NON-INVASIVE EVALUATION OF

HUMAN BRAIN FLUID DYNAMICS

AND SKULL BIOMECHANICS IN RELATION
TO COGNITIVE FUNCTIONING

THE BECKLEY FOUNDATION PRESS

 NON-INVASIVE EVALUATION OF
HUMAN BRAIN FLUID DYNAMICS
AND S KULL B IOMECHANICS IN R ELATION
TO C OGNITIVE F UNCTIONING

A REVIEW OF THREE YEARS OF SCIENTIFIC COLLABORATION BETWEEN THE

INSTITUTE OF EVOLUTIONARY PHYSIOLOGY AND BIOCHEMISTRY,
RUSSIAN ACADEMY OF SCIENCES;
THE BECKLEY FOUNDATION, UK;

PREPARED BY:
PROF. YURI MOSKALENKO, D. SCI, MAA, HONOUR SCIENTIST
OF THE RUSSIAN FEDERATION (PRINCIPAL INVESTIGATOR)
AMANDA FEILDING AND PETER HALVORSON.

IN COLLABORATION WITH:
GUSTAV WEINSTEIN, PHD, MD;
NATANIA RIABCHIKOVA, PHD AND TAMARA KRAVCHENKO, PHD, DO.
The investigations were conducted by Drs. G. Weinstein, V. Semernia and A.
Panov, physiologists in the Laboratory of Circulatory Physiology at the Sechenov
Institute, St. Petersburg; by Dr. N. Riabchikova, psycho-physiologist, Moscow
State University; by Dr. T. Kravchenko, Russian School of Osteopathic Medi-
cine; by Dr. N. Samus, neurologist, Hospital of Russian Academy of Sciences, St.
Petersburg; and by Prof. V. Mozhaev, neurosurgeon, Human Brain Institute,
Russian Academy of Sciences, St.Petersburg.

EDITING ASSISTANTS:
JONATHAN HAZELL, VIVIAN GARRIDO AND VALENTIN MITROFANOV

© 2009 YURI MOSKALENKO, AMANDA FEILDING, PETER HALVORSON

REPRODUCTION OF ANY FRAGMENT OF THE TEXT OR PICTURES
IS ONLY POSSIBLE WITH THE PERMISSION OF THE AUTHORS.
 CONTENTS

ABBREVIATIONS………………………………………………3

FOREWORD…………………… .…………………………….5

CHAPTER I …………………………………………………9
An Introduction to the Body’s Circulatory Systems
and to Cerebral Circulation

CHAPTER II………………………………………………....31
Analysing Cranial Compliance and the Moskalenko Method

CHAPTER III………………………………….……...……..61
Changes in Cranial Compliance under Different
Physiological and Patho-Physiological Conditions,
Including Craniotomy

CONCLUSIONS….…………………………………………..87

APPENDIX I……………….………………………………..89
Medical Applications for the Moskalenko Method

APPENDIX II………………………………………………..94
Articles Arising from the Research

1
2
 LIST OF ABBREVIATIONS
CAP Central arterial pressure
CBF Cerebral blood flow
CC Cranial compliance
CCc Cranial compliance compensation
CCe Cranial compliance elasticity
CCo Cranial compliance outflow
CO2 Carbon dioxide
CSF Cerebrospinal fluid
CV Cerebrovascular
CVR Cerebrovascular reactivity
ΔV Volume change
ΔP Pressure change
ICP Intracranial Pressure
MCA Middle cerebral artery
MM Moskalenko Method
N20 Nitrous Oxide
pCO2 Concentration of carbon dioxide
pH Alkalinity/acidity level
PI Pulsatile index
REG Rheoencephalography
s Second
TCD Transcranial dopplerogram
Tg Tangent
VIP Vasoactive polypeptides

3
4
 FOREWORD

This document provides a summary of the collaborative re-

search between the Beckley Foundation, UK, and the Institute of Evolu-
tionary Physiology and Biochemistry, Russian Academy of Science. It is
intended to be an introduction to our work on cerebral circulation and
the cranial system, accessible to the intelligent, but non-professional
reader. However, it is very difficult, if not impossible, to make a descrip-
tion which is neither over-simplified for the academic reader, nor so
complex as to be unintelligible to the lay reader. Nevertheless we hope
that this document will give an idea of the holistic approach employed,
and the potential implications of our findings to the growing field of life
sciences.
This research is pioneering in several ways: 1) the development of
a methodology and a system of analysis that enables the investigation of
the complex network of interactions that underpin cerebral metabolism
and cognitive functioning; 2) the finding of a correlation between the
level of cognitive functioning and the level of cranial compliance;
3) the development of our understanding of possible interventions to
counteract cerebral insufficiency and age-related declines in cognitive
functioning. With the costs of caring for an increasingly elderly popula-
tion expected to become ever greater, we hope that the knowledge pro-
vided through this research will prove vital in mitigating these costs by
helping to maintain cerebral health and cognitive functioning into old
age.
Our investigations have focused on a ‘systemic approach’ to fluid
circulation within the brain and throughout the central nervous system.
The movement of fluids through the brain depends upon a complex
physiological system made up of several subsidiary systems. The sys-
temic approach involves measuring and analyzing the various physical
forces that drive the brain circulation and how these forces interact with
the unique physical structures of the cranial system. The mechanisms
responsible for cerebral circulation include the cerebrovascular (CV) sys-
tem, the cerebrospinal fluid (CSF) system, and the biomechanics of the

5
cranium. The overarching aim of this complex system is to ensure suffi-
cient nutrient supply and waste removal to enable brain functioning.
Cerebral circulation is essential in maintaining a healthy brain and nor-
mal cognitive functioning. The dynamic interaction of these systems has
been the subject of our investigations, under both normal and, in some
cases, pathophysiological conditions. Due to the complexity of the sys-
tems involved, we employed multidisciplinary collaborations better to
understand the influences of fluid circulation in the brain on cognitive
functioning.
One focus of this study is to improve our understanding of the
phenomenology, the mechanisms and the physiological significance of
the ability of the cranium to accept the inflow of extra blood that accom-
panies the pulse stroke of the heart. This ability has been given the name
cranial compliance (CC). Our view of cranial compliance includes all the
forces and structures that determine the metabolic supply of the brain
tissue. During our research, specific indices of cranial compliance have
been developed that represent the capability of the system to accept nu-
trient delivery and to permit removal of waste products. We have also
sought to correlate these indices with the results of tests of cognitive
ability, in order to investigate the connection between cerebral circula-
tion and cerebral functioning.
Given the pioneering nature of this research, we are still in the
process of developing and refining the measurement of cranial compli-
ance. The CC indices in this document are therefore given in compara-
tive units, and the values given, although true to the research, are more
intended to illustrate the principles revealed by our research, rather than
reflect the absolute levels of cranial compliance. We hope that through
the continuation of this research by ourselves and other research groups,
the indices of CC will become a commonplace diagnostic tool, in the
same way that measurements of blood pressure or cholesterol levels are
in everyday use..
Until recently, cranial compliance and this systemic approach re-
ceived little scientific attention, because the systemic principle in physi-
ology had been replaced by the more fashionable analytic approach,

6
which focuses on the cellular and sub-cellular levels, down to mo-
lecular interactions. However, it is this study’s belief that only
through analysing the cranial system as a whole is it possible to
explore the many complex interactions that determine cranial
compliance and cerebral circulation, and also to monitor how
these systems change with age, and how their functioning is re-
lated to cerebral health and cognition. Furthermore, all the micro-
cosmic events that have been revealed through the analytic ap-
proach concerning brain chemistry and pharmacology take place
within the macrocosm of the cranial system, and can only be truly
understood through the context in which they occur. A simple
example is cellular hydration, which varies considerably depend-
ing upon the cranial pressure to cranial volume ratio, which itself
is a direct expression of cranial compliance.
It should be mentioned that at the same time as we have
been carrying out our investigations, the problems of CSF circula-
tion and cranial compliance have also been studied by others us-
ing magnetic resonance imaging technologies (MRI). However,
those studies have had a greater focus on the structural elements
of the cranial system, whereas our studies have had a greater fo-
cus on the functional elements. We look forward to combining
these two lines of investigation, which we hope will lead to a more
complete understanding of this important physiological system.
We foresee that in the next decades the measure of cranial
compliance will become accepted as an invaluable indicator of the
level of functioning of the cranial system.

7
8
 CHAPTER I

AN INTRODUCTION TO THE BODY’S CIRCULATORY SYS-

TEMS AND TO CEREBRAL CIRCULATION

This chapter serves as a basic introduction to the physio-

logical systems involved in cerebral circulation. One purpose of
this chapter is to highlight the functional similarities between the
lymphatic system and the cerebrospinal fluid system. These simi-
larities support a special emphasis on the importance of the cere-
brospinal fluid (CSF) system based on our knowledge of the lym-
phatic system. This is also important in general physiological
terms, as it highlights the common functional goals of all the
body’s fluid systems.
The chapter will also highlight certain idiosyncrasies of the
cerebrovascular (CV) system when compared with the vascular
systems of other body regions, particularly in regard to the cranial
volume/pressure interactions between the CV and the CSF sys-
tems.
The material included within this chapter is vital in order to
understand the physiological system that provides the functional
support to cerebral metabolism, upon which our cognitive func-
tioning is dependent. A further goal of this chapter is to illuminate
the complexities of this system, depending as it does not just upon
the cerebrovascular system and its functional coupling with the
cerebrospinal fluid system, but also upon the biomechanical
properties of the cranium. By simultaneous analysis of all these
subsidiary systems (the cerebral vascular system, the CSF system
and the cranium) it becomes possible to investigate the system of
cerebral metabolic support as a whole, and so to explore changes
in this system brought about by age, or as a result of a great range
of pathological conditions.

9
 1. FUNDAMENTAL BASIS OF BRAIN METABOLIC SUPPLY

A general principle of the structural and functional or-

ganization of the body’s vascular systems is that they are cou-
pled to supporting circulatory systems which assist in achieving
the systems’ functional goals: to supply nutrients to the body’s
tissue, to maintain the osmotic balance and to remove waste
products. For example, the lymphatic system assists in the re-
moval of waste products from the blood in the body and, simi-
larly, the cerebrospinal fluid system removes waste from the
tissues of the brain.

Fig.1 Schematic representation showing the structural organisation

of the circulatory “life support” systems of the body and brain: the
cerebrovascular system and its functional coupling to the lymphatic
system in the body, and the cerebrospinal fluid system in the central
nervous system.

Supporting circulatory systems (the lymphatic and CSF

systems in mammals) developed during the process of evolu-

10
tion at the stage of the more highly developed invertebrates, whose
blood circulatory systems became closed. The closing of these circula-
tory systems spurred, among other things, the development of blood
cells adapted to the transport of oxygen, and the development of com-
plex chemical compounds, but it also produced new problems such as
how to evacuate metabolic waste products. Most notably, it was the
large molecular structures, which could not penetrate back into the cir-
culatory system, which collected in the tissues of the body, that caused
the biggest problem. The next step of the evolutionary process, there-
fore, was to develop a supporting circulatory system that would help to
evacuate wastes from the tissues back into the circulatory system. This
resulted in the lymphatic and CSF circulatory systems (shown in Fig.
1).

LYMPHATIC SYSTEM
Lymphatic outflow
LYMPHATI C VESSEL

ARTERI AL VEN OU S
V E SS E L V E SSE L

CSF SYSTEM
CSF flow

ARTERI AL VEN OU S
V E S SE L V E SS E L

CHOROID ARACHNOID
P LEXUS VILLI

Fig. 2 Schematic representation of the lymphatic and CSF systems. Small dark
brown arrows represent the diffusion of nutrients from the vessels to the tissues;
dark blue arrows represent the process of absorption of wastes into the venous
parts of the capillary system; light green arrows represent the generalised proc-
ess of CSF circulation in the cranium; and magenta arrows show the direction of
lymph movements at the tissue level.

11
By comparing the CSF and lymphatic systems, as repre-
sented schematically in Fig. 2, we can see that these two sys-
tems have certain similarities in their structural-functional
organisation, but also significant differences. The most im-
portant similarity is that they both comprise the circulation
of an extra-cellular liquid through the tissues, which is re-
sponsible for the delivery of nutrients and for the removal of
wastes by convection. In both cases, these tissue fluids are a
product of the arterial blood, and are re-absorbed into the
venous blood.
There are three important differences between these
two systems: firstly, lymph flows through specialized struc-
tures, lymphatic vessels, which enables its active movement
from the tissue level back to the venous system near the
heart; by contrast, the CSF system has neither specialised
vessels nor pumping structures for its active movement. Sec-
ondly, lymph is primarily produced through the filtration of
blood plasma, whereas CSF is the product of active secretion
by specialised structures, known as the choroid plexus, located
in the lateral brain ventricles. Lastly, lymph is collected at the
tissue level by specialised structures – lymphatic capillaries,
whilst CSF is absorbed directly into the large veins on the
surface of the brain through the arachnoid villi. Thus the main
difference between the brain and the majority of other body
regions is the lack of specialized vessels and pumping struc-
tures for its supporting fluid circulatory system.
From an evolutionary point of view, the physiology of
the CSF system appears to be a relic of a more primitive
stage of evolution when compared with the lymphatic sys-
tem of ‘warm-blooded’ animals. In fact, the CSF system de-
veloped at the evolutionary stage when brain metabolism
became dependent on aerobic activity. The CSF system is
therefore a more recent development than the lymphatic sys-

12
tem in evolutionary terms, despite its similarities with the open
blood circulatory systems of some primitive invertebrates, such as
crabs.
The advanced nature of the CSF system is revealed by the
presence of structures specialized for its secretion, and by its func-
tional coupling with the closed system of blood circulation. In-
deed, the structural/functional organization of the system for CSF
circulation and drainage is optimal for brain functioning, as it has
all the advantages of the lymphatic system - in terms of nutrient
delivery and waste removal - without requiring specialized trans-
port vessels which would limit its circulation.
The free movement of CSF within the cranium also enables
the most important function of CSF – rapid volume compensation
for regional increases in brain blood volume, which not only ac-
company local and regional increases in oxygen and nutrient de-
livery to active brain areas, but also enables the even distribution
of force and pressure within the closed cranial system that accom-
panies each pulse stroke. This in turn serves to protect the soft
brain tissues from these pressure increases.
Generally, the fluids circulating within these complemen-
tary fluid systems are devoid of any cellular structures. The fluids
are produced from blood plasma, by the body’s tissues. The
chemical make-up of lymph is very similar to blood plasma, and
the mechanism for producing lymph is based upon blood filtra-
tion at the capillary level. These liquids, specialized in their com-
position in accordance with the precise body region they serve,
provide an alternative to the venous blood as a means of waste
removal by collecting the products of metabolism from the tissues.
In terms of its structural organisation, the lymphatic system
comprises a special circulatory bed with its own pumping mecha-
nisms that move lymph from the body’s tissues and organs to-
wards the heart. By contrast, CSF circulates freely through inter-
connected compartments inside the cranium and down the spinal

13
column, as well as through the brain tissue.
The compartments through which CSF circulates include
the brain ventricles and the special tube-like connections be-
tween them, and the sub-arachnoid space (the space between the
brain and the skull - arachnoidea), and the extension of this
space down the spinal column to the sacral region (called the
dural sac).

