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On the physics of CNS memory
J theor. Biol. (1978) 70, 33-49
On the Physics of CNS Memory IGOR E. MIKHALTSEV
Institute of Oceanology, Academy of Sciences, U.S.S.R. Moscow 117218, U.S.S.R. (Received 24 June 1976, and in revised form 25 April 1977) A hypothesis of engram formation and the retrieval process of the information engraved is formulated. The engram is considered to be a pattern of a fixed field of electrical impedance representing the perceived information spread in the domain of the cortex tissue. The retrieval mechanism is regarded as a process of associative generation of the full pattern of a spatial-temporal sequence of electrical pulses characteristic of the information to be retrieved, triggered by another sequence adequate to the information-stimulus. The progress of this process depends upon the existence of dominant (or slow potential shift) conditions on the proper areas of the cortex. The description of the suggested mechanism is given, supported by discussion of the published experimental data. Three direct corollaries of the hypothesis are mentioned. 1. Introduction This paper is concerned with a hypothesis of physical basis of the processes of engram formation and of the retrieval of the information memorized in the central nervous system (CNS). There exists many hypotheses of memory which are reviewed elsewhere (John, 1967; Glassman, 1968; Bogoch, 1968, Pribram, 1971). An attempt is made here to give a self-contained physical explanation for both engram formation and the retrieval mechanisms. The problems of transforming the information on the way to the cortex and the specificity of “short-term” memory will not be discussed. The first sections contain a description of the proposed concept with some comments on the terminology used. The validity of the hypothesis based on published experimental data is discussed in section 6. 2. The Hypothesis The engram is a fixed field of electrical impedance adequate to the memorized information and spread in the tissue of the cortex. This field is formed by persistent chemical transformations of the tissue structures under I.D. 33 3
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the influence of the flow of electrical currents representing the information to be remembered. The retrieval of the information involves the generation of a spatialtemporal distribution of a sequence of electrical pulses, characteristic of the information retrieved. The generation of this sequence is implemented by an associative influence mechanism of another pulse current sequence (characteristic of the information-stimulus), on the areas which store the engram. The action of the associative mechanism consists of induced activation of the appropriate neuron ensemble by either galvanic contacts or ephaptic interaction with the neurons located in the environment of this ensemble. The association-induced activation is provided by the specific ability of the neurons of cortical tissue to generate a full information pulse pattern under the influence of the activity, characteristic of a part of such pattern. The generation of a full information pulse pattern (electrical signal appropriate to the information retrieved) by its part is produced by active response of the neurons of cortical tissue to the applied spatial-temporal current pulse sequence which propogates in the direction of minimal impedance for this given spatial-temporal sequence (electrical signal appropriate to the information-stimulus). The existence of an increased level of the quasistatic activating electromagnetic field (dominant state) on appropriate cortex areas is a necessary condition for associative generation of a concrete informative pulse pattern.
3. Terminology (A)
ELECTRICAL
SIGNAL
Electrical signal in the cortex adequate to a concrete information is defined as the time varying field of electrical currents distributed in the space of the cortical tissue. Attention should be drawn to the importance of anatomical and physiological features of CNS which provides the conditions of proper organization or recoding of the signal before it reaches the areas of the cortex, and forms the field of electrical currents. These currents are determined by local values of potential difference and impedance. In other words, the electrical signal is the field of cortical currents, which has a concrete information significance, i.e., the field created by a concrete sensory or associative (induced in the cortex itself) stimulation and characterized by a certain temporal variability in each point of the tissue. For each point of the tissue the Fourier transformation may be applied and the field may be characterized in spectral or autocorrelation terms.
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It should be noted that the priority given here to the electric currents (flowing across the structure characterized by some impedance field) as compared with acting electromotive forces has certain grounds. The specific character of the neuronal mechanism of action potential formation, obeying the “all-or-none” law, creates conditions under which the values of electromotive forces (as these electromotive forces exist and act in some sections of the circuits and induce the current) do not change much. The gradual character of the currents flowing in the structure of the tissue is thus determined by the distribution of the impedance. The whole process of propagation of the signal in the cortex, and of electromagnetic field it induces, obeys the Maxwell equations along any correctly selected contours and sections. (B)
ENGRAM
DISTRIBUTION
IN
THE
SPACE
OF THE
CORTICAL
TISSUE
STRUCTURES
The given formulation needs three remarks: First, this statement takes account of the “structural character” of the cortical tissue. Namely, the architecture of the cortex and the anatomical structure of neuronal organization of the brain. I want to stress the deterministic approach to the problem of the routes of the electrical signal flow used here, in contrast to the widely interpreted principal statistical character of electrical processes in the cortex. Second, this statement, as a part of the hypothesis, does not exclude the significance of glial cells and intercellular substance on the background of neuronal net, leaving the possibility for localization of trace substrate in the composition of any cortical tissue component. In this case, without rejecting the idea of probable localization of trace substances in such “poles and zeros” of neural tissue as the areas of synaptic connections, the present formulation does not restrict the application of the hypothesis, requring exclusive recognition of synaptic connectionistic theory. The third point concerns the consequences of the engram distribution concept. On the basis of fixed neuronal organization of the cortex, it predetermines a high degree of multidimensionality of the cortical tissueits extremely large information capacity. This information capacity principally, a denumerable one-in the interpretation of the proposed hypothesis, (for example, for some chosen volume of the cortex tissue) is greater than the number of cells, or the number of synapses, or even the number of macromolecule complexes involved. The information capacity of this volume, or such system, is determined not by the number of elements of the set constituting the system, even taking into account a number of possible changes of their state (for example, conformational changes in macromolecules or the character of polarization of elements), but by the variety of
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spatial distributions of the states of these elements that characterize system as a whole. In our case, that is the variety of spatial distributions electrical conductivity or impedance field of the cortical tissue. (C)
FIXED
IMPEDANCE
the of
FIELD
Two points are important: First, it should be precisely determined what kind of impedance is meant. The cortex of the brain is an essentially anisotropic structure. It is commonly accepted, without any limits, to interpret the term impedance as the complex resistance to the electric current between any two points of a conducting medium. Here, the impedance values between two points of the tissue, in general case, should be equated neither with transmembrane resistance of neurons, nor with resistance of glial cells or intercellular substance, and by no means with mean value of volume electrical resistance of tissue. So, the cerebral cortex impedance field in question is the field of complex resistance to electric current along the route of its flow, changing with time. Obviously, this field is vectorial. Under the circumstances, we should keep in mind that the presence of nonlinear elements is the main property of such conducting structures as the cortical tissue. So the possibility of estimating impedance values becomes fundamentally difficult. The second remark concerns the essence of the term “fixed impedance”. The assumption of the possibility of persistent change of electrical characteristics of chemical structures of the cortical tissue under the impact of electrical current and its electromagnetic fields is a key point of the hypothesis. I mean the changes due to conformational transformations, breaches and formation of new connections, change of degree and direction of polarization in the complexes of macromolecules which are components of various cellular structures, membranes and intercellular substance. Using the term “fixed” I understand it as persistent, in the scale of the lifetime of the organism. In contrast to these persistent changes the reversible or temporal changes of electrical characteristics of the tissue should be mentioned; fluctuating potentials, slow potential shifts and the consequences of metabolic activity are responsible for them. 4. The Mechanism of Engram Formation Let us assume that certain presented information resulted in sensory stimulation. Then electrical stimulation induced at the beginning of the afferent tract, under the influence of numerous effects determined by the morphophysiological organization of the CNS, is transformed on the way to the cortex into an electrical signal characteristic of the information presented.
