Elsevier

NeuroImage

Volume 25, Issue 2, 1 April 2005, Pages 600-606
NeuroImage

Dissociation of neural systems mediating shifts in behavioral response and cognitive set

https://doi.org/10.1016/j.neuroimage.2004.12.054Get rights and content

Abstract

The ability to generate appropriate behaviors in response to changing situations requires both the alteration of ongoing behavior and the understanding of the global rules governing stimulus categorization in a given context. Neuropsychological tests that have been developed to measure this form of cognitive flexibility, such as the Wisconsin Card Sorting Test, have reliably demonstrated that individuals with lesions in regions of the prefrontal cortex and basal ganglia have difficulty generating a cognitive set and altering rule-governed behavior. Recent neuroimaging studies have supported the role of these brain regions in the performance of response shifting and cognitive set shifting. However, the precise role of these regions in the individual components of these tasks remains a contentious issue. Here, we used event-related functional magnetic resonance imaging (fMRI) to dissociate the neural circuitry involved in the alteration of ongoing behavior and the shifting of cognitive set. Participants viewed geometric shapes as they appeared individually in rapid succession and responded with an appropriate button press based upon whether the individual shape was a predetermined target stimulus. Responses were required for each shape presented. The fMRI results indicated that response shifting specifically activated a dorsal neural circuit comprised of the dorsolateral prefrontal cortex, anterior cingulate, and intraparietal sulcus. Shifts in cognitive set were mediated by ventrolateral prefrontal cortex, anterior cingulate, and striatum. These findings suggest that the alteration of ongoing behavior and shifting of cognitive set are mediated by two distinct neural systems interconnected by the anterior cingulate.

Introduction

The generation of appropriate behavioral responses requires the ability to understand the global rules governing stimulus classification, select the most fitting response among competing possibilities, and inhibit task-inappropriate prepotent responses. Successful implementation of these and other executive functions (EF) is commonly associated with intact functioning of prefrontal cortex (PFC). Lesions of PFC have been linked to impaired performance on tasks of cognitive flexibility, stimulus categorization, and planning (Milner, 1963, Robinson et al., 1980, Shallice, 1982, Stuss et al., 2000). In addition, the basal ganglia have been implicated in EF, as similar behavioral deficits have been observed in patients with Parkinson's disease (Gotham et al., 1988, Lees and Smith, 1983, Owen et al., 1993).

Functional neuroimaging studies have supported the role of frontal-striatal circuitry in EF, demonstrating activation of these regions during specific aspects of the Wisconsin Card Sorting Test (WCST) (Berman et al., 1995, Konishi et al., 1998, Konishi et al., 1999, Monchi et al., 2001) and similar set-shifting tasks (Rogers et al., 2000), the Tower of London (TOL) (Baker et al., 1996, Elliott et al., 1997, Owen et al., 1996), and tasks of inhibitory control, such as the go/no-go and stop tasks (Rubia et al., 1999, Rubia et al., 2001). However, the precise role of the basal ganglia or dorsal and ventral PFC during the generation of appropriate responses, inhibition of prepotent responses, and shifting of cognitive set has remained elusive. While some studies demonstrate striatal activation during mental shifts to a new response set (Monchi et al., 2001), others have observed striatal activation only during changes involving object alternation and not for changes in task rules (Cools et al., 2004). However, task differences across studies make it difficult to compare the neural processes required for these mental activities and may help explain conflicting results.

Similar to the conflicting findings for basal ganglia, at least two theories have emerged regarding the roles of dorsal and ventral PFC in the neural control of behavior. In one account, dorsolateral prefrontal cortex (DLPFC) is most closely associated with working memory (Barch et al., 1997, Cohen et al., 1997, McCarthy et al., 1996, Smith and Jonides, 1998, Smith and Jonides, 1999), target detection (Kirino et al., 2000, McCarthy et al., 1997), and the modification of stimulus–response contingencies or response strategies (Dove et al., 2000, Huettel and McCarthy, 2004, Huettel and Misiurek, 2004). Ventrolateral prefrontal cortex (VLPFC), on the other hand, has been associated with response inhibition (Konishi et al., 1999, Rubia et al., 2003) and response shifts (Smith et al., 2004). Alternatively, both regions mediate response inhibition (Casey et al., 1997, Casey et al., 2001, Liddle et al., 2001), but DLPFC is primarily associated with the attentional component of response switching, and VLPFC mediates the cognitive categorization of stimuli and stimulus–response contingencies (Dias et al., 1997, Nagahama et al., 2001). An additional view suggests that both DLPFC and VLPFC contribute to both response and rule shifting, and argues against the notion of functionally-distinct regions within PFC (Cools et al., 2004). These various accounts of frontal cortical function provide conflicting ideas of how regions within PFC may guide behavior during set shifting tasks. One goal of the current study was to more precisely categorize the role of distinct regions of PFC in isolated components of EF.

The present study used event-related functional magnetic resonance imaging (fMRI) to test the hypothesis that two dissociable neural systems exist within frontal-striatal regions mediating shifts in behavioral responses and cognitive set. We developed a variation of a novel task previously used in our lab (Kirino et al., 2000) in which participants viewed sequences of geometric shapes and were required to alter ongoing responses when a predetermined target shape appeared. Non-target distracter shapes that did not require a change in behavioral response were interspersed within the sequence of shapes. The shape identified as the target changed periodically throughout the study, leading to two conditions, a shift in behavioral response associated with the presentation of a target and a shift in the rules governing stimulus–response associations. We predicted that target stimuli would preferentially activate DLPFC, basal ganglia, and posterior parietal cortex relative to non-target “oddball” stimuli due to the role of these regions in target detection and execution of appropriate behavioral responses. Given the role of VLPFC in stimulus classification, we further predicted that changes in the target stimulus would lead to increased activation in a ventral prefrontal-striatal system.

Section snippets

Subjects

Subjects were fourteen healthy, young adult volunteers (12 male, 2 female), ages 20–39 years (mean 27.8 years), with no history of psychiatric or neurological disorder. All subjects received a complete verbal description of the study and provided written informed consent, approved by the University of North Carolina School of Medicine Committee on the Protection of the Rights of Human Subjects and the Duke University Health System's Institutional Review Board.

fMRI task

Subjects performed a target

Behavioral performance

Accuracy (percent correct) and reaction time (RT) data are shown in Fig. 2. Statistical analyses of RT data were performed only on correct trials in order to limit the effect of simple RT/accuracy trade-offs. Paired samples t tests compared performance for target versus non-target novel stimuli. Results indicated lower accuracy [t (11) = 4.53, P < 0.001] and longer RTs [t (11) = 4.15, P < 0.005] for target trials compared with novel trials. No significant differences in accuracy or RT were

Discussion

These results indicate that different neural systems are associated with shifts in behavioral response and shifts in cognitive set. Specifically, we found that trials requiring the alteration of ongoing behavior recruited a neural system comprised of the DLPFC, ACC, premotor and motor cortices, inferior frontal/anterior insula, IPS, and striatum. While some of these activations overlapped with brain regions recruited for non-target novel stimuli, activation within the DLPFC, ACC, and IPS was

Acknowledgments

The authors would like to thank Chuck Michelich and Joshua Bizzell for writing image analysis software, Kevin Tessner for programming the task, and MRI technologists Benjamin Chen, Jordan Tozer, and Natalie Goutkin for assistance with data acquisition. This research was supported by NIH grant 5U54MH66418-02.

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