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Impairment of recent memory after temporal lesions in man
Neuropsyehologia,
1964, Vol . 2, pp . 291
to
303
Pergamon Press Ltd. Printed in
England
IMPAIRMENT OF RECENT MEMORY AFTER TEMPORAL LESIONS IN MAN L . STEPIEN and S . SIERPINSKI Department of Neurosurgery, Polish Academy of Sciences, Warsaw, Poland (Received 3 July 1964)
Abstract-Five cases of recent memory impairment following unilateral temporal lesions are described. In three patients auditory and visual recent memory disturbances were produced by the epileptogenic lesion in one hippocampat zone giving afterdischarges in both temporal lobes . In all these cases recent memory deficit cleared completely after unilateral temporal lobectomy when EEG examinations showed no more abnormalities in the contralateral temporal region . In one patient in whom left temporal lobectomy was performed because of a malignant glioma grave impairment of auditory and visual recent memory was revealed 6 months after operation when the tumour began to generate EEG abnormalities in both temporal lobes . The last patient showed selective impairment of verbal recent memory following strict unilateral lesion in the left hippocampal zone . 1 . INTRODUCTION
THERE is now a large body of evidence to show that the medial temporal region and in particular the hippocampal complex is intimately and critically concerned with recent memory processes in man . In 1899 BECHTEREW [1] demonstrated a patient with prominent memory disturbances caused by bilateral softening of the temporal lobes mainly of the gyrus uncinatus and cornu Ammonis . Over 50 years later, GLEES and GRIEEITII [2] described a case-history of a 58 year old woman, who presented grave disturbances of recent memory with loss of emotional drive presumably after vascular accident . She died 15 years later after a series of grand mal attacks . On neuropathological examination the authors observed bilateral cystic degeneration of the hippocampus and of the hippocampal and fusiform gyri . Onn the basis of this case and the case reported five years earlier by GRiiNTHAL [3] they came to the conclusion that the hippocampus and the neighbouring structures are necessary for the maintenance of recent memory and normal mental activity . SCOVILLE'S psychosurgical operations must be considered as most important for elucidation of the problem of recent memory . SCOVILLE et al. [4] performed in 19 schizophrenic patients three different types of operations on the medial surface of the temporal lobes . In 5 cases "bilateral uncotomy" was performed, that is, the resection of the uncus, periamygdaloid and prepytiform cortex . In 8 cases the operation consisted in the ablation of the entire medial cortex of the temporal lobe, including the anterior hippocampus and all the structures lying medial to the inferior horn of the ventricle-"bilateral medial temporal lobotomy" . In the last 6 patients "bilateral orbito-temporal lobotomy" was performed consisting in combining the second operation with the isolation of the orbital surface of the frontal lobe by the cortical undercutting technique . All the removals have been bilateral, extending for varying distances along the medial surface of the temporal lobe, in most instances to a distance of 5 or 6 cm from the temporal tip . It should be noticed that in none of these cases was any pronounced memory deficit observed at the time of operation . 291
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In a later paper ScovILLE [5] stated that in two patients, one epileptic and the other a psychotic "undergoing bilateral resection of the entire complex including the hippocampal gyros extending posteriorly for a length of 8 to 9 cm from the tips of the temporal lobes", there appeared "a very grave, recent memory loss, so severe as to prevent the patient from remembering the location of the rooms in which he lives, the names of his close associates or even the way to toilet and urinal" . Later, these two patients were subjected to formal memory and intelligence testing by ScovILLE and MILNER [6] . Disturbances of recent memory persisted without improvement all the time two and a half and three years after operation . I would like to cite one or two of numerous illustrations of this deficit . "Ten months ago the family moved from their old house to a new one a few blocks away on the same street ; he still has not learned the new address, though remembering the old one perfectly, nor can he be trusted to find his way home alone ." . . . "This patient has even eaten luncheon in front of one of us without being able to name, a mere half-hour later, a single item of food lie had eaten ; in fact, he could not remember having eaten, luncheon at all" (p . 14) . There was no deficit in early memories and technical skills as well as no deterioration in personality or general intelligence . The discovery of severe memory deficit in these two patients led SCOVILLE and MILNER [6] to study other patients who had undergone similar, but less radical resections of the medial temporal region . It was the conclusion of these authors that : "Whenever the hippocampus and hippocampal gyrus were damaged bilaterally in these operations some memory deficit was found, but not otherwise" . . . "Removal of only the uncus and amygdala bilaterally does not appear to cause memory impairment" (p . 21) . It is generally held that a loss of recent memory occurs only if the lesions of the hippocampal complex are bilateral . Nevertheless, there area number of instances in which lesions apparently limited to one temporal lobe were associated with a serious loss of recent memory [7-I1] . We now know that even unilateral temporal lobectomy may cause an immediate and grave loss of recent memory when there is interference with the functioning of the hippocampal zone of the opposite hemisphere by contralateral pressure, or when the EEG examination points to bioelectrical abnormalities in both inferior temporal regions . In view of these clinical observations it has become increasingly important to study experimentally in animals the hypothesis that bilateral ablations of the hippocampal complex would cause severe and lasting recent memory deficit . Unfortunately, the problem of recent memory was poorly investigated after hippocampal lesions in animals . The recent studies of ORRACH el al. [12], MCCLEARY [13], KA.NDA et al. [14] and THOMPSON and LANGER [15] indicate that injuries to various limbic structures impair performance on tasks which require the animal to withhold either learned or unlearned conditioned responses . However the significance of these studies is limited by the great variability of lesions performed by different experimenters and by the lack of appropriate and standardized tests for examination of recent memory function . As pointed out recently by KONORSKI [16], those tests used in the past, such as conditioned inhibition or trace conditioned reflexes, are open to criticism with regard to their potentiality as true indicators of recent memory performances in respect to the modalities of stimuli used in these tests . For this reason he has suggested the use of a new testing procedure which eliminates most of the criticisms . This test uses compound stimuli in which each stimulus is made up of two signals of the same sensory modality separated by a short interval which may be varied from one to five seconds or more . Within this modality a compound stimulus consisting of any two identical signals is a positive
IMPAIRMENT OF RECENT MEMORY AFTER TEMPORAL LESIONS IN MAN
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reinforced) conditioned stimulus while a compound composed of any two different stimuli is a negative (non-reinforced) conditioned stimulus, or vice versa. The interesting feature in this testing procedure is that the first signal has no significance in itself ; it can be part of either a positive or a negative compound stimulus . The correct response is possible only when the animal retains the trace of the first signal up to and including the time of the second signal, so that the two can be compared . Thus when the first component of the compound stimulus is applied the animal does not "know" whether he will get reinforcement or not, because this depends on the comparison of the second component with the first one . Consequently, the animal cannot anticipate a particular kind of reaction, as is the case in delayed responses or in other tests in which the first signal of the compound already determines the positive or negative character of the conditioned reaction . The above described test for recent memory was applied in experiments on dogs by CHORAZYNA and SrEPIEN [17] and on monkeys by STEPIEN et al. [18] . It has been shown that bilateral ablation of the so called "ventral auditory area", e .g . Sylvian gyri in dog or anterior part of the first temporal gyrus in monkey, may produce grave disturbances in auditory recent memory while visual recent memory was fully preserved . Similarly bilateral removal of the inferior temporal cortex causes severe deficit in visual recent memory performances in monkeys . After bilateral excisions of the hippocampal complex in monkeys general impairment of recent memory was observed ; the animals were unable to solve our test for auditory and visual recent memory . It should be mentioned that most of animals which were not able to solve our test after bilateral ablations could learn a new task such as simple discrimination, conditioned inhibition and compound stimuli discrimination without interval between signals . This strongly suggests that the deficit in these animals was one of recent memory or "holding" capacity rather than general impairment of solving the difficult task . To sum up, there is increasing evidence coming from clinical observations and from experimental work that bilateral hippocampal lesions may produce a striking deficit in all those tasks in which recent memory is an indispensable factor for a solution of a given problem . The purpose of this report is to describe five cases of recent memory impairment following unilateral temporal lesions studied by means of the methods which were developed by KONORSKI for animals . (i.e.
