1983).

94 Robert Desimone, "Face-selective cells in the temporal cortex of monkeys," Journal of Cognitive Neuroscience 3 (Winter 1991).

94 Oliver Sacks, The Man Who Mistook His Wife for a Hat (Simon and Schuster 1985).

94 Changes in the labeling of facial emotional expressions with right posterior temporal stimulation are reported in Itzhak Fried, Catherine Mateer, George Ojemann, Richard Wohns, Paul Fedio, "Organization of visuospatial functions in human cortex: evidence from electrical stimulation," Brain 105:349-371 (1982). Evidence for right-brain lateralization of mechanisms for identifying facial emotional expressions, derived with a variety of techniques, is also reviewed there.

96 Changes in human temporal lobe neuronal activity with faces is reported in Jeff Ojemann, George Ojemann, Ettore Lettich, "Neuronal activity related to faces and matching in human right nondominant temporal cortex," Brain 115:1-13 (1992).

98 Justine Sergent, S. Ohta, Brennan MacDonald, "Functional neuroanatomy of face and object processing. A positron emission tomography study," Brain 115:15-36 (February 1992). A face-gender categorization resulted in activation changes in the right extrastriate cortex, and a face-identity condition produced additional activation of the fusiform gyrus and anterior temporal cortex of both hemispheres, and of the right parahippocampal gyrus and adjacent areas. Cerebral activation during an object-recognition task occurred essentially in the left occipito-temporal cortex and did not involve the right-hemisphere regions specifically activated during the face-identity task.

Justine Sergent, Jean-Louis Signoret, "Functional and anatomical decomposition of face processing: evidence from prosopagnosia and PET study of normal subjects," Philosophical Transactions of the Royal Society of London (Biology) 335:55-61 (29 January 1992). See the news story in American Scientist 80(6):537-539 (November-December 1992).

98 Localization of memories, see Martha J. Farah, "Neuropsychological inference with an interactive brain: a critique of the locality assumption," Behavioral and Brain Sciences (to appear, 1994).

99 The effects of cortical stimulation on simple arithmetic calculations are from an unpublished study of A. Forbes, G. Ojemann. A more general review of the brain basis for mathematical calculation is found in F. Grewel, volume 4 of Handbook of Neurology (Vinken and Bruyn, eds., Amsterdam, North Holland) pp. 181-194 (1969).

100 T. G. Bever, R. J. Chiarello, "Cerebral dominance in musicians and non-musicians," Science 185:137-139 (1974).

100 Changes in human temporal lobe neuronal activity while listening to various types of music are reported Otto Creutzfeldt, George Ojemann, "Neuronal activity in the human lateral temporal lobe. III. Activity changes during music," Experimental Brain Research 77:490-498 (1989). A particularly good discussion of the effects of brain damage on artistic abilities of all types, including professional musicians is found in chapter 8 of Howard Gardner, The Shattered Mind (Knopf 1975).

101 Gardner et al (1983).

Chapter 5. The Problems with Paying Attention

A good discussion of Penfield's "evoked memories" is in Larry R. Squire, Memory and Brain (Oxford University Press 1987), pp. 76-84.

105 Elizabeth F. Loftus, Geoffrey R. Loftus, "On the permanence of stored information in the human brain," American Psychologist 35:409-420 (May 1980).

106 Penfield's own summary of his experience with evoking memories is in Wilder Penfield, Phanor Perot, "The brain's record of auditory and visual experience - a final summary and discussion," Brain 86:595-696 (1963). That report indicates some of the association between the presence of experiential responses with stimulation, and as part of the same patient's seizures. Further evidence that these responses only occur when stimulation evokes a small seizure is provided by Pierre Gloor, Andre Olivier, L. Quesney, Fred Andermann, S. Horowitz, "The role of the limbic system in experiential phenomena of temporal lobe epilepsy," Annals of Neurology 12:129-144 (1982). The patient who heard Led Zeppelin is reported in more detail in George Ojemann, "Brain mechanisms for consciousness and conscious experience," in McMaster-Bauer Symposium on Consciousness, Canadian Psychology 27:158-168 (1986).

107 For each neurotransmitter such as glutamate, there are usually a number of somewhat different postsynaptic receptors, each controlling a channel through the membrane and/or an intracellular process of some sort. That acetylcholine had "nicotinic" and "muscarinic" receptors was known a half-century ago; now we are faced with dozens of serotonin receptors in postsynaptic cells. So synaptic actions are not merely a matter of how much membrane current they generate in the first millisecond after their arrival, but also a matter of how the affect regulatory processes in the cell on a slower time scale.

111 José V. Pardo, Peter T. Fox, Marcus E. Raichle, "Localization of a human system for sustained attention by positron emission tomography," Nature 349:61-64 (3 January 1991).

113 Michael I. Posner, Steven E. Petersen, Peter T. Fox, Marcus E. Raichle, "Localization of cognitive operations in the human brain," Science 240:1627-1631 (1988). Michael I. Posner, "Attention as a cognitive and neural system," Current Directions in Psychological Science 1:11-14 (February 1992).

117 The effects of thalamic stimulation on language and recent verbal memory performance are summarized in George Ojemann, "Language and the thalamus: object naming and recall during and after thalamic stimulation," Brain and Language 2:101-120 (1975).

119 Thalamic stimulation effects on recent memory for complex shapes, and the contrast with effects on recent verbal memory, is reported in George Ojemann, "Altering memory with human ventrolateral thalamic stimulation," in Modern Concepts in Psychiatric Surgery, edited by E. Hitchcock, T. Ballantine, B. Meyerson (Elsevier/North Holland Biomedical Press 1979) pp. 103-109.

119 Uta Frith, "Autism," Scientific American 268(6):108-114 (June 1993). Uta Frith, John Morton, Alan M. Leslie, "The cognitive basis of a biological disorder: Autism," Trends in the Neurosciences 14:433-438 (October 1991). Oliver Sacks, "A neurologist's notebook: an anthropologist on Mars," The New Yorker, pp. 106-125 (27 December 1993).

Chapter 6. The Personality of the Lowly Neuron

A good introduction to the physiology is by Charles F. Stevens, "The neuron," Scientific American 241(3):55-65 (September 1979). For the local circuits of cerebral cortex, see the special issue of the journal Cerebral Cortex 3 (September/October 1993) edited by Kathleen S. Rockland.

122 Santiago Ramón y Cajal, Histologie du système nerveux de l'homme et des vertébrés (Paris: Malone, 1909-1911).

123 Six layers of neocortex: The original classification has been subject to some lumping and splitting. Layers II and III can usually be lumped together; one will see "layer 2/3" or "the superficial layers" as a way of lumping them (layer I doesn't have many cell bodies in it, so the "cells of the superficial layers" usually means those of 2/3). But layer IV has had to be repeatedly subdivided, especially in the visual cortex where we talk about layers IVa, IVb, and IVc (and sometimes subdivide it into IVc and IVc).

125 The best pictures of the horizontal connections are in Barbara A. McGuire, Charles D. Gilbert, Patricia K. Rivlin, Torsten N. Wiesel, "Targets of horizontal connections in macaque primary visual cortex," Journal of Comparative Neurology 305:370-392 (1991) and in Charles D. Gilbert, "Circuitry, Architecture, and functional dynamics of visual cortex," Cerebral Cortex 3:373-386 (1993). Some axons continue for another gap to produce a second patch of terminals, and so forth. The dimensions are from Jennifer S. Lund, Takashi Yoshioka, Jonathan B. Levitt, "Comparison of intrinsic connectivity in different areas of macaque monkey cerebral cortex," Cerebral Cortex 3:148-162 (March/April 1993). The "0.5 mm" distance to the center of the terminal patch is about 0.43 mm in primary visual cortex, 0.65 mm in the secondary visual areas, 0.73 mm in sensory strip, and 0.85 mm in motor cortex of monkeys. The diameter of the patch of terminals (and that of the basal dendritic spread) is about half the center-to-center distance (our "block length"); thus, the "mass mailing" does not go only to the "third house on each block," but to a spread of addresses near it. In humans, the center-to-center dimensions (at least in the primary visual cortex) are in the range of 0.6-1.0 mm, about twice that of monkeys: Andreas Brukhalter, Kerry L. Bernardo, "Organization of corticocortical connections in human visual cortex," Proceedings of the National Academy of Sciences (U.S.A.) 86:1071-1075 (1989).

125 Horizontal connections are also found among the pyramidal neurons of the deep layers (V and VI), but the regular spacing has been noted only for the pyramids of the superficial layers. The latter also may send myelinated axons (the horizontal collaterals are unmyelinated) out of the cortical layers into the white matter; their eventual targets are other cortical areas, sometimes via the corpus callosum. Roughly 70 percent of the excitatory synapses on any superficial pyramid, but less than 1 percent of those on layer V pyramids, are derived from pyramidal neurons less than 0.3 mm away: Andrew Nicoll, Colin Blakemore, "Patterns of local connectivity in the neocortex," Neural Computation 5:665-680 (September 1993).

125 Charles F. Stevens, "How cortical interconnectedness varies with network size," Neural Computation 1:473-479 (1989).

127 The corpus callosum illustration is adapted from one in Jonas Szentágothai, "The neuron network of the cerebral cortex, a functional interpretation," Proceedings of the Royal Society, London B201:219-248 (1978).

