- Email: [email protected]
HIPPOCAMPUS AND MEMORY
1123
called for, the absence-rate rose-but so did weekly attendance. Since the war the normal weekly hours of work in British industry have fallen from 44.4 in 1949 to 40-2 in 1968 but the numbers involved in short-time working have been very small. These complicating factors are avoided by using the measures of frequency and severity described in this paper. The comparisons for 1961-62 in both the regions and the thirty-eight urban areas raise other problems by showing significant positive associations between unemployment and sickness absence. Although the chronic sick may find it difficult to get work and the unemployed may become depressed, there is no evidence to suggest that unemployment in the area actually causes illness in those employed. Indeed Morris and Titmuss 9 noted that unemployment seemed to reduce mortality from peptic ulcer. As might be expected, however, a comparison of the standardised mortality-ratios for the years 1959-631° with the data on sickness for these thirtyeight urban areas showed a significantly positive association (r=0-68), but not with the levels of unemployment (r=0-22). An analysis by Gardner et al.ll of mortality in the larger county boroughs of England and Wales revealed a significant relationship with a number of socioeconomic, climatic, and environmental variables. The rank order of sicknessrates in the thirty-eight urban areas studied by us relates closely to the " social factor " scores calculated by Gardner et al. and his colleagues. A positive association between unemployment and sickness does not necessarily imply causation and it is likely that both may be influenced by underlying socioeconomic and environmental factors such as the type of industry predominant in the area. It seems reasonable to conclude that the levels of unemployment experienced in Great Britain in the past two decades have not significantly influenced the rates of certified incapacity for work. In times or in countries with low social-security benefits such a relationship may well be found, but not under present conditions with comparatively high benefits. We thank members of the statistics divisions of the Department of Health and Social Security and the Department of Employment and Productivity for their help in obtaining the data, and for their constructive criticism in the preparation of this paper.
Requests
for
reprints should
be addressed to P.
J. T.
REFERENCES 1. Florence, P. S. Economics of Fatigue and Unrest. London, 1924. 2. Young, A. F. Soc. Sci. Q. 1961, 35, 65. 3. Behrend, H. PH.D. thesis, University of Birmingham, 1951. 4. Plummer N., Hinkle, L. E. Archs ind. Hlth, 1955, 11, 218. 5. Behrend, H. Occupt. Psychol. 1955, 27, 69. 6. Enterline, P. E. Archs envir. Hlth, 1966, 12, 467. 7. Ministry of Pensions and National Insurance. Report on an Enquiry into the Incidence of Incapacity for Work: part II. H.M. Stationery Office, 1965. 8. Buzzard, R. D., Liddell, F. D. K. Coalminers’ Attendance at Work. London, 1963. 9. Morris, J. N., Titmuss, R. M. Lancet, 1944, ii, 841. 10. Registrar General. Decennial Supplement England and Wales, 1961: area mortality tables. H.M. Stationery Office, 1967. 11. Gardner, M. J., Crawford, M. D., Morris, J. N. Br. J. prev. soc. Med. 1969, 23, 133.
Points of View HIPPOCAMPUS AND MEMORY ERIC TURNER
Department of Neurosurgery, Queen Elizabeth Hospital, Birmingham 15 seems that the hippocampus is concerned in human beings with imprinting and early recall of memories. Experiments on animals give confusing results but can be reconciled with this view. A theory is put forward to explain how the hippocampus may perform this function. By taking part temporarily in each fresh engram, and conveying temporal orientation by slow spatial scanning across its breadth, it can perform the two functions relating to memory that experience in clinical neurosurgery has caused us to attribute to it. With increasing age the hippocampus becomes less versatile. " A man is as old as his hippocampi."
Summary
It
INTRODUCTION
THE perennial popularity of schemes to improve memory testify to the widespread interest in this faculty which represents to us more than any other the significance of our existence. Everyone is involved if only because most of us would like to improve our own memory and are aware of subtle changes in its characteristics with advancing years: recently acquired knowledge is less easily memorised especially if it has little significance for us; and ability to recall information, like many other abilities, is more easily distracted by multiplicity of sensory stimuli-we are less able to concentrate with background noise or activity and need quiet surroundings for study and concentration more than we did when we were young.
The
neurophysiological basis of
memory is
begin-
be understood much better though a great deal remains to be done experimentally and a number of the gaps can be filled up to the present only by a reasonable
ning
to
conjecture. The different
to the word of what forms of memory are being discussed. For the purposes of this article, the function of memory will be analysed into a scheme that can be supported by experimental evidence:
memory call for
meanings attached
a statement
(a) Committal to memory of the current experience. (b) Consolidation of the memory traces: phase 1, the first hour (can be influenced, e.g., by electrical means); phase 2, the first five hours (can be influenced, e.g., by chemical means 1-3). (c) Recall: early, during the first five hours while consolidation is proceeding; late, after consolidation has taken place. These categories of the function of memory will be discussed in detail later but in general it can be said that in man, at least, the structure that plays the most crucial part in the functions of committal to memory and early recall is the hippocampus. Since Scoville and Milner’s4 reports of impairment of these functions
1124
after surgical damage to the hippocampus bilaterally, this fact, long suspected, has been securely established. It confirms a number of early ideas about hippocampal function in man. In 1933, Herricksuggested that the rhinencephalon, of which the hippocampus was reckoned to be a part, might have taken over the function of a non-specific activator of all cortical activity " lowering its threshold or increasing its sensitivity or exerting inhibitory influences ". Thus it might influence behaviour in the form of learning, capacity, memory, and so on, as a differential influence upon cortical and subcortical functions. Having no localising pattern of its own it might yet act on systems which have. Subsequent experimental work and argument have not substantially disproved any of that early conjecture.
