The Journey of the Default Mode Network: Development, Function, and Impact on Mental Health

It was formerly believed that the brain remained inactive during rest, and resting data were primarily collected for comparison with other cognitive tasks. Subsequent research challenged this notion, revealing increased activity in specific brain regions during passive periods and leading to the discovery of the Default Mode Network (DMN) through functional neuroimaging, particularly fMRI. Since its identification at the end of the 20th century, the DMN has become a focal point across neuroscience, psychology, and medicine due to its activity during rest and its role in internal cognitive processes and states of consciousness. Advances in neuroimaging technology have revealed the DMN’s involvement in episodic memory, emotional processing, mental narratives, and self-reflection. The DMN interacts dynamically with other large-scale brain networks, notably the executive control network (ECN), which shows reciprocal activity patterns (DMN decreases while ECN increases under high cognitive demand), and the Salience Network (SN), which detects relevant stimuli and acts as a switch between DMN and ECN. Recent studies emphasize the DMN’s dynamic connectivity that tracks affective states across multiple timescales, with strong internal connectivity at rest and adaptive shifts during emotional or cognitive demands. These interactions among DMN, ECN, and SN support cognitive and emotional flexibility and are linked to mental health. The DMN is implicated in neuropsychiatric disorders such as depression, anxiety, and ADHD, underscoring its potential to transform our understanding of brain function and its impact on mental health and well-being.

The review synthesizes decades of work on the DMN’s discovery, characterization, and clinical relevance. A timeline highlights key milestones: PET evidence of rest-related activity (1997); recognition of intrinsic activity during rest (2001); identification of consistent DMN patterns (2003); anti-correlation with task-positive networks (2005); links to mind-wandering (2007); modulation by pain and working memory load; structural–functional connectivity underpinnings (2008–2009); fractionation into subsystems (2008); advances in neuroimaging, genetics, and multimodal integration (2012–2015); computational modeling and machine learning (2016–2017); network dynamics and aging (2018–2020); non-invasive interventions (tDCS/TMS) and personalized approaches (2022–2024). The paper outlines 10 theoretical perspectives on DMN function, including the sentinel hypothesis and internal mental activity (spontaneous cognition), associative memory theory, self-construction, social connection, autobiographical memory, creative imagination, self-reflection, mental foresight, and temporal coherence. These frameworks converge on DMN’s roles in monitoring the environment, self-referential processing, memory-based simulation of past/future events, social cognition (empathy and theory of mind), and narrative identity.

- Neuroanatomy: The DMN comprises anterior and ventral medial prefrontal cortex (mPFC/vmPFC), posterior cingulate cortex (PCC), precuneus, inferior parietal lobule (IPL), and middle temporal gyrus (MTG). It can be subdivided into central core, medial temporal subsystem, and medial prefrontal subsystem. - Core nodes: PCC integrates subsystems and is linked to self-reflection and rumination; precuneus supports episodic memory, imagination, and attentional transitions. - Medial temporal subsystem: Hippocampus and parahippocampal cortex support episodic/autobiographical memory and future simulation; DMN–hippocampus interactions are central to memory and navigation; alterations are relevant to pediatric development and disorders (ASD, ADHD) and conditions such as temporal lobe epilepsy. - Amygdala and emotion: Amygdala’s bidirectional connectivity with mPFC, cingulate, hippocampus, and thalamus supports emotional evaluation and regulation; heightened amygdala activity often accompanies decreased DMN activity; dysregulation relates to anxiety, depression, and PTSD. - Orbitofrontal cortex: Involved in reward evaluation and emotion-based decision-making with limbic connectivity. - Network interactions: DMN dynamically anti-correlates with ECN and interacts with SN, which switches between internal and external focus; stress, sleep deprivation, and psychopathology can impair DMN deactivation during tasks. - Investigation tools: fMRI (high spatial resolution, limited temporal), DTI, sMRI, MEG/EEG (high temporal resolution, limited spatial), PET (metabolic, invasive/low temporal). Multimodal integration improves spatial–temporal characterization. - Development and adversity: DMN maturation is shaped by environment; childhood abuse/neglect, poverty, and chronic stress alter DMN connectivity (hypo-/hyperconnectivity), with structural changes in mPFC/PCC and white matter integrity associated with later depression and PTSD risk; enriched environments and early interventions can normalize/connectivity and improve outcomes. - Social cognition: DMN regions overlap with social brain areas; critical for theory of mind, empathy, and interpreting intentions; DMN alterations observed in ASD and related social deficits. - Influencing factors: Age-related reconfiguration (development to aging) with reduced connectivity in older adults; emotional states (fear, sadness, anger, happiness) modulate DMN; personality traits and genetics contribute to variability; states of consciousness (rest, sleep, meditation, psychedelics) change DMN activity; chronic stress impacts myelination and DMN efficiency. - Clinical associations: Alzheimer’s disease—reduced DMN connectivity and early dysfunction; Schizophrenia—DMN hypoconnectivity (mPFC/PCC) and disrupted coupling with ECN; Anxiety disorders—DMN hyperconnectivity linked to rumination; PTSD—DMN hypoconnectivity (mPFC–PCC) and hyperactivity in trauma-related rumination; Depression—DMN hyperconnectivity tied to rumination and negative self-reference; ADHD—DMN hypoconnectivity associated with inattention/impulsivity; mapping DMN supports surgical planning to spare eloquent cortex. - Neuroplasticity and interventions: Mindfulness meditation reduces resting DMN activity and reorganizes connectivity; CBT normalizes DMN patterns in social anxiety and depression; TMS/tDCS modulate DMN-related regions. These findings support DMN as a therapeutic target.

The review integrates structural, functional, and dynamic evidence to address how DMN supports self-referential cognition, autobiographical memory, social cognition, and emotional processing, while flexibly interacting with ECN and SN to meet task demands. It highlights the DMN’s developmental trajectory and susceptibility to environmental stressors, illustrating mechanisms by which early adversity alters connectivity and increases psychiatric risk. Clinical evidence across Alzheimer’s disease, schizophrenia, anxiety, PTSD, depression, and ADHD links specific DMN connectivity changes to hallmark symptoms (e.g., rumination, cognitive control deficits, social dysfunction). The synthesis underscores the DMN’s centrality to mental health and its responsiveness to neuroplasticity-inducing interventions (meditation, CBT, neuromodulation), positioning DMN connectivity as both a biomarker and a modifiable therapeutic target.

The DMN is a cornerstone network underpinning introspection, self-reflection, mental narrative construction, and the integration of memory and emotion. Its evolutionary relevance, developmental maturation, and dynamic coupling with other large-scale networks shape cognition and behavior across the lifespan. Altered DMN activity and connectivity in psychiatric and neurologic conditions highlight opportunities for targeted interventions, including neurofeedback, cognitive therapies, and neuromodulation, leveraging the network’s neuroplasticity. Future work should prioritize the DMN’s interplay with other networks, temporal dynamics, and personalized, multimodal approaches to diagnosis and treatment.