THE CHARACTERISTICS OF STIMULI
_Contents_: The quality of the stimulus. Positive and negative
alterations of the factors which act as vital conditions. Extent of
the alteration in vital conditions or intensity of the stimulus.
Threshold stimuli, sub-threshold, submaximal, maximal and supermaximal
intensities of stimulus. Relations between the intensity of stimulus
and the amount of response. The _Weber_ and _Fechner_ law. All or
none law. Time relations of the course of the stimulus. Form of
individual stimulus. Absolute and relative rapidity in the course of
the stimulus. Duration of the stimulus after reaching its highest
point. Adaptation to persistent stimuli. Series of individual stimuli.
Rhythmical stimuli. The _Nernst_ law.
We have found that stimuli are alterations in the external vital
conditions and that the irritability of living substance consists in
the capability to respond to stimuli by changes of the vital processes.
It now behooves us in the interest of experimental research to
investigate the relations between the nature of the alterations in the
external vital conditions on the one hand, and that of the alterations
of the vital process on the other; that is to say, to systematically
study the effects of stimulation on the living organism. For this
purpose it is above all necessary to become acquainted with the almost
countless numbers of alterations which take place in the external
vital conditions of an organism, and to create a systematic scheme of
stimulation which differentiates and presents in comprehensive order
those various elementary factors which, among the innumerable varieties
of stimuli, would prove effectual. For this purpose it is necessary to
select the various factors which are involved in an alteration of the
external vital conditions.
The first of these factors is the _quality of the stimulus_. The
external vital conditions are, in short, a series of chemical factors,
such as foodstuffs, water and oxygen; the presence of a certain
temperature; the existence of a certain light intensity; the existence
of a definite static pressure; and finally the presence of an equal
osmotic pressure. The stimulus according to its quality can be
differentiated into chemical, thermal, photic, mechanical and osmotic
varieties. To these must be added other forms of stimuli not ordinarily
operative, for instance, many uncommon chemicals, and certain kinds of
rays. The form of stimulation, par excellence, which has acquired the
greatest importance for the _experimental_ investigation of life, is
electricity. In its manifold forms it permits, as no other, of such
fine gradations of intensity and duration that it has become in the
hand of the physiologist an invaluable means of research.
Alterations in those factors which act as vital conditions compose the
great mass of physiological stimuli which act continuously on every
living organism. The first point to be considered in every alteration
is its _direction_. The alterations produced by stimuli may be of
two different kinds, either positive or negative. The quantity of
foodstuffs, water or oxygen, in the surrounding medium, can undergo an
increase or diminution; as may the temperature, intensity of light, the
atmospheric and osmotic pressure. The strength of the electric current,
which may be applied, can also be regulated. In accordance with the
definition of stimulation already referred to, we must consider these
alterations, whether negative or positive, as forms of _stimulation_.
Now the question arises: Is this point of view justifiable? Should one
also consider, for example, the lessening or total removal of a vital
condition as a stimulus? Should one consider the removal of water or
oxygen, cooling or darkening, as a stimulus? It has, in point of fact,
been occasionally attempted _not_ to regard these negative deviations
as forms of stimuli. These observers permitted themselves to be led by
the dogma, that only that which produces an excitation, that is, an
increase of the processes in the living substance, should be regarded
as a stimulus. Such a limitation of the conception of stimuli would
only result from the one-sided consideration of an all too limited
circle of facts. Considered from the point of view which results from a
broader range of experience, this narrow view becomes untenable.
In the first place it does not follow that only _positive_ fluctuations
of a factor, acting as a vital condition, result in _excitation_ in
the existing vital processes. The _withdrawal_ of water produces a
diametrically opposite effect. A muscle, from which water has been
removed, if exposed to dry air or placed in a hypertonic salt solution,
shows violent _excitation_, which manifests itself in great increase of
irritability and development of fibrillary contractions. The breaking
of a constant current which has for a long time flowed through a
nerve or muscle also elicits a momentary excitation. Further, the
abrupt removal of light may also bring about stimulation. To cite an
example from the physiology of the single cell, I should like to call
to your attention the interesting observations of _Engelmann_[17] on
the _Bacterium photometricum_, of which he was the discoverer. When
the field containing these organisms is suddenly darkened, all the
individuals contained in the drop immediately dart forward for some
distance, at the same time, as is usually the case, quickly rotating
around their own axis, and then after a moment of immobility, swim
on quickly in another direction. An analogous responsivity has also
been shown by other single cell organisms, as has been pointed out by
several observers and especially by _Jennings_.[18] In all these cases
the excitation was produced by a lessening or total withdrawal of the
factors which act as vital conditions; and even those who take the
standpoint that only such factors are to be considered as stimuli which
produce an _exciting_ effect, are compelled to regard these alterations
as stimuli, in spite of the fact that they are _negative_ variations of
external vital conditions.
[17] _Th. W. Engelmann_: “Bacterium photometricum ein Beitrag zur
vergleichenden Physiologie des Licht-und Farbensinns.” In Pflügers
Archiv. Bd. 30. 1883.
[18] _Jennings_: “Behavior of the lower organisms.” New York 1906.