2. METHOD OF EXAMINATION OF RECENT MEMORY Examination of recent memory was that used in our previous study [10]. We applied the pairs of identical or different auditory and visual signals, the duration of each signal being two see, and the interval between them 10-120 sec . The patient was instructed to press the dynamometer connected with the recording instrument when the two signals of the compound auditory or visual stimulus would be identical and not to press, when the second signal would differ from the first one . When the patient showed no difficulty in solving this problem with an interval of 120 sec between the signals, the task was made more difficult by introducing in the middle of the interval an additional, distracting stimulus from another analyser than that involved in the recent memory test . Usually, we performed recent memory examinations before as well as after operation . The daily test session consisted of 10-30 trials . On the first sign of weariness we stopped the examination,
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3 . CASE REPORTS aged 15 years . The case of this patient is described in full detail in our previous report as Case 3 [10] . In summarizing this case, we may say that this is an instance of distinct recent memory deficit resulting from a lesion in the right hippocampal zone giving afterdischarges in both temporal lobes . After the removal of the epileptogenic focus in the right temporal and fronto-opercular region impairment of recent auditory and visual memory cleared completely . The control examinations performed several times during the last four and a half years after operation showed that the patient had no difficulty whatever in solving our test even when the interval between two signals was 120 sec and when the distracting stimulus was given in this interval . Case 1 . H.K.,
Case 2 . I .L ., a 17-year-old boy, was admitted to the Department of Ncurosurgery, Polish Academy of Sciences, Warsaw, on February 6, 1963, because of recurrent seizures since the age of 13 years, which had been increasing in frequency and severity despite treatment by various anticonvulsant drugs . His birth was normal and his early childhood has been uneventful ; but he had a period of high temperature and unconsciousness during three days at the age of 8 years . Seizure pattern : His attacks were ushered in by a sudden illusion of interpretation . The situation in which he found himself seemed suddenly "quite different", "unreal", and "unpleasant" . The voices and sounds were also "different" and the patient had a feeling of fear . After that, he stared and became unresponsive for several minutes . During this time he performed many automatic and fumbling movements with his hands and movements of mastication . Sometimes he would fall to the floor motionless and his limbs were held stiff. Occasionally he might go out of home and run ahead . These attacks appeared usually every day, occasionally many times a day . Physical examination : The neurological examination, skull radiographs, and air encephalograms were normal . The Wasserman test on blood and cerebrospinal fluid was normal . Electroencephalographic findings : Numerous EEG examinations were summarized by Dr. T. BACIA as follows : "The EEG's showed an active epileptogenic focus in the right temporal lobe in the form of slow-wave complexes and high voltage spikes with phases reversals . Sporadic sharp waves occurred also in the left temporal region" . Pre-operative examination of recent memory : The patient showed no impairment of memory for old events and he was able to repeat series of numbers or names of objects seen after three and even five minutes if only no distraction was given in the interval . Examination of recent memory showed that the patient was able to solve the auditory and visual test only when the interval between two signals was not longer than 30 sec and when there was no distraction during the interval. When the distracting stimulus was interposed between the two signals he was unable to do so . (Table 1) . Operation : On February 22, 1963, a right fronto-temporal craniotomy was performed . When the dun was opened the sulci and blood vessels on the surface of the brain appeared normal but there was some pallor of the cortex on the second and third temporal gyri . Etectrocorticography revealed abnormal discharges recorded from the whole temporal lobe most distinct from the posterior part of it (Fig . 1) . During resection of the temporal lobe it was stated that the brain tissue in the region of the amygdaloid nucleus was tough and yellow . A 7-5 cm temporal lobectomy was performed including the hippocampal complex (Figs . 2 and 3) . Post-operative course : After operation the patient felt quite well and no epileptic attacks were observed . The neurological examination revealed a left upper homonymous quadrantopsy, but otherwise the status was quite normal. Control EEG's showed residual abnormality over the right temporal region without epileptfform discharges . Test of recent memory : The examinations of auditory and visual recent memory were performed 2 and 3 weeks and 14 months after operation . They showed that the patient no longer had difficulty in solving the test even when the interval between two signals was 120 sec and when distraction was interposed between them (Table 1) . Thus we may assume that after the removal of an epileptogenic focus in the right temporal lobe which generated afterdischarges in both temporal regions, the disorder of recent memory has been removed . Case 3 . J .K ., a 23-year-old woman, was admitted to our department on January 28, 1963, with a history of recurrent epileptic fits since the age of 7 years . Her birth was thought to have been normal and nothing significant was noticed in her early childhood . Seizure pattern . The attack began with a sensation of gastrointestinal activity in the midline of the abdomen above the umbilicus or with a feeling of warmness and palpitation in the precordium which rose to the head. This was followed by a loss of consciousness and generalized convulsive movements or by a minor seizure in which she had a feeling of fear and used to perform some uncoordinated automatic movements with her hands . Sometimes she noticed things about her looked larger and nearer . She was very much afraid and called her parents
FIG . 1 . Case 2, IL . Operation photograph .
Lettered tickets indicate sites of electrographic abnormality : A-spikes, spike-and-wave complexes ; B, D-stow waves and spikes ; C---spikes ; E-sharp waves ; F, 1--spikes and phase reversals . White thread indicates the Sylvian fissure and the proposed frontier of excision .
Fju . 2 . Case 2 . I .L . Photograph of operation after right temporal lobcctomy . The insutaa is exposed by the removal .
Flc . 4 . Case 3, J . K . Operation photograph . Lettered tickets indicate sites of electrographic abnormality : A, B, 1-slow waves C, F spikes, spike-and-wave complexes ; D-sharp waves ; White thread indicates the Sylvian fissure and the proposed frontier of escis n .
Pie . 5 . Case 3, .I .K . Photograph of operation after anterior left temporal lobectomp .
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IMPAIRMENT OF RECENT MEMORY AFTER TEMPORAL LESIONS IN MAN
Results of recent memory examinations in 1 .L . before and after removal of epileptogenic region No distraction Distraction Interval in interval in interval between two signals Errors (see) Trials Errors Trials Table 1 .
Before operation Auditory recent memory : 10 20 30 60 120 Visual recent memory : 10 20 30 60 120 Auditory recent memory : 30 60 120 Visual recent memory : 30 60 120
10 10 20 30 20
0 0 0 19 14
40 30 20
25 21 12
10 10 30 40 15
0 0 2 27 9 After operation
30 25 10
18 14 7
40 50 40
0 0 1
30 40 30
0 0 0
20 50 40 30 25 50
0 0 0
E7o . 3 . Case 2, I .L . Brain charts showing extent of the right temporal lobectomy- broken line ; hippocampal gyros removed completely.
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In spite of treatment by various anticonvulsant drugs these attacks increased in number and severity and they might appear even every day . She became nervous, stubborn and began to have conflicts with other girls . She made slow progress in learning and repeated two classes in the first school . Physical examination : The neurological examination, the plain films of the skull and pneumoencephalography were entirely negative. The routine examinations of blood and cerebrospinal fluid were normal . Electroencephalographic studies have consistently shown an active epileptogenic area in the left temporal lobe characterized mainly by high voltage spikes with phases reversals . Sporadic sharp waves and waveand-spike complexes occurred also in the right temporal region (Dr . T. BAcM) . Pre-operative recent memory examination : The patient was of average intelligence and showed no impairment of memory for the distant past or loss of attention, concentration or reasoning ability. She was able to reproduce geometrical forms from memory and performed arithmetic tests well . She could easily remember day-to-day happenings and recognized the various members of the staff . But she complained of being forgetful and could remember very little of what she read . Her immediate reproductions of the short stories was very poor and after 10 minutes she could recall with great difficulties only some small fragments or nothing at all of them . Recent memory examinations by using our method revealed definite disturbances . The patient was able to solve the auditory and visual test only when the interval between two signals was not longer than 60 sec and when there was no distracting stimulus . But when the distraction was interposed between the two signals she was quite unable to solve the task (Table 2) . Table 2 . Results of recent memory examinations in J .K. before and after removal of epileptogenic region . Interval between two signals (see)
No distraction in interval Trials
Distraction in interval Errors
Trials
Errors
Before operation Auditory recent memory : 30 60 120
20 30 30
0 0 18
30 30 50
0 16 26
Visual recent memory : 15 30 60 120
20 20 30 60
0 0 1 39
20 30 40 50
0 0 27 26
After operation Auditory recent memory : 30 60 120
20 50 60
0 0 0
30 50 60
0 0 3
Visual recent memory : 30 60 120
20 40 70
0 0 0
30 50 60
0 0 0
Operation : On February 8, 1963, a left temporal craniotomy was performed . After cutting the dura the lateral aspect of the temporal lobe appeared more or less normal, but the second temporal convolution was larger than usual . Electrocorticography showed abnormal discharges recorded by the electrodes which had been placed on the temporal lobe ; slight abnormalities have been also revealed in the operculum frontale and premotor area (Fig. 4) . In order to guard against postoperative aphasia it was decided to remove the anterior portion of the temporal lobe . During resection marked abnormalities were encountered in the region of amygdaloid nucleus and hippocampus ; the grey matter was yellow and tough . The most conspicuous abnormality was found in the hippocampus . The line of removalwas 5 cm from the tip of the temporal lobe and followed a fissure line in which the vein of Labb6 ran, then turned and ran perpendicularly to the base and across it to the brain stem (Figs . 5 and 6).
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Fin . 6. Case 3, J .K . Brain charts showing extent of the anterior left temporal lobectomybroken line . Post-operative course : The post-operative course was uneventful and no epileptic attacks were observed . Control electroencephalographic examinations showed slight abnormalities in the left temporal region but no afterdischarges in the right temporal lobe . Test of recent memory : The examinations of auditory and visual recent memory were performed 3 weeks and 15 months after operation . The patient was able to solve the problem quite easily even with the interval between two signals 120 sec and with the distracting stimulus presented in the middle of the interval (Table 2) . In summary, in this case epilcptogenic zone in the left temporal region produced striking abnormalities in both temporal lobes resulting in distinct impairment of recent memory . After removal of the epileptogenic area the patient has no more attacks and her recent memory has been improved .
