Defect memorizing of hippocampal-mammillary · psychiatrists like Seglas (1895), Regis (1923), and Dupre (1903) wholooked on the memory disorder as a mental aberration and stressed

J. Neurol. Neurosurg. Psychiat., 1963, 26, 127

Defect of memorizing of hippocampal-mammillaryorigin: a review

JACQUES BARBIZET

Paris

The history of 'amnesie de memoration' has evolvedthrough three stages. The first, a clinical one, startedin 1887 with Korsakoffs description of a morbidassociation characterized by two basic criteria.These were, first, a psychological disorder associatedwith degenerative polyneuritis, and secondly amental syndrome which included a special form ofamnesia. This syndrome captured the attention ofpsychiatrists like Seglas (1895), Regis (1923), andDupre (1903) who looked on the memory disorderas a mental aberration and stressed the interest ofthe psycho-polyneuritis syndrome, the clinicalactuality of which had been fully accepted. How-ever, the semeiotic significance of the amnesicsyndrome described by Korsakoff was not over-looked by authors like Bonhoeffer (1904) in Germanyand Chaslin (1895; 1912) in France. As pointedout by Angelergues (1958), Chaslin must be praisedfor emphasizing the importance of Korsakoff'smental syndrome which he was to define as asymptomatic triad of amnesia, fabrication, anddisorientation.

Jean Delay, in his book on disorders of memory(1942), directed interest to the type of amnesia, andhis thorough analysis led him to discard the con-ventional expression of 'fixation amnesia' and toadopt that of 'amnesie de me'moration' (defect ofmemorizing). A further stage in the elucidation ofthis type of amnesia had been started a few yearsearlier with the work of Gamper (1928), who insistedon the role of the mammillary bodies, and this hasdeveloped further through the more recent works ofScoville and Milner (1957) and of Penfield andMilner (1958) on the role of the gyri hippocampi.These studies now lead to the third stage (also madepossible by the present development of cyberneticmachines with memory capabilities), the study ofremembering in normal man.We know that remembering involves memorizing,

retention, and recalling, and by casting a new lighton the first of these three, a study of pathologicalconditions may enable us to analyse better theprocesses which go to constitute the complex mentalactivity referred to as memory.

CLINICAL FEATURES

Amne'sie de memoration is characterized by the in-ability to build new memories as opposed to thepreservation of those previously fixed, and this typeof amnesia is often associated with fabrication,including misrecognition and some disorientation.It has clearly defined features. The patient faces asituation, perceives and construes it, and reactsnormally, but he is unable to effect the neuronalchanges required to memorize, so that after a fewseconds he will not remember what he has justexperienced. Examples of such 'gradual forgetful-ness' are countless: the patient has forgotten the mealhe has just eaten, the visit he has just been paid, thequestion he has just been asked, the page he hasjust read, the hiding place where an object has beenconcealed a few minutes earlier, the object he hasbeen shown and asked to remember, and so on. Onepatient will not remember an application of faradiza-tion, although painful, and another will have norecollection of yesterday's air encephalography.Memory tests clearly demonstrate this dis-

sociation: the patient is able to reproduce on adraught-board the distribution of men he sees onanother board if ceaselessly referring to the modeland if proceeding one move at a time, but threeminutes later he is unable to reproduce by memorythe location of three or even two men. It is ofinterest to note that the 'capability of immediatememory' as assessed from the number of figures orof syllables reproduced immediately on hearingthem remains quite good, viz., about six digits forpatients in their fifties. Therefore, in such patientsthe condition does not affect immediate repetitionbut a more delayed type of memory, such as isrequired for an active memorizing process. Hencethe term 'amnesie de memoration' proposed byDelay (1942), which is preferred to the term 'fixationamnesia'.Owing to this failure to memorize, the patient

gathers no new acquisitions after the illness developsso that the period of retrograde amnesia widens fromday to day. To a certain extent therefore the duration

