neuroimaging & consciousnessneuroimaging & consciousness. laureys, trends in cognitive...

Georgios ANTONOPOULOS

PhD studentComa Science GroupGIGA ConsciousnessUniversity & University Hospital Liège, Belgium

Georgios.antonopoulos@ulg.ac.bewww.comascience.org

Neuroimaging & Consciousness

Laureys, Trends in Cognitive Sciences, 2005Laureys et al, Nature Clinical Medicine, 2008

Coma

General Anesthesia

Locked-in syndrome

Minimally Conscious

- command following MCS+- non-reflex movements MCS-

“Vegetative” unresponsive wakefulness

Conscious Wakefulness

Drowsiness

St I-II Sleep

St III-IV Sleep

LucidDreaming

REM Sleep

Consciousness | Neural correlates | Diagnosis | Treatment | Ethics

= necessary but not sufficient

Arousal & awareness

Boly et al, Ann NY Acad Sci, 2009Vanhaudenhuyse & Demertzi et al, J Cogn Neursoci, 2011

Measuring awarenessConsciousness | Neural correlates | Diagnosis | Treatment | Ethics

Boly et al, Ann NY Acad Sci, 2009Vanhaudenhuyse & Demertzi et al, J Cogn Neursoci, 2011

Measuring awarenessConsciousness | Neural correlates | Diagnosis | Treatment | Ethics

Measuring consciousness

EEG high density

FDG-PET

EEG-TMS

MRI fMRI

Consciousness | Neural correlates | Diagnosis | Treatment | Ethics

Measuring brain activity

Altered states of consciousness- Pathological: DoC- Pharmacological: anaesthesia- Physiological: hypnosis

Laureys et al., Lancet Neurology, 2004

Brain energy useConsciousness | Neural correlates | Diagnosis | Treatment | Ethics

Consciousness and global brain function

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Stender et al, J Cereb Blood Flow & Metab, 2015Thibaut et al, J Rehabil Med, 2012

Consciousness | Neural correlates | Diagnosis | Treatment | Ethics

“Global workspace” of consciousness

UNRESPONSIVE WAKEFULNESS / VEGETATIVE STATE

MINIMALLY CONSCIOUS STATE

Stender et al, Current Biology, 2016

Consciousness ≠ global brain function

Consciousness | Neural correlates | Diagnosis | Treatment | Ethics

Consciousness and global brain function

Laureys, Trends in Cognitive Sciences, 2005

“Global workspace” of consciousnessConsciousness | Neural correlates | Diagnosis | Treatment | Ethics

Precuneus seems a critical hub

Vanhaudenhuyse, Demertzi et al, J Cogn Neursoci 2011

EXTERNAL orSENSORY

AWARENESS

INTERNAL orSELF

AWARENESS

External & internal awarenessConsciousness | Neural correlates | Diagnosis | Treatment | Ethics

Vanhaudenhuyse et al, Brain, 2010Demertzi et al, Brain, 2015

Funct

ional

connec

tivi

tyin

"def

ault n

etw

ork

"

locked-insyndrome

MCS > VS/UWS

“Resting” fMRI after comaConsciousness | Neural correlates | Diagnosis | Treatment | Ethics

s fMRI

Stender & Gosseries et al, Lancet, 2014

PET

fMRI

35% clinical misdiagnosis

32% CRS-R misdiagnosis

Multi-modal imaging Consciousness | Neural correlates | Diagnosis | Treatment | Ethics

40% potential misdiagnosisSolution: Coma Recovery Scale Revised (CRS-R)

fMRI-based communication

Monti & Vanhaudenhuyse et al, New Eng J Med, 2010

Consciousness | Neural correlates | Diagnosis | Treatment | Ethics

Brain Computer Interfaces

Noirhomme et al NeuroImage 2015Lesenfants, Habbal et al J Neural Engineering 2014 Cruse et al Lancet, 2011, also see Goldfine et al, Lancet, 2013

Consciousness | Neural correlates | Diagnosis | Treatment | Ethics

Bruno et al, J Neurology, 2011

VEGETATIVE/UNRESPONSIVE

Aphasia and consciousnessConsciousness | Neural correlates | Diagnosis | Treatment | Ethics

Demertzi, Antonopoulos et al, Brain, 2015

support vector machine classifier

Classifying “resting” fMRIConsciousness | Neural correlates | Diagnosis | Treatment | Ethics

Di Perri et al, Lancet Neurol, 2016

Pathological hyper-connectivityConsciousness | Neural correlates | Diagnosis | Treatment | Ethics

Quality of life

Congruent PET & PCI resultsConsciousness | Neural correlates | Diagnosis | Treatment | Ethics