127 A. J. Rockel, R. W. Hiorns, T. P. S. Powell, "The basic uniformity in structure of the neocortex," Brain 103:221-244 (1980).

127 At least in the sensory cortices, there are "minicolumns" whose dimensions are about 30 m, such as the orientation columns of visual cortex; these may be due to vertical bundles of apical dendrites, as proposed by Alan Peters, C. Sethares, "Organization of pyramidal neurons in area 17 of monkey visual cortex," Journal of Comparative Neurology 306:1-23 (1991), and Alan Peters, Engin Yilmaz, "Neuronal organization in area 17 of cat visual cortex," Cerebral Cortex 3:49-68 (January/February 1993). Then there are "macrocolumns" of closer to 0.4-0.7 mm (e.g., eye preference columns, Mountcastle's original columns in the sensory strip). There are about 300 minicolumns in a macrocolumn, and about 100 neurons in a minicolumn (142 for monkey visual cortex). See Vernon B. Mountcastle, in The Neurosciences Fourth Study Program, edited by F. O. Schmitt and F. G. Worden, pp. 21-42 (MIT Press 1979). See the discussion of columns in association cortex in Trends in the Neurosciences 15:362-368 (1992) and 16:178-181 (1993).

132 Luigi F. Agnati, Börje Bjelke, Kjell Fuxe, "Volume transmission in the brain," American Scientist 80:362-373 (July-August 1992).

137 Impulses are not the only way to trigger release of the neurotransmitter packets; indeed, there are neurons that rarely use impulses. The photoreceptors in the eye, and the next layer or so of interneurons, normally operate without impulses. Any cell lacking a long axon is a candidate for such "graded release synapses," where the release rate is proportional to the net excitatory synaptic current. See Chapter 8 in W. H. Calvin, The Throwing Madonna: Essays on the Brain (Bantam 1991).

137 A synonym for impulse is action potential. Another common synonym is spike, but we have avoided it here because of the EEG terminology's use of "spike" for the characteristic resting activity of an epileptic focus, in between seizures. This EEG spike is not an impulse from a single neuron, but the summed activity of many synchronized excitatory postsynaptic potentials (EPSPs).

137 Myelinated conduction of the impulse is sometimes called saltatory, after the Latin saltare, "to leap." The gaps in the myelin insulation, about 1 mm apart, are where the sodium channels through the axon membrane cluster.

137 If the presynaptic neuron fires a few impulses in rapid succession, the successive EPSPs will add together to reach a higher peak voltage ("temporal summation"). EPSPs from other sources ("spatial summation") also sum together; a cortical neuron has between 3,000 and 60,000 input synapses, with about 40 percent of them being inhibitory.

We talk of the neuron "firing" as if the voltage trigger had finally been pulled hard enough to set it off. Sometimes the EPSPs are so brief that only one impulse occurs. But a neuron can fire an impulse every few milliseconds (usually to send a rather imperative signal). In many neurons of the brain and spinal cord, the firing rate is almost a linear function of the summed synaptic currents (to use the more precise word instead of flow), at least once past a minimum requirement. It is rather like court fines for speeding: no output when beneath the threshold (speed limit), court costs of $25 and $2 for each mph in excess of the threshold. So, too, a neuron may produce no impulses for below-threshold synaptic currents, then jump up to a minimum rhythmic firing rate (say, 25 each second), and add two more impulses per second for nanoampere current increments in excess of the minimum requirement. A few neurons, most notably the motor neurons of spinal cord that run the muscles, change their properties at a second threshold, rather like the sliding scale for speeding fines that goes up to $4 for each mph over 70 mph.

The neuron can appear to be remarkably "analog" (adding and subtracting linearly, for example) when the postsynaptic potentials are individually small and there are enough of them to keep the neuron above the repetitive firing minimum. The spinal cord "motor neurons" that run the muscles are a good example of this computational style. And a neuron's style can be more "digital" when postsynaptic strengths are larger, and a few EPSPs can stand on one another's shoulders to reach impulse threshold. Cortical neurons appear to be capable of both styles. That cortical neurons can grade their rhythmic firing rate over a wide range, analogous to motor neurons and many sensory neurons, is reviewed by William H. Calvin, "Normal repetitive firing and its pathophysiology," in Epilepsy: A Window to Brain Mechanisms (Joan S. Lockard, Arthur A. Ward, Jr., editors, Raven Press, New York), pp. 97-121 (1980). That many cortical neurons in awake monkeys demonstrate intervals between impulses that are more consistent with a nonrhythmic, and possibly digital, process is demonstrated by William R. Softky, Christof Koch, "Cortical cells should fire regularly, but do not," Neural Computation 4:643-646 (September 1992); "The highly irregular firing of cortical cells is inconsistent with temporal integration of random EPSPs," Journal of Neuroscience 13:334-350 (January 1993).

138 In neurons, the ten-fold higher concentration of sodium ions outside the cell constitutes a battery across the cell membrane of about 60 millivolts. The potassium inside the neuron is about thirty times more concentrated than it is just outside the neuron, and that acts as if a battery of -90 millivolts were straddling the cell membrane. Chloride ions are also pumped out the cell, and that produces a battery equivalent of nearly -90 millivolts.

The actual voltage inside the neuron depends on these (and other) opposing influences. It can be momentarily varied anywhere between +60 and -90 millivolts, much like a mixing faucet can give you any temperature between that of the hot water heater and that of the cold water source. Ordinarily most of the membrane pores that can pass sodium ions are kept closed, and the voltage inside the neuron stays down near -70 millivolts. But occasionally some sodium pores are opened, and the positive-charged sodium ions rush in, raising the internal voltage — sometimes a little, sometimes a lot. Sometimes the potassium or chloride pores are opened to move the voltage down nearer -90 millivolts.

The impulse is simply a result of enough sodium channels being opened so that the internal voltage shoots up from -70 to perhaps +30 millivolts, a 0.1 volt excursion. One consequence is that the potassium pores then open up — and that hauls the voltage back down again. If potassium didn't "reset" the internal voltage in this manner, the impulse would last much longer. And that would release even more neurotransmitter from the presynaptic terminal.

138 The flows are also equal at the resting potential, but this is a stable equilibrium; if the voltage is slightly displaced, it drifts back toward the resting potential in tens of milliseconds. Actually, sodium ion (Na+) and potassium ion (K+) are not the only players in this game; chloride ion, Cl-, also moves, but its membrane pores aren't as likely to open and close as those of the two positive ions. In some regions of the cell (though not usually the axon), calcium ion (Ca++) is also a major player.

139 "Sodium pores tend to slowly shut themselves off at higher voltages" is known as sodium inactivation, and it is largely responsible for the inability to initiate another impulse for a while (the refractory period).

140 Wrong-way impulses spreading down side branches along the way: this is known as the axon reflex. Sometimes the backward impulses will fail when reaching a branch point because of geometric considerations, a problem discussed by William H. Calvin, "Some design features of axons and how neuralgias may defeat them," in Advances in Pain Research and Therapy (John J. Bonica, ed.), 3:297-309 (1979).

144 Properly speaking, only the postsynaptic pores of a synapse can be excitatory or inhibitory. But the upstream neuron is often so labeled because its "mass mailings" usually all have the same type of postsynaptic effect at the thousands of synapses made by its axon terminals.

144 Edward L. White with Asaf Keller, Cortical Circuits: Synaptic Organization of the Cerebral Cortex (Birkhäuser 1989).

146 The nonpyramidal neuron axon almost never enters the white matter, while pyramidal neurons usually (but not always) have a more distant projection in addition to all their local axon branches. There is one type of nonpyramidal neuron in primate cerebral cortex that may be a modified pyramidal neuron and excitatory: Jennifer S. Lund, "Spiny stellate cells," in Cerebral Cortex, vol. 1 (A. Peters, E. G. Jones, eds.), pp.255-308 (Plenum 1984).

146 The illustration of three types of motor cortex neurons is from William H. Calvin, George W. Sypert, "Fast and slow pyramidal tract neurons: An intracellular analysis of their contrasting repetitive firing properties in the cat," Journal of Neurophysiology 39:420-434 (1976). The calibration bars represent 20 millivolts, 20 nanoamperes of injected current, and 20 milliseconds.

107 For each neurotransmitter such as glutamate, there are usually a number of somewhat different postsynaptic receptors, each controlling a channel through the membrane and/or an intracellular process of some sort. That acetylcholine had "nicotinic" and "muscarinic" receptors was known a half-century ago; now we are faced with dozens of serotonin receptors in postsynaptic cells. So synaptic actions are not merely a matter of how much membrane current is generated in the first millisecond, but also a matter of how the released neurotransmitter affects regulatory processes in the cell on a slower time scale.

149 Blood flow is some unknown function of the number of neurons active and their firing rates — but it doesn't distinguish between excitatory and inhibitory neurons. Were inhibitory neurons to increase their activity to the point of canceling out the excitatory activity, the blood-flow-based techniques would simply report that the cortex was twice as busy — when it was only stalemated.

149 Actually, synaptic strength isn't the only thing that can be adjusted for learning and memory. Some neurotransmitters and their second messengers inside the postsynaptic neuron can change the mode of impulse initiation from beating to bursty. But this affects the whole cell, and adjusting synaptic strengths at or near the synapse is capable of fine-tuning.