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of amnesia determines the date of onset of thecausative condition, and this will coincide accuratelywith the appearance of the responsible brain lesions.Thus, Maurice remembers the past 10 years of hislife accurately enough except that he has retained nomemory of the past year. When reminded of therefrigerator he bought eight months ago, or of atrip driving his relatives' car five months ago, he hasretained no recollection of these events. His memorygap coincided with the appearance of pyloric stenosiswith acute malnutrition, superimposed on a back-ground ofchronic alcoholism. Polyneuritis developeda few months later.The amnesic gap is not due to the fact that the

patient has forgotten but that he has not memorized.So much is this the case that no information can beobtained from him either about the history of hisillness or of his various periods in hospital. Thisdisorder involves also a spatial disorientation whichmakes the patient unable to locate his bed or hisroom. There is also a disorientation in time, so thata Korsakovian is liable to reduce a period actuallycovering several months to a few days.Though the lack of fixation is quite often a total

one, it can also be partial. This remaining capacityfor possible memorizing varies greatly with differentpatients. It can be a mere vague or unexpressedrecollection, as in one Korsakoff patient who dis-liked electrical treatment and would be upset andangry as soon as he saw the equipment, althoughhe then maintained that this was the first time he hadseen it. Other patients will be able, but after manyrepetitions, to remember such simple informationas the name of the hospital or the doctor, but thesefew and fragmentary acquirements will not enablethem to maintain an outline of daily events, most ofwhich will not be remembered at all.With no capacity to fix new elements, such patients

live from the items memorized and fixed before theirdisability developed.

It should be noted and emphasized that this stockof old memories remains relatively intact. Thepatient keeps at his disposal his native language andthose others he may have learnt in his youth; heidentifies and can quote by memory poems he usedto know. This holds true also for songs. He retainshis own aptitudes and physical abilities, and suchpatients will still be able to knit or to play chess,though they are respectively unable to learn a newpattern or a new game, even though of a muchsimpler type. Korsakoff reported the case of anauthor who could describe perfectly the literaryworks completed before his illness, but who, when itcame to a short story started just before the diseaseset in, could only remember the beginning: he had noidea of the way it was supposed to develop or to end.

Such patients therefore who no longer fix thepresent live constantly in a past which preceded theonset of their illness. Their disengagement fromthe present is, however, far from complete. Some areconscious of the disorder of memory, like Emilienne,who said: 'When I watch closely I know, but I soonforget. My brain feels like a sieve, I forget every-thing. Even in my tiny room, I keep losing things. Itall fades away'. Questioned on some events of theprevious day, most often she will merely say: 'I don'tremember'. However, if one insists and gives hersome details of these events, this stirs up some oldmemories which, mixed with the information justreceived, lead to an erroneous answer, sometimes ofsimple paramnesia, and sometimes a more elaborateand fabricated story; she remains hesitant, however,and unsure of her answer. Confronted with a doctorshe saw the day before, she says she does notrecognize him, but when pushed she answers: 'Imust have seen him last summer in Brehat'. Whenasked whether she is sure of this the answer is No.Thus, amnesie de memoration may be accompaniedby some awareness of memory difficulty. The param-nesia, misrecognition, and fabrication observed insuch cases are often suggested to a patient who haslittle confidence in his own answers.

In other instances, the patient is not aware of hisown inability to fix new facts, and consequently doesnot criticize his answers when these are drawn frompast memories and are used to clothe today's en-vironment and acquaintances. Thus, Germaine mis-takes the head nurse for her relative and the medicalstudent for her daughter. To Maurice, all doctors arecitizens from Murat, a town in his native Cantal.Both patients are unable to memorize the presentbut can tell without mistakes the events of theirchildhood, and it seems that fabrication is withthem an attempt to meet present situations using oldmemories in the absence of new ones, the acquire-ment of which has become impossible. These varioustypes of reaction will make it easier to understandthe way in which confusion may conceal memorydifficulties.

Pierre, a salesman in alcoholic beverages, abruptlyfell into a coma for several hours and experiencedsevere mental confusion on waking up. A fortnightlater, in addition to Parinaud's ophthalmoplegia,there remained a condition of agitation withdelirium. Pierre, visibly euphoric, pretends heknows doctors and medical students; he does notwant to stay in bed and addresses the medicalstudent as if he were a doctor himself and mustattend to other patients. Later on, he talks to hisroom-mates as though he were their commandingofficer, relieves men, gives orders, is mindful of theirfuture, and thinks he is in the Sahara or Morocco.

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He is completely disorientated in time and space; buthe still knows his wife who comes to see him. Tenminutes later, however, he will not remember hervisit. After a few days he is quieter but the inter-pretative delirium and fabrications continue: he is acommanding officer in the air force; he controls 100planes and has fought the Japanese. He is still dis-orientated in time and space and his old memoriesare few in number, inaccurate, and inconsistent.He has no ability to acquire new knowledge and ifhe correctly repeats the description and details givento him about a watch he is shown three minuteslater he can no longer remember them and seizes thewatch, claiming it belongs to him. However, he canimmediately repeat six digits correctly.

