The search for a so-called sleep center may
at first sight appear a paradoxical idea. In the
same manner as the waking state, so also does
sleep appear as such a complex biological
condition that the problem makes us at first sit
up and take notice. Indeed, our entire life
takes place in the alternating change of two
biological conditions, the waking and sleeping
state and in this way the problem might appear
primarily of the same category as the problem of
the center of life itself. The problem of a
center of life in the nervous system has often
been discussed in past centuries. But it has
been put away as life is a much too complex
condition as to be localized. So is sleep, too.
But the change of sleep and waking state might,
anyhow, have something to do with some special
centers of the nervous system and that question
has always been discussed over again. If we do
not give to the word "center" a too narrow
definition but if we agree that the expression
"nervous center" signifies only such an
accumulation of nervous grey matter the action
of which is of direct primary importance for the
production of a definite function, we might
nowadays again discuss the possibility of
locating sleep, regulation in some definite part
of the nervous system since we know that even so
complicated a biological function as the
temperature of our body has got a very definite
and localized regulating center in the
diencephalon.
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Most of the scientists, physiologists as
well as pathologists, were thoroughly contented
with these explanations of sleep. The former
attempts to locate sleep function were looked at
as obvious. Though some curious pathologic facts
were known, for instance, the occurrence of
sleep as a frequent symptom in cases of tumor of
the infundibulum and were especially mentioned
by Claude and Lherniitte, this Lhermitte himself
stated in 1910, during the discussion of
narcolepsy, "We absolutely object to the thought
of the existence of a nerve center attributed to
the function of sleep." Veronese expressed his
doubt in the sentence, "The conception of a
center for sleep is erroneous, as it disavows
the most simple principles of physiology." And
Dejerine said in 1914: "Sleep cannot be
localized."
So stood the facts when two years later the
appearance of lethargic encephalitis, which I
first described in 1916 -17, refuted all these
statements however well founded they appeared.
The lethargic epidemic encephalitis shows in its
most ordinary somnolent-ophthalmoplegic form,
outside of disturbances of the eye muscles, as
the most striking symptom, a sopor of different
degree varying from simple somnolence to the
deepest sopor in which the patients may sleep
for weeks and months but from which in the
majority of cases, it is possible to arouse
them. The disease is produced by an inflammation
of the central grey matter localized in the main
in the cap of the interbrain at its junction
with the thalamus. The inflammation may spread
frontally and caudally to other parts of the
nervous system and produce other symptoms. So it
could be shown later that those cases of
encephalitis which began with choreatic unrest
presented at the beginning a striking and
tormenting insomnia. The combinations chorea and
insomnia on the one hand, eye muscle
disturbances and sleep on the other hand, and
our knowledge that many choreiform diseases
originate in the region of the stem ganglia,
leads to the assumption that the inflammation in
cases associated with insomnia, is localized
anteriorly in the lateral wall of the third
ventricle, near the corpus striatum while it is
localized in cases showing disturbances of
ocular muscles with sopor in the posterior wall
of the third ventricle near the nuclei of the
oculomotorius in the cap of the interbrain.
The lethargic encephalitis produces,
furthermore, outside of insomnia and sopor, a
number of other disturbances of sleep, for
instance, the inversion of sleep, i.e., the
reversal of the periodicity of sleeping and
waking, patients sleeping in the day time and
being awake at night. Another very frequent
sleep disturbance in encephalitis it what I call
the dissociation of cerebral and body sleep and
observed in a series of akinetic cases, patients
being in day time mentally wideawake while their
bodies were akinetic and drowsy as in sleep; at
night these patients are again mentally asleep
while their bodies are restless, which
circumstance produces states of somnambulism. It
was supposed by many investigators that it might
be the toxic effect of lethargic encephalitis
being an infectious disease, that was the reason
for the sleep symptoms. But I called attention
to the fact that quite a number of other
diseases affecting the same region of the
nervous system, as lethargic encephalitis does,
namely, Wernicke's disease, Gayet's disease,
then tumors of the infundibular region present
outside of disturbances of the eye muscles, also
sopor. Some recent findings in cases of
softening (in hemorrhages) of this region have
shown the sanie syniptomatology. The
consideration that diseases of such different
nature can always be productive of sleep if they
occur in this region of the nervous system,
proves the correctness of the statement that not
the individuality of the disease as such, but
its localization at this very definite area of
the nervous system is decisive for the
occurrence of sleep. Inasmuch as furthermore in
lethargic encephalitis sleep is disturbed in
such various ways as sopor, insomnia, inversion
of sleep, dissociation of sleep, etc., we have
additional proof that we must consider this
region of grey matter as the site from which
sleep can be primarily and directly influenced.
