J. Neurolinguistics, Volume 4, Number 2, pp. 273-292, 1989.

Printed in Great Britain

091 l-6044/89 8.3.00 + .OO Pergamon Press plc

Paul Ivan Yakovlev and His Teachings on Cerebral Maturation and Asymmetries1

Andrk Roth Lecours2

Centre de recherche du Centre hospitalier Montr6alJ C&e-des-Neiges,

ABSTRACT Indications about the life and scientific career of Paul Ivan Yakovlev are presented in the first part of this paper. This is followed, in the second part, by a summary of his conceptions on the ontogenesis of the human telencephalon: his ideas concerning embryologically constrained distinctions (a) between telencephalon impar (rhinic). semipar (limbic), and totopar (supralimbic), as well as (b) between endokinetic (cellbound), ereismokinetic (body-bound), and telekinetic (object-bound) motilities are then discussed in relation to his teachings on primary (formal) as opposed to secondary (positional) symmetry. The third and fourth parts are devoted to Yakovlevs ideas concerned the asymmetries of the human brain; the research that he led with Pasko Rakic on the asymmetry of the pyramidal decussation and tracts is then summarized. The fifth and last part of the paper is based on an operational definition of the Yakovlevian notion ofmyelinogenetic cycle; a parallel is then drawn - in relation to differences in the moments at which auditory and visual information enter into play as parameters of functional ontogenesis as well as to differences in the functional determinisms of these two basic types of information - between the long biphasic cycle of the acoustic pathway as opposed to the short monophasic cycle of the optic pathway.

PAUL

IVAN YAKOVLEV

(1894-1983)4

The town of Turetz is located at 55,22 North and 29,15 East of the Greenwich meridian, at the median point of a line separating the Orient from the OccidenP. This is where Paul Ivan Yakovlev was born in December of 1894, the 15th according to the Julian and the 28th according to the Gregorian calendar. His

274

Journal of Neurolinguistics, Volume 4, Number 2 (1989)

aristocratic

mother

spoke

French

with members

of her family

(she considered

Russian to be a language one should speak with servants or at the market, but not with ones kins); his father was a retired imperial army officer who enjoyed taking his son for long walks in the snow. An orphan at the age of nine, Paul Ivan was sent to live in Wilno, with his widowed maternal aunt, who was the mother of three daughters and the director of a private gymnasium for girls. As an adolescent, Paul Yakovlev decided that he would become a philologist, perhaps an historian, or else a painter, or perhaps a sculptor. Then time passed and he changed his mind: he thought very highly of his fathers father, a military surgeon, and began to consider medicine as a potentially fulfilling career. An artist has to be a genius or else one isnt worth while , . . but in medicine allyou have to do is read books, remember it all and you know all the answers. In 1914, he obtained his baccalaureate from the Classical Gymnasium of Wilno. He was 21 years old, in 1915, when he was awarded a Sir Jacob Wylie Fellowshipband entered the Saint Petersburg Imperial Academy of Military Medicine, with the intention of becoming a psychiatrist, a doctor who would manipulate the soul, make it happier, healthier. During the period when Saint Petersburg was becoming Petrograd before it became Leningrad, Paul Ivan Yakovlev grew less and less interested in unleashing the secrets of the psyche and more and more in what was called in those days organic psychiatry, in which everything had to have a mechanical explanation. He studied histology with Alexandre Maximov, who was scholarly, H+th diligence qfpresentation, organic chemistry with Alexandre Borodine, who kept his grand piano in his laboratory at the Academy, and physiology with Vladimir Mikhailovitch Bekhterev, the founder of Russian neurology, who remained active although he had recently retired, and later with Ivan Petrovitch Pavlov, a most impressive and whose discussions man whose lectures on conditional reflexes were indeed fascinating, orientation was a topic of passionate antipsJ!chologj

extreme!) among the students of the Academy. This was a troubled period, but young Yakovlev had great masters and he was soon convinced that his own life could only be devoted to the acquisition of scientific knowledge. During the summer vacations of 1916 and 19 17, Paul Ivan Yakovlev served as a stretcher-bearer in the Imperial Army. Then came the October Revolution. Thereafter, the Academy was no longer Imperial though it was still a medical school, and a good one. In 1919, Petrograd fell prey to famine, typhus, Spanish influenza and civil war: the population was terrorized and confused. At the end of the year, Trotskys Red Army needed physicians: the students of the Academy therefore received their diplomas six months ahead of time, on 25th December. Paul Yakovlev was genuinely apolitical but he could not conceive how Russia might, in any future that he could now foresee, provide him with the opportunity to carry on

Paul Ivan Yakovlev and his Teachings

215

with his scientific

education.

Moved by a powerful

feeling of instinctive

biological to leave his Trachinski,

survival and after consulting with Maximov, he took the decision country. On the morning of 27th December, he and a Polish colleague,

