1. FMRI – Week 1 – Introduction Scott Huettel, Duke University Welcome to the fMRI courses. Please sign in before taking your seat.

2. FMRI – Week 1 – Introduction Scott Huettel, Duke University An Introduction to Functional MRI FMRI Undergraduate Course (PSY 181F) FMRI Graduate Course (NBIO 381, PSY 362) Dr. Scott Huettel, Course Director

3. FMRI – Week 1 – Introduction Scott Huettel, Duke University Some Introductions: People Course Director (Both Courses): Scott Huettel Associate Professor, Psychiatry, BIAC, CCN Research Interests: Decision making, neuroeconomics Teaching Assistants (Undergraduate Course): Simon Davis Graduate Student, Psychology & Neuroscience Research Interests: Memory, neural connectivity Melissa Libertus Graduate Student, Psychology & Neuroscience Research Interests: Development of numerical cognition

4. FMRI – Week 1 – Introduction Scott Huettel, Duke University Some Introductions: Places Duke-UNC Brain Imaging & Analysis Center (BIAC) www.biac.duke.edu MRI Scanners (3T, 4T), Duke Hospital Offices and Analysis Laboratory, Bell Building

5. FMRI – Week 1 – Introduction Scott Huettel, Duke University Overview of the Course(s) Lectures –Wednesdays 3-4:30pm –Room: 3031 Purple Zone, Duke Clinics Readings –Functional Magnetic Resonance Imaging (Huettel, Song, McCarthy) –Original papers, posted to website Laboratories –Introduction: Wed. 4:30-5:30pm –Other times arranged with TAs Grading Basis –Attendance –Weekly laboratory exercises (group) –Short Quizzes –Mid-term examination –Project presentation (group) –Project final report (individual) UndergraduateGraduate Lectures –Wednesdays 3-4:30pm –Room: 3031 Purple Zone, Duke Clinics Readings –Functional Magnetic Resonance Imaging (Huettel, Song, McCarthy) –Original papers, posted to website Laboratories –Times arranged with TAs and instructor (group) Grading Basis –Attendance –Weekly laboratory exercises (group) –Self-assessment exercises –Mid-term examination –Project presentation (group) Course auditors are welcome to attend lectures!

6. FMRI – Week 1 – Introduction Scott Huettel, Duke University Course Textbook First edition (2004): Required –Available at bookstore Selected chapters from new edition (2008) will be provided by instructor Self-assessment questions available on accompanying CD –Graduates: Required –Undergrads: Highly recommended

7. FMRI – Week 1 – Introduction Scott Huettel, Duke University Each week has lecture and laboratory components Labs start next week and run from Thursday to Tuesday; TAs will schedule. We will introduce the analysis package FSL in a combined session in this room. The midterm for both classes is on 10/17. Different exams, same time. Auditors welcome to take it for fun. In late October, you will form small groups for your fMRI projects. We’ll go over the project phase of the course in great detail around then. The last undergraduate session is a panel discussion; it is optional for graduate students. More info about the project presentations forthcoming.

8. FMRI – Week 1 – Introduction Scott Huettel, Duke University Course logistics… or “What you need to do!” 1.Get a BIAC account and laboratory access –TAs need your name, DukeID, etc. –Gives you access to BIAC computer labs and servers 2.Arrange laboratory times with TAs –Undergrads: Give them your schedule, and they will coordinate the groups and laboratories –Graduates: Sort into groups of up to 4, pick a day and time, and then ask the TAs about availability –These times will also be used for data collection and analysis on your projects 3.Download course materials from the class website: http://www.biac.duke.edu/education/courses/fall07/fmri/ http://www.biac.duke.edu/education/courses/fall07/fmri/ (all materials will also be available on BlackBoard)

9. FMRI – Week 1 – Introduction Scott Huettel, Duke University Any questions?

10. FMRI – Week 1 – Introduction Scott Huettel, Duke University Outline for Today Lecture: Introducing fMRI –What is fMRI? –History –Key concepts –Parts of a MR scanner –MR safety Laboratory: Scanner Visit (Dr. Jim Voyvodic) –Scanner hardware –Stimulus presentation and recording hardware –Demonstration of real-time fMRI Note: I will post all slides to the course web page!