It is interesting to note that this severe confabula-tory delirium subsided in a few weeks to leave onlya few misrecognitions and compensatory fabricationslike those of the other patients described. These willin turn disappear, and memory tests will show agradual return of limited memory capabilities. Thepatient retains a total amnesia for the first six weeksof his illness.Apart from this basic disorder of amne'sie de

memoration, it is usual in Korsakoff's syndrome tofind disorders of temper or mood. According toAngelergues (1958), these are controlled by twofactors: the patient's previous personality and thenature of the aetiological factor. Alcohol addictsmay show either euphoric elation, or irritability tothe point of explosive fits of anger. In other patientsthere may be a prevailing anxiety with depressionand a desultory type of confabulation. Anothergroup, mostly that of presbyophrenics, showsapathetic indifference.Although the occurrence of this defect of memoriz-

ing is a well-established clinical fact, and althoughthe associated disorders also occur so constantlythat no one would today deny the existence ofKorsakoff's syndrome, it still seems necessary todefine its limitations and its associations.The coexistence of confusion with Korsakoff's

syndrome is frequent but this should not be con-sidered a constant feature and it has to be evaluatedseparately. Moreover, as has been shown in the caseof Pierre, it is not infrequent to see an initial con-fusion subside to give way to the amnesia syndrome,the analysis of which was impossible during the stageof confusion. Further, as has already been pointedout, the failure of memorizing may be one of thefactors which lead to mental confusion.The same comments may be made regarding the

varying degrees of dementia which may be found inassociation with Korsakoff's syndrome. The sameretrograde amnesia is found, but in addition there isa degradation of memories and of reactions acquired

before the lesions responsible for the syndrome. Insuch dementia there is impoverishment of the totalstore of memories, and also selective deterioration inthe functions of language and activity which lead tovarious stages and types of aphasia, agnosia, orapraxia.

Thus, when memory disorders are but one of theconstituent factors of confusion or of insanity, theclinical picture has extended far beyond the scopeof Korsakoff's syndrome. At times it may be dimmedby associated lesions, but the basic characteristic ofKorsakoff's syndrome remains the inability tomemorize. This condition develops under theinfluence of various lesions.

AETIOLOGY

Although initially described by Korsakoff as a com-plication of chronic alcoholism, the mental syndromediscussed above also appears in other circumstances,and Henri Ey's (1954) view is that it should nolonger be defined as a mere alcoholic psychosis.However, chronic alcoholism is still the largestpurveyor of Korsakoffs syndrome and we now knowthat it acts by way of related deficiencies in which thewant of thiamine plays a significant but not exclusivepart. Korsakoff's syndrome occurs in various ways.It may appear as one element in Gayet-Wernicke'sdeficiency encephalopathy where the amnesia isassociated with mental confusion, tonic motor dis-orders, and ocular palsies. On the other hand it maypresent as the after-effect of an encephalopathywhich reacted favourably to thiamine, or as aconfabulatory amnesia which is but a chronic mentaleffect of Gayet-Wernicke's disease. In other cases,Korsakoff's mental syndrome becomes the majorelement in a psychic disorder which developedinsidiously during an episode of polyneuritis; or inrelation to cirrhosis of the liver; or abruptly after anattack of delirium tremens.

Closely related to this relatively homogeneousgroup of deficiency encephalopathies may bementioned the confabulatory amnesic state whichmay occur in confusional conditions of toxic (e.g.,CO) or infectious origin.A second aetiological group is concerned with the

dementias. Thus, Wernicke's presbyophrenia ischaracterized by a variable background of psychosis(usually moderate in degree), with a typical picture offabricational amnesia and the loss of all ability tomemorize current events. Such psychotic syndromesare of frequent occurrence in old people, and thedeficiency of memorizing may prevail to such anextent that it becomes difficult to distinguish the con-dition from Korsakoff's syndrome. This difficulty

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has induced Bessieres (1948) to suggest the name of'Wernicke-Korsakoff's syndrome' for such forms.Head injuries present a third group of patients

with a defect in memorizing. Countless studies havebeen devoted to this subject since Kalberlah (1904)first observed Korsakoff's syndrome after trauma tothe skull. Roussy and Lhermitte (1916) and Bouttier(1918) reported interesting case histories in this field;Flament (1957), in a recent paper, presented athorough study of fabrication in cases of traumaticKorsakoff syndromes, with special emphasis on thefrequency of fantasies about the circumstances of theaccident. Ritchie Russell (1959) recently publishedan important monograph on the same subject.

