Mechanisms underlying flexible adaptation of cognitive control: Behavioral and neuroimaging evidence in a flanker task

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Mechanisms underlying flexible adaptation of cognitive control: Behavioral and neuroimaging evidence in a flanker task Blandyna Żurawska vel Grajewskaa, b , Eun-Jin Sima , Klaus Hoeniga , Bärbel Herrnberger a , Markus Kiefera,⁎ a

Department of Psychiatry, University of Ulm, Leimgrubenweg 12, 89075 Ulm, Germany Department of Cognitive Psychology, University of Finance and Management in Warsaw, Pawia 55, 01-030 Warsaw, Poland

b

A R T I C LE I N FO

AB S T R A C T

Article history:

Cognitive control can be adapted flexibly according to the conflict level in a given situation. In the

Accepted 10 September 2011

Eriksen flanker task, interference evoked by flankers is larger in conditions with a higher, rather

Available online 17 September 2011

than a lower proportion of compatible trials. Such compatibility ratio effects also occur for stimuli presented at two spatial locations suggesting that different cognitive control settings

Keywords:

can be simultaneously maintained. However, the conditions and the neural correlates of this

Cognitive control

flexible adaptation of cognitive control are only poorly understood. In the present study, we

Conflict adaptation

further elucidated the mechanisms underlying the simultaneous maintenance of two

Compatibility ratio

cognitive control settings. In behavioral experiments, stimuli were presented centrally above

Flanker task

and below fixation and hence processed by both hemispheres or lateralized to stimulate

fMRI

hemispheres differentially. The different compatibility ratio at two stimulus locations had a differential influence on the flanker effect in both experiments. In an fMRI experiment, blocks with an identical compatibility ratio at two central spatial locations elicited stronger activity in a network of prefrontal and parietal brain areas, which are known to be involved in conflict resolution and cognitive control, as compared with blocks with a different compatibility ratio at the same spatial locations. This demonstrates that the simultaneous maintenance of two conflicting control settings vs. one single setting does not recruit additional neural circuits suggesting the involvement of one single cognitive control system. Instead a crosstalk between multiple control settings renders adaptation of cognitive control more efficient when only one uniform rather than two different control settings has to be simultaneously maintained. © 2011 Elsevier B.V. All rights reserved.

1.

Introduction

The control of action and thought plays an important role in the organization of human behavior. An important function of action control concerns the protection of the intended action against interference from conflicting response tendencies.

This cognitive function can be illustrated by a children game known in Poland (and presumably in many other countries), where players have to raise their arms in response to the game leader's announcement, “All animals with plumage fly…”, if the leader concludes this announcement with an object that, indeed, can fly as in “an eagle flies” or “a stork flies”. The

⁎ Corresponding author at: University of Ulm, Department of Psychiatry, Section for Cognitive Electrophysiology, Leimgrubenweg 12, 89075 Ulm, Germany. Fax: +49 731 500 61542. E-mail address: [email protected] (M. Kiefer). URL: http://www.uni-ulm.de/~mkiefer/ (M. Kiefer). 0006-8993/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2011.09.022

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players, however, have to keep the arms on the legs when the game leader's announcement ends with an object that cannot fly as in “a dog flies” or “a table flies”. The difficulty of performing this task lies in the fact that the leader raises her or his arms, irrespective of whether a flying or non-flying object is mentioned. In the case of a non-flying object, the players have to suppress the strong tendency to raise their arms in response to the game leader's misleading announcement and action. This game is one of numerous examples of a common situation, in which conflicting task-irrelevant information can interfere with our goal-directed action. In order to ensure that the intended action is executed in the presence of interfering response tendencies, response conflict needs to be monitored and resolved. Neuropsychological and cognitive theories therefore propose an executive control system that is assumed to protect the intended action against interference from action tendencies elicited by conflicting information (Botvinick et al., 2001; Kiefer and Martens, 2010; Kiefer et al., 2005; Norman and Shallice, 1986). This cognitive system is highly relevant for orchestrating human cognition and action, being concerned with the selection, scheduling and coordination of cognitive processes in congruence with the action goal (Norman and Shallice, 1986). As we will describe in more detail below, the activity level of the cognitive control system can be adjusted flexibly according to the control demands of the context. The present study aims at further elucidating the neurocognitive mechanisms underlying this flexible adaptation of cognitive control. One attempt to explain cognitive control in conflicting situations distinguishes two interconnected subsystems (Cohen et al., 1996): the conflict monitor and the attention controller. The conflict monitor registers the amount of conflict between all responses activated at a given time. To the extent that the registered conflict is high, the conflict monitor increases attention to the task-relevant stimulus–response association via the attention controller. The attention controller, in turn, codes the current action goal and adds activation to the mental representation of the task-relevant stimulus or stimulus dimension and/or reduces activation of task-irrelevant stimulus information. Executive control can be experimentally investigated with different types of interference paradigms (e.g., Simon, 1990; Stroop, 1935). A frequently used interference paradigm is the Eriksen flanker task (Eriksen and Eriksen, 1974) that is also administered in the present study. Participants respond to a target letter presented among strings of flanker letters, which are either identical with the target (compatible trials, HHHHH or SSSSS) or different from the target and associated with an alternative response (incompatible trials, HHSHH or SSHSS). Reaction time (RT) is typically slower, and responses are more error-prone to incompatible trials as compared with compatible trials. This effect of compatibility on behavioral performance (flanker effect: RT incompatible–RT compatible) is taken as a measure of interference (Eriksen and Eriksen, 1974). The flanker effect is also observed when compatible flankers are not identical with the target letter, but associated with the same response as the target (Eriksen and Eriksen, 1974; Eriksen and Schultz, 1979). Electrophysiological recordings of muscle activity (EMG) (Coles et al., 1985) and response preparation processes (lateralized readiness potential in the event-related potential) (Mattler,

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2003) show that during the first stage, all characters are processed in parallel, and both correct and incorrect responses are activated. At a later stage, the target location is determined, and the correct response is executed (Coles et al., 1985; Mattler, 2003). Delayed responses on incompatible trails are caused by response competition (Coles et al., 1985; Mattler, 2003; Mattler, 2005), but also by longer evaluation processes (Coles et al., 1985). Neuroimaging studies have shown that conflict resolution in interference tasks strongly relies on several prefrontal areas, including dorsolateral prefrontal cortex (dlPFC) (Botvinick et al., 2004; Bunge et al., 2002; Wittfoth et al., 2009) and anterior cingulate cortex (ACC) (Botvinick et al., 1999; Botvinick et al., 2001; Bush et al., 1998; Fan et al., 2003; MacLeod and MacDonald, 2000; Pardo et al., 1990; Rushworth et al., 2004; Sohn et al., 2007). However, the precise role of these prefrontal areas for executive control is still a matter of debate (Duncan, 2001; Hayward et al., 2004; Kessler and Kiefer, 2005; Kiefer et al., 2005; Mansouri et al., 2009). To date, there are essentially three prominent views on the differential roles of the dlPFC and ACC in cognitive control. The first view assumes that ACC hosts a response evaluation mechanism that monitors whether the activated behavioral responses match with the action goal (Botvinick et al., 2001; Botvinick et al., 2004; Kiefer et al., 1998; Ruchsow et al., 2002; Ruchsow et al., 2004). In particular, the ACC has been considered to be the neural basis of the conflict monitor subsystem for cognitive control that identifies the need for cognitive control by registering the current level of response conflict (Botvinick et al., 2001; Botvinick et al., 2004; Botvinick et al., 1999; Fan et al., 2003; MacLeod and MacDonald, 2000). Within this theoretical framework, the dlPFC is thought to implement the attention controller subsystem that exerts cognitive control (MacDonald et al., 2000). A second view assumes that ACC exerts a more direct regulatory function by implementing some of the executive control adjustments necessary to resolve conflict (Posner, 1995; Rölofs et al., 2006; Ward, 1948). A third view assumes that the dlPFC itself plays a pivotal role in the dynamic tuning of executive control during any kind of conflict-induced behavioral adjustments (Duncan, 2001; Mansouri et al., 2007; Mansouri et al., 2009). However, as the functional specialization of dlPFC and ACC is beyond the scope of our work, we do not elaborate further on this issue. Central to the present study, it is well documented that the activity level of the cognitive control system can be adjusted adaptively depending on the situational context. In particular, the expected conflict leads to a modulation of behavioral interference effects. If conflict expectation is high so that the activity level of the attention control system is increased, the interference effect is smaller compared with a condition of low conflict expectation. Typically, conflict expectation is manipulated by varying the compatible-to-incompatible trial ratio, in short “compatibility ratio”, across experimental blocks (e.g., 80% compatible vs. 20% compatible trials) (Bartholow et al., 2003; Corballis and Gratton, 2003; Gratton et al., 1992; Johnson and Yantis, 1995; Kane and Engle, 2003; Posner and Snyder, 1975). The notion of an adaptive adjustment of cognitive control is also supported by findings from neuroimaging studies which observed that activity in prefrontal areas in response to conflict resolution is modulated by conflict expectation. In blocks with a high proportion of compatible trials (i.e., with low conflict expectation), activity in dlPFC and ACC was increased for rare incompatible trials as compared with blocks with a low

