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Analysis and interpretation of studies on cognitive and affective dysregulation often draw upon the network paradigm, especially the Triple Network Model, which consists of the default mode network (DMN), the frontoparietal network (FPN), and the salience network (SN). DMN activity is primarily dominant during cognitive leisure and self-monitoring processes. The FPN peaks during task involvement and cognitive exertion. Meanwhile, the SN serves as a dynamic “switch” between the DMN and FPN, in line with salience and cognitive demand. In the cognitive and affective domains, dysfunctions involving SN activity are connected to a broad spectrum of deficits and maladaptive behavioral patterns in a variety of clinical disorders, such as depression, insomnia, narcissism, PTSD (in the case of SN hyperactivity), chronic pain, and anxiety, high degrees of neuroticism, schizophrenia, epilepsy, autism, and neurodegenerative illnesses, bipolar disorder (in the case of SN hypoactivity). We discuss behavioral and neurological data from various research domains and present an integrated perspective indicating that these conditions can be associated with a widespread disruption in predictive coding at multiple hierarchical levels. We delineate the fundamental ideas of the brain network paradigm and contrast them with the conventional modular method in the first section of this article. Following this, we outline the interaction model of the key functional brain networks and highlight recent studies coupling SN-related dysfunctions with cognitive and affective impairments.

Abstract Psychedelics are a unique class of drug that commonly produce vivid hallucinations as well as profound psychological and mystical experiences. A grouping of interconnected brain regions characterized by increased temporal coherence at rest have been termed the Default Mode Network (DMN). The DMN has been the focus of numerous studies assessing its role in self-referencing, mind wandering, and autobiographical memories. Altered connectivity in the DMN has been associated with a range of neuropsychiatric conditions such as depression, anxiety, post-traumatic stress disorder, attention deficit hyperactive disorder, schizophrenia, and obsessive-compulsive disorder. To date, several studies have investigated how psychedelics modulate this network, but no comprehensive review, to our knowledge, has critically evaluated how major classical psychedelic agents—lysergic acid diethylamide, psilocybin, and ayahuasca—modulate the DMN. Here we present a systematic review of the knowledge base. Across psychedelics there is consistent acute disruption in resting state connectivity within the DMN and increased functional connectivity between canonical resting-state networks. Various models have been proposed to explain the cognitive mechanisms of psychedelics, and in one model DMN modulation is a central axiom. Although the DMN is consistently implicated in psychedelic studies, it is unclear how central the DMN is to the therapeutic potential of classical psychedelic agents. This article aims to provide the field with a comprehensive overview that can propel future research in such a way as to elucidate the neurocognitive mechanisms of psychedelics.

The Default Mode Network (DMN) is a brain system that mediates internal modes of cognitive activity, showing higher neural activation when one is at rest. Nowadays, there is a lot of interest in assessing functional interactions between its key regions, but in the majority of studies only association of Blood-oxygen-level dependent (BOLD) activation patterns is measured, so it is impossible to identify causal influences. There are some studies of causal interactions (i.e., effective connectivity), however often with inconsistent results. The aim of the current work is to find a stable pattern of connectivity between four DMN key regions: the medial prefrontal cortex (mPFC), the posterior cingulate cortex (PCC), left and right intraparietal cortex (LIPC and RIPC). For this purpose functional magnetic resonance imaging (fMRI) data from 30 healthy subjects (1000 time points from each one) was acquired and spectral dynamic causal modeling (DCM) on a resting-state fMRI data was performed. The endogenous brain fluctuations were explicitly modeled by Discrete Cosine Set at the low frequency band of 0.0078-0.1 Hz. The best model at the group level is the one where connections from both bilateral IPC to mPFC and PCC are significant and symmetrical in strength (p < 0.05). Connections between mPFC and PCC are bidirectional, significant in the group and weaker than connections originating from bilateral IPC. In general, all connections from LIPC/RIPC to other DMN regions are much stronger. One can assume that these regions have a driving role within the DMN. Our results replicate some data from earlier works on effective connectivity within the DMN as well as provide new insights on internal DMN relationships and brain's functioning at resting state.

Abstract Meditation can exert a profound impact on our mental life, with proficient practitioners often reporting an experience free of boundaries between a separate self and the environment, suggesting an explicit experience of “nondual awareness.” What are the neural correlates of such experiences and how do they relate to the idea of nondual awareness itself? In order to unravel the effects that meditation has on the brain’s spatial topography, we review functional magnetic resonance imaging brain findings from studies specific to an array of meditation types and meditator experience levels. We also review findings from studies that directly probe the interaction between meditation and the experience of the self. The main results are (i) decreased posterior default mode network (DMN) activity, (ii) increased central executive network (CEN) activity, (iii) decreased connectivity within posterior DMN as well as between posterior and anterior DMN, (iv) increased connectivity within the anterior DMN and CEN, and (v) significantly impacted connectivity between the DMN and CEN (likely a nonlinear phenomenon). Together, these suggest a profound organizational shift of the brain’s spatial topography in advanced meditators—we therefore propose a topographic reorganization model of meditation (TRoM). One core component of the TRoM is that the topographic reorganization of DMN and CEN is related to a decrease in the mental-self-processing along with a synchronization with the more nondual layers of self-processing, notably interoceptive and exteroceptive-self-processing. This reorganization of the functionality of both brain and self-processing can result in the explicit experience of nondual awareness. In conclusion, this review provides insight into the profound neural effects of advanced meditation and proposes a result-driven unifying model (TRoM) aimed at identifying the inextricably tied objective (neural) and subjective (experiential) effects of meditation.