of these. Attention can be deliberately prolonged to the exclusion of subsequent stimuli so that the period of the original experience can be extended from a few moments up to a minute or two, and this is sufficient for some degree of permanent memory ultimately to form. Clear orientation and an ensuing period free of distractions especially of similar stimuli aid the process. As a strength-duration curve, this process is under the influence of emotional factors, self-interest, and goalseeking. A close relationship exists between the limbic lobe of Broca, including the hippocampal formation, and these emotional and temperamental factors. If the hippocampus takes part, as it almost certainly does, in the original committal to memory, it should be explained that it does not contain the ultimate permanent memory trace, but like an internal switch mechanism makes possible the laying down of the permanent memory elsewhere.
Learning in animals is an especially difficult subject and the experimental evidence is confusing and contradictory, often because the conditions of investigation 6 vary and are not comparable with the situation in man. Under certain circumstances in animals, learning is improved by hippocampal lesions. Thus Isaacson et al.,’ working with dogs and rats, found facilitation of one type of learning after lesions in the hippocampus
Consolidation of the Memory Trace Consolidation takes place in the ordinary pathways of cortex and subcortical structures of the parietal, occipital, temporal, and frontal lobes. Once it is fully established it takes widespread destruction, as in presenile dementia, to affect it grossly.
and found also that retention in these animals was perfect from day to day. Douglas,S however, after a comprehensive review of the evidence, is prepared to explain away any discrepancies between animal work and human findings on the basis that very extensive damage, especially in animals, must be made before its function is abolished, that the ways in which learning is tested are much simpler in animals than in man, and that it is only when more complex information is interfered with that the characteristic findings are made after hippocampal lesions as in man. The crux of his argument is that through hippocampal deficiency the subject lacks the inhibitory mechanism to prevent distractability. " It is suggested that the hippocampus might function to protect memory traces during a crucial stage of consolidation through an exclusion of interfering stimuli." I was thinking along the same lines some time ago.9s If we confine our attention, therefore, to the considerable clinical information which is available, particularly from surgical treatment of limbic epilepsy, we find that the extreme anterior tip of the hippocampus can be destroyed or isolated to a distance 1 cm. back from the tip, that is just at the junction between the uncus and the body of the hippocampus, without any significant effect on memory, the only semipermanent effect being an impairment of the ability to learn completely novel association of words; and even this refined impairment of learning becomes insignificant in younger people after three years. the hippocampus further back, profound memory defect affecting both committal to memory and early recall. We may turn our attention, therefore, to this set of facts and try to analyse the function of memory further.
Bilateral
damage
however, induces
to
a
MEMORY FUNCTION
Committal to Memory Committal to memory is a function of intensity of attention, alertness, and concentration together with the duration
Recall
Early recall is different physiologically from late recall, and this process of early recall is the one for which the integrity of the hippocampus is essential. Minor degrees of damage to the hippocampus, for example to the anterior parts of it in and near the uncus, unilaterally or bilaterally, will give rise to minor deficiencies of memorising and early recall.1O Complete bilateral destruction of the hippocampus or of its connections as far as the mammillary bodies, reticular formation, and mammillothalamic tract virtually abolishes early recall. Despite the resulting disturbance of orientation a certain amount of material gets through to permanent consolidation of memory but this amount is limited, and its nature has not been clearly analysed, though memory of sequential tasks (e.g., maze or jigsaw puzzles) is certainly not retained. How the nervous system records the sequence in which events occur is not known. In distant memory it is largely by associational and circumstantial means, but in recent recall there is straightforward memory of the order of events as a primary faculty. For this the hippocampus is required and it seems almost certain that the order is recorded in some spatial fashion. Late recall is independent of the hippocampal structures. Once permanent memory traces are established there are obviously other ways by which the memory pathways can be reached for recall of distant recollections. STRUCTURE AND RELATIONS OF HIPPOCAMPUS
The hippocampus
probably facilitates committal to both memory directly and by means of early recall. It has projections which can readily influence attention, and being itself phylogenetically ancient and surrounded by ancient or transitional cortex whose function is nowadays connected with emotion, autonomic functions, and temperament, it is well placed to fulfil both of these roles-i.e., to aid committal to memory at a first experience, to protect the trace from interference, with clear orientation at the time, and subsequently, and to fortify the initial committal to memory of the experience by promoting early recall on one or more
occasions.
