1. Sarah Keedy Aug. 22, 2014 Intro to Functional and Anatomical Brain MRI Research Seminar Series PLANNING MRI RESEARCH TO ADDRESS YOUR SCIENTIFIC QUESTION

2.  Thinking  Considering  Evaluating  Preparing  Consider all MRI options for your scientific question  fMRI task design  fMRI study design PLANNING

3.  Garbage in  garbage out  You are at risk of a poor MRI study if you are  Introverted  Unable to think things all the way through  You have one precious, expensive hour  Know how to use MRI analysis software before the study starts, or know someone who does  Task design feedback available in all packages  Check pilot/initial subjects’ data for expected effects  Check data as you acquire it for disastrous problems  Performance of task needs to be monitored too PLANNING: PRINCIPLES

4. Interested in how the brain conducts a mental activity?  Mental activity = perception, experiencing emotions, making a decision or judgment, etc.  Normal activity vs abnormal activity  Activity after an experimental manipulation or other intervention …fMRI is for you! (note you will always get a T1-weighted high resolution image for intersubject alignment) PLANNING: WHAT EXACTLY IS YOUR SCIENTIFIC QUESTION?

5. I nterested in brain integrity? Integrity = physical aspects of tissue and/or functional integrity  White/gray volume  Shape  Development …Structural techniques (volumetrics, morphometry, etc.) are for you!  Connectivity …DTI or task-based or resting state fMRI may be for you!  Brain tissue problems probably have functional impact …Consider fMRI: resting or task-based …or DTI…  COMBINATIONS ALLOWED and ENCOURAGED! PLANNING : WHAT EXACTLY IS YOUR SCIENTIFIC QUESTION?

6. Hypothesis: People have problematic anxiety because of their amygdala being dysfunctional Get high and low anxiety people and compare them on  Structure of amygdala  Overall size  Percent gray matter  Shape  Connectivity of amygdala  Resting State fMRI with amygdala as seed with rest of brain  DTI – integrity of white matter connections between amygdala and OFC  For both, may find both stronger and weaker connections  Function of amygdala during behavior  Task-based fMRI  Don’t forget the amygdala is part of functional networks EXAMPLE OF A BRAIN INTEGRITY QUESTION

7.  http://www.slideshare.net/rnja8c/fmri-study-design-9138161 http://www.slideshare.net/rnja8c/fmri-study-design-9138161 TASK DESIGN IN FMRI IS TRICKIEST

8.  Block design is great if sustained mental activity is of interest  but do not plan to contrast blocks occurring only 2 min. apart or more  consider making stimuli somewhat unpredictable, jittered, etc.  beware of habituation, boredom, etc.  Event related design  JITTER trial length or time between trials  Trials should consist of the simplest, shortest stimuli possible  Fine, you want numbers?  Aim for at least 30 trials per condition  Aim for a 4 sec (jittered) intertrial interval  Run it through an efficiency estimator  How long does that make your task? How robust do you think the signal will be? Don’t know? PILOT!  Time left in your hour? Get 5-6 min of resting state fMRI  Still have time?  Get DTI  Improve your MPRAGE (longer acquisition time) PRACTICAL SUGGESTIONS

9.  Simplify  Then simplify some more Example: A researcher developed a group therapy for schizophrenia patients that behaviorally enhances pathologically blunted responses to positive feedback. She wants to know what the neural mechanism is and whether change is sustained over time.  Design:  3 groups (example: schizophrenia, bipolar, healthy)  3 time points (before therapy, right after therapy, months after therapy)  Mental events of interest, each with two levels  Feedback, no feedback  Low frustration state (easy math), high frustration state (difficult math)  3x3x4 = an interaction you barely want to deal with in a behavioral study, let alone fMRI FMRI STUDY DESIGN

10.  ~30 people in each group  who lay still enough  who show up again/still qualify for the second scan  who perform similarly  To get N=90, you will need more than 90 people EXAMPLE: SAMPLE SIZE

11.  4s show a math equation  30 Easy trials, like “4 – 2”  30 Hard trials, like “213-154”  4s*60 trials = 4min  How much of each kind of feedback is expected for each type of trial?  Pilot behavioral data suggests  5% of easy trials will be answered incorrectly, so  30 trials with positive feedback  5 with negative – probably not enough to analyze!  50% of difficult trials will be answer incorrectly so  35 trials with positive feedback  35 trials with negative feedback  Main effect of task difficulty: SNR will be better for Difficult (60 trials vs 35  will you care?)  How will response occur?  Multiple choice button press?  Microphone?  Whatever, give people 4 more seconds for the response  Faster for easy, slower for difficult  Do you care about this mental event?  4s for each response * 60trials = 4 more min.  What about feedback? How long will it be?  Say it’s a 500ms auditory buzz for negative, ding for positive, each followed by 1.5s of silence and nothing on screen  100 2s feedbacks = 3:20  Is 1.5s long enough for the mental event of interest and effective intertrial interval???  Total task length: 11:20  Evaluation: On track but needs refinement THINKING THROUGH

12.  http://imaging.mrc-cbu.cam.ac.uk/imaging/DesignEfficiency INTERMEDIATE FMRI TASK DESIGN