The role of default network deactivation in cognition and disease

Abstract

A considerable body of evidence has accumulated over recent years on the functions of the default-mode network (DMN)--a set of brain regions whose activity is high when the mind is not engaged in specific behavioral tasks and low during focused attention on the external environment. In this review, we focus on DMN suppression and its functional role in health and disease, summarizing evidence that spans several disciplines, including cognitive neuroscience, pharmacological neuroimaging, clinical neuroscience, and theoretical neuroscience. Collectively, this research highlights the functional relevance of DMN suppression for goal-directed cognition, possibly by reducing goal-irrelevant functions supported by the DMN (e.g., mind-wandering), and illustrates the functional significance of DMN suppression deficits in severe mental illness.

Figure 1. Functional relevance of DMN suppression

(a) Left panel shows regions closely corresponding to the DMN that were identified as exhibiting a weaker signal for correct relative to incorrect trials while healthy adults performed a delayed object working memory task (black borders mark the DMN as originally defined by Fox and colleagues [4]). Top right panel shows the signal extracted out of all the identified foci displayed in the functional map. For each region a green line indicates correct trials whereas a red line marks incorrect trials. Average correct vs. incorrect signal for all DMN regions is shown in solid vs. dashed black lines respectively. (b) Functional connectivity between three a-priori defined large-scale networks (red=control; yellow=sensory- motor; blue=default mode network) and a lateral-prefrontal node that was stringently identified as being involved in cognitive control. Panels on the right show individual differences in IQ (assessed using Raven’s progressive matrices) and connectivity for a large sample of college-age adults (N=94). Both sensory and control network connectivity strength was positively associated with IQ, whereas the DMN network connectivity was inversely correlated with IQ, such that higher IQ individuals evidenced stronger anti-correlation. Figures adapted with permission from [29] and [67].

Figure 2. DMN deactivation findings across clinical, pharmacological and computational approaches

(a) We identified a set of regions (2 example foci shown) where patients (red) relative to healthy controls (blue) failed to show sustained activation (top) as well as appropriate suppression (bottom) during delayed WM [32]. This finding was present even in the context of matched performance. (b) Regions closely corresponding to FPCN and the DMN were modulated by an NMDA-receptor antagonist ketamine (red) relative to placebo control condition (blue) [37]. We highlight two regions with a similar pattern of modulation as observed in schizophrenia. (c) A computational model of WM, comprised of task-activated (top) and task-deactivated (bottom) modules highlighting a possible mechanism for deactivation (see Box 3), followed by results. We tested whether ‘disinhibition’ via reduced NMDA receptor conductance onto GABA cells (E–I) (small red arrow) would resemble activation/deactivation BOLD findings under ketamine and observations in schizophrenia. Figures adapted with permission from [32] and [37].