How the hippocampus does this is speculative, but it may be that the initial trace of any pathway through
1125
it persists for a day or so, after which it fades without consolidation. This could rather neatly fill in the gap before permanent memory traces are consolidated, and this hypothesis would explain why the hippocampus is not necessary for late recall. Its internal structure, with the curled appearance of Ammon’s horn on cross-section, its different sectors of pyramidal cells, its primitive four-layered cortex of origin, and the mossy-fibre system described by McLardy,l,2 all represent an intriguing puzzle. Complicated though it is, it may represent a unified function which will lend itself to analysis before the isocortex. The mossyfibre system, for example, with its syncytial network could well retain a facilitatory pathway for some hours. The
recording of stimuli in sequence demands another type of topography. The banks of pyramidal cells
spread out across the cross-section of the hippocampus. Now if a signal involving the hippocampus in part of its original engram pathway starts at the subicular end of C.A.I. of the pyramidal bank and becomes slowly displaced towards the other side, being replaced at the original end by more recent impulses, the result would be a spatial analysis of temporal events, and the only further requirement would be a suitable method of reading the result. Such a signal would become effete and would fade after reaching the " older " end of the cellular bank, by which time consolidation would be complete. The dentate gyrus and the mossy-fibre system could retain the trace for an intermediate period. My results from temporal lobotomy, with application in 47 of the cases of a lesion across the junction of the uncus with the main body of the hippocampus are
indicate that the effect
on
memory from such anterior
lesions is not obvious to the individual or the observer. It corresponds with the effect of ablation, as in the partial temporal lobectomies of Falconer. An interesting temporary effect of application of bilateral stereotaxic electrolytic lesions of radio frequency to the hippocampus under local anaesthesia is that a temporary hippocampal shock is produced lasting a few minutes up to an hour or so. The patient experiences a sensation of complete loss of memory. He is disoriented and does not know where he is, what time it is, or why he is in the place he sees round him. Nevertheless, he can remember his identity and past events usually extending backwards from the previous day. This passes off in an hour or so, leaving him completely oriented, but with amnesia for the period of time when he was disoriented. Thereafter memory function is normal except for the psychometric subtlety elicited by artificial test situations of learning. Thus learning of random pairs of words is impaired, but richly associational words and ideas are learned and remembered. The
separation of performance along the long axis hippocampus is clearly on an analytical not a spatiotemporal basis, and this leaves the analysis of
of the
function in a transverse direction open to the interpretation outlined above. The afferent flow from
parietal, occipital, and posterior temporal sources enters the subicular end of the molecular layer of C.A.I. behind the uncohippocampal junction 13 and contacts
the dendrites of cells of the hippocampus and dentate gyrus. The cells of the hippocampus not only have dendrites in the molecular layer, but also a second set of dendrites arising from the base of the pyramidal cells passing into the polymorphous layer, from which still other cells send axons back to the molecular layer. The axons of the pyramidal cells of course pass into the alveus, fimbria, and fornix. The axons of the dentate gyrus skirt the cellular layer of the hippocampus where they finally end after running some distance. Other axons pass directly into the alveus from the dentate gyrus. Such an anatomical arrangement would be perfectly suitable for the slow scanning of temporally presented impulses into a spatial pattern ending in a semipermanent trace without clearcut temporal orientation in the dentate gyrus and its multisynaptic connections. Disturbances of the function outlined could very
easily account for the deja-vu phenomenon seen not infrequently in temporal-lobe epilepsy and in many young people. This hippocampal analysis of temporal sequence into spatial configuration refers to cerebral " events " or perceptive " experiences ". The components of events occupy a shorter time and are analysed by the appropriate isocortical areas in sequential patterns, probably by successive orders of neural networks, each occupied by longer and longer spans of time, so that, for example, B-U-T can be distinguished in one span from T-U-B, when presented to the auditory pathway. This in turn invites consideration of the period of time that the
nervous system identifies as " the and what stretches of time the brain will present " in one moment of experience. Obviously this engulf is long by physical standards, but one perceptive experience may well incorporate many moments of present, before that passes into even immediate memory. If the smallest stretch of present time that need be considered is described as the minimal accumulative moment, this can be made as small as is required for any purpose, provided it does not become At the other end of the scale it may encompass zero. a continuous experience lasting minutes.
