Advances in Cognitive Neuroscience

1. Advances in Cognitive Neuroscience fMRI Graduate Course November 10, 2004

2. Business • Panel discussion for second part of course • Class projects being scheduled • New entrance to MRI scanners • Tentative date for presentations: 12/8

3. Main Questions for You • Are we just new phrenologists? • How has fMRI been received by the media? • What is translational medicine? • Can fMRI be extended to animal research? • Haven’t we studied everything? • How can we overcome existing limitations?

4. Phrenology, causality, and the advance of science

7. What does a “blob” mean? • Change in BOLD signal, assumed to be associated with change in neuronal activity, assumed to be associated with task, assumed to be associated with cognition... • What about… • Epiphenomena • Networks of activity • Differences in timing (feedback) • Errors in your hypotheses • Invalid cognitive constructs

9. What happens when research gets out into the wild (i.e., the mass media)

11. Fun Group ExerciseTM

12. Example II: Investing and the Brain

13. Why does this happen? • Journalists have little scientific training • Scientists are used to incremental work • We do not speak at the “big picture” level • Audience expects a single story • Limitations of localization • “Seeing is believing”

15. What is translational medicine and why will we all be doing it?

16. TRANSLATIONAL RESEARCH GRANTS IN BEHAVIORAL SCIENCE The National Institute of Mental Health (NIMH) and the National Institute on Drug Abuse (NIDA) seek to encourage the development of collaborative partnerships between scientists who study basic behavioral processes and those who study the etiology, diagnosis, treatment, and prevention of mental and behavioral disorders (including drug abuse and addiction) and the delivery of services to those suffering from those disorders. Duke Cancer Center wins $9.8M grant Duke Comprehensive Cancer Center's Breast Cancer Research Program has captured a Specialized Programs of Research Excellence grant by the National Cancer Institute. SPOREs are organized at cancer centers around a specific type of cancer. Each project must involve both basic and clinical scientists, must include a population-based research component and must focus on translational research. Toronto Western Hospital Functional Brain Imaging Center The primary goal of the center has been to promote translational research in fMRI, i.e. to develop tools that have a direct clinical impact on patients.

17. “It has been nearly a year since the National Institutes of Health (NIH) made public its Roadmap, an attempt to define the institutes’ priorities to accelerate biomedical progress. One of the main themes of the Roadmap is the reengineering of the clinical research enterprise, placing a special emphasis on the need to promote translational research. … Several NIH institutes have embraced a precise definition of translational research: “the process of applying ideas, insights and discoveries generated through basic scientific inquiry to the treatment or prevention of human disease.” But is this definition what the biomedical community has in mind when preparing a grant proposal or writing a paper? … Approximately 44 percent of the more than 3,000 Nature Medicine readers who completed our survey subscribe to a definition similar to that of the NIH. But a significant 30 percent said that only those studies with direct clinical application should be regarded as translational research. Even though the NIH has been criticized for being overly pragmatic in their support of translational research, a large fraction of scientists seem to overlook the fact that the NIH definition refers to the process of translating basic insights into therapies and not to the clinical applications per se. At one end of the spectrum, 10 percent of respondents had never come across the term. At the other, less than 1 percent of scientists held a more elaborate view of translational research, incorporating an aspect that is missing from the NIH definition and that we regard as particularly important—the bidirectional interplay between the laboratory and the clinic. For this small fraction of researchers, translational research goes full circle from bench to bedside and back.” Editorial, Nature Medicine (9/2004)

19. Costs of a Translational Focus • Risks undermining basic science • De-emphasizes technique development • Rests on accurate predictions of need • Risks the creation of conflicts of interest • Frequently tied to proprietary advances • Human-subjects concerns • Risks devaluing the academic enterprise • Knowledge for the sake of… • Confounds academic and financial/health missions Cf. Sugarman & McKenna (2003)

20. If we already know what the neurons do, what can fMRI of animals possibly tell us?

25. This is great! We can run human fMRI to get spatial coverage and to validate our tasks in humans. We can run primate electrophysiology to provide gold-standard data from a specific brain region. We can run primate fMRI to validate the links between these techniques (or to collect more data…).

26. What challenges arise? • Simple decision-making experiment (Platt et al.) • Monkeys fixate upon a light (200-800ms). • Two lights appear to left and right of fixation (200-800ms). • The monkey shifted gaze to either target within 350ms • Fixating the target for 500ms resulted in juice. • One target was stable (e.g., 2ml) and one risky (e.g., .1 to 4ml) • Assignment of targets was consistent for a block of trials • Then, after a short interval (<1s) the next trial began • How could we do this using fMRI? • In monkeys? • In humans?

27. Haven’t we already studied everything (and called it working memory)?

30. A Simple Idea: Working Memory

32. Challenges for a Taxonomy of Cognition • How do we define cognitive processes? • What exactly does working memory mean? • How do we avoid reductive behaviorism? • How do we encourage redefinition? • What if our definitions do not “carve nature at the joints”? • How do we incorporate new results?

33. Will we bump into limits or break through them?

34. Ways to break limits • Improved ecological validity • Realistic stimuli • Meaningful rewards • Parametric designs • Relation to behavior, genetics

38. FMC pMFG aINS pMFG FMC aINS Huettel, Song, McCarthy, in prep

40. Panel Discussion