Number 104 : December 2000 |
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The study of memory presents a difficult puzzle for research. In a sense, memory may be regarded as a central link between the mental and the physical aspects of existence; and as such, a prime feature of the human intellect and higher bodily functions. The main difficulty in studying memory is its inaccessibility, as well as its overlaps to various degrees with learning, cognition, intelligence, creativity, motivation, emotion, etc.
Memory, or the capacity to retain experience for future reference, is a truly magnificent phenomenon. It is the sine qua non of intelligence, or adaptive behavior. If prior experience would not exert a differential and normative influence upon subsequent behavior, life could be rather chaotic indeed. Habituation, stimulus and response generalizations, etc. would be inconceivable without the mediating effects of memory. The organism would be forced to make new responses to redundant environmental demands, being in a constant state of alert, quickly exhausting energy reservoirs, after which structural-functional breakdown and disintegration would inevitably follow. This magnificent neuropsychological capacity integrally contributes to minimal but indispensable psychophysical safety and efficient function on a routine basis.
Neither memory in particular, nor intelligence in general, may be regarded as a fixed 'hydraulic' trait; but as a dynamic adaptive capacity, that develops in response to environmental demands within the overall genetic framework. The structural equipment is inherited, while the functional abilities develop as prompted by environmental interactions. Heredity is the racehorse upon which the jockey of experience bounces from birth to death.
Is memory a structural capacity or a functional one? Perhaps both? There's no unequivocal consensus either way, and the venerable nature-nurture controversy is still unresolved. Most physiological psychologists would tend to gravitate toward the structural camp, while psychologists less rigorously trained in the natural sciences might favor the functional camp. There have been innumerable albeit unsuccessful attempts to localize memory as a structural feature, even down to the level of molecular biology. Memory research in physiological psychology continues largely in this vein, treating memory as both independent and dependent experimental variables, and hopes that the memory trace will eventually be found. Other psychologists, especially learning theorists, have argued that there's no need to assume that memory has to be a structural feature just because of genetics (remember, about 80% of 'pure' intelligence is inherited). Rather, memory may very well be a function of the various interconnections of the 10 billion neurons that make up its structural basis; just as the audiovisual experience of a working TV set cannot be equated with its wires and tubes. Some scholars propose that it may be a logical mistake to try to separate structure and function, just as the historical separation of mind and body in the sense of the old nature-nurture controversy was meaningless. Structure and function may be different sides of the same coin, similar to matter and energy; and any pigeonholing may be arbitrary and suspect.
While it may be possible to locate some physiological and biochemical features as primarily responsible for memory, it might be a gross oversimplification to attribute memory solely to differential synaptic transmissions or biochemical molecular combinations. Memory is not merely a storage capacity, it is not a warehouse into which bits of experience can be stuffed and retrieved upon demand. Rather, memory seems to be a dynamic capacity, in flexible interactions with structural changes, functional alterations, and various interrelated 'higher mental' processes, such as cognition, learning, intelligence, etc. Perhaps the concept of memory, along with other notions of 'mental function' may be regarded as a single concept of behavioral ability, which may manifest itself in a well-nigh infinite variety of responses. Whether we talk separately about memory, cognition, learning, intelligence, etc. may be for the sake of contextual convenience; but fundamentally, they are situation-specific manifestations of the same underlying capacity for adaptive behavior- i.e. as optimal survival as possible.
Most traditional sources (for example, Dorland's Medical Dictionary, 1965) define memory along the lines of a 'mental faculty' by which sensations, impression, and ideas are recalled. Such definitions might be objectionable because 'recall' implies voluntary or conscious recall, whereas memory also mediates many responses of which we are unaware; and memory has enough bodily correlates to make any clearcut 'mental-physical' distinction a bit obsolete. Many memory studies in the professional literature simply bypass this dilemma altogether.
'Physiological psychology' may be regarded as the scientific study of brain-behavior relationships, interchangeably with such terms as 'neuropsychology' or 'psychophysiology' and including the systematic study of any physiological function related to behavior. 'Memory' itself may be thought of as 'a neuropsychological CNS feature through which past experience may exert a differential influence on present behavior in response to actual or perceived environmental demands'. While this definition is admittedly quite a mouthful, it perhaps summarizes the above considerations; 1.) memory is a Central Nervous System feature, 2.) environmental stimuli differentially affect the organism in the sense of both duration and succession, and 3.) experience writes the book of life on the neonatally blank slate of behavior. Also, by implication, memory greatly facilitates adaptation dynamics.