pretending that they had been charged with a public health mission, boarded a train heading for the Finnish border where local Finn and White Russian as well as English, American and German troups were closely watching the movements of the Trotskyst army. In order to avoid showing theirmanufacrured.. . cerrificateand answering the questions of the red arm, inspector, the police, the inspector controlling the passports," the two companions navigated from one wagon to the next till they found themselves on the crowded rear platform of the train. Alongside the railroad tracks, there were snowy woods and, beyond the woods, the Gulf of Finland, frozen solid. In spite of bitter cold winds, Paul Yakovlev and his friend persuaded one another that the Gulf constituted the shortest and safest route out of Russia. Twenty kilometers or so before the border, in the middle of the night, dressed with several layers of clothes, they slipped off the slow moving train and they started walking in the snowstorm. Beside their certificates and diplomas, they carried black bread, bacon, a revolver, a compass, 800 Imperial Rubles and white blankets. The latter were used whenever the generators of searchlights were heard and beams rippled too close (one then flopped down, covered oneself, and hoped one had become invisible). At one point, Trachinski extirpated a bottle from his bag: it contained a pinkish mixture of laboratory alcohol and something else (cocaine?): Paul Ivans companion had stolen the ingredients at the Academy on Christmas Eve and the concoction now turned out to be of the greatest help. When the sun rose, on 28th December, the day of Paul Yakovlevs 25th Gregorian anniversary, the two reached the shore and sought safety inside empty barrels near a deserted cement factory. A dog passed by, sniffed at the terrorized fugitives, and wandered on: a stray dog that had long learned that minding ones own business was now a behaviour making ones survival more likely. With night coming, Yakovlev and Trachinski resumed their outing toward destiny. At the dawn of 29th December, as they emerged from the snowy bushes bordering on the Gulf, the pair were arrested by Finnish guards. Unbelievably, one of them recognized Paul Yakovlev from a previous visit to Petrograd. This made things easier but the comp>res were nonetheless sent to Coventry: the Finns accepted refugees from Russia only when sure that they were not attacked by typhus or some other dreadful disease. The two survived quarantine, shook hands, and parted forever: Trachinski was heading for Siam (where he intended to study butterflies). Paul Ivan Yakovlev spent a few months in Finland, attending to odd jobs in Helsingfors at one time and in AaboX at another time. He then decided that the day had come for him to find a place where he could resume his scientific quest: given the interest that he had in psychic disturbances resulting from brain damage, and

216

Journal of Neurolinguistics,

Volume 4, Number 2 (1989)

also given the advice of his professors

in Petrograd,

his target was the private clinic

which Hermann Oppenheim had opened in 1890, after having been denied Westphals succession by the Prussian Secretary of Education, and which had progressively outclassed the Charite as the international center of clinical neurology in Berlin (Weil 1970). The Russian in exile therefore presented himself at the German embassy with his Academy diploma and a few letters of recommendation written by his Russian professors: but Oppenheim had died earlier in 1919, before Yakovlevs mentors dated, wrote and signed their lettersand the recommendee was now suspected of counterfeiting. As these events required reflexion and reorientation, Paul Yakovlev decided to stay in Helsingfors a little longer. Until March 1920, he worked in the harbour where his job was to inspect a cargo of Swedish matches (Vu/can) that had been damaged by sea water: for a few months, he hand-picked boxes - dry matches on onesideand M-etones on the otherwhile pondering various scenarios: Germany being excluded, where to go next? France and the Salpetriere: after all. he was quite fluent in French and he had read everything that Charcot and his disciples and successors had written. In April, Paul Ivan Yakovlev boarded a ship to England. In London, as in the other great capitals of Western Europe, it was generally believed that Bolchevism would not survive and the Russian embassy had remained faithful to the Tzar: there, refugees would easily trade Rubles for Sterling. Yakovlev could survive and, after having by chance discovered the existence and seat of the British-Russian Brotherhood Society, he was even able to earn an extra hundred Pounds writing reports on the state of public health in Russia since the Fall of 1917. The fourth of October, 1920, was the day of the first commercial flight between London and Paris: Paul Yakovlev did not have enough money to buy a ticket and he experienced considerable frustration, but, the very same day, he procured a place on the boat-train that travelled from London to Paris via Doverand Bologne. In the Latin Quarter of Paris, Paul Ivan Yakovlev rented a room in Madame Bourdons boarding house, near the Pantheon. Of Madame Bourdon, he was later to say, with obvious fondness and gratitude, that she was very strict as to monthly payments but acted in a motherly manner with the petits metPques from Haiti, Paraguay and Mexico who were then her guests, including this petit metPque russe who, whatever the hour of day or night, paced back and forth his limited private space above the entresol dining room (Monsieur Yakovlev, vous Btes un maniaque!). A few days after his arrival in Paris, Yakovlev rang at Charles Richetsg door and told him that he came on behalf of a Professor Daniel Gardner, from Cambridge. He explained that he had met and befriended Gardner in London and he presented Richet with a recently written recommendation. Richet sympathetically introduced the young Russian physician to a dearest ,fiiend, Madame Abrikossov, one of the last of Charcots students, who had retained

