Changes in phase-amplitude coupling caused by propofol anaesthesia

63 Pages·2016·1.09 MB·English

Aalto University
School of Science
Degree programme in Engineering Physics and Mathematics
Elmo Sokka
Changes in phase-amplitude coupling caused
by propofol anaesthesia
Master’s thesis
Helsinki, 18.01.2016
Supervisor: Academy Professor Riitta Salmelin
Aalto University
Instructor: Dr. Afra Wohlschläger
Technische Universität München

Preface
This thesis is the result of international collaboration, made possible by a
number of people both at Aalto University and at Technische Universität
München.
First I want to express my gratitude to my thesis instructor, Dr. Afra
Wohlschläger, for her guidance throughout the project. Along the way, she
has offered invaluable insights and kept pushing the project forward. She has
also promoted active discourse with many collaborators who have offered me
their advice. I especially want to thank Dr. Denis Jordan for his contributions
and his interest in my project.
I also want to thank my supervisor at Aalto, professor Riitta Salmelin,
for her comments and encouragement. I was first introduced to brain research
while working in professor Salmelin’s Imaging Language group, and I am
especially grateful to Dr. Jan Kujala for taking up my mentoring back then.
Moving abroad for an exchange has its challenges. I want to thank the
people coordinating international affairs at both Aalto and TUM, particularly
Mari Dagnall and Dalma Alagha, for making my thesis exchange possible.
Finally,Iwanttothankmyfamilyfortheirsupportthroughoutmystudies
and Helen for being my inspiration and my motivation.
Helsinki, 18.01.2016
Elmo Sokka
ii
Aalto University ABSTRACT OF
School of Science MASTER’S THESIS
Degree Program of Engineering Physics and Mathematics
Author: Elmo Sokka
Title of thesis: Changes in phase-amplitude coupling caused by propofol
anaesthesia
Date: 18.01.2016
Pages: 7+55
Major: Biomedical engineering
Code: F3001
Supervisor: Professor Riitta Salmelin
Instructor: Dr. Afra Wohlschläger
Anaesthesia studies provide an excellent opportunity to study the changes in brain
signals brought about by loss of consciousness. In this thesis I analyse EEG data in
the awake and propofol-anaesthetised states, attempting to characterise the changes
in phase-amplitude coupling. This organisation of neuronal oscillations has been pro-
posed to act as a mechanism for neuronal processes to integrate information between
different spatial and temporal scales. I pay special attention to avoiding the usual
pitfalls in this type of analysis in order to obtain meaningful results.
In accordance with previous research, a strong and highly synchronous frontal al-
pha rhythm is observed during propofol anaesthesia, replacing the occipital alpha
rhythm of the awake state. I show here for the first time that this new rhythm is
strongly linked to frontal gamma activity through phase-amplitude coupling. The
result raises questions about the fundamental roles of phase-amplitude coupling in
the functioning of the brain.
Keywords: Phase-amplitude coupling, Propofol-induced loss of
consciousness
Language: english
iii
Aalto-yliopisto DIPLOMITYÖN
Perustieteiden korkeakoulu ABSTRAKTI
Teknillisen fysiikan ja matematiikan opinto-ohjelma
Tekijä: Elmo Sokka
Diplomityön aihe:Propofol-anestesian aiheuttamat muutokset vaihe-
amplitudikytkennässä
Päiväys: 18.01.2016
Sivumäärä: 7+55
Pääaine: Lääketieteellinen tekniikka
Koodi: F3001
Valvoja: Professori Riitta Salmelin
Ohjaaja: Tohtori Afra Wohlschläger
Anestesiatutkimus tarjoaa erinomaisen mahdollisuuden tutkia tajunnan menetyk-
sen aiheuttamia muutoksia aivoissa. Tässä diplomityössä analysoin EEG-mittauksia
valveilla olon ja propofol-anestesian aikana ja pyrin kuvailemaan muutoksia vaihe-
amplitudikytkennässä. Tämäntyyppisen järjestymisen aivojen rytmisessä toimin-
nassa on esitetty yhdistävän tietoa eri aika-ja pituusskaaloilla tapahtuvien prosessien
välillä. Kiinnitän erityistä huomiota menetelmiin siten, että tulokset ovat mahdol-
lisimman mielekkäitä.
Kuten aiemmissa tutkimuksissa on havaittu, anestesian aikana frontaalialueille
ilmestyy vahva, synkronisoitunut alfa-rytmi. Tässä työssä osoitan ensimmäistä
kertaa, että tämä rytminen toiminta on yhteydessä frontaaliseen gamma-
aktiivisuuteen vaihe-amplitudikytkennän kautta. Tämä tulos kyseenalaistaa vaihe-
amplitudikytkennän oletetun merkityksen aivojen toiminnassa.
Avainsanat: Vaihe-amplitudikytkentä, Propofolin aiheuttama tajunnan
menetys
Kieli: englanti
iv
Contents
List of abbreviations vii
1 Introduction 1
2 Theoretical background 3
2.1 Anaesthesia and unconsciousness . . . . . . . . . . . . . . . . 3
2.2 Electroencephalography . . . . . . . . . . . . . . . . . . . . . 5
