konorski's concept of gnostic areas and … · konorski's concept of gnostic areas and...

ACTA NEUROBIOL. EXT. 1975, 35: 417429

Memorial Paper in Honor of Jerzy Konorski

KONORSKI'S CONCEPT OF GNOSTIC AREAS AND UNITS: SOME ELECTROPHYSIOLOGICAL CONSIDERATIONS

E. Roy JOHN

Departments of Psychiatry and Physiology, New York Medical College New York, N. Y., USA

One of the most enjoyable aspects of my long friendship with Jerzy Konorski was that we viewed the problems of brain function from two very different vantage points. Jerzy had accumulated a tremendous volume of knowledge about the behavioral consequences of lesions of different brain regions, much of which was derived from his own innu- merable, ingenious experiments. My own work has consisted largely of trying to infer the functional significance of observations of electrophysiological processes in different brain regions during behavior.

Whenever Jerzy's travels brought him to the United States and whenever I found the opportunity to visit Warsaw, we resumed our private debate. Our meetings were always the same: we greeted each other with a warm hug, followed by inquiries about our family and mu- tual friends. Then Jerzy would rub his hands together briskly, his eyes sparkling with anticipation, and say: 'Well, tell me what's new'. Hours of joyous altercation then ensued, as we tried to reconcile our different data bases. Sometimes we ate during these discussions, but I doubt that Jerzy would have noticed if the plates had dissolved, he was so intent on the problem.

He was obsessed with the need to understand. I have seldom known a man who pursued knowledge with such brilliance, energy and lustiness. His death was all the more a shock because he was intellectually such a vigorous and youthful person.

I found it characteristic, in these discussions, that Jerzy never chose the easy solution of dismissing as of questionable functional relevance any electrophysiological findings which contradicted his expectations. Rather, he persisted in seeking ways to reconcile such findings with

418 E. R. JOHN

the more familiar results of his lesion studies, accepting the aggravating reality that the same central nervous system could generate two apparently contradictory kinds of evidence. It seems particularly appropriate to follow his lead in this regard in selecting the topic for a contribution to his memorial volume.

The concept of gnostic areas and units

In his monumental work, Integrative Activity of the Brain, Jerzy used psychological data and neurological observations to survey the main categories of unitary perceptions. By unitary perceptions he meant those stimulus-objects recognizable by a single non-analytic process, in contrast with complex perceptions requiring resolution into constitu- ent elements for recognition to occur. Among the principles and characteristics of unitary perceptions which he listed was the important feature that neurological evidence clearly shows that limited cortical lesions are capable of abolishing particular categories of perceptions, leaving other categories of the same afferent system practically unaffected. He cons- tructed an exhaustive catalogue of the perceptual deficits correlated with local cortical lesions in man. He argued that every category of perception was mediated by a specific portion of the associative areas of the cortex. The region of cortex subserving a particular class of perceptions was called a gnostic area or gnostic field. Individual neurons in afferent fields were envisaged as encoding sensory elements pertaining to a stimulus into more and more complex patterns. As the information about disparate features of the stimulus object converge upon successi- vely higher levels, these separate features no longer participate as separate items in further information processing, but become indissolubly amalgamated into a percept of the whole. Thus, Jerzy assumed that a t a sufficiently high level within analyzer systems, unitary perceptions are mediated by the discharge of single neurons, called gnostic units. Gnostic areas were considered as files of gnostic units representing all of the unitary perceptions established in a given subject. Jerzy envisaged redundant representation of each unitary perception by a number of gnostic units, constituting a set of gnostic units all representing the same stimulus features.

Finally, he proposed that once a potential gnostic unit had been preempted by a particular stimulus pattern so as to become transformed into an actual gnostic unit representing that unitary perception, it became resistant to any new stimulus pattern. In other words, a gnostic unit could only participate in representation of a single unitary perception. Representation of a new pattern requires establishment of a new gnostic unit or set of units. Establishment of a gnostic unit mediating a particul-

KONORSKI'S CONCEPT OF GNOSTIC UNITS 419

ar perception involves an increase in the transmissibility (facilitation) of synapses, transforming them from potential to actual connections.

