Mapping the subcortical connectivity of the human 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 micron 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.

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Basal forebrain contributes to default mode network regulation

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1712431115 ◽

2018 ◽

Vol 115 (6) ◽

pp. 1352-1357 ◽

Cited By ~ 19

Author(s):

Jayakrishnan Nair ◽

Arndt-Lukas Klaassen ◽

Jozsef Arato ◽

Alexei L. Vyssotski ◽

Michael Harvey ◽

...

Keyword(s):

Default Mode Network ◽

Basal Forebrain ◽

Cognitive Task ◽

Gamma Oscillations ◽

Anterior Cingulate ◽

Gamma Activity ◽

Sensory Stimuli ◽

Quiet Wakefulness ◽

Default Mode ◽

Brain States

The default mode network (DMN) is a collection of cortical brain regions that is active during states of rest or quiet wakefulness in humans and other mammalian species. A pertinent characteristic of the DMN is a suppression of local field potential gamma activity during cognitive task performance as well as during engagement with external sensory stimuli. Conversely, gamma activity is elevated in the DMN during rest. Here, we document that the rat basal forebrain (BF) exhibits the same pattern of responses, namely pronounced gamma oscillations during quiet wakefulness in the home cage and suppression of this activity during active exploration of an unfamiliar environment. We show that gamma oscillations are localized to the BF and that gamma-band activity in the BF has a directional influence on a hub of the rat DMN, the anterior cingulate cortex, during DMN-dominated brain states. The BF is well known as an ascending, activating, neuromodulatory system involved in wake–sleep regulation, memory formation, and regulation of sensory information processing. Our findings suggest a hitherto undocumented role of the BF as a subcortical node of the DMN, which we speculate may be important for switching between internally and externally directed brain states. We discuss potential BF projection circuits that could underlie its role in DMN regulation and highlight that certain BF nuclei may provide potential target regions for up- or down-regulation of DMN activity that might prove useful for treatment of DMN dysfunction in conditions such as epilepsy or major depressive disorder.

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Temporal circuit of macroscale dynamic brain activity supports human consciousness

Science Advances ◽

10.1126/sciadv.aaz0087 ◽

2020 ◽

Vol 6 (11) ◽

pp. eaaz0087 ◽

Cited By ~ 11

Author(s):

Zirui Huang ◽

Jun Zhang ◽

Jinsong Wu ◽

George A. Mashour ◽

Anthony G. Hudetz

Keyword(s):

Default Mode Network ◽

Functional Role ◽

Brain Activity ◽

Human Consciousness ◽

Attention Network ◽

Attention Networks ◽

Default Mode ◽

Dorsal Attention Network ◽

Brain States

The ongoing stream of human consciousness relies on two distinct cortical systems, the default mode network and the dorsal attention network, which alternate their activity in an anticorrelated manner. We examined how the two systems are regulated in the conscious brain and how they are disrupted when consciousness is diminished. We provide evidence for a “temporal circuit” characterized by a set of trajectories along which dynamic brain activity occurs. We demonstrate that the transitions between default mode and dorsal attention networks are embedded in this temporal circuit, in which a balanced reciprocal accessibility of brain states is characteristic of consciousness. Conversely, isolation of the default mode and dorsal attention networks from the temporal circuit is associated with unresponsiveness of diverse etiologies. These findings advance the foundational understanding of the functional role of anticorrelated systems in consciousness.

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Default Mode Network, Motor Network, Dorsal and Ventral Basal Ganglia Networks in the Rat Brain: Comparison to Human Networks Using Resting State-fMRI

PLoS ONE ◽

10.1371/journal.pone.0120345 ◽

2015 ◽

Vol 10 (3) ◽

pp. e0120345 ◽

Cited By ~ 39

Author(s):

Adam Sierakowiak ◽

Cyril Monnot ◽

Sahar Nikkhou Aski ◽

Martin Uppman ◽

Tie-Qiang Li ◽

...

