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 pictures Arrows

Familiar pictures Moving fixation

Noise detection ‘Rest’

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 5th image and ended on the 148th image (allowed for stabilization and return to baseline)

After last image, high resolution (1x1x1mm) structural scan was obtained

Functional Images (cont’d)

Images transformed into Talairach space

Transformation resulted in voxel size of

2.5 x 2.5 x 2.5 mm

Ten ROIs identified for analysis (perirhinal cortex, temporopolar cortex, entorhinal cortex, parahippocampal cortex, hippocampal region, each bilaterally analyzed)

Results

Four ROIs displayed significantly greater activity during the ‘rest’ task than during several other tasks:

Left/right parahippocampal cortex

Left/right hippocampal region

Results (cont’d)

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 (cont’d)

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, ROIs 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 (cont’d)

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 ROIs

Results (cont’d)

When odd/even digit task used as baseline, significant response to novel pictures found in eight of the ten ROIs

When odd/even digit task used as baseline, significant response to familiar pictures found in seven of the ten ROIs

Results (cont’d)

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 (cont’d)

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 (cont’d)

Authors’ potential reasons for decreased activity relative to‘rest’ 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 it’s appropriate for your study