What is odd in the oddball task?: Prefrontal cortex is activated by dynamic changes in response strategy

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Abstract

In the “oddball” target detection task, subjects respond to target stimuli that occur infrequently and irregularly within a series of standard stimuli. Although detection of these targets reliably evokes transient activity in prefrontal cortical regions, it has not been established whether this activity is due to selection of an infrequent response or to changes in response strategy. We investigated this issue using a novel variant of the oddball task that incorporated the Simon effect, while measuring hemodynamic brain activity in prefrontal cortex using functional magnetic resonance imaging (fMRI). Subjects viewed a series of circles and squares that required left and right button presses, respectively. On 90% of trials (“standard” trials), the stimuli were presented in the same visual hemifield as the hand of response, but on 10% of trials (“strategy-change” trials) they were presented in the opposite visual hemifield. Significant activation to the infrequent strategy-change trials was found in the anterior middle frontal gyrus (MFG), the posterior inferior frontal gyrus (IFG) and adjacent insular cortex, and in the anterior cingulate gyrus (ACG). These regions, which correspond to previous reports of oddball-related activation, were consistent across subjects. Behavioral results supported our interpretation that subjects potentiated a position-based response strategy, which was inhibited on the strategy-change trials. Activity within the MFG and ACG was much greater on error trials than on correct trials, while IFG activity was similar between error and correct trials. We conclude that the dorsolateral prefrontal cortex (dlPFC) is associated with dynamic changes in the mapping of stimuli to responses (e.g. response strategies), independently of any changes in behavior.

Introduction

Detection of an infrequent target stimulus evokes widespread neural activity that is reflected in both electrophysiological and hemodynamic measures. In the commonly used “oddball” paradigm, subjects identify infrequent “target” stimuli within a series of rapidly presented “standard” stimuli. For example, in a visual oddball task, there might be a 95% chance for a square to be presented and a 5% chance for a circle. When the targets (e.g. circles) appear, the subject must make a response, such as pressing a button or updating a mental count. The oddball task and its variants have been used in more than 1000 published electrophysiological studies (Herrmann & Knight, 2001, Picton, 1992), and recent studies have adopted the oddball design within event-related functional magnetic resonance imaging (fMRI). This popularity is a direct result of its success in evoking robust and reliable phenomena that have been used as markers of cognitive function (Polich, 1999).

Detection of a target elicits systematic fMRI activation in prefrontal and parietal cortices (Casey et al., 2001; Clark et al., 2001, Clark et al., 2000, Kirino et al., 2000; Linden et al., 1999; McCarthy et al., 1997, Stevens et al., 2000, Strange et al., 2000). Because the prefrontal cortex (PFC) activation, like that measured electrophysiologically (Daffner et al., 2000; Desmedt, Debecker, & Manil, 1965; Picton, 1992; Sutton, Braren, Zubin, & John, 1965), appears to be insensitive to stimulus modality or method of responding (Kirino et al., 2000), these regions have been associated with context-dependent control of behavior, consistent with evidence from other experimental designs (Knight & Grabowecky, 2000, Miller & Cohen, 2001). However, the oddball task, like any other complex paradigm, likely evokes activation in a network of brain regions representing various cognitive components of the task. Thus, despite the oddball task’s surface simplicity, the particular cognitive processes performed by the active prefrontal cortex regions are not well established.

One possible model for PFC function in the oddball task is that it selects among possible responses. When a new response is required, as to the target stimuli, PFC must inhibit the previous response and select the correct new one. But, when a subject makes the same response repeatedly, as to the standard stimuli, that action becomes efficiently coded and can be made in the absence of prefrontal control. A second model contends that PFC accesses, inhibits, or changes behavioral strategies, instead of behavior itself. In any experimental task, subjects form response strategies based upon the expected pattern of stimuli and required responses. For the oddball design task, because most stimuli are non-targets, subjects predict that non-targets are likely and thus set up a response strategy that is biased toward them. When a target occurs, the subjects must inhibit this response strategy so that they can correctly respond to the target.

These two possibilities are indistinguishable in the canonical oddball design because the infrequent target stimulus is (by definition) associated with a similarly infrequent response. Every time a target appears, it not only requires inhibition of the previous response, if any, and initiation of a new response, but also requires inhibition of any biasing strategy induced by its infrequency. However, these concepts are not inexorably confounded, as manipulation of response strategy independent of response changes, would allow them to be distinguished. If response strategy changes evoked no dlPFC activation when unassociated with a response change, then the first possibility would be supported. If response-strategy changes evoked dlPFC activation, even when not contingent upon response changes, then the second possibility would be supported.

We modified the standard oddball design to answer this question: are response changes necessary for evocation of dlPFC activation? Two stimuli, a circle and a square, were presented one at a time over many trials, requiring left and right button presses respectively. On most trials, the stimuli were presented on the same side of fixation as the hand of the response. Since response time is facilitated when stimulus position is compatible with response hand, as demonstrated by the Simon effect (Simon & Small, 1969), we hypothesized that a “position” response strategy would be potentiated. But, when the stimuli were presented oppositely from the required response hand (e.g. a circle on the right), we expected that subjects would inhibit the position strategy and change to the correct “shape” strategy. Thus, the infrequent, odd events in the current design are not response-change trials, but strategy-change trials.

Section snippets

Subjects

The subject sample consisted of 15 healthy adults (age=23±8 years; 8 females, 7 males). No participant reported any history of neurological injury or disease. Participants provided written informed consent in accordance with the policies of the Duke University Institutional Review Board.

Experimental task

The experimental task required subjects to classify rapidly presented stimuli on the basis of their shape (see Fig. 1). On each trial, a single circle or square was presented for 500 ms. The shapes subtended

Behavior

Response time and percentage of correct responses were compared across all trial types (see Fig. 2). Responses were not recorded for one subject due to an equipment failure, and all behavioral analyses use the remaining 14 subjects. Subjects were more accurate to standard trials than to strategy-change trials (97% versus 81%; t(13)=5.89; P<0.00001), and this effect was present for every subject both for circles and for squares. When responding correctly, subjects responded faster to standard

Discussion

The current study provides strong evidence that the oddball effect observed in prefrontal cortex does not require one behavioral response to be executed more frequently than another. Instead, the standard pattern of prefrontal activity can be evoked by an infrequent event that requires a different stimulus-response mapping than used for standard trials.

The behavioral results confirmed that response-strategy changes occurred independently of response changes. Although the infrequent

Acknowledgements

We thank Dr. Martin McKeown for assistance with partial-brain coregistration, and Cynthia Liu, Jonathan Smith, Richard Sheu, and Evan Gordon for assistance in data analysis. This research was supported by the US Department of Veterans’ Affairs, and by NINDS-41328, and NIDA-16214. Dr. McCarthy is a VA Research Career Scientist.

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