Case 4 . C .S., a 58-year-old man was admitted to our department on June 13, 1963, because of increased intracranical pressure, aphasia and right hemiparesis . The illness began three months previously with progressive headaches, disturbances of speech and weakness of the right arm and leg . Neurological examination revealed bilateral papilloedema, right homonymous hemianopsia, weakness of the lower portion of the right facial nerve, and of both right extremities ; the tendon and periosteal reflexes were all hyperactive on the right side. The patient had grave difficulties in naming, understanding and counting. The EEG's showed marked pathological activity predominantly in the posterior part of the left temporal region . Tumour of the left temporal lobe was diagnosed and because of the advanced neurological changes the operation was decided to be performed next day after admission . Operation : Under general anesthesia, a left temporal craniotomy was carried out on June 14, 1963 . When the dura was opened, marked changes in the temporal lobe were found . The Sylvian fissure was strongly elevated and the vein of Labbe slanted back farther posterior than usual over the temporal lobe . The first and second temporal gyri were enlarged and the fissures between them were flattened . The cerebral cortex of the anterior and medial part of the temporal lobe was anaemic and yellow . The puncturing of the second temporal gyros revealed just under the cortex a cystic tumour containing about 30 ml of xanthochromic fluid. The anterior part of the temporal lobe together with the tumour was then removed, including uncus and hippocampus . The brain tissue was destroyed by the invading masses of the tumour . The final line of resection is shown in the brain chart (Fig. 7). The posterior * part of the first temporal gyros was preserved. The second and third temporal convolutions were removed 6 cm from the temporal tip .
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7 . Case 4, C .S . Brain charts showing the extent of left temporal lobectomybroken line .
Histopathological examination of the tumour revealed the glioblastoma multiforme (Dr . J . WISLAWSKI) . Post-operative course : After the operation the patient became more aphasic . By the end of the second week aphasia and right hemiparesis were beginning to clear, although nomination and counting were still impaired. The patient received X-ray therapy and was discharged from the hospital . During 6 months after operation the patient has done rather well, He did not complain of headaches or weakness of right extremities . His speech was much better than before operation and his memory seemed to be normal . In January 1964 the patient became again more aphasic and paretic . At the same time grave disturbances of recent memory were noted . His wife said that he became forgetful and was not able to remember the every day events . He could read the same magazines over and over again without finding their contents familiar ; he did not remember the visits of his close friends . Several EEG examinations showed distinct abnormalities in the left temporal region producing afterdischarges in the right temporal lobe (Mgr. R . STADNICKI) .
Examination of recent memory : There was no impairment of attention or concentration. The patient was well oriented, recognized people and old surroundings . He was able to repeat nonsense syllables or series of numbers but he found it impossible to learn any difficult word associations or to remember 5 objects for as long as 5 min . He could not solve the most simple arithmetic tasks . The ability to solve our test for auditory and visual recent memory revealed very grave disturbances . He was able to perform the task only when the interval between two signals was not longer than 5 sec and when he was permitted to keep his attention upon it . But when the distraction was interposed between the two signals he was quite unable to keep in mind the first signal and very often he forgot that there was the first signal (Table 3) . In summary, in this case the malignant glioma destroying the left hippocampal zone has resulted in profound disturbances of auditory and visual recent memory . The lesion was unilateral but there is clear electroencephalographic evidence showing that the tumour caused bioefectricai abnormalities in both temporal lobes.
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Table 3 . Results of recent memory examinations in C.S. No distraction in interval
Distraction in interval
Interval between two signals (see)
Trials
Errors
Trials
Auditory recent memory : 5 10 30
60 50 36
2 32 18
52 50
34 31
Visual recent memory : 5 10 30
40 60 30
0 36 18
45 60
27 39 -
Errors
Case 5 . J .W., a 33-year-old houswife, was admitted to our department on January 8, 1964, with a history of headaches and epileptic attacks since 3 months . The attacks began with a sensation of heat in the neck and face. After this she lost consciousness and had general convulsions . There were altogether 6 attacks. Physical examination : There was bilateral papilloedema and slight paresis of the lower portion of the right facial nerve . Otherwise the neurological status was normal . The plain films of the skull showed the shifting of the pineal gland to the right side . EEG's revealed numerous slow wave complexes at frequencies between 2 and 3 per second from the left temporal lobe (Mgr. R, STADNICKI) .
. Fla
8. Case 5, J .W . Brain charts showing the extent of left temporal lobectomy-broken line .
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Operation : Tumour of the left temporal lobe was diagnosed and on January 22, 1964, under general anaesthesia a left frontotemporal craniotomy was performed . After dividing the dura, marked changes in the temporal lobe were noticed . The vessels in the Sylvian fissure were enlarged and elevated . The cortex of the second temporal gyros was destroyed by the tumour and no cyst was found . The removal of the tumour was accomplished by a resection of the second and third temporal gyri together with the hippocampal complex . The first temporal convolution was left intact The final line of removal is shown in the brain chart (Fig. 8). As measured from the anterior wall of the temporal fossa, the line of excision was 7 cm along the inferior temporal surface . The histological examination of the tumour revealed an astrocytoma fibrillarc (Dr . J . WISLAwSK1) . Post-operative course : The post-operative course was uneventful although the patient had very slight and transient difficulties in nomination of objects and in repetition of series of words . These disturbances appeared on the second day after operation and cleared completely after two weeks . The neurological examination revealed a right upper quadrantopsy but otherwise the status was normal . Post-operative EEG's showed marked abnormalities in the form of slow wave complexes over the left temporal region . Examination of recent memory : The patient was of an average intelligence and showed no impairment of memory for the past events and no dysphasia . The ability to solve our test for auditory and visual recent memory was fully preserved . She was able to perform the task even with 120 sec interval and with the distracting stimulus presented between two signals . At the same time the patient demonstrated a serious deficit in verbal recent memory tests . Although she easily repeated four or even five words immediately after she heard them she was quite unable to recall them after a lapse of two minutes or less if her attention has been diverted to another problem in the meantime . She did not know the names of doctors visiting her every day, including the doctor who operated upon her. She was not able to repeat after one minute even one name out of four names of doctors attending to the examination and belonging to the staff. Similarly she could not recall three abstract words (such as "hope", "gaiety", "pain"), numbers or objects after an interval of 1-2 min . Most often she repeated only two words correctly . In summary, in this case unilateral lesion involving the hippocampal complex of the dominant hemisphere caused severe impairment of verbal recent memory while auditory and visual recent memory was normal . 4 . DISCUSSION It is now almost generally accepted that recent or dynamic memory is intimately connected with circulating impulses in the reverberating chains of neurons, activation of which may persist for a relatively long time after the actual stimulation of neurons (HERB [19] ; KONORSKI [20]) . The evidence that the so called associative areas, i .e. the cortical areas lying in the immediate vicinity of the sensory projection areas, play an important role in recent memory processes is quite impressive . Recent experimental studies in animals support the view that recent memory traces of a given sensory modality may be irreversibly destroyed following lesions lying outside the sensory cortical projection areas (NEFF [21, 22] ; CHORAZYNA and STEPIEN [17] ; STEPIEN et al. [18]) . There is also increasing evidence that bilateral removal of the hippocampal complex in man produces grave and persistent loss of recent memory . Memory deficit in these cases is not specific to any one kind of sense modality as it used to be after ablations of the associative areas in animals, but is quite general affecting memory for all events subsequent to operation . The patient is unable to recall test material after a lapse of five minutes or less if his attention has been diverted to another topic in the meantime [5, 6] . The question of how these hippocampal structures contribute to recent memory processes is still a matter for speculation . In view of many afferent and efferent connexions between hippocampus and other cortical and subcortical areas of the brain it may be assumed that hippocampal lesions cause a disruption of reverberating neuronal circuits important for certain memory processes and recording of new experience . The results of experimental and clinical investigations seem to show that unilateral lesions situated in the ventro-medial parts of the temporal lobe--independent of the side
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(dominant or subordinate hemisphere)-do not produce an impairment of recent memory (MEYER and YATES [23] ; PENFIELD and MILNER [9] ; STEPIEN and SIERPINSKI [10] ; STEPIEN et al. [18]) .
Nevertheless, there is some evidence in the clinical literature that even unilateral temporal lobectomy may be responsible for the impairment of recent memory . Thus PENFIELD and MILNER [9] described grave and persistent loss of recent memory unaccompanied by other major changes of intellect or personality in two patients after operations on the dominant temporal lobe . In one, the resection was carried out in 2 stages separated by a 5-year interval ; the loss of memory followed the second operation at which time it was estimated that the uncus, hippocampus, and hippocampal gyrus were removed . In both instances the patients showed continuing EEG abnormalities in the contralateral (right) temporal lobe . Since careful study over a hundred other cases of unilateral temporal lobectomy had failed to reveal any such generalized memory impairment, the authors assumed that in these two cases there had been a destructive lesion of the right hippocampal zone also, so that when the epileptogenic hippocampal area on the left was excised the patients were functionally deprived of that zone bilaterally . WALKER [8] has also reported similar observations in four patients in whom a lasting memory defect was related to the ablation of one temporal lobe . The author has stressed that memory disturbances occur in 10 to 15 per cent of temporal lobe resections of either side, and may also be present before operation . However, he did not try to correlate his observations with EEG evidence of bilateral temporal dysfunction . Moreover, he stated that "several patients having bilateral temporal spikes have had unilateral lobectomies without their producing memory defects" . In recent study SERAFETINIDES and FALCONER [1 l] described severe recent memory impairment in seven of 34 epileptic patients in whom a temporal lobectomy was performed on the right and nondominant hemisphere . In six of these seven patients sphenoidal EEG studies revealed post-operatively a spike-discharging focus at the sphenoidal electrode beneath the opposite (or unoperated) temporal lobe . The authors concluded that "the presence of a spike-discharging focus at the opposite sphenoidal electrode indicates a dysfunction of that temporal lobe, if not a lesion, Therefore such cases can be considered as showing bilateral temporal lobe disturbances which are responsible for the memory defect" . Our own cases bring a good evidence to show that distinct impairment of both visual and auditory recent memory occurs in those cases in which persistent EEG abnormalities in both hippocampal areas are observed . Most interesting in this regard are the first three epileptic patients (Cases 1, 2 and 3) in whom long-standing epileptogenic lesion of one temporal region generated afterdischarges in the contralateral temporal lobe and caused in that way bilateral temporal dysfunction . It has been shown in our previous study [10] that the patients with unilateral temporal lesions had no difficulty in solving the auditory and visual test for recent memory used in our investigations, even with an interval of 120 sec between two signals and with the distracting stimulus applied in the middle of the interval . On the other hand, these three patients had severe disturbances in performing recent memory task before operation . In fact, they were quite unable to solve our test with a 60 sec (Cases 1 and 3) or even 30 sec (Case 2) interval between two signals if only the distraction was interposed in the middle of the interval . After removal of the epileptogenic area lying in one hippocampal region, the EEG examinations showed no pathological afterdischarges in the contralateral temporal lobe and since that time all three patients had no more difficulty in solving recent memory test .