Fig. 3 The structural organisation of the CSF circulatory system

Importantly, CSF is able to penetrate through the extra-

cellular spaces of the brain tissue and to evacuate by convection
some of the large waste products of brain cell metabolism. In
contrast to lymph, CSF, as already mentioned, is largely made
through the process of secretion by specialized cells in the vascu-
lar network in the ventricles, called the choroid plexus. The
process of CSF secretion results in a moderately saline solution
without any of the chemical components of blood.
CSF moves from the ventricles through passageways to
the sub-arachnoid space and down the spinal cord. It is impor-
tant to emphasize that a special cellular organization on the sur-
face of the 3rd ventricle also allows for CSF penetration through
the brain tissue to the sub-arachnoid space, thereby washing the
brain tissue from the inside to the outside.

14
 Fig. 4 Schematic representation of CSF circulation from the site of its
secretion, through the brain tissue, to its reabsorption by the arachnoid
villi. This circulation of CSF through the brain tissue is in addition to its
bulk movement through the brain ventricle system to the sub-arachnoid
space and the spinal column.

Movements of CSF are initiated by several factors: the pres-

sure of secretion, changes in blood volume in different regions of
the brain, pressure changes that accompany the heart beat and
respiratory pressure changes, body movements, and slow fluctua-
tions in the tone of cerebral arteries. Changes in intracranial blood
volume that accompany each pulse stroke play an important role
in moving CSF through the cranial system. Consequently, the
characteristics of pulse fluctuations of CSF contain important in-
formation regarding cranial compliance (CC), as will be described
in greater detail below.
There are some additional, comparatively small but func-
tionally important circulatory systems supported by complemen-
tary fluid systems, namely the intraöcular (eye) and the intraötic
(ear) systems. The fluids within these organs also serve to support
the goal of the circulation, and are similar to the CSF system in
terms of their structural/functional organization. Some re-
gions of the body also have arterial systems specialized ac-
cording to their function. The lungs have no complementary

15
circulatory system coupled to them, due to their very precise
functional role of oxygenating and removing carbon dioxide
from the blood which requires special circulatory parame-
ters. Consequently the pulmonary circuit is separated from
the rest of the body’s circulatory system (see Fig. 1).
Whilst the body’s blood circulatory systems share
some common properties, all display certain regional peculi-
arities. For example, the arterial blood supply for most or-
gans is organized from their centres outwards to their sur-
faces. This means that the largest arteries are in the interior
of an organ, and that they become smaller as they branch
toward the surface. The brain’s arterial system is just the op-
posite. The large arteries lie on the surface of the brain, sur-
rounding the brain tissue like a net, from where they pene-
trate to the interior in an increasingly finer web. Of course,
this physiological organization serves a functional purpose,
as will be explained below.
For the most part, the veins of the body contain
valves to facilitate the return of venous blood to the heart,
but an important exception to this general rule is the Azygos
vein, which returns blood from within the spinal column.
Again, this structural specialization is important from a func-
tional point of view, as it facilitates the return of CSF to the
cranium. Indeed, as body movements bring about pressure
changes in the inferior vena cava, this in turn leads to
changes in the volume of venous blood inside the vertebral
column. Because this volume of venous blood is directly con-
nected to the volume of CSF in the spinal cord, these volume
changes can trigger CSF movements towards the cranium if
resistance to CSF movement is sufficiently low, as is the case
in healthy individuals.

16
 2. BRAIN BLOOD CIRCULATION, CSF CIRCULATION AND
CRANIAL COMPLIANCE

Circulation of blood in the brain differs from that in

the other organs because the brain is encased within a nearly
-rigid container, the cranium. The situation is further com-
plicated by the complex interaction between the cerebrovas-
cular and CSF systems within this container. These two sys-
tems are interdependent, so any changes in the volume, pres-
sure or movements within one system must lead to concomi-
tant changes in the other, consistent with the laws of fluid
dynamics. The study of brain circulation therefore com-
prises the study of the bio-mechanical interaction between
the blood within its flexible vessels, the CSF moving freely in
its compartments outside the blood vessels, and the physical
properties of the nearly rigid cranium.
By considering the cranial system as a whole, it be-
comes clear that its various structural components are all
interacting towards a single purpose, namely to fulfil the
functional goal of the circulatory/metabolic supply of the
brain tissue.

17
 Fig. 5 Relationships between volumes and pressures of liquid media inside an
intact cranial-spinal cavity.

Given the functional goal of this complex system - to support cere-

bral activity - an important element of the systemic approach is to assess
the system’s level of functioning through tests of the highest level of
cerebral activity, i.e. cognition.
An important structural element supporting cerebral circulation
is the bio-mechanical properties of the cranial bones themselves. Their
properties determine the capability of the system to accept some addi-
tional volume of blood when the intracranial pressure increases during
the heart beat. These properties reflect the elasticity of the cranium as a
complex structural system, which in turn represents what has become
known as cranial compliance (CC).
CC is an indication of the interaction between intracranial fluid
volume (blood and CSF) and intracranial pressure (ICP). Cranial com-
pliance is not a completely new concept. It’s origins date back some four
decades when a mathematical model was presented that represented all

18
significant physical features of cerebral circulation. The model
required that an elastic coefficient be introduced so that the
mathematical model could exactly match actual blood flow meas-
urements in and out of the brain. Some years later investigators
reported that when a volume of artificial CSF was slowly injected
into the cranial cavity the internal pressure did not respond imme-
diately but as the volume was increased over time, the pressure
increased exponentially. This meant that there is some reserve
capacity within the brain container to allow for volume increases
without increasing pressure and, most importantly, that the re-
serve is limited. This elastic reserve capacity became known as
cranial compliance. However, measuring CC in this way reflects a
steady-state situation, when mean ICP is changing slowly enough
to establish moments of equilibrium between volumes and pres-
sures of blood and CSF inside the cranial-spinal cavity that could
be measured.
In real life, the situation is much more dynamic. Changes
in intracranial fluid volume and pressure take place over the
course of each heart-beat. By observing that the pressure/volume
ratios recorded during a single heart-beat have distinct features
(linear and non-linear) during specific time intervals, it became
possible to analyse the contribution of the different intervals to CC
as a whole. During the first 0.1 – 0.2 seconds (s) of the heart-beat
(heart systole), the ratio will reflect the elastic properties of the
cranium – designated CCe. During the next interval of the cardiac
cycle - 0.2s - 0.6s - the ratio will reflect the compensatory move-
ments of CSF inside the cranium and between the cranium and the
spinal cavity – designated CCc. During the final interval of the
cardiac cycle, the ratio reflects the conditions of venous outflow
from the cranium – designated CCo. Each reflects the influence of
a single element. Taken together they offer the possibility for
comparative evaluation of the movement of fluids within the cra-
nial system.

19
 The importance of adequate cerebral circulation to conscious-
ness and cognition stems from the fact that the brain has no reserve
of metabolites on which its functioning can rely. The brain, there-
fore, requires a continuous and intensive supply of blood to pro-
vide oxygen and other nutrients, and to remove waste products. It
is important to mention that under certain conditions of decreased
brain blood supply, when the level of nutrient delivery may still be
sufficient, a serious problem can arise due to reduced removal of
metabolic waste products from the brain tissue. This gives rise to
increasingly toxic conditions within the brain as the pH declines
due to the progressive accumulation of acid compounds. Thus the
first sign of cerebrovascular insufficiency is not a nutrient deficiency,
but rather a deficiency in the waste removal capability of the circu-
latory process.

To summarise, the functional roles of the CSF system are to:

• act as a special “lymphatic system” dedicated to the brain, which

removes waste products too large to pass back into the blood
stream;
• provide a protective “liquid suit” for the brain and central nerv-
ous system, which protects it from mechanical stresses;
• through its free movement, provide a means for compensating
for changes in brain blood volume as the concentration of blood
moves from one region of the brain to another, according to de-
mand, inside the nearly rigid cranium.
Thus the CSF system both cushions the brain and, through its
circulation, is responsible for cleansing the brain tissue of metabolic
waste products.

3. CONTROL PROCESSES IN THE CEREBROVASCULAR SYSTEM

As was established by Roy and Sherrington more than a cen-

tury ago, the cerebral vascular system is subject to a number of con-

20
trol mechanisms, such as metabolic, hormonal and neurogenic proc-
esses, which change the vascular tone to ensure adequate metabolic
supply for brain functioning under different environmental condi-
tions. As highlighted above, however, the cerebrovascular system is
just one component of a triad that also includes the structural element
of cranial biomechanics and the CSF system in determining cerebral
circulation.
The cerebrovascular system is the only element with the capa-
bility to respond actively to the changing conditions of brain function-
ing, thanks to the smooth muscle of brain blood vessels. The CSF sys-
tem and the cranium are physically passive and therefore their contri-
bution is dependent on the forces generated by the smooth muscle
control of the vascular system, as well as the energy of central arterial
pressure. Due to this, for a long period of time the attention of investi-
gators has been focused on control processes that govern brain circu-
latory-metabolic supply under different environmental conditions and
states of activity, while other components of the whole mechanism,
CSF mobility and cranium biomechanics, have been largely over-
looked.
Many decades of studying the control processes in the cere-
brovascular system have determined their phenomenology and their
ultimate goals: 1) maintaining brain blood flow as the system’s arterial
pressure is changing, and 2) maintaining local and regional blood
flow when activating different regions of the brain in response to dif-
fering functional demands. The first has received the name
“autoregulation” of brain blood flow, and the second the name local cere-
bral vascular control (functional hyperemia). These two control processes
work independently, but both of them are also responsible for main-
taining the osmotic balance of brain tissue.
The physiological mechanisms that underpin these control
processes in the cerebrovascular system remain unclear, and there are
presently too many factors which could play a role in controlling cere-
brovascular processes to be able to determine their individual contri-
butions effectively. First of all, there are two divisions of the central

21
nervous system – the sympathetic and the parasympathetic. The
first is responsible for constriction of brain blood vessels, and the
second for their dilation. Numerous investigations have found
the presence of nerve endings, both sympathetic and parasympa-
thetic, in brain blood vessels, from large arteries down to the cap-
illaries. Besides these, other kind of innervations could play a
role in brain vessel control processes: vasoactive polypeptides (VIP)
and purynergetic types of nerve systems. Also, numerous chemi-
cal compounds including nitrous oxide (N2O) and mediators
produced by the nervous system (such as bradikinin, and sero-
tonin), the products of cellular metabolism (such as CO2 and acid
metabolites), and non-organic ions (H+, K+ and others) could all
play a role. Thus brain blood vessels are influenced by numerous
factors. The final result of their simultaneous action on vascular
tone is to support the metabolic supply of the brain tissue and to
maintain its water balance.
Since the blood and CSF systems are directly interdepend-
ent, movements in one system drive movements in the other.
Both systems are driven by: 1) the cardiac activity, 2) respiratory
movements of the chest, 3) slow fluctuations in the tone of the
brain blood vessels, and 4) the slow fluctuations of central arte-
rial pressure. Whilst the effects of cardiac activity and respiratory
chest movements are clearly traceable, the origins of the third
driving-force of the brain circulation, the slow fluctuations in the
tone of the brain blood vessels, have only recently been eluci-
dated. These slow fluctuations result from the interaction of two
or more control processes, each of which operates on a different
latency (see Fig. 6). Once this was understood it became clear
that the mechanisms for maintaining the water balance (with a
latency of 4 - 8 seconds) and oxygen balance (with a latency of 2 -
5 seconds) are the cause of these slow fluctuations. Thus the wa-
ter/oxygen balance is maintained by relatively slowly occurring
changes in intracranial vessel tone. The efficiency of this system
can be determined by the spectral analysis of intracranial blood.

22
 Fig .6 Principle of “generation” of the slow fluctuation inside the cere-
bral vascular system: this is basedup on the interaction of two or more
control links with different latencies.

The frequency of slow fluctuations provides useful insights

into the dynamic conditions of the brain circulation. In a situation
where the metabolic supply of the brain tissue and its water con-
tent are in balance, the frequency of intracranial slow fluctuations
is 7 - 9 cycles per second. In the case where there is an increase in
the water content of the brain tissue the frequency of slow fluctua-
tions decreases by as much as 4 - 5 cycles per minute. On the other
hand, when the rate of brain metabolism increases, the frequency
of slow fluctuations also increases by up to 10 - 12 cycles per min-
ute. Any observed irregularities in the amplitude and frequency of
intracranial slow fluctuations can therefore indicate that control
processes, responsible for maintaining the oxygen and water bal-
ances in brain tissue, are not functioning perfectly.
The fourth influential element is slow fluctuations in the
brain circulatory system that arise from changes in central arterial
pressure (also the result of more than two regulatory processes).
These slow fluctuations are commonly known as Meyer (Traube-
Hering) oscillations. Both types occur spontaneously in conscious
subjects at a frequency lower than the rate of respiration.

23
 4. CEREBROVASCULAR REACTIVITY

The complicated functional and structural organization of

the control system of the brain blood supply is determined by its
most important property – cerebrovascular reactivity (CVR),
which objectively reflects the adaptability of the control system
responsible for stabilizing the physical and chemical indices of the
extra cellular brain media. The functioning of this biofeedback
system is central to the life support of the brain tissue. In simple
terms, CVR is the capacity of the brain vessels to change their di-
ameter as a means to regulate blood flow through the brain in a
wide variety of living situations (see Fig. 5 showing tone of the
brain blood vessels in the central position). In order fully to assess
the cranial system’s ability to respond to the variety of functional
demands encountered in everyday life, it is reasonable to evaluate
the level of CVR in response to some destabilizing stimuli of both
chemical and physical origins.
Taking into account that the final product of brain cellular
metabolism under normal physiological conditions is carbon diox-
ide (expressed by pCO2 or CO2 concentration), the response of the
cerebrovascular system to an increase in pCO2 in the extra cellular
media of the brain tissue is to increase the brain blood flow so that
this index returns to acceptable levels. This happens because in-
creased pCO2 mimics the condition of decreased cerebral blood
flow, as under normal conditions a decrease in blood flow leads to
an accumulation of CO2 in the brain tissue. The level of response
of the brain blood vessels to increased brain tissue pCO2 is there-
fore a convenient means of testing how well the control processes
of the brain circulatory system are functioning. There are two
practical means of performing this functional test: one is a 60-
second inhalation of an air mixture with pCO2 increased to 7%; the
other is a 30-second voluntary respiratory arrest.
It is reasonable to use the inhalation of a 7% CO2 mixture to
determine CVR under clinical conditions, in particular during the
period after brain surgery. This involves measuring changes in

24
cerebral blood flow (CBF) in a given brain region in response to the
functional test using transcranial Doppler ultrasound (TCD). If
during CO2 overload the CBF increases by as much as 10 - 15%, this
means that the CVR of the investigated brain region is within nor-
mal limits. However, under pathological conditions, including af-
ter some brain injury, CVR usually decreases. In less severe cases,
the response of the brain blood vessels remains positive, but under
more traumatic conditions the brain blood vessels at the injured
region may not respond positively, as evidenced by a decrease in
local CBF of as much as 5 - 15% in the injured area following pCO2
= 7% inhalation. This negative response provides an important di-
agnostic index, indicating a serious dysfunction of the cerebrovas-
cular control system, which should be treated with the highest pri-
ority. This negative response is based upon the fact that the blood
vessels in the investigated brain region have lost the ability to re-
spond to the increased level of CO2. The increase of blood flow in
the healthy, responsive brain regions therefore pulls blood away
from the injured brain region, where the blood vessels are para-
lysed. In such circumstances, sensitivity of brain blood vessels to
most pharmacological agents, including vasodilators, is also less-
ened and their effectiveness during the period after injury may by
diminished.
Another way of testing CVR is applicable to participants who
can voluntarily control their respiration. It is standardized on a
period of 30 seconds’ voluntary respiratory arrest. The response of
the brain blood vessels to this test can be measured by the rheoen-
cephalography (REG) method shown below.