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It is important to remember that the CNS organization admits a simultaneous flow of several electrical signals to the cortex-from heterogeneous, simultaneously presented information. These several electrical ‘signals may be interpreted as a complex electrical signal corresponding to the set of simultaneously presented information. If the conditions for perception of the presented information are provided in those areas of the cortex where the electrical signal arrives (Mikhaltsev, 1975), this electrical signal forms the engram. The areas of the cortex with the most pronounced branching of neuronal structure, and those layers of these regions that are characterized by high density of dentrites with the strongest dendro-dendritic interactions, are the cortical areas involved. The engram formation takes place simultaneously with the electrical signal passing through these areas without “consolidation” (Mikhaltsev, 1972) and is expressed in persistent changes of the local value of the impedance of the cortical tissue, induced by the flow of the current and electromagnetic fields generated by this current. The persistent changes of impedance are caused by changes in the electrical characteristics of the neural tissue, on the molecular level. The block diagram of the whole process is given on Fig. 1. The essential element of the hypothesis is the assumption of the mechanism of change in the impedance local values under the influence of currents and their electromagnetic fields. This mechanism may be reduced to the action of three factors: (i) decrease of the impedance in the region surrounding the source of electromagnetic field with appropriate spatial orientation and intensity, (ii) gradual restoration of the impedance to mean values characteristic of the given part of tissue in the absence of the field influence, and
FIG. 2. Schematic diagram of electrical events in some small area of cortical tissue. 0102 is a pathway of the pulse-train of spike activity current Zoo flowing through the tissue. AlAa, BIBS, C,Ca are some equiconductivity lines in the area surrounding OIOz with initial impedance (before the current of pulse sequence 200 flows) IZ,,I = lZobl = IZ,,I = ZO. Due to the difference in electrical properties of the substance surrounding OIOz these lines should not be equidistant from 0102. Under certain conditions (see Fig. 3, Fig. 4 and text) the induced activity I,, in CICa-but not in AlAz or BIBz-cccurs.
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MEMORY
39
I,, = f ( &IO + Es,,)
FIG. 3. Simplified temporal diagrams of the changeof impedance(for the scheme of Fig. 2) between the points on 00 and the corresponding points on AA, BB and CC represented as moduls l&,l, j&I and l-%,l; accompanying currentand field diagrams are shown. Z, is the initial impedance equal for three chosen combinations Zoloa = Zolob = Z,(,,; Z1 is the stepdown threshold impedance; Z,,, is the persistent minimum impedance. The amount of the decrease of impedance under the influence of electromagnetic field E,,,, of the current ZOOdepends upon mutial spatial configuration of 00 and AA, BB, CC; the restoration of the value of impedance to ZO level is gradual. The strongest interaction according to Fig. 2 is assumed between 00 and CC. In the presence of slow potential shift field E,,,, properly phased, and under the influence of the field Eoo the decrease of Z,, reaches Z,,, level and the current Z,, in CC is induced.
of a nonlinear and irreversible-“stepdown”-decrease of (iii) possibility impedance upon reaching a certain threshold (determined by specific character of the tissue structures in the chosen area) under the influence of the field created by a quantum of electrical signal. Figure 2 illustrates schematically the electrical events in some small area of the tissue. The spike activity-the current Zoo-on the pathway 00 changes
40
I. E. MIKHALTSEV
the impedance of the environment and induces the activity I,, on CC. The temporal diagram of these events is presented on Fig. 3, while Fig. 4 outlines the significance of the temporal distribution of the electrical activity in the same area for the spatial-temporal pattern achieved. So the change of the impedance will change the main directions of the currents which follow the pathways of minimal impedance. The described mechanism can explain how the quantized signal (sequence of spikes), say, with constant period of quantization, transforms into a signal with a variable quantization period due to the action of the three factors mentioned above. This effect, which has to my mind a major significance exceeding the limits of the explanation of the proposed hypothesis
FIG. 4. The significance of temporal distribution of electrical activity in the tissue for corresponding spatial-temporal pattern achieved. T,: the induced activity at some point p on CICa is formed under the intluence of electromagnetic field Eoo (as on Fig. 2). Tz: same spatial distribution as at TI. The difference is that at the moment Tz another pulsetrain exists on III&, generating the field Ebb equal to Eoo, but acting in opposite direction; in this case no induced activity on CICz is achieved.
mechanism, is caused by the electromagnetic field influencing in different ways various tissue structures in the sphere of this field’s activity. Thus, the “choice of routes” of further current flow, from any particular point in the cortical tissue, as well as the delay in propagation of the quantum of the signal along the different tracts and the spatial distribution of current will correspond to the distribution of impedance of the cortical tissue in the area surrounding this point. The current and its fields will result in those persistent changes of local values of the tissue impedance we have already spoken about. The trace changes along the route of current forms a new distribution of impedancea pattern of perceived information, or the engram.
CNS
MEMORY
Now, it remains to note that so far I have not used any character of electrical signal. This means that we can pass case of primary sensory stimulation, to the generalization process of the engram formation for the case of electrical within the brain without any external stimuli (Mikhaltsev,
41 limitations of the from a particular of the described signal generation 1972).
5. Retrieval Mechanism The block-diagram of the process of retrieval of some information . . . “a” . . . stored in the engram is shown in Fig. 5. As proposed earlier (Mikhaltsev, 1972) the retrieval of information is based on the existence of a proper conditional stimulus. In our example that is an applied external information-stimulus “c” or information-stimulus “n” appearing in the cortex as a result of internal cerebral activity. Let us first consider the case of the application of the external information “c” (the left part of Fig. 5). En route to the cortex the information “c” suffers the sensory transformation and multiple “recoding” determined by the morphophysiological structure of the afferent tract. As a result, a sequence of pulses-an activity pattern, or an electrical signal characteristic of information “c” is formed and applied to appropriate areas of the cortex. This electrical signal is a spatial-temporal sequence of impulses of the current in the cortical tissue passing along the ways of the minimal impedance for such a sequence. If information “c” has not been applied before, (perhaps together with some other previously perceived or simultaneously presented information) then it will produce the engram corresponding to information “c”. This case of novel information “c” is of no interest to our discussion. If information “c” has been applied earlier accompanying information “a”, the electrical signal will cause stimulation of the cortex area where the engram “c” is stored as a part of a larger engram in which information . . . “c+r” . . . “c+p” . . . , . . . “c+a” . . . is engraved. The central point of the retrieval hypothesis is the assumption of the existence of a mechanism which provides an associative generation of electrical signals (or activation of full patterns) characteristic of information . . . “c+v” . . . , . . . “c+p” . . . , . . . “,+a” . . . . This activation is implemented by the ability of the cortical tissue-especially of its layers, with pronounced dendro-dendritic connections-to produce inductive stimulation (as a result of the flow of currents and their electromagnetic fields characteristic of information-stimulus “c”) upon the nearby elements of the neuronal net, thus creating conditions for another sequence of spike activity and the currents to appear in the cortical tissue. The route of these currents
*
ELECTRICAL characteristic
SIGNAL informalion
“(”
By the action fields having of information
of the currents the spatial-temporal “L.’
and
uf
their electromagnet!c sequence characteristic
the
on-route
The current ,,I Lhe corlxnl IIIWC pawng along tracts of the minimal ampedzncc for the giwn spatial-temporal sequence ch.wcteristic of information “<,‘i e. stimukwon of the CUIIIC~~ area uhere the engram information “l” ib stored
of
transformations
I
to
the
I
J
/
imulatlon mformation
FURTHEK ---upon the for -< -.
of
Dommanr
left
,u,l
of the ‘)u
part a”
upon
dugr,u,,
of cortex is
of the
conditions
areas
the
\\,,h
wlwc
cortex
--I,”
engram
where
\uh\t,tu,cil
the
areas
1 I u U FIG. 5. Block-diagram of the retrieval process of information. . . “a”. . . , stored in the engram. Retrieval is initiated by the application of external stimulus . . . “6 . . . or stimulus . . . ‘W’ . . . generated within the cortex.
