Principles of Neuroimaging A

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Contents

[edit] General Information

[edit] Course Goals

The overall goal of this course, and of the NITP teaching program, is to give you a solid background in the concepts common to many types of neuroimaging, as well as a set of tools to think about and to analyze these images in the service of scientific hypothesis testing. My philosophy on this, is that there are ways of thinking about images that are shared across microscopy, positron emission tomography, EEG, X-ray, MRI and many others and that a good understanding of these will leave you prepared to take on not only the current armamentarium of imaging tools, but the newer methods that will arise during your careers.

[edit] Teaching Philosophy

At the graduate level, the courses are not about grades, but about learning at a professional level. I do not emphasize exams and papers except for 1) the institutional requirement that I have a means for evaluation and 2) because preparing for these tends to force one to think and consolidate information. Much more important, however, is your commitment to reading the material and participating in class. This means challenging the lecturers and students to be clear about concepts and to place their work in the broadest context possible.

Because the emphasis is on skills learning, as much as on content, I will prepare lectures and exercises on tools, including math, engineering and programming, that I hope will be useful to you for years into the future.

MATLAB will be required for the course. While I had tried in prior classes to allow students to use a variety of programming languages, I found that this made things complicated for everybody. Usually, the example data will be made available through the course web site and, in many cases, there will be matlab code associated with it, so that you can open the files and read the data. You can purchase student copies of MATLAB for $99 (which is a bargain, BTW). If, for some reason, this is a hardship, please let me know and I will make arrangements on your behalf. I will provide some basic training in the software, but you should go through the tutorials on your own.

I would like to collect some live example data during the course and will need volunteers willing to participate. If you would like to volunteer to have your brain studied, please contact me.

[edit] Further Reading

[edit] Instructor Information

Mark Cohen can be reached at mscohen@ucla.edu. Telephone is 310-980-7453.
Office hours will be after class on Mondays and Wednesdays in room C8-881 of the NPI.

[edit] Class List sign up

Class List

[edit] Catalog Course Description

Factors common to neuroimaging in multiple modalities including: Physiological Contrast mechanisms and Biophysics; Signal and Image processing, including transform approaches, Statistical Modeling and Inference, Time-Series Statistics, Detection Theory, Contrast Agents, Experimental Design, Modeling and Inference, Electrical Detection methods, Electroencephalography, Optical Methods, Microscopy.

[edit] Pre-Requisites

Functional Neuroanatomy (M292) and competence in 1) Integral calculus 2) Statistics 3) Electricity and Magnetism and 4) Computer Programming (any language). Waiver of some requirements may be possible by consent of the instructor.

[edit] Organizational notes

When sending mail about the course, please include the characters: NITP in the subject line somewhere, as that helps a great deal in file management. Thanks.

While most of the classes will be in lecture format, there will also be lab work in computing, electronics and image collection. It may be necessary to schedule these outside of standard class hours to accommodate the availability of the equipment we need.

[edit] Stats

A general philosophy of the course and of the NITP is that a sophisticated consumer of images uses these data as a test of a hypothesis. You will learn more about the instructor's feelings about truth by p-values, but it is important to have a good intuitive understanding of random processes, noise, reliability, estimation, etc... For this reason, stats comfort is a must.


Here are a few questions that you should be easily able to find the answers to:
Given a sample of student heights at UCLA in inches:

H("males") = [74, 71, 67, 69, 71, 70, 65, 67, 71, 68, 69, 66], and
H("females") = [62, 66, 68, 62, 65, 62, 63, 64]
  • What is the modal height of the males?
  • What is the difference in mean height between males and females?
  • Which of the following should be used to test if the average height of UCLA males and females differ significantly at "p"<0.01?
    1. Increase the number of females in the sample be eight, then perform a t-test on the means
    2. Continue collecting more data until the probability of a two-tailed t-test statistic comparing males and females is less tan 0.01.
    3. Collect the heights of "all" males and females at UCLA and then calculate the t--statistic to determine if the heights differ at the assigned probability level
    4. Collect height data from an age-matched sample in the surrounding community.
    5. Add to the sample until there are exactly 100 males and 100 females, and calculate if the heights differ by more than 1%.
    6. None of the above.
    7. All of the above

    [edit] Programming

    Formally, students are required to have a background in at least some programming language. The fact of the matter is that Neuroimaging is computationally intensive; programming is a basic skill for this work. I intend to prepare problem sets that will require programming to solve.
    This year, all of our programming will be done using MATLAB, purchase of which is a course requirement. The ASUCLA student store has the licenses for students at an incredibly discounted price of $99. You will not regret owning this.