150 LTP has both pre- and postsynaptic aspects, NMDA being an example of how the same amount of neurotransmitter can cause more postsynaptic current to flow. But LTP also has presynaptic aspects, where more transmitter seems to be released. It is thought that there are certain "retrograde neurotransmitters" that allow the postsynaptic cell to stimulate more transmitter release presynaptically by later impulses. Both NO and CO gases are candidates, e.g., Charles F. Stevens, Yanyan Wang, "Reversal of long-term potentiation by inhibitors of haem oxygenase," Nature 364:147-149 (8 July 1993) — and the news article in the same issue at pp. 104-105.

150 Atsushi Iriki, Constantine Pavlides, Asaf Keller, Hiroshi Asanuma, "Long-term potentiation of thalamic input to the motor cortex induced by coactivation of thalamocortical and corticocortical afferents," Journal of Neurophysiology 65:1435-1441 (1991).

Chapter 7. The What and Where of Memory

A prime reference is Larry R. Squire, Memory and Brain (Oxford University Press 1987). In addition, some background reading might include:

Daniel C. Alkon, Memory's Voice: Deciphering the Mind-Brain Code (HarperCollins 1992).

Neal J. Cohen, Howard Eichenbaum, Memory, Amnesia, and the Hippocampal System (MIT Press 1993).

Larry Squire, Stuart Zola-Morgan, "The medial temporal lobe memory system," Science 253:1380-1386 (1991).

Geoffrey E. Hinton, "How neural networks learn from experience," Scientific American 267(3):105-109 (September 1992).

Patricia S. Goldman-Rakic, "Working memory and the mind," Scientific American 267(3):73-79 (September 1992).

Endel Tulving, Elements of Episodic Memory (Oxford University Press 1983). And his "Remembering and knowing the past," American Scientist 77:361-367 (1989), or "What is episodic memory?" Current Directions in Psychological Science 2(3):67-70 (June 1993).

Suzanne Corkin, "Lasting consequences of bilateral medial temporal lobectomy: Clinical course and experimental findings in H.M.," Seminars in Neurology 4:249-259 (1984).

154 William Scoville, Brenda Milner, "Loss of recent memory after bilateral hippocampal lesions," Journal of Neurology, Neurosurgery and Psychiatry 20:11-21 (1957).

154 The autopsy findings in the patient with recent memory loss after a left temporal removal, showing focal damage in the remaining hippocampus, are in Wilder Penfield, G. Mathieson, "An autopsy and a discussion of the role of the hippocampus in experiential recall," Archives of Neurology 31:145-154 (1974).

155 A detailed summary of H.M.'s memory deficits is in Arthur Shimamura, "Disorders of memory: the cognitive science perspective," in Handbook of Neuropsychology, edited by François Boller, Jordan Grafman, v. 3, pp. 37-42 (Elsevier 1988).

158 G. Stillhard, T. Landis, R. Schiess, M. Regard, G. Sialer, "Bitemporal hypoperfusion in transient global amnesia: 99m-Tc-HM-PAO SPECT and neuropsychological findings during and after an attack," Journal of Neurology, Neurosurgery, and Psychiatry 53:339-342 (1990).

159 A good review of Milner's findings is "Hemispheric specialization: scope and limits," in The Neurosciences: Third Study Program, edited by F. O. Schmitt, FF. G. Worden (MIT Press 1974), pp. 75-89.

6 Hermann Ebbinghaus, Memory: A Contribution to Experimental Psychology (Dover 1964).

161 Ulric Neisser, Nicole Harsch, "Phantom flashbulbs: False recollections of hearing the news about Challenger," In E. Winograd, U. Neisser (Eds.) Affect and accuracy in recall: Studies of "flashbulb" memories (Cambridge University Press 1992).

162 Elizabeth F. Loftus, "When a lie becomes memory's truth," Current Directions in Psychological Science 1:121-123 (1992). Elizabeth F. Loftus, Geoffrey R. Loftus, "On the permanence of stored information in the human brain," American Psychologist 35:409-420 (May 1980). Actually, a videotape was not used but rather a series of 30 slides, and the yield sign misinformation was subtly incorporated into a different question, and then later tested by asking subjects to choose between a picture of the intersection and a nearly identical one in which the stop sign had been replaced by a yield sign.

163 D. Stephen Lindsay, "Eyewitness suggestibility," Current Directions in Psychological Science 2:86-89 (June 1993).

164 Tulving (1989) and David H. Ingvar, "Ideography: Mapping ideas in the brain," in Brain Work and Mental Activity, edited by N. A. Lassen, D. H. Ingvar, M. E. Raichle, L. Friberg (Munksgaard, Copenhagen 1991), pp. 346-359.

164 Cortical stimulation mapping effects on recent verbal memory are reported in George Ojemann, "Organization of short term verbal memory in language areas of human cortex: evidence from electrical stimulation," Brain and Language 5:331-340 (1978) and "Brain organization for language from the perspective of electrical stimulation mapping," Behavioral and Brain Sciences 6:189-206 (1983). Evidence that these cortical memory sites contribute to memory deficits after left temporal removals is found in George Ojemann, Carl Dodrill, "Verbal memory deficits after left temporal lobectomy for epilepsy: Mechanism and intraoperative prediction," Journal of Neurosurgery 62:101-107 (1985). The effects of stimulation elsewhere in brain, including hippocampus, are reviewed in George Ojemann, Otto Creutzfeldt, "Language in humans and animals: contribution of brain stimulation and recording," in Handbook of Physiology, the Nervous System, volume 5, Higher Functions of the Brain, edited by Vernon Mountcastle, Fred Plum, Steven Geiger, pp. 675-699 (American Physiological Society 1987).

Chapter 8. How Are Memories Made?

170 George A. Miller, "The magical number seven: plus or minus two. Some limits on our capacity for processing information," Psychological Review 9:81-97 (1956).

170 E. Paulesu, C. D. Frith, R. S. J. Frackowiak, "The neural correlates of the verbal component of working memory," Nature 362:343-346 (25 March 1993).

171 Philip Lieberman, Uniquely Human: The Evolution of Speech, Thought, and Selfless Behavior (Harvard University Press 1991).

171 P. M. Grasby, C. D. Frith, K. J. Friston, C. Bench, R. S. J. Frackowiak, R. J. Dolan, "Functional mapping of brain areas implicated in auditory-verbal memory function," Brain 116:1-20 (1993).

174 Joaquin Fuster, "Neuronal discrimination and short term memory in association cortex," in Neurobiology of Higher Cognitive Function, Arnold Scheibel, Adam Wechsler, editors, (Guilford Press 1990), pp. 85-102.

175 William H. Calvin, George A. Ojemann, Arthur A. Ward, Jr., "Human cortical neurons in epileptogenic foci: Comparison of inter-ictal firing patterns to those of `epileptic' neurons in animals." Electroencephalography and Clinical Neurophysiology 34:337-351 (1973).

175 George Ojemann, Otto Creutzfeldt, Ettore Lettich, Michael Haglund, "Neuronal activity in human lateral temporal cortex related to short-term verbal memory, naming and reading," Brain 111:1383-1403 (1988).

176 Michael Haglund, George Ojemann, Ted Schwartz, Ettore Lettich, "Neuronal activity in human lateral temporal cortex during serial retrieval from short-term memory," Journal of Neuroscience (in press 1993).

176 The learning-associated changes in cerebral blood flow patterns are especially pronounced in the supplementary motor area, e.g., R. J. Seitz, P. E. Roland, C. Bohm, T. Greitz, S. Stone-Elander, "Motor learning in man: a positron emission tomography study," NeuroReport 1:17-20 (1990). For language learning, PET blood flow changes have been better seen in the region of the cingulate gyrus and in the traditional language areas. Marcus Raichle, "Exploring the mind with dynamic imaging," Seminars in the Neurosciences 2:307-315 (1990).

179 William H. Calvin, "Binding forms a cerebral code which error corrects: Scattered feature detectors generate a hexagonal code via synchronizing excitation among pyramidal neurons," Society for Neuroscience Abstracts 19:398.22 (1993).

180 Malcolm P. Young, S. Yamane, "Sparse population coding of faces in the inferotemporal cortex," Science 256:1327-1331 (1992).

180 Simpler mechanisms for Post hoc ergo prompter hoc are discussed in chapter 9 of William H. Calvin, The Throwing Madonna: Essays on the Brain (Bantam 1991).

181 The washboarded road illustration is from William H. Calvin, lectures for Dutch National Science Week (October 1992).

181 Franklin B. Krasne, "Extrinsic control of intrinsic neuronal plasticity: a hypothesis from work on simple systems," Brain Research 140:197-206 (1978).

183 Eric R. Kandel, Robert D. Hawkins, "The biological basis of learning and individuality," Scientific American 267(3):52-60 (September 1992).

183 Anita M. Turner, William T. Greenough, "Differential rearing effects on rat visual cortex synapses. I. Synaptic and neuronal density and synapses per neuron." Brain Research, 329:195-203 (1985).

Fred R. Volkmar, William T. Greenough, "Rearing complexity affects branching of dendrites in the visual cortex of the rat." Science 176:1445-1447 (1972).

