Jürgen Krüger

Professor für Neurobiophysik im Ruhestand

Foto J. Krüger

Vorlesung jeweils im Wintersemester
über das Gehirn und das Bewusstsein. Das Bewusstsein läßt sich zwar nicht in die Naturwissenschaft integrieren,
aber man kann die Inhalte des phänomenalen Niveaus des Bewusstseins beschreiben und mit Kenntnissen aus
der Neurowissenschaft vergleichen. Besondere Bedeutung kommt der Zeitachse zu.
Näheres (Zeit und Ort) gebe ich jeweils in http://www.brain-kruger.de bekannt.
emailadr
Forschung

1. Spiegelneurone,
    Mirror neurones, in collaboration with Dip. Neuroscienze, Università degli Studi, Parma
2. Magneto-akustische Reizung des Nervensystems
    Magneto-acoustic stimulation of the nervous system, in collaboration with Neurologische Universitätsklinik, Freiburg

3. Schizophrenie und Affen
    Schizophrenia and monkeys
4. Physik und die phänomenalen Gehalte des Bewusstseins, cf.
http://www.brain-kruger.de
    Physics and the phenomenal contents of consciousness.
5. Frühere Arbeiten
    Previous work
6. Arbeitsweise des Ruheständlers.
    Mode of work of the retired scientist.


1. Mirror neurones
Recordings were done with 64 chronically implanted microelectrodes from the monkey "mirror neurone area" F5 in the ventral premotor cortex. The monkey was given food by hand, and also with a pliers which the animal never had seen before.  We could show that the  multineuronal excitation pattern elicited by viewing the pliers became very similar to the one evoked by the hand after three trials only.  In contrast, a device operating with a  thread and a tube, also delivering food to the monkey, but looking and functioning very differently as compared to the hand and the pliers, never evoked excitation patterns similar to those of the hand. Work done with R. Dalla Volta and F. Grammont.
With F. Caruana and G. Rizzolatti
(Dip. Neuroscienze, Università degli Studi, Parma) it will be attempted to confirm this observation on another monkey, using a greater variety of food-delivering instruments.
A more detailed report will soon be available here.
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2. Magneto-acoustic stimulation.
It is attempted to stimulate nervous tissue with a combination of ultrasound and a magnetic field oscillating at the same frequency. The basic idea is that the tissue moves in the instantaneous magnetic field, with the movement and the magnetic field directions inverting at the same instant so that the induced voltage continues to head in the same direction during many oscillation periods. With respect to focalisation and intensity we expect advantages over Transcranial Magnetic Stimulation and mere ultrasound stimulation. A 6 kW-generator of oscillating magnetic fields and an adequate ultrasound generator is now available. We currently explore the conditions of testing the desired effects in nervous tissues of different kinds. Work done with Neurologische Universitätsklinik, Freiburg and H. Kaube, München.
A more detailed report will soon be available here.
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3. Schizophrenia and monkeys

An evolutionary consideration about schizophrenia in monkeys.


A monkey model for human schizophrenia would be extremely valuable but it appears that there is no such model in a convincing way. This text concerns the possibility to study a derangement in monkeys which may be related to human schizophrenia, and thereby to offer a new gate to find a specific therapy. The likelihood of success may be small but the severity, the frequency, and the duration of the disease makes it worthwile to consider the present view.

General

Among neuroscientists there is a wide consensus about the differences between monkey and man: monkeys are "humans minus language" while the remaining faculties are present to a reduced extent. Other views will be discussed elsewhere.

The present view rests on a more specific statement on ".. minus language":

The biological construction principle of the head is remarkably stable from fish (or even insect) to frog to bird to rat. One may conclude that there is a particularly high obstacle on the way to possible alternatives. Here the relevant feature is that the principal effector, not for locomotion but for "mani"pulations, i. e. the mouth or the beak, is rigidly coupled to the eyes. In cases of visually guided actions, the animal has to take care only of two relevant positions: that of the object acted upon, and that of the eyes which in turn have some rigid neuronal coupling to the effector position.