25
Fig. 7 Principle of determining CVR, using voluntary respiratory arrest as a
functional test. The method of recording rheoencephalogram (REG) and transcra-
nial Dopplerogram (TCD) is described in Chapter II.

The response of the brain blood vessels to this functional test

is based upon the accumulation of CO2 in the blood and the brain
tissue during respiratory arrest. The response is expressed as a
change in the amplitude (increasing by about 10 - 20%) and in the
pattern of the REG pulse data. A comparative value of CVR can be
determined (as indicated in Fig. 7) by calculating the difference be-
tween the initial amplitude of the REG pulse (A1 - just before the
functional test begins) and the REG amplitude when the response
of the intracranial vessels first develops, but before the general re-
sponse of the central blood circulatory system has started. The
point at which the general response is deemed to have begun is
determined by the increase in the level of pulsation of TCD, which
occurs 15 - 20s after the start of the functional test. The optimal
pulse cycle for analyzing of CVR is therefore marked on Fig. 7 as
A2. Calculations of CVR can be made by using the formula:

26
 CVR= A2 –A1
A1

For the particular example shown in Fig.7 above: CVR= (0.85

- 0.58)/0.58 = 0.47
Under certain conditions, it is also reasonable to test CVR by
using a physical stimulus such as the Stookey test (moderate pres-
sure applied to the abdomen), or by tilting the head down. Using
these tests in conjunction with REG measurements, it is possible to
measure the response of the brain blood vessels to the increased
central venous pressure that the tests elicit. This means of determin-
ing CVR in response to a predictable change in central arterial or
venous pressure has certain benefits. It can help the diagnosis of a
patient’s status after some portion of the brain has been destroyed.
For example, it is possible that after a head injury neither the neuro-
logical symptoms nor the biochemical indices discussed above pro-
vide an exact reflection of the patient’s condition. In these cases the
determination of CVR using certain physical functional tests may
provide additional and important information on the real condition
of the patient. A decrease in, or the absence of, active responses to
such physical stimuli reflects severe destruction of the control proc-
esses that support brain blood circulatory supply. An example of
this situation is shown in Fig. 7a (taken from an earlier publication
by a member of our current research group). Responses to the
Stookey test of two different patients with a brain injury, 5 days
after the surgical removal of damaged brain tissue, are depicted.
Because the skull was fractured and the brain exposed for about
two weeks, REG recordings were made using platinum wire elec-
trodes (100μm in diameter, with a 1 mm exposed tip). The elec-
trodes were implanted into the brain tissue some distance from the
focal point of the injury, in tissue that appeared healthy. Together
with REG, the intracranial pressure (ICP) and central venous pres-
sure were measured using special transducers. These investigations
were performed during treatment of accidental head injury pa-

27
tients with different degrees of brain tissue damage, once the risk of
further complications had passed.

Fig. 7a Responses to Stookey test of patients with severe and very severe head
injury. REG was recorded from wire electrodes implanted in both the cortex and
the white matter. ICP and central venous pressure were measured by special trans-
ducers. Calibration scales for each recording are shown on the left and are special-
ised for each particular case. Decreasing electrical resistance between electrodes,
which leads to a downward shift in the recording curves, shows the increasing
volume of liquid media with comparatively low electrical resistance.

In the upper case, the active responses to the functional test

are very clear, which indicates the positive presence of CVR. A re-
serve capacity to receive an additional CSF volume is immediately
demonstrated. The control mechanism for the constriction/dilation
of the vessel walls is sufficiently intact to respond to an increase in
ICP. In the lower case no active response is observed – only grad-
ual passive changes in the levels of the recording curves during the
functional test, even though the test lasted longer than in the upper
case. The results suggest that there is little capacity to receive an

28
additional volume of CSF (meaning that the existing ICP is equal to
or greater than the force applied by the Stookey test) and that the
existing ICP pressing on the blood vessels has already signifi-
cantly compressed them, and can overpower their capability to re-
spond. At this point the patient is in extreme danger. If the blood
oxygen level is not sustained artificially the arteries would not have
the strength to dilate as a normal response to increased pCO2. Auto-
regulatory processes would respond by using central blood pres-
sure to accelerate and decelerate blood in an attempt to regulate
brain blood oxygen levels. This secondary control process is known
to have low sensitivity. Blood pressure could fluctuate erratically,
and flow velocities could easily exceed or even fall below accept-
able levels. Without timely intervention, the patient would suc-
cumb to deep coma or death.
These data demonstrate that CVR (as determined by REG
recordings) can provide important insights for evaluating the cur-
rent status of head-trauma patients, and suggest that monitoring
the relation of CSF movement capabilities to the capability of the
vessels to regulate their diameter may be useful in many other
situations.
Thus, determination of CVR provides an important index for
evaluating the quality of the control processes of the brain circula-
tory system. The recordings shown in Fig. 7 and 7a provide a fun-
damental understanding of how intracranial pressure and volume
changes influence brain physiological processes. On this basis, the
following chapters will demonstrate that cerebrovascular reactivity
and cognitive functioning are exceedingly sensitive to the pressure
and volume changes that are experienced throughout the human
life span, even before obvious external manifestations are exhibited.

29
 SUMMARY OF CHAPTER I

This chapter has covered many different topics and provided

a great deal of information, its principal purpose being to empha-
size that the cerebrovascular system, the CSF system and the bio-
mechanical properties of the cranium are the major components of
a unified system responsible for ensuring sufficient cerebral circula-
tion to maintain brain metabolism and cognitive activity. It was
also intended to emphasize that the CSF system has several func-
tions, which include serving as a lymphatic system specialized for
the brain, and to propose that CSF movement capabilities may play
a significant role in cerebral circulation and cognitive function.

30
 CHAPTER II

ANALYSING CEREBRAL FLUID CIRCULATION AND

THE ‘MOSKALENKO METHOD’

As highlighted in Chapter I, cerebral activity is dependent

upon a constant supply of oxygen and nutrients, as the brain has
no capacity for storing the metabolic substrates it requires. In or-
der to understand more about the mechanisms involved in ensur-
ing this constant supply, it is important to analyse the cranial sys-
tem as a whole: the brain tissue, the cerebrovascular system (CV),
the CSF system and the partially-flexible cranium.
This systemic approach to investigating cerebral circulation
required the development of a new methodological approach to
these investigations. This involves: the use of specially-adapted
technologies to provide the kind of data required for our studies;
the application of specific functional tests to analyse the function-
ing of a specific physiological system; and the use of computer-
aided data analysis to determine the level of cranial compliance.
We have named the method as a whole the ‘Moskalenko
Method’ (MM). The MM makes use of bio-impedance data
(recorded by rheoencephalography), and blood flow data
(recorded by transcranial dopplerography), to provide informa-
tion on the nature of cerebral blood flow (CBF) and the level of
cranial compliance (CC).
An important feature of the MM as a whole is its assess-
ment of how well the cranial metabolic support system is func-
tioning from the perspective of this system’s ultimate goal - ena-
bling cognitive activity. We have therefore used certain psycho-
physiological tests as part of our investigation to investigate how
cerebral circulation and cranial compliance are linked to cognitive
activity.

31
 This chapter therefore provides some background to, and
important details of, the MM. This includes information on the in-
strumentation involved, the principles of data analysis, the specific
functional tests employed and the psycho-physiological tests of
cognitive activity.

1. THE THREE INTERVALS OF CRANIAL COMPLIANCE

Our investigations have been conducted using a unique

monitoring method that allows for non-invasive monitoring of
fluid movement through the brain in response to the forces that
drive them. Recording the dynamic conditions of brain circulation
in a single subject can be completed in less than 15 minutes with
this method, enabling a much simpler method of monitoring cere-
bral fluid movements than by magnetic resonance imaging (MRI).
The Moskalenko Method (MM) is based upon using two es-
tablished technologies to measure cerebral fluid movements. Tran-
scranial Dopplerography (TCD) measures blood flow. Rheoen-
cephalagraphy (REG) measures CSF movements. Digital analysis
of the recorded data allows for assessment of the interaction be-
tween the two fluid systems (CV and CSF), both at rest and in re-
sponse to a series of tests that apply specific functional loads to
each system individually. Analysing the interaction between the
two systems enables us to determine the nature of the pressure/
volume relationship, which in turn reflects the quality and quantity
of the cerebral circulatory processes.
The velocity of blood movement in the large brain arteries,
such as the middle cerebral artery (MCA), is monitored by TCD,
both as a steady state flow and as a pulse index, which respectively
reveal an averaged (main) linear velocity of blood through the ar-
tery, and the volume changes that occur during the cardiac cycle.
These volume changes occur at such a rapid rate that they are de-
pendent on the passive mechanical properties (elasticity) of the

32
blood vessels. This means that the vascular volume can be deter-
mined by monitoring the linear velocity of the blood, which means
that fluctuations in the TCD signal correspond exactly to pulse-
related changes in cerebral blood velocity and volume that begin in
the arteries at the base of the cranium, and then expand through the
entire cranial cavity. It is therefore possible to interpret rapid
changes of the TCD signal as also reflecting fluctuations in intra-
cranial pressure (ICP).
Changes in the interaction between the blood and the CSF
systems within the cranium evoked by the pulse changes of ICP are
monitored by REG, which measures differences in the electrical
conductivity of the brain tissue, blood and CSF. The ratios of elec-
trical conductivity values are: 1.0 : 0.5 : 0.1 for CSF, blood and brain
tissue respectively. Thus the REG signal reveals the combined fluid
volume changes (tissue volume does not change) within the cranial
region that lies between the recording electrodes placed on the
scalp.
For the study of the relationship between the blood and CSF
systems within the cranium it is important to record TCD and REG
in the same vascular region. There are several possible recording
configurations, but the most convenient is to place the REG elec-
trodes at the fronto-mastoidal position on the same hemisphere as
those that record the TCD from the basement of the middle cerebral
artery (MCA). With this configuration it is possible to make obser-
vations on the vascular region supplied by the MCA.
The instrumental complex for this research consists of a spe-
cial analogue-digital converter (PowerLab 4), which enables pat-
tern, phase and spectral analysis of the TCD and REG recordings on
a MAC or PC. Additionally, the PowerLab 4 allows simultaneous
recording of respiratory chest movements and electrocardiogram
(ECG) to be uploaded as represented by the scheme below.

33
 Fig. 8 Schematic diagram of the instrument complex, functional tests and posi-
tioning of the TCD probe and REG electrodes for CBF and CSF studies in one
hemisphere.

Recording TCD and REG simultaneously and then superimpos-

ing their wave forms reveals distinctive interactions between the
blood and CSF during the three intervals of the heartbeat. This allows
for the study of the interactions between the cerebrovascular system,
the CSF system and the elasticity of the cranium. The precise charac-
teristics of these interactions provide a good indication of the quality
of cerebral circulation and of its metabolic supply. The principle of
data analysis using these physiological approaches is described in de-
tail below.

2. THE ROLE OF THE PULSATIVE FACTOR IN BLOOD

CIRCULATION WITHIN THE BRAIN

The system of cerebral metabolic supply is dependent upon

the complex interaction of a number of elements. Our investigations

34
have clarified that CSF movement plays a significantly important
role in this system, and its role has led to a more complete under-
standing of the interaction of the forces at work within the system
The circulatory-metabolic supply of the brain is based on the inter-
action of three elements. One of them is the cerebrovascular (CV)
system, which is responsible for the delivery of oxygen, glucose
and other nutrients carried by the blood to the brain tissue; a sec-
ond element is the CSF system, whose movements enable both the
inflow of the pulse volume (the volume of blood pumped with each
heart beat) to the cranium, and also the removal of the products of
metabolism from the brain tissue, as well as being involved in nu-
trient delivery to a small extent; the third element is the bio-
mechanical properties of the cranium. This element plays some part
in the ability of the cranium to accept an increase in the volume of
blood during the phase of systolic increase in central arterial pres-
sure. Cerebral blood flow consists of two components. One is the
steady state of flow through the brain, determined by the basal tone
of the brain blood vessels. The second occurs with each heart-beat,
which initiates arterial pressure increases and so drives the pulse
volume into the cranium. It is this component that is influenced by
the level of cranial compliance, which in turn depends on the flexi-
bility vs. rigidity of the cranium.
This increase in arterial pressure is of short duration – 0.1 -
0.2 seconds. This means that the cranium needs to accommodate
the increase in systolic blood volume very quickly in order to use it
to drive cerebral circulation. This is made possible due to the bio-
mechanical properties of the cranial system – its cranial compliance
– which enables an increase in the internal volume of the cranium
during the systolic phase of increasing arterial pressure. However,
the cranium is a rigid container with only limited capabilities to
accommodate internal volume changes in response to rapidly oc-
curring increases in intracranial pressure, such as the heart beat. It
is therefore important to evaluate the cranium’s volume reserves, or
in other words, its ability to accept an extra volume of blood fol-

35
lowing the systolic increase in arterial pressure, which is in addition
to the steady state level of the brain blood flow. Let us first consider
the steady state blood flow. Steady state blood flow can be esti-
mated by using some relatively simple calculations based upon long-
established physiological data. On the one hand, we know that 52 –
65 ml of blood flows through 100g of brain mass in 1 minute, so,
through an average-sized human brain (1200g), about 600ml flows
every minute. On the other hand, we know that the brain takes
about 20% of the stroke volume (the volume of blood pumped with
each heart-beat), which for normal physiological conditions is 60 ml.
This means that 12 ml of blood passes through the brain during one
heart beat, 6 - 7 ml of that is the steady state flow, determined by the
diastolic arterial pressure and the basal tone of brain blood vessels.
The cranium therefore needs to accommodate 5 - 6 ml during the
systolic increase of arterial pressure.

Fig. 9 Distribution of stroke blood volume supporting cerebral circulation.

In comparison with the total volume of the internal cavity of

the cranium, this volume is rather small – about 0.3%. Thus, under
normal physiological conditions, the processes associated with CCe
and CCc should enable the acceptance of this volume of extra blood,

36
and its use for brain metabolic supply. However, under certain
conditions of reduced CCe and CCc, the brain may lose up to 20 -
30% of its blood flow. Of course, these numbers are at the upper
limit, but if a decrease in CCe and CCc leads to a 1 - 1.5 ml reduc-
tion in the volume of blood accepted by the cranium, then the total
brain blood flow per minute will diminish by up to 10%, which is
significant in terms of normal brain functioning, and may be re-
flected in diminished cognitive functioning. This highlights the
importance and potential of the MM, when used in conjunction
with cognitive tests such as the ‘Prognosis 1’ test, in order to evalu-
ate the dynamics of cerebral circulation, and assess the effects of
any changes in cerebral circulation on cognitive functioning.
Evaluation of the pressure-volume relationships during the
cardiac cycle has enabled the determination of three inter-
dependant ‘intervals’ of each pulse cycle, which reflect different
processes inside the cranium:

1) The initial interval is a rapid, nearly linear, increase of pulse

pressure which lasts from 0.05 - 0.15 seconds and perfectly re-
flects the elastic properties of the cranium. It designates an in-
crease of intracranial blood volume, the extent of which is deter-
mined primarily by the biomechanical properties of the cranial
bone structure (its elasticity versus rigidity), and this interval
corresponds to an increase in central arterial pressure produced
by each pulse stroke as it enters the cranium. This interval is
designated as CCe. Because CCe increases in a nearly linear
fashion, it is possible to estimate its value (in comparative units)
by using a tangent (Tg) to the approximately straight line ( see
Fig. 11 below).