William T. Greenough, "Experiential modification of the developing brain," American Scientist 63:37-46 (1975).

183 Evidence that drugs that block protein synthesis interfere with formation of long term memories in experimental animals has been available for several decades. S. Barondes, H. Cohen, "Memory impairment after subcutaneous injection of acetoxycycloheximide," Science 160:556-557 (1968). However, interpretation of these findings is complicated by the possibility that these drugs also have other effects besides blocking protein synthesis.

184 Donald O. Hebb, The Organization of Behavior (Wiley 1949). Includes what we now call the "Hebbian synapse" which, like the modern NMDA synapse, strengthens when there are near-simultaneous arrivals on the same dendrite. Hebb also proposed the cell assembly, the "Hebbian ensemble," as the active form of the memory. And Hebb noted that memory really required a "dual trace" system with an underlying pattern of connectivities that allowed the cell assembly to recreate its characteristic activity. All of this Hebb recognized on a theoretical basis from the psychological and brain lesion experiments, a few years before the first microelectrode recordings were made from mammalian central nervous system. See Peter M. Milner, "The mind and Donald O. Hebb," Scientific American 268(1):124-129 (January 1993).

185 The NMDA channel at glutamate synapses was named after N-methyl-d-aspartate because it, rather than glutamate, is what opens the channel in the lowest concentrations. But glutamate opens it just fine, and that's what is usually released as a neurotransmitter.

14 John G. Taylor, When the Clock Strikes Zero (Pan Macmillan 1992) discusses the role of hippocampus rehearsing cerebral cortex during REM sleep.

Chapter 9. What's Up Front

For general background on the psychiatric disorders, see Nancy C. Andreasen, The Broken Brain (Harper and Row 1984) and Peter D. Kramer, Listening to Prozac (Viking 1993).

U. Halsband, N. Ito, J. Tanji, H.-J. Freund, "The role of premotor cortex and the supplementary motor area in the temporal control of movement in man," Brain 116:243-266 (February 1993).

191 The darwinian notion of consciousness is developed by W. H. Calvin, The Cerebral Symphony: Seashore Reflections on the Structure of Consciousness (Bantam 1989), and in "Islands in the mind," Seminars in the Neurosciences 3:423-433 (1991). It is an old idea, dating back to William James in 1880. [The 1996 book, The Cerebral Code, has much more on this topic.]

194 Justine Sergent, "Music, the brain, and Ravel," Trends in the Neurosciences 16:168-172 (May 1993). The illustration shows right-handed piano playing, sight-reading, and listening, subtracting the activity map obtained when merely playing scales; there is little activation of midline cortex such as supplementary motor area, and the only right-sided activation is in the rear of the superior parietal lobule.

Justine Sergent, Eric Zuck, Sean Terriah, Brennan MacDonald, "Distributed neural network underlying musical sight-reading and keyboard performance," Science 257:106-109 (3 July 1992).

197 Tim Shallice, Paul W. Burgess, "Deficits in strategy application following frontal lobe damage in man," Brain 114:727-741 (April 1991). A description of three patients with head injuries, more typical of frontal lobe patients than those discussed in our chapter, who had more localized lesions.

197 Wilder Penfield, J. Evans, "The frontal lobe in man: a clinical study of maximum removals," Brain 58:115-133 (1935). The meal preparation story is usually told, e.g., by William H. Calvin, The River That Flows Uphill: A Journey from the Big Bang to the Big Brain (Macmillan 1986) at p. 460, with the meal-preparation distress as part of the diagnosis of the tumor, but the 1935 paper reveals that it actually occurred 15 months after the surgery which removed all of right frontal lobe to within 1 cm of the motor strip.

197 A. J. Wilkins, Tim Shallice, R. McCarthy, "Frontal lesions and sustained attention," Neuropsychologia 25:359-365 (1987).

198 José V. Pardo, Peter T. Fox, Marcus E. Raichle, "Localization of a human system for sustained attention by positron emission tomography," Nature 349:61-64 (3 January 1991).

198 Paul J. Eslinger, Antonio R. Damasio, "Severe disturbances of higher cognition after bilateral frontal lobe ablation: patient E.V.R.," Neurology 35:1731-1741 (1985).

198 Nancy C. Andreasen, "Brain imaging: Applications in psychiatry," Science 239:1381-1388 (1988).

Judith L. Rapoport, "The biology of obsessions and compulsions," Scientific American 260(3):82-89 (March 1989). And her book The Boy Who Couldn't Stop Washing: The Experience and Treatment of Obsessive-Compulsive Disorder (E. P. Dutton 1989).

201 Evidence for reduced glucose metabolism in the left frontal lobe in several different types of depression is presented by L. Baxter, Jr., J. Schwartz, M. Phelps, J. Mazziotta, B. Guze, C. Selin, R. Gerner, R. Sumida, "Reduction of prefrontal glucose metabolism common to three types of depression," Archives of General Psychiatry 46:243-250 (1989).

202 Antonio R. Damasio, Daniel Tranel, Hanna Damasio, "Individuals with sociopathic behavior caused by frontal damage fail to respond autonomically to social stimuli," Behavioral Brain Research 41:81-94 (1990).

203 The dorsolateral prefrontal cortex projects directly to the superior colliculus, a midbrain structure that has a prominent role in the control of eye and head movements. The orbitofrontal cortex, in contrast, projects directly to the brain stem and the spinal visceral motor structures related to the autonomic nervous system and is also an important olfactory and visceral sensory area. See the review by Edward J. Neafsey, "Prefrontal autonomic control in the rat: anatomical and electrophysiological observations," Progress in Brain Research 85:147-166 (1990).

205 Simon LeVay, The Sexual Brain (MIT Press 1993). And see the news article on genetic linkages in Science 261:291-292 (16 July 1993).

Chapter 10.

When Things Go Wrong with Thought and Mood.

Elliot S. Gershon, Ronald O. Rieder, "Major disorders of mind and brain," Scientific American 267(3):89-95 (September 1992). For a text (from which most of the statistics in this chapter have been taken): Nancy C. Andreasen, Donald W. Black, Introductory Textbook of Psychiatry (American Psychiatric Press 1991). The preceeding year statistics are from the large survey by Ronald Kessler et al in Archives of General Psychiatry (January 1994).

Samuel H. Barondes, Molecules and Mental Illness (Freeman 1992).

Irving I. Gottesman, Schizophrenia Genesis (Freeman 1991).

209 Peter D. Kramer, Listening to Prozac (Viking 1993), p. 165.

210 Kay Redfield Jamison, Touched with Fire: Manic-depressive illness and the artistic temperament (Free Press 1993), p. 125.

212 M. M. Mesulam, "Slowly progressive aphasia without generalized dementia," Annals of Neurology 11:592-598 (June 1982).

212 Sergent (1993).

213 J. William Langston, "The case of the tainted heroin: a trail of tragedies leads to a new theory of Parkinson's disease," The Sciences 25(1):34-40 (January 1985). See also Science (25 February 1983).

213 Matti Virkkunen, Judith DeJong, John Bartko, Frederick K. Goodwin, Markku Linnoila, "Relationship of psychobiological variables to recidivism in violent offenders and impulsive fire setters. A follow-up study," Archives of General Psychiatry 46:600-603 (July 1989). Follow-up articles in the January and February 1994 issues of that journal explore the personality profiles and state-related aggressiveness in Finnish alcoholic, violent offenders, fire setters, and healthy volunteers, along with suicide attempts. Of particular importance are the CSF biochemistries, glucose metabolism, and diurnal activity rhythms.

214 Jamison (1993), p. 29. See also Arnold M. Ludwig, The Price of Greatness (Guilford, in press), who found that manic-depressives are 17 percent of actors, 13 percent of poets, but less than 1 percent of physical scientists (a rate like that of the general population).

216 Nancy C. Andreasen, "Creativity and mental illness: prevalence rates in writers and their first-degree relatives," American Journal of Psychiatry 144:1288-1292 (1987).

216 Jamison (1993), pp. 60-89. And see the New York Times feature (12 October 1993).

219 Eric R. Kandel, Robert D. Hawkins, "The biological basis of learning and individuality," Scientific American 267(3):79-86 (September 1992).

219 Evidence that many effective antidepressants (and electroconvulsive therapy) decrease the release of cyclic adenosine monophosphate that occurs within a neuron when norepinephrine or related compounds bind to their receptors is reviewed in Elliot S. Gershon, Ronald O. Rieder, "Major disorders of mind and brain," Scientific American 267(3):89-95 (September 1992).

220 Murray A. Falconer, "Reversibility by temporal-lobe resection of the behavioral abnormalities of temporal-lobe epilepsy," New England Journal of Medicine, 289:451-455 (1973).

220 R. L. Suddath, M. F. Casanova, T. E. Goldberg, D. G. Daniel, J. R. Kelsoe, Jr, D. R. Weinberger, "Temporal lobe pathology in schizophrenia: a quantitative magnetic resonance imaging study." American Journal of Psychiatry 146:464-472 (April 1989). The volume of temporal lobe gray matter was 20 percent smaller in the patients than in the control subjects (but this need not mean that there are fewer neurons: see Greenough 1975).

Rue L. Cromwell, "Searching for the origins of schizophrenia," Psychological Science 4:276-279 (September 1993).