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Similarly our patient C.S. (Case 4), after left temporal lobectomy which was performed because of a malignant glioma had no impairment of recent memory as long as the contralateral (right) temporal area showed no bioclectrical dysfunction . On the other hand, when 6 months later the recurrent tumour began to generate continuing afterdischarges in both temporal lobes, very grave and general deficit in recent memory could be revealed . The patient was unable to solve our test for recent memory even with 5 sec interval when the distraction was interposed between two signals . It looks as if a distracting stimulus applied in the interval "washed out" the memory traces of the first signal and the patient, therefore, could not compare it with the second signal and might even forget that the first signal was presented . These observations again support the thesis that unilateral lesions of the temporal lobe generating afterdischarges which cause bilateral dysfunction of hippocampal complex may produce severe and general impairment of recent memory . On the basis of our observations and those in the literature we may conclude that bilateral lesions or dysfunction of the hippocampal formation are capable of grave interfering with the recording and preserving recent memory traces, leaving intact other aspects of mental function . This conclusion seems to be in full agreement with PENFIELD's theory that the hippocampal complex plays an important role in recent memory function [9] . The mechanism whereby the hippocampal formation interact with other structures in memory recording is unknown and awaits further experimentation and clinical observations . While bilateral lesions or dysfunctions of the hippocampal complex lead to a general impairment of recent memory, it is not so after strict unilateral lesions in this area . However, the selective impairment of recent memory limited to definite types of stimuli is then possible . This is seen in our patient J .W. (Case 5) with temporal lobectomy including the hippocampal complex in the dominant hemisphere . Careful examination showed that the patient had no difficulty in solving our test for auditory and visual recent memory . On the other hand, she was very seriously impaired on verbal memory tests . She was not able to learn the name of her doctor in the ward or remember the names of her visitors . The defect was most clearly seen when she was asked to repeat abstract words or simple stories containing only two or three sentences which have been read to her . Similarly, she was not able to recall three or four words after an interval of two minutes or less if only her attention has been diverted to another problem . The patient was well aware of this learning difficulty and reported that she cannot read newspapers or books and follow television programmes . It should be mentioned that there was no dysphasia and her intelligence was quite good . Thus the patient J . W. demonstrated a specific deficit in learning and retention of verbal material following left hippocampal lesion, this deficit being most apparent when recall was examined after short interval and distraction in the meantime . This observation is in full agreement with findings of MEYER and YATES [23] and MILNER [24] who stressed the verbal learning difficulties after unilateral anterior temporal lobectomy in the dominant hemisphere . We may assume that the hippocampal complex in the dominant hemisphere plays an essential role in verbal recent memory processes contributing to learning and retention of verbal material . "Deprived of this area a man is not dysphasic, but he remains an inefficient listener and a poor reader since he can assimilate less verbal information in one sequence than formerly and forgets this little abnormally quickly" [24]. REFERENCES 1. 2.
BECHTEREW, W. Neurol. Centralbl. 19, 990, 1900 . GLEES, P. and GRIFFITH, H. B . Mschr. Psychiat. Neurol.
123,
193, 1952 .
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3 . GRONTHAL, E. Mschr. Psychiat . Neurol. 113, 1, 1947. 4 . SCOVILLE, W . B., DUNSMOKE, R . H ., LmERSON, W. T., HENRY, C . E. and PEPE, A. Res. Pub!. Ass. nerv. ment. Dis . 31, 347, 1953. 5 . Scovr.LE, W . B . J. Neurosurg. 11, 64, 1954. 6 . SCOVILLE, W . B . and MILNER, B . J. Neural. Neurosurg. Psychiat . 20, 11, 1957 . 7 . MILNER, B . and PENFIELD, W. Trans . Amer. neural. Ass . 80, 42, 1955. 8 . WALKER, A . E. Amer. Med. Arch . Assoc. Neural. Psychiat . 78, 543, 1957 . 9 . PENFIELD, W . and MILNER, B . Amer. Med. Arch . Assoc. Neural. Psyehial .79, 475, 1958 . 10 . STEPIEN, L. and SIERPINSKI, S . J. Neural. Neurosurg . Psychiat. 23, 334, 1960. 11 . SERAFETINIDES, E . A. and FALCONER, M . A . J. Neural. Neurosurg . Psychiat . 25, 251, 1962 . 12 . ORBACH, J., MILNER, B . and RASMUSSEN, T. Amer . Med. Assoc. Arch . Neural. 3, 230, 1960. 13 . MCCLEARY, R . A. J. camp . physiol. Psychol. 54, 605, 1961 . 14 . KAADA, B. R ., RASMUSSEN, E. W . and KVEIM, O . J. comp . physiol. Psychol. 55, 661, 1962. 15 . THOMPsoN, R . and LANGER, S . K . J. comp . physiol . Psychol. 56, 987, 1963. 16 . KONORSKI, J . Bull. Acad. pal. Sci ., Cf. VI. 7, 115, 1959 . 17 . CHORAZYNA, H. and STEPIEN, L. Aria Physiol. Poi 11, 672, 1960. 18 . STEPIEN, L ., CORDEAU, P . and RASmussEN, T. Brain 83, 470, 1960. 19 . HERB, D . O . The Organization of Behaviour : A Neuropsychological Theory . Wiley, New York, 1949 . 20 . KONORSKI, J . In Brain Mechanisms and Learning . A Symposium organized by The Council for International Organizations of Medical Sciences . Blackwell Scientific Publications, Oxford, 1961 . 21 . NEFF, W . D . Ann. Otol . RhinoL Laryngol. 66, 506, 1957 . 22. NEFF, W . D . Laryngoscope 68, 413, 1958 . 23 . MEYER, V. and YATES, A. J. J. Neural . Neurosurg . Psychiat . 18, 44, 1955 . 22. NEFF, W . D . Laryngoscope 68, 413, 1958 . 24. MILNER, B. In The Brain and Human Behavior, Vol. XXXVI, Proceedings of the Association for Research in Nervous and Mental Disease, The Williams and Wilkins Co ., Baltimore, 1958 .
Resume-5 cas de troubles de In memoire immediate sont decrits a la suite de lesions temporales unilaterales . Chez 3 sujets, les troubles de la m6moire de fixation auditive et visuelle sont determines par une lesion epileptogene siegeant dans une zone hippocampique et dormant des postdecharges dam les deux lobes tempomux . Dams tous ces cas, les troubles de la memoire de fixation disparaissaient completement apres lobectomie temporale unilaterale alors que I'EEG ne montrait plus d'anomalie daps la region temperate controlaterale . Chez un des sujets ayant subi une lobectomie temporale gauche pour care gliome malin, un trouble severe de la memoire immediate auditive et visuelle etait present 6 mois apres l'opemtion quand la tumeur commenca a determiner des anomalies EEG dans les deux lobes temporaux . Le dernier malade montrait une atteinte selective de la memoire immediate verbale a la suite Tune lesion strictement unilaterale dons la zone hippocampique . Zussammenfassung-Es werden funf Falle von Merkfahigkeitsstarung nach einseitigen temporalen Schadigungen geschildert . Bei 3 Kranken zeigten sich Beeintrachtigungen der akustischen and optischen Merkfahigkeit im Rahmen epileptischer Erscheinungen, die von einem einseitigen Herd im Hippocampus ausgingen and zu doppelseitigen Himstromveranderungen caber beiden Temporalregionen fiihrten . In allen diesen Fallen verschwand die Gedachtnisst&rung vollkonunen, als nach Vornahme einer einseitigen temporalen Lobektomie im Hirnstrombild die kontralateralen Kurvenveranderungen fiber der Schlitfenregion nicht mehr nachweisbar waren. Bei einem Kranken, der wegen eines malignen Gliorns linksseitig temporal lobektomiert worden war, zeigte sich eine erhebliche akustische and optische Merkschwache 6 Monate post operationem, als der tumorbse Prozess EEG-Veranderungen caber beiden Temporalregionen verursachte . Eine auf Worte beschrankte Merkschwache zeigte ein letzter Patient, bei welchem ein streng linksseitig begrenzter Herd im Hippocampusbereich vorlag.