Paul Ivan Yakovlev and his Teachings

277

friendly Fulgence

relationships Raymond

with the Salp&ri&re. Soon thereafter, des maladies and Joseph Jules Dejerine,

Paul Yakovlev

became

a stagiuire Ptrunger at the Clinique

du systeme nerveux

where, after

Pierre Marie had finally fulfilled his

desire to take over Jean-Martin Charcots chair. At the Faculty, Yakovlevs medical studies in Russia were recognized but, in view of local requirements, he would have to pursue further internship in obstetrics, paediatrics, gynecology and . . . infectious diseases. The candidate happily complied, agreeing that, at least for three out of four, these requirements appeared to be reasonable in view of the fact that he had graduated from a military institution. When Pierre Marie retired and yielded Charcots chair to Georges Guillain, Yakovlev went to work at the Pitit, next door to the Salpetritre, with Joseph Francois Felix Babinski: he had found the man who would guide him in his doctoral research and dissertation, and whom he would forever consider as his Mentor. It was at the Pitie that Paul Yakovlev began to develop an interest for the effects of sensory disturbances on motor behaviour; he became involved in discussions concerning cerebral lesions leading to paraplegia in flexion, a problem which one of his colleagues, Thtophile Alajouanine, was studying in the context of his doctoral research. Informed that his new student was somewhat needy, Babinski found a job for him: Yakovlev would work as an inrerne de nuit in a fashionable Neuilly Sanatorium, where many parients were politicians in need of temporary invisibility or rich American addicts taking a detoxication cure. Accommodations were exceptionally good and emergencies infrequent: the place was excellent for one who had an appointment in a large university hospital (the Pitie, then Sainte-Anne) and had to spend after-duty hours studying and writing a doctoral dissertation. Entitled Associations pithiato-organiques, i.e. motivated by one of Babinskis major preoccupations in those days, the dissertation was published at the end of 1924 - one year after Alajouanines - by the Presses Universitaires de France. Paul Yakovlev defended it publicly two days after the Epiphany of 1925 and his board of examiners was comprised of Professors Achard, Sichard and Balthazar! 11 At this point, Paul Ivan Yakovlev considered the prospect of pursuing his career in France. As a matter of fact, he enjoyed the idea but this scenario was excluded since it would mean having to take French citizenship, which in turn would imply waiting several years and regressing for a time to high-school level training and examinations. Other scenarios were also rejected: he remembered the ambiguous feelings he had experienced during a trip to Berlin, in 1923, and decided that his professional perspectives were no better in Germany than in France; and he definitely renounced the idea of returning to Russia where dust had not settled afier all. On the other hand, he was corresponding with Alexandre Maximov, who had migrated to the United States in 1921 and was now teaching at the University of

278

Journal of Neurolinguistics,

Volume 4, Number 2 (1989)

Chicago: Maximov now insisted that the land of opportunity for an ambitious scientist was no longer Western Europe but the USA. Moreover, Paul Yakovlev had had, as a patient in Neuilly, an American physician from Providence, Rhode Island: this colleague had introduced him to an attache of the American embassy in Paris; the attach& had an influential uncle who was an archbishop somewhere in Ohio; consequently, soon after defending his dissertation, Yakovlev was offered an extra quota American passport on the basis of his exceptionalproj&sional quallyications.12 He accepted without hesitation, packed his books, his brand new diploma from the Universite de Paris and a few other things and, on 15th March 1925, he boarded a ship leaving Le Havre for New York. In April, he became the assistant of a neurologist who was practicing in Providence; the newspapers told of (nothing less than) an eminent collaborator OjBabinski who had travelled all the way from Paris to Providence in order to complete his neurological training with a famous local practitioner. But the eminent collaborator found it difficult to live on 20 dollars a month and, above all, his idea of being a neuroscientist was indissociable from that of obtaining an appointment in a university of renown: Boston was the aim. At the Boston City Hospital, Stanley Cobb, William Lennox and Tracy Putnam had developed a major interest in epilepsy. Cobb and Lennox were preparing a monograph on the subject and a young enthusiastic competent polyglot neurologist who could review the foreign literature was a highly desirable collaborator. Paul Yakovlevs salary increased from 20 to 150 dollars a month: he served in the outpatients clinics of the hospital and, as a Harvard Research Fellow in Neurology, he read and took notes. The review was completed in June, 1926, and, in July, he began to work in Palmer, Massachusetts, as a neurologist and neuropathologist of the Monson State Hospital for the Epileptics. He had established good contacts within the Harvard Neurological Unit at the Boston City where, for several years, he would spend at least one week every month: he considered himself the Harvard liaison man at Monson. His research career had begun and his first American paper Epilepsy and Parkinsonism was soon to be published in the New England Journal of Medicine. In the Fall of 193 1, Paul Yakovlev borrowed 1000 dollars and travelled to Paris, then to Bern where the very first international meeting entirely devoted to neurology was taking place. This was for him the occasion to meet again with a man for whom he had the greatest admiration and respect: Ivan Pavlov, who had serenely begun his ninth decade, had travelled to Switzerland for the occasion. Harvey Cushing was also there to report on the more than one thousand cases of brain tumour on which he had operated, and no doubt to insist on the necessity of surgical treatment for patients with pituitary adenoma (now 78, retired and living on the C8te dAzur, Pierre Marie, whose studies of acromegalia have

Paul Ivan Yakovlev and his Teachings

219

become classical, although he has missed the adenoma, had not made the trip). After the meeting, Yakovlev took the train to Zurich where he spent seven months working with Mieczyslaw Minkowski (at Von Monakows Hirnanatomisches lnstitut) and acquired a Masters degree in neuroanatomy. Once in Zurich and as the result of Minkowskis intervention, he reclaimed the celloidin embedded anatomical specimen that he had brought in his luggage but had been forced to leave at the Swiss border in order to avoid the needle probing procedure of a zealous customs officer searching for smuggled diamonds. The specimen was the brain of a two year-old boy whom he had observed at Monson and whose autopsy he had performed. Remembering the Dejerines way of preparing brains in gapless serial sections, Paul Yakovlev planned to learn the technique in Minkowskis laboratory. He travelled back to New England in March, 1932, with heavier luggage: he brought back the slides of the first specimen of the Yakovlev Collection (a case of the condition which he would label as schizencephaly in a classical publication yet to come). Later that Spring, Paul Ivan Yakovlev received an appointment as Assistant in Neurology at Harvard Medical School. He then wed Mary McQuaid and spent his honeymoon in Montreal, a city he knew quite well as the result of a few gamboling expeditions during the prohibition years. Back home again, he started making plans to build his first giant microtome: modelled after a smaller one, designed and produced several years earlier by Milton and Robert GoddardiJ. Yakovlev remained at Monson until 1938, gathering materials for his Collection4, researching and publishing on topics such as neurosomatic deterioration in epilepsy, the anatomoclinical correlations of myoclonus in epilepsy, decerebrate rigidity, congenital ectodermoses, hepato-lenticular degeneration and paradoxical tendon reflexes. Paul Ivan Yakovlevs official baptism in Harvard Neurology (Livingston 1973) occurred in 1938 when he left Monson for the Fernald State School where, in 194 1, the Assistant in Neurology graduated to Instructor in Neurology. This was where he remained until 1947, relentlessly pursuing his researches: the giant microtome was perfected; new specimens were collected and prepared in serial sections. Topics already approached were further studied and new ones were tackled: tuberous sclerosis (and brain stones), the plantar reflex as a criterion of endurance preceded by locomotion and the plantar reflex in mental deficients as opposed to normals (Yakovlev remembered what he had learnt with his French Mentor), porencephalies (some of the most spectacular specimens of the Collection), Morquios disease, Hallervorden-Spatz disease, carbon monoxide poisoning, hydrocephaly, and so forth. In 1942, his postgraduate seminars in neurology and psychiatry, of which he later claimed that they were the beginning of continued education system in medicine (Kemper 1984), were published by the Waltham State Metropolitan Hospital (with the support of the Rockefeller