I. I. Gottesman, Schizophrenia Genesis: The Origins of Madness (Freeman 1991).

Daniel R. Weinberger, K. F. Berman, R. Suddath, E. F. Torrey, "Evidence of dysfunction of a prefrontal-limbic network in schizophrenia: a magnetic resonance imaging and regional cerebral blood flow study of discordant monozygotic twins," American Journal of Psychiatry 149:890-897 (July 1992). The more an affected twin differed from the unaffected twin in left hippocampal volume, the more they differed in prefrontal blood flow activation during the Wisconsin Card Sorting Test. In the affected twins as a group, prefrontal activation was strongly related to both left and right hippocampal volume, suggesting dysfunction within a widely distributed neocortical-limbic neural network that has been implicated in working memory.

221 Eric M. Reiman, Maureen J. Fusselman, Peter T. Fox, and Marcus E. Raichle, "Neuroanatomical correlates of anticipatory anxiety," Science 243:1071-1074 (1989). A PET study showing that the tip of the temporal lobe activates in both normal volunteers and panic disorder patients.

221 There is also evidence for a role of one of the structures on the inner side of the temporal lobe, the amygdala, in uncontrolled anger. There are rare patients with episodic uncontrolled rage. Few people have ever witnessed such rage behavior. It is not the anger of most domestic violence, barroom brawls or riots. Rather, these rare patients may be triggered into trying to kill a stranger by a stimulus as innocuous as a touch on the coat sleeve. Such patients may be too dangerous to be allowed near other people even in an institutional environment. This pattern of behavior has followed damage to the front and inner sides of the temporal lobe including the amygdala, and removal of those damaged structures has reversed the episodic rage behavior, though not preventing normal anger. Local destruction of the amygdala has also ameliorated episodic rage. An evaluation of this type of surgery for this problem is in Edward Hitchcock, V. Cairns, "Amygdalotomy," Postgraduate Medicine 49:894-904 (1973) and Vernon Mark, Frank Erwin, William Sweet in Neural Basis of Violence and Aggression, edited by William Sweet and William Fields (St. Louis, Warren Green, 1975) pp. 379-391.

225 See the news article "Psychosurgery: National Commission issues surprisingly favorable report," Science 194:299 (15 October 1976). And the Federal Register 43(221):53242 (1978).

226 E. Tan, I. M. Marks, P. Marset, "Bimedial leucotomy in obsessive-compulsive neurosis: a controlled serial enquiry," British Journal of Psychiatry 118:155-64 (1971). I. M. Marks, J. L. Birley, M. G. Gelder, "Modified leucotomy in severe agoraphobia: a controlled serial inquiry," British Journal of Psychiatry 112:757-69 (1966). R. Strom-Olsen, S. Carlisle, "Bi-frontal stereotactic tractotomy. A follow-up study of its effects on 210 patients," British Journal of Psychiatry 118:141-54 (1971). For the studies where behavioral and intelligence tests were done before and after, see N. Mitchell-Heggs, D. Kelly, A. Richardson, and McLeish, pp. 327-336 in Modern Concepts in Psychiatric Surgery, edited by Edward Hitchcock et al (Elsevier 1979); Corkin, Twitchell, Sullivan at pp. 253-272; N. Mitchell-Heggs, D. Kelly, A. Richardson, "Stereotactic limbic leucotomy--a follow-up at 16 months," British Journal of Psychiatry 128:226-40 (1976).

231 Robert M. Sapolsky, "Stress in the wild," Scientific American 262(1):116-123 (1990). And his book Stress, the Aging Brain, and the Mechanisms of Neuron Death (MIT Press 1992).

232 The behavioral tics of Torrette's are described by Oliver Sacks, "A surgeon's life," The New Yorker, pp. 85-94 (16 March 1992).

234 Jerome Kagan, J. Stephen Reznick, Nancy Snidman, "Biological basis of childhood shyness," Science 240:167-171 (1988). And see the discussion in Kramer (1993).

Chapter 11. Tuning Up the Brain by Pruning

A theoretical analysis of the left vs right eye zones in visual cortex, which includes many of the relevant citations to the literature, is by Kenneth D. Miller, Joseph B. Keller, Michael P. Stryker, "Ocular dominance column development: analysis and simulation," Science 245:605-615 (11 August 1989).

David H. Hubel, Eye, Brain, and Vision (Freeman 1988).

241 The retinal sketch is adapted from one in John E. Dowling, Brian B. Boycott, "Organization of primate retina: electron microscopy," Proceedings of the Royal Society, London B166:80-111 (1966).

? P. R. Huttenlocher, "Synapse elimination and plasticity in developing human cerebral cortex," American Journal of Mental Deficiency 88:488-496 (1984).

250 J. Tigges, J. G. Herndon, A. Peters, "Neuronal population of area 4 during the life span of the rhesus monkey." Neurobiology of Aging 11:201-208 (May-June 1990). A significant loss of approximately one-third was observed in the total number of motor strip neurons in maturing monkeys (less than 5.5 years). In contrast, in adult monkeys no age-associated loss of neurons was observed.

? Peter F. Drucker, Post-capitalist Society (HarperCollins 1993), p. 57.

255 David H. Hubel, "Effects of distortion of sensory input on the visual system of kittens," The Physiologist 10:43 (1967).

Chapter 12. Acquiring and Reacquiring Language

Patricia S. Kuhl, "Auditory perception and the evolution of speech," Human Evolution 3:21-45 (1988).

John L. Locke, The Child's Path to Spoken Language (Harvard University Press 1993).

Oliver Sacks, Seeing Voices: A Journey into the World of the Deaf (University of California Press 1989).

256 Noam Chomsky, "Language and the mind," Psychology Today (February 1969).

257 See, for example, the news story at p. 535 accompanying the article by Patricia K. Kuhl, Karen A. Williams, Francisco Lacerda, Kenneth N. Stevens, Björn Lindblom, "Linguistic experience alters phonemic perception in infants by 6 months of age," Science 255:606-608 (31 January 1992). For more, see M. J. S. Weiss, P. R. Zelazo (eds.), Newborn Attention (Ablex 1991).

258 Steven Harnad, editor, Categorical Perception (Cambridge University Press 1987).

259 Jon H. Kaas, "Plasticity of sensory and motor maps in adult mammals," Annual Reviews of Neuroscience 14:137-167 (1991).

William M. Jenkins, Michael M. Merzenich, Greg Recanzone, "Neocortical representational dynamics in adult primates: implications for neuropsychology," Neuropsychologia 28:573-584 (1990).

Michael M. Merzenich, Greg H. Recanzone, William M. Jenkins, K. A. Grajski, "Adaptive mechanisms in cortical networks underlying cortical contributions to learning and nondeclarative memory," Cold Spring Harbor Symposia for Quantitative Biology 55:873-887 (1990).

261 Alvaro Pascual-Leone, Fernando Torres, "Plasticity of the sensorimotor cortex representation of the reading finger in Braille readers," Brain 116:39-52 (February 1993).

261 Tim C. Pons, Preston E. Garraghty, Alexander K. Ommaya, Jon H. Kaas, Edward Taub, Mortimer Mishkin, "Massive cortical reorganization after sensory deafferentation in adult macaques," Science 252:1857-1860 (28 June 1991). See also Preston E. Garraghty, Jon H. Kaas, "Large-scale functional reorganization in adult monkey cortex after peripheral nerve injury," Proceedings of the National Academy of Sciences (U.S.A.) 88(16):6976-6980 (15 August 1991). Incidentally, these are the very "Silver Springs" monkeys that the animal rights people tried to gain custody of, claiming in lawsuits and publicity that it was worthless science. Many motorcycle riders who are thrown over the handlebars in an accident, while still hanging on tightly to the handgrips, tend to suffer injuries analogous to those created in these monkeys, severing the sensory axons that come from the hand and arm as they enter the spinal cord. After reading these scientific reports, it is instructive to read back over the journalistic accounts and see the role that arrogant ignorance played in the controversy. A popular treatment is Carolyn Fraser, "The raid at Silver Springs," The New Yorker (19 April 1993), pp. 66ff.

263 Maureen Dennis, Harry Whitaker, "Language acquisition following hemidecortication: Linguistic superiority of the left over the right hemisphere," Brain and Language 3:404-433 (1976),

265 An example of language localization in a four year old derived from stimulation mapping during naming of common objects can be found in George Ojemann, Jeff Ojemann, Ettore Lettich, Mitchell Berger, "Cortical language localization in left, dominant hemisphere", Journal of Neurosurgery 71:316-326 (1989).

266 The graph showing the acquisition of language is adapted from one in Eric H. Lenneberg, Biological Foundations of Language (Wiley 1966), p. 133.

270 Richard P. Meier, "Language acquisition by deaf children," American Scientist 79:60-70 (January-February 1991).

270 National Institutes of Health, Office of the Director, "Early identification of hearing impairment in infants and young children," NIH Consensus Statement 11 (1 March 1993). Their recommendation is that all hearing-impaired infants be identified, and treatment initiated, before six months of age.

271 Oliver Sacks, Seeing Voices (University of California Press 1989).

273 Susan Curtiss, Genie: A Psycholinguistic Study of a Modern-Day "Wild Child" (Academic Press 1977).

274 Lack of success with late-start relatives of the two successful bonobos: personal communication, E. Sue Savage-Rumbaugh, 1993.