But further, the restriction of the term stimulation to those
alterations which increase the course of the changes in the living
substance involves the observer in still greater contradictions. It
can easily be shown that one and the same factor in one and the same
form of living substance has now an exciting, now a depressing effect
on the vital processes. This fact can be readily demonstrated[19]
by means of the infusoria _Colpidium colpoda_, which can be grown
without difficulty in a hay infusion. A number of individuals in a
drop of fluid may be placed in a warm stage and observed under the
microscope; one then sees that at room temperature they swim about
by moving their ciliary processes at a definite rate. Now if the
temperature is raised to about 35° C., the ciliary movement becomes
enormously increased. The infusoria swim madly through the field of
vision. They are in a state of violent excitement. The increase has,
therefore, acted as a strong, exciting stimulus. But if one allows
the temperature to further increase only a few degrees the ciliary
movements are suddenly greatly retarded. The infusoria now swim
sluggishly through the field of vision and finally remain stationary.
In this case the increase in the temperature has had a depressing
effect. If the infusoria are not quickly removed, the depression is
followed by death. Should the increase in temperature be regarded in
the _first_ instance as a stimulus, and _not as such_ in the _second_,
in which the temperature rises only a few degrees higher? Here the
change in the vital conditions concerned is in both instances positive.
In all cases of overstimulation we are confronted by the same question.
Nevertheless it is not at all necessary to refer to such strong or even
life-endangering stimuli for the observation of these conditions. In
this connection I would like to cite an even more striking instance and
which is of special interest for the understanding of the phenomena
in nerve centers. If the posterior spinal roots of a _Rana temporara_
are severed, and the eighth root stimulated with a faradic current,
whilst the _musculus Gastrocnemius_ of the same side is connected
with a writing lever, one obtains, as _Vészi_[20] has found, at the
moment of the beginning of stimulation a contraction of the muscle.
The faradic stimulus has, therefore, produced an excitation reflexly.
If instead of the _eighth_ the _ninth_ posterior root is stimulated,
the result obtained is also an excitation of the muscle. In this case,
however, the excitation in the form of a tetanic contraction lasts
for some time, provided that the stimulation is not at once stopped.
If now during tetanic stimulation of the ninth root the eighth is at
the same time stimulated, with a strength of current equal to that
which previously brought about contraction of the muscle, instead of
an _increase_ and a _strengthening_ of contraction there is, on the
contrary, an _inhibition_ which continues throughout the time during
the stimulation of the eighth root. If the stimulation of the eighth
root is discontinued, the tetanic response of the ninth root reappears.
If, on the other hand, the faradic stimulation of the ninth root is
interrupted and the eighth root now again stimulated, one obtains once
more, as in the beginning, with each stimulation a contraction of the
muscle. This fact is illustrated by the accompanying tracings. (Figure
2.) In this investigation undertaken in the Göttingen laboratory it
was further shown that a faradic current of the same strength and the
same frequency had at one time an augmenting, at another an inhibitory
effect, and these effects could be produced alternately at will. Should
the faradic current at one time be called a stimulus, at another not?
It is here clearly shown to what absurd consequences it leads if the
conception of stimulation is limited solely to the cases in which an
external factor has an exciting effect; and yet an immense number of
instances of a like nature could be cited to show the untenability of
this view.
[19] _Max Verworn_: “Physiologisches Prakticum für Medizinen.” Jena
1907.
[20] _Julius Vészi_: “Der einfachste Reflexbogen im Rückenmark.” In
Zeitschrift f. allgemeine Physiologie Bd. XI, 1910.
[Illustration: Fig. 2.
Lower thick line shows duration of stimulation of 9th root; upper thick
line that of 8th root.]
It follows from this, that it is altogether impracticable to define
the stimulus itself in relation to the nature of the effects which
the stimulus has upon the substances in the living system. One can
only appreciate the nature of stimulation in relation to the vital
conditions and without considering the nature of the action of the
stimuli on the living substance. It is true that every stimulus is
followed by an alteration in living processes, but this is to be
expected when one clearly understands the nature of vital conditions.
A stimulus is in all cases an alteration in vital conditions and, in
that each of the vital conditions is necessary for the continuance
of life, it follows of necessity that every alteration in the vital
conditions, so intimately connected with the living processes, will
also be followed by an alteration in the processes occurring in the
living system. In short, response is produced. Nevertheless, a definite
alteration of an external vital condition, depending upon the state
of other vital conditions, that is, according to the state of living
substance at the moment, can produce quite opposite effects. Although
it may appear expedient to include in the conception of stimulation in
given instances, distinctions between stimuli according to the nature
of their effects upon the living substance, in all cases the conception
must under all circumstances be so formulated that it comprises _all_
alterations in the external vital conditions, either positive or
negative, that is to say, an increase or decrease, an augmentation or
diminution in those factors, acting as vital conditions.
Besides the quality there is another highly important factor to be
considered in the study of every alteration in the living process,
namely, its _amount_. The chemical concentration of the medium,
temperature, amount of light, the static and osmotic pressure may
undergo more or less variation. The electric stimulus can rise from
zero to great intensity and from great intensity can fall to zero. The
extent of the alteration determines the intensity of the stimulus.