Resting-state functional Magnetic Resonance Imaging (rsfMRI) of the human brain has revealed multiple large-scale neural networks within a hierarchical and complex structure of coordinated functional activity. These distributed neuroanatomical systems provide a sensitive window on brain function and its disruption in a variety of neuropathological conditions. The study of macroscale intrinsic connectivity networks in preclinical species, where genetic and environmental conditions can be controlled and manipulated with high specificity, offers the opportunity to elucidate the biological determinants of these alterations. While rsfMRI methods are now widely used in human connectivity research, these approaches have only relatively recently been back-translated into laboratory animals. Here we review recent progress in the study of functional connectivity in rodent species, emphasising the ability of this approach to resolve large-scale brain networks that recapitulate neuroanatomical features of known functional systems in the human brain. These include, but are not limited to, a distributed set of regions identified in rats and mice that may represent a putative evolutionary precursor of the human default mode network (DMN). The impact and control of potential experimental and methodological confounds are also critically discussed. Finally, we highlight the enormous potential and some initial application of connectivity mapping in transgenic models as a tool to investigate the neuropathological underpinnings of the large-scale connectional alterations associated with human neuropsychiatric and neurological conditions. We conclude by discussing the translational potential of these methods in basic and applied neuroscience. •Large-scale connectivity networks can be mapped with fMRI in mice and rats.•Both rats and mice have a putative default mode network (DMN) homologue.•We describe the topological and functional organisation of the rodent DMN.•Low anaesthesia levels preserve network topology.•Examples of fMRI connectivity mapping in transgenic mice are illustrated.

Employing a developmental psychopathology framework, we tested the utility of the hormesis model in examining the strengthening of children and youth through limited levels of adversity in relation to internalizing and externalizing outcomes within a brain-by-development context. Analyzing data from the Adolescent Brain and Cognitive Development study ( = 11,878), we formed latent factors of threat, deprivation, and unpredictability. We examined linear and nonlinear associations between adversity dimensions and youth psychopathology symptoms and how change of resting-state functional connectivity (rsFC) in the default mode network (DMN) from Time 1 to Time 5 moderates these associations. A cubic association was found between threat and youth internalizing problems; low-to-moderate family conflict levels reduced these problems. Deprivation also displayed a cubic relation with youth externalizing problems, with moderate deprivation levels associated with fewer problems. Unpredictability linearly increased both problem types. Change in DMN rsFC significantly moderated the cubic link between threat levels and internalizing problems, with declining DMN rsFC levels from Time 1 to Time 5 facilitating hormesis. Hormetic effects peaked earlier, emphasizing the importance of sensitive periods and developmental timing of outcomes related to earlier experiences. Strengthening through limited environmental adversity is crucial for developing human resilience. Understanding this process requires considering both linear and nonlinear adversity-psychopathology associations. Testing individual differences by brain and developmental context will inform preventive intervention programming.

The default mode network (DMN) is the most-prominent intrinsic connectivity network, serving as a key architecture of the brain’s functional organization. Conversely, dysregulated DMN is characteristic of major neuropsychiatric disorders. However, the field still lacks mechanistic insights into the regulation of the DMN and effective interventions for DMN dysregulation. The current study approached this problem by manipulating neural synchrony, particularly alpha (8 to 12 Hz) oscillations, a dominant intrinsic oscillatory activity that has been increasingly associated with the DMN in both function and physiology. Using high-definition alpha-frequency transcranial alternating current stimulation (α-tACS) to stimulate the cortical source of alpha oscillations, in combination with simultaneous electroencephalography and functional MRI (EEG-fMRI), we demonstrated that α-tACS (versus Sham control) not only augmented EEG alpha oscillations but also strengthened fMRI and (source-level) alpha connectivity within the core of the DMN. Importantly, increase in alpha oscillations mediated the DMN connectivity enhancement. These findings thus identify a mechanistic link between alpha oscillations and DMN functioning. That transcranial alpha modulation can up-regulate the DMN further highlights an effective noninvasive intervention to normalize DMN functioning in various disorders.