280

Journal of Neurolinguistics,

Volume 4, Number 2 (1989)

Foundation).

In 1942, with Roy Dennis

Halloran, and,

Paul Yakovleveven Harry

published Solomon,

a a

Course in Military Neuropsychiatry Manual of the same.

in 1944, with

Paul lvan Yakovlev thereafter spent four years at the Middletown State Hospital and at the Yale University Medical School as a Clinical Associate Professor of Neurology (1947-1951). He developed a training program which became very popular among Connecticut physicians, including residents and Faculty members. The first trinity paper - telencephalon impar, semipar, totopar; endokinesis, ereismokinesis, telokinesis (cf. infra) - was published in 1948; it was followed by publications on Hellers syndrome, various types of brain malformations, the anatomical substratum of seizures, and so forth. The Yale Venture came to an end due to divergencies with the local pundits qfpps?,~hoanal_vsis. Harvard knows a good man when it sees one, especially a man who has previously served Harvard and who is farmed out, so to speak, at another prestigious school. So Harvard invites Paul to come home (Livingston 1973): in 1951, he was appointed as a Clinical Professor of Neuropathology at Harvard Medical School. He thereafter went on with his research: the fronto-pontine bundle, fronto-thalamic projections, paraplegia in flexion (a tip of the hat to Theophile Alajouanine), meningo-facial angiomatosis, the cytology of the geniculate nuclei, the crowbar skull, leukodystrophies, the connections of the temporal lobe in man, cerebral calcifications, brain anatomy in mental retardation, the limbic nuclei of the thalamus and the connections of the limbic cortex, the cingulate gyrus and its cortico-cortical connections, stereotaxis, localization of thalamic lesions. handedness (cf. infra), myelinogenesis (cf. infra), Parkinsons disease, cerebral infarctions in the human fetus, the decussation of the bulbar pyramids(cf. infra), the development of the corpus callosum, and so forth: Paul Ivan Yakovlev was enjoying his Collection. In 195 1, he was elected President of the American Association of Neuropathologists. In 1954, with Singer, he published anatlas of the human brain in sagittal sections and, in 1974, with Angevine and Mancall, an atlas of the human cerebellum. Between the time of publication of the two atlases, Paul Yakovlev had been appointed consultant in neuropathology at the Peter Bent Brigham Hospital (1954) at the Childrens Medical Center (1956) and at the Massachusetts General Hospital (1961). He had become a Professor Emeritus (1961). the Curator of the Warren Anatomical Museum (1961); he had travelled the world overrs, and he had become a living legend (Figure 1). Year after year, he had been the respected fatherly and inspiring mentor of students and scholars from all over the world - in Derek Denny-Browns words, he has acted as a catalyst on generations after generations of neurologists and psychiatrists; he had taught clinical neurology, neuropathology, neuroembriology, neuroanatomy; he had explained the import-

Paul Ivan Yakovlev and his Teachings

281

ante

of seeking

relationships of behaviours,

between

brain

maturation

and the emergence Road, Brookline;

and

differentiation everyone

in humans

and in other animals;

he had invited he had

for sharp Cheddar

and vodka at 21 Addington

frightened everyone with his very peculiar manner of driving beat-up cars through the streets and tunnels of Boston; and he had earned both the indefectible friendship and the admiration of most. He lost neither when he relocated the Collection at the Eunice Kennedy Shriver Research Center, in 1969, and, in 1974, at the Walter Reed Medical Center. The Yakovlev Collectionrh: more than 1000 whole brains embedded in celloidin and prepared in gapless serial sections (27 tons of glass; Haleem 1984); brains of humans. monkeys, dolphins and other animals; normal brains and pathological

Figure 1.

Paul Ivan Yakovlev

(1 April 1982).