In one of our cases, the patient, Emmanuel, a managed 31 fell from his bicycle and was comatose for48 hours. One and a half months after his accidenthe remembered nothing of the period since the injury.Memory tests showed good immediate perceptionand memory, but a poor score in tests of retentionfor longer periods. Thus, if he managed to memorizefive items after 60 seconds, 15 minutes later his scoreshowed a 50% loss. This loss would be complete thenext day when he would have forgotten the test aswell as a visit from his sister and son. Six months latereverything was back to normal and memory testswere performed properly, and the preservation ofnew memories was normal. Emmanuel also sufferedfrom retrograde amnesia, a phenomenon oftenobserved in post-traumatic amnesia.The fourth group of cases is those with brain

tumours. Angelergues (1958) mentions some char-acteristics of the Korsakoff syndrome due to cerebraltumour. Thus, clouding of consciousness is oftenevident, and there is greater variation in the syn-drome and a tendency to transient abnormalities,with later progression to a confused stuporous orcomatose condition. The interest of Korsakoff'ssyndrome developing with intracranial tumoursrests on the anatomical findings.

Finally, a last group is that of amne'sie de me6mora-tion seen after bilateral ablation of the hippocampusand of the gyrus hippocampi by surgery in whichthe amnesia may be compared with that duringcertain temporal lobe epileptic fits in which eventshave been experienced but not memorized (auto-matic behaviour), and may be interpreted as atemporary failure of the normal functions of thetemporal lobes and perhaps more especially of thegyri hippocampi.

This review demonstrated that disorders whichselectively affect memorizing will occur under theinfluence of different pathogenic factors. Whateverthe cause, however, these disorders lead to a failureto recall information received or events experienceda few minutes or a few hours earlier and, sub-

sequently, a permanent retrograde amnesic gap forthe period during which the disorder remains. Thisimpossibility of acquiring new knowledge contrastswith the preservation of normal perception and thecapabilities of immediate memory as well as withthe preservation of items memorized before thelesions appeared. All case histories are not identicalbut they all have this common pattern of amne'siede medmoration which can be supplemented by avariable amount of fabrication, retrograde amnesia,and even disorders of the aphaso-apraxo-agnosiatype. In spite of these varied causes, the constancyof the defect in memorizing is probably due to thefact that this syndrome is not controlled by the causebut by the localization of lesions which impair ordestroy structures which are essential to certainaspects of remembering.

PATHOLOGICAL ANATOMY

Two anatomical structures at the base of the brainseem to play a significant part in this defect ofmemorizing-the mammillary body and the hippo-campus-and the clinical connexion is a relativelyrecent discovery. Korsakoff suggested that thepsychic disorders he described were due to degenera-tion of the subcortical association tracts, but theonly case he studied with Serbsky (Korsakoff andSerbsky, 1892) revealed only neuritic lesions, and aproliferation of connective tissue at spinal cord level.No lesions of the brain were seen. After him, authorswho studied the pathological anatomy of thissyndrome adhered to the description of corticallesions. Although atrophy of the mammillary bodieswas described by Gudden in 1896, it was not untilthe year 1928 that their role was referred to byGamper in relation to the amnesia of Korsakoff'ssyndrome. In an anatomical study involving 16 cases,Gamper showed that the injury of the mammillarybodies contrasted with the integrity of the braincortex.The responsibility of the hippocampus in fixation

amnesia was assessed at a still later date. Primarilysuggested by anatomical and clinical observationson bilateral destruction of the gyri hippocampi(Campbell and Biggart, 1939; Grunthal, 1923;Conrad and Ule, 1951; Glees and Griffith, 1952),it has been confirmed by Scoville at operation.Scoville and Milner (1957) reported disorders ofmemorizing after therapeutic bilateral resection ofthe hippocampal area in mental patients. Terzian andDalle Ore (1955), Walker (1957), and finally Penfieldand Milner (1958) were to confirm these findings.

LESIONS OF THE MAMMILLARY BODIES The connexionof cases of amne'sie de me'moration with injuries of the

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mammillary body have been most clearly demon-strated in relation to alcoholic encephalopathies andin tumours of the base of the brain. In a remarkablydocumented paper published in 1958 all the argu-ments supporting Gamper's mammillary theory wereconfirmed by Delay, Brion, and Elissalde (1958a)in connexion with an anatomical and clinicalsurvey of eight cases of Korsakoff's syndrome ofalcoholic origin with lesions of the mammillarybodies but without significant injury to the braincortex.