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IMPAIRMENT OF RECENT MEMORY AFTER TEMPORAL LESIONS IN MAN L . STEPIEN and S . SIERPINSKI Department of Neurosurgery, Polish Academy of Sciences, Warsaw, Poland (Received 3 July 1964)
Abstract-Five cases of recent memory impairment following unilateral temporal lesions are described. In three patients auditory and visual recent memory disturbances were produced by the epileptogenic lesion in one hippocampat zone giving afterdischarges in both temporal lobes . In all these cases recent memory deficit cleared completely after unilateral temporal lobectomy when EEG examinations showed no more abnormalities in the contralateral temporal region . In one patient in whom left temporal lobectomy was performed because of a malignant glioma grave impairment of auditory and visual recent memory was revealed 6 months after operation when the tumour began to generate EEG abnormalities in both temporal lobes . The last patient showed selective impairment of verbal recent memory following strict unilateral lesion in the left hippocampal zone . 1 . INTRODUCTION
THERE is now a large body of evidence to show that the medial temporal region and in particular the hippocampal complex is intimately and critically concerned with recent memory processes in man . In 1899 BECHTEREW [1] demonstrated a patient with prominent memory disturbances caused by bilateral softening of the temporal lobes mainly of the gyrus uncinatus and cornu Ammonis . Over 50 years later, GLEES and GRIEEITII [2] described a case-history of a 58 year old woman, who presented grave disturbances of recent memory with loss of emotional drive presumably after vascular accident . She died 15 years later after a series of grand mal attacks . On neuropathological examination the authors observed bilateral cystic degeneration of the hippocampus and of the hippocampal and fusiform gyri . Onn the basis of this case and the case reported five years earlier by GRiiNTHAL [3] they came to the conclusion that the hippocampus and the neighbouring structures are necessary for the maintenance of recent memory and normal mental activity . SCOVILLE'S psychosurgical operations must be considered as most important for elucidation of the problem of recent memory . SCOVILLE et al. [4] performed in 19 schizophrenic patients three different types of operations on the medial surface of the temporal lobes . In 5 cases "bilateral uncotomy" was performed, that is, the resection of the uncus, periamygdaloid and prepytiform cortex . In 8 cases the operation consisted in the ablation of the entire medial cortex of the temporal lobe, including the anterior hippocampus and all the structures lying medial to the inferior horn of the ventricle-"bilateral medial temporal lobotomy" . In the last 6 patients "bilateral orbito-temporal lobotomy" was performed consisting in combining the second operation with the isolation of the orbital surface of the frontal lobe by the cortical undercutting technique . All the removals have been bilateral, extending for varying distances along the medial surface of the temporal lobe, in most instances to a distance of 5 or 6 cm from the temporal tip . It should be noticed that in none of these cases was any pronounced memory deficit observed at the time of operation . 291
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In a later paper ScovILLE [5] stated that in two patients, one epileptic and the other a psychotic "undergoing bilateral resection of the entire complex including the hippocampal gyros extending posteriorly for a length of 8 to 9 cm from the tips of the temporal lobes", there appeared "a very grave, recent memory loss, so severe as to prevent the patient from remembering the location of the rooms in which he lives, the names of his close associates or even the way to toilet and urinal" . Later, these two patients were subjected to formal memory and intelligence testing by ScovILLE and MILNER [6] . Disturbances of recent memory persisted without improvement all the time two and a half and three years after operation . I would like to cite one or two of numerous illustrations of this deficit . "Ten months ago the family moved from their old house to a new one a few blocks away on the same street ; he still has not learned the new address, though remembering the old one perfectly, nor can he be trusted to find his way home alone ." . . . "This patient has even eaten luncheon in front of one of us without being able to name, a mere half-hour later, a single item of food lie had eaten ; in fact, he could not remember having eaten, luncheon at all" (p . 14) . There was no deficit in early memories and technical skills as well as no deterioration in personality or general intelligence . The discovery of severe memory deficit in these two patients led SCOVILLE and MILNER [6] to study other patients who had undergone similar, but less radical resections of the medial temporal region . It was the conclusion of these authors that : "Whenever the hippocampus and hippocampal gyrus were damaged bilaterally in these operations some memory deficit was found, but not otherwise" . . . "Removal of only the uncus and amygdala bilaterally does not appear to cause memory impairment" (p . 21) . It is generally held that a loss of recent memory occurs only if the lesions of the hippocampal complex are bilateral . Nevertheless, there area number of instances in which lesions apparently limited to one temporal lobe were associated with a serious loss of recent memory [7-I1] . We now know that even unilateral temporal lobectomy may cause an immediate and grave loss of recent memory when there is interference with the functioning of the hippocampal zone of the opposite hemisphere by contralateral pressure, or when the EEG examination points to bioelectrical abnormalities in both inferior temporal regions . In view of these clinical observations it has become increasingly important to study experimentally in animals the hypothesis that bilateral ablations of the hippocampal complex would cause severe and lasting recent memory deficit . Unfortunately, the problem of recent memory was poorly investigated after hippocampal lesions in animals . The recent studies of ORRACH el al. [12], MCCLEARY [13], KA.NDA et al. [14] and THOMPSON and LANGER [15] indicate that injuries to various limbic structures impair performance on tasks which require the animal to withhold either learned or unlearned conditioned responses . However the significance of these studies is limited by the great variability of lesions performed by different experimenters and by the lack of appropriate and standardized tests for examination of recent memory function . As pointed out recently by KONORSKI [16], those tests used in the past, such as conditioned inhibition or trace conditioned reflexes, are open to criticism with regard to their potentiality as true indicators of recent memory performances in respect to the modalities of stimuli used in these tests . For this reason he has suggested the use of a new testing procedure which eliminates most of the criticisms . This test uses compound stimuli in which each stimulus is made up of two signals of the same sensory modality separated by a short interval which may be varied from one to five seconds or more . Within this modality a compound stimulus consisting of any two identical signals is a positive
IMPAIRMENT OF RECENT MEMORY AFTER TEMPORAL LESIONS IN MAN
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reinforced) conditioned stimulus while a compound composed of any two different stimuli is a negative (non-reinforced) conditioned stimulus, or vice versa. The interesting feature in this testing procedure is that the first signal has no significance in itself ; it can be part of either a positive or a negative compound stimulus . The correct response is possible only when the animal retains the trace of the first signal up to and including the time of the second signal, so that the two can be compared . Thus when the first component of the compound stimulus is applied the animal does not "know" whether he will get reinforcement or not, because this depends on the comparison of the second component with the first one . Consequently, the animal cannot anticipate a particular kind of reaction, as is the case in delayed responses or in other tests in which the first signal of the compound already determines the positive or negative character of the conditioned reaction . The above described test for recent memory was applied in experiments on dogs by CHORAZYNA and SrEPIEN [17] and on monkeys by STEPIEN et al. [18] . It has been shown that bilateral ablation of the so called "ventral auditory area", e .g . Sylvian gyri in dog or anterior part of the first temporal gyrus in monkey, may produce grave disturbances in auditory recent memory while visual recent memory was fully preserved . Similarly bilateral removal of the inferior temporal cortex causes severe deficit in visual recent memory performances in monkeys . After bilateral excisions of the hippocampal complex in monkeys general impairment of recent memory was observed ; the animals were unable to solve our test for auditory and visual recent memory . It should be mentioned that most of animals which were not able to solve our test after bilateral ablations could learn a new task such as simple discrimination, conditioned inhibition and compound stimuli discrimination without interval between signals . This strongly suggests that the deficit in these animals was one of recent memory or "holding" capacity rather than general impairment of solving the difficult task . To sum up, there is increasing evidence coming from clinical observations and from experimental work that bilateral hippocampal lesions may produce a striking deficit in all those tasks in which recent memory is an indispensable factor for a solution of a given problem . The purpose of this report is to describe five cases of recent memory impairment following unilateral temporal lesions studied by means of the methods which were developed by KONORSKI for animals . (i.e.
