ACADEMIA Letters The Default Mode Network: Functioning in Healthy Adults and Major Depressive Disorder and Implications for Treatment CJ Healy The default mode network (DMN) is a functional network of brain hubs that is active during a resting state (for a review, see Raichle, 2015). It was discovered and identifed by chance: brain researchers noticed that when participants in neuroimaging studies began to perform goal-directed and non-self-referential tasks after being in a resting state, they saw consistent, uniform patterns of deactivation across a network of brain regions (Mak et al., 2016). These brain regions comprise discrete, bilateral, and symmetrical cortical areas in the medial and lateral parietal cortex, the medial prefrontal cortex, and the medial and lateral temporal cortex (Raichle, 2015). Resting-state functional connectivity (RSFC) of the DMN has been implicated in a vari- ety of psychiatric disorders, and changes in DMN RSFC have been associated with positive treatment outcomes (Mak et al., 2016; Raichle, 2015). This paper begins with a brief review of DMN anatomy and functioning in healthy adults. It then continues to review abnormalities in DMN RSFC found in major depressive disorder (MDD) and changes in DMN RSFC fol- lowing administration of classic psychedelics, particularly psilocybin, that have been shown to predict positive outcomes in both healthy and depressed participants. DMN Healthy Functioning Raichle (2015) presents a comprehensive review of the components and normal function- ing of the default mode network. The DMN represents organization within the brain’s in- trinsic or ongoing activity (Raichle, 2015). It was discovered not by showing activation in Academia Letters, June 2021 Corresponding Author: CJ Healy, cjhealy@newschool.edu Citation: Healy, C. (2021). The Default Mode Network: Functioning in Healthy Adults and Major Depressive Disorder and Implications for Treatment. Academia Letters, Article 1122. https://doi.org/10.20935/AL1122. 1 ©2021 by the author — Open Access — Distributed under CC BY 4.0