Physiological psychology studies its subject-matter, in this case memory, within the broad framework of empirical science, which rests upon the philosophy of science. The ultimate aim of this approach is the establishment of functional laws and reproducible processes; in short, the reliable and valid identification of invariances, as required by epistemology, which then advance knowledge. In this quest, physiological psychology relies heavily upon the guideleines of experimental psychology for the formation of its research strategies. Experiments are designed to investigate possible relationships among research variables, while holding other (extraneous) variables constant. Usually this involves the purposeful manipulation of independent variable(s) and the observation of the differential effects of these manipulations upon the dependent variable. Causal relationships may be discovered by careful experimentation; and faithfully observed methodological rigor may eventually lead to useful theories.
Most experimental designs in this context treat memory as the dependent variable, and the brain or its particular aspects as the independent variable(s). However, certain techniques, such as electroconvulsive shock, or various drug treatments, etc., may use memory or its specific features as the independent variable(s), and the effects of such manipulations, as assessed by behavioral indications, as the dependent variable. Examples of such techniques might be ablations, lesions, stimulation, recordings, etc.
Since Hebb’s famous postulates of 1949 in which he presented a "switchboard" model of neuropsychology based on the cytoarchitectonic structure of the brain involving various ’reverberating circuits’ (e.g. Hebb, D.O.: Textbook of Psychology, 3rd ed, Philadelphia: Saunders, 1972), there have been several theories of memory, based on neurophysiology and biochemistry, structural, functional, or both; attempting to explain short, intermediate, and long-term memory. For example, the statistical configuration theory maintains that the common mode of activity in massive numbers of neurons in anatomically extensive systems represent information about learned experience. Different brain regions share a common mode of function during learning. Stimulus activates a representational system, which causes the release of a common activity mode, which will be stored during the learning experience.
In order to illustrate the diversity and the flavor of relevant research, some recent approaches of physiological psychology to the study of memory might be worth mention.
Some biochemical approaches may be focused on the synaptic functions in the mammalian CNS (central nervous system). Memory, in this context, may be associated with either the general metabolism of synaptic junctions, or with the more specialized presynaptic metabolism of neurotransmitters as well as their postsynaptic actions. Such research is promising.
Other approaches classified memory phenomena into the types of image, emotional, and conditioned reflexes. In these contexts, it is assumed that the prefrontal area is critically involved in image memory, especially STM (short-term memory); and emotional and conditioned reflexes are thought to depend on other parts of the neocortex and the paleocortex. However, these approaches are somewhat uncertain about the location and mechanism of LTM (long-term memory).
Some neurological studies on information encoding have proposed a gene-depression model of permanent memory, and theorized about the nature of the association between memory and the neuronal synthesis of RNA and protein.
Others have noted that memory deficits in animals may be alleviated by reactivation treatments. Deficits emanating from immaturity, experimentally-induced amnesia, interference, state-dependent learning, etc. are similarly affected. It is hypothesized that such sources of forgetting impair the retrieval of memories by common mechanisms, either in terms of retrieval effectiveness or by altering the retrieval process itself.
Drug research with animal subjects has explored the facilitation of learning and memory, as well as the analysis of mechanisms that might underlie memory storage.
Other studies have explored the mechanisms involved in protein synthesis as well as the roles of DNA and RNA and related biochemical questions bearing on memory research. The techniques used have ranged from bioassays and radioautography to scintillation and Geiger counting, etc.
Still others, having used cell fractionation and electron microscopy studies, hypothesized a mechanism whereby excitatory input produces alterations in a neuron which results in a long-term increase in transmitter release at its terminals. It was shown that impulse bombardement increases the number of synaptic vesicles. Innate and acquired processes in CNS memory functions may thus be distinguished.
Some research considered memory to be a multidimensional concept effected by several macromolecular changes in the protoplasm. The evanescent arranging and reinforcing mechanisms of memory were discussed in the context of RNA molecules functioning as inducers to depress the gene site during protein synthesis.