In relation to the intensity, a differentiation of stimulation has
been introduced, which is not dependent upon the absolute intensity
of the stimulus, that is, upon the extent of the alterations in the
external vital conditions, but the intensity of the response that
can be observed. One refers frequently to threshold stimulation,
to stimulation beneath the threshold, to submaximal, maximal and
supermaximal stimulation. Such a classification is in many ways very
valuable. It is not only of practical value for the establishment of
definite intensities of stimulation, but also for the study of the
state of irritability in the living organisms.
_The threshold of stimulation_ furnishes roughly a standard for the
degree of irritability of a living system. The threshold value of a
stimulus is then that degree of intensity which is just sufficient
to bring about a perceptible response. The threshold of stimulation
is low, that is, the irritability is great, when the intensity of
the threshold stimulus is small; the threshold is high, that is, the
irritability of a system is small, if the intensity of the threshold
stimulus is great. All intensities of stimuli beneath the threshold
are sub-threshold stimuli. Here a point must not be overlooked, which
in older physiology did not generally meet with sufficient attention.
From the fact that the sub-threshold stimuli produce no apparent
effects, the wrong deduction must not be made, that they have no effect
whatsoever. The conception of the threshold of stimulation originated
in the field of muscle physiology and that of the special senses.
Here the indicator of the response is, on the one hand, contraction
of the muscles, and on the other, conscious sensation. There was a
great temptation to consider the stimulus altogether ineffectual, if
it produced no conscious sensation or no contraction of the muscle.
Today with our finer and more sensitive indicators for the study of
the alterations in the living substance, we know in reality that
sub-threshold stimuli, which produce no apparent effect in the living
substance, can have an effect in reality.
I will call your attention later to the fact that these sub-threshold
stimuli play a very important rôle under certain conditions in the
activities of the central nervous system. It only depends upon the
sensitivity of our special senses, or the indicators used for this
purpose, as to whether the alterations can be observed or not. The
conception of the threshold of stimulation, therefore, has meaning
only when used in relation to a certain indicator. The threshold of
the same living system may be different for different indicators.
When we use the term threshold we must necessarily know the indicator
employed in its determination. The threshold stimulus produces only
barely perceptible effects. The amount of response in most living
substances increases with the intensity to a certain limit. If this
limit is reached, that is, if the response is maximal, the stimulus
of the weakest strength necessary to produce this result is termed
the _maximal stimulus_, whereas all intensities lying between the
threshold and the maximal stimulus are termed _submaximal stimuli_. If
the intensity of the stimulus is increased _above_ that of the maximal,
the response, as in the case of the muscle, does not increase, and
therefore one could say that all intensities above the maximal could
also be called maximal stimuli.
In realty, however, the response to stimuli of different intensities
is never equal, even though it may appear so, when measured by
an indicator, as for instance, the height of the maximal muscle
contractions. This is clearly shown, for example, when the electrical
stimulus is increased far beyond that intensity which is necessary
to produce maximal effect. Injury is thereby produced, which is
manifested, for instance, in the muscle contraction by the nature of
its course and also by its height. One is, therefore, justified in
a certain sense in calling the intensities of the stimulus, which
are above the value which barely produces maximal contraction,
“_supermaximal stimuli_,” notwithstanding this is logically far from
being a happy expression. The term “maximal stimulus,” then, is limited
to the intensity of the stimulus which just produces a maximal effect.
I wish to point out this distinction between maximal and supermaximal
stimulus, as there is often a lack of clearness in the use of these
terms.
In that the nomenclature of intensity of stimulation is based upon the
intensity of response, the question arises as to the _relation between
the intensity of stimulus and the amount of response_. It is well known
that this question has met in one special field of physiology with a
very detailed and comprehensive treatment. I allude to the teaching
concerning sensation. _Ernst Heinrich Weber_[21] first called attention
to the relation between increase in sensation and that of the stimulus
in the case of the sense of touch. His observations, which have been
formulated into “_Weber’s law_,” have been the object of animated
discussion. A presentation of this law is the following: “The amount
of pressure necessary to produce a perceptible increase of sensation
always bears the same ratio to the amount of the stimulus already
applied.”
[21] _Weber_: “Annotationes anatomicæ et physiologicæ.” Lips.
1851. The same: “Der Tastsinn und das Gemeingefühl,” in Wagner’s
Handwörterbuch d. Physiologie Bd. III. 2. Braunschweig 1846.
If in accordance with _Ziehen_[22] we designate the relative increase
in pressure to that already applied, which is necessary to produce
a perceptible increase in sensation, as the _threshold of relative
differentiation_, we can formulate the law in the simplest way thus:
The _relative threshold of differentiation is constant_. _Fechner_,[23]
who indeed attempted to apply this law, applicable to the sense of
pressure, to all the other special senses, has given us a mathematical
formula, based on the assumption that the just perceptible increase of
sensation has the same value at all levels. By this assumption he was
able to establish for the first time a relation between the intensity
of sensation and that of stimulus, for it follows that “_the sensation
increases in intensity in arithmetical progression, whereas the
intensity of the stimulus increases in geometrical progression_.” From
this _Fechner has_ worked out a psychophysical formula, which today is
generally termed the _Fechner law_. This is the law: _The intensity of
sensation varies with the logarithm of the intensity of the stimulus._
[22] _Ziehen_: “Leitfaden der physiologischen Psychologie in 15
Vorlesungen.” VI Auflage. Jena 1902.