275 Factors influencing spontaneous recovery from aphasia are reviewed in Audrey Holland, "Recovery in aphasia," in Handbook of Neuropsychology, edited by François Boller, Jordan Graphman (Elsevier 1989) v. 2, pp. 83-90. Studies evaluating the effects of therapy on this are reviewed in Martha Sarno, "Recovery and rehabilitation in aphasia," in Acquired Aphasia, edited by Martha Sarno (Academic Press 1981) pp. 485-529.

276 Michael Gazzaniga, "Right hemisphere language following brain bisection: a 20-year perspective," American Psychologist 38:525-537 (1983).

276 Lack of naming sites in unusual places in stroke patients: G. A. Ojemann, unpublished data.

278 J. William Langston, "The case of the tainted heroin: a trail of tragedies leads to a new theory of Parkinson's disease," The Sciences 25(1):34-40 (January 1985). P. L. McGeer, E. G. McGeer, J. S. Suzuki, "Aging and extrapyramidal function," Archives of Neurology 34:33-35 (1977). And also P. L. McGeer, E. G. McGeer, "Aging and neurotransmitter systems," in Parkinson's Disease — II. Aging and Neuroendocrine Relationships, edited by C. E. Finch et al., pp.41-57 (Plenum 1978). For a more recent discussion, see James A. Mortimer, "Human motor behavior and aging," Annals of the New York Academy of Sciences 515:54-65 (1988).

Chapter 13. Taking Apart the Visual Image

David H. Hubel, Eye, Brain, and Vision (Scientific American Books 1988).

Semir Zeki, A Vision of the Brain (Blackwell Scientific Publications 1993).

Margaret Livingstone, David H. Hubel, "Segregation of form, color, movement, and depth: Anatomy, physiology, and perception," Science 240:740-749 (1988).

Dale Purves, D. R. Riddle, A.-S. LaMantia, "Iterated patterns of brain circuitry (or how the brain gets its spots)," Trends in the Neurosciences 15:362-368 (1992).

Jennifer S. Lund, "Anatomical organization of macaque monkey striate visual cortex," Annual Reviews of Neuroscience 11:253-288 (1988).

281 E. M. Gombrich, Art and Illusion: A Study in the Psychology of Pictorial Representation (Phaidon Press 1959).

283 Floyd Ratliff, Mach Bands: Quantitative Studies on Neural Networks in the Retina (Holden-Day 1965).

284 The maps showing responses from two retinal ganglion cells is adapted from Robert W. Rodieck, The Vertebrate Retina: Principles of Structure and Function (Freeman 1973).

287 Roy M. Pritchard, "Stabilized images on the retina," Scientific American pp. 72-91 (June 1961).

290 Margaret S. Livingstone, "Art, illusion and the visual system," Scientific American 258(1):78-85 (January 1988).

290 Margaret S. Livingstone, Glenn D. Rosen, Frank W. Drislane, Albert M. Galaburda, "Physiological and anatomical evidence for a magnocellular defect in developmental dyslexia," Proceedings of the National Academy of Sciences (U.S.A.) 88:7943-7947 (15 September 1991). The visual evoked potentials for low-contrast stimuli are delayed in dyslexics. While the lateral geniculate nucleus looks normal in the parvocellular layers, there is a 27 percent reduction in cell bodies in the magnocellular layers of dyslexics.

290 David H. Hubel, Torsten N. Wiesel, "Brain mechanisms of vision," Scientific American 241(3) (September 1979).

296 David H. Hubel, Torsten N. Wiesel, "Functional architecture of macaque monkey visual cortex," Proceedings of the Royal Society, London 198B:1-59 (1977). For a text, see John G. Nicholls, A. Robert Martin, Bruce G. Wallace, From Neuron to Brain, 3d ed (Sinauer 1992).

297 Gian E. Chatrian, Ettore Lettich, L. H. Miller, John R. Green, "Pattern-sensitive epilepsy. I. An electrographic study of its mechanisms," Epilepsia 11:125-149 (1970).

297 Margaret S. Livingstone, David H. Hubel, "Psychophysical evidence for separate channels for the perception of form, color, movement, and depth," Journal of Neuroscience 7:3416-3468 (1987).

297 Semir Zeki, "The visual image in mind and brain," Scientific American 267(3):42-50 (September 1992).

297 D. C. Van Essen, C. H. Anderson, D. J. Fellman, "Information processing in the primate visual system: an integrated systems perspective," Science 255:419 (1992).

299 Triangle detectors are actually possible: see Gyula Sáry, Rufin Vogels, Guy A. Orban, "Cue-invariant shape selectivity of macaque inferior temporal neurons," Science 260:995-997 (14 May 1993).

299 For color vision, see the entries "Colour vision" and "Thomas Young" in The Oxford Companion to the Mind, edited by Richard L. Gregory (Oxford University Press 1987). The cone types are discussed by Edward F. MacNichol, Jr., "Three-pigment color vision," Scientific American, p. 64 (December 1964).

301 The combination theory for taste is covered by Robert P. Erickson, "On the neural bases of behavior," American Scientist 72:233-241 (May-June 1984). An endnote in The Cerebral Symphony, at p. 359, discusses its application to orientation-sensitive neurons of visual cortex with eighteen types of elementary templates.

302 Donald O. Hebb, The Organization of Behavior (Wiley 1949). And see Peter M. Milner, "The mind and Donald O. Hebb," Scientific American 268(1):124-129 (January 1993).

302 Antonio Damasio, "Prosopagnosia," Trends in the Neurosciences 8:132-125 (1985). Antonio Damasio, Daniel Tranel, Hanna Damasio, "Facial agnosia and the neural substrates of memory," Annual Review of Neuroscience 13:9-109 (1990). Justine Sergent, Jean-Louis Signoret, "Varieties of functional deficits in prosopagnosia," Cerebral Cortex 2:375-388 (1992).

Chapter 14. How the Brain Subdivides Language

George A. Ojemann, Otto D. Creutzfeldt, "Language in humans and animals: contribution of brain stimulation and recording," In Handbook of Physiology. Section 1: The Nervous System, Volume 5 part 2, The Higher Functions of the Brain, edited by Vernon B. Mountcastle, Fred Plum, and Steven R. Geiger (American Physiological Society 1987).

Steven E. Petersen, P. T. Fox, A. Z. Snyder, "Activation of extrastriate and frontal cortical areas by visual words and word-like stimuli," Science 249:1041-1044 (1990).

306 M. Paradis, "Bilingualism and aphasia," Studies in Neurolinguistics 3:65-122 (1977).

307 George Ojemann, Harry Whitaker, "The bilingual brain," Archives of Neurology 35:409-412 (1978). Separate sites have even been identified as essential for naming in different Chinese dialects in one patient. Whether there are specific patterns for first or second languages, or for languages that one speaks more or less fluently, is not clear.

308 Ursula Bellugi, Howard Poizner, Edward S. Klima, "Language, modality, and the brain," Trends in Neurosciences 12(10):380-388 (1989). See also Michael M. Haglund, George A. Ojemann, Ettore Lettich, Ursula Bellugi, David Corina, "Dissociation of cortical and single unit activity in spoken and signed languages," Brain and Language 44:19-27 (January 1993).

309 A patient with preservation of naming for tools, but not animals, is described in Antonio Damasio, "Synchronous activation in multiple cortical regions; a mechanism for recall," Seminars in the Neurosciences 2:287-296 (1990). Another patient with preservation of one semantic category, but not another, after a stroke is presented in J. Hart, R. Berndt, A. Caramazza, "Category-specific naming deficit following cerebral infarction," Nature 316:439-440 (1985). Stimulation mapping evidence for separation of sites essential for naming, from those utilized to generate verbs from nouns, is presented in Jeff Ojemann, George Ojemann, Ettore Lettich, "Cortical stimulation during a language task with known blood flow changes," Society for Neuroscience Abstracts 19:1808 (1993). PET scan localization of the brain areas active during generation of verbs from nouns is described in Marcus Raichle, "Exploring the mind with dynamic imaging," Seminars in the Neurosciences 4:307-315 (1990). That group has recently presented evidence that the PET localization for this language function is different, depending on whether the subject has previous experience with the particular list of nouns from which the verbs are to be generated. Stimulation mapping effects on speech sound identification and orofacial speech gestures (movements) is in George A. Ojemann, Catherine Mateer, "Human language cortex: localization of memory, syntax, and sequential motor-phoneme identification systems," Science 205:1401-1403 (1979).

309 Syntax examples, see George A. Ojemann, "Brain organization for language from the perspective of electrical stimulation mapping," Behavioral and Brain Sciences 6(2):189-230 (1983).

315 The rate of change of sounds may be particularly important: J. Schwartz, Paula Tallal, "Rate of acoustic change may underlie hemispheric specialization," Science 207:1380-1381 (1980).

317 Itzhak Fried, George Ojemann, Eberhard Fetz, "Language-related potentials specific to human language cortex," Science 212:353-356 (1981) and George Ojemann, Itzhak Fried, Ettore Lettich, "Electrocorticographic (ECoG) correlates of language: I. Desynchronization in temporal language cortex during object naming," Electroencephalography and Clinical Neurophysiology 73:453-463 (1989).

