When zero is not zero: The problem of ambiguous baseline conditions in fMRI Stark & Squire (2001) By Mike Toulis November 12, 2002

OR Does rest really mean rest?

Objective: Determine if condition of rest is always an appropriate baseline in fMRI studies Determine if alternative baseline conditions could be more appropriate

Design Used both block and rapid event-related studies to examine 6 memory-encoding tasks along with a rest condition Participants Participants were the same for both studies: 3 men, 5 women; mean age of 27.6 yrs (range 24 – 31 yrs)

Tasks Novel picturesArrows Familiar pictures Moving fixation Noise detectionRest Odd/even digits

Experiment 1 - Block Design

Each task was presented three times in each run (21 blocks per run) in a fixed pseudorandom order Each block lasted 21 sec (1 run approx. 7.5 min) Four runs were completed for a total of 12 blocks of each task (data for each participant averaged over the four runs) Brief instruction appeared at top of screen for each task (e.g. Odd or Even or Rest)

Imaging Parameters Siemens 1.5T Vision scanner Whole-brain T2* images obtained using echoplanar single-shot pulse sequence (matrix size 64 x 64) TE = 43msec Flip angle = 90º In-plane resolution of 4 x 4 mm

Functional Images 32 4-mm-thick slices aligned with the principle axis of the hippocampus 153 images obtained for each slice TR = 3sec Stimulus presentation began on the 5 th image and ended on the 148 th image (allowed for stabilization and return to baseline) After last image, high resolution (1 x 1 x 1mm) structural scan was obtained

Functional Images (contd) Images transformed into Talairach space Transformation resulted in voxel size of 2.5 x 2.5 x 2.5 mm Ten ROI s identified for analysis (perirhinal cortex, temporopolar cortex, entorhinal cortex, parahippocampal cortex, hippocampal region, each bilaterally analyzed)

Results Four ROI s displayed significantly greater activity during the rest task than during several other tasks: Left/right parahippocampal cortex Left/right hippocampal region

Results (contd)

Authors Conclusions With rest as baseline, familiar picture task shows no activity in medial temporal lobe and activity associated with encoding novel pictures is limited to right parahippocampal cortex When either odd/even digit or noise detection task used as baseline, substantial medial temporal activity was observed in both familiar and novel pictures tasks

Authors Conclusions (contd) Appears that presence of activity during the rest condition masked activity throughout the medial temporal lobe during both novel and familiar pictures tasks 2 problems: rest was not rest – instruction displayed fMRI is difference in activity NOT presence of activity

Experiment 2 – Rapid Event-Related Design

Two rapid event-related designs used (trials all 3sec each) 1) Trial using novel picture task, familiar picture task, and rest (conventional design) 2) Trial using novel picture task, familiar picture task, and odd/even digit task No instructions displayed on screens for Exp. 2 (changed tasks from Exp. 1)

Imaging parameters, functional images, ROI s in Exp. 2 were all identical to those used in Exp. 1 Same 8 participants as in Exp. 1

Results Magnitude of response to both novel picture and familiar picture tasks greater when odd/even digit task used as baseline than when rest used as baseline

Results (contd) When rest used as baseline, significant response to novel pictures found in both left and right parahippocampal regions; but, no significant response to novel pictures found in hippocampal region When rest used as baseline, no response to familiar pictures found in any of the ten ROI s

Results (contd) When odd/even digit task used as baseline, significant response to novel pictures found in eight of the ten ROI s When odd/even digit task used as baseline, significant response to familiar pictures found in seven of the ten ROI s

Results (contd)

Authors Conclusions Effect of activity during rest trials reduced fMRI response; often to the point of apparently eliminating the effect of presenting novel or familiar stimuli

Other Findings Activity during baseline condition can reverse sign (direction) of hemodynamic response (Exp. 2) Left Parahippocamal Region Left Motor Cortex

Other Findings (contd) Activity in occipital regions decreased in noise detection task (a below) and odd/even digit task (b below) relative to rest (Exp. 1)

Other Findings (contd) Authors potential reasons for decreased activity relative torest in occipital areas: Possibility of scanning room during rest Suppression of visual cortical activity outside central focus of task Presence of visual imagery during rest Another possibility? – Presentation of word Rest (i.e. 4 characters) contains more visual stimuli than presentation of a digit (1 char.) or presentation of white field (0 char.)

Discussion Authors claim that results of studies demonstrate that even short periods of rest do not provide an optimal baseline for fMRI research Significant cognitive activity found during rest condition Study highlights key limitation of BOLD fMRI studies – it is a contrastive methodology with no true baseline

Takeaways Baseline is what you choose it to be Results only contrast blood oxygenation levels between conditions Can only infer differences in activity not whether or not activity exists Know ahead of time what you want to compare and ensure its appropriate for your study