Dissociation of neural systems mediating shifts in behavioral response and cognitive set
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.
References (46)
- et al.
Neural systems engaged by planning: a PET study of the Tower of London task
Neuropsychologia
(1996) - et al.
Dissociating working memory from task difficulty in human prefrontal cortex
Neuropsychologia
(1997) - et al.
Physiological activation of a cortical network during performance of the Wisconsin Card Sorting Test: a positron emission tomography study
Neuropsychologia
(1995) - et al.
Differential activation of right superior parietal cortex and intraparietal sulcus by spatial and nonspatial attention
NeuroImage
(1998) - et al.
Prefrontal cortex activation in task switching: an event-related fMRI study
Brain Res. Cogn. Brain Res.
(2000) - et al.
What is odd in the oddball task? Prefrontal cortex is activated by dynamic changes in response strategy
Neuropsychologia
(2004) - et al.
Neuroanatomic overlap of working memory and spatial attention networks: a functional MRI comparison within subjects
NeuroImage
(1999) - et al.
Inhibitory control in children with attention-deficit/hyperactivity disorder: event-related potentials identify the processing component and timing of an impaired right-frontal response-inhibition mechanism
Biol. Psychiatry
(2000) - et al.
Mapping motor inhibition: conjunctive brain activations across different versions of go/no-go and stop tasks
NeuroImage
(2001) - et al.
Right inferior prefrontal cortex mediates response inhibition while mesial prefrontal cortex is responsible for error detection
NeuroImage
(2003)
Wisconsin card sorting test performance in patients with focal frontal and posterior brain damage: effects of lesion location and test structure on separable cognitive processes
Neuropsychologia
Anterior cingulate cortex, conflict monitoring, and levels of processing
NeuroImage
The human prefrontal and parietal association cortices are involved in NO-GO performances: an event-related fMRI study
NeuroImage
Parallel organization of functionally segregated circuits linking basal ganglia and cortex
Annu. Rev. Neurosci.
Conflict monitoring and cognitive control
Psychol. Rev.
A developmental functional MRI study of prefrontal activation during performance of a go–nogo task
J. Cogn. Neurosci.
Sensitivity of prefrontal cortex to changes in target probability: a functional MRI study
Hum. Brain Mapp.
Temporal dynamics of brain activation during a working memory task
Nature
Differential responses in human striatum and prefrontal cortex to changes in object and rule relevance
J. Neurosci.
Dissociable forms of inhibitory control within prefrontal cortex with an analog of the Wisconsin Card Sort Test: restriction to novel situations and independence from “on-line” processing
J. Neurosci.
Prefrontal dysfunction in depressed patients performing a complex planning task: a study using positron emission tomography
Psychol. Med.
‘Frontal’ cognitive function in patients with Parkinson's disease ‘on’ and ‘off’ levodopa
Brain
Modulation of prefrontal cortex activity by information toward a decision rule
NeuroReport
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