Neuroimaging & Consciousness

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1 Neuroimaging & Consciousness Georgios ANTONOPOULOS PhD student Coma Science Group GIGA Consciousness University & University Hospital Liège, Belgium

2 Arousal & awareness Conscious Wakefulness Lucid Dreaming Locked-in syndrome Drowsiness REM Sleep St I-II Sleep Minimally Conscious St III-IV Sleep - command following MCS+ - non-reflex movements MCS- General Anesthesia Vegetative unresponsive wakefulness Coma = necessary but not sufficient Laureys, Trends in Cognitive Sciences, 2005 Laureys et al, Nature Clinical Medicine, 2008

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

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

5 Measuring consciousness Measuring brain activity Altered states of consciousness - Pathological: DoC - Pharmacological: anaesthesia - Physiological: hypnosis FDG-PET EEG high density MRI fmri EEG-TMS

6 Consciousness and global Brain energy usebrain function Laureys et al., Lancet Neurology, 2004

7 Global workspace of consciousness UNRESPONSIVE WAKEFULNESS / VEGETATIVE STATE ` MINIMALLY CONSCIOUS STATE Stender et al, J Cereb Blood Flow & Metab, 2015 Thibaut et al, J Rehabil Med, 2012

8 Consciousness and global brain function Consciousness global brain function Stender et al, Current Biology, 2016

9 Global workspace of consciousness Precuneus seems a critical hub Laureys, Trends in Cognitive Sciences, 2005

10 External & internal awareness INTERNAL or SELF AWARENESS EXTERNAL or SENSORY AWARENESS Vanhaudenhuyse, Demertzi et al, J Cogn Neursoci 2011

11 Resting fmri after coma Functional connectivity in "default network" MCS > VS/UWS locked-in syndrome Vanhaudenhuyse et al, Brain, 2010 Demertzi et al, Brain, 2015

12 Multi-modal imaging s fmri 35% clinical misdiagnosis 32% CRS-R misdiagnosis PET fmri 40% potential misdiagnosis Solution: Coma Recovery Scale Revised (CRS-R) Stender & Gosseries et al, Lancet, 2014

13 fmri-based communication Monti & Vanhaudenhuyse et al, New Eng J Med, 2010

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

15 Aphasia and consciousness VEGETATIVE/UNRESPONSIVE Bruno et al, J Neurology, 2011

16 Classifying resting fmri support vector machine classifier Demertzi, Antonopoulos et al, Brain, 2015

17 Pathological hyper-connectivity Di Perri et al, Lancet Neurol, 2016

18 Congruent PET & PCI results Quality of life Bodart et al, Neuroimage 2017

19 Consciousness thalamo-cortical thalamo-cortical reconnections in spontaneous recovery from vegetative / unresponsive wakefulness Laureys et al, Lancet 2000 thalamo-cortical stimulation induces recovery from minimally responsive state Schiff et al, Nature 2007

20 Consciousness thalamo-cortical thalamo-cortical reconnections in spontaneous recovery from vegetative / unresponsive wakefulness Transcranial direct current stimulation (tdcs) Laureys et al, Lancet 2000 Thibaut et al, Neurology 2014 & Brain Stim 2015, Thibaut et al, Brain Injury 2017 Cavaliere, Front Cell Neurosci 2016 Huang et al, Brain Stim 2017

21 Zolpidem treatment Thonnard et al, Funct Neurology, 2013 Chatelle et al, Front Hum Neurosci, 2014 Williams Schiff, Elife, 2013

22 Consciousness Neural correlates Diagnosis Treatment Ethics Amantadine treatment Schnakers et al J Neurol Neurosurg Psychiatry 2008 Giacino et al NEJM 2012

23 Pain in minimally conscious state Boly et al, Lancet Neurology, 2008

24 Conclusion 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

25 Contact:

26 PET & Machine Learning Quality of life What a machine can see? - Diagnosis - Brain Activity Patterns FDG-PET Automatic Classification Pipeline Preprocessing (spatial Normalization, Intensity Scaling)

27 Processing Challenges Quality of life - 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

28 Unresponsive Wakefulness Syndrome/Vegetative state (n=403) Non-Traumatic 100% Minimally conscious state (n=437) 100% Conscious MCS MCS 80% Conscious 80% UWS 60% 60% Dead Dead Dead Dead 40% 20% 40% 20% N=261 UWS UWS 0% % N= N=277 0% % 3 MCS 6 Conscious MCS 80% Conscious 80% Traumatic MCS MCS 60% 60% Dead Dead UWS 40% 40% Dead 20% N=142 UWS MCS 0% 1 3 Laureys et al, 2017 N=160 20% 0%

29 Pathological hyper-connectivity Hypo-connectivity in DOC Hyper-connectivity in DOC Di Perri et al, Neurology 2014

30 Predicting therapeutic response Thibaut et al, Brain Stimulation, 2015

31 End-of-life issues End-of-life issues 2,475 medical professionals North Central South Demertzi et al, J Neurology 2011

32 Functional MRI in resting state Jox, Bernat, Laureys, Racine, Lancet Neurology 2012

33 Should we trust the test? Credit : A Soddu

34 Near death experiences (n=190) Near death experiences (n=190) 99% positive 1% negative * 140 coma - anoxic (45) - traumatic (30) - other (65) 50 non-coma * * * * Charland et al, Front Hum Neurosci, 2014

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