2. METHOD OF EXAMINATION OF RECENT MEMORY Examination of recent memory was that used in our previous study [10]. We applied the pairs of identical or different auditory and visual signals, the duration of each signal being two see, and the interval between them 10-120 sec . The patient was instructed to press the dynamometer connected with the recording instrument when the two signals of the compound auditory or visual stimulus would be identical and not to press, when the second signal would differ from the first one . When the patient showed no difficulty in solving this problem with an interval of 120 sec between the signals, the task was made more difficult by introducing in the middle of the interval an additional, distracting stimulus from another analyser than that involved in the recent memory test . Usually, we performed recent memory examinations before as well as after operation . The daily test session consisted of 10-30 trials . On the first sign of weariness we stopped the examination,
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3 . CASE REPORTS aged 15 years . The case of this patient is described in full detail in our previous report as Case 3 [10] . In summarizing this case, we may say that this is an instance of distinct recent memory deficit resulting from a lesion in the right hippocampal zone giving afterdischarges in both temporal lobes . After the removal of the epileptogenic focus in the right temporal and fronto-opercular region impairment of recent auditory and visual memory cleared completely . The control examinations performed several times during the last four and a half years after operation showed that the patient had no difficulty whatever in solving our test even when the interval between two signals was 120 sec and when the distracting stimulus was given in this interval . Case 1 . H.K.,
Case 2 . I .L ., a 17-year-old boy, was admitted to the Department of Ncurosurgery, Polish Academy of Sciences, Warsaw, on February 6, 1963, because of recurrent seizures since the age of 13 years, which had been increasing in frequency and severity despite treatment by various anticonvulsant drugs . His birth was normal and his early childhood has been uneventful ; but he had a period of high temperature and unconsciousness during three days at the age of 8 years . Seizure pattern : His attacks were ushered in by a sudden illusion of interpretation . The situation in which he found himself seemed suddenly "quite different", "unreal", and "unpleasant" . The voices and sounds were also "different" and the patient had a feeling of fear . After that, he stared and became unresponsive for several minutes . During this time he performed many automatic and fumbling movements with his hands and movements of mastication . Sometimes he would fall to the floor motionless and his limbs were held stiff. Occasionally he might go out of home and run ahead . These attacks appeared usually every day, occasionally many times a day . Physical examination : The neurological examination, skull radiographs, and air encephalograms were normal . The Wasserman test on blood and cerebrospinal fluid was normal . Electroencephalographic findings : Numerous EEG examinations were summarized by Dr. T. BACIA as follows : "The EEG's showed an active epileptogenic focus in the right temporal lobe in the form of slow-wave complexes and high voltage spikes with phases reversals . Sporadic sharp waves occurred also in the left temporal region" . Pre-operative examination of recent memory : The patient showed no impairment of memory for old events and he was able to repeat series of numbers or names of objects seen after three and even five minutes if only no distraction was given in the interval . Examination of recent memory showed that the patient was able to solve the auditory and visual test only when the interval between two signals was not longer than 30 sec and when there was no distraction during the interval. When the distracting stimulus was interposed between the two signals he was unable to do so . (Table 1) . Operation : On February 22, 1963, a right fronto-temporal craniotomy was performed . When the dun was opened the sulci and blood vessels on the surface of the brain appeared normal but there was some pallor of the cortex on the second and third temporal gyri . Etectrocorticography revealed abnormal discharges recorded from the whole temporal lobe most distinct from the posterior part of it (Fig . 1) . During resection of the temporal lobe it was stated that the brain tissue in the region of the amygdaloid nucleus was tough and yellow . A 7-5 cm temporal lobectomy was performed including the hippocampal complex (Figs . 2 and 3) . Post-operative course : After operation the patient felt quite well and no epileptic attacks were observed . The neurological examination revealed a left upper homonymous quadrantopsy, but otherwise the status was quite normal. Control EEG's showed residual abnormality over the right temporal region without epileptfform discharges . Test of recent memory : The examinations of auditory and visual recent memory were performed 2 and 3 weeks and 14 months after operation . They showed that the patient no longer had difficulty in solving the test even when the interval between two signals was 120 sec and when distraction was interposed between them (Table 1) . Thus we may assume that after the removal of an epileptogenic focus in the right temporal lobe which generated afterdischarges in both temporal regions, the disorder of recent memory has been removed . Case 3 . J .K ., a 23-year-old woman, was admitted to our department on January 28, 1963, with a history of recurrent epileptic fits since the age of 7 years . Her birth was thought to have been normal and nothing significant was noticed in her early childhood . Seizure pattern . The attack began with a sensation of gastrointestinal activity in the midline of the abdomen above the umbilicus or with a feeling of warmness and palpitation in the precordium which rose to the head. This was followed by a loss of consciousness and generalized convulsive movements or by a minor seizure in which she had a feeling of fear and used to perform some uncoordinated automatic movements with her hands . Sometimes she noticed things about her looked larger and nearer . She was very much afraid and called her parents
FIG . 1 . Case 2, IL . Operation photograph .
Lettered tickets indicate sites of electrographic abnormality : A-spikes, spike-and-wave complexes ; B, D-stow waves and spikes ; C---spikes ; E-sharp waves ; F, 1--spikes and phase reversals . White thread indicates the Sylvian fissure and the proposed frontier of excision .
Fju . 2 . Case 2 . I .L . Photograph of operation after right temporal lobcctomy . The insutaa is exposed by the removal .
Flc . 4 . Case 3, J . K . Operation photograph . Lettered tickets indicate sites of electrographic abnormality : A, B, 1-slow waves C, F spikes, spike-and-wave complexes ; D-sharp waves ; White thread indicates the Sylvian fissure and the proposed frontier of escis n .
Pie . 5 . Case 3, .I .K . Photograph of operation after anterior left temporal lobectomp .
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Results of recent memory examinations in 1 .L . before and after removal of epileptogenic region No distraction Distraction Interval in interval in interval between two signals Errors (see) Trials Errors Trials Table 1 .
Before operation Auditory recent memory : 10 20 30 60 120 Visual recent memory : 10 20 30 60 120 Auditory recent memory : 30 60 120 Visual recent memory : 30 60 120
10 10 20 30 20
0 0 0 19 14
40 30 20
25 21 12
10 10 30 40 15
0 0 2 27 9 After operation
30 25 10
18 14 7
40 50 40
0 0 1
30 40 30
0 0 0
20 50 40 30 25 50
0 0 0
E7o . 3 . Case 2, I .L . Brain charts showing extent of the right temporal lobectomy- broken line ; hippocampal gyros removed completely.
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In spite of treatment by various anticonvulsant drugs these attacks increased in number and severity and they might appear even every day . She became nervous, stubborn and began to have conflicts with other girls . She made slow progress in learning and repeated two classes in the first school . Physical examination : The neurological examination, the plain films of the skull and pneumoencephalography were entirely negative. The routine examinations of blood and cerebrospinal fluid were normal . Electroencephalographic studies have consistently shown an active epileptogenic area in the left temporal lobe characterized mainly by high voltage spikes with phases reversals . Sporadic sharp waves and waveand-spike complexes occurred also in the right temporal region (Dr . T. BAcM) . Pre-operative recent memory examination : The patient was of average intelligence and showed no impairment of memory for the distant past or loss of attention, concentration or reasoning ability. She was able to reproduce geometrical forms from memory and performed arithmetic tests well . She could easily remember day-to-day happenings and recognized the various members of the staff . But she complained of being forgetful and could remember very little of what she read . Her immediate reproductions of the short stories was very poor and after 10 minutes she could recall with great difficulties only some small fragments or nothing at all of them . Recent memory examinations by using our method revealed definite disturbances . The patient was able to solve the auditory and visual test only when the interval between two signals was not longer than 60 sec and when there was no distracting stimulus . But when the distraction was interposed between the two signals she was quite unable to solve the task (Table 2) . Table 2 . Results of recent memory examinations in J .K. before and after removal of epileptogenic region . Interval between two signals (see)
No distraction in interval Trials
Distraction in interval Errors
Trials
Errors
Before operation Auditory recent memory : 30 60 120
20 30 30
0 0 18
30 30 50
0 16 26
Visual recent memory : 15 30 60 120
20 20 30 60
0 0 1 39
20 30 40 50
0 0 27 26
After operation Auditory recent memory : 30 60 120
20 50 60
0 0 0
30 50 60
0 0 3
Visual recent memory : 30 60 120
20 40 70
0 0 0
30 50 60
0 0 0
Operation : On February 8, 1963, a left temporal craniotomy was performed . After cutting the dura the lateral aspect of the temporal lobe appeared more or less normal, but the second temporal convolution was larger than usual . Electrocorticography showed abnormal discharges recorded by the electrodes which had been placed on the temporal lobe ; slight abnormalities have been also revealed in the operculum frontale and premotor area (Fig. 4) . In order to guard against postoperative aphasia it was decided to remove the anterior portion of the temporal lobe . During resection marked abnormalities were encountered in the region of amygdaloid nucleus and hippocampus ; the grey matter was yellow and tough . The most conspicuous abnormality was found in the hippocampus . The line of removalwas 5 cm from the tip of the temporal lobe and followed a fissure line in which the vein of Labb6 ran, then turned and ran perpendicularly to the base and across it to the brain stem (Figs . 5 and 6).
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Fin . 6. Case 3, J .K . Brain charts showing extent of the anterior left temporal lobectomybroken line . Post-operative course : The post-operative course was uneventful and no epileptic attacks were observed . Control electroencephalographic examinations showed slight abnormalities in the left temporal region but no afterdischarges in the right temporal lobe . Test of recent memory : The examinations of auditory and visual recent memory were performed 3 weeks and 15 months after operation . The patient was able to solve the problem quite easily even with the interval between two signals 120 sec and with the distracting stimulus presented in the middle of the interval (Table 2) . In summary, in this case epilcptogenic zone in the left temporal region produced striking abnormalities in both temporal lobes resulting in distinct impairment of recent memory . After removal of the epileptogenic area the patient has no more attacks and her recent memory has been improved .