1 Lesions shown in Korsakoff's syndrome areconstantly and selectively located in the mammillarytubercles. They are mostly glio-vascular andoccasionally neuronal lesions. There may beassociated lesions of the subependymal substantiagrisea of the hypothalamus and brain-stem from theanterior commissure to the pons.

2 There are no more cortical lesions in their casesthan in those described by Gamper (1928) or intwo-thirds of the cases described by Malamud andSkillicorn (1956). An association with neuronal orcortical lesions does at times occur, but this merelyreflects an associated intellectual degradation whichalso appears frequently in Korsakovians.

3 The anatomical process seen in Korsakoff'sdisease, histologically as well as topographically, isvery close to that of Wemicke's encephalopathy.The difference is a matter of degree; it is less acuteand the lesions are much less haemorrhagic, withless diffusion to the diencephalon and brain-stem.As regards lesions, mammillary injuries are the truecommon denominator of both conditions.Tumours of the base may also give rise to the most

genuine of Korsakoff's syndromes. Since the twocases reported by Baruk in 1926, a great manyothers have been reported and reviewed byAngelergues (1958): glioblastoma, craniopharyn-gioma and metastases, which, when involving thefloor of the third ventricle, may destroy the mammil-lary bodies and their connexions. In this respect, thesurvey of Williams and Pennybacker (1954) of 180cases of brain tumour in various sites is very interest-ing, as the authors reported 26 observations oncases with prominent memory disorders: 15 ofthese were of craniopharyngioma which developedin the third ventricle and the patients showed memorydisorders of the Korsakoff type, and in some agenuine Korsakoff's syndrome, while personality andintelligence were preserved.Amnesic conditions observed in connexion with

lesions of other parts of the brain are certainlyof a different type and are related either to frontalinattention, to a general deterioration, or tolanguage degradation. The type of injury varies inevery case. Mammillary bodies can be invaded and

destroyed or simply compressed by the tumour. Ad-jacent structures are often invaded, but neverthelessall these observations of basal tumours significantlyimplement the theory of a diencephalic origin ofmemorizing disorders with retrograde amnesia.The existence of Korsakoffs syndrome has also

been reported following wounds ofthe hypothalamus.Kleist (1934) reported several such cases withanatomical confirmation. Bender, Curran, andSchilder (1938) and Bender, Furlow, and Teuber(1949) described a case in which a shell splinterpenetrated the third ventricle, and von Czechmanec(1954) a similar case in which a grenade splinter hadlodged in the hypothalamic-hypophyseal area.

This aetiological survey of the mammillarytheory can be continued with the report of psychicsyndromes identical in every respect to Korsakoff'sdescription but following mammillary lesions ofencephalitic, vascular, traumatic, or senile origin.It should be noted, however, that in such cases thediffusion of lesions often interferes with the study ofthe anatomical correlations.

LESIONS OF THE GYRI HIPPOCAMPI Grunthal (1947)reported a case of rapidly developing psychosis inwhich the necropsy revealed bilateral softening ofAmmon's horns. This fact was confirmed in asimilar case of senile insanity observed by Gleesand Griffith (1952). In the history the Korsakovianelements-fabricated stories about the presentborrowed from past elements and misrecognition-were clearly distinguished. At necropsy the gyrihippocampi were seen to be completely destroyedon both sides, as was the gyrus fusiformis withdegenerated fornix; the mammillary bodies werenormal. The case reported by Conrad and Ule (1951)is less significant as the lesions of Ammon's hornswere accompanied by transneuronal degeneration ofthe mammillary bodies. Ritchie Russell and Espir(1961) reported several cases of wounds of the hippo-campal system with loss of memory.The experimental proof of the influence of the gyri

hippocampi was provided by the partial temporallobectomies made by Scoville and Milner (1957).These authors in eight patients made a more or lessextensive resection of the internal side of the tem-poral lobes, including the uncus and the foremosttwo-thirds of the gyri hippocampi. They assessedretrograde amnesia and found a severe defect ofmemorizing. This finding was confirmed by Penfieldand Milner (1958) who reached the same results intwo cases following a similar resection, but on oneside only. They thought that in both cases the gyrushippocampi on the opposite side must have beenabnormal and abnormality was supported by E.E.G.studies. It seems that the bilateral aspect of the lesions

