From Genetics to Neuroethics: Is Imaging “Visualizing” Human Thought?

1. From Genetics to Neuroethics:Is Imaging “Visualizing” Human Thought? Program in Neuroethics Stanford Center for Biomedical Ethics and Department of Pediatrics, Medical Genetics Stanford University Judy Illes, Ph.D. EMBO/EMBL Heidelberg, Germany November 2006

2. Outline • Definitions and key questions • Imaging capabilities and state of the art • Tackling some key questions • Conclusions

3. Neuroethics Adina Roskies, Neuron, 2002 • Ethics of neuroscience; neuroscience of ethics William Safire, The Dana Foundation, 2002: • “… the examination of what is right and wrong and good and bad about the treatment of, perfection of, or unwelcome invasion of and worrisome manipulation of the human brain […] It deals with our consciousness – our sense of self – and as such is central to our being.” Michael Gazzaniga, The Ethical Brain, 2005: • “… the examination of how we want to deal with the social issues of disease, normality, mortality, lifestyle, and the philosophy of living informed by our understanding of underlying brain mechanisms.” Judy Illes, Society for Neuroscience, 2006: • A discipline that aligns the exploration and discovery of neurobiological knowledge with human value systems.

4. Key Questions Does imaging visualize human thought? Why is neuroethics interested in the question of thought visualization? How does neuroethics interact with this question?

5. Outline • Definition and key questions • Imaging capabilities and the state of the art • Tackling the key questions • Conclusions

6. Frontier Neurotechnology

7. From Antiquity to Present

8. SOCIAL POLICY • Lie detection • Non-medical screening • Surveillance • Cognitive enhancement SELF • Responsibility • Free will • Consciousness • Reasoning Imaging Neurosciences CLINICAL PRACTICE • Diagnosis • Medical screening and prediction • Self referral • Safety • Technology transfer • Therapy • Image guided neurosurgery DISSEMINATION • Scientists as disseminators as well as citizens of scientific information • Self-referral (advertising and marketing) • Interfacing with the media and public • Data sharing • Training the next generation of neuroscientists Critical Pillars inNeuroethics Mapping the Field, The Dana Foundation, 2002; Illes et al., Neuroscience Imaging,2005

9. EEG: Electrical signals MEG: Current sources and sinks PET and SPECT:Blood flow and metabolic activity

10. HbO2 Hb arterial venous Functional MRI FunctionalBrain Anatomy Behavior Non-invasive, small clinical risk IncreasedNeuronalActivity IncreasedOxygenated Blood Flow Performa Task ActivationMap

11. The fMRI Experiment Stimulus A B A B A B A Response - = ”B" state images "A" state images Activation map Courtesy of Gary Glover, PhD

12. Trends in Research with fMRI Illes et al., Nat. Neuroscience, 2003

13. Trends in Research with fMRI

14. “The brain can’t lie: Brain scans reveal how you think and even how you might behave.” --The Guardian, 2003 Coverage of fMRI in theInternational Print Press # Year Racine, Bar-Ilan, Illes, fMRI in the Public Eye, NRN, 2005

15. Moral Judgement Emotional/Social Cognition Areas Posterior Cingulate/Precuneus Medial Frontal Cortex “Cognitive” Areas T Value Superior Temporal Sulcus 3 2 T Score % change MR signal Brain Activity 1 0 r = .20 Dorsolateral Prefrontal Cortex (PFC) -1 p = .24 L R Personal Moral Dilemmas Non-moral Dilemmas Impersonal Moral Dilemmas 3 Greene et al., Science, 2001 2 T Score 1 0 r = .71 -1 p < .002 30 40 50 Extraversion Score Rational Decision-making Personality Correlation with Extraversion Activation Mean Correlation Scatterplot Fear Happy Canli et al., Science, 2002 De Martino et al., Science, 2006

16. “Eventually we’ll be able to know a lot more about people through understanding more about how their brains work… This is a domain that offers enough that’s novel in the area of information about one’s own persona, that we ought to be thinking very seriously about it.” - Participant 201NS/M/AA

17. A Picture is Worth 100 Words: Disorders of Consciousness Control Patient Schiff et al., Neurology, 2005 Owen et al., Science 2006

18. “These results confirm that despite fulfilling the clinical criteria for a diagnosis of vegetative state, this patient retained the ability to understand spoken commands and to respond to them through her brain activity rather than through speech or movement. Moreover, her decision to cooperate with the authors by imagining particular tasks when asked to do so represents a clear act of intention.” Owen et al., Science, 2006

19. Structural Fetal MRI (Courtesy of D. Levine, BIDMC)

20. Anterior fＭＲＩ Left Right Image Data Posterior Rock Scissors Extraction of brain areas related to movement control Paper Brain activity measurement every second by fMRI Feature Vectors グー チョキ Pattern Extraction of Brain Activity Pattern Recognition パー Commands to Robot Robot hand moves Pattern recognition analysis Real-Time fMRI Decoding Courtesy of M. Kawato and Y. Kamitani, ATR Computational Neurosci. Labs and Masahiro Kumura, Honda Res. Inst., Japan

21. Outline • Definitions and key questions • Imaging capabilities and state of the art • Tackling the key questions • Conclusions

22. Does imaging visualize human thought?

23. Visualizing Human Thought No: Thought is a composite of cognitive functions involving - information processing, - the disposition of an individual to information, and - individual methods of integrating information into an internal schema and responding to it. Imaging does, however, visualize correlates of the cognitive functions that humans harness to create thought.