Jerzy assumed that activity of gnostic units corresponds to biolo- gically meaningful stimulus patterns used in associative processes. By careful analysis of the covariation between different sensory dimensions or modalities of perceptual deficits after local lesions, he derived dia- grams of the associations between different gnostic fields. These associations were interpreted as evidence that anatomical pathways connected the corresponding cortical regions.

Jerzy pointed out (p. 76) that there was, at the time he wrote, no direct electrophysiological evidence that perceptions were really represented by units in gnostic areas. He based his conclusions on indirect evidence from psychological considerations, neuroanatomical and neuro- pathological findings, and effects of brain stimulation in waking human subjects. In this paper I will present some of our current electrophysiological studies relevant to the question of whether gnostic areas and gnostic units exist.

Do gnostic areas exist?

Jacobo Grinberg-Zylberbaum and I recently carried out an electrophysiological experiment on human subjects which yielded results bear- ing upon the question of the existence of gnostic areas (unpublished observations). The experiment consisted of two portions. In the first part, subjects seated before a tachistoscope viewed brief presentations of a vertical line, followed by presentation of the number '2'. This stimulus sequence was repeated 50 times at intervals of 1 sec, while evoked responses to the vertical line were recorded from occipital (01 and O,), parietal (P3, P4 and P,), and temporal (T, and T6) derivations using a linked earlobe reference 1. The subject then viewed 50 presentations of the same vertical line, but now followed by the letter 'J'. Evoked responses to the vertical line were again recorded during this second stimulus sequence.

During the first sequence, in which the vertical line was followed by the number '2', it was perceived as the number '1'. During the second sequence, when the vertical line was followed by the letter 'J', it u.as perceived as the letter '1'. Thus, the same vertical line activated two different unitary perceptions, which should be represented by different gnostic units in the gnostic field for visual signs (V-SN). It is noteworthy that Jerzy located gnostic visual fields further lateral and rostra1 than areas 18 and 19. He reasoned that they probably encroached upon tem-

1 Derivation labels refer to positions in the International lo/,, Electrode System.

2 - Acta Neurobiologiae Experimentalis

420 E. R. JOHN

poral cortex (areas 37 and 22) and parietal cortex (area 39 and posterior part of area 7). In particular, he suggested that the gnostic field for visual signs (V-SN) was probably located in the dominant hemisphere around area 7B (p. 123). This locus would lie between electrode P, and P, in the 10120 system.

Using a PDP 12 computer, average evoked responses (AER) and standard deviations were computed from each derivation, for the vertical line in the two different sequences. The AER to the vertical line perceived as a number was then substracted from the AER to the vertical line perceived as a letter. The significance of the resulting difference wave was assessed at many points along the wave, each representing successive latency increments of 2 msec, by use of the t-test. The results from two typical subjects are illustrated in Fig. 1.

Figure 1 shows that no significant differences were found between the AERs to the vertical line under the two different perceptual sets in the primary visual receiving areas (01 and 0,). That is, the sensation caused by the vertical line was essentially the same in both stimulus sequences. However, significant differences did occur in the parietal and temporal derivation, presumably related to the two different perceptions. Essentially the same procedure was used by Johnston and Chesney (1974), who obtained results comparable to ours. Differences between the two perceptual sets were found in frontal but not occipital regions. No data were obtained from parietal or temporal derivations in that study.

In the second experiment, a four stimulus sequence was tachistosco- pically presented, consisting of a large A, a small a, a large E, and a small e. This sequence was repeated 50 times. AERs and standard deviations were again computed for the response to each stimulus from every derivation. The results are shown in Fig. 2.

When the AER's elicited by small and large versions of the same letter were compared, significant differences were found in the occipital derivations. That is, large and small letters produce different sensations. However, no significant differences were found in temporal or parietal derivations. Large and small versions of the same letter activate the same perception, denoting a particular symbol in the alphabet. Finally, when AER's elicited by A's and E's of the same size were compared, significant differences were found in all derivations. Both the sensations and the perceptions elicited by two different letters are different.

What does this experiment tell us about gnostic fields? First of all, it confirms Jerzy's expectation of qualitatively different processes in primary sensory projection areas and association areas. Second, the electrophysiological reflection of the unitary perception of letters and

KONORSKI'S CONCEPT 01;' GNOSTIC UNITS

" I "AS A NUMBER VS ' 1' ' AS A LETTER

i AS A NUMBER w DIFFERENCE WAVE w v -

c - -1 "" t TEST

S.J. S. J. S. J.