[23] _Fechner_: “Elemente der Psychophysik.” Leipzig 1860. 2 Auflage
1889.
Soon the _Weber_ as well as the _Fechner_ law had been extended over
the whole field of sensation and stimulation. In this connection
_Preyer_[24] has formulated his “myophysical law,” which states
that there is the same relation between strength of stimulus and
the intensity of response of the muscle as is laid down by the
_Fechner_ law for stimulation and sensation. _Pfeffer_[25] has
found that _Weber’s_ law applied also to the relations of the
chemotaxis of bacteria, to the intensity of the chemical stimulus,
and likewise the attempt has been made to show that all living
substances respond in the manner laid down by the _Weber-Fechner
law_. Unfortunately the innumerable investigations in this field have
shown more and more clearly that it is not possible to formulate a
general mathematical law, which strictly fixes the relations of the
intensity of the stimulus and the intensity of response. Even in
the field of the physiology of the special senses many voices have
opposed the general application of the _Weber_ and the _Fechner law_.
_Lotze_, _G. Meissner_, _Dohrn_, _Hering_, _Biedermann_ and _Löwitt_,
_Funke_ and numerous other investigators have already demonstrated
for some decades, partly by means of critical inquiry, partly by
experimentation, that these laws are not strictly valid. Above all
these experiments have shown that logarithmic relations are not
tenable and likewise are not applicable to very strong stimuli. The
assumption made by _Fechner_, that is, the acceptance that all barely
perceptible increases of sensation have an equal value, has been set
aside as incorrect, and with this his mathematical formulation within
those boundaries of intensity of the stimulus, in which the _Weber_
law has proven itself valid, must also be abandoned. That which we can
say today with certainty concerning the relation between the intensity
of stimulus and the amount of response is as follows: A law generally
applicable to the relation between the strength of the stimulus and the
amount of response cannot be mathematically formulated. For a great
number of living systems the rule which holds for the intensity of
stimulation within certain boundaries is the following: With increase
of the intensity of stimulation the _response_ at first increases
rapidly and later more and more slowly.
[24] _Preyer_: “Das myophysische Gesetz.” Jena 1874.
[25] _Pfeffer_: “Ueber chemotaktische Bewegungen von Bacterien,
Flagellaten und Volvocineen.” Untersuchungen aus dem botanischen
Institut zu Tübingen. Bd. II, 1888.
This rule of course only applies within the boundaries of the
intensity between the threshold of stimulation and maximal stimulus.
The interval, however, between these intensities varies considerably
in different living substances. In this connection there are several
forms of living substance which call for our special attention. In
these the surprising condition seems to exist, that the interval
between the threshold and the maximal stimulus is zero; that is,
every stimulus which acts at all always produces a maximal response.
_Bowditch_[26] first observed this behavior in the frog’s heart and
this has also been confirmed by _Kronecker_.[27] The induction current
produces, as _Bowditch_ says, either a contraction or nothing. If
the former, it is the strongest contraction which can be produced
by an induction shock at the given time. Here for the first time a
constancy of response was discovered which has been termed the _all or
none law_. _McWilliams_[28] has later verified the same fact for the
mammalian heart. _Gotch_[29] has also arrived at the same conclusion
in connection with the nerve. He states that “the comparison of
submaximal with maximal responses shows that although there is an
obvious difference in the amount of E. M. F., there is little or no
difference between such time relations as the moment of commencement,
the moment of culmination of E. M. F. and the rate at which E. M. F.
disappears.” Further: “the rate of propagation of the excitatory wave
is the same whether this is maximal or submaximal.” He likewise assumes
that the “all or none law” is applicable to the constituent fibers, and
that the variations in the strength of response with weak and strong
stimulation are brought about in the first instance by stimulation of
a few, in the latter by a greater number of fibers in the nerve trunk.
The same conclusion has been reached by _Keith Lucas_[30] for the
single cross-striated fiber of the skeletal muscle, founded on the fact
that by direct stimulation of a bundle of curarized muscle fibers,
the contraction only increases inconstantly and not regularly with the
increasing intensity of the stimulus. This is only comprehensible if
one takes into consideration that, with the increasing intensity of
the stimulus, a greater and greater number of fibers are stimulated.