    [edit] Mathematics

    Can you solve for y or \mathbf{Y} in these equations?
    y = \frac{d(e^x)}{dx}
    y = \int\sin x\,dx

    \mathbf{Y}=\left[\begin{array}{cc} 2 & 4\\ 5 & 7\end{array}\right]^{-1}
    If y = 3x2 + 6x + 2, what is \frac{d(e^x)}{dx}?
    If not, please let me know, and we will try to remedy things. In the meantime, there are a number of excellent online math tutorials. For matrices, may I suggest:

    These are all excellent free sources. Please feel free to suggest more.

    [edit] Functional Neuroanatomy

    A Functional Neuroanatomy study group exists under the direction of Nanthia Suthana (email). Please contact her with questions about how to get involved. You should know the major structures of the brain, such as the cortical gyri, and have a reasonable grasp of their known functions.

    [edit] Class Meetings

    Note: there is another room change!

    Class will meet from 2 to 4 pm on Mondays and Wednesdays. Our Monday classroom will be 78-215 and our Wednesday classroom will be 37-415, both in the NPI.

    [edit] Concepts and Teaching Plan

    We will start looking at a few papers that use images of various kinds to address neuroscientific questions. Here, you should be paying especial attention to how the images are used in a theoretical context. Did the investigator pose the question first then collect the data? What is the role of a posteriori interpretation (reverse inference)? What is assumed about the ground truth of the phenomena exposed by neuroimaging?

    After this, we will begin to look at the properties of neurons that might make them visible to our neuroimaging tools. We will consider signaling in neurons, its energetic costs, and the changes in the cellular milieu that are associated. We will begin to consider the optical properties of neurons and their size scale, and the chemical changes that are associated with neuroal activity. As best possible, I will try to incorporate neurogenetics here to consider cell identification and labeling.

    At the same time, we will start the practical work in MATLAB. If you are already MATLAB proficient, consider your assignment to include bringing the rest of the class up to speed as quickly as possible so that we can move on. As noted above, MATLAB will be used for our quantitative examples, but it is also a strong standard for image and numerical analysis in the sciences and a relatively easy programming language to use, with a pretty quick startup.

    We will start also, on developing the mathematical tools we will need to carry forward. In the digital age, we are dealing always with very large numbers of data points and are forced to deal with large sample sizes (at the very least, a large number of pixels) and we need means of quantitative summary. Our initial steps will be in very basic statistical concepts in anticipation of doing more and deeper work later.

    This will be followed by work on analytic math, building to transform theory. Depending on what I find out about your skills level in maths, we may start with some calculus review, or we may have to schedule one-on-one meetings to balance everyone’s background. The goal here is to develop a framework with which to understand what happens to the ground truth data we try to observe as it is filtered through our imaging tools. There are very powerful mathematical tools that can be applied here, particularly the field known as linear systems analysis that considers transfer functions and especially convolution. Each device we build or use can be analyzed, at least in part, within this framework. More importantly, for many classes of systems, the filtering they apply can be inverted – in some cases unblurring and recapturing much of the original data. Deconvolution is the general rubrick under which we will try to analyze this process.

    Mathematical transforms are, in general, ways to change the representation of equations into forms that are much easier to solve, or that offer additional insight into the underlying properties. We will look at a few transforms, particularly the LaPlace Transform and the Fourier Transform. The latter is simply a means of expressing and quantifying the frequencies contained in a signal. The maths for these includes a little bit of trigonometry and some basic calculus. By the time we start on these topics, you should make yourself responsible for knowing how to integrate sines and cosines, and reviewing properties of the natural logarithm, e. I will introduce, in class, the concepts and algebra of imaginary numbers, which we will need as well.

    The essential results of the Fourier transform find their way into literally every means we have of neuroimaging, the statistical processing of images, concepts of noise and a host of other applications in neuroscience. I truly believe, that although you may find this material difficult, you will be happy about knowing it for the rest of your career as a scientist, making it well worth the effort.

    Our first direct application of the analytic tools will be in the analysis and then creation of electrical circuits. We do this for several reasons. Unlike many real-world devices, electrical circuit elements: resistors, batteries, capacitors, inductors and operational amplifiers, act very much like their idealized representations, storing and converting energy in very predictable ways. The tools that have grown to analyze such circuit elements are very mature and quite powerful, making prediction of their behavior straightforward. For this reason, many real-world physics and imaging problems are modeled using electrical circuit elements where we can predict their input-output properties.