Keyword(s):

Basal Ganglia ◽

Rat Brain ◽

Default Mode Network ◽

Resting State ◽

Resting State Fmri ◽

Default Mode ◽

Motor Network ◽

Human Networks

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Reward Enhances Connectivity between the Ventral Striatum and the Default Mode Network

10.1101/2021.07.28.454086 ◽

2021 ◽

Author(s):

Ekaterina Dobryakova ◽

David V Smith

Keyword(s):

Default Mode Network ◽

Ventral Striatum ◽

Interaction Analysis ◽

Personality Characteristic ◽

Reward Processing ◽

Unique Contribution ◽

Default Mode ◽

Human Connectome Project ◽

Psychophysiological Interaction ◽

Multiple Regions

One of the central topics in cognitive neuroscience revolves around understanding how responses in the default mode network (DMN) relate to cognitive process and disease states. While there has been many investigations of the intrinsic patterns of activation and connectivity of the DMN with other networks at rest, i.e. when an individual is not engaged in any particular behavior, to truly understand the influence and significance of the DMN activation and connectivity, we must study it in association with a particular process. Reward processing is an integral part of goal-directed behavior that has been shown to rely on the striatum, a subcortical brain region that is connected to multiple regions of the prefrontal cortex (PFC) that belong to the DMN. Yet, it remains unclear how the DMN interacts with the striatum during reward processing. To investigate this issue, we analyzed card-guessing task data of 453 subjects from the Human Connectome Project and applied a novel network-based psychophysiological interaction analysis (nPPI) that quantified reward-dependent connectivity of the DMN. We show that only the DMN exhibits increased connectivity with the ventral striatum (VS) during the receipt of reward. This result was specific to the DMN and the strength of connectivity was associated with the personality characteristic of openness. These findings point to a novel role of the DMN during reward processing, and to the nPPI approach being able to capture a unique contribution of a collection of regions to task performance.

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Abnormal Topology of the Structural Connectome in the Limbic Cortico-Basal-Ganglia Circuit and Default-Mode Network Among Primary Insomnia Patients

Frontiers in Neuroscience ◽

10.3389/fnins.2018.00860 ◽

2018 ◽

Vol 12 ◽

Cited By ~ 10

Author(s):

Yunfan Wu ◽

Mengchen Liu ◽

Shaoqing Zeng ◽

Xiaofen Ma ◽

Jianhao Yan ◽

...

Keyword(s):

Basal Ganglia ◽

Default Mode Network ◽

Primary Insomnia ◽

Default Mode ◽

Structural Connectome

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Modulatory interactions between the default mode network and task positive networks in resting-state

10.7287/peerj.preprints.124v2 ◽

2014 ◽

Author(s):

Xin Di ◽

Bharat B. Biswal

Keyword(s):

Basal Ganglia ◽

Default Mode Network ◽

Resting State ◽

Brain Structures ◽

Brain Regions ◽

Salience Network ◽

Imaging Data ◽

Default Mode ◽

Task Positive Network ◽

And Task

The two major brain networks, i.e. the default mode network (DMN) and the task positive network, typically reveal negative and variable connectivity in resting-state. In the present study, we examined whether the connectivity between the DMN and different components of the task positive network were modulated by other brain regions by using physiophysiological interaction (PPI) on resting-state functional magnetic resonance imaging data. Spatial independent component analysis was first conducted to identify components that represented networks of interest, including the anterior and posterior DMNs, salience, dorsal attention, left and right executive networks. PPI analysis was conducted between pairs of these networks to identify networks or regions that showed modulatory interactions with the two networks. Both network-wise and voxel-wise analyses revealed reciprocal positive modulatory interactions between the DMN, salience, and executive networks. Together with the anatomical properties of the salience network regions, the results suggest that the salience network may modulate the relationship between the DMN and executive networks. In addition, voxel-wise analysis demonstrated that the basal ganglia and thalamus positively interacted with the salience network and the dorsal attention network, and negatively interacted with the salience network and the DMN. The results demonstrated complex modulatory interactions among the DMNs and task positive networks in resting-state, and suggested that communications between these networks may be modulated by some critical brain structures such as the salience network, basal ganglia, and thalamus.

