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US pet ownership and demographics sourcebook. Schaumberg, Illinois: Center for Information Management, American Veterinary Medical Association, 1997 8 Blane D, Davey Smith G, Bartley M. Social selection: what does it contribute to social class differences in health? Sociol Health Illness 1993;15:1-15. 9 Davey Smith G, Morris JN. Increasing inequalities in the health of the nation. BMJ 1994;309:1453-4. 10 Davey Smith G, Ben-Shlomo Y. Inequalities in health: what is happening and what can be done? In: Scally G, ed. Progress in public health. London: FT Healthcare, 1997. 7 11 House JS, Landis KR, Umberson D. Social relationships and health. Science 1988;241:540-5. 12 Marmot MG, Theorell T. Social class and cardiovascular disease: the contribution of work. Int J Health Services 1988;18:659-74. 13 Kunitz SJ, Levy JE. A prospective study of isolation and mortality in a cohort of elderly Navajo Indians. J Cross-Cultural Gerontol 1988;3:71-85. 14 Davey Smith G, Harding S. Is control at work the key to socio-economic gradients in mortality? Lancet 1997;350:1369-70. 15 Olshansky SJ, Carnes BA. Ever since Gompertz. Demography 1997;34: 1-15.
Snapshots from the decade of the brain
Exciting, but no cause for triumphalism
Clinical review pp 1696-708
he last 10 years of the 20th century have been designated the decade of the brain. But, with the notable exception of the revolution in brain imaging, the explosion of activity in neurobiology has failed to capture the imagination of most doctors. To remedy this, we asked six neuroscientists to write about what interested them most. If you thought that visual processing was restricted to the striate cortex of the occipital lobes, turn to Adam Zeman’s article (p 1696). More than 30 separate cortical representations of the visual field have now been identified, and positron emission tomography is revealing what each contributes to the analysis of complex visual stimuli. Richard Gregory also discusses vision, though from a different point of view (p 1693). He asks (and suggests an answer) why real time sensory inputs should be associated with conscious perception. Consciousness, however one defines it, seems to be a property of the brain as a functioning system—not something that resides in individual neurones. Almost the opposite seems to be true of the way the brain keeps track of time. The central circadian clock is localised in the suprachiasmatic nucleus of the
hypothalamus, but, as Michael Hastings explains, single nerve cells from this area retain the capacity to show a 24 hour rhythm even when isolated in culture (p 1704). Ian Deary and Susan Greenfield tackle issues of more immediate clinical relevance. Deary discusses the validity of attempts to measure cognitive ability (p 1701), while Greenfield explores how recent discoveries about central neurotransmitters could be exploited for treating neurodegenerative disease (p 1698). Understanding how the brain works requires more than knowledge of the intricacies of neuronal connections and neurotransmitters. In the last article Steven Rose points out the limitations of our current reductionist concepts (p 1707). He is especially scathing about the tendency to attribute complicated patterns of human behaviour—homosexuality or aggression, for example —to genetic polymorphisms. Along with A M Daniels’ cow slaughtering piece (p 1728), it provides a salutary warning against triumphalist neuroscientific hype. Christopher Martyn Associate editor, BMJ
“No longer Gage”: an iron bar through the head
Early observations of personality change after injury to the prefrontal cortex
n September 1848, in Cavendish, Vermont, an incident occurred which was to change our understanding of the relation between mind and brain. Phineas P Gage, a 25 year old railroad foreman, was excavating rock. In preparation for blasting he was tamping powder into a drill hole when a premature explosion drove the tamping iron—1.1 m long, 6 mm in diameter, and weighing 6 kg—through his left cheek and out of the vault of his skull with such force that it threw him on his back and fell several rods behind, “smeared with brain.”1 Despite his injuries he remained conscious and only a few minutes later was sitting in an ox cart writing in his work book. He recognised and reassured Dr Harlow, who had been summoned to the scene. The wound continued to bleed for two days; then followed a virulent infection that rendered Gage semiconscious for a month. His condition was so poor that a coffin had been prepared. Nevertheless, Dr Harlow continued treatment, and by the fifth week the infection had resolved and Gage had regained consciousness. He was blind in the left eye and had left facial weakness but no focal neurological deficits. Had
the story ended there it would have been a remarkable account of Gage’s endurance and Dr Harlow’s therapeutic skill. What made the event historic, however, was Dr Harlow’s subsequent observations of the change in Gage’s personality. Immediately after physical recovery he described Gage as follows: “Remembers passing and past events correctly, as well before as since the injury. Intellectual manifestations feeble, being exceedingly capricious and childish, but with a will as indomitable as ever; is particularly obstinate; will not yield to restraint when it conflicts with his desires.” Dr Harlow reports that Gage’s employers, “who regarded him as the most efficient and capable foreman . . . considered the change in his mind so marked that they could not give him his place again. . . . He is fitful, irreverent, indulging at times in the grossest profanity (which was not previously his custom), manifesting but little deference for his fellows, impatient of restraint or advice when it conflicts with his desires. . . . A child in his intellectual capacity and manifestations, he has the animal passions of a strong man. . . . His mind was
BMJ VOLUME 317
19-26 DECEMBER 1998