I
and
CNS MEMORY
43
is determined by directions of the minimal impedance characteristic of previously formed engrams of information . . . “c+r” . . . , . . . “c+p” . . . ) . . . “C+d’.
...
As in the case of information perception, i.e. engram formation (Mikhaltsev, 1975) the dominant conditions upon the cortex areas where the engram “c+u” is stored (as distinct from the areas storing the engrams . . . “c+r” . . . , . . . “c+p” . . . , etc.) are responsible for generation of the pattern characteristic of information “a”. At this point the process of retrieval of the information “a” comes to the end. The appearance of the cortex activity pattern characteristic of information “a” may result either in the efferent tract stimulation as a response to this information, or in successive associative generation of other patterns “U+x” . . . , “U+f’. . . ) “U+z,‘. . . for which “a” serves as an informationstimulus. The same functional mechanism described for the applied external information “c“ also holds in the case of information “n” characterized by a sequence of patterns associatively generated within the cortex (right side of Fig. 5). It remains to explain the mechanism of the learning process provided by the proposed hypothesis. From the general concept of memory (Mikhaltsev, 1972) it follows that the learning process is related not to the formation of the engram of some information (e.g. information “8) but to consolidation of associative connections necessary for the ability to retrieve that information. In Figure 5 (the lower part) the conditions involved in this process are marked with interrupted lines. I wish to call the reader’s special attention to the need for an additional stimulus which is essential for the learning process and facilitation of the retrieval ability or consolidation of the created associative connections of information to be retrieved. In our case this facilitation of the retrieval of information “a” was determined earlier, by consolidation of connections in the pattern characteristic of “c+u” associatively selected from the set of other possible patterns . . . “c+p” . . . , . . . “c+r”. . . , etc. This consolidation is achieved by the additional stimulus, leading to recurrence (“will”) or amplification (stress, attention, etc.) of the currents in the cortex areas which store the engram “c+u”.t Such stimulated activation of the areas where the engram “c+u” is stored results in domination of the association “~+a’‘-or in relative decrease of impedance (or relative amplification of the current) as compared to similar characteristics for . . . “c+p” . . . , . . . “c+r” . . . , etc. Under these conditions the application of the information-stimulus “c’‘-sometime later-will initiate the 7 1 use psychological terminology here; although physical interpretation of the processes determined by such terms as will, attention, etc. looks feasible, it is beyond the scope of this article.
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MIKHALTSEV
whole chain of the phenomena presented in the block-diagram Fig. 5 with the result of generation of the pattern characteristic of information “a” which is to be retrieved.
6. Discussion
I shall distinguish between two main groups relating to the concept. The first consists of the postulates which have no direct experimental proof today; the second comprise those points of the hypothesis based on existing experimental data. I consider two main postulates which should be possible to prove by experiments in the future. One is the possibility to achieve persistent changes of the electrical parameters (namely-the impedance) of some chemical structures of the brain tissue by application of the electromagnetic field of appropriate strength. A second-is the statement relating to the ability of the tissue under the influence of quasistatic electromagnetic field (of slow potential shift) and under the impact of spatial-temporal sequence of current pulses, to generate another pulse sequence which covers a wider area of the tissue and thus form a new spatial-temporal sequence. Though some indirect experimental support of these two statements could be mentioned I prefer not to speculate on their validity leaving them here as postulates awaiting direct experimental evidence. The second group incorporates three other important points to be discussed: (i) the distribution of the engram in the cortex, (ii) the change of the impedance of the tissue under the influence of electromagnetic field and (iii) the reality of significant non-synaptic connections in the developed neuronal system of upper cartical layers.
(A)
DISTRIBUTION
OF ENGRAM
IN
THE
CORTEX
The engram distribution is recognized now by most investigators as a concept experimentally substantiated. It is generally accepted to regard the classical experiments of Lashley (1929) as one of the first evidence of distribution of the engram across the cortex. Numerous more recent experimental studies give support to this concept; the appropriate summery is given in any monograph on memory problems, e.g. John, 1967; Pribram, 1971; Livanov, 1972; Beritashvili, 1974. Historically Lashley’s conclusions (1929, 1950) should be considered a stimulus for theoretical interpretations of memory as the process involving
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vast fields of the cortex. Apparently, Whyte’s work (1954) should be regarded the nearest to the hypothesis being discussed. Whyte’s suggestion to treat the engram as a distributed vector field in the cortex, was, no doubt, original for that time. Unfortunately, the author could not point out any physically real mechanism forming such a field. Here it should be mentioned that the proposed hypothesis is based just on the most general experimental data dealing with the distribution of the engram (or the electrical activity pattern corresponding to the engram) in the domain of cortical tissue. The hypothesis makes no assumptions requiring the use of any more elaborate approaches, like, for instance, the holographic concept, e.g. Longuet-Higgins, 1968; Pribram, 1971. (B)
THE
CHANGE
OF THE
BRAIN
TISSUE
IMPEDANCE
BY ELECTROMAGNETIC
FIELD
I do not want to give a historical review of this topic but in the sixties Adey and his associates (Adey, Kado & Walter, 1965; Adey, Dako, McIlwain & Walter, 1966; Wang, Kado & Adey, 1968; Elul & Adey, 1966; Adey, 1969) carried out the largest number of experiments on interstitial currents study based on determination of the impedance value. These studies dealt with the measurement of local impedance values in the cerebral tissue as well as impedance change in various behavioural situations (for example, Wang et al., 1968; Adey et al., 1966). The discussion confirming multiplicity of the data on impedance change in cortical activity is presented by Schmitt & Samson (1969). In recent years Llinas, Nicholson and Freeman have fulfilled a series of investigation-both theoretical and experimental-on the conductivity, extracellular field potentials and intrinsic currents in the brain tissue (Nicholson & Llinas, 1971; Llinas &Nicholson, 1974; Nicholson & Freeman, 1975; Freeman & Nicholson, 1975). Among other results the authors (Nicholson & Freeman, 1975) have obtained reliable data of the change of conductivity, correlating with induced stimulation of electrical activity of the tissue. The quantitative characteristics obtained show that it was slightly less than 1% of the mean value (of the conductivity between the microelectrodes 100 pm apart) while the measurement system allowed to have the resolution of 0.06 %. The authors comment this result saying that “no significant change of conductivity was observed” which is quite understandable from the point of view of their main tasks. Though these data were obtained on cerebellar tissue they might be applied to the brain cortex due to the similarity of structural organization of the dendrite field of both tissues. I regard this group of recent results as most significant for the discussed subject.
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I.
(C)
EPHAPTIC
E.