2) Immediately following the peak of pulse pressure described

above, there follows a second interval representing a compensa-
tory process (CCc), which reflects CSF movements. CCc repre-
sents the interval during which displacement of the liquid media

37
 inside the cranium occurs and the force of the pulse stroke from
the previous interval is dissipated as movement of blood and
CSF through and around the brain tissue. The level of CCc can
be determined by measuring the area under the transformed
volume/time graph that corresponds to this phase of CSF move-
ments.

3) The final interval of the pulse cycle reflects the outflow of venous
blood from the cranium (CCo). The nature of venous outflow
depends on the level of pressure in the Jugular veins and on the
level of functioning of the mechanism by which energy from the
arterial pulse stroke is transmitted to driving the outflow of ve-
nous blood from the cranium. The level of this index depends on
multiple factors including CSF mobility, cranial compliance and
perfusion blood pressure. It is therefore difficult to infer much
from this measure as it has such complex origins.

The figure below depicts the changes in volume and pressure

that occur over the course of these three time intervals, how these
time intervals are determined, and the nature of the information
yielded by analysis of that data. This picture also demonstrates how
the level of CBF is determined by both the steady state of arterial
pressure, and also the pulse pressure.

38
Fig. 10 Schematic diagram representing the mechanisms of cerebral metabolic sup-
port, including steady state and pulsatile components, and their relation to the
three components of cranial compliance.

It is important to emphasize that changes to the steady compo-

nent of brain blood flow, determined by the perfusion pressure, are
independent from the pulsative component. The total brain blood
supply is determined by the summation of the steady state as deter-
mined by the perfusion pressure (average level of arterial pressure)
and the pulsatile component of blood flow, which is determined by
the biomechanical properties of the skull and the mobility of cerebro-
spinal fluid within the skull.

3. COMPUTER-AIDED ANALYSIS OF RESULTS

The three intervals of CC, which together add up to about one

39
second, represent three distinct but interdependent phases of the
pulse-driven movements of the blood and CSF that occur in a single
heartbeat. Interdependent intervals mean that a change in one in-
terval proportionally influences either or both of the others. For
example, increasing the pulse-stroke volume during the CCe inter-
val directly influences the quality of CSF movement in the next in-
terval (CCc), when the two fluids begin to rebalance. The quantity
of CSF movement during the CCc interval in turn influences the
force with which the blood leaves the brain during the outflow in-
terval (CCo), when the heart’s contraction has finished. The interac-
tions between them comprise the special mechanism for ensuring
sufficient cerebral circulatory-metabolic supply, and are repre-
sented by the scheme shown below:

Fig. 11 Method of analysing simultaneous recordings of TCD and REG, which

includes the transformation from amplitude/time scale to TCD/REG scale over a

40
standardized time interval. Pulse pressure scale (Pp) changes from Pp = 0 at the
diastolic minimum up to maximal level of arterial pressure (Pp = max) in the
middle of the standardized scale. Physiological indices: CCe(Tgα) − dynamic cra-
nial compliance; CCc - CSF-mobility; and 1/h - skull rigidity. These indices are
included in the bottom diagram. The data represented in this figure come from a
typical, healthy middle-aged person.

The following section describes how the different intervals of

CC can be determined and the data interpreted. On the graphs
above (Fig. 11), the comparative values of CCe and CCc reflect the
predominant direction of CSF movements during the pulse cycle. It
should be noted that CSF movements associated with CCc also take
place during the phase of increasing pulse pressure. This indicates
that some small amount of CSF is mobile whilst the pulse pressure
is increasing. Due to this CSF movement, the first phase on the dia-
gram shown in Fig. 11 is slightly nonlinear. Were there no CSF
movement during this phase, the index would increase linearly as
purely elastic pressure-volume changes are directly proportional to
one another. Fig. 11 also includes a special index of skull rigidity,
designated 1/h. This index reflects the pure biomechanical proper-
ties of the skull, which in turn determines the cranium’s capacity to
expand in response to an increase in intracranial pressure or fluid
volume. At the bottom of Fig. 11, the two straight lines XY and YZ
represent the theoretical biomechanical response with no CSF
movements. The major direction of CSF movement is normally lo-
calised within the cranium, moving from the ventricles towards the
sub-arachnoid space, in which case the decline in REG values dur-
ing the CCc interval is comparatively slow, because the electrical
conductivity inside the cranium is slightly increased - the electrical
conductivity of CSF is higher than that of blood. Therefore, CCc is
localized above the hypothetical straight line which represents the
purely biomechanical response. CSF movements are shown by
green coloured areas in the bottom graph of Fig.11.
The capacity for CSF displacements is not identical in all

41
individuals, and it tends to vary with age. In people with normal
cognitive functioning, the level of CCc in relative units is usually
between 0.65 - 0.80, although it can be as much as 1.0 or more. There
appears to be a reciprocal relation between CCe and CCc levels: if
CCe is comparatively low (CCe = 0.4 - 0.6), CCc is usually quite high
(about 0.7 or more). CCc tends to be higher in older people, although
in certain individuals with severe cognitive impairments, CCc is sig-
nificantly decreased. When CCc is low, this may be due to a relative
increase in the spinal component of CCc compensations (i.e. CSF dis-
placement down the spinal cord). In cases when CCc is high, CSF
movements are very active inside the cranium, and the spinal com-
ponent is small, but if both CCe and CCc are low, a deficiency in
brain metabolic supply is indicated. (Fig. 12)

Fig. 12 An example of changing CC components in elderly individuals - one

with normal brain functioning and the other with pronounced dementia.

42
 During the CCc phase, when the major CSF displacements
occur, it is possible to chart the direction of these displacements from
the pattern of change in the REG signal. In the majority of cases,
where the bulk of CSF movements occur within the cranium
(moving from the ventricles towards the sub-arachnoid space), the
decline in REG values during the CCc interval is comparatively
slow. This is because CSF has a higher electrical conductivity than
blood, so intracranial conductivity remains relatively high.
However, if CSF predominantly moves out of the cranium and
down the spinal column, then the electrical conductivity decreases
more rapidly, as there is relatively more blood volume in the cra-
nium. This pattern of CSF movement is often found in patients with
some obstruction of intracranial CSF mobility, particularly certain
pathologies including brain tumours, hematoma or post-surgical
brain oedema. It is important to note that for these cases an increase
in intracranial pressure is particularly significant and should be
closely monitored. Fig. 13 provides a schematic representation of
results from a brain-tumour (meningeoma) patient, whose condition
places a severe limit on CSF movement capacity.

43
Fig. 13 Relations between REG and TCD pulse signals for a patient with limited
capacity for intracranial CSF movements and whose predominant pulse CSF
movements are therefore directed to the spinal cavity.

As can be seen in Fig.11, the normal pattern of CSF move-

ment involves an increase in mobility that begins during the phase
of increasing systolic pressure and continues after the point at
which Pp = max, but in the patient shown in Fig. 13 with some
cerebral pathology, CSF mobility begins to decrease after Pp =
max. To reflect the difference in the predominant direction of CSF
movements, it is reasonable to categorise mainly intracranial CSF
movements as positive CCc, or simply CCc, and for cases when
CSF predominantly moves to the spinal cavity as negative CCc (or
–CCc). Some examples of the latter are illustrated in Fig. 14 be-
low.

44
 Fig. 14 CCe, CCc and 1/h for some cases of pathology.

When considering the pattern of CC results associated with

cranial pathologies, it is important to note that CCe is usually not too
low, but CCc is often negative and 1/h is comparatively high. This
pattern of results arises from the interaction of the structural changes
within the skull and the activity of cerebrovascular control mecha-
nisms, which are responsible for making every adaptation possible
for supporting cranial metabolic supply at an optimal level across all
situations.

DETERMINING CCC

In addition to the method described above for assessing dy-

namic cranial compliance and CSF-mobility, there is also a simpler
means of determining the level of CSF–mobility. This is based on

45
measuring the interval between the peaks in the TDC and REG sig-
nals over the course of one cardiac cycle, and calculating, also in
comparative units, the area of a two dimensional figure on a trans-
formed REG-TCD scale (Fig. 15):

SQ = 0.43cu
1,0
0,5
0,0
-0,5
-1,0
-0,4 0,0 0,4 0,8

Doppler (V)
Fig. 15 Simplified ways of determining CSF mobility. In both cases CSF mobil-
ity corresponds to the interval between TDC and REG signal peaks –“t”(left),
or area “SQ” (right.)

It is necessary to mention that, using these different assess-

ment methods, there are sometimes small discrepancies in the re-
sults they produce, particularly for young people (up to 10 years
old), who have flexible skulls. From the age of 15 onwards, how-
ever, both means of assessing CSF mobility give similar results, al-
though some non-significant differences are sometimes observed.
Hence it is reasonable to use both of these methods simultaneously.

4. SLOW FLUCTUATIONS IN THE CEREBROVASCULAR

AND CSF SYSTEMS

Some important information concerning changes in the activ-

ity of the control mechanisms responsible for circulatory-metabolic

46
supply of the brain tissue can be obtained through the spectral
analysis of slow fluctuations of cerebrovascular tone. These slow
fluctuations are the result of the interaction of two groups of con-
trol links, responsible for maintaining metabolic supply and the
water balance of brain tissues, as shown in Fig. 6 (Chapter 1). The
principles of spectral analysis are based on the fact that any periodi-
cal fluctuations of a complicated waveform can be represented as a
sum of more simple sinusoidal fluctuations containing different
frequencies and amplitudes (see fig. 16).

Fig. 16 The principle of spectral analysis involves the evaluation of separate fre-
quency components which, when added together, compose the complex waveform.
The left part of this figure represents how comparatively complicated periodical
fluctuations can be represented as the sum of two simple sinusoids. At the top of
the graph on the right of this figure there is a fragment of REG recording and
displayed below are its spectral components. It is possible to see that there are
many spectrum lines of the REG recording due to the complexity of the wave form
of a REG curve. It is also possible to see groups of lines, which represent cardiac
pulse (about 1.4 Hz), respiration (about 0.3 Hz) and slow fluctuations (0.08 –
0.12Hz) which indicate the activity of the cerebrovascular control mechanism.

47
 Measurements of the amplitude and frequency of slow
fluctuations in the cerebrovascular system provide valuable infor-
mation concerning the peculiarities of the control processes respon-
sible for the brain’s circulatory metabolic support.

Fig. 17 Detailed spectral presentation of frequency components, following from

spectral analysis of the original recordings from REG. The amplitude index of the
spectral components is expressed by the comparative values of pulse (heart beat)
fluctuations, the maximal value of which is 1.0. This permits the comparison of
the values of spectral lines to the amplitudes of slow fluctuations at different levels
of investigation. During normal conditions the amplitudes range is between 0.3 -
0.6.
Spectral analysis of the REG recordings provides signifi-
cant information, because it makes visible the distinction between
fluctuations that belong to the brain’s circulatory system and simi-
lar fluctuations that arise from the central cardiovascular system. It
is possible to determine the origin of slow fluctuations by compar-
ing REG spectra (fluctuations in the volume of the intra-cranial
fluid contents - shown in green in Fig. 18) with TCD spectra
(representing blood flow as it enters the cranium - shown in ma-
genta in Fig. 18). The comparison demonstrates that the very slow

48
fluctuations in TCD have an extra-cranial origin. Extra-cranial
slow fluctuations depend mainly upon fluctuations in central arte-
rial pressure, and have a considerably slower frequency (2 to 5
cycles per minute) than those of intracranial origin. Both fre-
quency groups can be identified in the REG spectra and the TCD
spectra. The amplitude of the spectral lines of intracranial fluctua-
tions gives additional information concerning CSF mobility, and
roughly corresponds to CCc. However, if the CBF control systems
are depressed, the amplitude of the spectral lines of the slow fluc-
tuations might be decreased without any changes in CSF mobility.
As seen in Fig. 17, the frequency of the major spectral lines of the
slow fluctuations corresponds to the group of control links, which
support brain blood supply. If the metabolic control of the brain’s
parenchyma is the dominant control process, the major frequen-
cies of slow fluctuations will move from 8 – 10 cycles per minute
to 9 – 14 cycles per minute. If the control of parenchymal hydra-
tion is the dominant process, major frequencies will decrease to 5
– 7 cycles per minute. By simultaneously recording the respira-
tory movements of the chest, it is possible to determine that the
origin of the REG spectral components in the range of 20 cycles
per minute are due to respiration. An example of the results of
spectral analysis of these recordings is shown below:

49
 Fig. 18 Low frequency spectral components of simultaneously-recorded
REG, TCD and respiratory movements of the chest. It is possible to see
that all three spectra reflect respiratory movements, but the spectral lines
representing respiration are different from the slow fluctuations of REG,
which represent frequencies of 5 - 14 cycles per min. Spectral compo-
nents of TCD are characterized by slower frequencies of 2 - 5 cycles per
min.

5. UNDERSTANDING THE MM’S FUNCTIONAL TESTS.

One means of evaluating the efficiency of the mechanism of

brain circulatory-metabolic supply, as with investigations of any
functional system, involves the application of certain specially-
selected functional tests. The changes that these tests evoke enable

50
the evaluation of the role that a particular element of that system
plays in the functioning of the complex mechanism as a whole. A
functional test is a temporary and standardized artificial distur-
bance, in which a particular element of a system is manipulated
under experimental conditions, in order to investigate the reaction
of the system to the test. Such tests are selected based upon the
interaction of the test mechanism with elements in the selected
system. Functional tests can be of a physical or chemical nature. A
physical test models a physical action, such as a change in pres-
sure, volume or the configuration of some aspect of the investi-
gated system, for example, intracranial blood volume. Chemical
tests involve introducing, or changing, the concentration of a
physiologically active chemical, and tracking the changes that a
specific chemical evokes.
By observing the responses to a range of functional tests, it is
possible to establish the relative contributions of the blood and
CSF systems to cranial compliance and cerebral circulation. Re-
sponses to these functional tests can be evaluated in terms of
changes in cerebral blood volume, in intracranial pressure or in
CSF replacement, and also determine the level of functioning of
the components of the cranial system. However, to check the func-
tional stability and level of functioning of the system as a whole, it
is also necessary to apply tests evaluating cognitive functioning.
The tests act as functional loads that can independently
modulate either the blood circulatory system or the CSF system.
Temporary changes in the selected system evoked by the func-
tional test enable the evaluation of the role that a specific element
plays in the investigated parameter. For example, changes in the
conditions of outflow from the cranium, brought about by an in-
crease in central venous blood pressure, enable the evaluation of
the role that intravenous pressure plays in shaping the dynamic
components of CC. Temporary changes in mean ICP also allow
for the evaluation of the role that this factor plays in forming CC.
An important principle is that the effect of the functional test

51
should be reversible, and that it does not elicit too large a change
in the functioning of the system under investigation, i.e. the
changes evoked by the functional test should not exceed the nor-
mal physiological ranges for that system.
In these investigations of the interaction between the CV
and CSF systems a number of functional tests were used. To as-
sess the reactivity of the cerebrovascular system, we compared
patterns of pulse waves, recorded under different physiological
conditions, i.e. during a phase of deep inspiration, which leads to
a decrease in cerebral venous blood pressure, with those recorded
during a phase of deep expiration, which leads to an increase in
cerebral venous blood pressure. Evaluation of changes in CC
during these phases of inspiration and expiration enables one to
estimate the contribution that the volume of venous blood inside
the cranium makes to the level of CC.
If one compares pulsations recorded after 25 - 30s of res-
piratory arrest with recordings taken in rest conditions, it is pos-
sible to evaluate the role of increasing intracranial arterial vol-
ume. This functional test is accompanied by a rapid decrease in
oxygen availability in the brain tissues, and consequently by an
increase in the brain blood flow, due to dilation of the brain
blood vessels. After stopping respiratory arrest, cortical oxygen
increases with a very short latency - less than 1s - and blood
flow also increases with a latency of 1 - 3s (based upon an acute
experiment with rats).