Monkeys with huge brains have introduced the use of hands. The consequence is that they have to take into account three positions, namely those of the object, of the hand and of the eyes. Instead of the above rigid coupling they have evolved a powerful control machinery for visually guided manipulations.

One can learn from robot engineers who build video-guided grasping tools that the introduction of a foreign, similarly looking tool into the visual field of the camera will lead to a severe perturbation of the control circuitry. This is the "new problem" introduced by the evolutionary step towards monkeys. They had to evolve a supplementary control which is: "Sensorily controlled manipulations must be based on sensory impressions of own hands. Block the hand motor output if signals from foreign hands are recognised". Or stated otherwise: "Don't attempt to base motor commands on pertinent sensory impressions that are, in some sense, fictive." No such rule was necessary in other animals.

Another stream of cerebral evolution went towards increasingly complex and long-lasting non-repetititve procedures. ("Procedures" are "bicycle riding", or "eating with a spoon", or "building a nest". ) The longer they last, the more likely is an interruption. The usual way of restarting an interrupted procedure is to rely on the sensory recognition of one's own partial achievements: the rabbit need not recall how far it has dug its burrow. Rather, the half-dug burrow serves for a kind of external memory. Obviously, the drawback is that the relevant structures must remain constant during the pause. Typically this is not true if the results of a procedure are sent away, or otherwise are withdrawn from continued observation shortly after the moment of production, and the procedure does not allow a restart. A case in point is a prolonged medical treatment of a patient: it is impossible to found the next step of the treatment exclusively on actual observations of the patient, without taking into account which pills have already been given.

The limitation can be overcome by constructing a type of memory ("episodic") that stores the essential sensory features at the instant of interruption, and later reproduces them.

The present view is that this step alone characterises the transition from monkeys to humans.

However, the step is extremely dangerous: it implies that one generates a fictive sensory impression at another than the original instant. Progress towards humans brings about this "new problem". I do not believe that any animal species other than humans has ever done this step.  The excellent memory of monkeys and apes most probably is of the type "procedural"; one cannot prove that it is "episodic". The manifestation of fictiveness resides in the fact that this type of apparent sensory impression may not, or must not be altered by motor commands: one cannot change, by present own motor acts, the contents of a recalled sensory scene.

The particular point of the present text is this: The evolution towards humans would not have taken place if monkeys had not existed before, and if they had not prepared the way how to cope with "fictive" sensory impressions, although the view of a foreign hand is "fictive" in a much narrower sense than the view-like recall of my past hand, or any other past scene.  The common aspect, in both cases, is "Don't attempt to base behavioural output on pertinent sensory impressions that are, in some sense, fictive".

As soon as  the safe operation of the rule was established, monkeys could even turn the new situation into an advantage unrelated to sensorimotor control ("mirror neurones") allowing them to draw some conclusions about motor acts of conspecifics. With the advent of episodic memory, humans, too, could go beyond a mere interruption management, and begin to draw conclusions from past to future. Both monkey and man had to fuse the fictive signals with some real ones in an intricate way. In that fusion process the real signals have to dominate, i.e., in the case of hands, those originating from my hand (for monkeys), or my present hand (for humans). Only if this fusion is achieved appropriately, a motor behaviour can be generated. In the example of a medical treatment given above, it is not sufficient that the doctor generates a quasi-sensory impression ("recall") of the last step of the treatment, but he/she has also to make sure that the patient, and the pills for the next treatment, exist at present. With respect to the timing of motor output, the latter "real" components must have absolute priority.

This sounds trivial but such complications do not occur in a rat.

A peculiar example is human speech. The physical effects of speech are sent away so that an interrupted stream of speech (as it occurs in every dialog) could not be continued without the abovementioned interruption management. Monkeys cannot speak in a human sense because they lack that management. They can only use what in humans would correspond to the grammatical category of imperatives, whose simpler forms can run without that management. (A facial expression is an imperative.) Thus, the absence of speech is not a deficit of communication proper, but it is a lack of an evolutionary step within each individual monkey. This is meant by "... minus language".