1 AS A NUMBER w - p

0.0: LEVEL+[ 5; , .*- --, L .'::.! %L\c?~

L .T J.C. L.T.

Fig. 1. Top: Examples of averaged evoked potentials to a vertical line presented in a context of numbers (line 1) and in a context of letters (line 2). The difference wave obtained by subtracting line 2 from line 1 is shown in line 3. Line 4 shows the value of the t-test at each point along this analysis epoch. Statistical significant differences were obtained in parietal and temporal derivations in the evoked potential components located between 150 and 200 msec of latency. Each average evoked potential was computed from 100 samples. Average responses, variances,

difference waves and the t-test were computed using a PDP-12 computer. Bottom: Same data from a second subject.

4.522 E. R. JOHN

Fig. 2. Top: The difference wave (line 1) and the t-test (line 2) obtained by com- paring average evoked potentials (100 samples) elicited by a big "A" and a little

'caw . Only the occipital location shows a statistically significant difference. Bottom: The same calculations, but now between evoked potentials elicited by a capital "A" and a capital "Em. All the locations show highly significant differences

between, these evoked potentials.


numbers was found much more extensively than he predicted. Instead of being restricted to gnostic field V-SN, corresponding to the parietal regions, marked differences were also found in temporal and frontal regions. How can this be reconciled with the selective deficit called alexic agnosia, caused by lesions in this gnostic field, as illustrated in the six cases of Alajouanine et al. to which Jerzy referred?

One possibility is that the electrophysiological processes manifested in these various anatomical regions are not correlated with the neuronal processes underlying the perception of the stimuli which are responsible for the electrophysiological responses. They may not be relevant to such functions as unitary perception. While this possibility must be recognized, it is nonetheless evident that markedly different neuronal processes are released in temporal and frontal as well as parietal regions when a vertical line is perceived as a letter or as a number, and these different neuronal processes are manifested by different electrophysiological signs. Unless we prefer to prejudge the issue, we cannot assume that these processes are not functionally relevant just because alexic agnosia is not produced by temporal or frontal lesions.

Jerzy's inclination at this point, I believe, would have been to ask two questions: what is the significance of the appearance of these electrophysiological signs in more extensive regions than only the parietal, and why does alexic agnosia only result from damage in gnostic field V-SN?

First of all, I am not sufficiently well informed to know whether damage to temporal or frontal cortex can also produce alexic agnosia or whether damage to gnostic field V-SN invariably produces alexic agnosia. A thorough survey of the neurological literature would be ne- cessary to answer those questions. If damage to temporal or frontal cortex sometimes produces alexic agnosia or even causes increased fre- quency of errors in the interpretation of visual signs, or if correct interpretation of visual signs ever survives destruction of gnostic field V-SN, then we would have evidence that these functions are not exclusively localized within that cortical region.

However, in the absence of such information let us assume that no such evidence exists. Would this mean that the observed activity in temporal and frontal regions was functionally irrelevant and that gnostic units for letters of the alphabet only existed in field V-SN?

In our studies of neural readout from memory in cats (John et al. 1973), we showed that the AER contained exogenous processes, related to the afferent input of information about stimuli (sensation) and endogenous processes related to the interpretation of the meaning of that

424 E. R. JOHN

incoming information (perception and cognition). In later work (Bartlett and John 1973), we showed that these processes were separable and described computer methods to quantify the contribution of exogenous and endogenous processes to the electrophysiological activity of any brain region.

Application of these methods to data obtained from many different brain regions in a large sample of cats performing differential generalization to visual or auditory signals produced the results shown in Fig. 3.

The presence of information about the signal could be demonstrated in all of those various regions, but with a great quantitative difference in the signal-to-noise ratio, as reflected in the rank order of structures along the horizontal (exogenous) axis. The presence of activity related to the interpretation of that information could also be demonstrated in all of those brain regions. An even greater quantitative difference among

Fig. 3. Plot of mean correlation coefficients 40 between exogenous residuals vs. endogenous

FLICKER CLICKER 0

residuals for different neural systems and for different cue modalities.

