Default Mode Network

The default mode network (DMN) mediates self-awareness and introspection, core components of human consciousness. Therapies to restore consciousness in patients with severe brain injuries have historically targeted subcortical sites in the brainstem, thalamus, hypothalamus, basal forebrain, and basal ganglia, with the goal of reactivating cortical DMN nodes. However, the subcortical connectivity of the DMN has not been fully mapped, and optimal subcortical targets for therapeutic neuromodulation of consciousness have not been identified. In this work, we created a comprehensive map of DMN subcortical connectivity by combining high-resolution functional and structural datasets with advanced signal processing methods. We analyzed 7 Tesla resting-state functional MRI (rs-fMRI) data from 168 healthy volunteers acquired in the Human Connectome Project. The rs-fMRI blood-oxygen-level-dependent (BOLD) data were temporally synchronized across subjects using the BrainSync algorithm. Cortical and subcortical DMN nodes were jointly analyzed and identified at the group level by applying a novel Nadam-Accelerated SCAlable and Robust (NASCAR) tensor decomposition method to the synchronized dataset. The subcortical connectivity map was then overlaid on a 7 Tesla 100 µm ex vivo MRI dataset for neuroanatomic analysis using automated segmentation of nuclei within the brainstem, thalamus, hypothalamus, basal forebrain, and basal ganglia. We further compared the NASCAR subcortical connectivity map with its counterpart generated from canonical seed-based correlation analyses. The NASCAR method revealed that BOLD signal in the central lateral nucleus of the thalamus and ventral tegmental area of the midbrain is strongly correlated with that of the DMN. In an exploratory analysis, additional subcortical sites in the median and dorsal raphe, lateral hypothalamus, and caudate nuclei were correlated with the cortical DMN. We also found that the putamen and globus pallidus are negatively correlated (i.e., anti-correlated) with the DMN, providing rs-fMRI evidence for the mesocircuit hypothesis of human consciousness, whereby a striatopallidal feedback system modulates anterior forebrain function via disinhibition of the central thalamus. Seed-based analyses yielded similar subcortical DMN connectivity, but the NASCAR result showed stronger contrast and better spatial alignment with dopamine immunostaining data. The DMN subcortical connectivity map identified here advances understanding of the subcortical regions that contribute to human consciousness and can be used to inform the selection of therapeutic targets in clinical trials for patients with disorders of consciousness.

The default mode network (DMN) is believed to subserve the baseline mental activity in humans. Its higher energy consumption compared to other brain networks and its intimate coupling with conscious awareness are both pointing to an unknown overarching function. Many research streams speak in favor of an evolutionarily adaptive role in envisioning experience to anticipate the future. In the present work, we propose a process model that tries to explain how the DMN may implement continuous evaluation and prediction of the environment to guide behavior. The main purpose of DMN activity, we argue, may be described by Markov decision processes that optimize action policies via value estimates through vicarious trial and error. Our formal perspective on DMN function naturally accommodates as special cases previous interpretations based on (a) predictive coding, (b) semantic associations, and (c) a sentinel role. Moreover, this process model for the neural optimization of complex behavior in the DMN offers parsimonious explanations for recent experimental findings in animals and humans.

The default mode network (DMN) is engaged in a variety of cognitive settings, including social, semantic, temporal, spatial, and self-related tasks. Andrews-Hanna et al. (2010; Andrews-Hanna 2012) proposed that the DMN consists of three distinct functional-anatomical subsystems-a dorsal medial prefrontal cortex (dMPFC) subsystem that supports social cognition; a medial temporal lobe (MTL) subsystem that contributes to memory-based scene construction; and a set of midline core hubs that are especially involved in processing self-referential information. We examined activity in the DMN subsystems during six different tasks: 1) theory of mind, 2) moral dilemmas, 3) autobiographical memory, 4) spatial navigation, 5) self/other adjective judgment, and 6) a rest condition. At a broad level, we observed similar whole-brain activity maps for the six contrasts, and some response to every contrast in each of the three subsystems. In more detail, both univariate analysis and multivariate activity patterns showed partial functional separation, especially between dMPFC and MTL subsystems, though with less support for common activity across the midline core. Integrating social, spatial, self-related, and other aspects of a cognitive situation or episode, multiple components of the DMN may work closely together to provide the broad context for current mental activity.

Background and hypothesisDisorganized thinking is a prominent feature of schizophrenia that becomes persistent in the presence of treatment resistance. Disruption of the default mode network (DMN), which regulates self-referential thinking, is now a well-established feature of schizophrenia. However, we do not know if DMN disruption affects disorganization and contributes to treatment-resistant schizophrenia (TRS).Study designThis study investigated the DMN in 48 TRS, 76 non-TRS, and 64 healthy controls (HC) using a spatiotemporal approach with resting-state functional magnetic resonance imaging. We recovered DMN as an integrated network using multivariate group independent component analysis and estimated its loading coefficient (reflecting spatial prominence) and Shannon Entropy (reflecting temporal variability). Additionally, voxel-level analyses were conducted to examine network homogeneity and entropy within the DMN. We explored the relationship between DMN measures and disorganization using regression analysis.ResultsTRS had higher spatial loading on population-level DMN pattern, but lower entropy compared to HC. Non-TRS patients showed intermediate DMN alterations, not significantly differing from either TRS or HC. No voxel-level differences were noted between TRS and non-TRS, emphasizing the continuum between the two groups. DMN's loading coefficient was higher in patients with more severe disorganization.ConclusionsTRS may represent the most severe end of a spectrum of spatiotemporal DMN dysfunction in schizophrenia. While excessive spatial contribution of the DMN (high loading coefficient) is specifically associated with disorganization, both excessive spatial contribution and exaggerated temporal stability of DMN are features of schizophrenia that become more pronounced with refractoriness to first-line treatments.