24. Why is neuroethics interested in the question of thought visualization?

25. “Far more than our genomes, our brains are us, collectively defining us as human, and individually marking out the special character of our personal capacities, emotions and convictions.” - Kennedy, Society for Neuroscience, 2003

26. Lessons from ELSI Genetics • Discrimination, stigma, coercion • Medical privacy • Secondary and extended uses of data • Distributive justice • Commercial potential • Public perception

27. Lessons from ELSI Genetics(cont’d) • Diagnostic potential • Predictive potential • Benefits for life planning • Incidental findings • Risks of false positives and negatives

28. ELSI Unique to Neuroimaging • Physiologic variability due to day-to-day variation in physiology, gender • Paradigmatic variability due to design issues (protocols for data acquisition, statistics for data interpretation) • Interpretative variability due to investigator-subject bias, values and culture True bridging of technique and technology. Imaging genomics may be one of most powerful new tools.

29. ELSI Unique to Neuroimaging(cont’d) • Decision and discovery in that brain is both the seat of ethical decision-making and the target of ethics discovery • Experienceof brain health and brain disease is different than the experience of health and disease of other organ systems • Chimeras • Tissue engineering

30. Source of Neuroethics Interest in Neuroimaging Unique neuro ethical, legal and social implications.

31. How does neuroethics interact with the question of thought visualization with imaging?

32. Interaction of Neuroethics and Neuroimaging • Identify pragmatic starting points for imaging and alternatives for resolution of difficult ethical challenges through a negotiated scientific-social process • Empower, not encumber the scientific process

33. Surrogate and bio markers Commercialization Incidental findings Stakeholder engagement Regen. Med., Mol. Imaging Integration Evaluation Discovery Ethics analysis Tools Discovery Ethics analysis Discovery/ Pre-discovery 2006 2001

34. A Research protocol anticipates incidental findings B IRB protocol & informed consent articulate plan for managing incidental findings Subject option to decline to be informed Incidental findings are managed Incidental findings are not managed C Research Study Incidental finding is detected All scans reviewed Principal Investigator or Designee Physician qualified to read scans D Incidental finding is evaluated Principal Investigator or Designee No action taken Incidental finding is communicated Research subject or surrogate is encouraged to initiate clinical follow-up Illes, Kirschen, Edwards, Stanford et al., SfN 2005 and based on Science 2006

35. Interaction of Neuroethics and Neuroimaging(cont’d) Proactively engage deliberation from multiple stakeholders at multiple junctures Improve science literacy and communication

36. Knowledge Cycle Engaged world press dedicated to a close partnership between science and journalism Scientists and scholars seeking standards of practice and a common voice and language Critical voice of caregivers, stakeholders, and the public in matters of neuroscience discovery

37. International Neuroethics

38. International Neuroethics Networkan arm of theNeuroethics Society To foster international collaboration in neuroethics through the identification of common priorities and joint funding opportunities.

39. Outline • Definitions and key questions • Imaging capabilities and the state-of-the-art • Tackling the key questions • Conclusions

41. Conclusions There are compelling reasons for anticipating neuroethical issues at the bench, at the bedside, and in the public domain.

42. Expanded Roles in Neuroscience and Neurotechnology Adapted from Illes, Racine, Kirschen, in Neuroethics: Defining the Issues in Theory, Practice and Policy, Oxford University Press, 2006

43. Draw upon history of bioethics, genetics and other disciplines to inform the unique challenges that are raised by the opportunity to study and probe the brain. Keep up with the pulse of neuroscience and pursue an ethically coherent agenda based on the needs of the neuroscience community and its interface with society. Bridge cultural, linguistic and disciplinary barriers Develop capacity on an internationally relevant scale. Develop research, resource and reference tools that are flexible, practical and useful. Roles for Neuroethicists

45. Acknowledgements Bruce Arnow Vivian Chin Mildred Cho Pamela S.-Desmond Ray De Vries Margaret Eaton Martha Farah Agnieszka Jaworska Gary Glover Mike Grecius Henry T. (Hank) Greely Katrina Karkazis Matthew P. Kirschen Sophia Lombera Allyson Mackey Gladys Maestre David Magnus Eric Racine Allyson Rosen Jennifer Singh Jane Stewart HFM Van der Loos Adri, Kiah Van der Loos RO1 Advisory Board Many others collaborators NIH RO1 #NS 045831 & #CSI 8-17-04 The National Science Foundation The Dana Foundation The Greenwall Foundation The Henry J. Kaiser Foundation The New York Academy of Sciences The Children’s Health Initiative at Stanford http://neuroethics.stanford.edu