_Keith Lucas_[31] came to the same conclusion in the case of the
muscle stimulated indirectly through the nerve. He, therefore, sees,
because of the nature of the response of the single muscle cell, no
difference between heart muscle and skeletal muscle. The “_all or
none law_” applies to the individual muscle cells of both kinds. The
difference between the heart and skeletal muscle, according to him,
lies in the fact that in the heart the individual muscle cells in their
totality stand together as conductors of excitation, whereas in the
skeletal muscle the individual muscle fibers are separated, as far as
conduction of excitation is concerned, by the sarcolemma. Finally, the
recent investigations of _Vészi_[32] with strychnine poisoned ganglia
cells of the posterior horns of the spinal cord, have made it appear
probable that “the all or none law” can be applied likewise to the
individual ganglion cell. He draws this conclusion not only from the
fact that all reflex contractions of a muscle of a strychninized frog
are maximal, whether they are produced by weak or strong stimuli, but
also especially because of the loss in the strychninized spinal cord
of the capacity of the summation of irritability. The normal spinal
cord does not reflexly respond at all to weak single stimuli, but
responds to equally weak faradic stimulation very readily. Therefore,
the threshold lies very high for the individual induction shock and
very low for faradic shocks. But these differences are equalized in the
strychninized frog. This seems intelligible, when we assume that the
strychninized cell responds to every stimulus, to which it responds
at all, to the maximal extent which is permitted at that moment by
its stored up energy, otherwise the excitation would necessarily be
summated by faradic stimulation.
[26] _Bowditch_: “Ueber die Eigentümlichkeiten der Reizbarkeit,
welche die Muskelfasern des Herzens zeigen.” In Arbeiten aus der
physiologischen Anstalt zu Leipzig VI. Jahrgang 1872.
[27] _Kronecker_: “Das characteristische Merkmal der
Herzmuskelbewegung.” In Beiträge zur Anat. und Physiol. Als. Festgabe
Carl Ludwig gewidmet von seinen Schülern. Leipzig 1874.
[28] _McWilliams_: “On the rhythm of the mammalian heart.” Journal of
Physiology, Vol. IX, 1888.
[29] _Gotch_: “The submaximal electrical response of nerve to a
single stimulus.” Journal of Physiology, Vol. XXVIII, 1902.
[30] _Keith Lucas_: “On the graduation of activity in a skeletal
muscle fibre.” Journal of Physiology, Vol. XXXIII, 1905–06.
[31] _Keith Lucas_: “The all or none contraction of skeletal muscle
fibre.” Journal of Physiology, Vol. XXXVIII, 1909.
[32] _Vészi_: “Zur Frage des Alles oder Nichts-Gesetzes beim
Strychninfrosch.” Zeitschrift für allgemeine Physiologie Bd. XII,
1911.
Such are the instances to which one has up to the present applied
the “all or none law.” The question if, as a matter of fact, such a
condition has ever been realized in any living substance has until now
found no final answer. Most authors, who accept the validity of the
“all or none law” for certain living substances, do so with a certain
reserve and speak only of the possibility or probability of such
behavior. The subject has, however, as will be shown later, a great
and even vital interest in another direction. For this reason I should
prefer to postpone the treatment of the same to a later occasion. Here
I wish simply to say, that _if_ the “all or none law” is valid in a
strict sense for certain structures, then there exists no general
constancy of the relations of the intensity of the stimulation and the
amount of response, applicable to all living organisms.
We will now return from this digression concerning the relations
between the intensity of the stimulus and the response, to the
further characterization of the properties of the stimulus. Besides
the quality, the direction and the intensity of every alteration in
vital conditions, an equally important factor is the duration of
the alteration. The time relations, under which a deviation of the
external vital conditions takes place, present immense and manifold
variations in nature. In many cases the change is very complicated, as
for instance, the alteration of the static pressure or the temperature
under the influence of air or water currents, the osmotic pressure
or chemical factors in diffusion currents, and the light intensity
produced by the movement of clouds. These very irregular alterations
have practically little interest for us. Here we are concerned rather
with the differentiation of the time alterations of the processes of
the simplest fundamental types, which are of importance in studying
the course of the reaction. For it is of such simple elements that the
complicated and irregular alterations of the above-mentioned kinds are
composed.
The simplest form of an individual change in the external vital
conditions would be a regular and constant alteration of intensity
which can be graphically represented as a straight line, wherein the
intensities are the ordinates and the time the abscissa. (Figure
3, A.) A regularly rising pressure would, for instance, represent a
stimulus in its simplest form. But such forms of stimuli are only very
rare in nature and are also experimentally very difficult to produce.
It is, for example, not easy to give the _electrical_ stimulus, so much
used for experimental purposes, this form. _Fleichl_ and _v. Kries_
have only accomplished this by means of complicated apparatus. The
usual _form of the individual stimulus_ is not a straight line, but a
logarithmic curve. (Figure 3, B.) The alteration hardly ever progresses
with equal rapidity from its beginning until it reaches its highest
point, but as a rule, with decreasing rapidity. This is the usual
course of alterations of concentration, also of chemical and osmotic
stimuli, of changes of temperature and of electric stimulation.
[Illustration: _A_
_B_
Fig. 3.]
The _rapidity of alterations_ in vital conditions has quite an
important influence on the development of the response to stimulation.