Closed circles: Flicker frequencies as stimuli. a Auditory system: N = 305 (N - number of V)

independent measurements); Aud. Cx. (16 cats), Med. Genic. (16), Brach. Inf. Coll. (1). Limbic system: N = 303; Hippocampus (16), Dentate (5), Cingulate (51, Septum (5), Pre- pyriform (6), ~Med. Forebrain Bundle (61, Mamm. Bodies (5), Hypothalamus (7). Mesen- cephalic non-specific: N = 158; Retic. Form. (IS), Cent. Gray (I), Cent. Teg. Tract (1). Motor system: N = 146; Motor Cx. (4), Subs.

O SYSTEM Nigra (lo), Nuc. Ruber (4), Nuc. Vent. (91,

z 06 W

= 05.

04

Subthal. (5). Other sensory: N = 54; Sensori- motor Cx. (4), Nuc. Post. Lat. (I), Nuc. Vent. Post. Lat. (5), Nuc. Vent. Post. Med. (1). Tha-

00 10 20 30 40 50 60 lamic non-specific: N = 139; Cent. Lat. (13),

MEAN CORRELATION BETWEEN EXOGENOUS RESIDUALS Retic. (6)' (l)' Med' (5), Pulvinar (1).

Visual system: N = 394, Visual Cx (IS), Lat. Genic. (IS), Sup. Coll. (2). Open circles: Click frequencies as stimuli. Auditory system: N = 48; Aud. Cx. (5 cats), Med. Genic (5). Limbic system: N = 69; Hippocampus (5), Dentate (31, Cin- gulate (3), Septum (31, Prepyriform (2), Med. Forebrain Bundle (31, Mamm. Bodies (3), Hypothalamus (2). Motor system: N -- 37; Motor Cx. (I), Subs. Nigra (41, Nuc. Ruber (I), Nuc. Vent. Ant. (5), Subthal. (2). Non-specific system: N = 50, Mesen. Retic. Form. (6), Cent. Gray (I), Cent. Teg. Tract (I), Cent. Lat. (3), Nuc. Retic. (3).

Visual system: N = 55; Visual Cx. (6), Lat. Genic. (6), Sup. Coll. (1). Data from monopolar and bipolar derivations were combined. Replications varied

across cats and structures (Data from Bartlett et al. 1975).


various structures existed in the signal-to-noise ratio for this type of activity, as seen from the logarithmic scale of the vertical (endogenous) axis, although approximately the same rank order was preserved.

These data indicate that the endogenous processes reflecting particul- a r perceptual and cognitive functions have a very widespread distribution. The fact that the values found for these processes span a range of 1,000 indicates great quantitative differences between anatomical regions in the density or intensity of representation of gnostic function. Perhaps, under normal circumstances, the brain of an individual requires some threshold value for the signal-to-noise ratio to be exceeded in order for information represented by the corresponding neural activity to be functionally useful. If that threshold value is only surpassed by one particular brain region, damage to that region and to no other region will produce impairment of that function. Nonetheless, the relevant information is available in many other places. Perhaps, if the threshold value for the siglnal-to-noise ratio could be lowered, restoration of the impair- ed function might be achieved even though irreversible damage had been sustained by the region which previously achieved the highest signal-to- -noise ratio.

This reasoning seems particularly plausible if we consider that the greater informational reliability of a high signal-to-noise ratio, as life experiences accumulated, would tend to establish functional dependence upon the region displaying the highest signal-to-noise ratio and a learned threshold setting which would reject information from regions with a lower signal-to-noise ratio. Thus, a learned functional inhibition might even be established which prevented such alternate regions from resum- ing functional utility in the event that the region usually mediating that function were damaged.

These speculations offer a way to reconcile Jerzy's conclusions and the observations upon which they were based with the apparently contradictory electrophysiological findings in our studies. Perhaps the signal-to-noise ratios for activity related to the perception of letters and numbers is highest in V-SN, and the threshold in the normal brain is usually set to reject lower signal-to-noise ratios for that activity. Such lower signal-to-noise ratios might exist in temporal or frontal regions. Thus, although information relevant to the perception of letters and numbers is available in those regions, damage there will not result in alexic agnosia nor can they sustain such perception alone if gnostic field V-SN is damaged. While 1 have no evidence at present that these speculations are correct, they provide an attractive working hypothesis. At- tractive not only because thus no contradiction need exist between two bodies of data, both of which reflect real aspects of brain function, but

426 E. R. JOHN

also because were this hypothesis correct much functional deficit due to brain damage which we presently consider irreversible might even- tually prove to respond to treatments which lower the relevant thres- holds or block the learned functional inhibitions.