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is an absolute requirement, as these authors nevernoted memory disorders in 80 other cases of similartemporal lobectomy on one side only. However,Ritchie Russell and Espir (1961) think that lesions ofthe hippocampus in the dominant side of the brainmay be particularly important for memorizing.An analysis of these case histories shows that the

memory disorders in such patients make them unableto repeat a story or to identify three items pointedout to them a few minutes earlier. Their perceptionand immediate memory capabilities are normal, andso are their formerly acquired memories as testifiedby their retaining, not only past memories, but theirlanguage and individual professional abilities. Insuch patients, there is no fabrication but theiranswers show a certain amount of paramnesia andsome erroneous interpretations. Here again, someretrograde amnesia had been demonstrated for theperiod preceding surgery. Therefore, this type ofoperation achieves an actual surgical syndrome ofKorsakoff in which there is a pure deficiency inmemorizing recent facts with little fabrication andeuphoria.These findings clearly indicate the part played in

man's memory by the mammillary bodies and thegyri hippocampi. Considering the close anatomicalconnexions between the structures of the hippo-campus and the mammillary bodies linked by thefornix, of which one is the foremost and the otherthe hindmost part (Fig. 1), it is tempting to view thewhole as an integral system. Nevertheless, severingthe anterior pillar of the fornix on both sides involvedno disorder of memory in the patients of Dott (citedby Ule, 1900) and of Cairns and Mosberg (1951).

im

FIG. 1. Diagram of the fornix. I Hippocampus; II mam-millary bodies; III hippocampal commissure.

From this anatomical and clinical survey we arein agreement with Delay, Brion, and Elissalde (1958 aand b) that the integrity of the mammillary bodies andof other structures anatomically connected to them,especially Ammon's horns, are essential in man tosubserve this special function of memory, thememorizing of recent facts.

PHYSIOPATHOLOGY

The basic disorder in this defect of memorizing isthe impossibility of using present stimuli in adelayed manner so as to memorize them for integra-tion into the whole sum of past acquirements. Thisinability to memorize new elements prevents thepatients acquiring new information so that the oldwill be the only available knowledge. It is thereforepossible to identify the onset of the pathological dis-order by careful questioning, running backward intime to those periods when memories were properlyfixed. This is especially clear after trauma wherelesions have appeared abruptly, but it can also beevinced in cases of more gradually appearinglesions, as in some alcoholic encephalopathies, byquestioning both the patient and his family. Thus, apatient will retain a clear memory of his childhoodand military life and a dimmer memory two or threeyears after becoming a bartender; a woman will callup recollections of her life up to the time of herhusband's death and is barely capable of fragmentarydata from the very period when she took to drinking.Once this disorder is complete and permanent theretrograde amnesia involved keeps increasing. Otherpatients in whom lesions are less severe or have partlysubsided, as happens in some alcoholic cases whichreact to thiamine, may retain a certain rate ofmemorizing and preserve some new facts, althoughmost often few in number and after much repetition.

In contrast to this basic disorder, pure forms ofKorsakoff's syndrome allow of the absence of percep-tion disorders when the patient retains his ability tograsp the present situation, any familiar object, word,or person being readily identified. Memory acquire-ments recorded before the lesions are retained,as evinced by the preservation of language, of pastmemories, of past techniques and habits. Let usquote again the case of Korsakoff's chess player whocould tackle on the chessboard any new situationcalling upon the familiar tactics but was unable tolearn the rules of a simple new game. The capabilitiesof immediate memory remain normal, as the patientis able to remember a series of six or seven digits.

In the present state of our knowledge, therefore,we can accept the view that this type of deficiency isrelated to bilateral lesions of the hippocampus-mammillary system, and it can occur as much from

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lesions of the mammillary bodies as from both gyrihippocampi.The various pathological degenerations which may

affect both structures are often more widespread, andassociated lesions either in the neighbouring greystructures or more diffusely affecting the cortex andthe whole brain will result in numerous cases inwhich there is confusion or psychosis and in whichthe memory disorder will exist, but it will lose itsautonomy and will be overshadowed in the picture ofmore general deterioration.