282

Journal of Neurolinguistics, Volume 4, Number 2 (1989)

ones; foetal brains, young brains, adult brains, senescent brains. The giant microtomes had been put to good use. And, with the Collection, the personal library: some 2000 books and 5000 reprints. Altogether, a material that has proven tremendously useful in the past and should remain available, now that Paul Yakovlev has died, on 16 June 1983, to be used by generations to come. Those who knew him will cherish their memories of the kind, sensitive, gentle man who was a trusted and loyal friend, advisor, mentor, confidant, and constant source of inspiration (Kemper 1984). TELENCEPHALON IMPAR, SEMIPAR AND TOTOPAR

As mentioned in the biographical notes above, the first specimen of the Yakovlev Collection, the one that Paul Ivan Yakovlev carried in his luggage during his 193 l-32 European trip, was the brain of a schiiencephalic child. As a matter of fact, it was not so much malformation per se that motivated his curiosity for this and several other gross embryological CNS anomalies (in particular those determined at the time of emergence of the optic vesicles), but rather what could be learned about the normal ontogenesis of cerebral structures and functions through the morphological study of genetic aberrations (Yakovlev 1952). In this respect, Yakovlevs teachings about the parity of telencephalic structures vs that of structures caudal to the telencephalon (Yakovlev 1948, 1963, 1968, 1970) remain of particular interest to anyone working in the field of neurolinguistics. Yakovlevs basic argument in this respect is that paired structures located caudal to the telencephalon emerge from two symmetrical anlagen - one left-sided and the other right-sided - belonging to the floor plate or to the roof plate of the neural tube, whereas the original anlage of the telencephalon is a single midline neuroblastic fountainhead located in the dorsal lip of the neuropore of His. The cerebellar hemispheres, for instance, arise bilaterally, from anlagen located in the rhombic lips of the neural groove. Cerebellar neuroblasts thus migrate from these two symmetrical fountainheads and converge, dorsally and medially, until fusion occurs at the level of the vermis. The symmetry of the cerebellar hemispheres is therefore labelled as primary symmetry in Yakovlevs lexicon. Quoting Kingsburry (1922) as his source with regard to embryological events, Yakovlev goes on asserting that the telencephalon, unlike more caudal CNS structures, has neither a floor plate nor a roof plate but originally emerges from a part of the lamina terminalis embryonalis (lamina reuniens of His), a midline structure which, during the fourth gestational week, immediately after the emergence of the optic vesicles, grows on the midline and completes - but for the anterior neuropore of His - the closure of the rostra1 end of the neural tube of the embryo, i.e. occludes its verticomedian slit.

Paul Ivan

Yakovlev and his

Teachings

283

Around the end of the fourth foetal week, the telencephalon is represented, immediately rostra1 to the optic vesicle, by a holosphere that is growing from the median fountainhead (located in the dorsal lip of the neuropore left open at the center of the lamina terminalis embryonalis). This holosphere is the anlage of the telencephalon as a whole but, more specifically, it is the anlage of the structures (including the septum, the para-olfactory areas, the olfactory bulbs and the hippocampi; Figure 2) which Yakovlev labels as telencephalon impar or rhinic brain. According to him, the notions of parity and symmetry, and therefore those of right and left, have neither morphological nor functional significance with regard to telencephalon impar. He insists that the mode of projection of telencephalon impar is essentially ablateral, and teaches that it is related to endokinesis, or cell-bound movement (e.g. peristaltis, cardiac beats). Around the sixth foetal week (when the embryo reaches seven or eight millimeters in length), the rate of neuroblastic proliferation increases in the lateral aspects of the holosphere, thus causing the emergence of a first pair of evaginations; ventrally, these remain continuous over the midline. This first pair of evaginations constitutes the anlage of all but the rhinic telencephalon but, more specifically, it is the anlage of the structures (including the cingular gyrus, the isthmus, the parahippocampal gyrus, the limen and the insula; Figure 2) which Yakovlev labels as telencephalon semipar or limbic brain. According to him, the notions of parity and symmetry, and therefore those of right and left, bear only limited morphological and functional significance with regard to telencephalon semipar. He insists the mode of projection of telencephalon semipar is ambilateral and teaches that it is related to ereiskokinesis, or body-bound emotional motility (e.g., pain, mimicry, swearing). From around the ninth gestational week, neuroblastic proliferation becomes comparatively very active in the fundi of the first pair of evaginations and this results in the rapid growth of a second pair of evaginations dorsalaterally to the first one. This second pair of evaginations constitutes the anlagen of those neocortical telencephalic structures (including those of the frontal, parietal, occipital and temporal lobes; Figure 2) which Yakovlev labels as telencephalon totopar or supralimbic brain. According to him, the notions of parity and symmetry, and therefore those of right and left, bear full morphological and functional significance only with regard to telencephalon totopar. He underlines the fact that only telencephalon totopar has a predominantly controlateral mode of projection and teaches that it is related to telokinesis, or object-bound voluntary motility (e.g. tool manipulation, articulated propositional speech). In order to appreciate Yakovlevs conception of parity and symmetry within the human brain, one therefore has to follow him in the opposition that he establishes between the primary symmetry of structures such as the cerebellar hemispheres
IEL 4:2-H

284

Journal of Neurolinguistics,

Volume 4, Number 2 (1989)

(cf. supra), which grow by convergence from two lateralized and symmetrical anlagen, and the secondary symmetry of structures such as the cerebral hemispheres which, in last analysis, emerge by divergence from a single median neuroblastic fountainhead, as would two leaves of a lotus from a common stem (Yakovlev 1968).

TELENCEPHALON IMPAR SEMIPAR

cl TOTOPAR
CINCULAR GYRUS WlDIUINT) CALwsuY CORnlS HIWOCAUPAL

ANTBRIOR COUUISSURD

--kJ -

Dl#NCEPHALON HIPPOCAMIAL

Figure 2.

Main Structures of Yakovlevs

Three Brains in the Adult.

Black: Telencephalon impar. Dotted: Telencephalon semipar. White: Telencephalon totopar.