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proportion of compatible trials (Carter et al., 2000; Casey et al., 2000). These findings suggest that blocks with frequent compatible trials generally induce a low level of cognitive control, so that rare incompatible trials are associated with increased response conflict and, correspondingly, enhanced activity of the cognitive control system. Recent studies indicated that the activation level of the executive control system can be even more flexibly adjusted according to contextual demands. Several studies showed that cognitive control can be simultaneously, but selectively adjusted for two stimulus locations based on specific conflict expectations, thereby differentially influencing behavioral interference effects. Corballis and Gratton (2003) presented the letter arrays of the Eriksen flanker task on the left, on the right or in the middle of a display. Importantly, 75% letter arrays presented on the left side were compatible (and 25% incompatible), while 75% arrays presented on the right side were incompatible (and 25% compatible). The spatial location of the letter array varied randomly from trial to trial so that the frequency distribution of the incompatible trials varied within one block as a function of the spatial location. The flanker effect was significantly larger on the side with 75% compatible arrays and reduced for the opposite side, showing that at least two different conflict expectations can be simultaneously formed to adjust cognitive control (Corballis and Gratton, 2003). In one of their experiments, Corballis and Gratton (2003) examined whether the middle position is processed independently of the lateral spatial positions or whether the lateral (left and right) positions can also influence adjustment of cognitive control for the middle location. The compatibility ratio in the middle position was fixed throughout the experiment (i.e., 50% compatible) and ratios at the side positions were varied across blocks (25% compatible on both, left and right positions, or 75% on both positions). The interference effect for the middle position depended on the compatibility ratio of the lateral position: It was reduced when there were 25% compatible trials on both lateral positions, and enhanced when there were 75% compatible trials on both lateral positions. Thus, the supervisory system was not able to set and perform processing for the central position regardless of the lateral positions. The authors, therefore, concluded that hemispheric division seems to be necessary for differentially adjusting action control to two different conflict expectations. Based on these results, Corballis and Gratton (2003) proposed that there must be at least two executive control systems, one in each hemisphere that performs the adjustment of cognitive control because a single processor cannot adapt to different conflict expectations at separate spatial locations. The idea of two separate hemisphere-dependent executive control systems was questioned by more recent findings (Wendt et al., 2008). In this study, letter strings were presented at four possible locations, two in the left visual field (one above the horizontal midline and one below the horizontal midline) and two in the right visual field (again above and below the horizontal midline). Within one visual hemifield, the compatibility ratios of 25% and 50% were employed, within the other one, the compatibility ratios were 50% and 75%. The magnitude of the interference effect was most reduced for the 25% compatible location, intermediate for both 50% compatible positions and most enhanced for the 75% compatible location.

Moreover, the flanker effect for both locations associated with 50% compatible trials was independent of the overall compatibility ratio within a given visual hemifield, i.e., it did not differ between the 75%/50% hemifield and the 25%/50% hemifield. This pattern of results suggests that it is possible to set the action control level according to a specific conflict frequency (here: 50%) independently of the general conflict level within the visual hemifield (Wendt et al., 2008). Hence, differential adaptation of cognitive control does not seem to depend on hemisphere-specific presentation of compatibility ratios (see also Lehle and Hübner, 2004). This assumption was further supported by a recent study (Vietze and Wendt, 2009), in which stimuli in the flanker task were presented above/below the fixation point and centered at the vertical midline, which activates both hemispheres comparably. A compatibility ratio of 50% vs. 75% was assigned to each location in one block, in another block the compatibility ratio was 50% vs. 25%. As in the previous studies, the flanker effect was modulated according to the location-specific compatibility ratio: it was smaller for the 25% compatibility ratio location than for the 75% compatibility ratio location. This modulation of the flanker effect according to the local compatibility ratio was only observed for the reaction time data, but not for the error data. The latter indicated a crosstalk of cognitive control settings between locations: the interference effect on error rates at the 50% location varied according to the ratio of the other location. This suggests that the independence between locations is not complete as indicated already by Corballis and Gratton's (2003) experiment 3, in which the flanker effect at the central position associated with a compatibility ratio of 50% was influenced by the compatibility ratio of the lateral positions. Note also that in the Vietze and Wendt (2009) study, in contrast to previous experiments on adaptation of cognitive control the global compatibility ratio in one block averaged across locations was not 50%, but 37.5% vs. 62.5%, which could have influenced the results. The main aim of the present study was to further elucidate the neurocognitive mechanisms underlying adaptive adjustment of cognitive control. In two behavioral experiments and one fMRI experiment, we asked whether this adjustment of cognitive control, which is based on different conflict expectations for two spatial stimulus locations, is supported by a uniform executive control system or, alternatively, by two separate executive control systems as suggested by Corballis and Gratton (2003). As in previous experiments, differential conflict expectations were induced by manipulating the compatibility ratio for two stimulus locations in an Eriksen flanker task. Similar to Vietze and Wendt (2009), we presented stimuli at a central position of the display above and below fixation in order to stimulate both hemispheres equally. However, unlike Vietze and Wendt (2009), in order to avoid possible influences from the global conflict level, the global compatibility ratio averaged across stimulus locations was 50% in all conditions and experiments. In two behavioral experiments, we tested whether a different compatibility ratio at two central locations (Experiment 1a) differentially modulates the behavioral interference effect similar to the classical arrangement by Corballis and Gratton (2003), in which the stimuli were presented to locations in the left and right visual fields (Experiment 1b). Such a pattern of results would considerably strengthen the suggestion from

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previous studies by Wendt and colleagues (Vietze and Wendt, 2009; Wendt et al., 2008) that a differential adjustment of cognitive control does not depend on the stimulation of different hemispheres. However, as not only left and right visual fields, but also upper and lower visual fields project to different parts of visual cortex (Christman and Niebauer, 1997; Hagenbeek and Van Strien, 2002; Lavidor and Walsh, 2008) and may be the target of different attentional mechanisms (Fecteau et al., 2000; Hagenbeek and Van Strien, 2002), presentation to upper and lower central locations would not necessarily preclude the possibility that the formation of different conflict expectations and the differential adjustment of cognitive control occur in dissociate cognitive control systems. In a neuroimaging experiment (Experiment 2) we therefore specified the neural correlates underlying the flexible adjustment of cognitive control. Using event-related functional magnetic resonance imaging (fMRI) we investigated whether maintenance of two different adjustments of cognitive control (as in Experiment 1a), as compared with a uniform adjustment for both spatial locations, uses the same prefrontal executive control networks. This approach can clarify whether or not conflicting information regarding the proportion of incompatible stimuli can be handled by a unitary executive control system or requires two dissociate systems as suggested previously (Corballis and Gratton, 2003).