An emerging field of human brain imaging deals with the characterization of the connectome, a comprehensive global description of structural and functional connectivity within the human brain. However, the question of how functional and structural connectivity are related has not been fully answered yet. Here, we used different methods to estimate the connectivity between each voxel of the cerebral cortex based on functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) data in order to obtain observer-independent functional–structural connectomes of the human brain. Probabilistic fiber-tracking and a novel global fiber-tracking technique were used to measure structural connectivity whereas for functional connectivity, full and partial correlations between each voxel pair's fMRI-timecourses were calculated. For every voxel, two vectors consisting of functional and structural connectivity estimates to all other voxels in the cortex were correlated with each other. In this way, voxels structurally and functionally connected to similar regions within the rest of the brain could be identified. Areas forming parts of the ‘default mode network’ (DMN) showed the highest agreement of structure–function connectivity. Bilateral precuneal and inferior parietal regions were found using all applied techniques, whereas the global tracking algorithm additionally revealed bilateral medial prefrontal cortices and early visual areas. There were no significant differences between the results obtained from full and partial correlations. Our data suggests that the DMN is the functional brain network, which uses the most direct structural connections. Thus, the anatomical profile of the brain seems to shape its functional repertoire and the computation of the whole-brain functional–structural connectome appears to be a valuable method to characterize global brain connectivity within and between populations. •Structure–function connectivity relationship•Multi-modal data fusion•Voxel-wise connectivity analysis•Default mode network•Global fiber-tracking

Hemodynamic fluctuations in the default mode network (DMN), observed through functional magnetic resonance imaging (fMRI), have been linked to electrophysiological oscillations detected by electroencephalography (EEG). It has been reported that, among the electrophysiological oscillations, those in the alpha frequency range (8-13 Hz) are the most dominant during resting state. We hypothesized that DMN spatial configuration closely depends on the specific neuronal oscillations considered, and that alpha oscillations would mainly correlate with increased blood oxygen-level dependent (BOLD) signal in the DMN. To test this hypothesis, we used high-density EEG (hdEEG) data simultaneously collected with fMRI scanning in 20 healthy volunteers at rest. We first detected the DMN from source reconstructed hdEEG data for multiple frequency bands, and we then mapped the correlation between temporal profile of hdEEG-derived DMN activity and fMRI-BOLD signals on a voxel-by-voxel basis. In line with our hypothesis, we found that the correlation map associated with alpha oscillations, more than with any other frequency bands, displayed a larger overlap with DMN regions. Overall, our study provided further evidence for a primary role of alpha oscillations in supporting DMN functioning. We suggest that simultaneous EEG-fMRI may represent a powerful tool to investigate the neurophysiological basis of human brain networks.Hemodynamic fluctuations in the default mode network (DMN), observed through functional magnetic resonance imaging (fMRI), have been linked to electrophysiological oscillations detected by electroencephalography (EEG). It has been reported that, among the electrophysiological oscillations, those in the alpha frequency range (8-13 Hz) are the most dominant during resting state. We hypothesized that DMN spatial configuration closely depends on the specific neuronal oscillations considered, and that alpha oscillations would mainly correlate with increased blood oxygen-level dependent (BOLD) signal in the DMN. To test this hypothesis, we used high-density EEG (hdEEG) data simultaneously collected with fMRI scanning in 20 healthy volunteers at rest. We first detected the DMN from source reconstructed hdEEG data for multiple frequency bands, and we then mapped the correlation between temporal profile of hdEEG-derived DMN activity and fMRI-BOLD signals on a voxel-by-voxel basis. In line with our hypothesis, we found that the correlation map associated with alpha oscillations, more than with any other frequency bands, displayed a larger overlap with DMN regions. Overall, our study provided further evidence for a primary role of alpha oscillations in supporting DMN functioning. We suggest that simultaneous EEG-fMRI may represent a powerful tool to investigate the neurophysiological basis of human brain networks.

Accurate diagnosis of the early stage of Alzheimer’s disease (AD) is essential but very challenging. The objective of this study was to properly utilize the biomarkers for diagnosis of AD based on merging resting-state functional MRI brain networks and voxel features. The fMRI time series data have a potentiality of the specific numerical information as well as dynamic temporal information. Voxel and graphical analysis have gained the popularities to analyzing neurodegenerative disorders such as mild cognitive impairment (MCI) and AD. So far, these methods have been utilized separately for classification of AD and its prodromal stage MCI. In the major of studies classification of mild cognitive impairment which do not convertible for certain period known as stable MCI (MCIs) and which are convertible to AD (MCIc) is less commonly reported and have inconsistence results. In this study, we tested the efficacy of a purposed classification framework to identified AD and the stable mild cognitive impairment (MCIs) from convertible by utilizing the efficient features derived from functional brain networks of frequency band (0.01-0.027) at resting state and the voxel-based features ALFO, FFLO and ReHo. Pearson correlation coefficient to measuring functional brain network has been proof to be an efficient means to diagnose AD. Graphical theory was performed to calculate nodal features [nodal degree (ND), nodal path length (NL), and between centrality (BC)] as a graphical feature and analyze the relationship between changes in network connectivity. Subsequently, we extracted three-dimensional patterns calculating regional coherence, we performed univariate statistical t-test to generate 3-D mask that retained voxels showing significant changes. Finally, we implemented and compare the different features selection algorithm to integrate the brain networks and voxel features into one form to optimize the classifier, we used SVM classifiers. Experimental results verify the effectiveness of our proposed method; combination of brain network with multiple measure of rs-fMRI significantly enhance in accuracy over other approaches on AD. The accuracy obtained by the proposed method were reported on binary classification. More importantly classification results of less commonly reported group MCIs vs MCIc improved significantly.