The Putative Impact of Metabolic Health on Default Mode Network Activity and Functional Connectivity in Neuropsychiatric Disorders

Abstract

The default mode network (DMN) describes a distributed network of brain regions that are predominantly activated and engaged during periods of spontaneous, stimulus independent thought (i.e., at rest) and remain quiescent during attention-demanding, goal-directed tasks. Replicated evidence in functional neuroimaging studies suggests that midline cortical and subcortical brain regions responsible for memory, self-relevant emotional and mental processes, as well as information integration comprise the DMN. The DMN is posited to represent self-referential mental activity via a dynamic interplay of cognitive and emotional processes by integrating information from the external environment with introspective thoughts to generate an autobiographical concept of the self. It has been amply documented that irregularities in the DMN and its functional connectivity are associated with various neuropsychiatric disorders. Moreover, accumulating evidence also suggests that individuals with select medical disorders (i.e., metabolic disorders) demonstrate alterations in DMN activity and functional connectivity. However, there is a paucity of data evaluating whether individuals with metabolically-based medical conditions, exhibiting altered DMN activity and functional connectivity, are at increased risk for developing neuropsychiatric disorders. Likewise, potential mechanisms (e.g., altered brain metabolism, insulin resistance) mediating these changes and their implications for novel treatment approaches have yet to be elucidated. Taken together, the overarching aim of this review is to provide a synthetic overview that suggests that this neural circuit may represent a common (or convergent) substrate affected in individuals with select neuropsychiatric and metabolic disorders.

Delirium pathophysiology: An updated hypothesis of the etiology of acute brain failure

“…The DMN is a group of brain regions that is preferentially more active at rest than during attention‐demanding tasks and characterized by a high degree of functional connectivity . Anatomically, it includes the posteromedial cortex (including the posterior cingulate cortex), the anteromedial cortex, and temporoparietal junctions .…”

“…The DMN is a group of brain regions that is preferentially more active at rest than during attention-demanding tasks and characterized by a high degree of functional connectivity. [147][148][149][150][151] Anatomically, it includes the posteromedial cortex (including the posterior cingulate cortex), the anteromedial cortex, and temporoparietal junctions. 145,[151][152][153][154] The DMN in the healthy brain is associated with stimulus-independent thought and self-reflection and that greater suppression of the DMN is associated with better performance on attention-demanding tasks.…”

Cognitive impairment in major depressive disorder

“…32 Dysregulation of the normal reciprocity between nodal structures within default mode networks, therefore, may be involved in substrate disturbances and suboptimal functional outcomes resulting from cognitive impairments and reduced cognitive efficiency observed in individuals with MDD. 33 Mediators of aberrant neural circuitry, structure, and function are hypothesized to involve imbalances in hormonal regulation (ie, insulin resistance, glucocorticoid abnormalities), neurotrophin dysregulation (ie, brain-derived neurotrophic factor), immunoinflammatory activation, and oxidative stress. [34][35][36][37] There is wide recognition of reciprocal relationships between mood, cognition, and metabolic disorders.…”

“…For example, anti-correlation, which refers to the selective reciprocal activation and deactivation of various brain regions, is critical for proper cognitive functioning 32 . Dysregulation of the normal reciprocity between nodal structures within default mode networks, therefore, may be involved in substrate disturbances and suboptimal functional outcomes resulting from cognitive impairments and reduced cognitive efficiency observed in individuals with MDD 33 …”

Altered resting-state functional activity in isolated pontine infarction patients with pathological laughing and crying

“…The DMN consists of the medial prefrontal cortex (mPFC), the medial, lateral and inferior parietal cortices, and the precuneus/posterior cingulate cortex. Since the discovery of the DMN, there has been growing interest in its clinical utility and implications [ 10 – 13 ]. The clinical significance of the DMN has been established or implicated in neurological and neuropsychiatric disorders [ 14 – 16 ].…”