Manuel Schabus*

Sleep and residual cognitive processing in disorders of consciousness

*Laboratory for Sleep and Consciousness Research,

Division of Physiological Psychology, University of Salzburg

Overview

I. Background - Sleep and Brain Plasticity

II. Disorders of Consciousness – Recent data Quest for neuronal markers for diagnosis and prognosis in (i)

sleep and (ii) waking

III. Summary & Discussion

I. Introduction to Sleep

Sleep spindle (12-15Hz burst) is the electrographic landmark for thetransition from waking to sleep with loss of perceptual awareness.

Mesial Prefrontal Cortex

0 5 10 15 20 25 30 35

-0.4

-0.2

0

0.2

0.4

Time (seconds)

Res

pons

e A

mpl

itude

(a.u

.)

0 5 10 15 20 25 30 35-0.2

-0.1

0

0.1

0.2

Time (seconds)

Res

pons

e A

mpl

itude

(a.u

.)

Hippocampus

Postcentral Gyrus

0 5 10 15 20 25 30 35-0.2

-0.15

-0.1

-0.05

0

0.05

0.1

0.15

0.2

0.25

Time (seconds)

Time (seconds)

Precentral Gyrus

0 5 10 15 20 25 30 35

-0.2

-0.1

0

0.1

0.2

Memory Related Areas

Schabus et al., PNAS, 2007Nishida & Walker, PLoS One, 2007

In the sleep laboratory…

Spin

dle

Act

ivity

(C3)

Fast Spindles (>13 Hz)

Spindles and General CognitiveAbilities

Control Night Learning Night

15

16

17

18

19

20

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.

•General CognitiveAbility („g“)measured with

Raven‘sAdvancedProgressive Matrices (APM)

HighMediumLow

APM Groups

Finding 2

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.

Alzheimer`s disease and spindle decrease

Finding 3

More pronounced fast spindles decrease in AD than matchedelderly controls.

�Even ipsilateraldeviations after hemispheric strokes(e.g., Gottselig et al., 2002)

Disorders of Consciousness

In cooperation with the

• Albert-Schweitzer-Klinik (OA Dr. Pichler, Graz)

• “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 componentsVEGETATIVE

STATE

MINIMALLYCONSCIOUS

STATE

AR

OU

SAL

AW

AR

EN

ESS

AR

OU

SAL

AW

AR

EN

ESS

-Behavioral assessment remains the gold standard to monitor level of consciousness in patients with DOC

-Therefore, high rate of misdiagnosis (41%, Schnakers et al., 2009) for the vegetative state (VS).

� AUDITORY FUNCTION SCALE4 - Consistent Movement to Command *3 - Reproducible Movement to Command *2 - Localization to Sound1 - Auditory Startle0 – None� VISUAL FUNCTION SCALE5 - Object Recognition *4 - Object Localization: Reaching *3 - Visual Pursuit *2 - Fixation *1 - Visual Startle0 – None� MOTOR FUNCTION SCALE6 - Functional Object Use !5 - Automatic Motor Response *4 - Object Manipulation *3 - Localization to Noxious Stimulation *2 - Flexion Withdrawal1 - Abnormal Posturing0 - None/Flaccid

Quest for diagnostic and prognostic markers...Ongoing Project

Motor Imagination & Linguistic Tasks

PSGSleep/Wake Cycles, Spindles… Own Name &

Linguistic Tasks

24 hoursCa. 15+10 min Ca. 25+15 min

„The opposite ofblack is white.“

Mdavister (VS without SWS, REM, Spindles, Circadian Rhythm) Aesser (MCS with SWS, REM, Spindles and high arousal index)

Coma-Sleep Results- CRC analysis -

� Complexity of sleep architecture appeared higher in MCS than VS. – Especially, REM sleep, sleep spindles and cortical

desynchronization arousals appear to differentiate.

More complex sleep architectureappears to be present in MCS (n=15)

as compared to VS (n=19) patients(Chi2 = 5.87, p = .053).