It does not come as a surprise that the human Broca area has indeed been found to be homolog, or an extension, of the monkey mirror neurone area F5 in the ventral premotor cortex. In my opinion, the reason is not that human language evolved from manual gestures but rather that this region is the site of the proper treatment of fictive signals in the sense as explained above. To say it once more: in the present context "reality" means to receive correlating sensory feedback from own motor commands, and "fiction" means to have sensorily comparable situations where own motor commands have no such effect.

The obvious relationships to consciousness cannot be discussed here.

Derangement

A cerebral derangement that leads to a confusion of real and fictive situations might be the most general way of describing schizophrenia. If a patient hears non-existing voices, then this can only be based, perhaps indirectly, on a retrieval from some memory of an episodic type.

The purpose of the present text is to point out that a similar physiological disease in monkeys and humans, attaining the way how "fiction", in the present sense, is treated, would have different effects in these two species. It would be a derangement that is related to the way how sensory-like signals from past experiences (in humans), and sensory signals from foreign individuals (in monkeys), respectively, are brought together with own present sensory signals, in order to merge them into a reasonable behavioural output.

The disease is the price to be paid in evolution for becoming a monkey, and a human, respectively.

The conclusion is that one would have to look, in monkeys, for inappropriate behavioural signs of the treatment of sensory signals coming from other monkeys or humans ("monkey schizophrenia"). However, the ubiquitous social signals exchanged within all animal species must be excluded. (Each rat or each insect has to recognise its conspecifics but it cannot, and need not "know" that itself it is such a conspecific, too.) Rather, one would have to focus on signals that can originate from another individual as well as from the animal itself, just as in the case of viewing a hand. If one can find a means to damp or, on the other hand, to provoke such signs in monkeys, then there is a certain chance that these means are similarly effective also for human schizophrenia.

Practical

If the rate of occurrence of monkey and human schizophrenia is comparable, then some casual observations must already have been made in the numerous scientific institutes, monkey elevation stations, or zoological gardens. It would be a first step to collect such reports, in order to delimit typical or frequent cases. The outcome of that step may lay a better foundation for a more powerful attack. At this point, schizophrenia experts must guide the investigations.

At present there is a monkey at the Dip. Neuroscienze in Parma that apparently has no genuinely visual defect but that is unable to guide his hand appropriately when it has to execute different varieties of grasping. Instead of adjusting the type of grasp to the actual situation, the animal tends to use the same grasp as the previous one even if it is now inappropriate, and thus to deprive itself from receiving a reward. So far, the animal has not been examined for more pertinent defects. I do not mention this case because I am convinced that it is particularly relevant. Rather, it is an example for a case in which no one would have thought of an even remote link to schizophrenia.

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4. Physics and the phenomenal contents of consciousness.
See the website http://www.brain-kruger.de
.
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5. Previous work

(done with various collaborators, and guided by various directors)

Proton magnetic resonance at low magnetic fields. Resonance in a rotating frame of reference (Failure of finding some non-trivial effect under this condition). Resonance in a magnetic field gradient (Rescue program foreseen for the case of failure of the previous project). Multiple-quantum transitions. Until 1965; Diploma thesis, physics, Universität Karlsruhe.

Attempt to visualise the
dynamic spatial distribution of normal/supraconducting domains in supraconductors type 2, using a reflection electron microscope. Failure for reasons of organisation. Until 1969; CNRS-Basses Températures, Grenoble.

Thermal properties of demixing glasses at low temperatures.
Until 1971; Doctoral thesis. CNRS-Basses Températures, Grenoble.