2.

Results

2.1.

Experiments 1a and 1b

According to Corballis and Gratton (2003), the adjustment of cognitive control settings to different compatible proportions within one block is only possible if each conflict level is presented in different visual hemifields, i.e. is analyzed by different hemispheres. This claim was recently questioned by showing that the modulation of the flanker effect by compatibility ratio at lateral locations did not depend on the overall conflict level

Fig. 1 – Experiment 1a. Mean reaction times as a function of compatibility and compatibility ratio. 20% com=20% compatible and 80% incompatible trials at a given spatial position; 80% com=80% compatible and 20% incompatible trials at a given spatial position. The vertical bars indicate the standard error.

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Fig. 2 – Experiment 1b. Mean reaction times as a function of compatibility and compatibility ratio. 20% com=20% compatible and 80% incompatible trials at a given spatial position; 80% com=80% compatible and 20% incompatible trials at a given spatial position. The vertical bars indicate the standard error.

in each visual field (Wendt et al., 2008) and can also be obtained by central presentation (Vietze and Wendt, 2009). However, in these earlier studies, the global conflict ratio averaged across position deviated from 50% and was thus not neutral, which could influence the adjustment of cognitive control. We therefore used a global conflict ratio of 50% in all experiments. To gain some insight into possible differences in instantiation of cognitive control between lateralized and upper/lower stimulus displays, results of Experiment 1a, the crucial one, were contrasted with the effects in a second experiment (Experiment 1b), in which the 20% compatibility ratio and the 80% compatibility ratio were assigned to the left and right positions as in the classical Corballis and Gratton (2003) experiments.

2.1.1.

Results and discussion

2.1.1.1. Experiment 1a. For reaction time (RT) analysis, the mean correct RT was calculated per condition. A repeatedmeasures analysis of variance (ANOVA) with the factors compatibility and compatibility ratio (20% vs. 80%) was conducted. As in the Corballis and Gratton's (2003) study, we excluded the 50% compatibility ratio condition from our main analysis due to the fact it was not of theoretical interest. This analysis revealed a slower RT on incompatible than on compatible trials (573 vs. 508 ms) as shown by a main effect of compatibility, F(1, 23)= 293; p < .001; η2 = 0.9. Most importantly, compatibility interacted with compatibility ratio, F(1, 23) = 21.3; p < .001; η2 = .5. This interaction was due to a larger flanker effect (RT incompatible–RT compatible) for the location associated with 80% compatible trials as compared with the location associated with 20% compatible trials. The flanker effect size was 77 ms vs. 54 ms for 80% vs. 20% compatible ratio, respectively (Fig. 1). An ANOVA with the factors compatibility and compatibility ratio (20% vs. 80%) on error rate (ER) revealed only a significant main effect of compatibility: ER was higher on incompatible than on compatible trials. Error rate was 7% vs. 3% for incompatible and compatible trials, respectively; F(1, 23) = 23.3; p < .001; η2 = .5. The interaction compatibility × compatibility ratio was not significant (F < 1).

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2.1.1.2. Experiment 1b. For RT analysis, the mean correct RT was calculated per condition. A repeated-measures ANOVA with the factors compatibility and compatibility ratio (20% vs. 80%) was conducted. As in Experiment 1a, a main effect of compatibility indicated longer RT on incompatible than on compatible trials (617 ms vs. 538 ms), F(1, 23) = 251; p < .001; η2 = 0.9. Most importantly, compatibility interacted with compatibility ratio F(1, 23) = 9.1; p = .006; η2 = 0.3. This interaction was due to a larger flanker effect for the location associated with 80% compatible trials as compared with the location associated with 20% compatible trials. The flanker effect size was 90 ms vs. 67 ms for 80% vs. 20% compatible ratio, respectively (Fig. 2). An ANOVA with the factors compatibility and compatibility ratio (20% vs. 80%) on ER revealed only a significant main effect of compatibility. Similarly to Experiment 1a, ER was higher on incompatible than on compatible trials: 8% vs. 3% for incompatible and compatible trials, respectively; F(1, 23) = 32.3; p < .001; η2 = .6. The interaction compatibility × compatibility ratio was not significant (F < 1). When we compared the results of both experiments in an ANOVA with “experiment” as a between-subject factor, this analysis did not yield differences in the modulation of the flanker effect by compatibility ratio (20% vs. 80%) between these two experiments: the three-way interaction compatibility × compatibility ratio× experiment was not significant F(1, 46) < 1. Indeed, the difference between the flanker effect in 80% compatibility ratio vs. 20% compatibility ratio conditions in both experiments was comparable, although the flanker effect itself was generally larger in Experiment 1b (horizontal layout) as indicated by the significant interaction between compatibility and experiment: F(1, 46) = 4.3; p = .04; η2 = 0.1. Note that the flanker effect was larger in Experiment 1b at all three locations including the central location (51 ms vs. 43 ms) with a compatibility ratio of 50%, which was identical in both experiments. The results of Experiment 1a show that participants can adjust the activation level of the cognitive control system according to the specific conflict expectations assigned to two central vertical stimulus locations (above and below fixation). This modulation of the flanker effect by different compatibility ratios assigned at central locations was comparable to the classical assignment of compatibility ratios to locations in the left and right visual fields (Experiment 1b). Hence, the differential adjustment of cognitive control can also be achieved when the stimuli at two locations are presented to both visual hemifields and the compatibility ratio assessed by each hemisphere is equal (50%). They go beyond earlier work because we used in Exp. 1a central rather than a peripheral (left vs. right visual field) presentation (cf. Wendt et al., 2008), which differentially stimulates the left and right hemispheres, respectively. Furthermore, in both experiments the global compatibility ratio was 50% rather than deviating from 50% as in the Vietze and Wendt (2009) study, which minimizes biasing influences from the global conflict level. Thus, despite central stimulation and a neutral global compatibility ratio of 50, we observed a differential modulation of the flanker effect depending on the locationspecific conflict level. Our results therefore confirm and extend earlier studies demonstrating that the modulatory effect of two different compatibility ratios does not arise from hemispherespecific stimulation or is compromised by a differential global conflict level.