52
 Fig. 19 Schematic representation of mechanism of respiratory
functional test

In contrast to the respiratory-arrest test, the hyper-

ventilation test is accompanied by a constriction of the brain blood
vessels due to the removal of carbon dioxide from the blood
which allows for the increased mobility of CSF. The hyper-
ventilation test is of particular significance when considering the
possible effects of yogic respiratory exercises on cranial compli-
ance and cerebral circulation.
To assess the reactivity of the CSF system, we apply the
Stookey test. This involves pressing on the stomach region to in-
crease spinal CSF pressure, which leads to an increase in cranial
CSF volume. This enables the evaluation of the contribution that
intracranial CSF volume makes to forming the level of CC. As
well as increasing intracranial CSF volume, the Stookey test also
leads to an increase in ICP.

53
 Venous system
REST CONDITIONS

Diaphragm
Arterial system

ICP STOOKEY TEST

Viscera

Pressing 2 kg

Fig. 20 The principle of the Stookey functional test.

The application of these functional tests enables the

observation of deficiencies that are invisible at rest. It is pos-
sible that at rest CC components will look close to normal,
but application of functional tests could expose limitations in
an individual’s CC. Maximal inspiration and maximal expi-
ration bring about changes in cranial venous blood volume,
i.e. inspiration decreases and expiration increases cranial venous
blood volume. If there is a significant difference in cranial
venous blood volume at the end of deep inspiration com-
pared to the end of deep expiration, this suggests that the
intracranial volume has become comparatively smaller.
Similar insights can be gained from the respiratory
arrest functional test. After 10s arrest, there is significant
vaso-dilation of brain blood vessels, and after 20s we observe
a system-wide compensatory reaction, including an increase
in stroke volume (the amount of blood leaving the heart with

54
each heart-beat), and an increase in central arterial pressure.
There are also increases in intra-cranial pulse changes in blood
volume. In order to test the robustness of the system’s capability
to respond to environmental stresses, it was therefore necessary to
select for analysis a cardiac cycle of between 12 - 18s after the be-
ginning of respiratory arrest. As the graphs below show, func-
tional tests can bring about significant changes in each of the com-
ponents of CC, which can indicate some limitation of the cranial
system which is not evident under rest conditions.

Fig. 21 An example of how deficits in CC components, which are

“invisible” at rest are exposed by using functional tests. The resting value
(at inspiration) of the CC components are close to normal, but decrease un-

55
 der the action of the different functional tests. This indicates that the values
of the indices CCe, CCc and CCo vary in accordance with the differing
physiological conditions of real-life situations, associated with changes of
central venous pressure (inspiration, expiration phases and Stookey test)
and with changes in the tone of brain arterial vessels – dilation during res-
piratory arrest and constriction during hyperventilation.

The Stookey functional test can be particularly informa-

tive, as it increases mean ICP by directing extra CSF towards the
cranium, and so provides useful insights into the pressure/volume
relationships that determine CC. In the figure above, both CCe
and CCc are decreased during the Stookey test, but the compara-
tive value of their decrease depends upon the conductivity of CSF
in the spinal pathways. The Stookey test can therefore reveal any
vertebral column dysfunction that might be present.
It has long been known that the internal pressure changes
that accompany breathing play a significant role in the processes
that drive the evacuation of blood from the cranium. This raises
the possibility that exercises which involve focused breathing,
such as Yoga, could play an important part in the activation of
CSF dynamics. Initial insights into this possibility come from the
hyperventilation functional test. Hyperventilation leads to an in-
crease of volume capabilities in the cranium due to the constric-
tion of the brain arterial system as a response to a decrease in the
concentration of carbon dioxide in the blood.
The evaluation of slow fluctuations, as was mentioned
above, is based on the analysis of the REG recordings, using the
analogue-digital converter PowerLab-4 programme, which is in-
cluded in the MM instrumental complex. By considering the maxi-
mal frequency of slow fluctuations, it is possible to determine
which control mechanism is dominant in a particular situation. If
the maximal frequency of the spectrum is low, e.g. 6 - 7 cycles/
min., it indicates that the control processes responsible for main-
taining the osmotic balance in the brain tissue are comparatively

56
more active. So under these circumstances the water control proc-
ess is the most significant driver of slow fluctuations and may be
accompanied by an increase in brain tissue hydration. On the other
hand, if the main amplitude of REG slow fluctuations is high, e.g.
9+ cycles/min., it may be related to an increase of brain metabolic
processes. However, in order to be able to carry out this type of
analysis, it is necessary to receive at least 50 - 70s of continuous
REG recording without any interferences or artefacts, which is by
no means easy to achieve under normal research conditions.

Fig. 22 Changes in the amplitude and frequency of spectral components of

slow intracranial fluctuation may reflect insufficiencies of brain functioning
in patients with disturbances of cognitive capability due to ageing dementia.

57
 Thus, the method presented here makes possible the evalua-
tion of the indices that reflect different aspects of functioning of the
cerebrovascular and CSF systems, as well as the biomechanical
properties of the skull. These indices could reveal the current state
and changes in functioning of this complicated physiological sys-
tem.

6. USING THE PROGNOSIS-1 METHOD TO EVALUATE

COGNITIVE FUNCTIONING

Assessing the relationship between cognitive functioning

and the cerebral metabolic support system is a particularly impor-
tant focus of modern neurophysiology. It is also a particular focus
of the present study, as the ultimate functional goal of this system is
to support cognitive functioning, as was emphasized above. For
this reason, as part of our psycho-physiological investigations, par-
ticularly with regard to age-related changes in this functioning, we
included certain cognitive tests as part of the investigation’s meth-
odology.
After analysing numerous psycho-physiological methods
for the assessment of the quality of brain functioning, we selected
the Prognosis-1 method, which is based upon the prediction of ele-
ments in a sequence. This method was developed at the Biological
Faculty of Moscow State University. It is based upon special card
sequences that are to be held in short-term memory. In combina-
tion with the computer-aided analysis of the results, it is possible to
assess the prognostic capability and working memory of the test
subject. The test involves predicting the order of two symbols ("A"
and "B"), alternated in symmetric (ABBA) and asymmetric (ABAB,
BABBA) regular sequences. After the end of all sets, participants
have to repeat the order of symbols in each of three sequences.

58
 Based on the results of this test, participants were divided into
two groups: 1- adequate predictors (AP), and 2- inadequate predictors
(IP) (i.e. having prognosis difficulties). The AP group displays rapid
prognosis and the correct reproduction of the symbol sequences in all
three sets. In neuropsychological terms, human prognostic activity
requires the co-ordinated activity of multiple brain areas. The extent
and nature of this co-ordinated activity was tested by using dynamic
electro-cortical activity, which is based on EEG recordings and di-
rectly reflects changes in brain functioning. It is important also to
check the reaction of some vegetative functions, as well as orienting
reaction and changes in the conditions of solving choice-problem
situations during the test procedure.
By taking into account the number of mistakes made during
the testing procedure, we can categorise the tests into three groups,
which vary in terms of the difficulty in the prediction of results and
the recognition of the test cards. This method enables the categorisa-
tion of participants into a number of groups, based upon the number
of mistakes made. Results of the testing are indicative of the level of
cognitive functioning, which in turn can be indicative of the quality of
cerebral metabolic supply. For example, the decrease of CCe and CCc
indices for middle age groups (age 45 – 55 years) corresponds to an
increase in mistakes during the prognosis test. Similar correlations
between a decline in cranial compliance levels and worsening results
on the Prognosis-1 test have been observed in elderly individuals with
neurologically identified cerebrovascular insufficiency. It is important
to underline that the effective prognosis of events appearing in the
subject's sensory field is provided through integrated brain activity, in
combination with the effective realization of trace formation processes
in the brain. It is significant that the correlations discovered by the use
of this method allow us to consider the qualitative and quantitative
indices of the neuropsychological mechanisms underlying human
intellect.

59
 Therefore, this method can be used for the general evaluation of
the quality of the control processes supporting the circulatory- meta-
bolic supply of brain activity.

SUMMARY OF CHAPTER II

This chapter has described the complex ‘system’ analysis that

the Moskalenko Method comprises, and that has been the basis for
most of the investigations described within this document. As well as
describing the MM, this chapter also included a description of how
the MM can be applied to investigating the important concept of cra-
nial compliance, a subject that has only recently caught the attention
of researchers using MRI technology. In contrast to MRI, however, the
MM provides a much more accessible means of measuring the dy-
namic indices of cranial compliance, making it suitable for a wider
range of applications. An important feature of the MM is the use of
certain functional tests, which modulate the cerebrovascular and the
cerebrospinal fluid systems independently, depending on the test ap-
plied. These tests simulate the effects of the kinds of environmental
stresses that we face every day, and so enable an assessment of how
capable our cranial systems are of responding to such stresses. Finally,
the MM also includes a test of the system in terms of its ultimate pur-
pose: to support cerebral metabolism and therefore cognitive func-
tioning. Through such a comprehensive and holistic approach it is
possible realistically to investigate such a complex system.

60
 CHAPTER III

CHANGES IN CRANIAL COMPLIANCE UNDER

DIFFERENT PHYSIOLOGICAL AND PATHO-PHYSIOLOGICAL CON-
DITIONS, INCLUDING CRANIOTOMY

Having described the Moskalenko Method, the present chapter

will focus on some of the investigations that we have carried out using
the described methodology. These highlight the potential medical appli-
cations of the MM. The investigations focus on how CC changes as we
age; on the correlation between diminished CC, dementia and a range of
neurological and psychological deficits; and on what can be done to re-
store diminished CC.

1. CHANGING OF CRANIAL BIOMECHANICS AND CSF

MOBILITY WITH AGE

The cranial compliance model and the methods described above

have been the basis for the investigations conducted over the last three
years, whose results are described below. Using these technologies to
record and analyze data from a wide range of age-groups, (25 - 85 years
old, N = 120), has enabled us to establish standard physiological parame-
ters for the indices of cranial compliance across the healthy population
(CCe 0.8 - 1.1, CCc 0.25 - 0.45, and CCo 1.5 -2.5), and further to correlate
these indices with indices of cognitive functioning. Special investigations
were carried out with children (8 - 15 years old, N = 45), who have ex-
ceptional features in the functioning of the CBF and CSF systems due to
the increased mobility of their youthful skull-bones. Therefore the data
of these children have not been included in the statistical analysis of the

61
adult groups. If an individual’s cranial compliance results are less than
the lower values for their age range, it can be an indication of some cere-
bral circulatory insufficiency. Despite this, the decrease in brain blood
flow, which is a natural part of the ageing process, does not, in and of
itself, lead to a significant decline in brain cognitive function if the indi-
ces of CC components are within their normal ranges. However, if there
is a decline in CCe and CCc beyond the normal range, our investigations
have revealed that this is significantly correlated with a decline in cogni-
tive functioning. This is a new finding, which highlights how CC meas-
ures the cranial system’s ability to respond to the demands placed upon
it, and is therefore of great significance in terms of assessing the health of
an individual’s cerebral metabolic support system.

Fig. 23 Graph showing the normal age-related decline in cerebral blood flow, not
necessarily associated with a decline in cognitive functioning.

The decrease of CBF with age is accompanied by an increase in

CSF mobility. Cranial compliance of a healthy person increases after
middle age (45 – 50 years). Therefore, the interrelation of the compo-

62
nents of CC (CCe, CCc and CCo) also changes with age, and is deter-
mined by the comparative skull-bone mobility, by the degree of atro-
phy of brain cells, by CSF movements and by age-dependent struc-
tural changes of the walls of the brain blood vessels. These age-
related changes of CCe are shown below:

Fig. 24 Averaged changes of CCe for different age groups, showing the decline in
CCe in the middle-aged group.

Both CCe and CCc change with age, as can be observed from
pulse pattern analysis of the comparative values of the interval be-
tween TCD-REG peaks and by the values of the square of the two-
dimensional TCD-REG diagram. These indices are represented at the
top of Fig. 25.

63
Fig. 25 This figure displays the changes of CSF mobility with age, demonstrated
by changes in two indices. On the left changes in the interval “t” are shown
(interval between peaks of TCD/ REG pulse peaks. On the right of the diagram
changes in the area of “SQ” are shown. The informational meaning of “t” and
“SQ” and the dependence between these indices were explained above (see Fig.
15).

As can be seen from Fig. 25, for children below 10 years old,
the index derived from the time interval between the TCD and REG
peaks is negative. This means that the pulse volume has been com-
pletely accepted into the cranium before maximal arterial pulse pres-
sure has been reached. Between the ages of 10 – 15 years, results are
characterized by short periods between TCD - REG peaks, with con-
siderable variation between individuals. Then, from 16 – 20 years,
the index is definitively positive. These changes reflect the increasing
significance of compensatory CSF movements (CCc) to cranial com-
pliance, in part due to the decreasing flexibility of the skull as we age
and, as a consequence, the decreasing contribution of CCe to cranial
compliance as a whole. As the CC components are interdependent in
healthy subjects, a decline in CCe should result in a compensatory
increase in CCc.