    The second reason for looking at electrical circuits is that they are present in more or less every lab instrument you are likely to use. Towards the end of the first quarter, we will build, in class, an EEG system based on your understanding of these devices. This will also give us an entrée into the important study of noise, which is present in any experiments. We will look at the many sources of noise in neuroimaging and experiments, and consider ways in which modeling the noise can help us to reduce it. Conversely, we will discuss ways in which we can study the characteristics of the noise in order to better understand either our devices, or the actual features of our images.

    We will cover principles of optics, emphasizing the issues of resolution, optical spectrum (frequency ranges), distortion and digital imaging. One way to think about the effects of lenses is as convolution filters (see above) that color the signal. Color, as used here, is a rather broad concept. The process of whitening the signal can be considered a deconvolution. Undoing the lens convolution is a way of removing the blur or distortion produced by a lens. As we go on, we will see this theme of convolution blurring and deconvolution sharpening applied to the many modalities used in modern neuroimaging. Similarly, statistical variance or noise can be reduced or at least better understood in this context, sharpening our statistical inferences and improving detection power.

    Our next foray will be into electroencephalography (EEG), which is a simply a measure of the differences in electrical voltage from point to point on the scalp or brain. In addition to looking at the biological basis of the EEG, we will build and test an EEG system in class and we will look at some software approaches to interpreting the EEG both as spatially-resolved (i.e., image) data and as cognitive/physiological signals.

    [edit] Assignments

    [edit] Weekly Reading and Blogging

    For our first meeting, we will look at:

    • "Can cognitive processes be inferred from neuroimaging data?" Poldrack, 2006
    • Making sense of neuroimaging in psychiatry

      [edit] Schedule

      [edit] Week 1: Orientation to Neuroimaging, Organizational, Neurons

      Wednesday 1/7/09

      Readings (for Wednesday and coming Monday)

      Answers to in-class pop quiz

      The chart below shows the number of people responding correctly to each of the nine questions in the pop quiz. Message: Don't panic

      Pop quiz results
      Pop quiz results

      MatrixSolutions

      [edit] Week 2

      I suggest very strongly that you start brush up on linear algebra during this week and the next. In particular, I would like you to have an understanding of :

      Matrices as solutions to linear equations - determinants and inverses
      Matrix multiplication

      For these, I strongly recommend the Hefferon text noted above.

      This would also be a good time to review your calculus fundamentals:

      Derivatives of Polynomials (based on the quiz results, it looks like most of you know this)
      Integrals of polynomials
      Basic trig + derivatives and integrals of sine and cosine functions

      When we start on the linear systems section, we will be using these fundamentals to develop the LaPlace and Fourier transforms, which involve the use of imaginary numbers. The math content for that section is largely contained in this link: Mathematical Tools.

      Please let me know by email oor other means if this material looks too difficult.

      [edit] Monday 1/12: Neurons (cont'd)

      Today we will continue the discussion of basic cellular energetics. If desired, we can review the pop quiz, for clarification of the answer sheet. We will start on a discussion of the general organization of the human brain, and the regional specialization of cortical areas.

      Suggested readings

      Washington University Programmed text in Neuroanatomy This is an excellent free resource
      These books, by Squire and by Kandel, are intended as full textbooks for neuroscience courses. I find both of them very readable If you want to get into more depth than we can cover in class, of if you feel that you would benefit from a review of neuroscience, I don't think you could do much better.
      Fundamental Neuroscience - Squire
      Principles of Neural Science - Kandel

      [edit] Wednesday 1/14

      Stats 101 We will consider the general problems of statistical inference, with a concentration on developing an intuitive understanding of statistical concepts. The first problem set for the course will be a matlab assignment. If you have not already done so, please make certain that you have the program available.

      Suggested reading

      Statsoft online text (free)
      The Cartoon Guide to Statistics - Gonick $17.95 new
      The latter teaches stats at what I feel to be the right level - developing intuitions about the kinds of questions that can be answered using stats and about the statistical tests and measures

      Slides (with notes) as presented in class

      [edit] Problem Set 1

      Problem set using in stats and MATLAB
      More practice with stats and MATLAB

      [edit] Week 3:

      [edit] Statistical Modeling and Inference in Neuroimaging - guest lecturer, Jeanette Mumford

      Dr. Mumford is one of the most talented and clear-thinking statisticians I have ever had the pleasure to work with. My experience is that she likes to make her lectures fully self-contained; The topic she has agreed to is fairly advanced, however, so I recommend strongly that you pay focussed careful attention. The slides posted here develop the key principles of matrix math - if you have not seen this however, you should look the content over in advance and let me know if you don't feel you can get the fundamentals in order before her lecture.