This area is therefore selective for the
function of sleep and as in more than 85 per
cent of the cases of encephalitis there occur
some troubles of the sleep function, we must
suppose that the virus of encephalitis has a
special affinity to these accumulations of grey
matter which are of special importance for the
sleep and which I designate as the "center for
regulation of sleep."
We must insist on the anatomical fact that
the center for regulation of sleep is in the
immediate vicinity of the other important
vegetative centers located in the infundibular
region and we can suppose that it forms with
them a larger physiological entity but that it
is, anyhow, to be distinctly separated from the
other vegetative centers by its localization as
well as by its chemical affinity as its affinity
to the virus of encephalitis proves, because in
the acute stage of that disease we generally do
not find other disturbances of the vegetative
nervous system.
The action of that sleep-regulating center
probably consists in a coordination of the
different changes which occur in sleep in our
vegetative animal and psychic system. As to the
psychic system, the center for regulation of
sleep has the rôle of initiating the
cerebral sleep which, as we know, is
characterized by partial extinction of
consciousness and by the difficulty of
conduction in the brain. How does this mechanism
act physiologically? I think that Pawlow's
experiments give us a precious hint to answer
this question. We know by these experiments on
conditional reflexes that a repeated
interruption of these reflexes have a local
inhibitory action on the cerebral cortex which
can with a certain experimental arrangement,
spread over the entire cerebral cortex. If that
inhibition spreads over the whole cortex, it
suddenly produces sleep. This experimental fact
suggests that normal cerebral sleep might be
considered as an inhibitory action brought about
by the center of sleep regulation upon the
cerebrum and thalamus. We are acquainted with
different similar inhibitory processes in the
nervous system in other conditions, for instance
the inhibition of antagonists during stimulation
of motor centers or the inhibitory fibers of the
heart, etc. This way of acting by a nervous
inhibition explains also the possibility of
being aroused from sleep and many other
particularities of normal sleep much better than
the theories of anemia or the chemical theories
can do because in chemical and vasomotor states
we can't admit such sudden changes.
Outside of the effects of cerebral
functions, the center of sleep regulation
certainly exerts a regulating influence as
previously mentioned, on the other vegetative
and animal components of sleep which we might
call "body sleep" for instance the change of
respiration, perspiration, metabolism, etc. That
influence is effected directly on the
neighboring vegetative centers as for instance
the centers of temperature, for sugar and
calcium content of the blood, for regulation of
the water metabolism, etc., which all change
during sleep and the centers of which are
located in the subthalamic region and in the
wall of the third ventricle.
To fall asleep is therefore to be regarded
as a very complex function. Its coordination and
release is effected by the center of sleep
regulation although the character of sleep and
its periodicity is as previously mentioned, much
more deeply and more generally anchored in the
vegetative organism, somewhat similar to the
hormonal explanation.
Now we must put forward the question "what
sets the regulation center into action?" It
seems most plausible to admit that this center
is ordinarily and normally set into action by
fatigue substances while circulating in the
blood in an amount yet insufficient to bring
about intoxication but acting already in small
quantities specifically on that center of sleep.
The latter then inhibits by an active nervous
inhibition, the action of brain and thalamus
which produce cerebral sleep and directs, in the
meantime, the coordination of the different
subthalamic centers concerned with body sleep.
In this sense, the statemerit of
Claparède that we sleep not because we
are intoxicated by hypnotoxins but in order not
to get intoxicated by them, is probably quite
correct. This also differentiates the normal
sleep from other abnormal sleep-like states. We
might say the normal sleep is an active nervous
inhibition, whilé syncope, narcosis, and
other similar states are conditions which differ
from it by their being passive intoxicatory and
mechanical interruptions of nervous function. In
consequence the latter are not immediately
reversible as normal sleep is, which ends in the
very moment the nervous inhibition by the sleep
regulating center is set off.