This leads us to the study of the physiopathologicalprocesses in symptoms which often accompany adefect of memorizing, viz., misrecognitions and dis-orientations, which have been considered as integralto Korsakoff's syndrome. It should be recalled in thefirst place that such companion disorders are lackingin many cases. The patient is aware of the disorderin his memory and, like my patient Emilienne, affirmsthat 'it all fades away'. When such disorders exist,they may appear in a variety of forms: from occa-sional paramnesia and misrecognition suggested bythe doctor, with the patient approving without beingsure of his answer, to severe fabrication deliriumassociated with disorientation in time and space, andto important disorders in temper and consciousness.

Various physiopathological processes may bementioned. Some see this as an active process, acompensatory attempt to re-create a seeminglyconsistent psychological content in spite of thesevere memory gaps involved by existing memorizingand recollection disorders. Such is the opinion ofPick (1915), who stresses the unconscious need tofill the gaps of thought, whence the 'compensatory'feature in fabrication. Such is also the opinion ofJaspers (1933) who considers such patients unableto reach an accurate result on account of their lossof basic associations. They unwittingly make upwhat seems the most likely to them.We think in fact that a Korsakovian reacts to the

present situation with what he has, that is, with hisstock of past memories, because he has nothing else.Stimulation will act as extracting stimuli which willstart old neuronal patterns acquired before themammillo-hippocampal lesion. Only in the incom-plete syndrome does one observe an attempt to usesome recent acquirements which, confronted withpast ones, result in a fabricated reconstruction of astory from the recent past.Whatever the process involved, another factor

enters: the patient's previous personality. Theamnesic's mental activity proceeds from his know-ledge, ideas, feelings, emotions, and instincts. Thequality of the disorder is likely to vary according totypes of personality and of background. Moreover,such is the opinion of Flament who has shown how4

a personality's deepest urges would influence thecontent of the fabrications.The part played by each of these factors-disorder

of memorizing, of recollection, desire for com-pensation, and the patient's previous personality-will vary in every case, which explains the widediscrepancy in the case histories studied. They canbe roughly classified as: 1 pure amnesie dememoration; 2 amnesie de memoration withfabrication and disorientation; and 3 amnesie dememoration associated with various grades ofaphasia, apraxia, and agnosia.

OPERATION OF MEMORY As this pathology indicatesa dissociation between the capacity to memorizeand the preservation of old memories, it is suggestedthat there must be different structures in the brainfor these two varieties of remembering. It seemsthat the hippocampo-mammillary system is essentialfor memorizing whereas retention of old informationrequires the integrity of the neuronal, cortical, andsubcortical areas which support memorized activities,say praxic, gnostic, or motor skill, or, to put it in adifferent way, sensory, intellectual, or motor.We may assume that the reshuffling of the numer-

ous stimulations which reach us at the same time-some being inhibited, others reinforced-produces a'common final stimulation' (to apply in the sensoryfield an expression used by Sherrington for motion)that reaches the brain. It seems that the integrity ofthe cortex is essential for its conscious perception,as localized degradations of the cortex result inspecific deteriorations of perception (agnosia ofsight, hearing). This common final stimulation is adynamic impulse, therefore, endowed with animmediate future which may be thought of as oftwo types. The impulse acts as an extracting stimulus,when it actuates a previously memorized circuitwhich will operate to yield, according to the mosaicsof its component nerve cells, either a motor,emotional, or verbal answer, or a sensation, or arecognition, these various activities embodying aconscious attitude adapted to the situation whichgave rise to the stimuli. In this case, consciousnesshardly records the extracting stimulus itself butrather the whole pattern of perceptions and re-actions it involves. In all the above cases, the com-mon final stimulation actually alters the subject'strain of thought or action but does not enrich hisstock of knowledge. It actuates old circuits withoutcreating new ones. In other circumstances, theinformation contained in the common final stimu-lation is not used immediately but stored forsubsequent availability. It is a conscious activity.The new information does not alter the presentsituation, but goes to increase the stock of memories.

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Jacques Barbizet

In this case, new circuits must be created. Of course,if both processes can occur independently, in normalsubjects this common final stimulation is very likelyto result in a joint action and to start an immediatereaction while it integrates into a new circuitconnected to old structures.One fact to emphasize is that the study of

Korsakoff's syndrome and its defect ofmemorizing isthe only one to allow the identification of both typesof reaction, thanks to the dissociation it involves.