CONNECTIONS
MIKHALTSEV
IN THE UPPER
CARTICAL
LAYERS
Apparently, Gerard may be considered as one of the first investigators to raise the question on electrical interaction of neurons and their non-synaptic connections most directly (Gerard, 1932; 1941). He has presented direct experimental data on ephaptic connections and electrotonic stimulation not limited by the low-frequency band and pointed, in particular, to parallel orientation of dendrites in the cortex of great hemispheres as an anatomical factor predetermining effectiveness of the connections by electrical field. Later investigations of different trends confirm the significance and give quantitative characteristics of ephaptic connections, sometimes emphasizing the role of electrotonic stimulation. The studies of Morrel (1963), Nelson (1966), Rusinov 8c Ezrokhi (1967), Chirkov (1973) Bennet (1974), Sotelo (1975) could be mentioned. The book by Chirkov (1973) contains a good bibliographical review on the matter; his own convincing conclusions on the effectiveness of non-synaptic transmission of spike activity across the cortical tissue are based on the results obtained in numerous experiments (on more than 60 cats) in uioo on semi-isolated cortical slabs. Adey (1975b) gives additional evidence of the influence of the lowlevel electromagnetic field (of several orders of magnitude lower than estimated for synaptic action) on the neuronal electrical activity in brain tissue. The importance of anatomical structure of the first layers of the cortex for dendro-dendritic interactions was emphasized by many investigators. Rall (1970), Colonnier (1974)-in the framework of synaptic connections, van der Loos (1974), Bennet (1974), Scheibel & Scheibel (1975)-assuming the importance of both synaptic and non-synaptic interactions, Sotelo (1975) -featuring the role of ephaptic junctions, have shown on morphological level the functional significance and the specificity of the branching and high spatial density of dendrites in these layers. Discussing the matter, Adey (1969, 1975~) draws attention to probable specific functions provided by such tissue structure. I consider as his real finding the introduction of the term “nonlearning neurons” applied to the structures of spinal cord in contrast to the learning abilities of neuronal structures of the upper layers of the cortex. To conclude the discussion of the hypothesis I want to point out the work of Schmitt, Dev & Smith (1976) on electrotonic interactions in CNS, who have summarized a quantity of experimental data, demonstrating the existence and significance of the field effect interactions in the brain tissue.
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7. Three Corollaries Three corollaries might be derived from the proposed hypothesis. (A)
THE PHYSICS
OF THE CONDITIONED-REFLEX
MECHANISM
I proceed from the assumption that a general concept of biological memory based on the principles of the conditioned reflex and of the dominant is correct (Mikhaltsev, 1972, 1975). If so, the memory mechanism must underlie the conditioned reflex mechanism. In turn, it means that the explanation of processes caused by the conditional stimulus and reinforcement, can be derived directly from the explanation provided by the proposed hypothesis for the physics of the engram formation, associative connections, and dominant selection of the information significant to the organism, by mere substitution of the terms. (B) REVERSIBILITY
OF CONDITIONED-REFLEX
CONNECTIONS
According to the suggested hypothesis the selection of information to be retrieved is determined by dominant conditions upon the areas of the cortex where the patterns of the conditional stimulus and reinforcement are associatively connected. It means that, the conditional irritant and the reinforcement are equivalent in respect to their presence in the engram. In other words, what is the stimulus and what is the reinforcement is determined by dominant conditions in the specific areas of the cortex in accordance with the significance of the stimulus for the organism. I do not persist that Pavlov’s dog will necessarily hear the bell while eating the meat-in this case the irritant and the reinforcement are not equivalent to the object. However, it does follow from the proposed hypothesis that the effect is a quantitative one and if the difference in significance is not as dramatic as in this example (and the dominant conditions are phylogenetically not predetermined) or if the dominant conditions are artificially shifted, the conditional stimulus and the reinforcement will be equivalent, which reveals the reversibility of the conditioned-reflex connections. (C)
ON PHYSICAL
INTERPRETATION
OF THE PROCESS
OF THINKING
A possible mechanism of the higher function of CNS, namely of thinking, can be suggested. This mechanism can be interpreted as a logical corollary of the hypothesis and the general conditioned-reflex concept of memory outlined above. A great number of psychological investigations and observations points to the fact that, phenomenologically, the function of the mechanism of thinking is a process of scanning of associatively connected image sequences,
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interrupted by application of stimuli from the environment (in the broad sense). Thus an explanation of the physics of the phenomena involved in the process of thinking can be reduced to the explanation of the mechanism of the associative image generation. The proposed hypothesis provides physical interpretation of the generation of sequences of spatial-temporal patterns adequate to some specific information or image stored in the engram. Within the framework of the hypothesis the process of inventing or creating of new information can be explained as a result of the internal electrical activity of the cortex caused by the sliding slow potential shift in a vast area of the cortex which leads to remote and “illogical” associations. In such cases unconnected engrams of heterogeneous information, being simultaneously activated, become associatively connected which results in formation of a new combined pattern characteristic of novel information. Such specific features as strong interconnections by the field and high spatial density of the dendrites used as keypoints in the hypothesis are adequate to the morphophysiological cortical characteristics known for the representatives of higher levels in the evolutional hierarchy who are capable of thinking. 8. Conclusion The suggested concept leaves open the experimental support for the validity of two postulates used. What concerns the first, the problem might be defined as an oriented search among the chemical components which constitute the cortical tissue, of one or any, having the ability for persistant change of electrical characteristics under the influence of electromagnetic field. An attempt of a straightforward experimental attack on the associative mechanism organized in this laboratory failed due to the difficulties concerned with the instrumental and technical arrangement needed for adequate method of investigation. Nevertheless, I trust the hypothesis (which was formulated about two years ago) might find proper experimental support in future and remain as a useful tool for those who are still involved “in search of the engram”. REFERENCES ADEY, W. R., KADO, R. T. & WALTER, D. 0. (1965). Expl. Neural. 11, 190. ADEY, W. R., KADO, R. T., MCILWAIN, J. T. & WALTER, D. 0. (1966). Expl. Neural. 15, 490. ADEY, W. R. (1969). In Biocybernetics of the Central Nervous System (L. D. Proctor, cd.), p. 1. Boston: Little, Brown.
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ADEY, W. R. (19750). In Behavior and Brain Electrical Activity (H. Altshuler & H. Burch, eds). New York: Plenum Press. ADEY, W. R. (19756). In Functional Linkage in Biomolecular System (F. 0. Schmitt et al., eds), p. 325, New York: Raven Press, Publ. BENNET, M. V. L. (1974). Neurosciences Res. Progr. BUN. 12, 1, 92. BERITASHVILI, I. S. (1974). Pamyat pozvonochnykh zhivotnyktz, ego kharakteristika i proiskhozhdenie. (“Memory of vertebrates, its characteristic and origin”) Nauka. (In Russian.) BOGOCH, S. (1968). ‘T/ze Biochemistry of Menzory. New York: Oxford University Press. CITIRKOV, V. D. (1973). Rol nesinapticheskogo (ephapticheskogo) phaktora v proiskhozhdenii epileptiphormnykh origin of epileptiform
sostoyanii. (“The role of non-synaptic (ephaptic) factor m me conditions”) Gorky VVK Izd. (In Russian.) In Essays on the Nervous System. A Festschrift for Professor J. Z.