15th. he died in status epilepticus. Our cry for 1999 is “let the news be new. or person. BMJ bans anniversaries We promise our readers no more boring anniversaries fter an orgy of anniversaries in 1998 and with the prospect of the mother of all anniversaries causing civilisation to grind to a halt in 2000. L9 7LJ Gage’s skull. therefore. 150th. almost a year before it happens. 3rd ed. 150 years of the Public Health Act. years.4 He would know that the cardinal function of the prefrontal cortex is the temporal organisation of behaviour supported by the subordinate functions of short term memory. the faculty of the attentive and intelligence observation. Boston Med Surg J 1848. the absence of paralysis in this case is quite in harmony with the results of experimental physiology. And yet. Walton Centre for Neurology and Neurosurgery. He then worked in livery stables. . 20th. weeks. and a dozen other unremembered anniversaries. but they were enfeebled in their manifestations. and that the phenomena of cortical lesions will vary according to their seat and also according to their character. affecting affect and emotion. and 500th anniversaries and so on for ever of the birth. Harlow JM. they had lost. important medical development. In 1860 he returned to his family in San Francisco. 200th. Ferrier D. Harlow might be surprised to read in a recent publication. “To date.39:389-93. Liverpool. to all appearance. Next year you will be missing (because we’ve already said no) the 50th anniversary of a famous BMJ paper on the fate of the foreskin. and we won’t call you. BMJ BMJ VOLUME 317 BMJ 1998. the 40th anniversary of the contraceptive pill in Britain. but not in degrees or quantity. while it is difficult to state in precise terms the nature of the change. institution. The prefrontal cortex: anatomy. Please do not contact us about the anniversary of your favourite institution. the BMJ is declaring 1999 an (almost) anniversary free year (because of popular demand Christmas will be retained). On the basis of experimental physiology he concluded.2:327-47. Dr Harlow observed that “mentally the recovery certainly was only partial. we are also banning days. and decades devoted to different diseases or age groups. Already we dread the day when the BMJ will be filled with nothing but obituaries. first in Vermont and then in Chile.”4 He could take comfort. Mr Gage travelled with his tamping iron throughout New England. I could perceive a very decided alteration in the animal’s character and behaviour.” (And once we’ve got over the decade of the brain (p 1673). “and that. So if we don’t give up marking anniversaries we will be overwhelmed. Fuster JM. the 200th anniversary of British government financial support for biomedical research. invention. and great paper and so on ad infinitum. A Anniversaries can silt up journals. 1997. so decidedly that his friends and acquaintances said he was ‘no longer Gage. 250th. that knowledge has remained by and large either ignored or shrouded in speculation. and inhibitory control.i:443-7. At Barnum’s Circus he displayed himself as a curiosity. 12 years after the injury.” Kieran O’Driscoll Consultant neuropsychiatrist John Paul Leach Specialist registrar in neurology Department of Neuroscience. and in May 1861. . his mental operations being perfect in kind. 50 (or is it 100?) years since the first randomised controlled trial. Consider the possibilities.317:1674 1674 19-26 DECEMBER 1998 www. death. And we are bored already by the millennium. Recovery from the passage of an iron bar through the head. 50 years since the first injection of cortisone. and journal and of every government act. without other apparent neurological deficits.” He noted that “while not actually deprived of intelligence. but not totally lost. 175th. 75th. . The Goulstonian Lectures on the localisation of cerebral diseases. physiology.bmj. and 175 years of the Lancet. following his injury.”3 Gage had through a tragic natural experiment caused Dr Harlow to observe what Ferrier’s animal studies later showed— that injury to the prefrontal cortex of the frontal lobes of the brain can cause profound personality changes.”3 Tracing the trajectory of the tamping iron through Gage’s brain he concluded that its track included the prefrontal region.4 The change in Gage’s personality would be consistent with damage to the orbitofrontal cortex of the ventral aspect of his frontal lobe. 100th. however. New York: Lippincott-Raven. Passage of an iron rod through the head. we are a step forward in our understanding of the relation between mind and brain and the reason why. And by definition this is cumulative.”3 On removing prefontal lobes in monkeys he had found that “removal or destruction by the cautery of the antero-frontal lobes is not followed by any definite physiological results .’”2 Unemployed. with the tamping iron 1 2 3 4 Harlow JM. 10th. This year we have celebrated 50 years of the NHS.) Richard Smith Editor. If Dr Harlow were alive today he would witness an explosion of research into the frontal cortex. 50th. in the knowledge that 150 years after his original observations. The consequence would be that the journal would be living permanently in the past.Editorials radically changed. Fazakerley Hospital.com BURNS COLLECTION . motor attention. He had developed epilepsy. notwithstanding this apparent absence of physiological symptoms. his intellectual faculties being decidedly impaired. BMJ 1878. It was 10 years before David Ferrier came to the rescue in the Goulstonian lectures of 1878. Mr Phineas Gage was “no longer Gage. but anniversaries might get there first. 150 years since Phineas Gage blew out his frontal lobes (p 1673). 25th. We could celebrate the 5th. Publ Mass Med Soc 1868. nothing like dementia. and year of great achievement of every individual. “There are certain regions in the cortex to which definite functions can be assigned.”2 Against a background of phrenology and Brocas’s writings on aphemia (1861) there was considerable resistance to Dr Harlow’s hypothesis. They are a boring device invented by public relations companies to hijack public attention. and neuropsychology of the frontal lobe.
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