11. FMRI – Week 1 – Introduction Scott Huettel, Duke University 1. What is fMRI ?

12. FMRI – Week 1 – Introduction Scott Huettel, Duke University 1. What is fMRI ? isn’t

13. FMRI – Week 1 – Introduction Scott Huettel, Duke University fMRI is not bumpology

14. FMRI – Week 1 – Introduction Scott Huettel, Duke University Phrenology claimed that bumps on the skull reflected exaggerated functions/traits It lacked any mechanism underlying its claims. It used anecdotal, rather than scientific, evidence. Nevertheless, its central idea persisted: Localization of Function Franz Joseph Gall (1758-1828) Johann Spurzheim (1776-1832) from Gall (c. 1810)

15. FMRI – Week 1 – Introduction Scott Huettel, Duke University fMRI is not mind-reading This is not a thought.

16. FMRI – Week 1 – Introduction Scott Huettel, Duke University fMRI is not a window on the brain “Mirror neuron activity in the right posterior inferior frontal gyrus – indicating identification and empathy - while watching the Disney/NFL ad.” rIFG “Ventral striatum activity – indicating reward processing - while watching the Disney/NFL ad.” vent Str [Citations omitted to protect the offenders.]

17. FMRI – Week 1 – Introduction Scott Huettel, Duke University fMRI is not invasive Positron Emission Tomography (PET) Intracranial Stimulation / Recording

18. FMRI – Week 1 – Introduction Scott Huettel, Duke University FMRI is… a technique for measuring metabolic correlates of neuronal activity Uses a standard MRI scanner Acquires a series of images (numbers) Measures changes in blood oxygenation Use non-invasive, non-ionizing radiation Can be repeated many times; can be used for a wide range of subjects Combines good spatial and reasonable temporal resolution

19. FMRI – Week 1 – Introduction Scott Huettel, Duke University fMRI is a Measurement Technique… BRAINBEHAVIOR Measurement Techniques fMRI, PET, EEG Manipulation Techniques Lesions, TMS, Stimulation

20. FMRI – Week 1 – Introduction Scott Huettel, Duke University … that provides information about a wide range of topics. Cheng, Waggoner, & Tanaka (2001) NeuronBerns et al. (2006) Science From what we see… (ocular dominance columns) … to what we feel. (the dread of an upcoming shock)

21. FMRI – Week 1 – Introduction Scott Huettel, Duke University 2. History of fMRI

22. FMRI – Week 1 – Introduction Scott Huettel, Duke University Timeline of MR Imaging 192019301940195019601970198019902000 1924 - Pauli suggests that nuclear particles may have angular momentum (spin). 1937 – Rabi measures magnetic moment of nucleus. Coins “magnetic resonance”. 1944 – Rabi wins Nobel prize in Physics. 1946 – Purcell shows that matter absorbs energy at a resonant frequency. 1946 – Bloch demonstrates that nuclear precession can be measured in detector coils. 1952 – Purcell and Bloch share Nobel prize in Physics. 1972 – Damadian patents idea for large NMR scanner to detect malignant tissue. 1959 – Singer measures blood flow using NMR (in mice). 1973 – Lauterbur publishes method for generating images using NMR gradients. 1973 – Mansfield independently publishes gradient approach to MR. 1975 – Ernst develops 2D-Fourier transform for MR. NMR becomes MRI MRI scanners become clinically prevalent. 1990 – Ogawa and colleagues create functional images using endogenous, blood-oxygenation contrast. 1985 – Insurance reimbursements for MRI exams begin. MR

23. FMRI – Week 1 – Introduction Scott Huettel, Duke University Early Uses of NMR Most early NMR was used for chemical analysis –No medical applications 1971 – Damadian publishes and patents idea for using NMR to distinguish healthy and malignant tissues –“Tumor detection by nuclear magnetic resonance”, Science –Proposes using differences in relaxation times –No image formation method proposed 1973 – Lauterbur describes projection method for creating NMR images –Mansfield (1973) independently describes similar approach

24. FMRI – Week 1 – Introduction Scott Huettel, Duke University The First ZMR NMR Image Lauterbur, P.C. (1973). Image formation by induced local interaction: Examples employing nuclear magnetic resonance. Nature, 242, 190-191.