COLONNIER, M. (1974). Yoltng (R. Bellairs & E. G. Gray, eds). Oxford: Clarendon Press. ELUL. R. & ADEY. W. R. (1966). Nature 212. 1422. FREEMAN, J. A. &‘Nicwo~so~, c. (1975). J. heurophysiol. 38, 369. GERARD, R. W. (1932). Physiol. Rev. 12, 546. GERARD, R. W. (1941). Ohio. J. Sci. XLI, 3, 160. GLASSMAN, E. (1968). Ann. Rev. Biochem. 38, 605. JOHN, E. R. (1967). Mechanisms of Memory. New York: Academic Press. LASHLEY, K. S. (1929). Brain Mechanisms and Intelligence. Chicago: University of Chicago Press. LASHLEY, K. S. (1950). Ph~~siological Mechanisnzs in Animal Belzavior. New York: Academic Press. LIVANOV, M. N. (1972). Prostranstvennayu orgunizatsiya protsessov golovnogo mozga. (“Spatial organization of processes of the brain”) M. Nauka. (In Russian.) LLINAS, R. & NICHOLSON, C. (1974). In Handbook of Electroencephalography and Clinical Neuroplzysiology (C. E. Stevens, ed.), Vol. 2, part B, p. 61. Amsterdam: Elsevier. LONGUET-HIGGINS, H. C. (1968). Nature 217, 104. MIKHALTSEV, I. (1972). J. theor. Biol. 37, 587. MIKHALTSEV, I. (1975). J. theor. Biol. 49, 245. MORREL, F. (1963). In Information Storage arzd Neural Colztrol (W. Fields & W. Abbot, eds). Springfield, Ill.: Thomas Publ. NELSON, P. (1966). J. Neurophysiol. 29, 275. NICHOLSON, C. & LLINhS, R. (1971). J. Neurophysiol. 34, 509. NICHOLSON, C. & FREEMAN, J. A. (1975). J. Neurophysiol. 38, 356. PRIBRAM, K. H. (1971). Languages of the Brain. Englwood Cliffs, New York: Prentice-Hall, inc. RALL, W. (1970). In The Neurosciences: Second Study Program (F. 0. Schmitt, ed.), p. 552. New York: Rockefeller University Press. RUSINOV, V. S. & EZROKHI, V. L. (1967). Zhurzzal vysslzei nervrzoi deyatebzosti. (J. Higher Ner. Activ.) XVII, 5, 947. (In Russian.) SCHEIBEL, M. E. & SCHEIBEL, A. B. (1975). In Golgi Sentenial Symposium Proceedings. New York: Raven Press. SCHMITT, F. 0. & SAMSON, F. E., JR. (1969). Neurosci. Res. Prog. Bull. 7, 4. SCHMITT, F. O., DEV, P. & SMITH, B. H. (1976). Science 193, 114. SOTELO, C. (1975). In Golgi Sentenial Syrzzposium Proceeditzgs. New York: Raven Press. VAN DER Loos, H. (1974). Neurosciences Res. Progr. Bull. 12, 1, 86. WANG,
H., KADO,
R. T. & ADEY,
W. R. (1968).
Fed. Proc.
27,749.
WHYTE, L. L. (1954). Brain 77, 1, 158.
T.B.
4
On the Physics of CNS Memory IGOR E. MIKHALTSEV
Institute of Oceanology, Academy of Sciences, U.S.S.R. Moscow 117218, U.S.S.R. (Received 24 June 1976, and in revised form 25 April 1977) A hypothesis of engram formation and the retrieval process of the information engraved is formulated. The engram is considered to be a pattern of a fixed field of electrical impedance representing the perceived information spread in the domain of the cortex tissue. The retrieval mechanism is regarded as a process of associative generation of the full pattern of a spatial-temporal sequence of electrical pulses characteristic of the information to be retrieved, triggered by another sequence adequate to the information-stimulus. The progress of this process depends upon the existence of dominant (or slow potential shift) conditions on the proper areas of the cortex. The description of the suggested mechanism is given, supported by discussion of the published experimental data. Three direct corollaries of the hypothesis are mentioned. 1. Introduction This paper is concerned with a hypothesis of physical basis of the processes of engram formation and of the retrieval of the information memorized in the central nervous system (CNS). There exists many hypotheses of memory which are reviewed elsewhere (John, 1967; Glassman, 1968; Bogoch, 1968, Pribram, 1971). An attempt is made here to give a self-contained physical explanation for both engram formation and the retrieval mechanisms. The problems of transforming the information on the way to the cortex and the specificity of “short-term” memory will not be discussed. The first sections contain a description of the proposed concept with some comments on the terminology used. The validity of the hypothesis based on published experimental data is discussed in section 6. 2. The Hypothesis The engram is a fixed field of electrical impedance adequate to the memorized information and spread in the tissue of the cortex. This field is formed by persistent chemical transformations of the tissue structures under I.D. 33 3
34
I.
E.
MIKHALTSEV
the influence of the flow of electrical currents representing the information to be remembered. The retrieval of the information involves the generation of a spatialtemporal distribution of a sequence of electrical pulses, characteristic of the information retrieved. The generation of this sequence is implemented by an associative influence mechanism of another pulse current sequence (characteristic of the information-stimulus), on the areas which store the engram. The action of the associative mechanism consists of induced activation of the appropriate neuron ensemble by either galvanic contacts or ephaptic interaction with the neurons located in the environment of this ensemble. The association-induced activation is provided by the specific ability of the neurons of cortical tissue to generate a full information pulse pattern under the influence of the activity, characteristic of a part of such pattern. The generation of a full information pulse pattern (electrical signal appropriate to the information retrieved) by its part is produced by active response of the neurons of cortical tissue to the applied spatial-temporal current pulse sequence which propogates in the direction of minimal impedance for this given spatial-temporal sequence (electrical signal appropriate to the information-stimulus). The existence of an increased level of the quasistatic activating electromagnetic field (dominant state) on appropriate cortex areas is a necessary condition for associative generation of a concrete informative pulse pattern.
3. Terminology (A)
ELECTRICAL
SIGNAL
Electrical signal in the cortex adequate to a concrete information is defined as the time varying field of electrical currents distributed in the space of the cortical tissue. Attention should be drawn to the importance of anatomical and physiological features of CNS which provides the conditions of proper organization or recoding of the signal before it reaches the areas of the cortex, and forms the field of electrical currents. These currents are determined by local values of potential difference and impedance. In other words, the electrical signal is the field of cortical currents, which has a concrete information significance, i.e., the field created by a concrete sensory or associative (induced in the cortex itself) stimulation and characterized by a certain temporal variability in each point of the tissue. For each point of the tissue the Fourier transformation may be applied and the field may be characterized in spectral or autocorrelation terms.
CNS
35
MEMORY
It should be noted that the priority given here to the electric currents (flowing across the structure characterized by some impedance field) as compared with acting electromotive forces has certain grounds. The specific character of the neuronal mechanism of action potential formation, obeying the “all-or-none” law, creates conditions under which the values of electromotive forces (as these electromotive forces exist and act in some sections of the circuits and induce the current) do not change much. The gradual character of the currents flowing in the structure of the tissue is thus determined by the distribution of the impedance. The whole process of propagation of the signal in the cortex, and of electromagnetic field it induces, obeys the Maxwell equations along any correctly selected contours and sections. (B)
ENGRAM
DISTRIBUTION
IN
THE
SPACE
OF THE
CORTICAL
TISSUE
STRUCTURES
The given formulation needs three remarks: First, this statement takes account of the “structural character” of the cortical tissue. Namely, the architecture of the cortex and the anatomical structure of neuronal organization of the brain. I want to stress the deterministic approach to the problem of the routes of the electrical signal flow used here, in contrast to the widely interpreted principal statistical character of electrical processes in the cortex. Second, this statement, as a part of the hypothesis, does not exclude the significance of glial cells and intercellular substance on the background of neuronal net, leaving the possibility for localization of trace substrate in the composition of any cortical tissue component. In this case, without rejecting the idea of probable localization of trace substances in such “poles and zeros” of neural tissue as the areas of synaptic connections, the present formulation does not restrict the application of the hypothesis, requring exclusive recognition of synaptic connectionistic theory. The third point concerns the consequences of the engram distribution concept. On the basis of fixed neuronal organization of the cortex, it predetermines a high degree of multidimensionality of the cortical tissueits extremely large information capacity. This information capacity principally, a denumerable one-in the interpretation of the proposed hypothesis, (for example, for some chosen volume of the cortex tissue) is greater than the number of cells, or the number of synapses, or even the number of macromolecule complexes involved. The information capacity of this volume, or such system, is determined not by the number of elements of the set constituting the system, even taking into account a number of possible changes of their state (for example, conformational changes in macromolecules or the character of polarization of elements), but by the variety of
36
I.