Demonstration of vigorous discharges in cat retinal ganglion cells elicited by far peripheral stimuli ("periphery effect", later "shift effect"). (1972-1979) Neurologische Universitätsklinik, Freiburg

Colour processing in visual cortical areas of the monkey
(1975-1977) Neurologische Universitätsklinik, Freiburg

Recording with 30, later 64 microelectrodes from monkey visual cortex
(1979-1999) Neurologische Universitätsklinik, Freiburg,
AG Hirnforschung, Freiburg.

Recording with 64 chronically implanted
microelectrodes from the mirror neurone area F5 in monkey ventral premotor cortex (2000-today; Dip. Neuroscienze, Università degli Studi, Parma)

Considerations, partly related to monkeys, how the phenomenal contents of consciousness are related to neuronal activity (1998 until today).

Comments on my previous work:
The transition from physics to neuroscience was facilitated by a 2-year stipend from Volkswagen Foundation (1972-73). My immediate interest was to
get new types of insight into cerebral activity by using large numbers of electrodes. I wanted to be able to "orient myself" within the neuronal activity alone, i.e. to know what is going on without relying, at the same time, on the knowledge about the environment of the animal. This is in fact the way how the animal uses its brain.

The attempt was delayed by several years. Looking back, and including the work of other scientists one can summarize that there has never been any great breakthrough brought about by the use of many electrodes although the required technologies soon became easily available. Still today one cannot say that the desire to understand the neuronal activity by itself (so to speak, from within the brain) is a major branch of neuroscience, although it is a prerequisiste for neuronal prosthesis programs. This may partly be impeded by the implicit, hidden expectation that the "neuronal order" should correspond to the entities as they appear on the phenomenal level of consciousness of the experimenter. Thus, instead of a neuronal procedure of "eating soup with a spoon", one may (falsely) expect, within the neuronal activity, a manifestation of "the spoon" as an object or "stimulus", or a "hand movement"  as a motor event, which is independent of further procedural circumstances.
With these thoughts in mind I shall contribute soon to an exploration of the prefrontal cortex of the monkey at Dip. Neuroscienze, Parma.
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6. Mode of work of the retired scientist.

A great problem of research organisation is how to carry out research on an interesting topic if the risk of success is too high. It is well known that the main body of the research community, consisting of doctorands and post-docs, cannot take the risk of total failure after several years of hard work. The only persons who can actually carry out such work are the directors themselves if their positions are secure, auxiliary personel not striving for a research career, and retired researchers. The directors cannot delegate high-risk research to the "common" researcher (except for some smaller cases in which a "rescue program" is prepared from the outset for the case of failure; see my previous work) . Usually, the more "successful" a director is, the more doctorands and post-docs are associated to him/her, with the consequence that
barely any time is left to execute him/herself a high-risk project.  Unfortunately, they must even encourage work for which the risk of success is not too high. Yet, often they carry some unconventional ideas in their minds for which they cannot see any way to get them realised. In addition, if too many scientific prerequisites are lacking for such projects, there is no way to receive a supporting grant, so that the path via paid auxiliary personel is blocked, too.

Thus, only retired scientists can offer a way out of this dilemma, all the more so as the general life expectation has greatly increased during the last decennies, while the age of retirement has remained rather constant in many countries. to tackle such work, a director of a large group, charged with lots of organisatorial tasks, has to wait until he/she reaches retirement him/herself.

The fraction of retired researchers willing to follow such a path may be small. Yet, it might be greater if the research institutions had clear plans how to use the potential of the retirees, how to make use of otherwise non-used material and rooms, and on the other hand, how to cope with clearly esoteric projects, and with researchers becoming senile. It would also be desirable to initiate a clearcut open competition between retired and younger scientists, and to create prices or awards for contributions obtained after retirement age. Certainly, to begin with, one would not consider the question of how a retired scientist should be paid. "Nothing" would be fine for at least some of them. Rather, "results per Euro of total costs" should be taken into consideration. An advantage of "fundamental research", as compared to other branches of human activity, is that no retiree "steals the work" of a younger person. There is enough work for everyone.


While waiting for adequate organisatorial steps, the retired researcher has to behave in similar ways as the members of medieval mendicant orders.

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