It is well known that if a constant current, which reaches its highest
intensity rapidly, is permitted to act upon a muscle, the effect
differs from that following the application of a current of the same
intensity but in which this is reached very slowly. In the first case
there is a sudden strong twitch, in the second none at all. In spite
of this there can be no doubt whatever of the current in the last case
being effective. That the muscle is also excited when the current is
slowly increased is shown by the contracture, which grows more and more
plainly perceptible with the increasing intensity of the current and
in higher intensities by the so-called _Porret’s_ phenomenon, which
consists in a curious wave-like movement of the muscle-substance. In
reference to the rapidity of the alterations in the factors which
act as stimuli, the behavior varies greatly. Many stimuli because of
their nature never have a steep ascent or descent of intensity, as, for
instance, alterations in the concentrations of soluble substances, that
is, chemical or osmotic stimuli; likewise temperature variations may be
mentioned. They always act relatively slowly. On the contrary there are
forms of stimuli which have now a rapid, now a slow, ascent or descent
of their intensity, such as the photic and mechanical stimuli. Finally,
there are other stimuli that nearly always show a very abrupt change of
intensity, such as the electrical form.
The most important factor to be considered in producing the response
to variations of intensity, is not the _absolute rapidity_, but rather
the _relative rapidity_; that is, the rapidity in relation to the
characteristic rapidity of reaction of the particular living substance
concerned. The rapidity of the reaction to stimuli is very different
in various forms of living substance. On the one hand, we have forms
reacting very quickly, as the nerve and the striated muscle; on the
other, those which respond very slowly, such as a great number of
unicellular organisms. Between these are a great number of living
substances which, as far as the rapidity of the reaction is concerned,
occupy intermediate positions of every varying degree. It is clear
that the adequate stimuli for slowly reacting substances must be those
having also a slow change of intensity; for quickly reacting, those
having a rapid change of intensity.[33] If a nerve muscle preparation
is simulated with the single induction shock, the “break” as well as
the “make” shock has effect. But even here a difference is noticeable.
The “make” shock has a weaker effect than the “break” shock. This
difference is due to the difference of abruptness in its course, which
when the current is made is less than that of opening, for, when the
current is made, the ascent of the primary current is retarded by
the extra current flowing in the opposite direction, whereas, when
broken, with the fall of the intensity of the primary current, the
extra current in the primary coil flows in the same direction. In
consequence of this there is a perceptible difference in the rapidity
of the alteration of the “make” and “break” shocks. (Figure 4.)
[33] Vergl. _Julius Schott_: “Ein Beiträg zur electrischen Reigung
des quergestreiften Muskels von seinen Nerven aus.” Pflügers Archiv
Bd. 48, 1891.
[Illustration: Fig. 4.
Course of induction shocks. 1 and 2 make and break of the primary
current. 1_{1} and 2_{1} make and break induction shocks. (After
_Hermann_.)]
Now slowly reacting forms of living substance, such as certain
foraminifera, in which the extended pseudopods are stimulated with
single induction shocks, the break as well as the make shocks are
wholly without effect, as both take place far too quickly for the
slow responsivity of these organisms. I have made such observations
on various forms of foraminifera of the Red Sea, on _Orbitolites_,
_Amphistegina_ and others. The movement of granules in the pseudopods
is not influenced by the induction shocks in the least. It also
continues without interruption when the pseudopods are extended. Even
with the strongest induction shocks at my disposal I could _not_ induce
them to contract; the faradic current, also, the intensity of which
I found quite unbearable, remained utterly without effect.[34] These
two extreme cases, the nerve and the foraminifera, show plainly that
the effect of a stimulus is not produced by the absolute rapidity of
the increase of intensity, but is solely influenced by the relative
rapidity of the same.
[34] _Max Verworn_: “Untersuchungen über die polare Erregung der
lebendigen Substanz durch den constanten Strom.” III Mitteilung,
Pflügers Arch. Bd. 62, 1896.
[Illustration:
A B C
Fig. 5.]
A further point for consideration in the duration of an alteration in
a vital condition in producing a stimulant action is the _length of
time the stimulus remains after reaching its highest point_. In the
forms of stimuli occurring in nature the duration of the alteration
after reaching its highest level can vary considerably. The stimulus
may remain indefinitely at a certain level, when this is once reached.
(Figure 5, A.) The alteration likewise persists. This would be the
case, for instance, with the changes of concentration in the transfer
of an organism from fresh into sea water. The alteration can also,
however, immediately after attaining its highest level, return, so that
the original state is at once reestablished. (Figure 5, B and C.) Here
it is a case of a quick deviation in the external vital conditions. A
_sudden jar_ would be a case in point. Between these two extremes we
have all variations in the duration of all natural and experimental
forms of single stimuli.
Now we arrive at the question: Has a prolonged stimulation really a
prolonged effect? This question might seem superfluous, as from a
conditional standpoint it is self-evident that every alteration in
any one of the conditions of a system is followed by an alteration in
the system. But this very question played an important rôle in older
physiology and led to prolonged discussions for the reason that a
special case was taken into consideration in this connection, which
at that time was not clearly understood. _Du Bois-Reymond_,[35] as a
result of his investigations on the nerve muscle preparation of the
frog, formulated a law of nerve excitation, according to which it is
not the _absolute value_ of the intensity of the constant current which
produces an excitation of the nerve and contraction of its muscle, but
an alteration of the intensity from one moment to another. The more
rapidly these changes are produced, the greater is the excitation.
His arguments were based upon the fact that a contraction can only
take place on the “making” or “breaking,” or by rapidly strengthening
or weakening the constant current; it is possible to subject a nerve
muscle preparation to a current of considerable strength without a
muscle contraction resulting, provided it is slowly increased. One
might be disposed to conclude from this that the constant current,
when showing no fluctuations, has no stimulating effect whatsoever.