E.
MIKHALTSEV
spatial distributions of the states of these elements that characterize system as a whole. In our case, that is the variety of spatial distributions electrical conductivity or impedance field of the cortical tissue. (C)
FIXED
IMPEDANCE
the of
FIELD
Two points are important: First, it should be precisely determined what kind of impedance is meant. The cortex of the brain is an essentially anisotropic structure. It is commonly accepted, without any limits, to interpret the term impedance as the complex resistance to the electric current between any two points of a conducting medium. Here, the impedance values between two points of the tissue, in general case, should be equated neither with transmembrane resistance of neurons, nor with resistance of glial cells or intercellular substance, and by no means with mean value of volume electrical resistance of tissue. So, the cerebral cortex impedance field in question is the field of complex resistance to electric current along the route of its flow, changing with time. Obviously, this field is vectorial. Under the circumstances, we should keep in mind that the presence of nonlinear elements is the main property of such conducting structures as the cortical tissue. So the possibility of estimating impedance values becomes fundamentally difficult. The second remark concerns the essence of the term “fixed impedance”. The assumption of the possibility of persistent change of electrical characteristics of chemical structures of the cortical tissue under the impact of electrical current and its electromagnetic fields is a key point of the hypothesis. I mean the changes due to conformational transformations, breaches and formation of new connections, change of degree and direction of polarization in the complexes of macromolecules which are components of various cellular structures, membranes and intercellular substance. Using the term “fixed” I understand it as persistent, in the scale of the lifetime of the organism. In contrast to these persistent changes the reversible or temporal changes of electrical characteristics of the tissue should be mentioned; fluctuating potentials, slow potential shifts and the consequences of metabolic activity are responsible for them. 4. The Mechanism of Engram Formation Let us assume that certain presented information resulted in sensory stimulation. Then electrical stimulation induced at the beginning of the afferent tract, under the influence of numerous effects determined by the morphophysiological organization of the CNS, is transformed on the way to the cortex into an electrical signal characteristic of the information presented.
38
I.
E.
MIKHALTSEV
It is important to remember that the CNS organization admits a simultaneous flow of several electrical signals to the cortex-from heterogeneous, simultaneously presented information. These several electrical ‘signals may be interpreted as a complex electrical signal corresponding to the set of simultaneously presented information. If the conditions for perception of the presented information are provided in those areas of the cortex where the electrical signal arrives (Mikhaltsev, 1975), this electrical signal forms the engram. The areas of the cortex with the most pronounced branching of neuronal structure, and those layers of these regions that are characterized by high density of dentrites with the strongest dendro-dendritic interactions, are the cortical areas involved. The engram formation takes place simultaneously with the electrical signal passing through these areas without “consolidation” (Mikhaltsev, 1972) and is expressed in persistent changes of the local value of the impedance of the cortical tissue, induced by the flow of the current and electromagnetic fields generated by this current. The persistent changes of impedance are caused by changes in the electrical characteristics of the neural tissue, on the molecular level. The block diagram of the whole process is given on Fig. 1. The essential element of the hypothesis is the assumption of the mechanism of change in the impedance local values under the influence of currents and their electromagnetic fields. This mechanism may be reduced to the action of three factors: (i) decrease of the impedance in the region surrounding the source of electromagnetic field with appropriate spatial orientation and intensity, (ii) gradual restoration of the impedance to mean values characteristic of the given part of tissue in the absence of the field influence, and
FIG. 2. Schematic diagram of electrical events in some small area of cortical tissue. 0102 is a pathway of the pulse-train of spike activity current Zoo flowing through the tissue. AlAa, BIBS, C,Ca are some equiconductivity lines in the area surrounding OIOz with initial impedance (before the current of pulse sequence 200 flows) IZ,,I = lZobl = IZ,,I = ZO. Due to the difference in electrical properties of the substance surrounding OIOz these lines should not be equidistant from 0102. Under certain conditions (see Fig. 3, Fig. 4 and text) the induced activity I,, in CICa-but not in AlAz or BIBz-cccurs.
CNS
MEMORY
39
I,, = f ( &IO + Es,,)
FIG. 3. Simplified temporal diagrams of the changeof impedance(for the scheme of Fig. 2) between the points on 00 and the corresponding points on AA, BB and CC represented as moduls l&,l, j&I and l-%,l; accompanying currentand field diagrams are shown. Z, is the initial impedance equal for three chosen combinations Zoloa = Zolob = Z,(,,; Z1 is the stepdown threshold impedance; Z,,, is the persistent minimum impedance. The amount of the decrease of impedance under the influence of electromagnetic field E,,,, of the current ZOOdepends upon mutial spatial configuration of 00 and AA, BB, CC; the restoration of the value of impedance to ZO level is gradual. The strongest interaction according to Fig. 2 is assumed between 00 and CC. In the presence of slow potential shift field E,,,, properly phased, and under the influence of the field Eoo the decrease of Z,, reaches Z,,, level and the current Z,, in CC is induced.
of a nonlinear and irreversible-“stepdown”-decrease of (iii) possibility impedance upon reaching a certain threshold (determined by specific character of the tissue structures in the chosen area) under the influence of the field created by a quantum of electrical signal. Figure 2 illustrates schematically the electrical events in some small area of the tissue. The spike activity-the current Zoo-on the pathway 00 changes
40
I. E. MIKHALTSEV
the impedance of the environment and induces the activity I,, on CC. The temporal diagram of these events is presented on Fig. 3, while Fig. 4 outlines the significance of the temporal distribution of the electrical activity in the same area for the spatial-temporal pattern achieved. So the change of the impedance will change the main directions of the currents which follow the pathways of minimal impedance. The described mechanism can explain how the quantized signal (sequence of spikes), say, with constant period of quantization, transforms into a signal with a variable quantization period due to the action of the three factors mentioned above. This effect, which has to my mind a major significance exceeding the limits of the explanation of the proposed hypothesis
FIG. 4. The significance of temporal distribution of electrical activity in the tissue for corresponding spatial-temporal pattern achieved. T,: the induced activity at some point p on CICa is formed under the intluence of electromagnetic field Eoo (as on Fig. 2). Tz: same spatial distribution as at TI. The difference is that at the moment Tz another pulsetrain exists on III&, generating the field Ebb equal to Eoo, but acting in opposite direction; in this case no induced activity on CICz is achieved.
mechanism, is caused by the electromagnetic field influencing in different ways various tissue structures in the sphere of this field’s activity. Thus, the “choice of routes” of further current flow, from any particular point in the cortical tissue, as well as the delay in propagation of the quantum of the signal along the different tracts and the spatial distribution of current will correspond to the distribution of impedance of the cortical tissue in the area surrounding this point. The current and its fields will result in those persistent changes of local values of the tissue impedance we have already spoken about. The trace changes along the route of current forms a new distribution of impedancea pattern of perceived information, or the engram.
CNS
MEMORY
Now, it remains to note that so far I have not used any character of electrical signal. This means that we can pass case of primary sensory stimulation, to the generalization process of the engram formation for the case of electrical within the brain without any external stimuli (Mikhaltsev,
41 limitations of the from a particular of the described signal generation 1972).