THE YAKOVLEVIAN

TORQUE

Either because of dissociated rates in neuronal and/ or glial migration from the midline fountainhead and/or from secondary anlagen, or else because of postmigrational, i.e. of maturational phenomena such as would be, at the term of

Paul Ivan Yakovlev and his Teachings

285

synaptic competition, greater cellular elimination in a given cortical region as compared to its controlateral homologue, the supralimbic parity is, at least from the end of the seventh month of gestation, partly broken by regional asymmetries (Rosen and Galaburda 1985). Clearly, the best known such difference between homologue regions of the cerebral hemispheres is the one related to the speech area (Galaburda 1980; Galaburda er al. 1978a; Galaburda et al. 1978b) but these supralimbic asymmetries are often globally visible as a relative proeminence of the right prerolandic and left retrorolandic regions (Galaburda er al. 1978a), which represents part of the phenomenon that Yakovlev (1972) qualified as the torque of the human brain. As we will now see summarizing Yakovlevs research on the ontogenesis of the corticospinal tracts, telencephalic asymmetry will secondarily determine asymmetry within caudal structures in which there existed no asymmetry to begin with, i.e. in structures belonging with zones of primary parity (cf. supra). PYRAMIDAL DECUSSATION AND TRACTS

A topic which readily triggered Yakovlevs gift of the gab was handedness, which he invariably associated to his conceptions concerning telokinesis, or objectbound motility (cf. supra). Thus, his 1963 presidential address at the eighteenth annual meeting of the Society of Biological Psychiatry focused on this topic (Yakovlev 1963). His manuscript opens on Aristophanes assertion that Zeus had originally created man as a spherical entity, with eyes facing up to heaven and bottom firmly set on the ground, and that it was only at a later stage, after the creature had become proud and insolent, that the Thunderer split it, by way of punishment, into dimidiated hemispheres, with a right and a left side. In his concluding remarks, Yakovlev (1963) argues, that the preferential lateralization of the spearhead action to one side of the plane of bilateral symmetry, or handedness, is a unique property of organization of the specifically human telokinesis and he adds that there is growing evidence that preferential, either right or left, handedness in skilled acts of human dexterity is one of the most recent products of evolution, indissolubly bound with . . . language. With Pasko Rakic, Yakovlev (1966) later published a shorter and more factual paper on the ontogenesis (as of the 16th gestational week) and morphology of the corticospinal tracts, i.e. of the axonal system which he considered to be the privileged centripetal pathway of telokinesis. Yakovlev and Rakic (1966) first report on their study of the pyramidal decussation in 100 foetal and neonatal brains, Their finding in this respect is that, in more than 85% of the specimens, the first bundle to cross the midline (1) comes from the left hemisphere7 and (2) is bulkier than the immediately caudal bundle decussating from the right hemisphere; another finding is that, on the whole, more than two thirds of the specimens show a

286

Journal of Neurolinguistics,Volume 4, Number 2 (1989)

RIGHT

LEFT

PYRAMIDAL PATHWAY
Figure 3. Pattern of the Pyramidal Decussation and Dominance of the to

Right Pyramidal Pathway at Cervical Level (According Yakovlev and Rakic 1966).

greater number of fibers decussating from left to right than from right to left. Data on 130 foetal and neonatal cervical cords are then provided: in more than two thirds of the specimens, the number of direct pyramidal fibers is, at cervical level, greater on the right than on the left side. The authors summarize their observations by stating that with regard to corticospinal (pyramidal) innervation, the right side of the spinal cord appears to be the preferred (dominant) side (Yakovlev and Rakic 1966). In another publication, Yakovlev (1972) reports on his study of the pyramidal pathway in 105 adult specimens: dominance of the right cervical cord is present in 72 cases (80%); moreover, the few gross anomalies observed among the foetal specimens (total absence of decussation in three cases and, in another, total decussation from the left together with absence of decussation from the right) are not found among adult specimens 18.Yakovlev leaves it for his readers to ponder on

Paul Ivan Yakovlev and his Teaching

281

the eventual relationship between these data and the fact that most human beings are right-handed. MYELOGENETIC CYCLES

Although he had long been interested in myelination and had indeed discussed it at some length in the context of an earlier paper on morphological criteria of brain growth (Yakovlev 1963) Paul Yakovlev was nearly 75 years of age when he published his classical paper on the subject (Yakovlev and Lecours 1967). This is where he put forward the original notion of myelogenetic cycle as a regional parameter of brain maturation and empirically defined it, for any given axonal system, as the period extending from the time of foetal or early postnatal appearance of stainableI myelin sheaths in that system to the age when its stained bulk and tinctorial intensity are comparable, under the dissection microscope to those in the normal adult brain. Various fiber systems or regions may thus begin to myelinate early or late and, in either case, myelination can attain its apparent term more or less rapidly or slowly: among the specific radiations of the thalamus, for instance, the visual ones have a short cycle (Figure 4), the somesthetic a cycle of intermediate duration, extending from the ninth lunar month of gestation to about one and a half year postnatally, and the acoustic ones a cycle about three times longer than the latter (Figure 4); as to the nonspecific thalamic radiations, for instance those linking the pulvinar to the temporo-parietal cortex, they have a still longer cycle, with incipient myelination occurring about two months after birth and the process going on for about seven years thereafter before it is completed. Although he never thought in terms of cause-effect relationships, Yakovlev postulated that such differences in outset and duration of myelogenetic cycles somehow witnessed to a species-specific hierarchy of functional organization in the nervous system. When he wished, usually in the context of Sunday-afternoon discussions at the Warren Anatomical Museum, to illustrate the interest of his cycle concept as a parameter of functional brain maturation, one of Paul Yakovlevs favorite examples was that of the myelogenesis of the pre-thalamic and post-thalamic acoustic pathways, which he opposed to myelogenesis of their optic counterparts (Lecours 1975). Both components of the latter, the retinogeniculate and the geniculocalcarine, display short cycles, completed in one rapid spurt between the eighth foetal and the fourth or fifth postnatal month (Figure 4). Optic myelogenesis is therefore precocious and brief, and it is monophasic. In sharp contrast, acoustic myelogenesis is biphasic: largely prenatal and very brief in the helicogeniculate component, where the cycle begins as early as the 2 I st foetal week and is completed up to collicular level at the 34th, and up to thalamic level around the third or fourth

