Definition and characterization of an extended multiple-demand network

Abstract

Neuroimaging evidence suggests that executive functions (EF) depend on brain regions that are not closely tied to specific cognitive demands but rather to a wide range of behaviors. A multiple-demand (MD) system has been proposed, consisting of regions showing conjoint activation across multiple demands. Additionally, a number of studies defining networks specific to certain cognitive tasks suggest that the MD system may be composed of a number of sub-networks each subserving specific roles within the system. We here provide a robust definition of an extended MDN (eMDN) based on task-dependent and task-independent functional connectivity analyses seeded from regions previously shown to be convergently recruited across neuroimaging studies probing working memory, attention and inhibition, i.e., the proposed key components of EF. Additionally, we investigated potential sub-networks within the eMDN based on their connectional and functional similarities. We propose an eMDN network consisting of a core whose integrity should be crucial to performance of most operations that are considered higher cognitive or EF. This then recruits additional areas depending on specific demands.

Keywords: Executive functioning; Functional connectivity; Hierarchical clustering; Higher cognitive functions; Meta-analytical connectivity modeling.

Figure 1

Seed regions (shown in dark blue) derived from the meta-analytically defined multiple-demand network by Müller et al. 2015 (shown in red).

Figure 2

Workflow used for the delineation of the extended multiple demand network entailing the computation of task-free (RS-FC) and task-based (MACM) connectivity maps for each seed region which were then converged to identify the eMDN.

Figure 3

Results showing the different resulting extended networks depending on the number of overlapping consensus maps. Eight overlapping consensus maps yielded clusters located in the bilateral IFJ/IFG, bilateral aINS, and bilateral pre-SMA (in red). Seven overlapping maps resulted in the addition of the bilateral IPS, right MFG/IFS and left dPMC (in yellow). Six overlapping maps resulted in the addition of the left MFG/IFS (in green). Five overlapping maps additionally included the right dPMC, left putamen, left thalamus and left ITG (in cyan). Four overlapping maps resulted in the addition of the right putamen and right thalamus (in blue).

Figure 4

Clustering of the extended MDN regions based on resting state connectivity, whole brain co-activation and behavioural domains and paradigm classes. The different colours represent the grouping that resulted from the different clustering analyses.

Figure 5

Functional differences between each pair of sub-networks (cluster consisting of the pre-SMA, aINS and the MFG/IFS is shown in green; cluster consisting of the IFJ, IPS, dPMC and left ITG is shown in red; sub-cortical cluster i.e., bilateral putamen and thalamus is shown in yellow). “Behavioral Domain” meta-categories in the BrainMap database were used to perform forward inference to determine the above-chance differences in activating either set of regions given a particular behavioural domain. The baserate denotes the general probability of BrainMap activation of the given seeds.

Figure 6

Summary figure illustrating results obtained from hierarchical clustering and functional decoding analyses revealing three main cliques.