Such a gross slowing of cerebral processes is likely be achieved at least in part by reverberating circuits through groups of cells and their associated synaptic networks. Repeated pathways will pass through contiguous but not identical routes, a feature which renders them less vulnerable to physiological and pathological changes, cellular loss and other forms of to
decay. Two kinds of reverberation are proposed here, one kind of microreverberation involving the internal structure of the hippocampus. An impulse comes into this structure somewhere along its length by a feed-in from other cortical areas. This impulse, if favoured, secures attention for its engram and a certain amount of reverberation in the whole engram circuit ensues. When this ceases, the hippocampal part of the trace remains available for short-term memory and early recall, but I suggest that it gradually a
1126
transfers its facilitation medially by means of microscopic internal hippocampal reverberations which convey to the pathway a stacking order, as if successive impulses were put in like articles on a production line in a factory. After the immediate memory need is past, and depending probably on the number of fresh experiences presented to the hippocampus within a given time, the immediate raw sequential memory fades and is replaced by the permanent memory trace which has meanwhile become consolidated by chemical means in the rest of the cortical and subcortical structures. According to this proposal, therefore, the hippocampus is involved in two kinds of reverberation : first, the global reverberation that exists at the holistic level of the engram to which, secondly, the other microscopic internal hippocampal reverberation contributes a temporary temporal orientation. In man the part of the hippocampus involved in associational integrative speech and abstract function is large, whereas in animals this probably occupies quite a small part of the hippocampus. Simpler, more emotional, and less complicated in the intellectual sense are the functions residing in the extreme tip of the hippocampus in man and probably a larger part in animals. The analysis proposed here refers particularly to this posterior part of the hippocampus which is so largely represented in the human brain. It is banal to remark that a man is as old as his
Occasional
Survey
MANAGEMENT OF THE ADOLESCENT WITH CEREBRAL PALSY I. A. WILLIAMS Wells and Tunbridge Hastings Hospitals Group, and Thomas De la Rue and Dene Park Schools, Spastics Society,
Tonbridge, Kent The cerebral palsied patient needs more diverse specialist treatment than any other. Above all, it is a continuing treatment and needs to be reassessed regularly. It requires the knowledge of the orthopædic surgeon, physical medicine specialist and psychiatrist, besides medical, social, educational, speech therapy, and rehabilitation experts. It also requires the interest of parent and, above all (and this is very often forgotten) it needs the help and cooperation of the patient. Many cerebral palsied patients are not mentally subnormal and attain a good insight into their disability as they grow older, and if their advice and active cooperation are sought, this insight can be invaluable in programming their treatment. Above all, it is important to remember that cerebral palsied babies
Sum ary
grow up. INTRODUCTION
WHEN a child with cerebral palsy reaches adolescence it is reasonable to assume that the diagnosis has been established, that the relevant neurological investigations have been performed, and that the child has been receiving medical care, usually in a pxdiatric or ortho-
arteries. It is probably truer that we are as old and as efficient as our hippocampus. It is often said also that ageing begins at twenty-five yet obvious dementia is still a long way off. It is more a modification of hippocampal function that takes place with age, a restriction of the ability to take in several impressions at once, an
increasing vulnerability
to
distraction,
a
restriction of the number of completely new facts that can be imprinted on the memory in a day, and a reduction in the speed with which successive tasks can be undertaken without confusion. These are familiar accompaniments of age, and they are, all of them, explained better than in any other way by changing ability of the hippocampus with age to cope with the incoming stimuli. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.
John, E. R. Mechanisms of Memory; p. 39. London, 1967. Albert, D. J. Neuropsychologia, 1966, 4, 49. Albert, D. J. ibid. p. 65. Scoville, W. B., Milner, B. J. Neurol. Neurosurg. Psychiat. 1957, 20, 11. Herrick, C. J. Proc. natn Acad. Sci. U.S.A. 1933, 19, 7. McGuiness, J. Personal communication. Isaacson, R. L., Douglas, R. J., Moore, R. Y. J. comp. Physiol. Psychol. 1961, 54, 625. Douglas, R. J. Psychol. Bull. 1967, 67, 416. Turner, E. Lancet, 1955, ii, 1305. Blakemore, C. B., Falconer, M. A. J. Neurol. Neurosurg. Psychiat. 1967, 30, 364. McLardy, T. Prog. Brain Res. 1963, 3, 71. McLardy, T. Perspect. Biol. Med. 1959, 2, 443. Schneider, R. C., Crosby, E. C., Kahn, E. A. Prog. Brain Res. 3, 191.
