Elsevier

NeuroImage

Volume 19, Issue 4, August 2003, Pages 1694-1708
NeuroImage

Regular article
Mixed blocked/event-related designs separate transient and sustained activity in fMRI

https://doi.org/10.1016/S1053-8119(03)00178-2Get rights and content

Abstract

Recent functional magnetic resonance imaging (fMRI) studies using mixed blocked/event-related designs have shown activity consistent with separable sustained task-related processes and transient trial-related processes. In the mixed design, control blocks are intermixed with task blocks, during which trials are presented at varying intervals. Two studies were conducted to assess the ability of this design to detect and dissociate sustained task-related from transient trial-related activity. Analyses on both simulated and empirical data were performed by using the general linear model with a shape assumed for sustained effects, but not transient effects. In the first study, simulated data were produced with sustained time courses, transient time courses, and the sum of both together. Analyses of these data showed appropriate parsing of sustained and transient activity in all three cases. For the empirical fMRI experiment, counterphase-flickering checkerboard stimuli were constructed to produce sustained, transient, and combined sustained and transient responses in visual cortex. As with the simulation, appropriate parsing of sustained and transient activity was seen in all threecases; i.e., sustained stimuli produced sustained time courses and transient stimuli produced transient time courses. Combined stimuli produced both transient and sustained time courses. Critically, transient stimuli alone did not produce spurious positive sustained responses; sustained stimuli alone produced negligible spurious transient time courses. The results of these two studies along with supplemental simulations provide strong evidence that mixed designs are an effective tool for separating transient, trial-related activity from sustained activity in fMRI experiments. Mixed designs can allow researchers a means to examine brain activity associated with sustained processes, potentially related to task-level control signals.

Introduction

The human brain is able to initiate different responses to the same set of stimuli in different situations. For example, a student taking a vocabulary test might write down the meaning of a word after hearing it. On the other hand, during a spelling test, that same student would spell the word upon hearing it. Out of the myriad possible information processing pathways, the appropriate ones must be organized to make the correct, context specific response to the situation. How does this organization take place?

One approach to this question would be to dissociate signals related to the task per se (adopting a vocabulary test “set”) from signals related to lower-level task components (recalling the meaning of a specific word). The goal of this report is to describe and validate a method for dissociating these different kinds of signals based on their temporal profiles of activity.

In a laboratory setting, neural activity related to each trial of a task can be expected to occur in a similar way, producing a transient time course associated with each trial. Such “transient trial-related activity” would include processing specifically involved in each trial of a task.

Activity related to maintenance of the organized state or set of the system might be sustained throughout the performance of the task. The neural activity sustained across trials of a task will be referred to as “sustained” activity. This activity could be related to several different processes, including the attentional state or set of a subject during a task, or the subject’s level of arousal.

Because different time courses of activity are likely to play different roles in processing, the ability to detect and distinguish between transient trial-related activity and sustained activity should allow a more complete understanding of the functional roles of the neural activity observed.

While powerful for their own goals, two of the most commonly used functional magnetic resonance imaging (fMRI) paradigms are not suited for dissociating sustained from transient trial-related activity. Blocked designs Bandettini et al 1992, Kwong et al 1992, Ogawa et al 1992, Donaldson and Buckner 2001 compare overall activity during a block when subjects perform one task to overall activity during a block when subjects perform a control task. In a blocked design, all activity that takes place during one task block contributes to a single estimate, potentially confounding sustained and transient trial-related activity. In contrast, event-related designs Buckner et al 1996, Dale and Buckner 1997, Josephs et al 1997, McCarthy et al 1997, Zarahn et al 1997a extract only activity that is transient and associated with the event of interest (e.g., the trials of a task) ignoring sustained activity.

Several recent fMRI studies have examined sustained and transient trial-related activity by using various methods Kato et al 1998, Chawla et al 1999, Fernandez et al 1999, Mitchell et al 2000, Otten et al 2002. For example, a study by Donaldson and colleagues (2001) used a “mixed blocked/event-related design” to dissociate sustained and transient trial-related activity (see also complementary designs using electroencephalography and positron emission tomography by Duzel et al., 1999).

In the mixed design, trials are presented during task blocks, which are alternated with control blocks (Fig. 1A). The difference between a mixed design and a blocked design is that in a mixed design, trials are presented with different intervals between them, as in rapid event-related designs (Fig. 1B). This method allows estimation of the temporal profile of activity related to each trial Friston et al 1995, Buckner et al 1996, Dale and Buckner 1997, Josephs et al 1997, Miezin et al 2000. Interspersing task blocks with control blocks, as in a blocked design, allows estimation of sustained activity throughout a task block, presumably separated from transient trial-related activity.

Donaldson and colleagues’ (2001) experiment described transient trial-related activity in a recognition memory experiment as well as sustained activity related to blocks of trials. Sustained effects alone were observed in some regions, transient trial-related effects alone in others, and both were observed together in still other regions. The sensitivity and selectivity of the mixed design has not yet been tested. For example, if it were the case that the mixed design caused transient trial-related activity to be misinterpreted as sustained, then the mixed design would not be selective. The experiments described in this study examine aspects of the sensitivity and selectivity with which mixed designs can detect and dissociate sustained and transient trial-related effects. To test the sensitivity and selectivity of the design, well-characterized inputs were used to test the output of analysis by using the mixed design in two studies. The first study, on simulated data, probed whether mixed designs confound sustained and transient signals when no noise is present, or in the presence of physiologically plausible noise. However, the simulations cannot completely model the actual characteristics of fMRI data from the human brain. Therefore, an fMRI feasibility experiment was also performed.

In this second experiment, different durations of activity were produced in the visual cortex by using flickering checkerboard stimuli. Similar stimuli have been shown to elicit robust and well-localized hemodynamic responses Fox et al 1986, Boynton et al 1996, Menon and Goodyear 1999; Miezin et al 2000, Ollinger et al 2001a.

The results of the two primary studies prompted further simulations exploring conditions under which the mixed design could fail to cleanly separate transient from sustained activity.

Section snippets

Methods and results

The general form of the mixed design is shown in Fig. 1A. For the specific experiments described here, control blocks included 20 acquisitions of a whole brain volume (about 54 s), and task blocks included 41 acquisitions (about 110 s). Each acquisition lasted 2.5 s and will be referred to as an “MR frame.” Sustained effects were assumed to occur over the entire 110 s of the task block. Transient “trials” were presented so that the time between successive stimuli varied across a block, as in

Discussion

The experiments presented here suggest that the mixed design can extract effects with sustained and transient temporal profiles from fMRI data and dissociate them from each other. Though the evidence implies that sustained activity is most often not misapplied to the transient effect, some evidence suggests that it may be misapplied in certain situations. These findings place constraints on the application of mixed designs, which will be discussed in the “Constraints on the use of the mixed

Acknowledgements

We thank Heather Lugar for help with data collection. Thanks to Avi Snyder, Tom Conturo, and Erbil Akbudak for assistance with MRI procedures. Support for this research came from NIH grants NS31279 and NS41255.

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