- Preliminary SBG analysis -

CRS-R (global score) isassociated with spindle intensity at central andfrontal recordings sites(e.g. C4, r32=.34, p<.05)

Coma-Sleep ResultsCRS-R x Sleep Spindles

Perrin, Schnakers, Schabus et al, Arch Neurol, 2006

Sequences of 8 equiprobable first names: the own name and 7 non familiar first names

Helmut Simon Patrick Hector Helmut Victor

Brain response to the patient’s first name

„Active“ EEG paradigm(extended analyses from Schnakers, Perrin, Schabus et al., 2008)

12 controls (CO)

13 minimallyconscious patients(MC)

8 vegetative statepatients (VS)

Event-related theta synchronisation to counted own vs. other names even in VS patients, yet delayed!!

Fellinger, Schnakers,..., & Schabus in revision

n.s.p <.001 p<.021

Fellinger,…& Schabus, (2011)

Theta (3.5-6.5Hz) phase locking

controls

MCS

VS

controls

MCS

VS

0 100 200 300 400 500 time [ms]

Own Name (ON)passive listening• residual activation of

frontal networks in MCS duringappearance of thesubject‘s own firstname

Target unfamiliar name(TUN)active counting

• residual activation of frontal networks in MCS patients whilecounting of an unfamiliar name

(Lechinger, ..& Schabus, in preparation)

Linguistic Paradigm - sentencecomprehension

Antonym sentence paradigmAuditory 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)

Antonym vs. unrelated sentence endings -Time-frequency differences

MCS patients showed upper-alpha (10-12Hz) ERD (0-400ms) 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

Lechinger...,& Schabus (submitted)

Theta, lower alpha and SMR responses

c) While SMR (12-15Hz) frequency desynchronizes incontrol subjects, MCS patients synchronize.

Lechinger...,& Schabus (submitted)

b) Lower alpha band (8-10Hz) desynchronization isstrongest in controls during video observation. Again asimilar response in MCS patients can be observed

a) Theta band (4-7Hz) activation. Note the strong evokedresponse in the early time window (0-500ms after videoonset) in controls, but also MCS patients.

Lower alpha + SMR topography

Strong desynchronization duringobservation of a motor behaviour�„Mirroring“

Occipital desynchronization in thelower alpha band �attention-modulated visual processing?

Central synchronization in theSMR band � integration ofsomatosenory information? (cf. Beta synchronization in imagery)

Lechinger...,& Schabus (submitted)Lower alpha band

(8-10Hz)SMR band(12-15Hz)

Overall Conclusion

� Residual cognitive processing in DOC can be identifiedusing EEG, which would be undetected using classicalbehavioral assesments (ethical relevance; diagnosis/prognosis)

� Sleep in DOC might be a potential tool to distinguish VS from MCS.

� Yet to-date very hard to do reliably statements on a singlesubject level…

Recent Joint COST PublicationsDemertzi, A., Schabus, M., Weilhart, K., Roehm, D., Bruno, M-A., & Laureys, S. (in press). Wachkoma: medizinische Grundlagen und neurowissenschaftliche Revolution. In R. J. Jox, G. D. Borasio, & K. Kühlmeyer (Hrsg.), Leben im Koma: Interdisziplinäre Perspektiven auf das Problemdes 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 time-frequency 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 consciousstate 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), 570-578.

Cologan, V., Schabus, M., LeDoux, D., Moonen, G., Maquet, P., & Laureys, S. (2010). Sleep in disorders of consciousness. Sleep Medicine Reviews, 14, 97-105

TeamLaboratory for Sleep and Consciousness

Research

Manuel Schabus Kerstin Hödlmoser

Dominik HeibHermann Griessenberger

Nicole ChwalaJulia Lechinger

Tina MöcklMarit Petzka

Sandra Riegler

Theresa StemesederChristoph Pelikan

THE END.