Various others felt that memory might reside in the morphology of neuronal arborescences. Namely, at birth the neurons are present in a ’primitive’ form; but as a result of sensory experiential bombardement, rapid proliferation and branching occurs., keeping pace with the growth of memory and learning. The persistence of memory through topological lesions was cited as empirical support, among others.
Comparative studies have examined data from animal and human memory studies, within the theoretical frameworks of various models. Accesses to memory traces (’engrams’) have been found facilitated by habituation and associative learning, and so on. These studies have made extensive use of electrophysiological analyses.
Electrical stimulation of various brain regions is a popular research technique in the study of memory. Among the recent interests is stimulation of the amygdala, or the substantia nigra, as well as other specific brain regions.
Electrical current had also been used for aversive conditioning in many thousands of experimental animals, especially rats. Following aversive conditioning, transcranial subconvulsive voltages had been used at various intervals to observe changes in memory.
Electroconvulsive shock(ECS) and amnesia induced thereby had been extensively employed in memory research. Most results seemed to indicate that ECS might interfere with retrieval rather than with storage. Usually reexposure to the training situation improves memory retrieval despite amnesia.
There were studies which had performed ablations of the visual cortex in rats and have observed that postoperative recovery of discrimination does not involve the relearning of new and independent engrams.
Some research concerned with brain lesions in the study of memory has associated the frontal lobes with STM and /or ITM (intermediate-term memory), and the temporal lobes with LTM, and examined information-processing mechanisms.
Others applied physicochemically induced spreading depression to the problems of interhemispheric memory transfer and subcortically controlled and associative and recovery-of-function processes.
Hibernation and cryogenic techniques had been used to test memory in Citellus Lateralis. It was found that hibernated or ’frozen’ subjects had better retention of learned material than the control groups.
Neonatal mice were trained in T-mazes to observe the subsequent developmental changes. Some interesting longitudinal results have thus been obtained.
Paradoxical sleep as well as sleep disturbances by the use of EEG had been studied in relation to memory. EEG had also been used to test voluntary and involuntary memory in behavioral testing and various psychometric situations.
The complexity of the environment had also been manipulated in order to test memory storage differences.
Animal studies using behavioral indices in the testing of memory had been done for apes, goats, chickens equipped with monocular or binocular goggles, and others.
Somatic measures, cardiac and other physiological measures had also been used to test retention.
Immunology had been used to examine the role of antibodies with respect to memory. Brain homogenate was used to immunize rabbits, whose sera with Gamma-globulin was injected into recipient subjects. Significant memory suppression was found.
State-dependent memory processes had been studied from alcohol intoxication to the influence of various other drugs, such as Metrazol. Chronic users of marijuana showed no performance impairment when tested by psychometric techniques. However, marijuana may cause euphoria, visual and memory disturbances, as well as impairment of performance on verbal tasks, as shown by numerous studies in psychopharmacology. Magnesium pemoline (Cylert) increases depression, while methylphenidate (Ritalin) reduces fatigue; but these drugs have no differential effects on memory per se. Piracetam (UC13 6215) is nontoxic, does not interfere with general behavior, autonomic functions, arousal or the limbic system, yet it selectively improves memory on several counts, acting on the telencephalic integrative mechanisms (’nootropic’). Blockade of cholinergic structures at engram formation moments may be a determining factor in the mechanisms of the effects of scopolamine and benzacine (impaired conditioning). 100 mg/kg I.P. administration of orotic acid had been found to reduce extinction induced by both normal and electric shock. Camptothecin (as compared to actinomycin) intracranial injections (10-75 micrograms) had been found to depress LTM while having no effect on STM in goldfish. The involvement of biogenic amines in memory formation had been examined. Saline, reserpine, reserpine & DOPA, reserpine & 5-HTP, DOPA, 5-HTP, etc., were injected and found that normal levels of indole amines are important for memory formation. They seem to be primarily involved in passive avoidance, while catecholamines in active avoidance; and memory is affected accordingly. Other drugs that have been investigated in the study of memory would include flurothyl, puromycin, cholinergics, and various combinations with piracetam (SKF38462) and alcohol, etc.