Do gnostic units exist?

I want now to turn to the second question addressed by this paper: to gnostic units exist? Let us recall that Jerzy assumed that gnostic units were neurons which were transformed by a process of synaptic facilitation so that silbsequently they responded only when the corresponding unitary perception occurred. Further, these gnostic units were resistant to future changes, specifically excluded from participation in multiple perceptions by certain aspects of Jerzy's theoretical argument.

Several kinds of evidence seem to controvert Jerzy's expectations. In another article (John 1972), I reviewed much of the data which op- poses the conclusion that a process of synaptic facilitation recruits neurons to the representation of perceptual experiences. Among the findings cited in that article were numerous reports that changes in neuronal response during learning only occur in polysensory units which respond to all of the associated stimuli before the learning experience. Since Jerzy presented compelling arguments that gnostic units must be ini- tially uncommitted and come to represent unitary percepts as the result of experiences, such findings cannot be reconciled with his contention that gnostic units become committed by the transformation of potential to actual connections.

In the same article, I reviewed the evidence that a high proportion of units, ranging from 10°/o to 60°/o in various studies, change their response even in simple learning tasks. Given the high probability of modification of unit activity with experience which is apparent from these reports, it seems very unlikely that a gnostic unit, once committed, could be 'immunized' or protected against subsequent involvement in the mediation of new perceptions, as required by Jerzy's formulation.

Finally, for five years my colleagues and I have been studying unit behavior in discrimination learning (John and Morgades 1969abc, Ra- mos and Schwartz 1974, Ramos et al. 1974ab, John 1974). In those studies we have utilized chronically implanted, movable microelectrodes to exa- mine the responses of small groups of neurons and, more recently, well-isolated single neurons, during correct responses and errors in tasks requiring differentiated behavioral responses to discriminated visual stimuli, and also during differential generalization to ambiguous stimuli delivered to differentially trained animals.

KONORSKI'S CONCEPT O F GNOSTIC UNITS 42 7

Evoked potentials and unit responses were simultaneously recorded from both cortical and subcortical microelectrodes in these cats. Cortical electrodes were located both in specific projection and association areas. Using computer pattern recognition techniques described elsewhere in detail (Barlett, John, Shimokochi and Kleinrnan 1975), single evoked potentials from trials resulting in correct vs. erroneous performance to the same conditioned stimulus or from differential generalization trials in which two different behaviors were elicited by the same novel test stimulus were classified. This classification procedure identified the e- voked potentials as belonging to one or another of the 'readout modes' which reflected the activation of memories about different stimulus-response contingencies. Particular readout modes were found to be differentially correlated, at extremely high significance levels, with the subsequent behavioral performance. Therefore, occurrence of a particular readout mode can be interpreted as evidence that the stimulus eliciting that electrophysiological and behavioral response was perceived as a signal with a particular significance.

When the pattern recognition procedure had identified the readout mode activated by each stimulus in the behavioral trial, the firing patterns of the simultaneously recorded unit activity corresponding to each readout mode were separately analyzed. We found two types of neurons in these analyses. One type showed an invariant average pattern of response to a given stimulus, no matter how it was perceived (i.e., no matter what behavioral response ensued). These units might be described as 'stimulus-bound', responding to the signal in the same way independent of perception. The second type of neuron showed one average temporal pattern of response during one readout mode and a different average temporal pattern of response during another readout mode. These units might be described as 'gnostic' units, with a response pattern related to the perception rather than determined by the sensation. Such units showed great variability in their responses during a specified readout mode, but displayed a characteristic and specific average response in each mode. Different units of this type in the same anatomical region showed closely similar average responses during the same mode, although their responses to single stimuli were poorly synchronized. These findings suggested an 'ergodic' hypothesis, that is, the average response across the set of units of th.is type to a sing7e stimulus presentation eliciting a specified readout mode corresponded to the average response of any unit of this type to a set of stimulus presentationseliciting that specific readout mode. In view of these data, it would seem that the perception of a stimulus is mediated by the averaged temporal firing pattern of an ensemble or set of units of this type. The activity of any sin-

428 E. R. JOHN

gle unit is important only insofar as it contributes to the statistical behavior of the ensemble.

