Overview
I.
Background - Sleep and Brain Plasticity
II.
Disorders of Consciousness – Recent data
Sleep and residual cognitive processing in
disorders of consciousness

Manuel
Quest for neuronal markers for diagnosis and prognosis in (i)
sleep and (ii) waking
Schabus*
III. Summary & Discussion
*Laboratory for Sleep and Consciousness Research,
Division of Physiological Psychology, University of Salzburg
I. Introduction to Sleep
Memory Related Areas
Precentral Gyrus
Hippocampus
0.2
Response Amplitude (a.u.)
0.2
0.1
0.1
0
0
-0.1
-0.1
-0.2
-0.2
0
5
15
20
25
Time (seconds)
30
0
35
Mesial Prefrontal
Cortex
0.4
Response Amplitude (a.u.)
10
10
15
20
25
Time (seconds)
30
35
Postcentral Gyrus
0.25
0.2
0.2
0.15
0.1
0
0.05
0
-0.2
-0.05
-0.1
-0.4
Sleep spindle (12-15Hz burst) is the electrographic landmark for the
transition from waking to sleep with loss of perceptual awareness.
5
-0.15
0
5
10
15
20
25
Time (seconds)
30
35
-0.2 0
Nishida & Walker, PLoS One, 2007
5
10
15
20
25
Time (seconds)
30
35
Schabus et al., PNAS, 2007
Finding 2
Spindles and General Cognitive
Abilities
In the sleep laboratory…
Fast Spindles (>13 Hz)
Spindle Activity (C3)
•General
Cognitive
Ability („g“)
measured with
Raven‘s
Advanced
Progressive
Matrices (APM)
20
APM Groups
High
19
Medium
Low
18
17
16
15
Control Night
Learning Night
Schabus, M. et al. (2006). Sleep spindle-related activity in the human EEG and its relation to general cognitive and
learning abilities. European Journal of Neuroscience, 23(7), 1738-1746.
Finding 3
Alzheimer`s disease and spindle decrease
Disorders of Consciousness
More pronounced
fast spindles
decrease in AD
than matched
elderly controls.
Even ipsilateral
deviations after
hemispheric strokes
(e.g., Gottselig et al., 2002)
In cooperation with the
• Albert-Schweitzer-Klinik (OA Dr. Pichler, Graz)
Rauchs, G.*, Schabus, M.*, et al. (2008). Is there a link between sleep changes and memory in Alzheimer's disease?
Neuroreport, 19(11), 1159-1162.
• “Apalliker Care Unit” im Geratriezentrum am Wienerwald (Prim. Dr. Donis, Wien)
• Universitätsklinik für Neurologie, PMU (Prof. Dr. Trinka; PD Dr. Golaszewski; Dr. Kronbichler,
Salzburg)
Consciousness‘ 2 components
Mdavister
AWARENESS
MINIMALLY
CONSCIOUS
STATE
AROUSAL
AWARENESS
AROUSAL
VEGETATIVE
STATE
AUDITORY FUNCTION SCALE
4 - Consistent Movement to Command *
3 - Reproducible Movement to Command *
2 - Localization to Sound
1 - Auditory Startle
0 – None
VISUAL FUNCTION SCALE
5 - Object Recognition *
4 - Object Localization: Reaching *
3 - Visual Pursuit *
2 - Fixation *
Schnakers
et al.,
2009)
1 - Visual
Startle
0 – None
MOTOR FUNCTION SCALE
6 - Functional Object Use !
5 - Automatic Motor Response *
4 - Object Manipulation *
3 - Localization to Noxious Stimulation *
2 - Flexion Withdrawal
1 - Abnormal Posturing
0 - None/Flaccid
-Behavioral assessment remains the gold standard
to monitor level of consciousness in patients with
DOC
-Therefore, high rate of misdiagnosis (41%,
for the vegetative state (VS).
(VS without SWS, REM, Spindles, Circadian Rhythm)
Ongoing Project
Quest for diagnostic and prognostic markers...
Ca. 15+10 min
Motor Imagination &
Linguistic Tasks
24 hours
Ca. 25+15 min
PSG
Sleep/Wake Cycles, Spindles…
Own Name &
Linguistic Tasks
„The opposite of
black is white.“
Aesser
(MCS with SWS, REM, Spindles and high arousal index)
- Preliminary SBG analysis -
Coma-Sleep Results
- CRC analysis -
More complex sleep architecture
appears to be present in MCS (n=15)
as compared to VS (n=19) patients
Complexity of sleep architecture appeared higher in MCS
than VS.
(Chi2 = 5.87, p = .053).
– Especially, REM sleep, sleep spindles and cortical
desynchronization arousals appear to differentiate.