Schema of the median section of the
interbrain; the dotted line is the boundary of
the field, in which the center for brain
regulation is lying. We may, then, assume that
the localized mechanism we postulate. for the
supervision of sleep is really existing and we
must look out how best we can localize it. Our
experience with cases of lethargic encephalitis
and other infundibular processes shows that
sopor may occur in these diseases as an isolated
symptom but that it appears principally
associated with paralysis of eye muscles,
especially with ptosis. That corresponds to the
most frontal part of the nucleus oculomotorius,
so we must place the posterior border of the
center for sleep regulation immediately in front
of the nuclei of the eye muscles in the grey
junction of interbrain and thalamus where the
aqueduct of Sylvius opens into the third
ventricle.
The anterior part of that center may be
located further frontally in the grey walls of
the third ventricle near the caput of the corpus
caudatum, as we find the symptom of insomnia
combined with choreatic disturbances.
Pathological-anatomical examination of
encephalitis material has not resulted in a more
exact localization but I am under the impression
that we have to do not so much with a narrowly
circumscribed grey nucleus but with a mass of
grey substance spreading over the posterior and
lateral walls of the third ventricle and
reaching laterally also into the hypothalamus.
The different parts of that grey matter act in a
sort of balancing way. I arrive at this
conclusion on account of the multiplicity of
sleep disturbances observed in the course of
encephalitis.
To return then once again to the previously
discussed definition of the words "nervous
center," the center of sleep regulation cannot
be classified within a narrow definition of this
term. It is not considered a narrowly
circumscribed seat of sleep function but as a
center in a wider sense, i.e., as an
accumulation of grey matter the function of
which is of primary importance for the normal
course of sleep.
The problem of more exact localization could
only be solved in a conclusive way by
physiological experiments. Different attempts in
this direction have been made by Spiegel, Inaba,
Demole, Marinesco. But all these attempts are
surpassed by the very recent experiments of Hess
in Zurich. He succeeded in making cats fall
asleep normally with all symptoms of fatigue, of
yawning and position of rest, by electrical
stimulations with very fine electrodes
introduced into the brain and by very weak
currents which acted upon the anterior region of
the aqueduct and the posterior wall of the third
ventricle. If these results are verified in the
future, irrefutable proof is furnished for the
correctness of our conception of a center for
the supervision of sleep situated at the
junction of the thalamus and the interbrain from
which sleep is actively initiated. It is
therefore manifest by all these recent studies,
that there is an apparatus which controls the
general periodic alternation of sleeping and the
constellation of our organism similar to high
and low tide and similar to other vegetative
function centers of the central nervous
system.
As we have seen not only lethargic
encephalitis but also other diseases of that
region in the diencephalon may produce sleep
disturbances. It is very probable though not yet
proved, that the narcolepsy of Gélineau,
Westphal and Redlich has its primary cause in a
yet unknown disease of that region.
Now you may think the statement of the
existence of such a regulating center for sleep
is a very interesting physiological fact but you
will ask for the practical consequence of such a
statement. I will first point out to you that
all knowledge of localization has a practical
effect inasmuch as it helps us to localize
different diseases, for instance, tumors, and
helps us to get at them practically in a
curative way. On the other hand, you know we are
ardently seeking to find methods to excite
externally either by electricity or rays or
diathermy through the skull,4he centers of our
nervous system in the intention of producing a
therapeutic effect. Some initial results have
already been obtained in that direction by
diathermy. Imagine we once had an effective
method of influencing deep lying centers, in
this case the exact knowledge of the
localization of the center for sleep regulation
which I have attempted to give you, would make
it possible to treat insomnia and other sleep
disturbances in a better and more active way
than by drugs or by the roundabout way of
hydrotherapy and psychotherapy. Let us express
the hope that we shall soon be able to have such
results.
Encéphalite léthargique
Cruchet, Moutier, Calmettes Soc méd hop
Paris 27 avril 1917