Should this observation be carried even further and the attempt made to
extend it into a general law of excitation by assuming that the effects
of stimulation are only produced by variations in the intensity, not
by its continued duration, one would commit the error of judging the
occurrence of a stimulus only by the unsatisfactory criterion of an
abrupt muscle contraction. Today we know with positiveness that a
continued effect also exists during the uninterrupted flowing of a
constant current in nerve or muscle, though much weaker, however, than
in the case of the excitations produced by sudden fluctuations of the
intensity. This is shown in the nerve by an altered excitability, which
continues at the poles during the whole duration of the current. In
the region of the anode the excitability is diminished, in that of
the cathode it is increased. An excitation can also be demonstrated
which extends from the cathode through the nerve, which can easily
be detected by sufficiently delicate methods. Among other effects of
prolonged stimulation is that of cathodal contracture, which remains
localized in the region of the cathode and which excitation persists
as long as the current continues. This permanent excitation can be
particularly well observed in the single cells of the rhizopods. If a
constant current is allowed to flow through an _Actinosphærium_,[36]
the straight, smooth, ray-shaped pseudopods of the cell body at the
moment of “making,” show evidence of contraction by being drawn _in_,
particularly those directed towards the anodic and in less degree also
those towards the cathodic pole. This excitation, greatest at the time
of “making” of the current, though diminishing rapidly in intensity
during its continuance, remains, however, to a less degree, and leads
to a progressive disintegration of the protoplasm on the side towards
the anode, which lasts until the current is again broken. (Figure 6.)
Thus even though there can be no doubt, on the one hand, that the
effect of stimulation, which appears at the moment of the entrance,
is to produce alterations, which develop very rapidly, and that by a
continuation of this state there is a more or less rapid fall to a low
level; on the other hand, it is just as certain that the alterations
in the living system persist throughout the duration of the changed
external conditions, or to put it more concisely: the effect of the
stimulus never wholly disappears unless the changes in the external
vital conditions return to their original state.
[35] _Du Bois-Reymond_: “Untersuchungen über tierische electricität.”
Bd. I. Berlin 1848, p. 258.
[36] _Kühue_: “Untersuchungen über das Protoplasma und die
Contractilität.” Leipzig 1864. _Max Verworn_: “Die polare Erregung
der Protisten durch der galvanischen Strom.” Pflügers Arch. Bd. 35,
45, 1889.
[Illustration: Fig. 6.
_Actinosphaerium eichhornii._ Four stages showing the progressive
influence of a constant current. Protoplasmic disintegration at the
side toward the anode.]
But more, an effect of the stimulus cannot indeed take place _without_
a certain duration of stimulation, which is related in _its_ turn to
the rapidity of reaction of particular living system. This can be much
more readily observed in more slowly reacting substances. _Fick_[37]
first proved this fact on the muscle of the _Anodonta_. I have also
been able to demonstrate the same fact in the slowly reacting sea
rhizopods[38] by the use of the constant current. When _Orbitolites_
is stimulated with a constant current lasting approximately the tenth
of a second, no response is seen in its extended pseudopods, which
are directed towards the poles. The same is the case if the induction
current is employed. Only when the constant current of the uniform
strength lasts approximately .05 seconds, a barely perceptible response
occurs, manifested by the sudden stoppage of the centrifugal flowing of
granules in the anodic pseudopods, which, however, after the lapse of
one to three seconds continues again unaltered. Should the duration of
the constant current be still further prolonged, typical symptoms of
contraction are seen being manifested by a heaping up of the protoplasm
in the pseudopods in the form of spindles and balls, whilst the
protoplasm flows in a centripetal direction towards the central cell
body. (Figure 7.)
[37] _A. Fick_: “Beiträge zur vergleichenden Physiologie der
irritablen Substanzen.” Braunschweig 1863.
The same: “Untersuchungen über die electrische Nervenreizung.”
Braunschweig 1864.
[38] _Max Verworn_: “Untersuchungen über die polare Erregung der
lebendigen Substanz,” etc. III Pflügers Arch. Bd. 62, 1896.
Two effects can be realized by the alteration in the living system as
the result of prolonged stimulation. Either a new state of equilibrium
is established by the prolonged action, or sooner or later death
develops. In considering both results, however, we will ignore for
the present the fact that every living system in the absence of
such prolonged stimulation is always in a state of change, i.e.,
development. Only with this restriction can an equilibrium of the
living system be spoken of.
[Illustration:
A Fig. 7. B
_Orbitolites complanatus._ A--Before stimulation. B--Under influence of
a constant current.]
It is sometimes the case that under the influence of a stimulus a new
equilibrium is developed, which may remain as long as the stimulus
persists. This most frequently occurs as a result of _weak_ stimuli.
That which is usually termed “individual adaptation” belongs in this
category. Likewise some of the natural and artificial immunizations may
also be included. The continued stimulation in such cases of adaptation
as we learned before in the example of _Amœba limax_ and _radiosa_ or
_Branchipus stagnalis_ and _Artemia salina_ becomes a vital condition
for the living substance in its new state.