that a certain been given. It is make these assumpand when an adolescent with apparent tions, seeing cerebral palsy for the first time it is important to undertake a medical and surgical reassessment and, if necessary, arrange for further investigation. Before considering the future, the child’s previous treatment should be evaluated. Generally, the types of physical treatment a child has had, fall into the following
paedic department. amount of physical
One also
assumes
treatment has not, however, always safe to
categories: (1) The child may not have had treatment of any type (medical, surgical, physiotherapy, speech therapy). This is not unusual since, in many areas, treatment offered by the Health Service is scanty; the parents may not be able to spare or afford the time to convey the child to a local hospital or centre for treatment. In some cases parents will deliberately avoid medical advice or treatment to prevent their abnormal child being exposed to the outside world. (2) The child may have been fortunate and received adequate treatment at either a residential or non-residential centre. Deformities may have been helped by surgery, and mobility by physiotherapy or provision of appliances. Visual and aural disabilities may have been recognised and rectified as far as possible. A dysphasic child may have had the benefit of speech therapy. (3) The child may have been overtreated. Anxious, enthusiastic parents, who are very often unaware of the nature of the child’s disability, fail to appreciate that treatment can modify but never alter the underlying cerebral lesion. REASSESSMENT
The primary object of treatment in a cerebral palsied adolescent is the attainment of independence. But this
called for, the absence-rate rose-but so did weekly attendance. Since the war the normal weekly hours of work in British industry have fallen from 44.4 in 1949 to 40-2 in 1968 but the numbers involved in short-time working have been very small. These complicating factors are avoided by using the measures of frequency and severity described in this paper. The comparisons for 1961-62 in both the regions and the thirty-eight urban areas raise other problems by showing significant positive associations between unemployment and sickness absence. Although the chronic sick may find it difficult to get work and the unemployed may become depressed, there is no evidence to suggest that unemployment in the area actually causes illness in those employed. Indeed Morris and Titmuss 9 noted that unemployment seemed to reduce mortality from peptic ulcer. As might be expected, however, a comparison of the standardised mortality-ratios for the years 1959-631° with the data on sickness for these thirtyeight urban areas showed a significantly positive association (r=0-68), but not with the levels of unemployment (r=0-22). An analysis by Gardner et al.ll of mortality in the larger county boroughs of England and Wales revealed a significant relationship with a number of socioeconomic, climatic, and environmental variables. The rank order of sicknessrates in the thirty-eight urban areas studied by us relates closely to the " social factor " scores calculated by Gardner et al. and his colleagues. A positive association between unemployment and sickness does not necessarily imply causation and it is likely that both may be influenced by underlying socioeconomic and environmental factors such as the type of industry predominant in the area. It seems reasonable to conclude that the levels of unemployment experienced in Great Britain in the past two decades have not significantly influenced the rates of certified incapacity for work. In times or in countries with low social-security benefits such a relationship may well be found, but not under present conditions with comparatively high benefits. We thank members of the statistics divisions of the Department of Health and Social Security and the Department of Employment and Productivity for their help in obtaining the data, and for their constructive criticism in the preparation of this paper.
Requests
for
reprints should
be addressed to P.
J. T.
REFERENCES 1. Florence, P. S. Economics of Fatigue and Unrest. London, 1924. 2. Young, A. F. Soc. Sci. Q. 1961, 35, 65. 3. Behrend, H. PH.D. thesis, University of Birmingham, 1951. 4. Plummer N., Hinkle, L. E. Archs ind. Hlth, 1955, 11, 218. 5. Behrend, H. Occupt. Psychol. 1955, 27, 69. 6. Enterline, P. E. Archs envir. Hlth, 1966, 12, 467. 7. Ministry of Pensions and National Insurance. Report on an Enquiry into the Incidence of Incapacity for Work: part II. H.M. Stationery Office, 1965. 8. Buzzard, R. D., Liddell, F. D. K. Coalminers’ Attendance at Work. London, 1963. 9. Morris, J. N., Titmuss, R. M. Lancet, 1944, ii, 841. 10. Registrar General. Decennial Supplement England and Wales, 1961: area mortality tables. H.M. Stationery Office, 1967. 11. Gardner, M. J., Crawford, M. D., Morris, J. N. Br. J. prev. soc. Med. 1969, 23, 133.
Points of View HIPPOCAMPUS AND MEMORY ERIC TURNER
Department of Neurosurgery, Queen Elizabeth Hospital, Birmingham 15 seems that the hippocampus is concerned in human beings with imprinting and early recall of memories. Experiments on animals give confusing results but can be reconciled with this view. A theory is put forward to explain how the hippocampus may perform this function. By taking part temporarily in each fresh engram, and conveying temporal orientation by slow spatial scanning across its breadth, it can perform the two functions relating to memory that experience in clinical neurosurgery has caused us to attribute to it. With increasing age the hippocampus becomes less versatile. " A man is as old as his hippocampi."
Summary
It
INTRODUCTION
THE perennial popularity of schemes to improve memory testify to the widespread interest in this faculty which represents to us more than any other the significance of our existence. Everyone is involved if only because most of us would like to improve our own memory and are aware of subtle changes in its characteristics with advancing years: recently acquired knowledge is less easily memorised especially if it has little significance for us; and ability to recall information, like many other abilities, is more easily distracted by multiplicity of sensory stimuli-we are less able to concentrate with background noise or activity and need quiet surroundings for study and concentration more than we did when we were young.
The
neurophysiological basis of
memory is
begin-
be understood much better though a great deal remains to be done experimentally and a number of the gaps can be filled up to the present only by a reasonable
ning
to
conjecture. The different
to the word of what forms of memory are being discussed. For the purposes of this article, the function of memory will be analysed into a scheme that can be supported by experimental evidence:
memory call for
meanings attached
a statement
(a) Committal to memory of the current experience. (b) Consolidation of the memory traces: phase 1, the first hour (can be influenced, e.g., by electrical means); phase 2, the first five hours (can be influenced, e.g., by chemical means 1-3). (c) Recall: early, during the first five hours while consolidation is proceeding; late, after consolidation has taken place. These categories of the function of memory will be discussed in detail later but in general it can be said that in man, at least, the structure that plays the most crucial part in the functions of committal to memory and early recall is the hippocampus. Since Scoville and Milner’s4 reports of impairment of these functions
1124
after surgical damage to the hippocampus bilaterally, this fact, long suspected, has been securely established. It confirms a number of early ideas about hippocampal function in man. In 1933, Herricksuggested that the rhinencephalon, of which the hippocampus was reckoned to be a part, might have taken over the function of a non-specific activator of all cortical activity " lowering its threshold or increasing its sensitivity or exerting inhibitory influences ". Thus it might influence behaviour in the form of learning, capacity, memory, and so on, as a differential influence upon cortical and subcortical functions. Having no localising pattern of its own it might yet act on systems which have. Subsequent experimental work and argument have not substantially disproved any of that early conjecture.
