Using fMRI to decompose the neural processes underlying the Wisconsin Card Sorting Test
Introduction
The ability of a subject to effect contextually appropriate behavior involves a range of executive functions. The term ‘executive functions’ refers to a number of higher-order cognitive processes including planning, initiation, hypothesis generation, cognitive flexibility, decision making, regulation, judgment, feedback utilization and self-perception.
A clinically widely used test to assess executive functions is the Wisconsin Card Sorting Test (WCST) (Grant and Berg, 1948). Although the WCST is sensitive to frontal lobe dysfunction, it has proved difficult to determine the specific contributions of different cerebral regions to the task because of its complexity. A number of previous imaging studies used the WCST, aiming to delineate the neural representations of selected task components such as set-shifting, working memory, or inhibitory control processes (Monchi et al., 2001, Konishi et al., 1999, Konishi et al., 2003). However, integrating the findings of these studies in order to elucidate the specific contributions of particular brain regions to specific cognitive components has been problematic due to differences in experimental design. We therefore aimed at integrating and extending the findings of previous studies by fractionating the different cognitive components underlying the WCST within the same group of subjects. We thereby intended to translate the clinically well-established WCST into a functional neuroimaging paradigm, which can be used to delineate the neural correlates of the different task components in each subject. Determining the ‘neural signature’ of specific cognitive components in healthy subjects may allow dysexecutive syndromes (e.g. Parkinson's disease) to be characterized on a pathophysiological basis. Such simple efficient experimental designs could then be used in future studies of patient populations to establish functional imaging as an additional diagnostic and prognostic tool. With this ultimate aim in mind, we implemented a computerized version of the WCST with 3 different test variants (A, B, C) in a simple but efficient blocked-design, which allowed us to segregate different cognitive components of the WCST within the same individual.
A cognitive gradient in task demands was introduced across conditions (A > B > C), while the experimental setting remained otherwise unchanged. Task A was very similar to the original WCST, in which subjects have to match a stimulus card to one of four reference cards. The four reference cards show different geometric figures; they also differ in the number of objects displayed and their color (see Fig. 1). The stimulus card can be matched to one of the four reference cards by either color, shape, or number of objects. The subject is not informed about the sorting dimension but rather deduces the sorting rule in part by trial and error, relying upon the feedback provided by the investigator. If the correct sorting criterion has been found and if four correct answers have been given consecutively, the sorting dimension is changed by the examiner. The subject then has to adapt to the change and has to search again for the new correct sorting criterion. In task B, subjects are explicitly instructed about the dimensional changes, which occur once every four trials. The (instructed) dimension thus only has to be maintained/retrieved during the following four trials, until the next dimensional change occurs. In task C, the task is further simplified by providing the respective sorting dimension prior to each trial, thereby reducing working memory demands to a minimum. In the HLB, each stimulus card is identical to one of the four reference cards. The HLB thus includes no set-shifting operations and basically controls for perceptual, motor and identity matching and response selection components inherent to the WCST.
Accordingly, contrasting C with the HLB delineates the basic cognitive network engaged in the matching task (i.e. matching a non-identical card according to a criterion, relative to identifying identical cards as involved in the HLB) plus the neural processes underlying (instructed) set-shifting relative to no set-shifting. Contrasting B with the HLB additionally reveals simple working memory operations. Contrasting A with the HLB shows the whole neural network underlying WCST performance. Additionally, contrasting A with B depicted the neural correlates of error detection/feedback utilization, complex working memory operations and (uninstructed relative to instructed) set-shifting. Contrasting B with C extracts neural representations of simple working memory operations. Based upon previous data, we hypothesized that A–B would reveal increased neural activity in the dorsolateral prefrontal cortex (DLPFC), while B–C would show activity in the ventral prefrontal cortex, reflecting known functional dissociations within the prefrontal cortex regarding simple and complex working memory operations (Petrides, 2000). We furthermore expected the ACC to be increasingly engaged the higher the task demands are (A > B > C), reflecting processes of response selection (Barch et al., 2000), attentional control (Posner and Petersen, 1990) and error detection (Gehring et al., 1993).
Section snippets
Subjects
Twelve healthy right-handed volunteers (10 males, 2 females; age range: 19–36 years, mean 24 ± 5 years) were investigated using fMRI. No volunteer had a history of neurological or psychiatric diseases. All subjects gave informed prior consent; the study protocol was approved by the local ethics committee of the Medical Faculty of the RWTH-Aachen. None of the participating subjects had experience of the WCST beforehand. Subjects were informed that the task consisted of matching a stimulus card
Behavioral data
As expected, cognitive ‘costs’ were highest for task A (380 ms ± 192) and decreased with reduced task complexity (B: 345 ms ± 123; C: 243 ms ± 107). The within-subject ANOVA demonstrated a significant effect of ‘cognitive costs’ (F = 4.96; df = 1.2, P < 0.04) across the different task conditions. While cognitive costs for task A were not significantly higher as compared to B (F = 0.34; df = 1, P < 0.572), cognitive costs for task B relative to C (F = 16.96; df = 1, P < 0.002) and for A relative
Discussion
Using the same group of volunteers, we deployed three different variants of the WCST to fractionate the different cognitive processes and associated neural network components involved. As the three different test variants differed in task complexity, different cognitive components were extracted using a serial subtraction design. Imaging data were further subjected to a correlational analysis, accounting for individual behavioral parameters.
Conclusion
We have provided a neural framework for the cognitive processes involved in the WCST and suggest a principal role for the right prefrontal cortex with regard to executive components of working memory. This locus of activation may underlie the particular sensitivity of the WCST to frontal lobe pathology, although specificity is limited by the extended network involved. Our data further indicate a functional dissociation of the rostral and caudal parts of the ACC in the implementation of
Acknowledgments
We are grateful to our colleagues from the MR and Cognitive Neurology groups. We thank Oliver Haumann and the radiographic staff of the Institute of Medicine for technical assistance. This study was supported by a grant from the Bundesministerium für Bildung und Forschung (BMBF, Project No. 01/BC01G-Modkog) to GRF.
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