fMRI in Impaired Consciousness

7th May 2010

Christian SchwarzbauerAberdeen Biomedical Imaging Centre

Future diagnostic opportunities

and ethical challenges

Levels of consciousness

Adapted from Laureys (2007), Sci American

Psychosis ?

Hallucinations Delusions

Thought disorder

Example 1: fMRI in Schizophrenia

fMRI in SchizophreniaHallucination (Hearing voices) Acoustic stimulation

T. Dierks et al., Neuron 22, 615 1999.

S = Speech; R = Reversed speech; T = Pulsed tone

Ethical issuesThis study shows that hallucinations are ‘real’ from

the patients’ point of view (activation of primary auditory cortex)

Differentiation between hallucinations and real auditory input is:(i) not possible based on the actual perception(ii) may be possible by means of logical reasoning(e.g. ‘There is nobody in the room, so it must be a hallucination’)

Would it be ethically acceptable to use fMRI of hallucinations as evidence in support of mitigating circumstances in a court case?Assumption: fMRI reliably detects hallucinationsProblem: Detecting hallucinations in an fMRI experiment does not imply that the patient suffered from hallucinations at the time of the offence

Example 2: fMRI in Vegetative State

fMRI – Detecting awareness in the vegetative state

A. M. Owen et al., Science 313, 1402 (2006)

Communication scans

Is your father’s name Alexander?Yes response with the useof motor imagery

Vegetative state patient

Healthy control

Do you have any brothers?Yes response with the useof motor imagery

Monti et al, New England Journal of Medicine 362, 579-589 (2010)

Communication scans

Is your father’s name Thomas?No response with the useof spatial imagery

Vegetative state patient

Monti et al, New England Journal of Medicine 362, 579-589 (2010)

Healthy control

Do you have any sisters?No response with the useof spatial imagery

Ethical issues ‘The differential diagnosis of disorders of

consciousness is challenging. The rate of misdiagnosis is approximately 40%, and new methods are required to complement bedside testing...’

Communication scans: What if a patient expresses the wish to die?

Communication scans: fMRI response is a sufficient but not a necessary condition of consciousness (mathematical logic):fMRI response patient is conscious [true statement]fMRI response patient is conscious [not necessarily true]So the problem is: the fact that we see no fMRI response does not imply that the patient is unconscious

Monti et al, New England Journal of Medicine 362, 579-589 (2010)

Future diagnosticopportunities

Patient pathways following TBI

Brain death

Coma

Vegetative state

Minimally conscious state

Conscious state

Time

Level of consciousness

TBI

Diagnostic challenges Detection of level

of consciousnessPrediction of outcome

The Cambridge/Liege studyThe new england journal of medicine

10.1056/nejmoa0905370 nejm.org4

Table1.Characteristicsof thePatients.*

PatientNo. Location Age Sex

Diagnosison Admission

Causeof Disorder

IntervalsinceIctus

ResponseonMotor Imagery

Task

ResponseonSpatial Imagery

Taskyr mo

1 Cambridge 58 Male VS TBI 6.0 No No2 Cambridge 43 Female VS Anoxicbraininjury 50.0 No No3 Cambridge 41 Female VS TBI 10.0 No NA4 Cambridge 23 Female VS TBI 6.0 Yes Yes5 Cambridge 42 Male VS Anoxicbraininjury 8.0 No No6 Cambridge 46 Male VS TBI 2.0 Yes No7 Cambridge 52 Female VS Anoxicbraininjury,

encephalitis8.0 No NA

8 Cambridge 23 Male VS TBI 19.0 No No9 Cambridge 48 Female VS Anoxicbraininjury 18.0 No No10 Cambridge 34 Male VS TBI 13.0 No No11 Cambridge 35 Male VS Anoxicbrain injury 10.0 No No12 Cambridge 29 Male VS TBI 11.0 No No13 Cambridge 67 Male VS TBI 14.0 No No14 Cambridge 21 Male VS TBI 6.0 No No15 Cambridge 49 Male VS TBI 3.0 No NA16 Cambridge 56 Female VS Anoxicbrain injury 9.0 No No17 Liege 87 Male VS CVA <1.0 No No18 Liege 62 Male VS CVA 1.0 No No19 Liege 15 Male VS Anoxicbraininjury,

TBI20.5 No No

20 Liege 70 Female VS Meningitis 2.5 No No21 Liege 47 Male VS Anoxicbraininjury 18.8 No No22 Liege 22 Female VS TBI 30.2 Yes Yes23† Liege 22 Male VS TBI 60.8 Yes Yes24 Cambridge 23 Male MCS TBI 11.0 No No25 Cambridge 38 Female MCS TBI 3.0 No NA26 Cambridge 18 Male MCS TBI 8.0 No No27 Cambridge 26 Male MCS TBI 11.0 No NA28 Cambridge 64 Male MCS TBI 6.0 No No29 Cambridge 54 Female MCS Brain-stemstroke 5.0 No No30 Cambridge 29 Female MCS TBI 2.0 No NA31 Cambridge 19 Female MCS TBI 1.0 No No32 Cambridge 34 Male MCS TBI 52.0 No NA33 Cambridge 17 Male MCS TBI 7.0 No NA34 Cambridge 56 Male MCS Anoxicbrain injury 6.0 No No35 Cambridge 21 Male MCS TBI 51.0 No No36 Cambridge 53 Female MCS Anoxicbrain injury 13.0 No No37 Cambridge 36 Male MCS TBI 30.0 No NA38 Cambridge 25 Male MCS TBI 8.0 No No

Copyright © 2010 Massachusetts Medical Society. All rights reserved.Downloaded from www.nejm.org at TRIAL - UNIVERSITY OF ABERDEEN on February 9, 2010

Monti et al, New England Journal of Medicine 362, 579-589 (2010)

17%

83%

fMRI response

no fMRI response

Functional connectivity in the Default Network during resting state is preserved in a vegetative but not in a brain dead patient

Boly et al (2009), Human Brain Mapping 30:2393–2400

Functional connectivity: Default Network

Differences between minimally conscious patients and unconscious patients (vegetative state & coma):

Vanhaudenhuyse et al (2010), Brain 133; 161–171

Functional connectivity: Default Network

minimally conscious > unconscious

Main differences in posterior cingulate cortex / precuneus

Graph theoretical analysis of connectivity

Bullmore et al (2009), Neuroimage 47:1125

MRI Data

Parcellation

Signal decomposition

Pairwise association(e.g. correlation)

Thresholding

Display

Example of graph theoretical analysisAnaesthesia (unconscious) Control (conscious)

Schwarzbauer et al (2010), unpublished data

Future research and ethical implicationsResearch questionsWhat are the neuronal correlates of

consciousness? Is there a suitable biomarker?

(i) to identify level of consciousness(ii) to predict clinical outcome

Ethical implications It will be important to distinguish between direct

measures (e.g. fMRI communication scan) and indirect measures (e.g. network connectivity) of consciousness

Ethical decisions based on indirect measures will be considerably more challenging, but necessary (over 80% of vegetative state patients unresponsive to fMRI)

Thank youc.schwarzbauer@abdn.ac.uk