Synopsis
A presention on fMRI paradigm design for students and
researchers with no or limited experience in setting up BOLD fMRI studies in
terms of paradigm (task) designTarget audience
Students and researchers with no or limited experience in setting up BOLD fMRI studies in terms of paradigm (task) design Outcome/Objectives
After this presentation,
the audience will know (i) what BOLD fMRI can
and cannot tell you of brain activity,
(ii) how this is affected by the BOLD hemodynamic response function, (iii) what
paradigm design comprises in BOLD fMRI studies and why it is so important to
correctly design your experiment, and (iv) the different types of experimental
designs commonly used.
Purpose
FMRI
experiments generate 4-dimensional datasets, i.e. series of volumes acquired in
time. From these, we aim to extract specific patterns in time and space, to
ultimately reveal neuronal activity
information about the brain. To do this, first a pattern has to be brought into
the system, which is typically accomplished by presenting a subject with a task
(‘paradigm’). The aim of paradigm design is to choose and optimize a set of stimulus
types and their organization in time. The final design completely determines
the interpretation of the end result: statistical
activity (t-) maps.
Methods
The choice of
a paradigm depends on the objective of a study and your hypothesis. A very specific hypothesis (what brain
functions? which regions?, importance of timing?) greatly benefits the
interpretation of the end result. Important
to note is that the fMRI brain response is an relative measure and thus has no
meaning independent of the control condition. Therefore, to evaluate the
brain’s response to an experimental manipulation we will always, at least,
contrast one experimental condition
to a control condition. Conditions can be organized according to various
schemes, such as a subtraction, conjunction, factorial or parametric design,
and their timing (block, or
event-related design). The choice of a particular scheme and control condition
is one of the most difficult issues and will involve optimizing the scheme in
terms of validity (am I measuring what I thing I am measuring?), sensitivity (can I measure what I want to
measure?), and reliability (will my results be reproducible?). Lastly and most
importantly, your subjects should be able to perform the tasks with consistent
task performance (or find ways to measure/control for subject performance), especially
when comparting healthy subjects and patients.
Results
A carefully
designed experimental fMRI paradigm that maximises the validity, reliability, sensitivity,
and proper interpretation of the brain imaging results.
Discussion/Conclusion
The main goal of
paradigm design is to isolate the activity related to mental processes of
interest in a BOLD fMRI experiment. This depends above all on your hypothesis
and question. A wide variety of experimental design types can be employed with
identifiable pro and cons (block vs event-related, factorial, parametric etc.).
An optimal scheme can be estimated based both on the temporal features of the
invoked processes, and on the mathematical characteristics of the scheme in
terms of efficiency, time between stimuli, collinearity between conditions, and
degrees of freedom in the statistical analysis. As such, the statistical image
analysis plays a significant role in paradigm design. Many of the important
design issues can be dealt with before any fMRI scans are acquired, based on
prior knowledge and the ability to isolate and identify the processes of
interest (but also those that are hidden), technical constraints, mathematical
properties of the stimulus scheme, and subject performance (patients vs
controls).
Acknowledgements
Prof. dr. Nick Ramsey who provided me some of his previously presented course materials.
my email: j.c.w.siero@umcutrecht.nl
References
1) Worsley
and Friston. (1995). Analysis of fMRI time-series revisited - again. Neurolmage, 2(3):173 – 181
2) Friston
et al. (1996). The trouble with cognitive subtraction. NeuroImage,
4(2):97-104
3) Ramsey
et al. (2001). Combined analysis of language tasks in fMRI improves assessment
of hemispheric dominance for language functions in individual subjects.
Neurolmage, 13(4):717-733
4) Price
and Friston. (1997). Cognitive conjunction: a new approach to brain
activation experiments. NeuroImage. 5(4):261-270
5) Buckner
et al. (1996). Detection of cortical activation during averaged single
trials of a cognitive task using functional magnetic resonance imaging.
PNAS. 93(25): 14878-14883
6) d'Esposito
et al. (1999) Event-related functional MRI: implications for cognitive
psychology. Psychol. Bull. 125(1):155-164.
7) Price
and Friston. (1999) Scanning patients with tasks they can perform. Hum
Brain Mapp. 8(2):102-108
8) Ramsey
et al. (2002). Excessive recruitment of neural systems subserving logical reasoning in
schizophrenia. Brain. 125(8):1793-1807