Although the observed location-specific influence of compatibility ratio on the flanker effect is fully in line with the notion of flexible adjustment of cognitive control, these effects can in principle be explained by two alternative mechanisms. (i) It has been suggested that the modulatory effects of two different compatibility ratios within one block can be explained by associative learning that links a certain stimulus with a location and a response (Wendt and Luna-Rodriguez, 2009). However, this origin of the flanker effect modulation in our study is not very likely for several reasons: the stimuli were identical at each location. Thus, stimulus location rather than identity signaled the compatibility ratio. Furthermore, contingencies between flanker type and most frequent response were different for the upper and the lower locations as well as for the central location (not analyzed), which render them hard to learn in a short time. However, the reported pattern of results was present already in the first block. (ii) The location-specific modulation of the flanker effect could be potentially caused by location-specific inter-trial sequence effects instead of or in addition to location-specific conflict levels. Typically, the flanker effect in a given trial is reduced if an incompatible rather than compatible trial was the direct predecessor trial and enhanced when n−1 trial is compatible, the so called Gratton effect (Gratton et al., 1992; Verguts et al., 2011). If this sequential modulation operates in a location-specific manner, reduced interference at a location associated with frequent conflict trials may be driven by a larger number of direct predecessor trials involving conflict at the same location. Although this mechanism could have in principle influenced our results, the possible contribution of this mechanism is limited in our experiments because presentation order of trials was randomized for each location and compatibility condition. As in only 33% of trials the trial n was preceded by a trial n−1 in the same location, sequential modulations of cognitive control settings operating in a location-specific manner can impact the performance only in one third of trials. In addition, even if the present compatibility ratio effects were fully influenced by location-specific sequential inter-trial modulations, the present results would

Fig. 3 – Experiment 2. Mean reaction times as a function of compatibility and compatibility ratio in homogeneous and mixed blocks. 30% com=30% compatible and 70% incompatible trials at a given spatial position; 70% com=70% compatible and 30% incompatible trials at a given spatial position. The vertical bars indicate the standard error.

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still demonstrate a flexible adjustment of cognitive control settings to different stimulus locations. In conclusion, Experiments 1a and 1b demonstrate a simultaneous maintenance of two different cognitive control settings even when stimuli were presented at two central positions in the visual field. This flexible adaptation of cognitive control was observed although the global compatibility ratio (i.e. compatibility ratio averaged across positions) was 50% in all blocks and thus neutral with regard to the induction of global control settings. The present behavioral results therefore considerably strengthen the notion that location-specific adaptation of cognitive control does not depend on a hemisphere-specific presentation of stimuli in the left and right visual fields, respectively. However, as upper and lower visual fields have different cortical projections (Christman and Niebauer, 1997; Hagenbeek and Van Strien, 2002) and may be modulated by different attentional mechanisms (Fecteau et al., 2000; Hagenbeek and Van Strien, 2002), presentation to upper and lower central locations does not exclude the possibility that two separable cognitive control systems are involved in adjusting cognitive control for spatial locations along the central vertical axis.

2.2.

Experiment 2

In the second experiment, we specified the neural correlates of the differential adjustment of cognitive control induced by different compatibility ratios at two central spatial locations. Using event-related fMRI, we tested whether a unitary or two dissociate cognitive control systems monitor the conflict level for two locations and adjust the level of cognitive control accordingly. Similar to Corballis and Gratton (2003) in their Experiment 2, we modified the experimental paradigm of Experiment 1a such that participants performed the Eriksen flanker task in two different types of blocks (homogeneous vs. mixed blocks). In homogeneous blocks, the same compatibility ratio was assigned to two spatial locations above and below fixation. For one-half of the homogeneous blocks, the compatibility ratio was 70%/30%, whereas for the other half, the ratio was 30%/70%. In the mixed blocks, in contrast, the compatibility ratio was different at these spatial locations within one and the same block: it was 70%/30% at one location and 30%/70% at the other location. The mixed blocks therefore correspond to the stimulation of Experiment 1a, whereas the homogenous blocks were introduced in order to determine behavioral performance and brain activity during the maintenance of one single vs. two different adaptations of cognitive control. Please note that the mixed blocks had a global compatibility ratio of 50% as in our Experiment 1a. In order to collect sufficient MR data samples in Experiment 2, we used less pronounced manipulations of the compatibility ratio than in Experiment 1 (where the ratio was 80%/20%). If the differential adjustment of cognitive control engaged two dissociate prefrontal executive control networks, performing the Eriksen flanker task in the mixed blocks should recruit additional prefrontal areas compared with the homogeneous blocks, possibly in a hemisphere-specific manner: for instance, simultaneous formation of two different conflict expectancies and, thus, application of two differential cognitive control adjustments in the mixed blocks might activate prefrontal areas bilaterally, whereas a uniform control adjustment in the

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homogeneous blocks can be exerted by prefrontal areas in one hemisphere only. Moreover, at the behavioral level, we would expect a similar modulation of the flanker effect by the compatibility ratio manipulation across both block types. Alternatively, if a single prefrontal cognitive control network adjusts cognitive control in both the mixed and homogeneous blocks, mixed blocks would not activate additional prefrontal areas as compared with homogeneous blocks. As simultaneous maintenance and application of two different control adjustments can render cognitive control less efficient due to interfering control settings, prefrontal activity might be even higher for the homogeneous than for the mixed blocks. At a behavioral level, the compatibility ratio should modulate the flanker effect in the homogeneous blocks more strongly than in the mixed blocks.

2.2.1.

Results and discussion

2.2.1.1. Behavioral data. The mean correct RT per condition was submitted to a repeated-measures analysis of variance (ANOVA) with the factors of block homogeneity, compatibility ratio and compatibility. Reactions on compatible trials were faster than on incompatible trials (559 vs. 604 ms) as shown by a main effect of compatibility F(1, 16) = 55.2; p < .001; η2 = .8. Most importantly, the interaction compatibility ratio× compatibility was significant F(1, 16) = 7.1; p = .02; η2 = .3, demonstrating that the flanker effect was larger in the 70% compatibility ratio condition than in the 30% compatibility ratio condition (52 vs. 32 ms). The modulation of the flanker effect by compatibility ratio was numerically stronger in the homogeneous blocks (the flanker effects for the 70% compatible and 30% compatible condition were 54 and 30 ms, respectively) than in the mixed block (55 vs. 40 ms), although the three-way interaction, homogeneity × compatibility ratio× compatibility, failed to reach significance (Fig. 3): F(1, 16) = 0.7; p = .4; η2 = .04. In order to assess whether compatibility ratio significantly modulated the flanker effect within each block type, we performed separate ANOVAs for the mixed and homogenous blocks, respectively. These subsidiary analyses revealed a significant compatibility ratio× compatibility interaction only in the homogenous (F(1,17) = 5.6; p = 0.03; η2 = .3), but not in the mixed blocks. The analysis of ER showed that errors were more frequent on incompatible than on compatible trials (5.5% vs. 4.2%) as indicated by a significant main effect of compatibility F(1, 16) = 7.1; p = .02; η2 = .3. No other main effects or interactions were significant. The behavioral results of our experiment with central presentation are in line with the earlier results by Corballis and Gratton (2003), in which stimuli were presented lateralized in the left and right visual fields, respectively (Experiment 2). In the present and in this earlier experiment, the flanker effect was overall significantly larger for the condition with a high than with a low compatibility ratio as indicated by the significant interaction between compatibility ratio and compatibility. Although statistically not significant, this influence of compatibility ratio on the flanker effect was numerically larger in the homogenous blocks, in which the same compatibility ratio was presented at both locations, compared with the mixed blocks, in which conflicting compatibility ratios were presented. As in Corballis and Gratton (2003) the corresponding higherorder interaction including the factor homogeneity was not

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Fig. 4 – Regions in prefrontal cortex activated significantly greater in the homogeneous than in the mixed block. Bar charts depict the size of effect for each of the four conditions at the peak voxel within each cluster. Small vertical bars indicate the 95% confidence intervals. ACC = anterior cingulate cortex; Homo = homogeneous block (one compatibility ratio within a block); Mixed = mixed block (two different compatibility ratios within a block assigned to spatial locations above and below fixation); 30% com = 30% compatible and 70% incompatible trials at given position; 70% com = 70% compatible and 30% incompatible trials at given position); extent threshold k = 26, p < .05 FDR corrected.