of these. Attention can be deliberately prolonged to the exclusion of subsequent stimuli so that the period of the original experience can be extended from a few moments up to a minute or two, and this is sufficient for some degree of permanent memory ultimately to form. Clear orientation and an ensuing period free of distractions especially of similar stimuli aid the process. As a strength-duration curve, this process is under the influence of emotional factors, self-interest, and goalseeking. A close relationship exists between the limbic lobe of Broca, including the hippocampal formation, and these emotional and temperamental factors. If the hippocampus takes part, as it almost certainly does, in the original committal to memory, it should be explained that it does not contain the ultimate permanent memory trace, but like an internal switch mechanism makes possible the laying down of the permanent memory elsewhere.
Learning in animals is an especially difficult subject and the experimental evidence is confusing and contradictory, often because the conditions of investigation 6 vary and are not comparable with the situation in man. Under certain circumstances in animals, learning is improved by hippocampal lesions. Thus Isaacson et al.,’ working with dogs and rats, found facilitation of one type of learning after lesions in the hippocampus
Consolidation of the Memory Trace Consolidation takes place in the ordinary pathways of cortex and subcortical structures of the parietal, occipital, temporal, and frontal lobes. Once it is fully established it takes widespread destruction, as in presenile dementia, to affect it grossly.
and found also that retention in these animals was perfect from day to day. Douglas,S however, after a comprehensive review of the evidence, is prepared to explain away any discrepancies between animal work and human findings on the basis that very extensive damage, especially in animals, must be made before its function is abolished, that the ways in which learning is tested are much simpler in animals than in man, and that it is only when more complex information is interfered with that the characteristic findings are made after hippocampal lesions as in man. The crux of his argument is that through hippocampal deficiency the subject lacks the inhibitory mechanism to prevent distractability. " It is suggested that the hippocampus might function to protect memory traces during a crucial stage of consolidation through an exclusion of interfering stimuli." I was thinking along the same lines some time ago.9s If we confine our attention, therefore, to the considerable clinical information which is available, particularly from surgical treatment of limbic epilepsy, we find that the extreme anterior tip of the hippocampus can be destroyed or isolated to a distance 1 cm. back from the tip, that is just at the junction between the uncus and the body of the hippocampus, without any significant effect on memory, the only semipermanent effect being an impairment of the ability to learn completely novel association of words; and even this refined impairment of learning becomes insignificant in younger people after three years. the hippocampus further back, profound memory defect affecting both committal to memory and early recall. We may turn our attention, therefore, to this set of facts and try to analyse the function of memory further.
Bilateral
damage
however, induces
to
a
MEMORY FUNCTION
Committal to Memory Committal to memory is a function of intensity of attention, alertness, and concentration together with the duration
Recall
Early recall is different physiologically from late recall, and this process of early recall is the one for which the integrity of the hippocampus is essential. Minor degrees of damage to the hippocampus, for example to the anterior parts of it in and near the uncus, unilaterally or bilaterally, will give rise to minor deficiencies of memorising and early recall.1O Complete bilateral destruction of the hippocampus or of its connections as far as the mammillary bodies, reticular formation, and mammillothalamic tract virtually abolishes early recall. Despite the resulting disturbance of orientation a certain amount of material gets through to permanent consolidation of memory but this amount is limited, and its nature has not been clearly analysed, though memory of sequential tasks (e.g., maze or jigsaw puzzles) is certainly not retained. How the nervous system records the sequence in which events occur is not known. In distant memory it is largely by associational and circumstantial means, but in recent recall there is straightforward memory of the order of events as a primary faculty. For this the hippocampus is required and it seems almost certain that the order is recorded in some spatial fashion. Late recall is independent of the hippocampal structures. Once permanent memory traces are established there are obviously other ways by which the memory pathways can be reached for recall of distant recollections. STRUCTURE AND RELATIONS OF HIPPOCAMPUS
The hippocampus
probably facilitates committal to both memory directly and by means of early recall. It has projections which can readily influence attention, and being itself phylogenetically ancient and surrounded by ancient or transitional cortex whose function is nowadays connected with emotion, autonomic functions, and temperament, it is well placed to fulfil both of these roles-i.e., to aid committal to memory at a first experience, to protect the trace from interference, with clear orientation at the time, and subsequently, and to fortify the initial committal to memory of the experience by promoting early recall on one or more
occasions.