64
 A significant trend revealed by this index is that, after
continuing to rise from the age of 16 onwards, there is, on average,
a slight decrease in CCc that occurs some time between 40 - 50
years of age. This decline is also observable in Fig. 24. The impor-
tant point here is that these data are indicative of a reduction in
CCe and CCc that reflects a decrease in cranial elasticity and CSF
compensatory movements. This indicates a reduction in the vol-
ume capabilities of the cranial system. Moreover, these declines
are correlated with a decrease in mental functions and other neu-
rological symptoms that occur in this same age group (40 – 50
years). The decline in the indices, as well as changes in CCe and
CCc from middle age onwards, correspond closely to the results
of other researchers, who have found that mild cognitive dysfunc-
tion starting around this age occurs against a backdrop of slow
neural atrophy in the cortex. This trend is highly significant as it
indicates that this middle-aged group can have problems with
compensatory fluid displacements, and thus is at an increased risk
of developing cerebrovascular insufficiency. It is important to take
into account that with diminished CCe and CCc there is a decline
in the movement of CSF and thus a reduced removal of waste
products. This deficiency is included in the term cerebrovascular
insufficiency. Cerebrovascular insufficiency, therefore, reflects a
range of problems, including biomechanical problems with the
cranium, vascular problems of blood supply, and CSF-related
problems with the removal of waste products. To our knowledge,
this is the first empirical demonstration of a connection between
middle-aged mental decline and a decline in cranial compliance.
We are investigating a variety of possible interventions to restore
diminished CC, and thereby to improve cerebral circulation.
Investigations were conducted to ascertain any relation
between changes in CC and cognition in an older population,
through the comparative investigation of thirty-nine subjects aged
from 70 to 84 years of age, who had been divided into four groups
on the basis of the results of psycho-physiological testing using

65
the “Prognosis-1” method, which enables an objective evaluation of
the level of cognitive disturbance. The first group consisted of sub-
jects whose cognitive results were in the normal range (N = 11), the
second group displayed initial signs of dementia (N = 10), the third
group displayed moderate dementia (N = 9), and the fourth group
had pronounced dementia (N = 9) (as shown in Figs. 25 and 26).
The index of CCe decreased progressively across these groups by
up to 40% at rest conditions, in direct correlation to declining cogni-
tive capability. Moreover, decreased CCe was accompanied by de-
creased CCc. This means that dementia in the ageing population
has a direct connection to a decline in both CCe and CCc indices.
This serves to highlight how age-related declines in CC and in cog-
nitive functioning can both be related to the biomechanical proper-
ties of the cranial system. Again, the linear velocity of blood flow
showed little correlation with declines in CCe indices or in levels of
cognitive disturbances (Figs. 26 and 27).

Fig. 26 This graph shows how declines in cognitive functioning (as deter-
mined by the Prognosis-1 test) are significantly correlated with declines
in the indices of CCe at rest and in response to functional tests.

66
 In addition to CCe, declines in cognitive functioning are
also correlated with a diminution of CCc. However, there appears
to be no correlation between cognitive ability and the rate of blood
flow in the middle cerebral artery (MCA), or with CVR (in response
to respiratory arrest) (Fig. 27)

Fig. 27 This graph demonstrates significant changes in CBF, CVR (for

respiratory arrest) and CCc indices with a decrease in cognitive func-
tioning.

Analysis of the responses to the functional tests enabled the

evaluation of the comparative contributions to the level of CCe of
the different liquid media within the cranium. It is interesting that
the value of CCe is determined by the incompressible volume
within the cranium, and by the volume of CSF, which does not de-
crease under any condition. This incompressible volume is com-
posed of the brain tissue volume and the volumes of the liquid
components inside the cranium. This is demonstrated in Fig. 28,
which shows that while the comparative changes of the responses
to different functional tests are connected with changes in the liq-
uid components inside the skull (arterial, venous blood and CSF),

67
nonetheless the comparative levels of CCe remain nearly the same.
Because the comparative donations of liquid media (arterial and ve-
nous blood and CSF) do not depend on the CCe level – their compara-
tive value is nearly the same when CCe decreases - this means that the
volumes of liquid media inside the cranium do not play a role in
forming CCe during the development of dementia. Indeed, it has pre-
viously been observed that the principal component of CCe is cranial
bio-mechanics (about 90% for people in this age range), and that the
other components account for about 9 - 10%, as is shown in Fig. 28.

Fig. 28 Graph showing the contribution of compensatory fluid movements to CCe as

a whole. The left scale shows CCe values as calculated from the original data, the
right scale shows the total comparative changes of CCe during functional tests – the
difference between the value of CCe at rest and during the functional tests, related to
the total value of CCe at rest. Colour segments display the comparative values of the
relative contribution of particular factors – blue: difference between maximal inspira-
tion and expiration, which shows the role of changes in venous volume in the cra-
nium; yellow: data obtained during Stookey test, which show the change in volume of
CSF inside the cranium; and red: the reaction to respiratory arrest, which changes the
volume of arterial blood in the cranium.

The contributions of the liquid components inside the cra-

nium are comparatively small, and are roughly equivalent (9 - 10%)

68
across all the experimental groups. Additionally, the role played by the
volume of venous blood and CSF diminishes in relation to the severity
of dementia.
These findings have important public health implications. Moni-
toring CCe and CCc can serve as a new diagnostic tool on which to
base pre-emptive interventions for those whose declining CCe and CCc
indices have identified them as being at risk of developing cognitive
problems later in life. The use of cranial compliance as a model of cere-
bral circulation, together with the method of analysis described in this
document, might mitigate some of the predicted social costs of an ever
more elderly population, by enabling better diagnoses and the applica-
tion of pre-emptive interventions to limit cognitive dysfunction.
As well as age-related disorders, the physiological origin of con-
ditions such as decreased working capability, concentration deficits,
headaches, depression and hyperactivity have, until now, been difficult
to establish by routine medical examinations, but have been hypotheti-
cally linked to cerebral insufficiency, as has been an increased risk of
strokes. The MM could easily be included in routine medical examina-
tions, and so be used to test the association between cranial compliance,
conditions of cerebral insufficiency and various pathological condi-
tions. Further studies should be focused on the study of the relation of
CC to the above-mentioned symptoms.

2. CRANIOTOMY AS A MEANS OF INFLUENCING

CRANIAL COMPLIANCE

Given the link between diminished CC and various pathological

conditions, it is vitally important to learn more about how we can re-
store, or prevent diminished CC. Our investigation has already estab-
lished that it is possible to decrease cerebral insufficiency by modulat-
ing CC through certain physical means. However, in all cases it must
first be determined that the cerebral insufficiency is due to decreased
CC and not to arteriosclerosis, which also leads to a reduction in steady
state brain blood flow. This distinction can be easily and inexpensively

69
made using the functional tests described previously. The tests deter-
mine if the brain arteries are able to respond to normal regulatory
stimuli, such as carbon dioxide overloading (hypercapnia) or oxygen
overloading (hyperoxia). When the responses to these tests, i.e. cere-
brovascular reactivity, are within the normal ranges, it means that the
vessels are not blocked with plaque. After eliminating arteriosclerosis
as a cause, any cerebral insufficiency noted can be due to a lack of
elasticity in the cranial system. This lack of elasticity can be addressed
- special procedures may be taken to enhance brain blood circulation,
that also significantly affects the pattern and extent of circulation of
CSF.
Our research has shown that trepanation, the removal of a
piece of bone from the skull, practiced since pre-history, can be an
effective means of restoring the elasticity of the cranial system. Mak-
ing an opening in the cranium dramatically increases the indices of
CCe. This significant increase in CCe after trepanation is based upon
the increased potential of the cranial system to expand in response to
rapid increases of ICP.The membranes surrounding the brain are
able to expand against the space created by the craniotomy with the
force of each heart-beat.

Fig. 29 Averaged CCe values before and after trepanation. Changes in the biome-
chanical elasticity of the skull allow the cranium to accept additional blood with each
pulse stroke.

70
 This change in CCe is mostly due to the change in cranial
biomechanics, although some of it comes from changes to the liquid
media. However, the percentage contribution of the different liquid
media to CCe is preserved at the same level as that prior to trepana-
tion, although the results of the functional tests showed that the
relative contributions of the arterial blood, venous blood and CSF
should change. It is also significant that, although the absolute val-
ues for the contributions of the liquid components to CCe before
and after trepanation are different, the comparative (percentage)
value remains the same at around 27%.

Fig. 30 The contribution of the skull biomechanics to the value of CCe increased
by about 50% after trepanation. The total percentage contribution of the fluids to
CCe remained unchanged, although their individual contributions varied consid-
erably.

Making a skull opening also contributes significantly to the

CSF mobility during the CCc interval. It has already been demon-
strated using cine-phase contrast MRI and using MRI (signal void
phenomena) that a skull opening allows CSF to move more freely

71
throughout all the compartments of the cranial system. Our re-
search confirms these findings. An opening in the skull-bone allows
for a partial redistribution of the CSF movement from between the
ventricles and the spinal sac in the intact skull to between the ven-
tricles and the sub-arachnoid space in the trepanned skull. Look-
ing back to Fig. 4 (showing penetration of CSF through the brain
tissue and the location of the arachnoid villi) it can be understood
that active movement of CSF between the ventricles and the sub-
arachnoid space plays an important role in the cleansing of the
brain tissue and in the elimination of waste products via the arach-
noid villi.

Arterial system
Venous system

Fig. 31 Comparative changes in CSF dynamics as a result of cranial

trepanation. Brown arrows indicate the predominant direction of CSF
mobility. It should be noted that more CSF is circulating within the
cranium than between the cranium and the spinal sac after trepanation,
thereby improving the removal of the waste products of metabolism.

It is possible to determine the predominant direction of CSF

circulation by observing some characteristics of the ∆V/∆P (change
of volume : change of pressure) relationship that take place during

72
the CCc interval (when CSF compensations are taking place). After
the pulse pressure has reached its maximum (beginning of CCc inter-
val), blood volume is no longer increasing, so any increases in fluid
conductivity are due to CSF movement between the ventricles and the
sub-arachnoid space—the signal increases because the most conduc-
tive fluid moves from the interior to the surface of the brain. The more
significant the increase of conductivity, the more predominant the
intracranial CSF movement. Conversely, when there is little increase
of fluid conductivity after the maximum pulse pressure, this means
that CSF is more predominantly tending to translocate down the spi-
nal column. Changes in the predominant direction of CSF movement
can be evaluated by the relative increase of conductivity. However, a
lack of any increased conductivity whatsoever is indicative of the lack
of possibility for intracranial volume processes to occur. A potential
reason for this may be the changes in volume processes in the brain
tissue, brought about, for example, by a brain tumour. Thus, a de-
crease of CSF mobility may indicate some underlying pathology and
indicate a need for further investigation using MRI, and for possible
surgical intervention. Such data highlight another potential advantage
of the MM in indicating abnormal volume processes inside the cra-
nium.
As a result of trepanation, the response to functional tests in the
investigation of CCc shows that the range of changes in venous blood
volume inside the cranium increases by about 30% following trepana-
tion. This is indicated both by a more pronounced response to respira-
tory arrest, and also by a reduced response to the Stookey test. This
means that volume capabilities inside the cranium definitely increase
after trepanation and that, after trepanation, responses to the Stookey
test can be analysed to test for some disturbance in CSF cranial/spinal
circulation, which may be mechanical in origin, e.g. vertebral column
deformation.

73
Fig. 32 Changes (M±SD,n=15) in CSF mobility (reflecting changes in CCc) as
shown by different functional tests before and after trepanation. The graph shows
the increase in cranial volume reserves after trepanation.

This data demonstrating the effects of trepanation was addi-

tionally confirmed by observing how the pulse amplitude fluctuates
with the phase of the respiratory cycle both before and after trepana-
tion. If, before trepanation, the pulse volume of blood accepted into
the cranium was significantly related to the phase of the respiratory
cycle, (a relationship that indicates reduced cranial volume capabili-
ties), this relation disappeared following trepanation - i.e. respiratory
changes were no longer a limiting factor on the volume of blood that
can be accepted by the cranium. These observations have therefore
highlighted a further possible diagnostic tool for assessing the health
of the cranial system: observation of whether the phase of the respira-
tory cycle is a significant determinant of the amplitude of intracranial
volume. Our research has also indicated that trepanation might prove
to be a suitable means of restoring normal volume capabilities to the
cranial system.

74
Fig. 33 This recording indicates how the changes in the volume inside the cra-
nium during respiratory chest movements after cranial trepanation are due to
an activation of CSF movements, reflecting an increase in intra-cranial volume
capabilities. When the volume capabilities inside the cranium are restricted,
pulse amplitude does not change with respiratory fluctuations. After trepana-
tion however, when this restriction disappears, it is immediately reflected by
changes in the amplitude of the pulse fluctuations during the respiratory cycle –
making them independent of the changes of respiratory intracranial blood vol-
ume fluctuations.

Importantly, these investigations have established that the

increased elasticity produced by a 4 cm2 opening in the skull does
not cause the normal limits of cerebral blood flow to be exceeded.
In other words, cranial openings of this size are safe in that their
effects do not exceed the upper limits of blood flow of 60 ml/
minute/100gms of brain tissue.

75
 Fig. 34 Changes of blood flow in MCA and the pulsatile index after trepanation.
At rest the blood flow in the trepanned skull is somewhat increased and PI (or
peripheral resistance) is lessened.

During respiratory arrest, the arterial dilation is somewhat

reduced in the trepanned skull, and the peripheral resistance - the
resistance of the cerebrovascular tree (Pi) - is also somewhat re-
duced. During the Stookey test, when CSF is being pushed from the
spinal sac back into the cranial cavity, the blood flow in the tre-
panned skull responded more directly than in the intact skull.
Trepanation also had a significant effect on cerebral blood
flow (CBF), measured by TCD. An important caveat with regard to
these changes in CBF is that there was a great variety in individual
results. This meant that there were no statistically significant
changes in CBF before and after trepanation. However, analysis of
the individual responses to trepanation has shown that if CBF was
within normal ranges before trepanation, then it did not change after
trepanation. But if CBF was below normal before trepanation, then it
increased afterwards. It is possible to understand this phenomenon
by considering the activity of the mechanism of auto-regulation of

76
CBF, which maintains CBF and central arterial pressure (CAP) at
the optimal level for any particular situation (CBF approximately at
50 – 60 ml/100 gm/min and CAP at approximately 120 mmHg). If
CBF was normal before the intervention, then its initial increase
following trepanation is brought back to normal levels by the above
-mentioned mechanism. However, if CBF was below normal before
trepanation, then a skull opening can bring the CBF back to a nor-
mal level. This is a highly significant point and indicates that trepa-
nation offers an effective means of restoring CBF in such individu-
als. Additionally, these data illustrate an important shortcoming
concerning the use of statistical analysis. In this particular case, if
our conclusions were based only on simple statistical analysis, this
important finding would be lost.
Use of spectral analysis of the REG recording, during ap-
proximately one minute of non-stop recording without interfer-
ences, shows that the slow fluctuations related to the oxygen and
water balancing dynamic were altered positively after cranial trepa-
nation.

Fig. 35 Spectral analysis shows, that after trepanation the frequency of intra-
cranial slow fluctuations increased to normal limits and their amplitude in-
creased. It means that after trepanation the level of intracranial pressure de-
creased and CSF- mobility increased.

77
 Given these effects of trepanation on the cranial system, it is
of great importance to neurosurgeons that some comparative data
is collected in order for them to assess when a skull opening should
be closed following neurosurgery. Currently, every surgeon de-
cides this question by following his own experience. However the
data presented above now provide the possibility that this decision
be made more objectively. The data presented also show that, in
some selected cases, when CCe and CCc are low, trepanation may
be a useful tool in increasing the compensatory capabilities of the
cranium.

Fig. 36 As can be seen after trepanation, both CCe and CCc increase, but after
closing the opening both decrease. This means that leaving the hole in the cranium
open after surgery can play a protective role (compare upper and lower pictures on
the right). Changes in CCe and CCc after closing the hole in the cranium show
that intracranial CBF and CSF mobility have adapted to the conditions brought
about by the open cranium, and decrease after the reconstruction of the cranial
bone.
It is possible to see that after neurosurgery, with the conse-
quent open trepanation hole, CCe and CCc significantly increase.