In order to highlight the appropriateness of physiological psychology to the study of memory, it may be considered that there is little doubt that the psychologist needs the physiologist for both verification and explanation. It would be foolhardy to continue to hypothesize a permanent long-term memory if no permanent change can be found physiologically; likewise for any theoretical belief about a neurological change in the organism that is initiated by the reception and encoding of information. The psychologist is limited to behavioral indices of memory changes, but he is free to theorize what these changes may be as long as he does not demand that physiological structure and function be other than what they have been demonstrated to be.
Because of the physiologists’ indispensable importance in the chain of verification and explanation of behavior change, a view has been leveled by students of memory which asks why psychologists who study memory are necessary at all. If the physiologists have to do all the explaining, why not leave the study of memory to them altogether. The answer to this query is really quite simple. The task of the research psychologist has always been descriptive and will remain so in the field of memory. But the (specialist) physiologist will need these (general) descriptions and theories in order to explain memory. It would be extremely difficult and perhaps misleading to attempt an explanation of memory without first having some theoretical orientation and description of what memory is. The stages of memory, its interactions between these stages and between other psychological variables, must all be described and comprehended before an explanation can begin. The physiologist is primarily trained to describe physiological structure and function. The psychologist is trained to describe overt (motor) behavior. Both types of description must occur before an explanation by correlation or causation may even be attempted. Obviously, what is needed are more neuro-and physio-psychologists; but the necessity for specialization in description at both ends of the spectrum must also remain and be approved.
So, if we imagine a spectrum of empirical research relevant to memory, psychologists would be found on one end while physiologists on the other. While the task of the first is behavioral description, that of the other is painstaking experimentation. It is thus evident, that physiological psychologists, by virtue of their combined training and research competence, occupy an intermediate portion of this spectrum. It may perhaps even be said, that the study of memory is a premise of (interdisciplinary, even eclectic) physiological psychology par excellence.
The approach that physiological psychology takes when studying memory may perhaps be best conceptualized as a multitude of various approaches, some more theoretical, others more empirical, etc. The past half-a-century of research, in particular, has shown that no single approach, whether structural, functional, or both, may be adequate to handle all the known facts about memory. Recent approaches are perhaps best described as combinations of various theories, methods, etc., that ’attack’ memory by multivariate design, whether experimental or correlational. Undoubtedly, this refers to physiological psychology only. The physiologist, the pharmacologist, the biochemist, the molecular biologist, etc. handle specific, small details; while the psychologist, whether learning theorist or of some other orientation, would handle more broad or global observations. Physiological psychologists must draw on all angles, eclectically taking the best from every neighbor and relative, to handle the problem of memory most appositely. The physiological psychologist, armed with his psychological knowledge, knows how to evaluate behavior, which observation to use, and what theory to take to the laboratory for empirical verification and further experimentation. For he must be equally at home in the laboratory, he must be well-versed in all aspects of experimentation, and he must have a solid knowledge of physiology and psychopharmacology as well, if he is to handle the riddles of memory in his laboratory in a meaningful fashion. His approach may be likened to a bridge between the concrete and the abstract, or between tangible data and theory. In our era of overspecialization, his task is a formidably frustrating one, yet he is the only one in the proper position of handling such complex problems as memory.
A few words about theoretical approaches to memory might be appropriate. There have been theorists who have conceptualized memory as a single mechanism whereby learned experience is permanently stored. They have speculated that stimulus modalities by virtues of repetitive exposures will bring about structural changes in the CNS. Historical origins of such theories may be dated as far back as the times of the British empiricists. Most theories of this type would perhaps be best described as structural in nature. For example, neuronal growth or the structure of synapses, or the chemical composition of the transmitter substance itself, etc. have all been considered as possible structures responsible for memory storage. However, most of these theories use LTM techniques, while if memory decay occurs at all, it is most evident in the unstable STM phase. Nevertheless, research in this vein continues very actively, especially on the biochemical and the neuropharmacological levels.
While some scholars prefer to conceptualize memory as a single mechanism, the majority of physiological psychologists, especially since Hebb’s 1949 postulates, have come to regard memory as a dual process consisting of a very short, unstable phase, usually lasting but a few seconds, designated as STM; and a permanent, long-term structural change, whereby memory is stored, designated as LTM. To this dual concept, a third newcomer was added, intermediate-term-memory or ITM; that is more enduring than STM, but has not been transformed into permanent forms of storage as yet.