How the hippocampus does this is speculative, but it may be that the initial trace of any pathway through
1125
it persists for a day or so, after which it fades without consolidation. This could rather neatly fill in the gap before permanent memory traces are consolidated, and this hypothesis would explain why the hippocampus is not necessary for late recall. Its internal structure, with the curled appearance of Ammon’s horn on cross-section, its different sectors of pyramidal cells, its primitive four-layered cortex of origin, and the mossy-fibre system described by McLardy,l,2 all represent an intriguing puzzle. Complicated though it is, it may represent a unified function which will lend itself to analysis before the isocortex. The mossyfibre system, for example, with its syncytial network could well retain a facilitatory pathway for some hours. The
recording of stimuli in sequence demands another type of topography. The banks of pyramidal cells
spread out across the cross-section of the hippocampus. Now if a signal involving the hippocampus in part of its original engram pathway starts at the subicular end of C.A.I. of the pyramidal bank and becomes slowly displaced towards the other side, being replaced at the original end by more recent impulses, the result would be a spatial analysis of temporal events, and the only further requirement would be a suitable method of reading the result. Such a signal would become effete and would fade after reaching the " older " end of the cellular bank, by which time consolidation would be complete. The dentate gyrus and the mossy-fibre system could retain the trace for an intermediate period. My results from temporal lobotomy, with application in 47 of the cases of a lesion across the junction of the uncus with the main body of the hippocampus are
indicate that the effect
on
memory from such anterior
lesions is not obvious to the individual or the observer. It corresponds with the effect of ablation, as in the partial temporal lobectomies of Falconer. An interesting temporary effect of application of bilateral stereotaxic electrolytic lesions of radio frequency to the hippocampus under local anaesthesia is that a temporary hippocampal shock is produced lasting a few minutes up to an hour or so. The patient experiences a sensation of complete loss of memory. He is disoriented and does not know where he is, what time it is, or why he is in the place he sees round him. Nevertheless, he can remember his identity and past events usually extending backwards from the previous day. This passes off in an hour or so, leaving him completely oriented, but with amnesia for the period of time when he was disoriented. Thereafter memory function is normal except for the psychometric subtlety elicited by artificial test situations of learning. Thus learning of random pairs of words is impaired, but richly associational words and ideas are learned and remembered. The
separation of performance along the long axis hippocampus is clearly on an analytical not a spatiotemporal basis, and this leaves the analysis of
of the
function in a transverse direction open to the interpretation outlined above. The afferent flow from
parietal, occipital, and posterior temporal sources enters the subicular end of the molecular layer of C.A.I. behind the uncohippocampal junction 13 and contacts
the dendrites of cells of the hippocampus and dentate gyrus. The cells of the hippocampus not only have dendrites in the molecular layer, but also a second set of dendrites arising from the base of the pyramidal cells passing into the polymorphous layer, from which still other cells send axons back to the molecular layer. The axons of the pyramidal cells of course pass into the alveus, fimbria, and fornix. The axons of the dentate gyrus skirt the cellular layer of the hippocampus where they finally end after running some distance. Other axons pass directly into the alveus from the dentate gyrus. Such an anatomical arrangement would be perfectly suitable for the slow scanning of temporally presented impulses into a spatial pattern ending in a semipermanent trace without clearcut temporal orientation in the dentate gyrus and its multisynaptic connections. Disturbances of the function outlined could very
easily account for the deja-vu phenomenon seen not infrequently in temporal-lobe epilepsy and in many young people. This hippocampal analysis of temporal sequence into spatial configuration refers to cerebral " events " or perceptive " experiences ". The components of events occupy a shorter time and are analysed by the appropriate isocortical areas in sequential patterns, probably by successive orders of neural networks, each occupied by longer and longer spans of time, so that, for example, B-U-T can be distinguished in one span from T-U-B, when presented to the auditory pathway. This in turn invites consideration of the period of time that the
nervous system identifies as " the and what stretches of time the brain will present " in one moment of experience. Obviously this engulf is long by physical standards, but one perceptive experience may well incorporate many moments of present, before that passes into even immediate memory. If the smallest stretch of present time that need be considered is described as the minimal accumulative moment, this can be made as small as is required for any purpose, provided it does not become At the other end of the scale it may encompass zero. a continuous experience lasting minutes.