The other result, namely, that of death ensuing sooner or later, is
most frequently produced by stronger stimulation. Through the effect of
the prolonged stimulation, the change in the living system is so great
that all harmonious interaction of the various processes of life become
after a time impossible. The disturbance of this equilibrium after a
longer or shorter time becomes so great that life ceases. By far the
greater number of all diseases furnish examples of this kind. Disease
is nothing else but reaction to stimulation. Should a constant stimulus
persist and if the development of a new equilibrium of this system is
not established, the result is premature death.
In most cases, as, for instance, the nerve impulses which move
toward an organ, or better still the electrical stimuli as used for
experimental purposes, it is not a question of a permanent but of a
temporary alteration in the external vital conditions. The stimulus
starts, then ceases after a longer or shorter period. In this way
there is added to the deviation at the start also the alteration at
its termination. The latter takes place with different degrees of
rapidity, in a manner analogous to that of the initial alteration,
and can bring about response. With this the curve of the duration of
the course of the stimulus becomes somewhat more complicated and in
consequence a like effect is observed in the response. The “making,”
duration and “breaking” of the constant current furnishes the example
of this type. The “making” of the current being a quick alteration
calls forth a strong and sudden excitation (in the muscle contraction);
the continuation of the current maintains weak excitation of equal
intensity (in the muscle a continued contraction) and the “breaking,”
being a sudden alteration, is followed again by a stronger excitation
(in the muscle a contraction). The duration of the change can, however,
be so short that its intensity does not remain at two periods of
time at the same height, but instead the ascent of the intensity is
immediately followed by its descent to zero. Induction shocks of short
duration, the duration of which have been observed more in detail
especially by _Grützner_,[39] offer typical examples. Here a single
effect of the stimulus results from the rise and fall of the intensity
curve. Hence the induction shocks as momentary stimuli are universally
used for experimental purposes.
[39] _Grützner_: “Über die Reizwirkungen der Stöhrer’schen Maschine
auf Nerv und Muskel.” Pflügers Arch. Bd. 41, 1887.
In contrast to the single stimuli, which find their ideal in induction
shocks, another form of stimulation should receive our attention,
namely, the series of stimuli which produce a rhythmical alteration
of vital conditions. These show among their complex combination of
simultaneous and successive actions of their single stimuli relatively
the simplest and most easily understood regularity in their effects.
They are of particular interest, because they develop in the normal
physiological happenings of the animal body in the form of rhythmical
intermittent impulses of the nervous system.
Here again it is self-evident that with regard to the course of
response, we must first consider the character of the single stimulus
of the series, and this must be done from all those standpoints
already here discussed. However, a new factor is met with here, that
is, the frequency of the single stimuli of the series, or that which
has the same meaning, the duration of the intervals between them.
This is a feature upon which the result of stimulation depends in a
very high degree. But here, too, however, it is not a case of the
absolute frequency of the single stimulus, but simply of the relative
frequency in regard to the rapidity of reaction of the particular
living system. I should like to remark here that it is of greatest
importance whether the interval between the two single stimuli of the
series is sufficiently long or not to allow the living system time
to completely recover from the effect of the _preceding_ stimulus.
In the cases, for instance, where we have recovery, we have the same
rhythm of stimulation as that of response. When recovery _does not_
occur, interferences of the response are developed, which are of great
physiological importance, with the analysis of which we shall later
on find occasion to occupy ourselves in detail. The physiological
example for these stimuli is the rhythmical discharge of impulses of
the nerve centers; the physical method, which is most widely used for
experiments, is the faradic current.
It is apparent that the question of frequency must again be combined
with all those factors previously discussed in connection with the
_single_ stimulus. In consequence another complication arises and
with this another point must be taken into consideration, namely, the
fact that the duration of the single stimulus in a series undergoes
alteration by increasing frequency beyond a certain limit. Beyond
this limit the duration of the single stimulus must become less and
less. As the result of the fact that stimulation is, as we have seen,
dependent on the duration of stimulus, it is evident that, depending
upon the rapidity of response of the living system, sooner or later
the rhythmical stimulation must become ineffectual. Nevertheless,
this effect of shortening the duration of the single stimulus can be
compensated by a corresponding increase of its intensity. In this
connection _Nernst_[40] showed a very simple relation for induction
currents of higher frequency of interruption, which furnishes a law
according to which such a compensation takes place. In conjunction
with _Barratt_ he found, namely, that the intensity must increase
proportionately to the square root of the number of single stimuli if
the threshold value of the stimulus is to be maintained, that is, I :
√m = const., in which _I_ is the intensity of the current and _m_ the
frequency of interruptions. The limits of the validity of this law
cannot at present be conclusively established.
[40] _Nernst und Barratt_: “Ueber electrische Nervenreizung durch
Wechselströme.” Zeitschrift für Electrochemie 1904.
This exhausts the small number of elementary factors concerned in the
course of the stimulation, and which are of importance in considering
its effect. The combination of the different varieties of these single
factors, that is, the nature, the direction, the intensity, the
rapidity, the duration and number of alterations in the external vital
conditions of the organism produce the enormous variety of effects of
stimulation which we observe in the living world.