Further, firing of any unit per se seems to have no unique informational value. All units thus far observed not only fire 'spontaneously' and show great variability in response to any stimulus, but show a differential response consisting of differences in graded temporal patterns, rather than the all-or-none behavior postulated in Jerzy's theory.

As yet, we have not observed a single neuron which fired only during one readout mode and not in another, or which displayed patterned discharge in m e mode and random activity in all other modes. Thus, we have so far failed to observe any neuron with the characteristics of the gnostic units which Jerzy postulated.

In spite of this apparent failure to confirm Jerzy's predictions, I must hasten to point out that even after years of study we have succeeded in analyzing only a small number of units and most of those have not been in associative cortex.

It may well be that further studies, especially studies conducted in other cortical regions more relevant to the peculiar stimulus dimensions critical for the discriminations required in our behavioral tasks, will re- veal the existence of gnostic units with the predicted features. We are continuing to pursue these studies in the hope that we will either find such units or amass a sufficient volume of data to justify rejection of the hypothesis.

I deeply regret that Jerzy Konorski is no longer alive to discuss these findings, to guide us with his intuition and vast knowledge, and to in- spire us with his unlimited enthusiasm for the quest after understanding. When the answer to these intriguing problems finally becomes clear, whether Jerzy's hypotheses were right or wrong, I am sure that his contributions will have been invaluable. He was a rare one and I miss him.

This work was supported in part by Grant No. MH 20059 from the National Institute of Mental Health.

REFERENCES

ALAJOUANINE et al. Quoted Konorski (1967). BARTLETT, F. and JOHN, E. R. 1973. Equipotentiality quantified: the anatomical

distribution of the engram. Science 181: 764-767. BARTLETT, F., JOHN, E. R., SHIMOKOCHI, M. and KLEINMAN, D. 1975. Electro-

physiological signs of readout from memory. 11. Computer classification of single evoked poter~tial waveshapes. Behav. Biol. 14: 409-449.

JOHN, E. R. 1972. Switchboard versus statistical theories of learning and memory. Science 177: 850-864.

KONORSKI'S CONCEPT O F GNOSTIC UNITS 429

JOHN, E. R. 1974. Cellular mechanisms in conditioning. Paper presented at XXVI Int. Congr. Physiol. Sci. (New Delhi).

JOHN, E. R., BARTLETT, F., SHIMOKOCHI, M. and KLEINMAN, D. 1973. Neural readout from memory. J. Neurophysiol. 36: 893-924.

JOHN, E. R. and MORGADES, P. P. 1969a. Neural correlates of conditioned responses studied with multiple chronically implanted moving microelectrodes. Exp. Neurol. 23: 412-415.

JOHN, E. R. and MORGADES, P. P. 1969b. Patterns and anatomical distribution of evoked potentials and multiple unit activity elicited by conditioned stimuli in trained cats. Comm. Behav. Biol. 3: 181-207.

JOHN, E. R. and MORGADES, P. P. 1969~. A technique for the chronic implanta- tion of multiple movable microelectrodes. Electroenceph. Clin. Neurophy- siol. 27: 205-208.

JOHNSTON, V. L. and CHESNEY, G. L. 1974. Electrophysiological correlates of meaning. Science 186: 944-946.

KONORSKI, J. 1967. Integrative activity of the brain. An interdisciplinary ap- proach. Univ. Chicago Press, Chicago. 531 p.

RAMOS, A. and SCHWARTZ, 'E. 1975. Observation of assimilation of the rhythm at the unit level in behaving cats. Physiol. Behav. (in press).

RAMOS, A., SCHWARTZ, E. and JOHN, E. R. 1974. Unit activity and evoked potentials during readout from memory. Proc. XXVI Int. Congr. Physiol. Sci. (New Delhi).

RAMOS, A., SCHWARTZ, E. and JOHN, E. R. 1974. Unit activity and evoked potentials during readout from memory. Abstract in Society for Neuro- science, IV Annual Meeting (St. Louis), p. 416.

Received 6 February 1975

E. Roy JOHN, Brain Research Laboratories, New York Medical College, New York, New York 10029, USA.

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