Causal interactions between fronto-parietal central executive and default-mode networks in humans

Abstract

Information processing during human cognitive and emotional operations is thought to involve the dynamic interplay of several large-scale neural networks, including the fronto-parietal central executive network (CEN), cingulo-opercular salience network (SN), and the medial prefrontal-medial parietal default mode networks (DMN). It has been theorized that there is a causal neural mechanism by which the CEN/SN negatively regulate the DMN. Support for this idea has come from correlational neuroimaging studies; however, direct evidence for this neural mechanism is lacking. Here we undertook a direct test of this mechanism by combining transcranial magnetic stimulation (TMS) with functional MRI to causally excite or inhibit TMS-accessible prefrontal nodes within the CEN or SN and determine consequent effects on the DMN. Single-pulse excitatory stimulations delivered to only the CEN node induced negative DMN connectivity with the CEN and SN, consistent with the CEN/SN's hypothesized negative regulation of the DMN. Conversely, low-frequency inhibitory repetitive TMS to the CEN node resulted in a shift of DMN signal from its normally low-frequency range to a higher frequency, suggesting disinhibition of DMN activity. Moreover, the CEN node exhibited this causal regulatory relationship primarily with the medial prefrontal portion of the DMN. These findings significantly advance our understanding of the causal mechanisms by which major brain networks normally coordinate information processing. Given that poorly regulated information processing is a hallmark of most neuropsychiatric disorders, these findings provide a foundation for ways to study network dysregulation and develop brain stimulation treatments for these disorders.

Keywords: fMRI; neuromodulation; task negative network; task positive network.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.

Outline of the procedures in this study. The study consisted of two sessions occurring on separate days.

Fig. 2.

(A) The theorized model for an inhibitory relationship between the DMN and CEN/SN. (B) Single-pulse TMS was used to excite CEN or SN nodes. (C) rTMS (1 Hz) was used to inhibit CEN or SN nodes. (D) TMS stimulation sites (determined using an ICA on rs-fMRI data from an independent set of healthy subjects) and primary motor cortex (M1) by subject. (E) Network a priori ROIs, defined using an ICA across all rs-fMRI scans in the experimental group.

Fig. 3.

TMS modulates network-level PPI connectivity. Single-pulse excitatory TMS to the pMFG (CEN node), but not to the aMFG (SN node), resulted in (A) negative DMN PPI connectivity with the combined CEN and SN, which was furthermore observed only for the MPFC node of the DMN, (B) negative DMN PPI connectivity with the CEN alone (also driven by the DMN’s MPFC component), and (C) negative DMN PPI connectivity with only the dACC component of the SN (also driven by the DMN’s MPFC component). (D) Illustrative voxelwise map of the MPFC-seeded PPI connectivity difference in response to pMFG (relative to aMFG) single-pulse TMS (P < 0.005, uncorrected). Positive signals indicate greater negative connectivity in response to single-pulse TMS to the pMFG. (E) Within-SN PPI connectivity is preferentially induced by aMFG stimulation, whereas (F) within-CEN PPI connectivity is induced by both stimulation sites.

Fig. 4.

Disinhibition of endogenous DMN activity after 1-Hz rTMS to the pMFG (CEN node), as reflected by (A) a shift of DMN signal, primarily in the MPFC (B), from lower frequencies (0.008–0.1 Hz) to (C and D) higher frequencies (0.1–0.25 Hz), plotted for the DMN (MPFC and PCC) or MPFC alone. The illustrative voxelwise maps show the difference in LF (B) or HF (D) signal amplitude for the difference between resting-state scans after 1-Hz pMFG rTMS compared with after 1-Hz aMFG rTMS (P < 0.005, uncorrected).