      [edit] Monday 1/19

      Campus Holiday - Martin Luther King Day

      [edit] Wednesday 1/21

      Part I Lecture slides: Statistical Modeling and Inference (pdf)

      [edit] Week 4:

      [edit] Monday 1/26

      Part II - Lecture slides: Statistical Modeling and Inference (pdf)

      [edit] Wednesday 1/28

      Transforms and the Convolution Theorem

      Required Reading - Mathematical Tools

      Please see MATLAB linearity demo

      If you are the type who sees beauty in mathematics, the Euler identity may be one of the most beautiful pieces of math in the world.

      [edit] Week 5:

      Monday 2/2

      Signal processing continued

      Example transform derivations
      The Convolution theorem
      Oddness (and Even-ness)

      Please see MATLAB demo of Fourier transforms and convolution

      Problem Set 3 is in two parts: Problem Set 3A and Problem Set 3B

      Wednesday 2/4
      Followup: The Fourier shift theorem

      Noise: It is what you don't want.

      Additive noise
      White Noise
      Boltzmann noise
      Colored Noise
      Gaussian Noise
      Coherent noise
      Sampling Errors
      Aliasing
      Quantization noise
      Spectral filtering

      Time allowing: Intro to Laplace

      [edit] Week 6:

      Monday 2/9

      TEACHING SLIDES on Circuits: Circuits 1 & 2 <- Revised 2-12-09

      Electrical circuits

      If you have not had any of this background, you might want to have a look at this handout, Electrical Circuits, in advance. There are near infinite numbers of resources on the web that cover similar material (nearly enough to inifinite that by the time you read all of them, there would be a whole new set.) I have recently come across a link to Online Books: All About Circuits IF you want practical hands-on knowledge about this material, my all-time favorite text is "Horowitz and Hill: The Art of Electronics." The latest edition, however, is dated 1989 and a new third edition is promised. I have therefore stopped short of recommending a purchase unless your need to make circuits is immediate. In this book, you will find an excellent education on the fundamental principles of electrical circuits and an incredible compendium of practical data, such as how to assemble circuit boards, how to make measurements, etc...)

      I found a nice intro lecture on charge, current and voltage.

      Wednesday 2/11

      Electrical Circuits, cont'd

      We will discuss:

      Gain
      Trasformers
      Rectifiers
      Active Elements
      Amplifiers
      Transistors
      Op Amps
      Op Amp Circuits
      Higher order filters

      [edit] Week 7:

      Monday 2/16 - President's Day UCLA holiday
      Wednesday 2/18

      Active electronics, cont'd Midterm assigned.

      [edit] Week 8:

      Monday 2/23

      Review session

      Wednesday 2/25

      Midterm due in class. Live EEG collection (I hope)

      [edit] Week 9:

      Monday 3/2

      Loose ends: In today's class I want to make sure that we have covered the necessary technical topics to begin the units on MRI and PET next quarter.

      Bandwidth and SNR
      Interpretation of FT space as phase
      Formal discussion of electricity and magnetism
      Line broadening
      Mixing and modulating
      Wednesday 3/4

      Alex Korb, Ian Cook - (slide handout): "Applications of EEG in Psychiatry"

      [edit] Week 10

      Monday 3/9

      Jonathan Wynn - EEG in Schizophrenia Research.

      Dr. Wynn has suggested looking at these two articles:

      Tallon-Baudry, C., & Bertrand, O. (1999). Oscillatory gamma activity in humans and its role in object representation. Trends in Cognitive Sciences, 3, 151- 162.

      Roach, B. J., & Mathalon, D. H. (2008). Event-related EEG time-frequency analysis: An overview of measures and an analysis of early gamma band phase locking in schizophrenia. Schizophrenia Bulletin, 34, 907-926.

      Wednesday 3/11

      Marc Nuwer - Clinical Applications of EEG

      [edit] Week 11:

      Monday 3/15
      Wednesday 3/18 - Final Exam
      Next Step: Principles of Neuroimaging B / functional MRI
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