Case 4 . C .S., a 58-year-old man was admitted to our department on June 13, 1963, because of increased intracranical pressure, aphasia and right hemiparesis . The illness began three months previously with progressive headaches, disturbances of speech and weakness of the right arm and leg . Neurological examination revealed bilateral papilloedema, right homonymous hemianopsia, weakness of the lower portion of the right facial nerve, and of both right extremities ; the tendon and periosteal reflexes were all hyperactive on the right side. The patient had grave difficulties in naming, understanding and counting. The EEG's showed marked pathological activity predominantly in the posterior part of the left temporal region . Tumour of the left temporal lobe was diagnosed and because of the advanced neurological changes the operation was decided to be performed next day after admission . Operation : Under general anesthesia, a left temporal craniotomy was carried out on June 14, 1963 . When the dura was opened, marked changes in the temporal lobe were found . The Sylvian fissure was strongly elevated and the vein of Labbe slanted back farther posterior than usual over the temporal lobe . The first and second temporal gyri were enlarged and the fissures between them were flattened . The cerebral cortex of the anterior and medial part of the temporal lobe was anaemic and yellow . The puncturing of the second temporal gyros revealed just under the cortex a cystic tumour containing about 30 ml of xanthochromic fluid. The anterior part of the temporal lobe together with the tumour was then removed, including uncus and hippocampus . The brain tissue was destroyed by the invading masses of the tumour . The final line of resection is shown in the brain chart (Fig. 7). The posterior * part of the first temporal gyros was preserved. The second and third temporal convolutions were removed 6 cm from the temporal tip .
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7 . Case 4, C .S . Brain charts showing the extent of left temporal lobectomybroken line .
Histopathological examination of the tumour revealed the glioblastoma multiforme (Dr . J . WISLAWSKI) . Post-operative course : After the operation the patient became more aphasic . By the end of the second week aphasia and right hemiparesis were beginning to clear, although nomination and counting were still impaired. The patient received X-ray therapy and was discharged from the hospital . During 6 months after operation the patient has done rather well, He did not complain of headaches or weakness of right extremities . His speech was much better than before operation and his memory seemed to be normal . In January 1964 the patient became again more aphasic and paretic . At the same time grave disturbances of recent memory were noted . His wife said that he became forgetful and was not able to remember the every day events . He could read the same magazines over and over again without finding their contents familiar ; he did not remember the visits of his close friends . Several EEG examinations showed distinct abnormalities in the left temporal region producing afterdischarges in the right temporal lobe (Mgr. R . STADNICKI) .
Examination of recent memory : There was no impairment of attention or concentration. The patient was well oriented, recognized people and old surroundings . He was able to repeat nonsense syllables or series of numbers but he found it impossible to learn any difficult word associations or to remember 5 objects for as long as 5 min . He could not solve the most simple arithmetic tasks . The ability to solve our test for auditory and visual recent memory revealed very grave disturbances . He was able to perform the task only when the interval between two signals was not longer than 5 sec and when he was permitted to keep his attention upon it . But when the distraction was interposed between the two signals he was quite unable to keep in mind the first signal and very often he forgot that there was the first signal (Table 3) . In summary, in this case the malignant glioma destroying the left hippocampal zone has resulted in profound disturbances of auditory and visual recent memory . The lesion was unilateral but there is clear electroencephalographic evidence showing that the tumour caused bioefectricai abnormalities in both temporal lobes.
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Table 3 . Results of recent memory examinations in C.S. No distraction in interval
Distraction in interval
Interval between two signals (see)
Trials
Errors
Trials
Auditory recent memory : 5 10 30
60 50 36
2 32 18
52 50
34 31
Visual recent memory : 5 10 30
40 60 30
0 36 18
45 60
27 39 -
Errors
Case 5 . J .W., a 33-year-old houswife, was admitted to our department on January 8, 1964, with a history of headaches and epileptic attacks since 3 months . The attacks began with a sensation of heat in the neck and face. After this she lost consciousness and had general convulsions . There were altogether 6 attacks. Physical examination : There was bilateral papilloedema and slight paresis of the lower portion of the right facial nerve . Otherwise the neurological status was normal . The plain films of the skull showed the shifting of the pineal gland to the right side . EEG's revealed numerous slow wave complexes at frequencies between 2 and 3 per second from the left temporal lobe (Mgr. R, STADNICKI) .
. Fla
8. Case 5, J .W . Brain charts showing the extent of left temporal lobectomy-broken line .
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and
S . SIERPINSKI
Operation : Tumour of the left temporal lobe was diagnosed and on January 22, 1964, under general anaesthesia a left frontotemporal craniotomy was performed . After dividing the dura, marked changes in the temporal lobe were noticed . The vessels in the Sylvian fissure were enlarged and elevated . The cortex of the second temporal gyros was destroyed by the tumour and no cyst was found . The removal of the tumour was accomplished by a resection of the second and third temporal gyri together with the hippocampal complex . The first temporal convolution was left intact The final line of removal is shown in the brain chart (Fig. 8). As measured from the anterior wall of the temporal fossa, the line of excision was 7 cm along the inferior temporal surface . The histological examination of the tumour revealed an astrocytoma fibrillarc (Dr . J . WISLAwSK1) . Post-operative course : The post-operative course was uneventful although the patient had very slight and transient difficulties in nomination of objects and in repetition of series of words . These disturbances appeared on the second day after operation and cleared completely after two weeks . The neurological examination revealed a right upper quadrantopsy but otherwise the status was normal . Post-operative EEG's showed marked abnormalities in the form of slow wave complexes over the left temporal region . Examination of recent memory : The patient was of an average intelligence and showed no impairment of memory for the past events and no dysphasia . The ability to solve our test for auditory and visual recent memory was fully preserved . She was able to perform the task even with 120 sec interval and with the distracting stimulus presented between two signals . At the same time the patient demonstrated a serious deficit in verbal recent memory tests . Although she easily repeated four or even five words immediately after she heard them she was quite unable to recall them after a lapse of two minutes or less if her attention has been diverted to another problem in the meantime . She did not know the names of doctors visiting her every day, including the doctor who operated upon her. She was not able to repeat after one minute even one name out of four names of doctors attending to the examination and belonging to the staff. Similarly she could not recall three abstract words (such as "hope", "gaiety", "pain"), numbers or objects after an interval of 1-2 min . Most often she repeated only two words correctly . In summary, in this case unilateral lesion involving the hippocampal complex of the dominant hemisphere caused severe impairment of verbal recent memory while auditory and visual recent memory was normal . 4 . DISCUSSION It is now almost generally accepted that recent or dynamic memory is intimately connected with circulating impulses in the reverberating chains of neurons, activation of which may persist for a relatively long time after the actual stimulation of neurons (HERB [19] ; KONORSKI [20]) . The evidence that the so called associative areas, i .e. the cortical areas lying in the immediate vicinity of the sensory projection areas, play an important role in recent memory processes is quite impressive . Recent experimental studies in animals support the view that recent memory traces of a given sensory modality may be irreversibly destroyed following lesions lying outside the sensory cortical projection areas (NEFF [21, 22] ; CHORAZYNA and STEPIEN [17] ; STEPIEN et al. [18]) . There is also increasing evidence that bilateral removal of the hippocampal complex in man produces grave and persistent loss of recent memory . Memory deficit in these cases is not specific to any one kind of sense modality as it used to be after ablations of the associative areas in animals, but is quite general affecting memory for all events subsequent to operation . The patient is unable to recall test material after a lapse of five minutes or less if his attention has been diverted to another topic in the meantime [5, 6] . The question of how these hippocampal structures contribute to recent memory processes is still a matter for speculation . In view of many afferent and efferent connexions between hippocampus and other cortical and subcortical areas of the brain it may be assumed that hippocampal lesions cause a disruption of reverberating neuronal circuits important for certain memory processes and recording of new experience . The results of experimental and clinical investigations seem to show that unilateral lesions situated in the ventro-medial parts of the temporal lobe--independent of the side
IMPAIRMENT OF RECENT MEMORY AFTER TEMPORAL LESIONS IN MAN
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(dominant or subordinate hemisphere)-do not produce an impairment of recent memory (MEYER and YATES [23] ; PENFIELD and MILNER [9] ; STEPIEN and SIERPINSKI [10] ; STEPIEN et al. [18]) .
Nevertheless, there is some evidence in the clinical literature that even unilateral temporal lobectomy may be responsible for the impairment of recent memory . Thus PENFIELD and MILNER [9] described grave and persistent loss of recent memory unaccompanied by other major changes of intellect or personality in two patients after operations on the dominant temporal lobe . In one, the resection was carried out in 2 stages separated by a 5-year interval ; the loss of memory followed the second operation at which time it was estimated that the uncus, hippocampus, and hippocampal gyrus were removed . In both instances the patients showed continuing EEG abnormalities in the contralateral (right) temporal lobe . Since careful study over a hundred other cases of unilateral temporal lobectomy had failed to reveal any such generalized memory impairment, the authors assumed that in these two cases there had been a destructive lesion of the right hippocampal zone also, so that when the epileptogenic hippocampal area on the left was excised the patients were functionally deprived of that zone bilaterally . WALKER [8] has also reported similar observations in four patients in whom a lasting memory defect was related to the ablation of one temporal lobe . The author has stressed that memory disturbances occur in 10 to 15 per cent of temporal lobe resections of either side, and may also be present before operation . However, he did not try to correlate his observations with EEG evidence of bilateral temporal dysfunction . Moreover, he stated that "several patients having bilateral temporal spikes have had unilateral lobectomies without their producing memory defects" . In recent study SERAFETINIDES and FALCONER [1 l] described severe recent memory impairment in seven of 34 epileptic patients in whom a temporal lobectomy was performed on the right and nondominant hemisphere . In six of these seven patients sphenoidal EEG studies revealed post-operatively a spike-discharging focus at the sphenoidal electrode beneath the opposite (or unoperated) temporal lobe . The authors concluded that "the presence of a spike-discharging focus at the opposite sphenoidal electrode indicates a dysfunction of that temporal lobe, if not a lesion, Therefore such cases can be considered as showing bilateral temporal lobe disturbances which are responsible for the memory defect" . Our own cases bring a good evidence to show that distinct impairment of both visual and auditory recent memory occurs in those cases in which persistent EEG abnormalities in both hippocampal areas are observed . Most interesting in this regard are the first three epileptic patients (Cases 1, 2 and 3) in whom long-standing epileptogenic lesion of one temporal region generated afterdischarges in the contralateral temporal lobe and caused in that way bilateral temporal dysfunction . It has been shown in our previous study [10] that the patients with unilateral temporal lesions had no difficulty in solving the auditory and visual test for recent memory used in our investigations, even with an interval of 120 sec between two signals and with the distracting stimulus applied in the middle of the interval . On the other hand, these three patients had severe disturbances in performing recent memory task before operation . In fact, they were quite unable to solve our test with a 60 sec (Cases 1 and 3) or even 30 sec (Case 2) interval between two signals if only the distraction was interposed in the middle of the interval . After removal of the epileptogenic area lying in one hippocampal region, the EEG examinations showed no pathological afterdischarges in the contralateral temporal lobe and since that time all three patients had no more difficulty in solving recent memory test .