318 The usually transient but dramatic language deficits after removal of the supplementary motor area are described in detail in Robert Rostomily, Mitchell Berger, George Ojemann, Ettore Lettich, "Postoperative deficits and functional recovery following removal of tumors involving the dominant hemisphere supplementary motor area," Journal of Neurosurgery 75:62-68 (1991).

Investigations into monkey vocalization, using both stimulation mapping and neuronal recording, are reviewed in George Ojemann, Otto Creutzfeldt, "Language in humans and animals: contribution of brain stimulation and recording," in Handbook of Physiology, the Nervous System, volume 5, Higher Functions of the Brain, edited by Vernon Mountcastle, Fred Plum, Steven Geiger, pp. 675-699 (American Physiological Society 1987).

Chapter 15. Why Can We Read So Well?

For general background on language per se, see David Crystal, The Cambridge Encyclopedia of Language (Cambridge University Press 1987).

Antonio Damasio, Hanna Damasio, "The anatomic basis of pure alexia," Neurology 33:1573-1583 (1983).

Albert M. Galaburda (ed.), Dyslexia and Development (Harvard University Press 1993).

Margaret Livingstone, "Parallel processing in the visual system and the brain: Is one subsystem selectively affected in dyslexia?", in Dyslexia and Development, edited by Albert M. Galaburda (Harvard University Press 1993).

Paula Tallal, Roslyn Holly Fitch, "Hormones and cerebral organization: implications for the development and transmission of language and learning disabilities," in Dyslexia and Development, edited by Albert M. Galaburda (Harvard University Press 1993).

325 Alexia and attentional disorders are reviewed by Michael I. Posner, "Attention as a cognitive and neural system," Current Directions in Psychological Science, 1:11-14 (February 1992).

327 Margaret S. Livingstone, Glenn D. Rosen, Frank W. Drislane, Albert M. Galaburda, "Physiological and anatomical evidence for a magnocellular defect in developmental dyslexia," Proceedings of the National Academy of Sciences (U.S.A.) 88:7943-7947 (15 September 1991).

327 Dyslexia is more common in males, though with a somewhat smaller predominance than previously thought. See W. James, "The sex ratios of dyslexic children and their sibs," Developmental Medicine and Child Neurology 34:530-533 (1992). Evidence linking abnormalities in chromosome 15 to some cases of familial dyslexia is presented in S. Smith, W. Kimberling, B. Pennington, H. Lubs, "Specific reading disability: identification of an inherited form through linkage analysis," Science 219:1345-1347 (1983). A recent evaluation of Geschwind's hypothesis on the origin of dyslexia, allergies, left handedness and unusually good mathematical abilities is to be found in Albert Galaburda, "The testosterone hypothesis: reassessment since Geschwind and Behan," Annals of Dyslexia 40:18-38. More on mice with autoimmune and learning disorders can be found in V. Dennenberg, G. Sherman, L. Schrott, G. Rosen, A. Galaburda, "Spatial learning, discrimination learning, paw preference, and neocortical ectopias in two autoimmune strains of mice," Brain Research 562:98-104 (1991).

329 George A. Ojemann, "Some brain mechanisms for reading," in Brain and Reading, edited by Curt von Euler (Macmillan 1989), pp. 47-59.

331 The costs and patient numbers for the neurological disorders are those assembled by the Society for Neuroscience in 1993 from various federal sources. The 1990 estimate of 3.3 percent R&D expenditures is from Donald C. Harrison, "Science for the 21st Century: the coming biomedical revolution," in Preparing for Science in the 21st Century, edited by Donald C. Harrison, Marian Osterweis, Elaine R. Rubin (Association of Academic Health Centers, Washington DC, 1991), p.5.

333 Paperwork costs, see article and editorial in New England Journal of Medicine (5 August 1993).

334 Christina Enroth-Cugell, John G. Robson, "The contrast sensitivity of retinal ganglion cells of the cat," Journal of Physiology 187:517-552 (1966).

335 Ignorance abounds concerning how useful discoveries actually come about, and so legislatures tend to earmark research funds for specific diseases rather than allowing researchers to simply follow their well-honed instincts about "interesting problems."

337 The quotations from Lewis Thomas are reprinted with his permission and that of the New England Journal of Medicine, where they originally appeared. They may be found reprinted in Lewis Thomas, The Lives of a Cell (Viking 1974), pp. 36-42.

Chapter 16. Stringing Things Together

Recent overviews of human language cortical organization include the following:

Doreen Kimura, Neuromotor Mechanisms in Human Communication (Oxford University Press 1993).

George A. Ojemann, "Cortical organization of language," Journal of Neuroscience 11:2281-2287 (August 1991); "Cortical organization of language and verbal memory based on intraoperative investigations," Progress in Sensory Physiology 12:193-230 (1991).

David Corina, Jyotsna Vald, Ursula Bellugi, "The linguistic basis of left hemisphere specialization," Science 255:1258-1260 (6 March 1992).

339 George A. Ojemann, Catherine Mateer, "Human language cortex: localization of memory, syntax, and sequential motor-phoneme identification systems," Science 205:1401-1403 (1979).

341 J. P. Mohr, "Broca's area and Broca's aphasia," in Studies in Neurolinguistics, edited by Harry Whitaker, Hanna A. Whitaker (Academic Press 1976).

344 Many primatologists would expand Jane Goodall's list of 36 vocalizations in The Chimpanzees of Gombe (Harvard University Press 1986). But the point remains: the human list of meaningless phonemes is about as long as the chimpanzee list of meaningful vocalizations.

344 For hominid brain changes, see Dean Falk, Braindance (Henry Holt 1992). For a more general discussion of infolding, see John W. Prothero, John W. Sundsten, "Folding of the cerebral cortex in mammals," Brain, Behavior, and Evolution 24:152-167 (1984).

345 John Hughlings Jackson, "Remarks on evolution and dissolution of the nervous system." The Journal of Medical Science 33:25-48 (1887-88).

346 William H. Calvin, "A stone's throw and its launch window: timing precision and its implications for language and hominid brains," Journal of Theoretical Biology 104:121-135 (1983).

347 Otto Creutzfeldt, George Ojemann, Ettore Lettich "Neuronal activity in the human lateral temporal lobe. I. Responses to speech," Experimental Brain Research 77:451-475 (1989).

Otto Creutzfeldt, George Ojemann, Ettore Lettich "Neuronal activity in the human lateral temporal lobe. II. Responses to the subject's own voice," Experimental Brain Research 77:476-489 (1989).

Otto Creutzfeldt, George Ojemann, "Neuronal activity in the human lateral temporal lobe. III. Activity changes during music," Experimental Brain Research 77:490-498 (1989).

348 Doreen Kimura, "Sex differences in the brain," Scientific American 267(3):81-87 (September 1992).

349 Sequencing abilities as the key element in hominid brain evolution: see W. H. Calvin, The Ascent of Mind: Ice Age Climates and the Evolution of Intelligence (Bantam 1990).

349 A modern discussion of the confusions generated by talking of cortical specializations can be found in Robert Efron, The Decline and Fall of Hemispheric Specialization (Erlbaum 1990), pp. 3-16.

Chapter 17.

Deep in the Temporal Lobe, Across from the Brain Stem

The proper name of the usual epilepsy operation is anterior temporal lobectomy. Some background may be found in Wilder Penfield, Theodore Rasmussen, The Cerebral Cortex of Man (Macmillan 1950). The Latin appellation for the scarring of the uncus is mesial sclerosis. Our illustration of uncal herniation is adopted from that in John Nolte, The Human Brain: An Introduction to its Functional Anatomy, 3rd edition (Mosby 1993); note that the level of section is different on left and right sides, and that the uncus is actually located two-third of the way forward along the undersurface of the temporal lobe.

357 R. Ivnik, F. Scharbough, E. Laws, "Effects of anterior temporal lobectomy on cognitive functions," Journal of Clinical Psychology 43:128-137 (1987); Robert Efron, Paul Crandall, "Central auditory processing. II. Effects of anterior temporal lobectomy," Brain and Language 19:237-253 (1983); Robert Efron, Paul Crandall, B. Koss, P. Divenyi, E. Yund, "Central auditory processing. III. The `cocktail party' effect and anterior temporal lobectomy," Brain and Language 19:254-263 (1983).

363 Evidence that the reinnervation that is part of the repair process of human hippocampus in epilepsy may lead to further hyperexcitability can be found in Thomas Babb and others, "Aberrant synaptic reorganization in human epileptic hippocampus: evidence for feedforward excitation," Dendron 1:7-25 (1992) and Tom Sutula and others, "Mossy fiber synaptic reorganization in epileptic human temporal lobe," Annals of Neurology 26:321-330 (1989).

365 Five years after epilepsy surgery, those patients who are seizure free view their quality of life as having significantly improved, using several standardized measures. Those who were employed are likely to have a better job, and those who were in school at the time of operation and have joined the work force in the five years since operation are much more likely to be employed that are similar patients who were managed medically during those five years. Larry Batzel, Robert Fraser, "Resection surgery for epilepsy: outcome and quality of life," in Epilepsy Surgery, edited by Dan Silbergeld, George Ojemann, Neurosurgical Clinics of North America, 4:345-351 (April 1993). That study found, as have others, that in contrast to these two groups of patients, those who were out of school but unemployed seldom became employed even when their seizures were controlled by surgery. This is a major argument for considering surgery in adolescence for those patients with seizures not responding to antiepileptic drugs.

