tion of generalized seizures. Directed field's latest book, "The Mystery of that bridge. Perhaps he is right, but frequently against misconceptions of the Mind", published in 1975,21 which many have been inspired by his efforts. Penfield's hypothesis, they have not yet was written when he was over 80 years His legacy to neurolo.gy and to hu- provided us with a better theory. of age. It was expressed beautifully manity will extend far into the future. On the other hand, microelectrode as follows: "The two units: 1) the studies of the firing of single brain mechanism, the action of which is es- References cells in waking animals and during sential to the existence of conscious- 1. PENFIELD W: Epileptic automatism and the neurosurgical procedures in conscious ness; and 2) the mechanisms of sensory- centrencephalic integrating system. Patterns man have provided strong support for motor coordination, may be said to of organization in the central nervous system. Res Pub! Assoc Res Neri' Ment Dis 30: 513, the anatomic specificity of a central constitute the central integrating sys- 1952 integrating system; for example, there tem. 2. Idem: The cerebral cortex in man: 1. The In their combined action they cerebral cortex and consciousness (Harvey are cells in the temporal or parietal make sensory input available and motor lecture). Arch Neurol Psychiatry 40: 417, 1938 association cortex that fire only during output purposeful." What a simple ex- 3. Mo.uzzi G, MAGOUN HW: Brain stem reti- attention or during intentional pression for the cular formation and activation of the EEG. goal- most highly complex Electroencephalogr C/in Neurop/zysiol 1: 455, directed movements, cells in the human mechanisms of the brain! 1949 4. PENFIELD W: L'&orce c.r.brale chez Ihom- thalamus that seem to respond only to Penfield's lifelong search for a better me. 1. L'.corce c.r.brale et Ia conscience. novelty or during the initiation of vol- understanding of the functional organ- Ann Psycho! 39: 1, 1938 5. JASPER HH, DROOGLEEVER-FORTUYN J: Ex- untary movements, and cells in the ization of the brain and its disorders perimental studies on the functional ana- tomy of petit mal epilepsy. Res Pub! Assoc brain stem that seem to be specifically during epileptic seizures is symbolized, Res Ners' Ment Dix 26: 272, 1946 involved in the regulation of states of in a way, by his hypothesis of the 6. PENFIELD W, JASPER H: Highest level seizures. cen- Ibid, p 252 sleep and waking.18 Refined neuro- tral integrating system. It is never to 7. PENFIELD W: Memory mechanisms. Arc/i Neurol Psychiatry 67: 178. 1952 chemical and histochemical methods be localized in any specific area of 8. Idem: Mechanisms of voluntary movement. and new techniques for the tracing of gray matter but in "wider ranging Brain 77: 1, 1954 9. Idem: Centrencephalic integrating system. anatomic pathways are rapidly adding mechanisms". It is a sort of conceptual Brain 81: 231, 1958 10. Idem: Neurophysiological basis of the higher further dimensions to our understand- bridge he has built between the brain functions of the nervous system. Introduction. ing of central integrating systems in the and the mind. He concluded that in Handbook of Physiology, vol 3, Neuro- we physiology, Washington, Am Physiol Soc, brain stem and cortex and their interre- shall probably never be able to cross 1960, pp 1441-45 11. PEN FIELD W, JASPER HH: Epilepsy and the lations, consistent with Penfield's hypo- Functional Anatomy of the Human Brain, thesis.19 Boston, Little, 1954 12. WALSHE FMR: The brain stem conceived as In his most recent reconsideration of ;.7. 4 -1. the "highest level" of function in the nervous the evidence,20 in 1969, Penfield re- system; with particular reference to the / OTPOTNETICAL\. ,' "automatic apparatus" of Carpenter and to ferred to "petit mal automatism" and STOEAB4OF . . the "centrencephalic integrating system" of ,, ,INPOLSES (VOLUNTARY)0 7I Penfield. Brain 80: 510, 1957 "generalized convulsion" as expressions FROM HIGHER BRAIN 13. PENFIELD W: Consciousness and STEM TO CEREBRAL / centrence- '.'¶.. 0B CORTEX // phalic organization, in Proceedings of the of two separate divisions of the hypo- % 00 First International Congress of Neurological thetical centrencephalic system that 11. %% . Sciences, Brussels, July 1957, VAN BOGAERT L, RADEMECKER J (eds), London, Pergamon, might be called mental and motor 1959, pp 7-18 (Fig. 3). In automatism ow. 1::. 14. AJMONE MARSAN C: Pathophysiology of the they become z '.'\ -- EEG pattern characteristic of petit mal epil- dissociated, so that preprogramed be- epsy, a critical review of some of the ex- '.. /4' perimental data, in The Physiopathogenesis of haviour that is coordinated and semi- the Epilepsies, GASTAUT H, JASPER HH, BANCAUD J, et al (eds), Springfield, IL, CC purposeful may continue during a petit Thomas, 1969, pp 237-48 mal seizure even though conscious 15. GLOOR P: Neurophysiological basis of gen- II eralized seizures termed centrencephalic, ibid, mental activity is arrested; "the same pp 209-36 neuronal mechanism ... may be paral- CORTICO-BOLBAR & 16. MARCUS EM: Experimental models of petit CORTICO-SPINAL TRACT mal epilepsy, in Experimental Models of Epilepsy, PURPURA DP, PENRY JK, yzed secondarily by bombardment from GRAY MATTER TOWER FOR D, et al (eds), New York, Raven Pr, 1972, an epileptogenic focus in frontal or OTFOTOETICAL BILATERAL pp 113-46 temporal cortical areas. The beginning MOTOR CONTROL 17. GASTAUT H, JASPER HH, BANCAUD J, et al (eds): The Physiopathogenesis of the Epilep- is different, the eventual automatism sies, op cit 18. JASPER HH: Neurophysiological basis of much the same". (It may be significant (.L. generalized epilepsies, ibid, pp 201-8 that the term "centrencephalic seizures" 19. Idem: Conclusions, ibid, pp 311-16 20. PENFIELD W: Epilepsy, neurophysiology and was not used by Penfield in this dis- some brain mechanisms related to conscious- FIG. 3-Penfield's most recent conception ness, in Basic Mechanisms of the Epilepsies, cussion.) of centrencephalic integration for "bila- JASPER HH, WARD AA, POPE A (eds), Boston. This view of the duality of central teral motor control", Little, 1969, pp 791-805 from his 1969 book20 21. Idem: The Mystery of the Mind, Princeton, integrating systems was refined in Pen- (p 801). Princeton U Pr, 1975