significant in our Experiment 2, presumably due to a lack of statistical power. Subsidiary analyses in each block type revealed a significant interaction between compatibility ratio and compatibility only in the homogenous, but not in the mixed blocks. The influences of compatibility ratio on the behavioral flanker effects in the mixed blocks thus show the same direction as the results of Experiment 1a, but do not replicate them at a significant level. This difference between Experiments 1a and 2 can be attributed to several factors associated with the adaptation of the behavioral paradigm of Experiment 1a to the prerequisites of an fMRI experiment: the manipulation of the compatibility ratio in Experiment 2 was less pronounced compared with Experiment 1a (70/30% vs. 80/20%), in order to be able to collect sufficient fMRI data for the rare compatibility condition without considerably increasing the length of the scanning session. We also had to decrease the sample size in Experiment 2 compared with the behavioral Experiment 1a (18 vs. 24 participants), thereby loosing statistical power. Finally, overall reaction times were longer and more variable in Experiment 2, presumably due to the unusual horizontal positioning of the participant in the MR scanner. Nevertheless, the influence of

compatibility ratio in Experiment 2 at the behavioral level was qualitatively comparable with that in Experiment 1a.

2.2.1.2. fMRI data. As our main theoretical focus rested on differential brain activation between the mixed (i.e., different compatibility ratios at two spatial locations) and homogeneous blocks (the same compatibility ratio at both locations), we first compared the MR signal between these conditions (Fig. 4). Homogeneous blocks activated brain regions that are typically involved in cognitive control and executive attention more strongly than mixed blocks (p < .05, FDR corrected across the entire brain). In homogeneous blocks, we found increased activation in several dorsolateral and medial prefrontal areas: left and right middle frontal gyri (BA 9, 45 and 46), right superior frontal and right medial frontal gyrus (BA 32). Homogeneous blocks elicited higher activity in the left and right anterior cingulate gyri (BA 32) and in the left supplementary motor area (BA 6). We also observed activation in the inferior parietal cortex (BA 40/48), in the parahippocampal gyrus (BA 20), cerebellum and thalamus. Table 1 provides an overview of the activations in the homogenous blocks as compared with the mixed blocks.

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Table 1 – Main effect of homogeneity. Brain regions showing stronger activation in the homogeneous than in the mixed blocks. Extent threshold k = 26, p < .05 FDR corrected. Anatomical description

No. of voxels

Hemisphere Homogeneous > conflict Cerebellum

Vermis Thalamus Middle frontal gyrus

Fusiform gyrus Parahippocampal gyrus Anterior cingulate gyrus Medial frontal gyrus Inferior orbital frontal gyrus Inferior parietal gyrus Superior medial frontal gyrus Middle cingulate gyrus Supplementary motor area Middle temporal gyrus Calcarine gyrus Superior frontal gyrus

BA

L L R (R)

10 9 27 –

R R R L L R L R R R R L R R R L L R R

Z score

9 45/46 6 46 20 20 32 32 32 48 38 48 40 10 23 6 21 17/18 9

2991 91 165 145 1551 286 279 33 56 62 52 212 33 355 177 146 132 150 76 138 62 54 84 33

4.90 3.95 3.82 3.98 4.6 4.13 4.02 3.66 3.56 4.12 4.06 3.99 3.31 3.99 3.95 3.61 3.95 3.84 3.79 3.74 3.54 3.35 3.3 3.27

MNI coordinates x

y

z

−22 −4 46 4 −22 38 40 38 −32 −34 32 −10 8 10 48 34 −48 58 14 2 −16 −50 8 18

− 42 − 52 − 52 − 34 − 14 30 58 10 46 − 26 − 24 38 38 40 42 20 − 48 − 46 64 − 18 12 − 40 − 88 50

− 40 − 44 − 42 − 12 −6 46 14 60 16 − 22 − 20 16 8 28 −2 − 22 36 50 12 38 66 8 2 40

L = left, R = right, BA = Brodmann's area, voxel size 2 × 2 × 2 mm3, x right to left, y anterior to posterior, z superior to inferior.

No brain region exhibited a higher MR signal in the mixed blocks as compared with the homogeneous blocks, even when we lowered the statistical threshold to p < .001, uncorrected for multiple comparisons.

We also tested whether the compatibility ratio differentially influenced brain activity in the homogeneous and mixed blocks and found a corresponding interaction effect (homogeneity× compatibility ratio; p<.001, uncorrected) in the right anterior

Fig. 5 – Interaction between block homogeneity and compatibility ratio. Activity in the ACC was greater in the 70% than in the 30% compatibility condition in the homogeneous blocks only. In the mixed blocks, compatibility ratio did not modulate ACC activity. The bar chart depicts the size of effect for each of the four conditions at the peak voxel within the cluster. Small vertical bars indicate the 95% confidence intervals. Homo = homogeneous block (one compatibility ratio within a block); Mixed = mixed block (two different compatibility ratios within a block assigned to spatial locations above and below fixation); 30% com = 30% compatible and 70% incompatible trials at given position; 70% com = 70% compatible and 30% trials incompatible at given position). Extent threshold k = 21, p < .001 uncorrected.

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Table 2 – (a) Interaction effect between block homogeneity (homogeneous vs. mixed) and compatibility ratio (30% vs. 70%). Brain regions showing significantly greater activity for the 70% compatibility ratio in the homogeneous blocks. (b) Main effect of compatibility (compatible vs. incompatible). Brain regions with greater activation for incompatible than compatible trials. Extent threshold k = 21. p < .001 uncorrected. Anatomical description Hemisphere (a) Interaction: 70–30% × homogeneous conflict Anterior cingulate cortex R Precuneus R (b) Incompatible > compatible Insula Precentral Postcentral Cerebellum

L L L L R L

No. of voxels

Z score

32 29

33 38

4.14 3.78

18 8

38 − 44

16 16

48 6 6 43 6 8

43 69 31 43 26 113

4.15 3.83 3.74 3.81 3.65 3.56

− 38 − 32 − 38 − 56 22 − 40

24 − 14 −2 − 18 − 52 − 34

10 70 62 16 − 30 44

BA

MNI coordinates x

y

z

L = left, R = right, BA = Brodmann's area, voxel size 2 × 2 × 2 mm3; x right to left, y anterior to posterior, z superior to inferior.

cingulate cortex (ACC, BA 32). In this region (Fig. 5), the compatibility ratio modulated the MR signal only in the homogeneous block, but not in the mixed blocks, with greater activity in the 70% compatible condition than in the 30% compatible condition. Although the triple interaction between homogeneity, compatibility ratio and compatibility was not significant, inspection of Fig. 5 reveals that this effect was numerically more pronounced for incompatible than for compatible trials. Hence, within the homogeneous blocks, activity in the ACC was increased, when the general activity level of the cognitive control system was low, but rare incompatible trials occasionally induced a strong response conflict. In the mixed blocks, in contrast, the compatibility ratio did not modulate the MR signal in the ACC (see also Table 2). Brain activity also varied as a function of compatibility (p < .001 uncorrected). Greater activation on incompatible than on compatible trials was observed in the left insula (BA 48) as well as in the left precentral (BA 6) and left postcentral gyri (BA 43) (see Table 2).

3.