25. FMRI – Week 1 – Introduction Scott Huettel, Duke University Early Human MR Images (Damadian)

26. FMRI – Week 1 – Introduction Scott Huettel, Duke University Mink5 Image – Damadian (1977)

27. FMRI – Week 1 – Introduction Scott Huettel, Duke University Digression: 2003 Nobel Controversy Paul Lauterbur Peter Mansfield

28. FMRI – Week 1 – Introduction Scott Huettel, Duke University Raymond Damadian

29. FMRI – Week 1 – Introduction Scott Huettel, Duke University New York Times October 9, 2003

30. FMRI – Week 1 – Introduction Scott Huettel, Duke University Nobel Press Release October 6, 2003 Summary Imaging of human internal organs with exact and non-invasive methods is very important for medical diagnosis, treatment and follow-up. This year's Nobel Laureates in Physiology or Medicine have made seminal discoveries concerning the use of magnetic resonance to visualize different structures. These discoveries have led to the development of modern magnetic resonance imaging, MRI, which represents a breakthrough in medical diagnostics and research. … This year's Nobel Laureates in Physiology or Medicine are awarded for crucial achievements in the development of applications of medical importance. In the beginning of the 1970s, they made seminal discoveries concerning the development of the technique to visualize different structures. These findings provided the basis for the development of magnetic resonance into a useful imaging method. Paul Lauterbur discovered that introduction of gradients in the magnetic field made it possible to create two- dimensional images of structures that could not be visualized by other techniques. In 1973, he described how addition of gradient magnets to the main magnet made it possible to visualize a cross section of tubes with ordinary water surrounded by heavy water. No other imaging method can differentiate between ordinary and heavy water. Peter Mansfield utilized gradients in the magnetic field in order to more precisely show differences in the resonance. He showed how the detected signals rapidly and effectively could be analysed and transformed to an image. This was an essential step in order to obtain a practical method. Mansfield also showed how extremely rapid imaging could be achieved by very fast gradient variations (so called echo-planar scanning). This technique became useful in clinical practice a decade later.

31. FMRI – Week 1 – Introduction Scott Huettel, Duke University Timeline of MR Imaging 192019301940195019601970198019902000 1924 - Pauli suggests that nuclear particles may have angular momentum (spin). 1937 – Rabi measures magnetic moment of nucleus. Coins “magnetic resonance”. 1944 – Rabi wins Nobel prize in Physics. 1946 – Purcell shows that matter absorbs energy at a resonant frequency. 1946 – Bloch demonstrates that nuclear precession can be measured in detector coils. 1952 – Purcell and Bloch share Nobel prize in Physics. 1972 – Damadian patents idea for large NMR scanner to detect malignant tissue. 1959 – Singer measures blood flow using NMR (in mice). 1973 – Lauterbur publishes method for generating images using NMR gradients. 1973 – Mansfield independently publishes gradient approach to MR. 1975 – Ernst develops 2D-Fourier transform for MR. NMR becomes MRI MRI scanners become clinically prevalent. 1990 – Ogawa and colleagues create functional images using endogenous, blood-oxygenation contrast. 1985 – Insurance reimbursements for MRI exams begin. MRIf

32. FMRI – Week 1 – Introduction Scott Huettel, Duke University Physiology (BOLD Contrast) Blood-Oxygenation- Level Dependent contrast

33. FMRI – Week 1 – Introduction Scott Huettel, Duke University Using MRI to Study Brain Function Kwong, et al., 1992 Visual Cortex

34. FMRI – Week 1 – Introduction Scott Huettel, Duke University Growth in fMRI : Published Studies Medline search on “functional magnetic resonance”, “functional MRI”, and “fMRI”. Year 2004 = ~1500; Years 2005+ > 2000 …

35. FMRI – Week 1 – Introduction Scott Huettel, Duke University 3. Key Concepts

36. FMRI – Week 1 – Introduction Scott Huettel, Duke University Key Concepts Contrast Spatial Resolution Temporal Resolution Functional Resolution

37. FMRI – Week 1 – Introduction Scott Huettel, Duke University Contrast: Conceptual Overview

38. FMRI – Week 1 – Introduction Scott Huettel, Duke University Contrast: Anatomical Contrast: 1) An intensity difference between quantities: “How much?” 2) The quantity being measured: “What?” Contrast-to-noise: The magnitude of the intensity difference between quantities divided by the variability in their measurements.

39. FMRI – Week 1 – Introduction Scott Huettel, Duke University Contrast: Functional Contrast-to-noise is critical for fMRI: How effectively can we decide whether a given brain region has property X or property Y?