Bodart et al, Neuroimage 2017

Schiff et al, Nature 2007

thalamo-cortical stimulationinduces “recovery” from

minimally responsive state

Consciousness ≈ thalamo-cortical

thalamo-cortical “reconnections” in spontaneous recovery from

vegetative / unresponsive wakefulness

Laureys et al, Lancet 2000

Consciousness | Neural correlates | Diagnosis | Treatment | Ethics

thalamo-cortical “reconnections” in spontaneous recovery from

vegetative / unresponsive wakefulness

Laureys et al, Lancet 2000

Transcranial direct current stimulation (tDCS)

Thibaut et al, Neurology 2014 & Brain Stim 2015, Thibaut et al, Brain Injury 2017Cavaliere, Front Cell Neurosci 2016Huang et al, Brain Stim 2017

Consciousness ≈ thalamo-corticalConsciousness | Neural correlates | Diagnosis | Treatment | Ethics

Thonnard et al, Funct Neurology, 2013Chatelle et al, Front Hum Neurosci, 2014Williams… Schiff, Elife, 2013

Zolpidem treatmentConsciousness | Neural correlates | Diagnosis | Treatment | Ethics

Schnakers et al J Neurol Neurosurg Psychiatry 2008Giacino et al NEJM 2012

Amantadine treatmentConsciousness | Neural correlates | Diagnosis | Treatment |Ethics

Pain in minimally conscious stateConsciousness | Neural correlates | Diagnosis | Treatment | Ethics

Boly et al, Lancet Neurology, 2008

Human conscious awareness ≈ emergent property of collective critical neural network dynamics, involving a frontoparietal global workspace

Awareness can be subdivided into internal and external awareness supported by different networks

Diagnostic use ≈ 40% misdiagnosis multimodal imaging

Therapeutic use pain treatment / DBS thalamus / tDCS

ConclusionConsciousness | Neural correlates | Diagnosis | Treatment | Ethics

Contact:

coma@ulg.ac.be

Quality of life

PET & Machine LearningConsciousness | Neural correlates | Diagnosis | Treatment | Ethics

What a machine can “see”?- Diagnosis- Brain Activity Patterns

FDG-PET Automatic Classification

Pipeline → Preprocessing (spatial Normalization, Intensity Scaling)

Quality of life

Processing ChallengesConsciousness | Neural correlates | Diagnosis | Treatment | Ethics

- Very big deformation- No reference region can be selected

In squirrel Monkeys: No suitable cerebral reference region is available,

quantify brain receptors using muscle as reference region (Le Foll et al. 2007)

Antonopoulos et al, in progress…

Unresponsive WakefulnessSyndrome/Vegetative state (n=403)

Minimally conscious state (n=437)T

rau

mati

cN

on

-Tra

um

ati

c

UWS

Dead

Dead

MCS

MCS

MCS

Dead

Dead

MCS

MCS

1 3 6 12 240%

20%

40%

60%

80%

100%

N=142

1 3 6 12 240%

20%

40%

60%

80%

100%

N=261UWS

Dead

MCS

Conscious

UWS

Dead

Conscious

MCS

1 3 6 12 240%

20%

40%

60%

80%

100%

N=160MCS

Dead

UWS

Conscious

N=

0.01 3 6 12 240%

20%

40%

60%

80%

100%

N=277

Dead

MCS

UWS

Conscious

Laureys et al, 2017

Di Perri et al, Neurology 2014

Hypo-connectivity in DOC

Hyper-connectivity in DOC

Pathological hyper-connectivityConsciousness | Neural correlates | Diagnosis | Treatment | Ethics

Thibaut et al, Brain Stimulation, 2015

Predicting therapeutic responseConsciousness | Neural correlates | Diagnosis | Treatment | Ethics

End-of-life issues

Demertzi et al, J Neurology 2011

2,475 medical professionals

N o r t h

S o u t h

C e n t r a l

End-of-life issuesConsciousness | Neural correlates | Diagnosis | Treatment | Ethics

Functional MRI in “resting state”

Jox, Bernat, Laureys, Racine, Lancet Neurology 2012

Consciousness | Neural correlates | Diagnosis | Treatment | Ethics

Should we trust the test?

Credit : A Soddu

Consciousness | Neural correlates | Diagnosis | Treatment | Ethics

Near death experiences (n=190)

Charland et al, Front Hum Neurosci, 2014

99% positive1% negative

140 coma- anoxic (45)- traumatic (30)- other (65)50 non-coma

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Near death experiences (n=190) Consciousness | Neural correlates | Diagnosis | Treatment | Ethics