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The neurology of consciousness:what can we learn from the vegetative state ?

Steven Laureys

Coma Science GroupCyclotron Research Centre& Neurology Dept.University of Liège, Belgium

www.comascience.org

Disorders of consciousness Behavioural evaluation Electrophysiology Neuroimaging Ethics & quality of life

Terry Schiavo °1963, vegetative 1990, † 2005

Overviewdisorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

www.comascience.org

Mind brain beliefs

Zeman 2005 in The Boundaries of Consciousness (Ed) Laureys

www.comascience.orgLaureys, Trends in Cognitive Sciences, 2005

Consciousness

Coma

GeneralAnesthesia

Locked-in syndrome

Minimally Conscious State

Vegetative state

ConsciousWakefulness

Drowsiness

Light sleep

Deep Sleep

LucidDreaming

REM Sleep

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Disorders of consciousness

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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Clinical entities

Laureys, Scientific American, 2007

PermanentMinimally Conscious

State

?

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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Clinical evaluation

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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Motor activity in brain death

Lazarus' sign in brain deathBueri et al Mov Disord. 2000, 15:583-6

residual spinal activity: • finger jerks• undulating toe flexion sign• triple flexion response• Lazarus sign• pronation-extension reflex• facial myokymia

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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Blink and you live

Laureys et al., Progress in Brain Research, 2005

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

Laureys et al., Progress in Brain Research, 2005

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Electrophysiology

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

www.comascience.orgSchnakers, Majerus and Laureys, Neuropsychological Rehabilitation, 2005

disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

EEG-BIS in comadisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

coma VS MCS recovery

Bis

pect

rali

ndex

Coma Recovery Score

Bis

pect

rali

ndex

www.comascience.orgLaureys, Perrin et al., Neurology, 2004

disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Cognitive evoked potentialsdisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

minimally conscious stateµV

0.0

-2.5

-5.0

-7.5

-10.0

2.5

5.0

7.5

10.0

OTHER NAMES

N1

ms100 300 500 800 1000 1300200 400 600 700 900 1100 1200 15001400

P3

OWN NAME

www.comascience.orgPerrin et al, Archives in Neurology, 2006

disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

P300 to given namedisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

n=4

n=5

n=5

n=6

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Neuroimaging

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

resting brain functionbrain activation studies

passive paradigmsactive paradigms

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Neuroimaging

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

www.comascience.orgLaureys, Owen & Schiff, Lancet Neurology, 2004 (sleep data from Pierre Maquet; anesthesia data from Mike Alkire)

disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Resting metabolismdisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Laureys, Maquet, Moonen, Encyclopedia of Neuroscience, 2007

Global metabolismdisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Laureys et al, New Encyclopedia of Neuroscience (Ed.) Larry Squire, in press

Regional changesdisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

n=60

www.comascience.orgRaichle & Snyder Neuroimage, in press

“default” resting statedisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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default activity predicts perceptiondisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

Boly et al, PNAS, Epub ahead of print

•default lateral fronto-parietal activity is high ⇒ stimuli will be perceived

•default medial parietal activity is high ⇒ stimuli will be missed

3 seconds before simulation:

www.comascience.orgLaureys et al., Lancet, 2000

disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Functional connectivitydisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

www.comascience.orgSchiff et al., Nature, 2007

disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Thalamic stimulationdisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

www.comascience.orgSchnakers et al, JNNP in press

Pharmacological stimulationdisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

amantadine amantadine

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Neuroimaging

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

resting brain functionbrain activation studies

passive paradigmsactive paradigms

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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Laureys, Nature Reviews Neuroscience, 2006

Vegetative is not brain deaddisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

www.comascience.orgLaureys et al., Neuroimage, 2002

disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

(n=15)

(n=15)

Cortical activationdisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

www.comascience.orgLaureys et al., Neuroimage, 2002

disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Disconnected S1disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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"…a (wo)men’s brain is a mystery...and even more so in this state."

Abla con Ella

Pedro Almodóvar

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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Do they hear anything?disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

Laureys et al., Brain, 2000Boly et al, Archives of Neurology, 2004

www.comascience.orgLaureys et al., Neurology, 2004

Emotional processingdisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

www.comascience.org

Neuroimaging

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

resting brain functionbrain activation studies

passive paradigmsactive paradigms

www.comascience.orgBoly et al, NeuroImage 36 (2007) 979-92

disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

TEN

NIS

NA

VIG

ATIO

NWhen thoughts become action

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Owen, Coleman, Boly, Davis, Laureys and Pickard, Science, 2006

Passive paradigmsdisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

www.comascience.orgOwen, Coleman, Boly, Davis, Laureys and Pickard, Science, 2006

disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Active paradigmsdisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

www.comascience.orgDi et al, Neurology, 2007

fMRI precedes the clinic vegetative minimally conscious

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

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Ethics &quality of life

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

www.comascience.orgLaureys et al., Progress in Brain Research, 2005

disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Locked-in syndrome (LIS)disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

www.comascience.orgLaureys et al., Progress in Brain Research, 2005

disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Quality of life in LISdisorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

Short Form-36n=17duration 6±4 y

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Conclusions

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

www.comascience.org

disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | methods, ethics & quality of life | perspectives

Laureys, Owen and Schiff, Lancet Neurology, 2005

Not all “coma”disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

NORMALCONSCIOUSNESS

AR

OU

SAL

AW

AR

ENES

SCOMA

AR

OU

SAL

AW

AR

ENES

S

VEGETATIVESTATE

AR

OU

SAL

AW

AR

ENES

S

MINIMALLYCONSCIOUS

STATE

AR

OU

SAL

AW

AR

ENES

S

LOCKED-INSYNDROME

AR

OU

SAL

AW

AR

ENES

S

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Take home

• Need for objective markers of consciousness in comatose states

• Vegetative state : disconnection syndrome with dysfunction of fronto-parietal network of “higher order” cortices (default network)

• Minimally conscious state : intact pain & emotional perception

• Locked-in syndrome : unexpected self-scored quality of life

• Much more research is needed

disorders of consciousness | behavioural evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

www.comascience.org

disorders of consciousness | clinical evaluation | electrophysiology | neuroimaging | ethics & quality of life | conclusion

www.comascience.org