78
Closing of the hole after a certain period of time, after the patient
has recovered from all the consequences of neurosurgery, is accom-
panied by some decrease in CCe and CCc, but this decrease is not
dangerous for the recovered brain. However, if the hole is closed
immediately after brain surgery, particularly for operations to re-
lieve brain edema, it can have a negative effect on brain function
due to an increase in ICP, which can require surgical correction in
some cases. Not surprisingly, in a survey conducted more than
sixty years ago, which reviewed the outcome of neurosurgical in-
terventions on Russian soldiers who had sustained battlefield head
traumas, it was reported that those patients whose skulls were not
closed after surgery had the highest level of recovery.
Investigations of the effects of trepanation have revealed the
new and very interesting possibility of asymmetry in the indices of
CCe and CCc between the hemispheres. This asymmetry is signifi-
cantly greater in trepanned individuals compared with untre-
panned, healthy participants. This asymmetry is observed as a rela-
tive increase in the dynamic component of cranial compliance
(CCe) and a decrease in CSF-mobility (CCc) compared with the in-
tact hemisphere. The level of asymmetry depends upon the size
and locality of the cranial opening. In the case of a lateral opening
of 3 - 5 cm2, CCe and CCc indices differ by up to 7 - 10% for the
trepanned side. If the opening is larger, for instance up to 15 - 20
cm2, the asymmetry in CCe and CCc indices may be very signifi-
cant as is shown on Fig. 37 .

79
Fig. 37 Asymmetry in CCe, CCc and 1/h indices, observed with a patient who was
injured in 1996, and whose consequent cranial opening has been preserved up to
the present time. Cranial opening localised on the right temporal bone, about 18
cm2 in area.

This property of asymmetric CSF movements between the two

hemispheres is particularly prominent over short periods of time –
i.e. a single cardiac cycle. What it reveals is the effect of some hydro-
dynamic resistance to CSF movements between hemispheres, which
might be significant for some pathological conditions. However, the
time parameters of this resistance are unknown at the present time.
This new finding on hemispheric asymmetry needs to be the subject
of special investigations, in particular of the time-course over which
it operates, and of what its physical basis is. The bi-hemispheric re-
cordings on this particular subject also reveal that even after an ex-
tensive healing period a skull opening of such size retains significant
elastic properties .

80
 3. EVALUATION OF THE RESULTS OF OSTEOPATHIC TREATMENT

Trepanation is not the only possible means of increasing the

volume capabilities of the cranium. One alternative intervention is
cranial osteopathy, and particularly the technique of manipulating
the 3rd ventricle, a technique labelled “the drainage of venous si-
nuses”, which is known as the “king” of cranial osteopathic tech-
niques. However, the real physiological mechanism of this tech-
nique is more complicated than its name suggests. This technique
has recently been shown significantly to increase CCe. Observa-
tions of the effect of osteopathic treatment, especially with children
suffering the consequences of brain injury such as can occur during
child birth, show that such injuries may be effectively corrected by
applications of some osteopathic techniques.
Through the analysis of TCD and REG recordings it is possi-
ble to demonstrate the results of osteopathic treatment, which are
usually invisible. For instance, using the MM it was possible to see
the results of the application of the “venous sinus drainage” osteo-
pathic technique to a boy of 11 years of age who had suffered brain
injury, which was manifested in regular headaches. After treatment
the clinical symptoms were significantly diminished.

81
 Fig.38 The increase in CCe, CCc and CCo after 10 minutes of
application of osteopathic Technique “Drainage of venous si-
nuses”
.
From these findings it is possible to hypothesise that
the application of some osteopathic techniques in the cranial
field may have an effect similar to trepanation. This indicates
osteopathy as a possible treatment for people in the middle
age group (45 – 55 years of age) who have experienced a de-
crease in CCe and CCc. It is also possible that osteopathic
treatment may be effective for patients after neurosurgery,
especially for those whose surgical openings have been pre-
maturely closed. In order to investigate these hypotheses, it
would be necessary to determine more precisely the changes
in CCe and CCc brought about by osteopathy using the
‘Moskalenko Method’.
A further finding of interest with regard to interven-
tions to restore cranial compliance comes from our prelimi-
nary data showing changes in CCe and CCc after 30 seconds

82
of deep inspiration and deep expiration (hyperventilation),
at the same rhythm as normal respiration. It was found that
10 - 20 seconds after hyperventilation, CCe increased by 23%
and CCc increased by 26%. This can be taken as a very tenta-
tive model for the effects of yogic breathing, and indicates
that the effect of yoga on cranial compliance and on cerebral
circulation merits further research. Indeed, it gives rise to the
possibility that yoga could be useful for persons with de-
creased cranial volume capabilities. This is an area of investi-
gation that we are extending and expanding, as it holds
promise for the treatment of middle-aged patients with
symptoms of circulatory insufficiency.

4. ADAPTATIONS FOR DIVING

Investigations under different physiological condi-

tions, specifically if the person investigated is already
adapted for this particular condition, can give valuable infor-
mation concerning the plasticity of the system responsible
for circulatory-metabolic supply of brain functioning. An
example of such a case may be found in training for diving,
which is accompanied by an oxygen deficit to the brain tis-
sue and, as a result, adaptation to these conditions. To inves-
tigate this problem 14 young (19 - 22 years old) participants
were studied, using a technique to simulate diving training,
which included not only respiratory arrest, but also cooling
the face by application of a cold wet towel.
This investigation has shown that the adaptation of
these individuals to this functional load is reflected in a dis-
tinct pattern in the REG – TCD data: the time difference be-
tween maximal values of REG and TCD pulse, are approxi-
mately twice as long in the diving group as for control

83
groups of the same age. Significantly, the initial changes for respiratory
arrest in REG – TCD pulse patterns emerge earlier than in control
groups of the same age with no diving experience. These facts indicate
that certain adaptations for diving can be observed during resting con-
ditions. Changes in the values of CCe and CCc during diving simula-
tion are shown below:

Fig. 39 Changes of CC indices as result of diving simulation in participants adapted to

this load.

Figure 39 shows that changes of CCe and CCc go in opposite directions

during diving simulation. This indicates that training for hypoxia has
taken place. Some decreases of CCe can be explained by the increase in
intracranial blood volume due to arterial vasodilatation in response to
hypercapnia. However, this effect is compensated for by an increase in
CCc. The adaptation for diving involves the development of a special
mechanism that supports the brain’s metabolic supply by significantly
increasing CSF mobility to compensate for the process of circulatory
deficit in the brain tissue during diving. This example demonstrates the

84
high compensatory capabilities of the mechanism responsi-
ble for the brain’s circulatory metabolic supply, and its high
plasticity. This is not particular to certain individuals, but is
universal, and may be enhanced as a result of specialized
training.

SUMMARY OF CHAPTER III

The materials presented in this chapter have demonstrated

that there are a number of ways for restoring diminished CC
components – CCe and CCc. Furthermore, it has shown that
it is possible to obtain stable and beneficial results from cra-
nial trepanation, and this may prove to be a useful interven-
tion for middle-aged patients with cerebrovascular insuffi-
ciency. We will continue to investigate the possible applica-
tion of osteopathic treatment and yogic respiratory exercises
to counteract the age-related decline in cranial compliance.
Although yogic breathing is mentioned last, this is only be-
cause we currently have the least data on its effects. Al-
though our research into this is at a very preliminary stage,
the data we have received so far makes us sufficiently opti-
mistic to continue this avenue of research.

85
86
 CONCLUSIONS

The research thus far has produced the following outcomes:

1) The development of a unique method of non-

invasively obtaining new data about the working of
the cerebral circulatory system, named the Moskalenko
Method.
2) The development of a new systemic understanding of
the dynamic interrelation of the three inter-dependent
systems which together determine cerebral circulation
and the health of the brain.
3) New data indicating the importance of cranial compli-
ance in assessing changes in intra-cranial circulation
and its direct effect on cognitive functioning.
4) The discovery of important new information about age
-related declines in cerebral sufficiency and mental
functioning around middle age, and a direct correla-
tion between declines in cranial compliance and pro-
gressively worsening symptoms of dementia.
5) The development of possible pre-emptive interventions
and treatments for declining cerebral circulation, and
means to assess their effectiveness.
6) The first physiological explanation of the effects of
trepanation, i.e. increased elasticity of the cranium that
brings with it some significant changes of cerebral cir-
culation.
7) The investigation of other methods of counteracting
deteriorating indices of cranial compliance, such as
yogic deep breathing, extreme exercise and cranial os-
teopathy.

87
8) The way forward:

a. Developing the ‘Moskalenko Method’ for easy diagnosis of cra-

nial compliance levels across the population to help diagnose
and treat age-related cerebral insufficiencies. This will be
achieved through developing automatic read-out analysis of the
data provided.
b. Developing the ‘Moskalenko Method’ to provide a non-
invasive means of monitoring and measuring intracranial pres-
sure (ICP). Currently the only way to directly measure ICP is to
make a cranial opening and insert a transducer into the brain. A
non-invasive monitor of ICP will be an invaluable tool for the
rapid diagnosis and treatment of life-threatening head injuries.
By measuring ICP within the “Golden Hour” after an accident
many more lives could be saved and permanent brain damage
may be prevented.
c. Extending research into trepanation and other techniques of
improving cranial compliance with the aim of optimizing cere-
bral functioning and wellbeing in both the afflicted and in the
apparently healthy general population.

88
 Appendix I

MEDICAL APPLICATIONS FOR THE MOSKALENKO METHOD

The data presented in this document illustrate that an un-

derstanding of cranial bio-mechanical properties and CSF mobil-
ity is critically important in order to inform the treatment of a
number of medical problems that are connected with diseases of
the cerebral circulatory system. A better understanding of the
implications of the indices of CC is also vital when monitoring
the results of treatment after serious brain injury and surgery.
For all these cases, the ‘Moskalenko Method’ provides a conven-
ient, comparatively simple and inexpensive method for diagnos-
tic purposes, and for population screening for deficiencies in
cerebral circulation.
It is also reasonable to take into account the possible effect
of special respiratory exercises on CC. It is quite clear that our
forefathers had some intuitive knowledge of this subject, illus-
trated by the observation that rhythmic Yogic breathing counter-
acts cerebral insufficiency by altering cranial compliance. We are
currently developing a programme of investigation into the ef-
fects of yogic breathing on cranial compliance.
It is apparent that a number of invaluable new insights
into healthy cerebral functioning have so far been discovered
through the application of the ‘Moskalenko Method’, and that
the scope for extending these findings and applying them to the
diagnosis and treatment of age-related cerebral insufficiencies,
such as dementia, offers great promise. The application of these
insights will become increasingly crucial as the social costs of an
ever more elderly population are felt. Furthermore, we are using
this technology to investigate possible means with which such
insufficiencies can also be prevented, as well as treated. By ex-
tending our understanding of the human brain system, we

89
might also learn how mental functioning can be influenced
through interventions focussed on cerebral circulation.
The research findings reviewed in this document provide
an up-to-date picture of our understanding of the mechanisms
responsible for the brain’s metabolic supply, and have led to our
developing an all-inclusive view-point of the system responsible
for enabling cerebral activity and cognitive functioning. This
functioning is dependent on a complex physiological mecha-
nism, consisting not only of the cerebro-vascular system, but also
of the CSF system and of the bio-mechanical properties of the
cranium. Whilst numerous investigations have described the
peculiarities of the functioning of brain blood vessels, there is
much less data concerning the CSF system and how it interacts
with the cerebro-vascular system, and even less on the role
played by the biomechanics of the cranium.
Commonly used parameters may be correct for normal
physiological conditions, but are not valid for numerous patho-
logical conditions. It is therefore not only acceptable but advis-
able to use the quality of cognitive functioning, of the brain’s
physiological mechanism, as a diagnostic factor in assessing the
level of functioning of this complex system. Using this conceptu-
alization, the studies here presented have focused on elucidating
the hitherto uncertain roles played by the various components of
this complex mechanism, namely, the functional roles of CC and
CSF movements, and how these components contribute to the
mechanism of circulatory-metabolic supply of the brain, or,
more precisely, how they support its cognitive functioning.
Having identified the contribution of CSF movements to
cerebral circulation, one of the most important directions of our
current research is to determine how certain portions of CSF can
become stagnant in pools of inactivity, and thus reduce cerebral
circulation. This sluggish movement of CSF may be a contribut-
ing factor in the build up of beta-amyloid free radicals in the

90
brain tissue. Beta-amyloids are known to be involved in the de-
velopment of Alzheimer’s disease. Our attention will therefore
be directed specifically to how our methodology might demon-
strate the capacity for changes in CCe and CCc, and thereby
cause CSF more actively to wash out the toxic build-up of parti-
cles from the brain tissue.
Improving the diagnosis and treatment of age-related de-
teriorations in mental health is not the only medical application
of this research. The physiological origin of conditions such as
decreased working capability, concentration deficits, headaches,
depression, hyperactivity and an increased risk of strokes have
been hypothetically linked to cerebral insufficiency, but until
now the origins of these have been difficult to establish by rou-
tine medical examinations. Therefore, further studies should also
be focused on the study of CC in relation to these symptoms, as
the Moskalenko Method could easily provide a means of rou-
tinely screening for such medical conditions.
The Moskalenko Method’s instrument complex is low-
cost and portable, and so could readily be adapted for use in
emergency situations to assess cerebral dynamics. A very urgent
direction of our efforts, therefore, is to develop further the Mos-
kalenko Method into a user-friendly package with automated
read-out analysis. This should enable the rapid measurement of
cerebral functioning, brain circulatory dynamics and intracranial
pressure (ICP) at the scene of accidents or soon after. The devel-
opment of a non-invasive monitor of ICP is the Holy Grail for
head injury treatment, as it facilitates diagnosis and application
of the appropriate intervention necessary to prevent brain
trauma during the time-period known as the “Golden Hour”.
The “Golden Hour” refers to the first hour following an
accident, during which any treatments applied have the greatest
impact, so greatly increasing the chances of a patient making a
full recovery. Head trauma is currently the greatest killer in

91
people aged 45 and under in the developed world, and in India
alone accounts for many hundreds of thousands of deaths per
year. Delays in evaluating intracranial dynamics following head
injuries mean that many more people die or suffer permanent
brain damage than would be the case if a portable means of evalu-
ating intracranial dynamics were more readily available to ambu-
lance crews and to mobile medical services. The Moskalenko
Method can also be employed when access to expensive and im-
mobile brain-imaging technologies is limited, such as in remote
locations, on the battlefield or in much of the developing world.
The most pressing directions of our continuing investiga-
tions are both to develop a non-invasive ICP monitor and also to
chart in greater detail the age-related changes in intracranial dy-
namics. This latter includes determining more precisely at what
age the elasticity of the cranial system begins to diminish, com-
paring the effectiveness of a variety of interventions to restore
cranial compliance, and better determining how the indices of
CCe and CCc can be used to diagnose the level of decline at
which pre-emptive interventions to restore cranial compliance
could be required. From the ageing perspective, the decrease in
CCe between the ages of 40 and 50 deserves our special attention,
and we plan further studies to build upon the numerous neuro-
logical observations already made. Preventing any circulatory
and cognitive declines in this age group would have enormous
social benefits, as people in this age group are of great value to
society, having already gained a great deal of life-experience and
still having time and energy before them to realize their mental
potential.
The broad potential and benefits of this research mean that
its continuation could prove vitally important, not only to those
who are suffering a decline in cognitive ability with old age, but
also to trauma patients with head injuries, to those in middle age
who are suffering from a decline in mental functions due to cere-
bral insufficiency, and to those seeking to utilize these concepts of

92
fluid movement within their own brain for the purpose of reaching
their optimal potential. To these ends, we greatly look forward to
the continuation of this exciting research.