Neurochemistry

K. ALLAN C. ELLIQTT,* PH D, Sc D, FRCS

In the early 1 940s the Montreal Neuro- that time, however, brain chemistry sciences to lead to advances in the logical Institute (MNI) was already a was a weak subject, of interest to few promotion of health and the treatment leading centre of brain and nerve researchers. Wilder Penfield was not of disease. science. Neuropathology and neuro- himself versed in brain chemistry, yet In 1944 Penfield (and Herbert Jasper) physiology were developed and pro- he had a major influence on the extra- brought me from a little laboratory in ductive branches of this science. At ordinarily rapid development of this a psychiatric institute in Philadelphia subject in recent years. He had the in- to conduct chemical studies in Mont- *Former neurochemist, Montreal Neurological Institute; and emeritus professor of biochemistry, tuition that this field had to be nur- real on problems relevant to brain sur- McGill University tured and joined with the other basic gery and epilepsy. He invented the 1372 CMA JOURNAL/JUNE 18, 1977/VOL. 116 term "neurochemistry" and applied it the operating room so that I could informed many of us. I have been to our clinical and research laboratories appreciate the problems. My awe stim- especially affected by "The Mystery of and to my position, so that the first ulated a permanent interest in the the Mind".13 I have believed that the person to be officially called a neuro- mechanism of brain function and epi- mystery will remain, but Penfield chemist was at the MNI. Today there lepsy. With Penfield a group of us showed that concrete thinking, based are about a thousand recognized neuro- from various departments of the MNI on remarkable observation and ana- chemists around the world, many in published a survey of early studies on tomic-physiologic knowledge, can be various national and international or- epileptogenic areas of the brain.4 The applied to the mystery. With neuro- ganizations for neurochemistry. introduction to this article referred to chemical knowledge now added I be- I believe that our neurochemistry Penfield's earlier conclusion that there lieve the mechanisms behind the mys- laboratory was the first research labo- is a decrease in the richness of the tery are soon to be at least definable ratory of the MNI to become individu- capillary bed within an epileptogenic in much clearer detail. ally endowed. Penfield was able to focus, leading to the possibility of dis- The influence of Penfield has been communicate his intuition to W.H. turbance of homeostasis and conse- felt in tangible ways in his personal Donner and allowed me the pleasure quent local metabolic changes. Penfield works and in his organization and en- of imparting some of our enthusiasm also often expressed his idea that an couragement. But I, and I think others, to that friendly philanthropist, so in "x-substance" may be produced that have felt his presence in less definable 1951 it became the Donner Laboratory triggers the epileptogenic activity. In ways. There was warmth, yet with con- for Experimental Neurochemistry. my opinion these are valid and related trolled severity, an expectation of ex- In 1955 the first comprehensive sur- ideas. We now know that there are cellence and a benign dominance that vey of brain and nerve chemistry ap- a number of factors - electrolytes, keyed one up and also made one feel peared. Called "Neurochemistry",1 it metabolites and transmitter substances part of a whole vital enterprise. An was edited in our laboratory in colla- - that affect neuronal activity. Their era has ended. We must live without boration with I.H. Page and J.H. production and release are affected by Penfield. But he has made sure that Quastel. A second edition2 appeared in metabolic conditions, and they, to- we can. 1962. Thereafter it became no longer gether or individually, could corre- possible to condense the field into a spond to the "x-substance". Thus al- References "con- tissue meta- single volume. (An eight-volume most any study on brain I. ELuorr KAC: Neurochemistry, PAGE IH, densation" has lately been edited by bolism and the "action substances" of QUASTEL JH (eds), Springfield, IL, CC Thomas, 1955, p 900 Abel Lajtha in New York). nervous