Coma-Sleep Results
CRS-R x Sleep Spindles
Brain response to the patient’s first name
Sequences of 8 equiprobable first names: the
own name and 7 non familiar first names
Helmut
Simon
Patrick
Hector
Helmut
Victor
CRS-R (global score) is
associated with spindle
intensity at central and
frontal recordings sites
(e.g. C4, r32=.34, p<.05)
Perrin, Schnakers, Schabus et al, Arch Neurol, 2006
Theta (3.5-6.5Hz) phase locking
„Active“ EEG paradigm
(extended analyses from Schnakers, Perrin, Schabus et al., 2008)
Own Name (ON)
controls
passive listening
12 controls (CO)
• residual activation of
frontal networks in
MCS during
appearance of the
subject‘s own first
name
13 minimally
conscious patients
(MC)
p <.001
p<.021
MCS
VS
n.s.
controls
8 vegetative state
patients (VS)
Fellinger, Schnakers,..., & Schabus in revision
Event-related theta synchronisation to counted own
vs. other names even in VS patients, yet delayed!!
Fellinger,…& Schabus, (2011)
Linguistic Paradigm - sentence
comprehension
Antonym sentence paradigm
Auditory presentation of 3 different word pairs embeded in
the sentence
„The opposite of X is Y“
20 x antonym pairs (e.g. black – white)
20 x pairs of related words (e.g. black – yellow)
20 x pairs of unrelated words (e.g. black – nice)
Schabus et al. (2011)
Target unfamiliar name
(TUN)
active counting
• residual activation of
frontal networks in
MCS patients while
counting of an
unfamiliar name
MCS
VS
(Lechinger, ..& Schabus, in preparation)
0
100
200
300
400
500
time [ms]
Antonym vs. unrelated sentence endings Time-frequency differences
MCS patients showed upperalpha (10-12Hz) ERD (0400ms) after the presentation
of the antonym Post-hoc
semantic integration rather
than predictive processing.
Controls revealed significant
upper alpha ERS (0-600ms) in
response to critical antonyms,
as well as a small alpha ERD
in response to the semantic
violation (unrelated words)
Schabus et al. (2011)
Observation and imagination of a simple
motor behaviour
Theta, lower alpha and SMR responses
a) Theta band (4-7Hz) activation. Note the strong evoked
response in the early time window (0-500ms after video
onset) in controls, but also MCS patients.
b) Lower alpha band (8-10Hz) desynchronization is
strongest in controls during video observation. Again a
similar response in MCS patients can be observed
c) While SMR (12-15Hz) frequency desynchronizes in
control subjects, MCS patients synchronize.
Lechinger...,& Schabus (submitted)
Lower alpha + SMR
topography
Strong desynchronization during
observation of a motor behaviour
„Mirroring“
Lechinger...,& Schabus (submitted)
Overall Conclusion
Residual cognitive processing in DOC can be identified
using EEG, which would be undetected using classical
behavioral assesments (ethical relevance; diagnosis/prognosis)
Occipital desynchronization in the
lower alpha band attentionmodulated visual processing?
Central synchronization in the
SMR band integration of
somatosenory information?
(cf. Beta synchronization in imagery)
Lower alpha band
(8-10Hz)
SMR band
(12-15Hz)
Lechinger...,& Schabus (submitted)
Sleep in DOC might be a potential tool to distinguish VS
from MCS.
Yet to-date very hard to do reliably statements on a single
subject level…
Recent Joint COST Publications
Demertzi, A., Schabus, M., Weilhart, K., Roehm, D., Bruno, M-A., & Laureys, S. (in press).
Team
Laboratory for Sleep and Consciousness
Research
Wachkoma: medizinische Grundlagen und neurowissenschaftliche Revolution. In R. J. Jox, G. D.
Borasio, & K. Kühlmeyer (Hrsg.), Leben im Koma: Interdisziplinäre Perspektiven auf das Problem
des Wachkomas. Stuttgart, Germany: W. Kohlhammer GmbH.
Fellinger, R., Klimesch, W., Schnakers, C., Perrin, F., Freunberger, R., Gruber, W., Laureys, S., &
Schabus, M. (2011). Cognitive processes in disorders of consciousness as revealed by EEG timefrequency analyses. Clinical Neurophysiology, 122(11), 2177-84.
Schabus, M., Pelikan, C., Chwala-Schlegel, N., Weilhart, K., Roehm, D., Donis, J., Michitsch, G.,
Pichler, G., Klimesch, W. (2011). Oscillatory brain activity in vegetative and minimally conscious
Manuel Schabus
Kerstin Hödlmoser
Dominik Heib
Hermann Griessenberger
Nicole Chwala
Julia Lechinger
state during a sentence comprehension task. Functional Neurology, 36(1), 31-36.
Vanhaudenhuyse, A., Demertzi, A., Schabus, M., Noirhomme, Q., Bredart, S., Boly, M., Phillips,
C., Soddu, A., Luxen, A., Moonen, G., & Laureys, S. (2011). Two distinct neuronal networks
mediate the awareness of environment and of self. Journal of Cognitive Neuroscience, 23(3), 570-
Tina Möckl
Marit Petzka
Sandra Riegler
578.
Cologan, V., Schabus, M., LeDoux, D., Moonen, G., Maquet, P., & Laureys, S. (2010). Sleep in
disorders of consciousness. Sleep Medicine Reviews, 14, 97-105
THE END.
Theresa Stemeseder
Christoph Pelikan