2.3 Oscillations and neuronal communication . . . . . . . . . . . . 6
2.4 Phase-amplitude coupling . . . . . . . . . . . . . . . . . . . . 8
2.5 Phase synchronisation . . . . . . . . . . . . . . . . . . . . . . 9
3 Methods 11
3.1 Study design . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
3.2 Data preprocessing . . . . . . . . . . . . . . . . . . . . . . . . 11
3.3 Spectral analysis . . . . . . . . . . . . . . . . . . . . . . . . . 13
3.4 Estimation of instantaneous phase and amplitude . . . . . . . 15
3.5 Measures of phase-amplitude coupling . . . . . . . . . . . . . . 17
3.6 Phase lag index . . . . . . . . . . . . . . . . . . . . . . . . . . 19
3.7 Statistics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
4 Empirically derived parameters 22
4.1 Selection of the PAC frequency bands . . . . . . . . . . . . . . 22
4.2 Time window length . . . . . . . . . . . . . . . . . . . . . . . 25
5 Results 28
5.1 Distribution of phase-amplitude coupling . . . . . . . . . . . . 28
5.2 Distribution of relative and absolute band power . . . . . . . . 29
5.3 Correlation between relative signal power and the modulation
index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
5.4 Statistically significant coupling . . . . . . . . . . . . . . . . . 37
5.5 Group statistics for phase-amplitude coupling . . . . . . . . . 38
5.6 Preferred phase . . . . . . . . . . . . . . . . . . . . . . . . . . 41
5.7 Coupling between channels . . . . . . . . . . . . . . . . . . . . 42
v
5.8 Phase synchronisation across the electrodes . . . . . . . . . . . 46
6 Discussion 49
7 Summary 51
References 52
vi
List of abbreviations
LFP Local field potential
EEG Electroencephalography
CFC Cross-frequency coupling
PAC Phase-amplitude coupling
RSN Resting-state network
CNS Central nervous system
fMRI Functional magnetic resonance imaging
DMN Default mode network
IIT Information integration theory
GABA Gamma-aminobutyric acid
PI-LOC Propofol-induced loss of consciousness
ECoG Electrocorticography
MEG Magnetoencephalography
PSP Postsynaptic potential
SG Synchronised gating
ICA Independent component analysis
FFT Fast Fourier transform
MI Modulation index
PLI Phase lag index
IAAFT Iterated amplitude-adjusted Fourier transform
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1 Introduction
General anaesthesia causes unresponsiveness and amnesia and is therefore
used to suppress patient consciousness during surgery. While anaesthesia has
for a long time served its purpose as a surgical aid, the mechanism by which
anaesthetics induce unconsiousness remains incompletely understood. How-
ever, as our knowledge of the brain increases and our research methods de-
velop, the mystery of anaesthesia is slowly unraveling. This could bring us
closer to an understanding of why we experience the unique and seemingly
inexplicable sensation that we call consciousness.
Neuronal ensembles oscillate at distinct frequencies. These oscillations are
thought to reflect various brain processes at different timescales. Oscillations
have been recorded from the level of local field potentials (LFP) in groups
of tens of thousands of neurons to the whole-brain level of the electroen-
cephalogram (EEG). It is generally assumed that oscillations reflect processes
that have significant roles in the functioning of the brain. These processes
are also likely to interact among themselves, which could be manifested as
cross-frequency coupling (CFC) between the oscillations.
CFC means that different frequencies influence each other. This has been
proposed [1] as a potential mechanism to transmit information across spatial
and temporal scales in the brain. CFC would therefore link together the fast
local processing in specialised brain regions and slower integration between
the regions [2].
How different frequencies could communicate is still open. One proposed
mechanism is phase-amplitude coupling (PAC), in which the phase of low
frequency oscillations modulates the amplitude of high frequency oscillations.
This type of CFC has already been observed in tasks requiring attentional
control [3]. PAC is also present in the inactive brain - there is even evidence
[1]thatthebrain’sresting-statenetworks(RSN)mayemergeasaconsequence
of PAC. PAC could therefore play a role in the integration of information in
the cortex.
As anaesthetics reduce integration of information in the cortex [4], PAC
couldbeaffectedifitinfactdoesactasamediatorofcorticalintegration.The
1
aim of this thesis is to find new information about how the loss of conscious-
ness affects PAC using the method described by Tort and others [5]. Special
attention is paid to avoid the common pitfalls of PAC analysis, following the
recommendations by Vicente and others [6].
2