The document discusses brain imaging technologies such as MRI, fMRI, and emerging techniques. It describes how these methods can be used to image individual neurons, neuronal networks, and the whole brain. Examples are given of how fMRI has been used to study basic brain functions and diagnose neurological disorders. The document also suggests ways for non-experts to access and analyze brain imaging data through open access repositories and analysis tools.

1. Brain imaging for fun and profit Daniel Marcus, PhD Director, Neuroinformatics Research Group @ Washington University School of Medicine

2. Outline Brain imaging 101 Brain imaging & emerging technologies Brain imaging for hackers

3. 100 billion neurons in the human brain 100 trillion synapses in the human brain Neuron is the basic computational unit in the brain

4. Neurons are organized into circuits in the cerebral cortex

5. Neuron  Network  Whole brain

6. Brain imaging: single neuron Misgeld & Kerschensteiner, 2006 In vivo microscopy

7. Brain imaging: neuronal networks Livet, et al. Nature (2007) Transgenics & fluorescence microscopy

8. Brain imaging: whole brain Magnetic Resonance Imaging (MRI) Structural MRI Functional MRI Functional connectivity MRI Computed tomography (CT) Positron emission tomography (PET) EEG, MEG, MRS, SPECT, DTI,…

9. Structural MRI Essential in clinical care. Radiologists perform qualitative “lightbox” reads. Most psychiatric and neurological disorders are invisible to reading radiologists.

10. Aging of the brain 20s 80s with mild Alzheimer’s 80s aging gracefully http://www.oasis-brains.org

11. Brain volume declines with age Marcus et al., 2007

12. Advanced structural methods Van Essen et al., 2006 Csernansky et al., 2005

13. fMRI

14. fMRI depends on functional localization

15. The sad tale of Phineas Gage “ [P]ossessed a well-balanced mind, and was looked upon by those who knew him as a shrewd, smart businessman, very energetic and persistent” “ fitful, irreverent, indulging at times in the grossest profanity (which was not previously his custom), manifesting but little deference for his fellows, impatient of restraint or advice when it conflicts with his desires, at times pertinaciously obstinate, yet capricious and vacillating...” Harlow, J.M. (1868)

17. Natural History Museum, London

18. Another sad tale “ A preexisting strong interest in pornography dating back to adolescence ...” “ An increasing interest in pornography... acquired an expanding collection of pornographic magazines and increasingly frequented Internet pornography sites.” “ Much of this prurient material emphasized children and adolescents and was specifically targeted to purveyors of child pornography . He also solicited prostitution , which he had not previously done.” “ Despite his strong desire to avoid prison, he could not restrain himself from soliciting sexual favors from staff at the rehabilitation center. ” Burns and Swerdlow, 2003

19. Another sad tale

20. Anatomy of an fMRI study Buckner & Wheeler, 2001 Study Test (in scanner)

21. Anatomy of an fMRI study Buckner & Wheeler, 2001 - = Old New

22. Applications of fMRI Discovery of basic brain function Discovery of brain dysfunction in disease Evaluation of treatment efficacy Sketchy things

23. http://www.noliemri.com

24. “ This is your brain on politics”, NY Times, Nov. 11, 2007

25. Voters sense both peril and promise in party brands. Emotions about Hillary Clinton are mixed. The gender gap may be closing. Mitt Romney shows potential. In Rudy Giuliani versus Fred Thompson, the latter evokes more empathy. John Edwards has promise — and a problem. Barack Obama and John McCain have work to do.

27. Where are the language areas? Where are the motor areas?

29. With fMRI, patients must perform an action, which is unreliable in clinic.

30. Functional connectivity MRI (fcMRI) requires NO task. Highly reliable.

33. Functional connectivity MRI (fcMRI) requires NO task.

35. Emerging technology: quantitative radiology Patient visits doctor. Doctor orders fcMRI. fcMRI brain scan. Quantitative analysis Doctor receives report. Doctor makes dx. and plans treatment. Quantitative report provides diagnostic measures, guides treatment, assesses response.

36. Emerging technology: digital lab on the cloud Input: Raw MRI scans Output: Quantitative reports

37. Emerging technology: Patient-driven care Microsoft HealthVault

38. Google Health (prototype) Emerging technology: Patient-driven care

39. Brain imaging for hackers Get yourself some brain images Get yourself some brain analysis tools Discover something, invent something

40. Get your own brain scanned Buy a scanner and install it in your basement

41. Get your own brain scanned Buy a scanner and install it in your basement Inflict severe brain injury

42. Get your own brain scanned Buy a scanner and install it in your basement Inflict severe brain injury Volunteer for a study Contact local research centers Ask for your scans (“I’ve brought a blank CD with me. Will you please copy the DICOM files of my scans onto it?”)

43. Use open access data Neuron: Neuron Database @ Yale Sense Lab Gene expression: Allen Brain Atlas Structural MRI: Open Access Structural Imaging Series (OASIS), mBIRN Data Repository Functional MRI: fMRI Data Center, fBIRN Data Repository Functional connectivity MRI: Brainscape

44. oasis-brains.org

45. brainscape.org

46. Get yourself some tools Neuron  Network  Whole brain Genesis Neuron Slicer, Caret, AFNI, Freesurfer, SPM, FSL, ImageJ See also NITRC ( http:// www.nitrc.org / ) Ed Boyden, Thursday 11:50 “ Synthetic Neurobiology: Towards Engineering Brain Circuits for Health and Human Augmentation”

47. Some unsolved problems Automated brain extraction How many networks are in the brain Methods for distinguishing differences between populations Predicting disease and aptitude Data sharing Individual differences in performance (“gifted”, “savant”) Neuroethics “ Deidentifying” images Bridging the spatial divide Security and privacy Data mining

48. Start hacking.

49. Brain imaging: gene expression Lein et al. Nature (2007)

50. Veber den Kreislauf des Blutes in Menschlichen Gehirn (Concerning the circulation of the blood in the human brain) Verlag von Viet & Company: Leipzig, 1881 Functional Brain Imaging and Brain Blood Flow Angelo Mosso

51. Monday noon, September 23, 1878 From: Angelo Mosso (1881) Resting quietly Forearm Brain Arrow: room clock strikes 12 noon and of church bells heard Brain Forearm Arrow: Mosso asked Bertino if the Ave Maria should have been said Brain Forearm Arrow: “What is 8 x 12?” ω : response Brain Forearm

52. Michael Faraday 1845 Linus Pauling 1937 The Background & Basis of the BOLD Effect in fMRI Seiji Ogawa 1990 Room Air 100% Oxygen Room Air 100% Oxygen “ BOLD” Contrast

53. fMRI depends on blood oxygenation levels ∆ Blood Flow > ∆ Oxygen Consumption fMRI BOLD Signal Difference Image “ Rest” “ Activation”