General discussion

In the present study, the neurocognitive mechanisms underlying the adaptive adjustment of cognitive control were investigated in three experiments. Using the Eriksen flanker task, we assessed whether a differential adjustment of cognitive control for two stimulus locations is exerted by a single executive control system or, alternatively, by two functionally and neuroanatomically separate executive control systems. The results of our study support the notion of a single cortical cognitive control network that is able to handle different adjustments of cognitive control simultaneously (Cohen et al., 1996). Behavioral results of Experiment 1a showed for the first time that simultaneous adaptation of cognitive control to different conflict levels can be achieved, when the flanker arrays stimulate both hemispheres comparably and the global compatibility ratio is 50% and thus neutral with regard to cognitive control settings in all blocks. Unlike in previous studies with lateralized stimuli (Corballis and Gratton, 2003; Wendt et al., 2008), we presented in

Experiment 1a the flankers at two central positions; nevertheless, we observed a larger behavioral flanker effect at the location with 80% compatible trials as compared to the location with 20% compatible trials. This modulation of the flanker effect by compatibility ratio assigned to two central locations was comparable to the assignment of the corresponding compatibility ratios to two lateral locations in the left vs. right hemifields (Experiment 1b). Hence, adaptation of cognitive control does not depend on hemisphere-specific processing of the flanker stimuli in contrast to previous claims (Corballis and Gratton, 2003). Our behavioral results therefore strengthen the notion that adaptation of cognitive control is location-specific, but not visual field-specific (Vietze and Wendt, 2009; Wendt et al., 2008). This finding was qualitatively replicated in Experiment 2 with a modified design, which allows comparing performance and neural activity in conditions with two different vs. one compatibility ratios. In mixed blocks, different compatibility ratios (30% vs. 70% compatible trials) were assigned to upper and lower positions as in Experiment 1a, whereas in homogeneous blocks the same compatibility ratio (either 30% or 70%) was presented at both spatial locations. Behavioral data showed a modulation of the flanker effect for both the homogeneous and the mixed blocks by compatibility ratio, although in separate analyses of the homogenous and mixed blocks, the interaction between compatibility ratio and compatibility was significant only for the homogenous blocks. This failure to fully replicate the behavioral results of Experiment 1a is presumably due to adaptation of the experimental design to the requirements of an MR experiment (for a detailed discussion, see the Results and discussion section of Experiment 2). Overall, the flanker effect was larger for the location with 70% congruent trials as compared with the location with 30% congruent trials. Although not statistically significant, the modulation of the flanker effect by compatibility ratio was numerically smaller in the mixed than in the homogeneous blocks. This observation suggests that flexible adaptation of cognitive control might be less efficient in dealing with two conflicting compatibility ratios assigned to two spatial locations compared with a single one.

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The somewhat inferior performance of the cognitive control system in dealing with conflicting compatibility ratios is most likely the result of a crosstalk of control settings induced by compatibility ratios at both local and global levels (Corballis and Gratton, 2003; Vietze and Wendt, 2009). Although two locationspecific cognitive control settings can be simultaneously maintained as shown by the present study (particularly Experiments 1a and 1b) as well as by previous work (Corballis and Gratton, 2003; Vietze and Wendt, 2009; Wendt et al., 2008), these control settings are not completely independent, but seem to influence each other to some extent: for instance, in Corballis and Gratton's (2003) Experiment 3 interference at the central location associated with a compatibility ratio of 50% was larger when the lateral locations were associated with a larger compatibility ratio. Furthermore, in Vietze and Wendt's (2009) Experiment 1 the interference effect at a 50% location varied according to the ratio of another location in the error analysis. Hence, there seems to exist a crosstalk between attentional control settings associated with different locations so that the level of attentional control associated with one location is biased by the control level associated with a different location. In addition to the possibility of a crosstalk between locationspecific control settings, the global compatibility ratio averaged across locations could also have influenced control settings associated with specific locations. With regard to Experiment 2 of the present study, the global compatibility ratio averaged across locations was different in homogenous and mixed blocks, which could result in a differential crosstalk between global and local control settings for these block types. In our homogenous blocks, the global compatibility ratio always corresponded to the congruous location-specific compatibility ratios. This congruency of global and local compatibility ratios might have enhanced adaptation of cognitive control to the high and low compatibility ratios, respectively. In our mixed blocks, however, the global compatibility ratio was 50% and thus neutral with respect to the induction of cognitive control settings so that the global compatibility ratio attenuates location-specific adaptation of cognitive control. This differential bias of the global compatibility ratio can therefore additionally explain the more pronounced modulation of the flanker effect by compatibility ratio in the homogenous than in the mixed blocks in the present as well as in Corballis and Gratton's (2003) Experiment 2. Thus, crosstalk of control settings induced by conflicting compatibility ratios at both local and global levels renders location-specific adaptation of cognitive control in conflicting situations (here: mixed blocks) less efficient than in homogenous situations (here: homogenous blocks). The neuroimaging data of Experiment 2 confirmed the conclusion that simultaneous maintenance of two locationspecific control settings is less efficient as compared with a single one. In the homogeneous blocks, brain activity was generally higher than in the mixed blocks in a network of prefrontal and parietal areas typically associated with cognitive control. We propose that a crosstalk between conflicting control settings reduces the efficiency of the cognitive control system to adapt to location-specific compatibility ratios and to adjust cognitive control accordingly. As a result, the cognitive control system is less active in the mixed blocks, which translates into reduced activity in cortical cognitive control circuits. In contrast, in the homogenous blocks the more efficient flexible adjustment of

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the cognitive control system to one single compatibility ratio, translates into generally higher activity in the cortical cognitive control network. Specifically, in the homogenous blocks we found increased activity compared with the mixed blocks in the middle and superior frontal gyri (BA 9, 45 and 46), which have been associated with conflict resolution in previous studies (Bunge et al., 2002; Carter et al., 2000; Fan et al., 2003). Stronger activity in homogeneous than in mixed blocks was also found in medial frontal areas, including the anterior cingulate cortex (BA 32) as well as the adjacent medial frontal gyrus and the supplementary motor area (BA 6). The importance of these medial frontal structures for cognitive control and conflict resolution has been already recognized in several earlier studies (Botvinick et al., 2001; Botvinick et al., 1999; Bush et al., 1998; Chen et al., 2009; Fan et al., 2003; MacLeod and MacDonald, 2000; Nachev et al., 2005; Pardo et al., 1990; Rushworth et al., 2004; Sohn et al., 2007; Taylor et al., 2007). Greater brain activity in response to homogeneous than to mixed blocks was also obtained in the bilateral inferiorparietal cortex. This posterior brain region may implement a trial-by-trial strategic process because in an earlier study its activation lasted to the next trial (Carter et al., 2000). It has been suggested that in interference tasks the parietal cortex mediates representations of possible responses, while the lateral prefrontal cortex selects the correct response among competing ones (Bunge et al., 2002). Modulation of this prefrontal-parietal cognitive control network has likewise been observed when interference from competing meanings of ambiguous words has to be resolved (Hönig and Scheef, 2009), demonstrating the involvement of this network in a variety of cognitive control tasks. As the mixed blocks did not elicit a significantly higher MR signal in any brain region than the homogeneous blocks, our results suggest that the simultaneous maintenance of two conflictive cognitive control settings is supported by a unitary cognitive control system, albeit less efficiently compared with a single control setting in the homogeneous blocks. In further support of this interpretation, ACC activity was modulated by the compatibility ratio only in homogeneous blocks, but not in the mixed blocks. Within the homogeneous blocks, the MR signal in the ACC was increased in the condition with 70% compatible trials, i.e., when rare incompatible events increase the response conflict because the general activity of the cognitive control system is low. A similar modulation of ACC activity by compatibility ratio was also obtained in earlier studies, in which greater ACC activity was observed in the 70% than in the 30% compatibility ratio condition (Carter et al., 2000; Casey et al., 2000). Both the present and the earlier neuroimaging findings support the proposal that the ACC monitors the demands for cognitive control in a given situation. The pattern of ACC activity was mirrored by our behavioral data, where the flanker effect was larger in the 70% condition, particularly in the homogeneous blocks. Less central to the goal of this study, but in line with previous findings, greater activation for incompatible than for compatible trials was observed in the left insula (BA 48) (Botvinick et al., 1999) as well as in the left precentral (BA 6) (Bunge et al., 2002) and left postcentral gyrus (BA 43). In conclusion, the results of our study show that the human cognitive control system can be adjusted flexibly according to the particular compatibility ratios at two spatial positions. This flexible adjustment of cognitive control can occur, even