THE MECHANISM OF MEMORIZING The hippocampus,fornix, and mammillary bodies are elements in amore extensive circuit reaching from the mammillarybodies through Vicq d'Azyr's bundle to the anteriorthalamic nuclei and from there to the cingular cortex.The cortico-cortical circuit thus connects the tem-poral cortex to the cingular one with an exchangewith the opposite hemisphere through the fornix(F-ig. 2). Papez (1942) confirmed its autonomy oncm1,%oyological grounds and Grunthal (1923) with,Bhylogenetic arguments. According to Gruinthal, themammillary bodies hold a very special position inthe hypothalamus; they should not be considered aspart of its vegetative structure but actually belongto a recently implanted autonomous system.Whereas Papez initially thought that this circuit wasthe theoretical anatomical basis of emotion, weknow today that lesions of the mammillary bodiesand of the hippocampus mostly result in amnesicdisorders. This brought Benedek and Juba (1941),and later on Orthner (1957), to agree that Papez'circuit plays a role in memory functions.

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There is an obvious risk in being too adventurous,and we know the outcome of considering variouscircuits as supports of different functions, whether oflanguage or motion coordination. Nevertheless,Papez' circuit is an anatomical identity which con-nects the temporal and cingulo-frontal cortex ofboth hemispheres and its interruption, as long as itis a bilateral one, at the levels of Ammon's horns andof the mammillary bodies, and prevents the memori-zing of recent facts.

Let us now come back to the functional aspect ofthe phenomenon of memorizing.The volley of sensory influx represented by the

common final stimulation has but a limited life;unused or overlooked it can no longer be used,e.g., the forgotten actions of the driver unable toremember how many times he has used the brake orthe gears during a given journey. It would be theproper role ofthe hippocampo-mammillar structures,as components in cortico-cortical association circuits,to retain such information and to effect an activeintegration by bringing the new information closerto one of several previously memorized elements.In fact, we remember new information in relationto old information, and it is exactly at the pointwhere we have located it that we shall come and lookfor it later on. The more carefully the structuralwork has been thought out, that is, the more con-necting points and bridges that have been establishedwith old acquirements, the more efficient the fixationand the easier the recollection. In this respect, weunderstand the significance of repetitions which willgive better structural opportunities, and the role of

FIG. 2. Diagram of thehippocampus-mammillarysystem and of the circuitofPapez.

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Defect of menmorizing of hippocampal-mammillary origin: a reviewv

structures which, owing to their central site and theiranatomical connexions, provide for the 'circulation'of information as long as is necessary for itsintegration in cortical and subcortical circuits whichsupport acquired activities, i.e., memorized ones.Remembering is a complex activity which, in order toselect what will be remembered, calls upon stockednotions, whether deep emotional motivations or'reasons', both depending on previous acquisitions.This shows the complexity of the structures involvedin memory, but, among them, the hippo-campo-mammillary system plays a major role sinceits destruction selectively prevents memorizing.

SUMMARY

Defect of memorizing (amnesie de memoration), firstdescribed by Korsakoff (1889), is characterized bythe inability to acquire new memories as opposed tothe preservation of previously fixed ones. Thiscondition is frequently accompanied by fabricationwith misrecognition and disorientation. On accountof the deficiency of memorizing, the patient acquiresno new memories and this gap will broaden fromday to day as a retrograde amnesia. Unable as he isto retain new elements, the patient lives on thememory stock fixed before his illness, and this isoften wholly preserved. Fabrication is a consequenceof such amnesia; a Korsakovian reacts to a newsituation with what he has, that is, with his stock ofold memories, because he has no others. In incom-plete forms only, an attempt to use new certainacquisitions may be found.Amnesie de memoration is often found in its pure

form, but it can coexist with confusion or insanityin which it is but one element.Amnesie de mimoration appears in various aetio-

logical circumstances: chronic alcoholism, by way ofdeficiency processes; toxic or infectious encephalo-pathy; Wemicke's presbyophrenia; skull trauma;tumours of the base of the brain. It is also found inbilateral surgical excision of the hippocampus. Thisimplies that this syndrome does not depend on thecause but on the location of the lesions.

It seems that two structures, the mammillarybodies and the hippocampus, play a predominantrole in defects of memorizing, whereas old memoriesrequire the integrity of various cortical and sub-cortical areas.Thus an organized sensory stimulation is likely to

start a joint action in normal subjects, viz., animmediate reaction plus the integration to a newcircuit related to old memories. The study ofKorsakoff's syndrome and of amnesie de memoration,

owing to the dissociation it brings about, helps toidentify and separate both types of reaction.

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Defect memorizing of hippocampal-mammillary · psychiatrists like Seglas (1895), Regis (1923), and Dupre (1903) wholooked on the memory disorder as a mental aberration and stressed