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Modulatory interactions between the default mode network and task positive networks in resting-state

10.7287/peerj.preprints.124 ◽

2014 ◽

Cited By ~ 1

Author(s):

Xin Di ◽

Bharat B. Biswal

Keyword(s):

Basal Ganglia ◽

Default Mode Network ◽

Resting State ◽

Brain Structures ◽

Brain Regions ◽

Salience Network ◽

Imaging Data ◽

Default Mode ◽

Task Positive Network ◽

And Task

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Dopaminergic modulation of human consciousness via default mode network connectivity

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2111268118 ◽

2021 ◽

Vol 118 (31) ◽

pp. e2111268118

Author(s):

Brian L. Edlow

Keyword(s):

Default Mode Network ◽

Network Connectivity ◽

Human Consciousness ◽

Default Mode ◽

Dopaminergic Modulation

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Osteogenic Mechanisms of Basal Ganglia Calcification and its ex vivo Model in the Hypoparathyroid Milieu

Endocrinology ◽

10.1210/endocr/bqab024 ◽

2021 ◽

Vol 162 (4) ◽

Author(s):

Parmita Kar ◽

Tabin Millo ◽

Soma Saha ◽

Samrina Mahtab ◽

Shipra Agarwal ◽

...

Keyword(s):

Basal Ganglia ◽

Gray Matter ◽

Molecular Mechanisms ◽

Ex Vivo ◽

Ex Vivo Model ◽

Caudate Nuclei ◽

Basal Ganglia Calcification ◽

Cortical Gray Matter ◽

Autopsy Tissues ◽

High Phosphate

Abstract Context Basal-ganglia calcification (BGC) is common (70%) in patients with chronic hypoparathyroidism. Interestingly, cortical gray matter is spared from calcification. The mechanism of BGC, role of hyperphosphatemia, and modulation of osteogenic molecules by parathyroid hormone (PTH) in its pathogenesis is not clear. Objective We assessed the expression of a large repertoire of molecules with proosteogenic or antiosteogenic effects, including neuroprogenitor cells in caudate, dentate, and cortical gray matter from normal autopsy tissues. The effect of high phosphate and PTH was assessed in an ex vivo model of BGC using striatum tissue culture of the Sprague-Dawley rat. Methods The messenger RNA and protein expression of 39 molecules involved in multiple osteogenic pathways were assessed in 25 autopsy tissues using reverse-transcriptase polymerase chain reaction, Western blot, and immunofluorescence. The striatal culture was maintained in a hypoparathyroid milieu for 24 days with and without (a) high phosphate (10-mm β-glycerophosphate) and (b) PTH(1-34) (50 ng/mL Dulbecco’s modified Eagle’s medium–F12 media) for their effect on striatal calcification and osteogenic molecules. Results Procalcification molecules (osteonectin, β-catenin, klotho, FZD4, NT5E, LRP5, WNT3A, collagen-1α, and SOX2-positive neuroprogenitor stem cells) had significantly higher expression in the caudate than gray matter. Caudate nuclei also had higher expression of antiosteogenic molecules (osteopontin, carbonic anhydrase-II [CA-II], MGP, sclerostin, ISG15, ENPP1, and USP18). In an ex vivo model, striatum culture showed an increased propensity for calcified nodules with mineral deposition similar to that of bone tissue on Fourier-transformed infrared spectroscopy, alizarin, and von Kossa stain. Mineralization in striatal culture was enhanced by high phosphate and decreased by exogenous PTH through increased expression of CA-II. Conclusion This study provides a conceptual advance on the molecular mechanisms of BGC and the possibility of PTH therapy to prevent this complication in a hypoparathyroid milieu.

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