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when stimuli are centrally presented above and below fixation and comparably stimulate both hemispheres. The present neuroimaging findings further demonstrate that the simultaneous maintenance of two conflicting control settings does not require the recruitment of additional neural circuits, i.e., the mixed blocks were not associated with a greater MR signal than the homogeneous blocks in any area of the brain. Thus, flexible adaptation of cognitive control settings does not depend on additional cortical networks suggesting the involvement of one single cognitive control system. Instead, homogenous blocks elicited stronger activity in a network of prefrontal and parietal brain areas known to be involved in conflict resolution and cognitive control. Furthermore, compatibility ratio modulated ACC activity only in the homogenous, but not in the mixed block. In line with earlier behavioral work (Corballis and Gratton, 2003; Vietze and Wendt, 2009), the present neuroimaging findings indicate that a crosstalk between multiple control settings renders adaptation of cognitive control more efficient when only one uniform rather than two different control settings has to be simultaneously maintained.

4.

Experimental procedures

4.1.

Experiments 1a and 1b

4.1.1.

Subjects

24 (22 females) healthy, 23 right-handed and one left-handed volunteers (mean age= 21 years, range = 19–31 years) participated in Experiment 1a, and 24 (19 females) right-handed volunteers (mean age = 21.5 years, range= 19–40 years) in Experiment 1b. All participants were free from neurological or psychiatric disorders with normal or corrected-to-normal visual acuity and were recruited from the population of psychology students at the University of Finance and Management in Warsaw. Written informed consent was obtained from all participants. The experiment was conducted in accordance with the Declaration of Helsinki. Subjects obtained course credit in exchange for their participation.

4.1.2.

Stimuli and procedure

Cognitive control during interference processing was investigated with the Eriksen flanker task (Eriksen and Eriksen, 1974), in which the letters H and S served as targets and flankers. Letter strings comprised of five letters were presented as stimuli on a computer screen. The target letter was in the center of the array and was underlined. Flankers were either identical with the target (HHHHH or SSSSS, compatible trials) or not (HHSHH, SSHSS, incompatible trials). All stimuli were presented in black font on a white background. From a viewing distance of about 60 cm, a letter array subtended a visual angle of 6.2° (6.5 cm) with a height of about 1°. Letter arrays were randomly presented at one of three possible locations. In Experiment 1a stimuli were presented at central fixation (the fixation point was in the center of the display), 4.3° above fixation or 4.3° below fixation. In Experiment 1b stimuli were presented at central fixation, 4.3° to the left or to the right of fixation. The probability of the letter array appearing at any of the three locations was 33.3%. The probability of the central (target) letter of the array being an “H” or an “S” was 50% for all locations. At the beginning of each trial, participants were presented with a fixation dot in the center for 500 ms followed by a

letter array at one of the three possible spatial positions for 500 ms. Participants were instructed to press the left button of a response pad with the index finger of one hand when the central, underlined letter was an “H” and the right button with the middle finger of the same hand when it was an “S” while ignoring the flanker letters. Letter–finger assignments were reversed for half of the subjects. Instructions emphasized speed and accuracy equally. The next trial automatically started after an interval of 500 ms following participants' response. In one block, all responses were performed with the right hand and in the other one with the left hand. Assignment of response hands to the experimental blocks was counterbalanced across subjects. The experiment was administered on a PC, 22" CRT screen, using Presentation software (v. 9.7, Neurobehavioral Systems Inc.) in a darkened, soundproof chamber. The compatibility ratio (i.e., relative frequency of compatible vs. incompatible trials) differed between the three stimulus locations. In Experiment 1a, for half of the participants, the upper position was assigned to a ratio of 20% compatible trials and 80% incompatible trials, and the lower position to a ratio of 80% compatible trials and 20% incompatible trials. For the other half of the participants, the assignment of the compatibility ratio conditions to the upper and lower positions was reversed. Similarly, in Experiment 1b for half of the participants, the left position was assigned to a ratio of 20% compatible trials and 80% incompatible trials, and the right position to a ratio of 80% compatible trials and 20% incompatible trials. For the other half of the participants, the assignment of the compatibility ratio conditions to the left and right positions was reversed. At the central screen position, the compatibility ratio was 50% for all participants in both experiments. Observers were told in advance about the contingency between array location and compatibility ratio, however, without any particular instruction about it. There were 720 trials in Experiments 1a and 1b. Trials were divided into two identical blocks with 360 trials each. Trial order within blocks was randomized. Number of trials per condition depended on the compatibility ratio assigned to each spatial location. For the 20% compatible/80% incompatible condition at the given spatial position, there were 48 compatible trials and 192 incompatible trials. Similarly, for the 80% compatible/20% incompatible condition assigned to a different location, there were 192 compatible and 48 incompatible trials. For the central position (50% compatible–50% incompatible trials) there were 120 compatible and 120 incompatible trials. Prior to the two blocks of the main experiment, each participant was presented with an instruction and a practice block of 16 trials, which was repeated until participants' performance was error-free. There was a short break between the two experimental blocks. The entire experiment, including practice and instruction, lasted about 25 min.

4.2.

Experiment 2

4.2.1.

Subjects

18 (10 females) healthy, right-handed (Oldfield, 1971) students from the University of Ulm (mean age= 25.3 years, range = 20– 34 years) with normal or corrected-to-normal visual acuity were recruited. All of them were free from neurological or psychiatric disorders according to an in-house questionnaire.

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Written informed consent was obtained from all participants. The experiment was conducted in accordance with the Declaration of Helsinki. Subjects were paid for participation (20 €).

4.2.2.