40. FMRI – Week 1 – Introduction Scott Huettel, Duke University Spatial Resolution: Voxels Voxel: A small rectangular prism that is the basic sampling unit of fMRI. Typical anatomical voxel: (1.5mm) 3. Typical functional voxel: (4mm) 3.

41. FMRI – Week 1 – Introduction Scott Huettel, Duke University Spatial Resolution: Examples ~8mm 2 ~4mm 2 ~2mm 2 ~1.5mm 2 ~1mm 2

42. FMRI – Week 1 – Introduction Scott Huettel, Duke University Temporal Resolution Determining factors –Sampling rate, usually repetition time (TR) –Dependent variable, usually BOLD response BOLD response is sluggish, taking 2-3 seconds to rise above baseline and 4-6 seconds to peak –Experimental design Most FMRI studies have temporal resolution on the order of a few seconds –With specialized designs and data acquisition, this can be improved to ~100ms

43. FMRI – Week 1 – Introduction Scott Huettel, Duke University

45. Functional Resolution The ability of a measurement technique to identify the relation between underlying neuronal activity and a cognitive or behavioral phenomenon. Functional resolution is limited both by the intrinsic properties of our brain measure and by our ability to manipulate the experimental design to allow variation in the phenomenon of interest.

46. FMRI – Week 1 – Introduction Scott Huettel, Duke University 4. MRI Scanners

47. FMRI – Week 1 – Introduction Scott Huettel, Duke University GE 3T Scanner (cf. BIAC’s)

48. FMRI – Week 1 – Introduction Scott Huettel, Duke University Siemens 3T Scanner Phillips 3T Scanner (Vanderbilt) Phillips 0.6T Open Scanner FONAR 0.6T MR Operating Room

49. FMRI – Week 1 – Introduction Scott Huettel, Duke University Main Components of a Scanner 1.Magnetic: Static Magnetic Field Coils 2.Resonance: Radiofrequency Coil 3.Imaging: Gradient Field Coils Shimming Coils Data transfer and storage computers Physiological monitoring, stimulus display, and behavioral recording hardware

50. FMRI – Week 1 – Introduction Scott Huettel, Duke University 1. Magnetic: Static Field Coils The scanner contains large parallel coilings of wires. These generate the main magnetic field (B 0 ), which gives the scanner its field strength (e.g., 3T).

51. FMRI – Week 1 – Introduction Scott Huettel, Duke University Surface CoilVolume Coil 2. Resonance: Radiofrequency Coils Electronic coils tuned to radio signals send energy into the brain and record an emitted “echo”.

52. FMRI – Week 1 – Introduction Scott Huettel, Duke University 3. Imaging: Gradient Coils Three gradient coils are used, one in each of the cardinal directions. These allow spatial encoding of the MR signal.

53. FMRI – Week 1 – Introduction Scott Huettel, Duke University The scanner is controlled by a pulse sequence.

54. FMRI – Week 1 – Introduction Scott Huettel, Duke University Pulse Sequences Recipes for controlling scanner hardware Allow MR to be extremely flexible T1T1 T2T2

55. FMRI – Week 1 – Introduction Scott Huettel, Duke University 5. MRI Safety

56. FMRI – Week 1 – Introduction Scott Huettel, Duke University Hospital Nightmare Boy, 6, Killed in Freak MRI Accident July 31, 2001 — A 6-year-old boy died after undergoing an MRI exam at a New York-area hospital when the machine's powerful magnetic field jerked a metal oxygen tank across the room, crushing the child's head. … ABCNews.com

57. FMRI – Week 1 – Introduction Scott Huettel, Duke University MR Incidents Pacemaker malfunctions leading to death –At least 5 as of 1998 (Schenck, JMRI, 2001) –E.g., in 2000 an elderly man died in Australia after being twice asked if he had a pacemaker Blinding due to movements of metal in the eye –At least two incidents (1985, 1990) Dislodgment of aneurysm clip (1992) Projectile injuries (most common incident type) –Injuries (e.g., cranial fractures) from oxygen canister (1991, 2001) –Scissors hit patient in head, causing wounds (1993) Gun pulled out of policeman’s hand, hitting wall and firing –Rochester, NY (2000)