288

Journal of Neurolinguistics,

Volume 4, Number 2 (1989)

postnatal month; long lasting and entirely postnatal in the geniculotemporal component, where faintly myelinated fibers are first seen only at or around birth at term, and where the cycle is not completed before the child is three to four years of age (Figure 4). Yakovlev insisted that this sequence of events in anatomical maturation closely parallels the timetable following which the two corresponding sensory modalities enter into play as factors of behavioral development in the human foetus and infant. Early during gestational life, the foetus is submitted to gravitational (vestibular) and acoustic stimuli (movements of its own body, external sounds such as voices and music, and sounds of maternal life - cardiac beats, respiratory noises, borborigms and so forth - transmitted through the amniotic sac and the maternal body walls, i.e. through structures which are impermeable to photic information; in view of the precocity and shortness of the pre-thalamic acoustic cycle, Yakovlevs suggestion is that, during the earlier phases of human life, the central apparatus for the intergration of such stimuli lays in the tegmentum of the brainstem. Dramatic changes occur from the time of birth as to the types of inputs that besiege the newborns central nervous system. On the one hand, taught Paul Yakovlev, the relative importance of statoacoustic information decreases greatly as the now omnipresent visual informations enter into play as factors of behavioral development, and, if the short perinatal cycle of the retinocortical pathways is to be taken as a reliable indicator, rapidly assume a role which will remain physiologically unchanged from infancy to maturity. Acoustic informations, on the other hand, assume a radically different role, soon to be largely oriented toward speech acquisition; the existence of a chronological parallel is therefore striking between the long period during which this acquisition takes place and the protracted cycles not only of the post-thalamic acoustic pathway but also of

5m -------

I
Birth

iv

2v

3V

4v

Figure 4.

Myelinogenesis. Perinatal monophasic cycle of the optic pathway (A: pre-thalamic. B: post-thalamic). Biphasic cycle of the acoustic pathway (C: pre-thalamic, perinatal. D: postthalamic, postnatal and protracted).

Paul Ivan Yakovlev his Teachings and

u19

the corticocortical associations between the acousticcorticesand other regions ofthe hemispheric surfaces (Yakovlev and Lecours 1967; Lecours 1975). Clearly, such parallels should be of interest to those contemporary researchers working in the domain of neonate cognition, especially with regard to the prelinguistic abilities of the human newborn (Mehler and Fox 1985). As mentioned above, the myelinogenetic cycles of non-specific thalamic radiations is late-blooming and long-lasting. The same is true of those long association bundles, whether commissural or intrahemispheric, especially those to and from non-specific association cortices such as that of the inferior parietal lobule. The longest cycles of them all, and Yakovlev never missed an occasion to give credit to Theodore Kaes (1907) for having provided convincing documents in this respect, are no doubt those of the intracortical neuropil within such non-specific association cortices: there, myelinogenesis does not seem to begin before several years after birth and it lasts several decades at least; as a matter of fact, and although he never wrote this to our knowledge, Yakovlevsometimes wondered whethercompletecessation of myelination within the non-specific association neuropil might be a marker of beginning cognitive involution. Clearly, such observations and parallels should be of interest to those contemporary researchers working in the domain of cognitive senescence and senility, especially with regard to the changes that occur in language abilities among the elderly (Obler and Albert 1980, 1984; Ulatowska 1985).

NOTES 1. 2. 3. Work supported

Qubbec.

by Grant 6178 of the Fonds de la recherche en santC du

Faculte de Medecine, Universitt de Montreal. Centre de recherche, Centre hospitalier Cotedes-Neiges, 4565 Chemin QueenMary, Montreal, Quebec, Canada (H3W-1 W5). 4. Although with modifications, this section is to a large extent excerpted from a previously published In memoriam (Lecours 1986). 5. Direct quotes from Paul Yakovlev, printed in Italics, arefrominterviews led by Marjorie LeMay, Thomas Kemper or the author. 6. Jacob Wylie: of Scottish origin, the founder of the Saint Petersburg Imperial Academy of Military Medicine, was physician to Catherine the Great and Surgeon General of the Russian armies until his death in 1834. 7. Now Helsinki. 8. Now Turku. 9. Nobel prize in medicine and physiology, 19 13, for his discovery of anaphylaxis. 10. Who succeeded Guillain in 1947 (Lhermitte et al. 1981).

290 II.

Journal of Neurolinguistics,

Volume 4, Number 2 (1989)

12. 13. 14. 15.

16.

17. 18. 19.