365 Michael M. Haglund, Linda Moretti Ojemann, "Seizure outcome in patients undergoing temporal lobe resections for epilepsy," Neurosurgical Clinics of North America 4:337-344 (April 1993).

365 "National Institutes of Health Consensus Conference: Surgery for Epilepsy," Journal of the American Medical Association 264:729-733 (1990). The conference concluded that resective surgery for epilepsy had been proven effective for control of seizures in appropriate patients.

365 One state, Oregon, initially tried to eliminate state funding for epilepsy surgery in their rationing effort to increase the availability of other medical care.

Chapter 18. In Search of the Narrator

The general background for this chapter may be found in W. H. Calvin, The Cerebral Symphony: Seashore Reflections on the Structure of Consciousness (Bantam 1989).

Christof Koch, Joel E. Davis, editors, Large-Scale Neuronal Theories of the Brain (MIT Press, 1994).

Michael S. Gazzaniga, editor, The Cognitive Neurosciences (MIT Press, 1994).

Marvin Minsky, The Society of Mind (Simon & Schuster 1985).

Antonio R. Damasio, "Synchronous activation in multiple cortical regions: a mechanism for recall," Seminars in the Neurosciences 2:287-296 (August 1990).

Francis Crick, Christof Koch, "The problem of consciousness," Scientific American 267(3):111-117 (September 1992). And their "Towards a neurobiological theory of consciousness," Seminars in the Neurosciences 2:262-276 (August 1990).

Howard Eichenbaum, "Thinking about brain cell assemblies," Science 261:993-994 (20 August 1993).

376 B. L. J. Kaczmarek, "Neurolinguistic disturbances of verbal utterances in patients with focal lesions of frontal lobes," Brain and Language 21:52-58 (1984).

376 The extrastriate visual area known as Middle Temporal (MT) in monkeys is sometimes called V5 because, in humans, it appears to be located on the border of occipital and temporal lobes, somewhat on the undersurface but mostly peeking around the lateral edge. The visual areas may have scaled up only about twofold between monkey and human, while the overall cortical area increase is more like tenfold. Consequently many of the visual cortical areas that in monkeys are located in the middle temporal lobe may, in humans, be much closer to the occipital lobe.

377 Antonio R. Damasio, Daniel Tranel, "Nouns and verbs are retrieved with differently distributed neural systems," Proceedings of the National Academy of Sciences (U.S.A.) 90:4957-4760 (1 June 1993).

Gregory McCarthy, Andrew M. Blamire, Douglas L. Rothman, Rolf Gruetter, Robert G. Shulman, "Echo-planar magnetic resonance imaging studies of frontal cortex activation during word generation in humans," Proceedings of the National Academy of Sciences (U.S.A.) 90:4952-4956 (1 June 1993).

378 John Hart, Barry Gordon, "Neural subsystems for object knowledge," Nature 359:60-64 (1992). Offers evidence for a major division between visually based and language-based higher-level representations. Some background is in The New York Times article, p. C3 (15 September 1992).

381 The areas of the lingual gyrus associated with color concepts are thought to be the homologues of the extrastriate visual areas known in the monkey literature as V2 and V4. See Hanna Damasio, Antonio R. Damasio, Lesion Analysis in Neuropsychology (Oxford University Press 1989).

382 Antonio R. Damasio, Hanna Damasio, Daniel Tranel, John P. Brandt, "Neural regionalization of knowledge access: preliminary evidence," Cold Spring Harbor Symposia on Quantitative Biology, 55:1039-1047 (1990).

Antonio R. Damasio, "Time-locked multiregional retroactivation: a systems-level proposal for the neural substrates of recall and recognition," Cognition 33:25-62 (1989).

384 Daniel C. Dennett, Consciousness Explained (Little Brown 1991).

384 Peter M. Milner, "A model for visual shape recognition," Psychological Reviews 81:521-535 (1974).

384 Andreas K. Engel, Peter König, Andreas K. Kreiter, Thomas B. Schillen, Wolf Singer, "Temporal coding in the visual system: new vistas on integration in the nervous system," Trends in Neuroscience 15:218-226 (June 1992). And Wolf Singer, "Synchronization of cortical activity and its putative role in information processing and learning," Annual Review of Physiology 55:349-374 (1993). See also Steven H. Strogatz, Ian Stewart, "Coupled oscillators and biological synchronization," Scientific American 269(6):102-109 (December 1993).

385 Venkatesh N. Murthy, Eberhard E. Fetz, "Coherent 25- to 35-Hz oscillations in the sensorimotor cortex of awake behaving monkeys," Proceedings of the National Academy of Sciences (U.S.A.) 89:5670-5674 (June 1992).

385 Temporal patterns of thalamic neuronal activity in humans that seem to be specific for particular semantic categories have been reported by Natalia Bechtereva and her associates at the Institute for Experimental Medicine in St. Petersburg. See N. P. Bechtereva, P. V. Bundzen, Y. L. Gogolitsin, V. N. Malyshev, P. D. Perepelkin, "Neurophysiological codes of words in subcortical structures of the human brain," Brain and Language 7:145-163 (1979). Temporal lobe neurons apparently with specific patterns of activity for specific words are illustrated in Otto Creutzfeldt, George Ojemann, Ettore Lettich, "Neuronal activity in human lateral temporal lobe. I. Responses to speech," Experimental Brain Research 77: 451-475 (1989).

386 Frances H. Rauscher, Gordon L. Shaw, Katherine N. Ky, "Music and spatial task performance," Nature 365:611 (14 October 1993). Listening to Mozart improves subsequent performance on spatial IQ tests by about nine points for perhaps fifteen minutes.

386 Peter F. Drucker, Post-capitalist Society (HarperCollins 1993).

388 Kenneth J. W. Craik, The Nature of Explanation (Cambridge University Press 1943), p. 61.

390 Ursula Bellugi, A. Bihrle, T. Jernigan, D. Trauner, S. Doherty, "Neuropsychological, neurological, and neuroanatomical profile of Williams syndrome," American Journal of Medical Genetics, Supplement 6:115-125 (1990). Language and cognitive functions in Williams syndrome adolescents, in contrast to age- and IQ-matched Down's syndrome adolescents. The Williams syndrome individuals exhibit an unusual fractionation of higher cortical functioning, with marked cognitive deficits, but selective sparing of syntax.

394 William H. Calvin, "The brain as a Darwin Machine," Nature 330:33-34 (5 November 1987).

394 Another example is the computational technique called the "genetic" algorithm, e.g., John H. Holland, "Genetic algorithms," Scientific American 267(1):66-72 (July 1992). By tapping evolution's creative power, genetic algorithms have become a widely used search technique, used in nonlinear symbolic regression, automatic programming, plant scheduling, etc.

The Darwinian thought story is continued in both 1996 books:
How Brains Think
(Science Masters), a Book of the Month Club Selection,
The Cerebral Code
(MIT Press)
are now in US bookstores.
399 William H. Calvin, "Islands in the mind: dynamic subdivisions of association cortex and the emergence of a Darwin Machine," Seminars in the Neurosciences 3(5):423-433 (1991).

400 Frederick David Abraham with Ralph H. Abraham, Christopher D. Shaw, A Visual Introduction to Dynamical Systems Theory for Psychology (Aerial Press, Santa Cruz, 1990). James Gleick, Chaos (Viking 1987), p.140.

400 John H. R. Maunsell, William T. Newsome, "Visual processing in monkey extrastriate cortex," Annual Review of Neuroscience 10:363-401 (1987).

402 William H. Calvin, "Error-correcting codes: Coherent hexagonal copying from fuzzy neuroanatomy," World Congress on Neural Networks 1:101-104 (1993). And William H. Calvin, "The emergence of intelligence," Scientific American (September 1994).

[The 1996 book, The Cerebral Code, has much more on this topic.]


Our first book, Inside the Brain (NAL 1980), has been out of print for years; while it also followed a patient named Neil through a day of neurosurgery, the present book is not a revision of that book. Except for several pages on psychosurgery and a few illustrations, this is an entirely new book using a similar literary device. Inside the Brain covers a number of topics, such as pain and regeneration, which we have not been able to include in this book because of our focus on the cerebral cortex. In the fourteen years between books, our understanding of cortical mechanisms has increased enormously.

INSTRUCTORS: You may create hypertext links to glossary items in THE CEREBRAL CODE if teaching from Chapters 6-8 of this book, e.g.,
<a href=http://www.williamcalvin.com/bk9gloss.html#postsynaptic>Postsynaptic</a>

Conversations with Neil's Brain:
The Neural Nature of Thought and Language
(Addison-Wesley, 1994), co-authored with my neurosurgeon colleague, George Ojemann. It's a tour of the human cerebral cortex, conducted from the operating room, and has been on the New Scientist bestseller list of science books. It is suitable for biology and cognitive neuroscience supplementary reading lists. ISBN 0-201-48337-8.
AVAILABILITY widespread (softcover, US$12).
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