activity is relevant to the 2. Idem: Neurochemistry, 2nd ed, PAGE IH, Because of wartime concerns my problem of epilepsy. One of my first QUASTEL JH (eds), Springfield, IL, CC Thomas, 1962, p 1035 first research assignment at the MNI publications from the MNI described 3. ELLIOTT KAC, JASPER HH: Measurement of swell- a study of the metabolism of focal epi- experimentally induced brain swelling and was to work with Jasper on brain shrinkage. Am J Physiol 157: 122, 1949 ing in relation to head injuries.3 This leptogenic human brain tissue;5 Penfield 4. POPE A, MORRIs AA, JASPER H, et al: Histo- chemical and action potential studies on epi- influenced me to become Jasper's pupil was coauthor. leptogenic areas of cerebral cortex in man in neurophysiology and established the Much of our early work68 on brain and the monkey. Proc Assoc Nerv Ment Dis 26: 218, 1946 close relation of the Donner laboratory tissue metabolism, electrolytes, trans- 5. ELLIoTT KAC, PENFIELD W: Respiration and with neurophysiology that has ex- mitter substances and active amino glycolysis of focal epileptogenic human brain tissue. I Neurophysiol 11: 485, 1948 pressed itself in much further work. acids has been forgotten but it has led 6. ELLIOTT KAC, WOLFE LS: Brain tissue respiration and glycolysis, in Neurochemistry, The interest in brain swelling has re- to rapid and exciting developments in 2nd ed, op cit, pp 177-211 mained a major preoccupation of the many other laboratories. And such 7. WOLFE LS, ELLIOTT KAC: Chemical studies in relation to convulsive conditions, ibid, Donner laboratory and has involved work in many of these other labora- pp 694-727 cooperation with other departments tories is being carried out by our 8. ELLIOTT KAC: 'y-aminobutyric acid and other inhibitory substances. Br Med Bull 21: 70, within and outside the MNI. former students and coworkers. Mean- 1965 Penfield's feeling for the unity of while in our laboratory Wolfe has be- 9. WOLFE LS: Possible roles of prostaglandins in the nervous system, in Advances in Neuro- the sciences and their clinical aspects come an authority on, and contributor chemistry, vol 1, AGRANOFF BW, APRISON MH (eds), New York, Plenum Pr, 1975, promoted integration of the objectives to basic understanding of, various pp 1-45 and the work of the neurochemistry neurologic diseases,9'10 and Pappius has 10. WOLFE LS, No YING KIN NMK: Storage and excretion of oligosaccharides and glyco- laboratory with other aspects of the carried on our old interest in brain peptides in the gangliosidoses. Adv Exp Med MNI and the Montreal Neurological swelling and has become a leading Biol 68: 15, 1976 11. KATEMAN R, PAPPIUS HM: Brain Electrolytes Hospital. authority on cerebral edema.'1"2 and Fluid Metabolism, Baltimore, Williams in- Penfield's legacy to neurology is part & Wilkins, 1973, p 419 Penfield sought to integrate my 12. PAPPIUS H, FEINDEL W (eds): Dynamics of terests with the major interests of of his more universal legacy. His scien- Brain Edema, Heidelberg, Springer-Verlag, 1976, p 404 others at the MNI working in the field tific books and his historical novels 13. PENFIELD 'N: The Mystery of the Mind, of epilepsy. He would invite me into and other writings have pleased and Princeton, Princeton U Pr, 1975, p 123 The frontal lobe

DONALD HEBB,* PH D, D SC, LL D, FRS, FRSC

What Wilder Penfield did with respect theory of frontal lobe function and the emotion, abstract ideas, planning and to the frontal lobe can be reported basis of so-called frontal-lobe signs. In initiative were localized there, although simply. Ably backed up by William doing so he made fundamental changes those who reported loss of some Cone and the rest of the staff of the in our conceptions of brain functions. of these attributes following dam- Montreal Neurological Institute (MNI) Up to 1940 or 1945 the frontal lobes age to the frontal area were far from he changed the whole doctrine and were considered to be the locus of all agreeing among themselves just which *Emeritus professor of psychology and former that is noble and good about human was the crucial attribute. They did chancellor, McGill University beings. At various times moral ideas, agree, however, that the frontal area CMA JOURNAL/JUNE 18, 1977/VOL. 116 1373