5. Retrieval Mechanism The block-diagram of the process of retrieval of some information . . . “a” . . . stored in the engram is shown in Fig. 5. As proposed earlier (Mikhaltsev, 1972) the retrieval of information is based on the existence of a proper conditional stimulus. In our example that is an applied external information-stimulus “c” or information-stimulus “n” appearing in the cortex as a result of internal cerebral activity. Let us first consider the case of the application of the external information “c” (the left part of Fig. 5). En route to the cortex the information “c” suffers the sensory transformation and multiple “recoding” determined by the morphophysiological structure of the afferent tract. As a result, a sequence of pulses-an activity pattern, or an electrical signal characteristic of information “c” is formed and applied to appropriate areas of the cortex. This electrical signal is a spatial-temporal sequence of impulses of the current in the cortical tissue passing along the ways of the minimal impedance for such a sequence. If information “c” has not been applied before, (perhaps together with some other previously perceived or simultaneously presented information) then it will produce the engram corresponding to information “c”. This case of novel information “c” is of no interest to our discussion. If information “c” has been applied earlier accompanying information “a”, the electrical signal will cause stimulation of the cortex area where the engram “c” is stored as a part of a larger engram in which information . . . “c+r” . . . “c+p” . . . , . . . “c+a” . . . is engraved. The central point of the retrieval hypothesis is the assumption of the existence of a mechanism which provides an associative generation of electrical signals (or activation of full patterns) characteristic of information . . . “c+v” . . . , . . . “c+p” . . . , . . . “,+a” . . . . This activation is implemented by the ability of the cortical tissue-especially of its layers, with pronounced dendro-dendritic connections-to produce inductive stimulation (as a result of the flow of currents and their electromagnetic fields characteristic of information-stimulus “c”) upon the nearby elements of the neuronal net, thus creating conditions for another sequence of spike activity and the currents to appear in the cortical tissue. The route of these currents
*
ELECTRICAL characteristic
SIGNAL informalion
“(”
By the action fields having of information
of the currents the spatial-temporal “L.’
and
uf
their electromagnet!c sequence characteristic
the
on-route
The current ,,I Lhe corlxnl IIIWC pawng along tracts of the minimal ampedzncc for the giwn spatial-temporal sequence ch.wcteristic of information “<,‘i e. stimukwon of the CUIIIC~~ area uhere the engram information “l” ib stored
of
transformations
I
to
the
I
J
/
imulatlon mformation
FURTHEK ---upon the for -< -.
of
Dommanr
left
,u,l
of the ‘)u
part a”
upon
dugr,u,,
of cortex is
of the
conditions
areas
the
\\,,h
wlwc
cortex
--I,”
engram
where
\uh\t,tu,cil
the
areas
1 I u U FIG. 5. Block-diagram of the retrieval process of information. . . “a”. . . , stored in the engram. Retrieval is initiated by the application of external stimulus . . . “6 . . . or stimulus . . . ‘W’ . . . generated within the cortex.
I
and
CNS MEMORY
43
is determined by directions of the minimal impedance characteristic of previously formed engrams of information . . . “c+r” . . . , . . . “c+p” . . . ) . . . “C+d’.
...
As in the case of information perception, i.e. engram formation (Mikhaltsev, 1975) the dominant conditions upon the cortex areas where the engram “c+u” is stored (as distinct from the areas storing the engrams . . . “c+r” . . . , . . . “c+p” . . . , etc.) are responsible for generation of the pattern characteristic of information “a”. At this point the process of retrieval of the information “a” comes to the end. The appearance of the cortex activity pattern characteristic of information “a” may result either in the efferent tract stimulation as a response to this information, or in successive associative generation of other patterns “U+x” . . . , “U+f’. . . ) “U+z,‘. . . for which “a” serves as an informationstimulus. The same functional mechanism described for the applied external information “c“ also holds in the case of information “n” characterized by a sequence of patterns associatively generated within the cortex (right side of Fig. 5). It remains to explain the mechanism of the learning process provided by the proposed hypothesis. From the general concept of memory (Mikhaltsev, 1972) it follows that the learning process is related not to the formation of the engram of some information (e.g. information “8) but to consolidation of associative connections necessary for the ability to retrieve that information. In Figure 5 (the lower part) the conditions involved in this process are marked with interrupted lines. I wish to call the reader’s special attention to the need for an additional stimulus which is essential for the learning process and facilitation of the retrieval ability or consolidation of the created associative connections of information to be retrieved. In our case this facilitation of the retrieval of information “a” was determined earlier, by consolidation of connections in the pattern characteristic of “c+u” associatively selected from the set of other possible patterns . . . “c+p” . . . , . . . “c+r”. . . , etc. This consolidation is achieved by the additional stimulus, leading to recurrence (“will”) or amplification (stress, attention, etc.) of the currents in the cortex areas which store the engram “c+u”.t Such stimulated activation of the areas where the engram “c+u” is stored results in domination of the association “~+a’‘-or in relative decrease of impedance (or relative amplification of the current) as compared to similar characteristics for . . . “c+p” . . . , . . . “c+r” . . . , etc. Under these conditions the application of the information-stimulus “c’‘-sometime later-will initiate the 7 1 use psychological terminology here; although physical interpretation of the processes determined by such terms as will, attention, etc. looks feasible, it is beyond the scope of this article.
44
1.
E.
MIKHALTSEV
whole chain of the phenomena presented in the block-diagram Fig. 5 with the result of generation of the pattern characteristic of information “a” which is to be retrieved.
6. Discussion
I shall distinguish between two main groups relating to the concept. The first consists of the postulates which have no direct experimental proof today; the second comprise those points of the hypothesis based on existing experimental data. I consider two main postulates which should be possible to prove by experiments in the future. One is the possibility to achieve persistent changes of the electrical parameters (namely-the impedance) of some chemical structures of the brain tissue by application of the electromagnetic field of appropriate strength. A second-is the statement relating to the ability of the tissue under the influence of quasistatic electromagnetic field (of slow potential shift) and under the impact of spatial-temporal sequence of current pulses, to generate another pulse sequence which covers a wider area of the tissue and thus form a new spatial-temporal sequence. Though some indirect experimental support of these two statements could be mentioned I prefer not to speculate on their validity leaving them here as postulates awaiting direct experimental evidence. The second group incorporates three other important points to be discussed: (i) the distribution of the engram in the cortex, (ii) the change of the impedance of the tissue under the influence of electromagnetic field and (iii) the reality of significant non-synaptic connections in the developed neuronal system of upper cartical layers.
(A)
DISTRIBUTION
OF ENGRAM
IN
THE
CORTEX
The engram distribution is recognized now by most investigators as a concept experimentally substantiated. It is generally accepted to regard the classical experiments of Lashley (1929) as one of the first evidence of distribution of the engram across the cortex. Numerous more recent experimental studies give support to this concept; the appropriate summery is given in any monograph on memory problems, e.g. John, 1967; Pribram, 1971; Livanov, 1972; Beritashvili, 1974. Historically Lashley’s conclusions (1929, 1950) should be considered a stimulus for theoretical interpretations of memory as the process involving
CNS
45
MEMORY
vast fields of the cortex. Apparently, Whyte’s work (1954) should be regarded the nearest to the hypothesis being discussed. Whyte’s suggestion to treat the engram as a distributed vector field in the cortex, was, no doubt, original for that time. Unfortunately, the author could not point out any physically real mechanism forming such a field. Here it should be mentioned that the proposed hypothesis is based just on the most general experimental data dealing with the distribution of the engram (or the electrical activity pattern corresponding to the engram) in the domain of cortical tissue. The hypothesis makes no assumptions requiring the use of any more elaborate approaches, like, for instance, the holographic concept, e.g. Longuet-Higgins, 1968; Pribram, 1971. (B)
THE
CHANGE
OF THE
BRAIN
TISSUE
IMPEDANCE
BY ELECTROMAGNETIC
FIELD
I do not want to give a historical review of this topic but in the sixties Adey and his associates (Adey, Kado & Walter, 1965; Adey, Dako, McIlwain & Walter, 1966; Wang, Kado & Adey, 1968; Elul & Adey, 1966; Adey, 1969) carried out the largest number of experiments on interstitial currents study based on determination of the impedance value. These studies dealt with the measurement of local impedance values in the cerebral tissue as well as impedance change in various behavioural situations (for example, Wang et al., 1968; Adey et al., 1966). The discussion confirming multiplicity of the data on impedance change in cortical activity is presented by Schmitt & Samson (1969). In recent years Llinas, Nicholson and Freeman have fulfilled a series of investigation-both theoretical and experimental-on the conductivity, extracellular field potentials and intrinsic currents in the brain tissue (Nicholson & Llinas, 1971; Llinas &Nicholson, 1974; Nicholson & Freeman, 1975; Freeman & Nicholson, 1975). Among other results the authors (Nicholson & Freeman, 1975) have obtained reliable data of the change of conductivity, correlating with induced stimulation of electrical activity of the tissue. The quantitative characteristics obtained show that it was slightly less than 1% of the mean value (of the conductivity between the microelectrodes 100 pm apart) while the measurement system allowed to have the resolution of 0.06 %. The authors comment this result saying that “no significant change of conductivity was observed” which is quite understandable from the point of view of their main tasks. Though these data were obtained on cerebellar tissue they might be applied to the brain cortex due to the similarity of structural organization of the dendrite field of both tissues. I regard this group of recent results as most significant for the discussed subject.