Such a gross slowing of cerebral processes is likely be achieved at least in part by reverberating circuits through groups of cells and their associated synaptic networks. Repeated pathways will pass through contiguous but not identical routes, a feature which renders them less vulnerable to physiological and pathological changes, cellular loss and other forms of to
decay. Two kinds of reverberation are proposed here, one kind of microreverberation involving the internal structure of the hippocampus. An impulse comes into this structure somewhere along its length by a feed-in from other cortical areas. This impulse, if favoured, secures attention for its engram and a certain amount of reverberation in the whole engram circuit ensues. When this ceases, the hippocampal part of the trace remains available for short-term memory and early recall, but I suggest that it gradually a
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transfers its facilitation medially by means of microscopic internal hippocampal reverberations which convey to the pathway a stacking order, as if successive impulses were put in like articles on a production line in a factory. After the immediate memory need is past, and depending probably on the number of fresh experiences presented to the hippocampus within a given time, the immediate raw sequential memory fades and is replaced by the permanent memory trace which has meanwhile become consolidated by chemical means in the rest of the cortical and subcortical structures. According to this proposal, therefore, the hippocampus is involved in two kinds of reverberation : first, the global reverberation that exists at the holistic level of the engram to which, secondly, the other microscopic internal hippocampal reverberation contributes a temporary temporal orientation. In man the part of the hippocampus involved in associational integrative speech and abstract function is large, whereas in animals this probably occupies quite a small part of the hippocampus. Simpler, more emotional, and less complicated in the intellectual sense are the functions residing in the extreme tip of the hippocampus in man and probably a larger part in animals. The analysis proposed here refers particularly to this posterior part of the hippocampus which is so largely represented in the human brain. It is banal to remark that a man is as old as his
Occasional
Survey
MANAGEMENT OF THE ADOLESCENT WITH CEREBRAL PALSY I. A. WILLIAMS Wells and Tunbridge Hastings Hospitals Group, and Thomas De la Rue and Dene Park Schools, Spastics Society,
Tonbridge, Kent The cerebral palsied patient needs more diverse specialist treatment than any other. Above all, it is a continuing treatment and needs to be reassessed regularly. It requires the knowledge of the orthopædic surgeon, physical medicine specialist and psychiatrist, besides medical, social, educational, speech therapy, and rehabilitation experts. It also requires the interest of parent and, above all (and this is very often forgotten) it needs the help and cooperation of the patient. Many cerebral palsied patients are not mentally subnormal and attain a good insight into their disability as they grow older, and if their advice and active cooperation are sought, this insight can be invaluable in programming their treatment. Above all, it is important to remember that cerebral palsied babies
Sum ary
grow up. INTRODUCTION
WHEN a child with cerebral palsy reaches adolescence it is reasonable to assume that the diagnosis has been established, that the relevant neurological investigations have been performed, and that the child has been receiving medical care, usually in a pxdiatric or ortho-
arteries. It is probably truer that we are as old and as efficient as our hippocampus. It is often said also that ageing begins at twenty-five yet obvious dementia is still a long way off. It is more a modification of hippocampal function that takes place with age, a restriction of the ability to take in several impressions at once, an
increasing vulnerability
to
distraction,
a
restriction of the number of completely new facts that can be imprinted on the memory in a day, and a reduction in the speed with which successive tasks can be undertaken without confusion. These are familiar accompaniments of age, and they are, all of them, explained better than in any other way by changing ability of the hippocampus with age to cope with the incoming stimuli. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.
John, E. R. Mechanisms of Memory; p. 39. London, 1967. Albert, D. J. Neuropsychologia, 1966, 4, 49. Albert, D. J. ibid. p. 65. Scoville, W. B., Milner, B. J. Neurol. Neurosurg. Psychiat. 1957, 20, 11. Herrick, C. J. Proc. natn Acad. Sci. U.S.A. 1933, 19, 7. McGuiness, J. Personal communication. Isaacson, R. L., Douglas, R. J., Moore, R. Y. J. comp. Physiol. Psychol. 1961, 54, 625. Douglas, R. J. Psychol. Bull. 1967, 67, 416. Turner, E. Lancet, 1955, ii, 1305. Blakemore, C. B., Falconer, M. A. J. Neurol. Neurosurg. Psychiat. 1967, 30, 364. McLardy, T. Prog. Brain Res. 1963, 3, 71. McLardy, T. Perspect. Biol. Med. 1959, 2, 443. Schneider, R. C., Crosby, E. C., Kahn, E. A. Prog. Brain Res. 3, 191.
that a certain been given. It is make these assumpand when an adolescent with apparent tions, seeing cerebral palsy for the first time it is important to undertake a medical and surgical reassessment and, if necessary, arrange for further investigation. Before considering the future, the child’s previous treatment should be evaluated. Generally, the types of physical treatment a child has had, fall into the following
paedic department. amount of physical
One also
assumes
treatment has not, however, always safe to
categories: (1) The child may not have had treatment of any type (medical, surgical, physiotherapy, speech therapy). This is not unusual since, in many areas, treatment offered by the Health Service is scanty; the parents may not be able to spare or afford the time to convey the child to a local hospital or centre for treatment. In some cases parents will deliberately avoid medical advice or treatment to prevent their abnormal child being exposed to the outside world. (2) The child may have been fortunate and received adequate treatment at either a residential or non-residential centre. Deformities may have been helped by surgery, and mobility by physiotherapy or provision of appliances. Visual and aural disabilities may have been recognised and rectified as far as possible. A dysphasic child may have had the benefit of speech therapy. (3) The child may have been overtreated. Anxious, enthusiastic parents, who are very often unaware of the nature of the child’s disability, fail to appreciate that treatment can modify but never alter the underlying cerebral lesion. REASSESSMENT
The primary object of treatment in a cerebral palsied adolescent is the attainment of independence. But this