The process whereby STM is gradually transformed into LTM is referred to as the consolidation hypothesis. This is based on clinical data of retrograde amnesia, and maintains that the establishment of a permanent memory engram is the function of time. This consolidation process may take a variable time interval for its completion, and it is subject to interference and disruption. Hebb had suggested that this process may take place in the form of reverberatory activity in various neuronal circuits (ibid).
It must be mentioned that the consolidation hypothesis is not indispensable. Most suggestions regarding the permanent storage of memory have given little more than ad hoc consideration to the consolidation hypothesis. However, the view that the consolidation hypothesis is incorrect is not currently popular- most theorists would accept the notion, even if somewhat reluctantly. On the other hand, none of the suggested storage mechanisms appear to be dependent on the consolidation notion, and some may even be less cumbersome without it.
Before examining in a little more detail the approach of physiological psychology to STM and LTM, it must be said, that theories of these forms of memory are legion, both in physiological psychology and other interested fields. Yet, despite a plethora of exhaustive literature on memory, we still don’t know just what memory is. We know that there is something whereby previous experience modifies subsequent behavior in any temporal sense, whether long-term, or short-term or both. Everyone knows that even in the absence of environmental demands, we can remember. How we remember, what precise mechanisms are involved, and what the nature of memory is; is still a mystery.
The study of short-term memory is intimately bound up with investigations of the consolidation process. Since STM by definition is unstable, it was assumed that the dividing line between STM and LTM was drawn by ITM, at the point of which memory becomes stable. This point was very difficult to locate in time. There were great variations from individual to individual, from task to task, etc. Two trends of thought have emerged from the varieties of research findings; the more physiological point of view held that stable memory is LTM and everything else is STM; and the more psychological point of view that held the consolidation hypothesis to be a flexible, time and task- dependent process, which may take anywhere from seconds to weeks to stabilize the engram. In this view, STM was meant to be the immediate recall upon single exposure to stimulus material, usually a few seconds. Interestingly enough, in physiological psychology STM was studied backwards, i.e. if the consolidation process was successfully disrupted at various time intervals, memory was assumed to be still in the STM phase. It soon became clear, however, that it is not reasonable to assume that memory in the consolidation process is qualitatively the same as in STM. Consolidation was increasingly referred to as a continuum, from STM to LTM, and as such, a function of time and stimulus repetition or rehearsal.
There were two different approaches to the study of the consolidation process, hence, indirectly, to the study of STM. These are techniques for the disruption, or techniques for the facilitation of the consolidation process. These techniques range from ECS, lesions, direct stimulation, etc. to the use of various drugs.
Electroconvulsive shock in clinical practice produced retrograde amnesia. ECS had gradually become one of the major tools for studying the consolidation process. The early research paradigms had shown that if ECS is given soon after training, it disrupts memory, but not if given later.
For example, rats exhibited impaired avoidance behavior following ECS. This was interpreted as evidence in favor of the consolidation hypothesis, which was assumed to last approximately 15 minutes.
However, in recent years there has been an increasing reluctance to accept such studies as these, as evidences to the correctness of the consolidation hypothesis. Not only has the validity of the consolidation hypothesis itself been questioned, but it has been pointed out that ECS has many other consequences that may have confounding effects on the studies. ECS seems to interfere with memory retrieval and performance, rather than with memory per se.
There have been numerous attempts to localize the consolidation process by lesions or direct electrical stimulation. However, these attempts have been unsuccessful. The entire cerebral cortex seems to be involved. No single area can be reliably and validly demonstrated to be responsible for memory consolidation.
Local depressing agents have been used to create waves of spreading depressions whereby consolidation may be studied. Potassium chloride (KCl) is such an agent. It changes the potassium concentration of extracellular fluid (ECF) and creates a state of transient hyperpolarization. The resulting electrical activity can be monitored on EEG which will show a characteristic flattened-wave pattern. However, this technique, while yielding valuable data about the cerebral cortex, does not show any localization of the engram or its consolidation at all.
Retrograde amnesia or memory blockage has been produced by conditioned competing responses, as well as puromycin, physostigmine, and anticholinergic drugs.
Facilitation of memory has been observed by hibernation, and such drugs as flurothyl, strychnine, picrotoxin, caffeine, amphetamines, etc. It has been hypothesized, that such a facilitation may be due either to an acceleration of consolidation, or to an intensification of the reverberating electrical activity, or both. However, it has not been clear, whether memory storage or retrieval was facilitated. This takes us to LTM.
