Cognitive Flexibility: A Default Network and Basal Ganglia Connectivity Perspective

Abstract

The intra/extradimensional set-shifting task (IED) provides a reliable assessment of cognitive flexibility, the shifting of attention to select behaviorally relevant stimuli in a given context. Impairments in this domain were previously reported in patients with altered neurotransmitter systems such as schizophrenia and Parkinson's disease. Consequently, corticostriatal connections were implicated in the mediation of this function. In addition, parts of the default mode network (DMN), namely the medial prefrontal and posterior cingulate/precuneus cortices, are also being progressively described in association with set-shifting paradigms. Nevertheless, a definitive link between cognitive flexibility and DMN connectivity remains to be established. To this end, we related resting state functional magnetic resonance imaging (fMRI)-based functional connectivity of DMN with IED task performance in a healthy population, measured outside the scanner. The results demonstrated that greater posterior cingulate cortex/precuneus (DMN) connectivity with the ventromedial striatopallidum at rest correlated with fewer total adjusted errors on the IED task. This finding points to a relationship between DMN and basal ganglia connectivity for cognitive flexibility, further highlighting this network's potential role in adaptive human cognition.

Keywords: basal ganglia; cognitive flexibility; default mode network; functional connectivity; intra/extradimensional set-shifting; striatum.

FIG. 1.

The simple and compound discrimination blocks of the intra/extradimensional set-shifting task (IED). Focusing specifically on cognitive/attentional flexibility, the IED task is part of the CANTAB battery of neuropsychological tests, designed to assess the integrity of frontostriatal connections. While the intradimensional (shapes are relevant) set-shifts represent lower order switching, the extradimensional (lines are relevant) set-shifts denote higher order abstract rule shifts. Color images available online at www.liebertpub.com/brain

FIG. 2.

Posterior cingulate cortex/precuneus seed-based functional connectivity reveals an extensive default mode network (DMN). (A) A meta-analysis map based on 1018 functional imaging studies was overlaid with an Automated Anatomical Labeling mask of the posterior cingulate cortex/precuneus (PCC/PCUN), resulting in the final seed used for the functional connectivity analysis. (B) General linear model, including seed signal as the variable of interest, revealed a DMN compatible with previous reports (Andrews-Hanna et al., 2014). The results are displayed on a smooth MNI152 brain. Color images available online at www.liebertpub.com/brain

FIG. 3.

Posterior cingulate cortex/precuneus (PCC/PCUN) connectivity with the ventromedial striatopallidum correlates with IED task errors. (A) Regressing the DMN connectivity with the total adjusted IED task errors for each subject (corrected for age) revealed a connection between PCC/PCUN and ventromedial striatopallidum, including the bilateral ventromedial putamen head and left tail, bilateral ventromedial caudate (parts of the nucleus accumbens), and right ventromedial pallidum (FWE_cluster p = 0.007). (B) Greater functional connectivity between DMN and ventromedial striatopallidum with a global peak on the left ventromedial putamen [MNI: −28 6 0] predicted fewer total adjusted IED errors, and thus better performance. Further linear regression with the higher order extradimensional set-shifting errors revealed a significant correlation with the signal from the same regions; however, this relationship did not exist for the errors in the lower order intradimensional set-shifting stage. Color images available online at www.liebertpub.com/brain