58. FMRI – Week 1 – Introduction Scott Huettel, Duke University Issues in MR Safety Known acute risks –Projectiles, rapid field changes, RF heating, claustrophobia, acoustic noise, etc. Potential acute/chronic risks –Current induction in tissue at high fields? –Changes in the developing brain? Epidemiological studies of chronic risks –Extended exposure to magnetic fields does not cause harm Difficulty in assessing subjective experience –In one study, 45% of subjects exposed to a 4T scanner reported unusual sensations (Erhard et al., 1995)

59. FMRI – Week 1 – Introduction Scott Huettel, Duke University Projectile Effects: External “Large ferromagnetic objects that were reported as having been drawn into the MR equipment include a defibrillator, a wheelchair, a respirator, ankle weights, an IV pole, a tool box, sand bags containing metal filings, a vacuum cleaner, and mop buckets.” -Chaljub et al., (2001) AJR Chaljub (2001) Schenck (1996) The Scanner is Never Off!

60. FMRI – Week 1 – Introduction Scott Huettel, Duke University

61. Any questions?

62. FMRI – Week 1 – Introduction Scott Huettel, Duke University BIAC Scanner Tour Dr. Jim Voyvodic will demonstrate real-time fMRI –We will see the 3T BIAC scanner in action –Go through the mock scanner You’ll go through low-field areas of the MR center –Anyone with pacemaker, other implanted metal (shunts, clips, etc.) should tell instructor –Fillings, piercings fine (for console room) –Please be considerate while walking through the hospital! We’ll travel in groups –Undergraduates: Go now with Simon Davis –Graduates: Go with Melissa Libertus momentarily –Auditors: Go with Scott Huettel, after the other groups

63. FMRI – Week 1 – Introduction Scott Huettel, Duke University

64. Timeline of MR Imaging 192019301940195019601970198019902000 1924 - Pauli suggests that nuclear particles may have angular momentum (spin). 1937 – Rabi measures magnetic moment of nucleus. Coins “magnetic resonance”. 1944 – Rabi wins Nobel prize in Physics. 1946 – Purcell shows that matter absorbs energy at a resonant frequency. 1946 – Bloch demonstrates that nuclear precession can be measured in detector coils. 1952 – Purcell and Bloch share Nobel prize in Physics. 1972 – Damadian patents idea for large NMR scanner to detect malignant tissue. 1959 – Singer measures blood flow using NMR (in mice). 1973 – Lauterbur publishes method for generating images using NMR gradients. 1973 – Mansfield independently publishes gradient approach to MR. 1975 – Ernst develops 2D-Fourier transform for MR. NMR becomes MRI MRI scanners become clinically prevalent. 1990 – Ogawa and colleagues create functional images using endogenous, blood-oxygenation contrast. 1985 – Insurance reimbursements for MRI exams begin.

65. FMRI – Week 1 – Introduction Scott Huettel, Duke University Rabi and the Measurement of the Nuclear Magnetic Moment (1937)

66. FMRI – Week 1 – Introduction Scott Huettel, Duke University Discovery of Nuclear Magnetic Resonance Absorption (1946) Bloch and Purcell independently discovered how to measure nuclear moment of bulk matter (1946) They showed that energy applied at a resonant frequency was absorbed by matter, and the re-emission could be measured in detector coils They shared the 1952 Nobel Prize in Physics Felix Bloch Edward Purcell

67. FMRI – Week 1 – Introduction Scott Huettel, Duke University Timeline of MR Imaging 192019301940195019601970198019902000 1924 - Pauli suggests that nuclear particles may have angular momentum (spin). 1937 – Rabi measures magnetic moment of nucleus. Coins “magnetic resonance”. 1944 – Rabi wins Nobel prize in Physics. 1946 – Purcell shows that matter absorbs energy at a resonant frequency. 1946 – Bloch demonstrates that nuclear precession can be measured in detector coils. 1952 – Purcell and Bloch share Nobel prize in Physics. 1972 – Damadian patents idea for large NMR scanner to detect malignant tissue. 1959 – Singer measures blood flow using NMR (in mice). 1973 – Lauterbur publishes method for generating images using NMR gradients. 1973 – Mansfield independently publishes gradient approach to MR. 1975 – Ernst develops 2D- Fourier transform for MR. NMR becomes MRI MRI scanners become clinically prevalent. 1990 – Ogawa and colleagues create functional images using endogenous, blood-oxygenation contrast. 1985 – Insurance reimbursements for MRI exams begin.