93
 Appendix II
ARTICLES ARISING FROM THE RESEARCH

Articles for which we have an English translation can be found on

the Beckley Foundation website: www.beckleyfoundation.org

1. “Age Related Peculiarities of Ratio of Parameters of Functioning of

Hemo- and Liquorodynamics Systems.”
¹Moskalenko Yu.E., ¹Weinstein G.B, ²Halvorson P., ¹Riabchikova N.A.,
¹Kravchenko T.I.,
²Feilding A., ¹Panov A.A., ¹Semernia V.N., ¹Markovets S.P.
¹Sechenov Institute of Evolutionary Physiology and Biochemistry, Rus-
sian Acad. Sci.,
St. Petersburg, Russia and ²Beckley Foundation, Oxford, U.K.
Journal of Evolutionary Biochemistry and Physiology. 2006. v.42, No.6,
p. 759-768.
http://www.beckleyfoundation.org/bib/doc/bf/2006_Yu_211310_1.pdf

2. “Effect of the Skull Trephination Opening on the Interaction between

Intracranial Vascular and CSF Systems.”
Y. Moskalenko¹, W. Hachatryan², G. Weinstein¹, K. Samochernyh²,
P.Halvorson³, A. Feilding³,
N. Ryabchikova¹, A. Moskvin¹, A. Panov¹
¹Sechenov Institute of Evolutionary Physiology and Biochemistry Rus-
sian Acad. Sci.,
St. Petersburg, Russia, ²Polenov Institute of Neurosurgery, St Peters-
burg, Russia,
and ³Beckley Foundation, Oxford, U.K.
Proc.of the 24th Annual National Neurotrauma Society Symposium.
(St.Louis, MO, USA.
July 7-9, 2006.)
Journal of Neurotrauma. 2006. v. 23, n.6, p.1000.
http://www.beckleyfoundation.org/bib/doc/bf/2006_Y_211476_1.pdf

94
3. “The Elderly and Old Age Correlation of Intracranial Hemo – and Li-
quoro- Dynamics Systems.”
¹Moskalenko Yu.E., ¹Weinstein G.B., ²Halvorson P., ¹Ryabchikova N.A,
¹Kravchenko T.I.,
²Feilding A., ¹Semernia V.N., ¹Panov A.A., ¹Mayorova N.F., ¹Markovets
S.P.
¹Sechenov Institute of Evolutionary Physiology and Biochemistry Rus-
sian Acad. Sci.,
St. Petersburg, Russia, and ²Beckley Foundation, Oxford, U.K.
Proc. of the Conference “Cerebrovascular pathology in Leningrad Siege
survivors and in elderly persons ". St. Petersburg, 2006. p.19-21.
http://www.beckleyfoundation.org/pdf/Elderly_and_Old_2006.pdf

4. “Age-Related Characteristics of Relationships Between Brain Blood

Flow, Liquorodynamics and Biomechanical Properties of Human Cra-
nium.”
¹Moskalenko YuE., ¹Weinstein GB., ²Halvorson P., ¹Kravchenko TI.,
²Feilding A.,
¹Riabchikova NA., ¹Semernia VN., ¹Panov AA.
¹Sechenov Institute of Evolutionary Physiology and Biochemistry Rus-
sian Acad. Sci. St.Petersburg, Russia , and ²Beckley Foundation, Oxford,
U.K.
Russian Journal of Physiology. 2007. v.93, n.7, p.788-798.
Abstract in English on: http://www.ncbi.nlm.nih.gov/pubmed/17912852

5. “Age Dependent Correlation between Cerebral Blood Circulation,

Cerebrospinal Fluid Dynamics and the Cranial Compliance. “
Yu.E. Moskalenko1, P. Halvorson2, T.I. Kravchenko3, G.B. Weinstein1,
N.A. Ryabchikova4, A. Feilding5, A.A. Panov1
1Sechenov Institute of Evolutionary Physiology and Biochemistry, Rus-

sian Acad. Sci., Laboratory of Cerebral Circulation, St.Petersburg, Rus-

sia; 2ITAG Foundation, Philadelphia, USA;
3Russian School of Osteopathic Medicine, St.Petersburg, Russia;

4Moscow State University, Moscow, Russia; and 5Beckley Foundation,

Oxford, U.K.
(Proc. of the 6th European Congress of the Intern. Assoc. of Gerontology
and Geriatrics “Healthy and active ageing for all Europeans”.
St.Petersburg, Russia, 2007). “Advances in Gerontology”. 2007. v.20, n.3,

95
 p.58.

http://www.beckleyfoundation.org/bib/doc/bf/2007_Yu_211478_1.pdf
6. “Noninvasive Dynamic Evaluation of Functioning of the Intracranial
System.“
¹Moskalenko Yu.E., ¹Weinstein G.B., ¹Kravchenko T.I., ²Feilding A.,
²Halvorson P.,
¹Ryabchikova N.A.
¹Sechenov Institute of Evolutionary Physiology and Biochemistry Rus-
sian Acad. Sci.,
St Petersburg, Russia, and ²Beckley Foundation, Oxford, U.K.
Proc. of the 4th International Conference “Development and applying
of high technologies in science, industry and education. St.Petersburg,
Russia, 2007. Vol.10. p. 214-215.

7. “Slow Wave Oscilations in the Cranio-Sacral Space: a Hemo- Li-

quorodynamic Conception of Origination.“
¹Moskalenko Yu.E., ¹Kravchenko T.I., ¹Weinstein G.B., ²Halvorson P.,
²Feilding A., ¹Mandara A, ¹Panov A.A., ¹Semernia V.N.
¹Sechenov Institute of Evolutionary Physiology and Biochemistry, Rus-
sian Acad. Sci.,
St Petersburg, Russia, and ²Beckley Foundation, Oxford, U.K.
Russian Journal of Physiology. 2008. v.94, n.4, p.441-447.
Neurosci Behav Physiol 2009. v.39, No.4, p.377-381.
http://www.beckleyfoundation.org/bib/doc/bf/2001_Yu_211072_1.pdf

8. “Relationships between Indices of Cerebral Circulation, Liquorody-

namics, Cranial Biomechanics and Prognostic Brain Ability.”
¹Moskalenko Yu., ¹Weinstein G., ²Ryabchikova N., ¹Kravchenko T.,
¹Samus N., Feilding A., Halvorson P., ¹Semernia V.
¹Sechenov Institute of Evolutionary Physiology and Biochemistry Rus-
sian Acad. Sci., St.Petersburg, Russia; ²Moscow State University, Mos-
cow, Russia; ³Beckley Foundation, Oxford, UK.
Proc. of the 4th All-Russian Conference on Circulatory Physiology.
Moscow, 2008. p.68.
http://www.beckleyfoundation.org/bib/doc/
bf/2008_Moskalenko_211481_1.pdf

96
9. “The Effect of Craniotomy on the Intracranial Hemodynamics and
Cerebrospinal Fluid Dynamics in Humans”
¹Moskalenko Yu.E., ³Feilding A., ³Halvorson P., A. C., ²Mozhaev
S.V., ¹Semernia V.N, ¹Weinstein G.B., ¹Kravchenko T.I., ²Medvedev
S.V.
¹Sechenov Institute of Evolutionary Physiology and Biochemistry
Russian Acad. Sci., St.Petersburg, Russia; ²Institute of Human Brain
Russian Acad. Sci., St.Petersburg, Russia; and ³Beckley Foundation,
Oxford, U.K.
Human Physiology. 2008. Vol. 34, No. 3, pp. 299–305.
http://www.beckleyfoundation.org/bib/doc/
bf/2008_Yu_211368_1.pdf

10. “Biomechanical Properties of Human Cranium: Ageing Aspects“

¹Moskalenko Yu.E., ¹Weinstein G.B., ²Halvorson P., ¹Kravchenko
N.I., ¹Ryabchikova N. A.,
²Feilding A., ¹Semernia V.N., ¹Panov A.A.
¹Sechenov Institute of Evolutionary Physiology and Biochemistry
Russian Acad.Sci., St.Petersburg, Russia and ²Beckley Foundation,
Oxford, U.K.
Journal of Evolutionary Biochemistry and Physiology, 2008. Vol. 44,
No. 5, pp. 605-614.
http://www.beckleyfoundation.org/pdf/JEBP-2008-5.pdf

11. "Dynamic evaluation of functional condition of the mechanism

promoting the circulatory-metabolic support of human brain ac-
tivity.”
¹Moskalenko Yu., ¹Weinstein G., ²Riabchikova N., ¹Kravchenko T.,
³Feilding A., ³Halvorson P.
¹Sechenov Institute of Evolutionary Physiology and Biochemistry
Russian Acad. Sci., St.Petersburg, Russia; ²Moscow State Univer-
sity, Moscow, Russia; ³Beckley Foundation, Oxford, UK.
Proc. of the 5th International Conference “Development and apply-
ing of high technologies in science, industry and education”. St.
Petersburg, Russia, 2008. Vol.12, p.363-367.
http://www.beckleyfoundation.org/bib/doc/

97
12. "Liquorodynamic and hemodynamic effects of cranial trepanation.”
¹Moskalenko Yu., ¹Weinstein G., ¹Kravchenko T., ²Mozhaev S., Riab-
chikova N., ³Feilding A., ³Halvorson P., ¹Semernia V., ¹Panov A., ²Med-
vedev S.
¹Sechenov Institute of Evolutionary Physiology and Biochemistry Rus-
sian Acad.Sci., St.Petersburg, Russia; ²Institute of the Human Brain
Russian Acad.Sci., St. Petersburg, Russia; and ³Beckley Foundation,
Oxford, U.K.
Proc. of the All-Russian Conference “The Prof. A.L.Polenov Readings -
2008”. St.Petersburg, Russia. 2008. p.62-63.
http://www.beckleyfoundation.org/bib/doc/
bf/2008_AUTHOR_211480_1.pdf

13. “Relation of Age Cognitive Disorders with Cranial Compliance,

Cerebrospinal Fluid Mobility and Cerebral Circulation.”
¹Moskalenko Y., ¹Weinstein G., ³Feilding A., ³Halvorson P., ²Riab-
chikova N., ¹Kravchenko T., ¹Panov A., ¹Semernia V.
¹Sechenov Institute of Evolutionary Physiology and Biochemistry Rus-
sian Acad. Sci.,
St. Petersburg, Russia; ²Department of Biology Lomonosov State Uni-
versity, Moscow, Russia; ³Beckley Foundation, Oxford, UK.
(Proc. of the 14th World Congress of Psychophysiology “The Olympics
of the Brain”. St.Petersburg, 2008)
International Journal of Psychophysiology. 2008. v.69, No.3, p.307.
http://www.beckleyfoundation.org/pdf/
Age_cognitive_disorders_2008.pdf
doi:10.1016/j.ijpsycho.2008.05.312

14. “Effects of Cranial Trepanation on The Functioning of Cerebrovascu-

lar and Cerebrospinal Fluid Systems.”
Yu. Moskalenko¹, S. Mozhaev, G. Weinstein¹, T. Kravchenko, N. Riab-
chikova², N. Samus¹, A. Feilding³, P. Halvorson³, V. Semernia, A. Panov,
S. Medvedev.
¹Sechenov Institute of Evolutionary Physiology and Biochemistry Rus-
sian Acad.Sci., St.Petersburg, Russia; ²Institute of the Human Brain
Russian Acad.Sci., St. Petersburg, Russia; and ³Beckley Foundation,
Oxford, U.K.

(Proc. of the 14th World Congress of Psychophysiology “The Olym-

98
 pics of the Brain”. St.Petersburg, 2008)
International Journal of Psychophysiology. 2008. v.69, No.3,
p.302-303.
doi:10.1016/j.ijpsycho.2008.05.301

15. “The Role of Disturbances of Liquorodynamics and Cranial

Biomechanics in Neurosurgery”.
¹Moskalenko Y., ¹Weinstein G., ¹Semernia V., ¹Panov A., ²Riab-
chikova N., ¹Kravchenko T., ³Feilding A., ³Halvorson P.
¹Sechenov Institute of Evolutionary Physiology and Biochemis-
try Russian Acad. Sci.,
St. Petersburg, Russia; ²Department of Biology Lomonosov
State University, Moscow, Russia; ³Beckley Foundation, Oxford,
UK.
Proc. of the All-Russian Conference “The Prof. A.L.Polenov
Readings - 2009”. St.Petersburg, Russia. 2009. p. 224 - 225.

16. “Age peculiarities of relations between brain blood flow,

liquorodynamics and biomechanical properties of the skull”.
Yu. Moskalenko1, G. Weinstein1, N. Riabchicova2, T.
Kravchenko1, N. Samus5,P. Halvorson4, A. Feilding3, V. Semer-
nia1, A. Panov1.
1Sechenov Institute of Evolutionary Physiology and Biochemis-

try Russian Acad.Sci. (St.Petersburg, Russia); 2Moscow State

University (Moscow, Russia); 3Beckley Foundation (Oxford,
U.K.); 4ITAG (PA, USA), 5Hospital RAS, (St. Petersburg, Russia).
Proceedings of the 5th International Interdisciplinary Congress
“Neuroscience for Medicine and Psychology” (Sudak, Crimea,
Ukraine, June 3-13, 2009). Moscow. Max-Press. 2009. p.158.

99
 ACCEPTED FOR PUBLICATION IN 2009:

17. “Relation of CBF, CSF Mobility and Skull Mechanics to Cognitive

Brain Function in the Aged Persons”.

,¹Moskalenko Yu, ¹Weinstein G., ²Riabchikova N., ¹Kravchenko T.,

¹Samus N., ³Feilding A., ³Halvorson P., ¹Panov A.,. V. Semernia¹.
Sechenov Institute of Evolutionary Physiology and Biochemistry Rus-
sian Acad. Sci.,
St. Petersburg, Russia; ²Moscow State University, Moscow, Russia;
³Beckley Foundation, Oxford, UK.
Accepted for publication in:
Proceedings of the 19th IAGG World Congress of Gerontology and
Geriatrics. ( Paris, France. July 5-9, 2009).

18. “Age Relations of Cerebral Blood Flow, Cerebrospinal Fluid Mobility

and Cranial Compliance”.

¹Moskalenko Yu, ¹Weinstein G., ¹Kravchenko T., ¹Samus N., ²Riab-

chikova N., ¹Panov A., ¹Semernia V., ³Feilding A.³Halvorson P.
¹Sechenov Institute of Evolutionary Physiology and Biochemistry
Russian Acad. Sci.,
St. Petersburg, Russia; ²Moscow State University, Moscow, Russia;
³Beckley Foundation, Oxford, U.K.; 4Russian School of Osteopathic
Medicine, St. Petersburg, Russia.
Accepted for publication in: Proceedings of the 19th IAGG World
Congress of Gerontology and Geriatrics. (Paris, France. July 5-9,
2009).

100