3 02
L, STEPIEN
and s .
SIERPINSKI
Similarly our patient C.S. (Case 4), after left temporal lobectomy which was performed because of a malignant glioma had no impairment of recent memory as long as the contralateral (right) temporal area showed no bioclectrical dysfunction . On the other hand, when 6 months later the recurrent tumour began to generate continuing afterdischarges in both temporal lobes, very grave and general deficit in recent memory could be revealed . The patient was unable to solve our test for recent memory even with 5 sec interval when the distraction was interposed between two signals . It looks as if a distracting stimulus applied in the interval "washed out" the memory traces of the first signal and the patient, therefore, could not compare it with the second signal and might even forget that the first signal was presented . These observations again support the thesis that unilateral lesions of the temporal lobe generating afterdischarges which cause bilateral dysfunction of hippocampal complex may produce severe and general impairment of recent memory . On the basis of our observations and those in the literature we may conclude that bilateral lesions or dysfunction of the hippocampal formation are capable of grave interfering with the recording and preserving recent memory traces, leaving intact other aspects of mental function . This conclusion seems to be in full agreement with PENFIELD's theory that the hippocampal complex plays an important role in recent memory function [9] . The mechanism whereby the hippocampal formation interact with other structures in memory recording is unknown and awaits further experimentation and clinical observations . While bilateral lesions or dysfunctions of the hippocampal complex lead to a general impairment of recent memory, it is not so after strict unilateral lesions in this area . However, the selective impairment of recent memory limited to definite types of stimuli is then possible . This is seen in our patient J .W. (Case 5) with temporal lobectomy including the hippocampal complex in the dominant hemisphere . Careful examination showed that the patient had no difficulty in solving our test for auditory and visual recent memory . On the other hand, she was very seriously impaired on verbal memory tests . She was not able to learn the name of her doctor in the ward or remember the names of her visitors . The defect was most clearly seen when she was asked to repeat abstract words or simple stories containing only two or three sentences which have been read to her . Similarly, she was not able to recall three or four words after an interval of two minutes or less if only her attention has been diverted to another problem . The patient was well aware of this learning difficulty and reported that she cannot read newspapers or books and follow television programmes . It should be mentioned that there was no dysphasia and her intelligence was quite good . Thus the patient J . W. demonstrated a specific deficit in learning and retention of verbal material following left hippocampal lesion, this deficit being most apparent when recall was examined after short interval and distraction in the meantime . This observation is in full agreement with findings of MEYER and YATES [23] and MILNER [24] who stressed the verbal learning difficulties after unilateral anterior temporal lobectomy in the dominant hemisphere . We may assume that the hippocampal complex in the dominant hemisphere plays an essential role in verbal recent memory processes contributing to learning and retention of verbal material . "Deprived of this area a man is not dysphasic, but he remains an inefficient listener and a poor reader since he can assimilate less verbal information in one sequence than formerly and forgets this little abnormally quickly" [24]. REFERENCES 1. 2.
BECHTEREW, W. Neurol. Centralbl. 19, 990, 1900 . GLEES, P. and GRIFFITH, H. B . Mschr. Psychiat. Neurol.
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3 . GRONTHAL, E. Mschr. Psychiat . Neurol. 113, 1, 1947. 4 . SCOVILLE, W . B., DUNSMOKE, R . H ., LmERSON, W. T., HENRY, C . E. and PEPE, A. Res. Pub!. Ass. nerv. ment. Dis . 31, 347, 1953. 5 . Scovr.LE, W . B . J. Neurosurg. 11, 64, 1954. 6 . SCOVILLE, W . B . and MILNER, B . J. Neural. Neurosurg. Psychiat . 20, 11, 1957 . 7 . MILNER, B . and PENFIELD, W. Trans . Amer. neural. Ass . 80, 42, 1955. 8 . WALKER, A . E. Amer. Med. Arch . Assoc. Neural. Psychiat . 78, 543, 1957 . 9 . PENFIELD, W . and MILNER, B . Amer. Med. Arch . Assoc. Neural. Psyehial .79, 475, 1958 . 10 . STEPIEN, L. and SIERPINSKI, S . J. Neural. Neurosurg . Psychiat. 23, 334, 1960. 11 . SERAFETINIDES, E . A. and FALCONER, M . A . J. Neural. Neurosurg . Psychiat . 25, 251, 1962 . 12 . ORBACH, J., MILNER, B . and RASMUSSEN, T. Amer . Med. Assoc. Arch . Neural. 3, 230, 1960. 13 . MCCLEARY, R . A. J. camp . physiol. Psychol. 54, 605, 1961 . 14 . KAADA, B. R ., RASMUSSEN, E. W . and KVEIM, O . J. comp . physiol. Psychol. 55, 661, 1962. 15 . THOMPsoN, R . and LANGER, S . K . J. comp . physiol . Psychol. 56, 987, 1963. 16 . KONORSKI, J . Bull. Acad. pal. Sci ., Cf. VI. 7, 115, 1959 . 17 . CHORAZYNA, H. and STEPIEN, L. Aria Physiol. Poi 11, 672, 1960. 18 . STEPIEN, L ., CORDEAU, P . and RASmussEN, T. Brain 83, 470, 1960. 19 . HERB, D . O . The Organization of Behaviour : A Neuropsychological Theory . Wiley, New York, 1949 . 20 . KONORSKI, J . In Brain Mechanisms and Learning . A Symposium organized by The Council for International Organizations of Medical Sciences . Blackwell Scientific Publications, Oxford, 1961 . 21 . NEFF, W . D . Ann. Otol . RhinoL Laryngol. 66, 506, 1957 . 22. NEFF, W . D . Laryngoscope 68, 413, 1958 . 23 . MEYER, V. and YATES, A. J. J. Neural . Neurosurg . Psychiat . 18, 44, 1955 . 22. NEFF, W . D . Laryngoscope 68, 413, 1958 . 24. MILNER, B. In The Brain and Human Behavior, Vol. XXXVI, Proceedings of the Association for Research in Nervous and Mental Disease, The Williams and Wilkins Co ., Baltimore, 1958 .
Resume-5 cas de troubles de In memoire immediate sont decrits a la suite de lesions temporales unilaterales . Chez 3 sujets, les troubles de la m6moire de fixation auditive et visuelle sont determines par une lesion epileptogene siegeant dans une zone hippocampique et dormant des postdecharges dam les deux lobes tempomux . Dams tous ces cas, les troubles de la memoire de fixation disparaissaient completement apres lobectomie temporale unilaterale alors que I'EEG ne montrait plus d'anomalie daps la region temperate controlaterale . Chez un des sujets ayant subi une lobectomie temporale gauche pour care gliome malin, un trouble severe de la memoire immediate auditive et visuelle etait present 6 mois apres l'opemtion quand la tumeur commenca a determiner des anomalies EEG dans les deux lobes temporaux . Le dernier malade montrait une atteinte selective de la memoire immediate verbale a la suite Tune lesion strictement unilaterale dons la zone hippocampique . Zussammenfassung-Es werden funf Falle von Merkfahigkeitsstarung nach einseitigen temporalen Schadigungen geschildert . Bei 3 Kranken zeigten sich Beeintrachtigungen der akustischen and optischen Merkfahigkeit im Rahmen epileptischer Erscheinungen, die von einem einseitigen Herd im Hippocampus ausgingen and zu doppelseitigen Himstromveranderungen caber beiden Temporalregionen fiihrten . In allen diesen Fallen verschwand die Gedachtnisst&rung vollkonunen, als nach Vornahme einer einseitigen temporalen Lobektomie im Hirnstrombild die kontralateralen Kurvenveranderungen fiber der Schlitfenregion nicht mehr nachweisbar waren. Bei einem Kranken, der wegen eines malignen Gliorns linksseitig temporal lobektomiert worden war, zeigte sich eine erhebliche akustische and optische Merkschwache 6 Monate post operationem, als der tumorbse Prozess EEG-Veranderungen caber beiden Temporalregionen verursachte . Eine auf Worte beschrankte Merkschwache zeigte ein letzter Patient, bei welchem ein streng linksseitig begrenzter Herd im Hippocampusbereich vorlag.