46
I.
(C)
EPHAPTIC
E.
CONNECTIONS
MIKHALTSEV
IN THE UPPER
CARTICAL
LAYERS
Apparently, Gerard may be considered as one of the first investigators to raise the question on electrical interaction of neurons and their non-synaptic connections most directly (Gerard, 1932; 1941). He has presented direct experimental data on ephaptic connections and electrotonic stimulation not limited by the low-frequency band and pointed, in particular, to parallel orientation of dendrites in the cortex of great hemispheres as an anatomical factor predetermining effectiveness of the connections by electrical field. Later investigations of different trends confirm the significance and give quantitative characteristics of ephaptic connections, sometimes emphasizing the role of electrotonic stimulation. The studies of Morrel (1963), Nelson (1966), Rusinov 8c Ezrokhi (1967), Chirkov (1973) Bennet (1974), Sotelo (1975) could be mentioned. The book by Chirkov (1973) contains a good bibliographical review on the matter; his own convincing conclusions on the effectiveness of non-synaptic transmission of spike activity across the cortical tissue are based on the results obtained in numerous experiments (on more than 60 cats) in uioo on semi-isolated cortical slabs. Adey (1975b) gives additional evidence of the influence of the lowlevel electromagnetic field (of several orders of magnitude lower than estimated for synaptic action) on the neuronal electrical activity in brain tissue. The importance of anatomical structure of the first layers of the cortex for dendro-dendritic interactions was emphasized by many investigators. Rall (1970), Colonnier (1974)-in the framework of synaptic connections, van der Loos (1974), Bennet (1974), Scheibel & Scheibel (1975)-assuming the importance of both synaptic and non-synaptic interactions, Sotelo (1975) -featuring the role of ephaptic junctions, have shown on morphological level the functional significance and the specificity of the branching and high spatial density of dendrites in these layers. Discussing the matter, Adey (1969, 1975~) draws attention to probable specific functions provided by such tissue structure. I consider as his real finding the introduction of the term “nonlearning neurons” applied to the structures of spinal cord in contrast to the learning abilities of neuronal structures of the upper layers of the cortex. To conclude the discussion of the hypothesis I want to point out the work of Schmitt, Dev & Smith (1976) on electrotonic interactions in CNS, who have summarized a quantity of experimental data, demonstrating the existence and significance of the field effect interactions in the brain tissue.
CNS
47
MEMORY
7. Three Corollaries Three corollaries might be derived from the proposed hypothesis. (A)
THE PHYSICS
OF THE CONDITIONED-REFLEX
MECHANISM
I proceed from the assumption that a general concept of biological memory based on the principles of the conditioned reflex and of the dominant is correct (Mikhaltsev, 1972, 1975). If so, the memory mechanism must underlie the conditioned reflex mechanism. In turn, it means that the explanation of processes caused by the conditional stimulus and reinforcement, can be derived directly from the explanation provided by the proposed hypothesis for the physics of the engram formation, associative connections, and dominant selection of the information significant to the organism, by mere substitution of the terms. (B) REVERSIBILITY
OF CONDITIONED-REFLEX
CONNECTIONS
According to the suggested hypothesis the selection of information to be retrieved is determined by dominant conditions upon the areas of the cortex where the patterns of the conditional stimulus and reinforcement are associatively connected. It means that, the conditional irritant and the reinforcement are equivalent in respect to their presence in the engram. In other words, what is the stimulus and what is the reinforcement is determined by dominant conditions in the specific areas of the cortex in accordance with the significance of the stimulus for the organism. I do not persist that Pavlov’s dog will necessarily hear the bell while eating the meat-in this case the irritant and the reinforcement are not equivalent to the object. However, it does follow from the proposed hypothesis that the effect is a quantitative one and if the difference in significance is not as dramatic as in this example (and the dominant conditions are phylogenetically not predetermined) or if the dominant conditions are artificially shifted, the conditional stimulus and the reinforcement will be equivalent, which reveals the reversibility of the conditioned-reflex connections. (C)
ON PHYSICAL
INTERPRETATION
OF THE PROCESS
OF THINKING
A possible mechanism of the higher function of CNS, namely of thinking, can be suggested. This mechanism can be interpreted as a logical corollary of the hypothesis and the general conditioned-reflex concept of memory outlined above. A great number of psychological investigations and observations points to the fact that, phenomenologically, the function of the mechanism of thinking is a process of scanning of associatively connected image sequences,
48
I.
E.
MIKHALTSEV
interrupted by application of stimuli from the environment (in the broad sense). Thus an explanation of the physics of the phenomena involved in the process of thinking can be reduced to the explanation of the mechanism of the associative image generation. The proposed hypothesis provides physical interpretation of the generation of sequences of spatial-temporal patterns adequate to some specific information or image stored in the engram. Within the framework of the hypothesis the process of inventing or creating of new information can be explained as a result of the internal electrical activity of the cortex caused by the sliding slow potential shift in a vast area of the cortex which leads to remote and “illogical” associations. In such cases unconnected engrams of heterogeneous information, being simultaneously activated, become associatively connected which results in formation of a new combined pattern characteristic of novel information. Such specific features as strong interconnections by the field and high spatial density of the dendrites used as keypoints in the hypothesis are adequate to the morphophysiological cortical characteristics known for the representatives of higher levels in the evolutional hierarchy who are capable of thinking. 8. Conclusion The suggested concept leaves open the experimental support for the validity of two postulates used. What concerns the first, the problem might be defined as an oriented search among the chemical components which constitute the cortical tissue, of one or any, having the ability for persistant change of electrical characteristics under the influence of electromagnetic field. An attempt of a straightforward experimental attack on the associative mechanism organized in this laboratory failed due to the difficulties concerned with the instrumental and technical arrangement needed for adequate method of investigation. Nevertheless, I trust the hypothesis (which was formulated about two years ago) might find proper experimental support in future and remain as a useful tool for those who are still involved “in search of the engram”. REFERENCES ADEY, W. R., KADO, R. T. & WALTER, D. 0. (1965). Expl. Neural. 11, 190. ADEY, W. R., KADO, R. T., MCILWAIN, J. T. & WALTER, D. 0. (1966). Expl. Neural. 15, 490. ADEY, W. R. (1969). In Biocybernetics of the Central Nervous System (L. D. Proctor, cd.), p. 1. Boston: Little, Brown.
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