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, 98 (22), 12760-6

When Zero Is Not Zero: The Problem of Ambiguous Baseline Conditions in fMRI

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When Zero Is Not Zero: The Problem of Ambiguous Baseline Conditions in fMRI

C E Stark et al. Proc Natl Acad Sci U S A.

Abstract

By using blocked and rapid event-related functional MRI studies of memory, we explored the implications of using rest periods as a baseline condition in functional MRI studies. Activity in the medial temporal lobe (as well as in other brain regions) was substantially higher during rest than during several alternative baseline conditions. The effect of this elevated activity during rest was to reduce, eliminate, or even reverse the sign of the activity during task conditions relevant to memory functions. The results demonstrate that periods of rest are associated with significant cognitive activity and, therefore, provide a nonoptimal baseline for memory tasks. These results were observed not only when relatively long blocks of rest were used (experiment 1), but also when rest consisted of the short null trials typically used in rapid event-related designs (experiment 2). The findings have important implications for the design and interpretation of a wide range of fMRI studies of cognition.

Figures

Figure 1
Figure 1
(a and b) Activity within anatomically defined ROIs in the medial temporal lobe during six tasks from experiment 1. Bars show the mean percent signal change during each task relative to the mean signal during the Rest task. (Error bars = SEM). (a) Activity in the left and right parahippocampal cortex. The Novel Picture task was associated with increased activity relative to rest in the right parahippocampal cortex. Bilaterally, activity during three of the tasks (Arrows, Noise Detection, and Odd/Even Digits) was significantly less than activity during Rest. The Familiar Picture task was not associated with detectable activity when compared with Rest. When compared with the Odd/Even Digit task, viewing novel or familiar pictures was associated with bilateral activity. (b) Activity in the left and right hippocampal region. Bilaterally, there was significantly less activity during two of the tasks (Noise Detection and Odd/Even Digits) than during Rest. Neither the Novel Picture nor the Familiar Picture task was associated with more activity than Rest, but activity was detected in comparison with the Odd/Even Digits task. (c and d) Hemodynamic response from experiment 2 showing activity over time (3 s per sample) within anatomically defined parahippocampal cortex (c) and hippocampal (d) ROIs. When the Odd/Even Digit task was used as the baseline for activity in a rapid event-related design, both Novel and Familiar Pictures were associated with a significant response in both the parahippocampal cortex and the hippocampus, bilaterally. In contrast, when Rest was used as a baseline for activity in a rapid event-related design, a significant response was found only for Novel Pictures in the parahippocampal cortex.
Figure 2
Figure 2
Hemodynamic response showing activity over time (3 s per sample) within functionally defined ROIs in experiment 2. (a) Activity in a subregion of the left parahippocampal cortex functionally defined from experiment 1 (see text). When the Odd/Even Digit task was used as the baseline for activity in a rapid event-related design, both Novel and Familiar Pictures were associated with increased activity. When Rest was used as a baseline for activity, Novel Pictures were not associated with detectable activity, and Familiar Pictures were associated with decreased activity. (b) Activity in a subregion (see text) of the left motor cortex where the button pushes in the Odd/Even Digit task would be expected to be associated with significant activity. Here, the activity associated with Novel and Familiar Pictures was greater when Rest was used as a baseline than when the Odd/Even Digit task was used as a baseline. Thus, the effect of activity during a baseline task can be to reduce, eliminate, or even reverse the sign of the activity during the conditions of interest.
Figure 3
Figure 3
fMRI data from two of the baseline tasks used in experiment 1, Noise Detection (a) and Odd/Even Digits (b), are shown in axial sections as colored overlays on the average structural images (transformed to the atlas of Talairach and Tournoux, ref. 22). Regions shown in yellow and orange exhibited greater activity in the baseline task than in Rest. Regions shown in blue exhibited greater activity in Rest than in the baseline condition. Deactivations relative to rest were observed not only in the medial temporal lobes, but in many regions throughout the brain. The relative absence of significant activity in the frontal lobe may be the result of the limited coverage of the radio frequency (RF) coil that was used.

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