The approach of physiological psychology to the study of long-term memory has been centered around mechanisms of storage. Even though storage per se has never been demonstrated, its hypothesized existence is still the most plausible explanation that the physiological psychologist is prepared to offer. Indeed, it would be difficult to conceive just how memory can persist, albeit with distortions due to time (interferences, forgetting, senility, etc.), if it is not somehow ’stored’ for subsequent reference. While the ultimate answer (if there’s such thing) is still to be found, recent theories favor either increased neuronal growth, or some permanent biochemical change, resulting from repeated stimulus bombardments, as possible storage mechanisms.
With respect to the first theoretical mechanism, several studies have reported increased brain weight, as a result of environmental complexity; or differences in memory storage because of environments of varying complexity. Neuronal growth alone was thought to be responsible for the development of storage capacity. Also, synaptic changes might account for the phenomenon. However, it was soon suggested that neuronal changes as the result of environmental manipulations may be due to a shift in the levels of cholinesterase. This has led to vigorous research on the biochemical level to find memory storage mechanisms.
Change in biochemical composition as a factor that explains the storage of memory has been approached by physiological psychologists on two levels: molar and molecular.
The molar approach would focus on synaptic changes, transmitter changes, and intraneuronal activity. Acetylcholine and cholinesterase levels have been investigated through this molar approach. However, the concentration changes in these substances are transient, which militates against the notion of storage mechanism. Neuronal changes have been considered, but to little avail. Despite the failure of the molar approach to explain memory storage, research on synaptic changes, transmitter and neuronal changes continues to be quite active.
However, it is the molecular approach that has been the most popular in recent investigations of long-term memory. This approach would focus upon the changes in biochemical configuration induced by impulse modalities. In other words, storage of memory within the neuron was hypothesized to be in the sequences of macromolecules. Specifically, DNA, RNA, and various protein molecules have been proposed as storage sites of memory. However, DNA has been ruled out. Even though it has been demonstrated that DNA plays a very important role in genetic inheritance, DNA is a very stable molecule. If DNA would store memory, memory should be inheritable. Since there is no evidence to suggest this, and the stability of DNA would make it impossible for experience to modify its biochemical structure, DNA has been discounted.
The unstable nature of RNA makes this substance a good candidate for LTM storage studies. At least, RNA is modifiable relatively easily. Therefore, experience may influence its composition. RNA has been shown to be continuously resynthesized to ensure its relative stability. It is thus conceivable that the encoding of the engram may take place in RNA. Indeed, qualitative changes in RNA have been observed as a result of training. However, interanimal transfer studies of ’trained’ RNA were largely inconclusive. These attempts may have failed because the transfer itself may be sensitization; RNA extraction techniques may still be somewhat crude, and testing criteria may still need precision and refinement. Yet, this line of research is promising.
Another possible candidate for LTM storage is protein synthesis. Despite a certain skepticism, there have been several studies either facilitating protein synthesis by such drugs as TCAP, or inhibiting it by such drugs as puromycin or other antibiotics. Even though such studies can be replicated more reliably, it is possible that drug injections alone fail to confirm the hypothesis, since they influence not only RNA but other substances as well. In spite of such potential or actual confounding, there have been enough encouraging results to allow some cautious optimism.
Finally, in the medical literature it is the temporal lobe that has been postulated as the possible location of memory, based on clinical observations of seizures, bilateral lobotomies, and psychic memory disturbances associated with temporal lobe stimulations. While this hypothesis may fit the clinical data, the definite location of memory in the temporal lobe has yet to be demonstrated.
Modern physiological psychology is the outgrowth of the empirical tradition of experimental psychology, physiology, learning theory, etc.; it thus lends support to the study of memory on every count. In this tradition, memory studies have been conducted in psychological research on learning, clinical psychology, and several other interested fields. However, it is physiological psychology, the combination of behavioral description and solid experimental empiricism, that has been shown to be the most appropriate vehicle for the study of the stubbornly elusive phenomenon of memory.
Frank Luger (frankluger@hotmail.com)
Written: Ottawa, March, 1974.
Revised: Budapest, March, 2000.