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Disentangling the prefrontal network for rule selection by means of a non-verbal variant of the Wisconsin Card Sorting Test.

ABSTRACT: This study disentangles the prefrontal network underlying executive functions involved in the Wisconsin Card Sorting Test (WCST). During the WCST, subjects have to perform two key processes: first, they have to derive the correct sorting rule for each trial by trial-and-error, and, second, they have to detect when this sorting rule is changed by the investigator. Both cognitive processes constitute key components of the executive system, which is subserved by the prefrontal cortex. For the current fMRI experiment, we developed a non-verbal variant of the WCST. Subjects were instructed either to respond according to a given sorting rule or to detect the correct sorting rule, like in the original version of the WCST. Data were obtained from 14 healthy male volunteers and analysed using SPM and a random effects model. All conditions activated a fronto-parietal network, which was generally more active when subjects had to search for the correct sorting rule than when the rule was announced beforehand. Significant differences between these two conditions were seen in the dorsolateral prefrontal cortex (PFC) and the parietal lobe. In addition, the data provided new evidence for the assumption of differentiated roles of the left and right prefrontal cortex. Although the right PFC showed a general involvement in response selection and the execution of goal directed responses, based on given rules, the left PFC was only activated when inductive reasoning and feedback integration was required.

SUBMITTER: Specht K

PROVIDER: S-EPMC6870978 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Cognitive flexibility is a critical component of executive function and is strongly influenced by genetic factors. We conducted a genome-wide association study of cognitive flexibility (as measured by perseverative errors on the Wisconsin Card Sorting Test) in two sets of African American (AA) and European American (EA) subjects (Yale-Penn-1: 1,411 AAs/949 EAs; Yale-Penn-2: 1,178 AAs/1,335 EAs). We examined the association of cognitive flexibility with genotyped or imputed SNPs across the genome. In AAs, two correlated common single nucleotide polymorphisms (SNPs) (rs7165213/rs35633795) in the downstream region of the noncoding gene LOC101927286 on chromosome 15 showed genome-wide significant (GWS) associations with cognitive flexibility (Yale-Penn-1: p = 6.0 × 10-9 /1.3 × 10-8 ; Yale-Penn-2: p = .029/.010; meta-analysis: p = 4.2 × 10-7 /1.0 × 10-7 ) in the same effect direction. In EAs, no GWS associations were observed. Enriched gene sets identified by Data-driven Expression-Prioritized Integration for Complex Traits (DEPICT) analysis of the top SNPs (pmeta-analysis < 10-5 ) included the signalosome and ubiquitin-specific peptidase 9, X-linked (USP9X) subnetwork in AAs, and abnormal frontal and occipital bone morphology in EAs. We also performed polygenic risk score (PRS) analysis to examine the genetic correlation of cognition-proxy phenotypes (general cognitive function, education attainment, childhood intelligence, and infant head circumference) and cognitive flexibility in EAs. The PRS derived from general cognitive function-associated SNPs was significantly associated with cognitive flexibility. Nongenetic factors (age, education, sex, and tobacco recency) also exerted significant effects on cognitive flexibility. Our study demonstrates that both genetic and nongenetic factors impact cognitive flexibility, and variants in genes involved in protein degradation and brain development may contribute to population variation in cognitive function.

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Disentangling the prefrontal network for rule selection by means of a non-verbal variant of the Wisconsin Card Sorting Test.

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