fMRI Paradigm DesignHow do you design a BOLD/fMRI study?
Task-based BOLD/fMRI studies can be divided into three basic types: 1) block, 2) event-related, and 3) mixed.
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Block Designs
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Block designs are the oldest functional imaging paradigms, widely used for PET studies prior the invention of fMRI. Task periods (also known as epochs) are alternated with periods of rest. Lower BOLD signal during rest periods are digitally "subtracted" from higher BOLD signal during task states to reveal focal areas of cortical activation.
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Three designs of BOLD/fMRI experiments |
Finger tapping fMRI study using simple block design comparing signals during activity and at rest. Because the "on-off" pattern of activation resembles the passing of a train, the paradigm is often referred to as a "boxcar" design.
Block designs are the simplest and most straightforward paradigms to implement. They are most widely used for clinical fMRI studies whose purpose is to identify eloquent cortical areas prior to surgery. In the classic "finger tapping" experiment shown left and described in a separate Q&A, the patient taps her fingers for 15 seconds followed by an equal length period of rest. After correcting for noise and spatial distortions, areas whose net BOLD signals exceed certain statistical thresholds are said to be "activated".
Compared to other fMRI paradigms, block designs possess the highest signal-to-noise, statistical power, and maximal time efficiency. In addition to the simple "on-off" block design described above, more complex block designs are possible. For example, two or more activities can be alternated with each other and with periods of rest.
Notwithstanding these advantages, block designs have limited utility especially within the setting of more complex neuropsychological experiments involving non-binary tasks. Even with simple tasks, subjects can anticipate the order or duration of the simple blocks, introducing confounding variables. Finally, because blocks are measured over relatively long periods (10-20 sec), information about the hemodynamic response and fMRI signal timing are difficult to measure.
Event-related Designs
Event-related designs allow for single or multiple tasks and stimuli to take place at short and variable time intervals. These paradigms provide the high degree of flexibility required for sophisticated neuropsychological experiments. Events can be randomized and different types of events can be mixed. The subject cannot predict when or what will occur, allowing for surprises. Event-related designs allow for better temporal resolution and estimation of the hemodynamic response function (HRF) time course. It is possible to assess the "learning curve" and practice effects during an experiment, as well as the effect of the interstimulus interval.
Disadvantages of event-related designs include lower signal-to-noise and statistical power, with longer imaging times and more trials per subject required. Analysis of the data is significantly more complex and dependent on accurate modeling of the HRF. At the same time, post hoc analysis allows events to be resorted and reclassified after the study. For example, correct and incorrect responses can be separated and independently analyzed.
Disadvantages of event-related designs include lower signal-to-noise and statistical power, with longer imaging times and more trials per subject required. Analysis of the data is significantly more complex and dependent on accurate modeling of the HRF. At the same time, post hoc analysis allows events to be resorted and reclassified after the study. For example, correct and incorrect responses can be separated and independently analyzed.
Mixed Designs
Mixed paradigms embody features of blocked and event-related designs. Here, semirandomized events take place during the task blocks, with rest periods in between. Mixed paradigms thus tend to preserve the favorable signal-to-noise characteristics of blocked methods with the flexibility of even-related ones.
References
Amaro E Jr, Barker GJ. Study design in fMRI: basic principles. Brain Cognition 2006; 60:220-232.
Blamire AM, Ogawa S, Ugurbil K, et al. Dynamic mapping of the human visual cortex by high-speed magnetic resonance imaging. Proc Natl Acad Sci USA 1992; 89:11069–11073. (first demonstration of difference between long-duration/block and short-duration/event-related brain responses)
Buckner RL. Event-related fMRI and the hemodynamic response. Human Brain Mapping. 1998; 6:373–377. (shows linear response to multiple short-term stimuli)
Dale AM. Optimal experimental design for event-related fMRI. Hum Brain Mapping 1999; 8:109-114.
Huettel SA. Event-related fMRI in cognition. NeuroImage 2012; 62:1152–1156. (good review)
Liu TT, Frank LR, Wong EC, Buxton RB. Detection power, estimation efficiency, and predicability in event-related fMRI. NeuroImage 2001; 13:759-773.
Maus B, Van Breukelen GJP, Goebel R, Berger MPF. Optimization of blocked designs in fMRI studies. Psychometrika 2010; 75:373-390.
Price CJ, Veltman DJ, Ashburner J, Josephs O, Friston KJ. The critical relationship between the timing of stimulus presentation and data acquisition in blocked designs with fMRI. NeuroImage 1999; 10:36-44.
Stark CEL, Squire LR. When zero is not zero: the problem of ambiguous baseline conditions in fMRI. Proc Natl Acad Sci USA 2001; 98:12760-12766. (Shows that the brain is active during periods of rest, confounding both block and event-related design experiments).
Amaro E Jr, Barker GJ. Study design in fMRI: basic principles. Brain Cognition 2006; 60:220-232.
Blamire AM, Ogawa S, Ugurbil K, et al. Dynamic mapping of the human visual cortex by high-speed magnetic resonance imaging. Proc Natl Acad Sci USA 1992; 89:11069–11073. (first demonstration of difference between long-duration/block and short-duration/event-related brain responses)
Buckner RL. Event-related fMRI and the hemodynamic response. Human Brain Mapping. 1998; 6:373–377. (shows linear response to multiple short-term stimuli)
Dale AM. Optimal experimental design for event-related fMRI. Hum Brain Mapping 1999; 8:109-114.
Huettel SA. Event-related fMRI in cognition. NeuroImage 2012; 62:1152–1156. (good review)
Liu TT, Frank LR, Wong EC, Buxton RB. Detection power, estimation efficiency, and predicability in event-related fMRI. NeuroImage 2001; 13:759-773.
Maus B, Van Breukelen GJP, Goebel R, Berger MPF. Optimization of blocked designs in fMRI studies. Psychometrika 2010; 75:373-390.
Price CJ, Veltman DJ, Ashburner J, Josephs O, Friston KJ. The critical relationship between the timing of stimulus presentation and data acquisition in blocked designs with fMRI. NeuroImage 1999; 10:36-44.
Stark CEL, Squire LR. When zero is not zero: the problem of ambiguous baseline conditions in fMRI. Proc Natl Acad Sci USA 2001; 98:12760-12766. (Shows that the brain is active during periods of rest, confounding both block and event-related design experiments).
Related Questions
What is the best way to identify the motor cortex using fMRI?
Why do you have to do an "on-off" comparison? Why not just measure the absolute BOLD signal instead?
What is the best way to identify the motor cortex using fMRI?
Why do you have to do an "on-off" comparison? Why not just measure the absolute BOLD signal instead?