Stimuli and procedure

As in Experiments 1a and b, stimuli were arrays of five letters comprised of the letters H and S. Stimuli were presented through MR-compatible video goggles. A letter array was randomly presented at one of two central locations above or below fixation (the fixation point was in the center of the display). Due to the presentation with video goggles, the eccentricity of the two stimulus locations above and below fixation could not be precisely determined, but roughly corresponded to a visual angle of 4.3° above and below fixation. The probability of the array appearing on any of two locations was 50%. The probability of the central (target) letter of the array being an “H” or an “S” was always 50%. Each trial started with a small black square (width 1° visual angle) as fixation point, presented at the center of a blank gray screen. After a fixation interval of 700 ms, the letter array was displayed for 500 ms at either the upper or lower position, while the fixation point remained on the display. A blank screen without the central square indicated the inter-trial interval (ITI). Participants were instructed to press the left button of a response pad with the index finger of the right hand when the central underlined letter was an “H” and the right button with the middle finger when it was an “S”. Response assignments were counterbalanced across subjects. In contrast to Experiment 1, all subjects responded with their right hand. Instruction emphasized speed and accuracy equally. The next trial started after a mean ITI of 4800 ms, which was jittered between 3300 and 6300 ms. In randomly intermixed null events trials (40 trials per block), only the fixation square was presented. Experiment 2 consisted of three different types of blocks, each comprised of 200 trials. There were two types of homogeneous blocks (A and B) with identical compatibility ratios at the two locations above and below fixation: either 30% compatible trials at both locations (homogeneous block A) or 70% compatible trials at both locations (homogeneous block B). The third block (block C) was mixed in that different compatibility ratios were present above and below fixation. In one variant of the mixed block (C1), 30% compatible (and 70% incompatible) trials were presented at the upper position, while 70% compatible (and 30% incompatible) trials were presented at the lower position. In the second variant of the mixed block (C2), the contingency between compatibility ratios and spatial position was the opposite. In order to keep the length of the experiment reasonable, half of the participants were presented with block C1 and the other half with block C2. All participants received both types of homogeneous blocks (A and B). All possible presentation orders of the three experimental blocks (A, B, C1/ C2) were counterbalanced across participants. Each of the three experimental blocks was further subdivided into two separate imaging runs, lasting for 12 min and consisting of 100 experimental trials plus 20 null event trials. Hence, the entire experiment was comprised of 720 trials, including null events. Before MR scanning, participants first read information about fMRI scanning, filled out questionnaires and signed the informed consent. Then they received written instructions and practiced the experiment outside the scanner on 16 training trials, where her or his performance was directly controlled by the

63

experimenter. Thereafter, each participant performed another practice block inside the scanner that was comprised of 22 training trials and lasted about 2.5 min (MR images were not collected during this practice block). Participants were not informed about the contingency between array location and compatibility probability. Post-experimental debriefing showed that participants did not notice any contingencies.

4.2.3.

MR scanning and data analysis

Functional and structural MR images were recorded with a 3Tesla Allegra MRI system (Siemens, Erlangen, Germany). For the functional scans, a T2*-weighted single-shot gradient-echo EPI sequence (TE = 38 ms, TR= 2000 ms, flip angle= 90°, matrix 64 × 64 pixels, field of view (FOV) 210 × 210 mm2, voxel size 3.3 × 3.3 × 4.9 mm3) was used. Starting from the bottom of the brain, 30 transversal slices were acquired in interleaved order. Slice orientation was parallel to a line connecting the bases of the frontal lobe and the cerebellum. The entire fMRI experiment consisted of six imaging sessions (two imaging runs for blocks A, B, C1/C2) of about 12 min each, resulting in a total of 2160 functional volumes. Structural images were acquired with a T1-weighted MPRAGE sequence (TR = 2300 ms, TE= 3.9 ms, flip angle= 12°, matrix 256 × 256 pixels, FOV = 256 × 256 mm2, voxel size 1 × 1 × 1 mm3). Functional data were preprocessed and statistically analyzed with SPM5 (http://www.fil.ion.ucl.ac.uk/ spm/software/spm5). Preprocessing included correction for differences in slice timing, spatial realignment to the first volume of the first session, normalization to the MNI reference brain (re-sampled to a voxel size of 2 × 2 × 2 mm3), and smoothing with an isotropic Gaussian kernel of an 8 mm FWHM. Statistical analysis in SPM5 used a random effects model with two levels (Penny and Friston, 2004). In the first level analysis, single-subject fMRI responses were modeled by a design matrix comprising the letter arrays of the following 8 conditions: compatibility (compatible vs. incompatible), compatibility ratio (30% vs. 70%), and homogeneity (homogeneous blocks vs. mixed blocks). Error trials were modeled separately. All these regressors were convolved with the canonical hemodynamic response function and the first temporal derivative (Friston et al., 1998). Realignment parameters were entered as covariates. A temporal highpass filter with a cutoff frequency of 1/128 Hz was applied to the data, and temporal autocorrelation in the fMRI time series (AR1) was estimated (and corrected for) using a first-order autoregressive model. The variation of the compatibility ratio essentially required a different number of trials per condition. Moreover, in each subject, more trials were presented in the homogeneous than in the mixed blocks due to the between-subject presentation of the mixed C1/C2 blocks. As the number of trials strongly influences goodness-of-model estimation in fMRI analysis, only a certain number of trials was included as critical trials into the analysis of the MR data in order to make the number of trials per condition equal and to ensure a comparable signal-to-noise ratio in all conditions. The other trials were modeled, but not used to create the contrast images for the second-level analysis. From the homogeneous block A (30% compatible trials), only trials presented at the upper spatial position were used as critical trials for participants performing the mixed block C1, in which the 30% compatibility ratio was also presented at the upper position). For the other half of the participants, who performed the

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mixed block C2, only trials presented at the lower position in block A were included in the analysis, because in block C2, the 30% compatibility ratio was presented also at the lower position. Similarly, for those participants who performed block C1, only trials at the lower location in block B (70% compatible condition) were included, because the 70% compatibility ratio was presented in block C1 at the lower position. As a result, an equal number of critical trials for a given compatibility ratio was taken from mixed and homogeneous blocks for all spatial locations. Further exclusion of trials concerned uneven number of trials for the compatible and incompatible conditions. In the 70% compatibility ratio condition, there were 70 compatible and 30 incompatible trials at a given spatial position, while for the 30% compatibility ratio condition, there were 30 compatible and 70 incompatible trials at a given spatial position. The number of critical trials of the 70% conditions was closely matched to the number of trials in the 30% conditions (34 vs. 30 trials) by selecting only trials with the letter “H” as the target in the first imaging run (17 trials) at a given spatial position and trials with the letter “S” as the target in the second imaging run (17 trials) at a given spatial position. To allow for inferences at the population level, a second-level analysis (within-subject ANOVA), in which subjects were treated as a random effect, was performed on the images resulting from the contrasts for each subject. Eight contrast images per subjects were submitted to a 2×2×2 ANOVA with the factors compatibility (compatible vs. incompatible trials), compatibility ratio (30% vs. 70%) and homogeneity of block (homogeneous blocks vs. mixed blocks). Comparisons between homogeneous and mixed blocks were thresholded at a significance level of p<.05 and corrected for multiple comparisons across the entire brain (false discovery rate, FDR). All further comparisons were thresholded at a significance level of p<.001 (uncorrected). The spatial extent threshold of clusters was determined according to the expected number of voxels per cluster in all comparisons. All functional group activation maps were overlaid on the MNI reference brain.

Conflicts of interests/disclosure statement All authors reported no biomedical financial interests or potential conflicts of interest.

Role of the funding source Funding for this study was provided by the Polish Ministry of Science and Higher Education, the German Academic Exchange Service (DAAD) and the German Research Foundation (DFG); the Polish Ministry of Science and Higher Education, the DAAD and the DFG had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

Acknowledgments This research was supported by grants from the Polish Ministry of Science and Higher Education (N N106 0190 33 for 2007–2009) and the German Academic Exchange Service (DAAD)—

scholarship for 2008 to Blandyna Żurawska vel Grajewska (née Skalska) and by a grant from the German Research Foundation (DFG; Ki 804 3–1) to Markus Kiefer. The authors thank Gerwin Müller and Kathrin Brändle for their help with fMRI data acquisition, and Alicja Chodowska for her help in conducting a pilot experiment. This manuscript is devoted to Piotr Jaśkowski, our friend, colleague, and teacher, who passed away on January 6, 2011 at the age of 53 years, who stimulated us to conduct this study. Blessed be his memory.

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