And Henri Claude. Which I must admit were flimsy indeed, was later to add Paul Yakovlev. Who, Yakovlev insisted, was the inventor of the rocket*. For instance, two cases of paraplegia in flexion of cerebral origin (Kemper 1984). Including to his homeland, Paul Yakovlevs first trip back to Russiatookplace in 1958, in the context of a U.S. scientific exchange mission to the U.S.S.R.; while in Leningrad, 39 years after he had left Saint Petersburg, a hostess wondered where on earth could an American scholar have learned to speak Russian exactly the way her grandmother used to. Several other voyages to Russia followed thereafter: renting a car in Paris and driving alone to Leningrad was something he utterlyenjoyedduringthesixties. Yakovlevs travels to Russia included a period of several months of scientific work in Moscow, in 1978, as well as a farewell trip, in 1979, at the age of 83. There is no other collection of neuroanatomical material in serial sections consistently fixed, embedded, cut, stained and mounted to such exacting standards [. . .] the Yakovlev Collection is an irreplaceable reference material, patiently collected over a period of 42 years (Denny-Brown 1972, quoted by Kemper 1984). Yakovlev used to characterize this fact by saying that pyramidal axones from the left hemisphere have the right of way. Perhaps suggesting that such anomalies are not compatible with life. Using Loyez modification of Weigerts haematoxylin stain (Bertrand 1930).

REFERENCES Bertrand, 1. Paris: Masson. 1930 Techniques histologiques de neuropathologie, Denny-Brown, D. P.I. Yakovlev, M.D., Unpublished Manuscript, 1972. n.d. Galaburda, A. M. 1980 La region de Broca, Revue Neurologique 136,609-616. Galaburda, A.M., M. LeMay, T. L. Kemper and N. Geschwind 1978a Right-Left Asymmetries in the Brain, Science 199, 852-856. Galaburda, A.M., F. Sanides and N. Geschwind 1978b Human Brain: Cytoarchitectonic Left-Right Asymmetries in the Temporal Speech Region, Archives of Neurology 35,8 12-8 17. Haleem, M. 1984 Paul Ivan Yakovlev (1894-1983), in Newsletter, 2-3, J. D. Balentine (ed.), Charleston: The International Society of Neuropathology.

Paul Ivan Yakovlev and his Teachings

291

Kemper, T. 1984 Paul

536-540.

Ivan Yakovlev

(1894-1983),

Archives

of

Neurology

41,

Kingsburry, B. F. 1922 The Fundamental

parative Neurology

Plan of the Vertebrate Brain, Journal of Com34,46 149 1.

Lecours, A. R. 1975 Myelogenetic Correlates of the Development of Speech and Lanof Language Development, Vol. I, guage, in Foundations pp. 121-135, E. H. Lenneberg and E. Lenneberg (eds), New York: Academic Press. 1986 In Memoriam: Paul Ivan Yakovlev (1894-1983), in The Biological Foundations of Gesture, pp. I-10, J. L. Nespoulous, P. Perron and A. R. Lecours (eds), Hillsdale: Erlbaum. Lhermitte, F., A. R. Lecours and J. L. Signoret 1981 Theophile Alajouanine (I 890- I980), Brain and Language 13, 19 l196. Livingston, R. B. Presentation of a Portrait of Paul Ivan Yakovlev to Harvard Medical n.d. School, Unpublished Manuscript, 1973. Mehler, J. and R. Fox (eds) 1985 Neonate Cognition: Beyond the Blooming Buzzing Confusion, Hillsdale: Erlbaum. Obler, L. and M. Albert 1980 Language and Communication in the Elderly, Toronto: Lexington. Rosen, G. D. and A.M. Galaburda 1985 Development of Language: A Question of Asymmetry and Deviation, in Neonate Cognition: Beyond the Blooming Buzzing Confusion, pp. 307-325, J. Mehler and R. Fox (eds), Hillsdale: Erlbaum. Ulatowska, H. K. (ed.) 1985 The Aging Brain: Communication in the Elderly, San Diego: College Hill. Weil, A. 1970 Hermann Oppenheim (1858-l 9 19), in The Founders of Neurology, W. Haymaker and F. Schiller (eds), pp. 492-495, Springfield: Thomas. Yakovlev, P. I. 1948 Motility, Behavior and the Brain: Stereodynamic Organization and Neural Co-ordinates of Behavior, Journal of Nervous and Mental
Disease 107, 3 12-335. 1952

Malformations

of the Brain: A Neglected Source of Basic Knowledge

292

Journal of Neurolinguistics, Volume 4, Number 2 (1989)

on the Development
and Pediatrics

of Cerebral Structures and Functions, Journal

40,626-627.

1962 Morphological Criteria of Growth and Maturation of the Nervous System in Man, in Mental Retardation, pp. 3-46, ARNMD (ed.), New York: Grune & Stratton. in 1963 Telekinesis and Handedness: An Empirical Generalization, Recent Advances in Biological Psychiatry 6, pp. 2 l-30, J. Wortis (ed.), New York: Plenum. 1968 Telencephalon Impar, Semipar and Totopar: Morphogenetic, Tectogenetic and Architectonic Definitions, International Journal of
Neurology 6,245265.

1969 Localization of Lesions in theThalamus, in Bings Local Diagnosis in neurological Diseases, pp. 441-464, W. Haymaker (ed.), Saint Louis: Mosby. 1970 The Structural and Functional Trinity of the Body, Brain and Behavior, Current Research in Neurosciences 10,197-208. 1972 A Proposed Definition of the Limbic System, in Limbic System Mechanisms and Autonomic Function, pp. 241-283, H. Hockman (ed.), Springfield: Thomas. Yakovlev, P.I. and A.R. Lecours 1967 The Myelogenetic Cycles of Regional Maturation of the Brain, in Regional Development of the Brain in Early L$e, pp. 3-70, A. Minkowski (ed.), Oxford: Blackwell. Yakovlev, P.1. and P. Rakic 1966 Patterns of Decussation of Bulbar Pyramids and Distribution of Pyramidal Tracts on Two Sides of the Spinal Cord, Transactions of the American Neurological Association, pp. 366-367.