Evidence map›Paper›PMID 41074653›Full record

ArticleHuman brain mapping2025

Subcortical Hubs of Brain Networks Sustaining Human Consciousness.

Morgan K Cambareri, Andreas Horn, Laura D Lewis, Jian Li, Brian L Edlow

Abstract read
In one paragraph

Article in Human brain mapping, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Morgan K CambareriDepartment of Neurology, Center for Neurotechnology and Neurorecovery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.ORCID 0009-0006-9179-461X
Andreas HornDepartment of Neurology, Center for Neurotechnology and Neurorecovery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Laura D LewisDepartment of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Jian Li *Department of Neurology, Center for Neurotechnology and Neurorecovery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Brian L Edlow *Department of Neurology, Center for Neurotechnology and Neurorecovery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Funding

BRAIN CONNECTS: The center for Large-scale Imaging of Neural Circuits (LINC)UM1NS132358 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI Suzanne N Haber, Elizabeth M. C. Hillman · 2023 to 2026
$17.5M
Viral Tool Development Core: Visualization and manipulation of brain fluid dynamics by recombinant viral vectorsU19NS128613 · NINDS · UNIVERSITY OF ROCHESTER · PI Douglas H Kelley · 2022 to 2026
$13.6M
Using human brain connectivity to identify the causal neuroanatomical substrate of depression symptomsR01MH113929 · NIMH · BRIGHAM AND WOMEN'S HOSPITAL · PI MICHAEL D FOX · 2017 to 2026
$6.9M
Toward Connectomic Deep Brain Stimulation in Obsessive Compulsive DisorderR01MH130666 · NIMH · BRIGHAM AND WOMEN'S HOSPITAL · PI MICHAEL D FOX · 2022 to 2026
$3.9M
Using Brain Lesions and Deep Brain Stimulation to Identify an Epilepsy CircuitR01NS127892 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI MICHAEL D FOX · 2022 to 2026
$3.4M
Sleep-dependent modulation of cerebrospinal fluid flow in aging and across genetic risk for Alzheimers diseaseR01AG070135 · NIA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LEWIS, LAURA DIANE · 2021 to 2025
$3.3M
A Connectome-Based Clinical Trial Platform to Promote Early Recovery of Consciousness after Traumatic ComaDP2HD101400 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI EDLOW, BRIAN L. · 2019 to 2019
$2.5M
Measuring Brain Complexity to Detect and Predict Recovery of Consciousness in the ICUR01NS138257 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI Melanie Boly, Brian L. Edlow · 2024 to 2026
$1.9M
CRCNS: Waste-clearance flows in the brain measured using physics-informed neural networkR01AT012312 · NCCIH · UNIVERSITY OF ROCHESTER · PI Douglas H Kelley · 2022 to 2026
$1.6M
Brainstem Connectome Mapping to Guide Targeted Stimulant Therapy in Patients with Traumatic ComaR21NS109627 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI EDLOW, BRIAN L. · 2019 to 2020
$480k
Imaging neurovascular physiology in persistent fatigue after COVID-19R21NS123412 · NINDS · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI LEWIS, LAURA DIANE · 2021 to 2021
$469k
Deutsches Zentrum für Luft- und Raumfahrt (DynaSti grant within the EU Joint Programme Neurodegenerative Disease Research, JPND)German Research Foundation (Deutsche Forschungsgemeinschaft, 424778381 - TRR 295)MIT/MGH Brain Arousal State Control Innovation Center (BASCIC) projectNCCIH NIH HHS R01 AT012312New Venture Fund (FFOR Seed Grant)NIA NIH HHS R01 AG070135NIA NIH HHS R01AG070135NICHD NIH HHS DP2 HD101400NIH BRAIN Initiative U19NS128613NIH Office of the Director DP2HD101400NIMH NIH HHS R01 MH113929NIMH NIH HHS R01MH113929NIMH NIH HHS R01 MH130666NIMH NIH HHS R01MH130666NINDS NIH HHS R01 NS127892NINDS NIH HHS R01NS127892NINDS NIH HHS R01 NS138257NINDS NIH HHS R01NS138257NINDS NIH HHS R21 NS109627NINDS NIH HHS R21NS109627NINDS NIH HHS R21 NS123412NINDS NIH HHS R21NS123412NINDS NIH HHS U19 NS128613NINDS NIH HHS U19NS128613NINDS NIH HHS UM1 NS132358NINDS NIH HHS UM1NS132358Schilling FoundationThe Chen Institute MGH Research Scholar AwardTiny Blue Dot FoundationU.S. Department of Defense CDMRP HT9425-24-1-1081
6 · The paper itself

Abstract

Neuromodulation of subcortical network hubs by pharmacologic, electrical, or ultrasonic stimulation is a promising therapeutic strategy for patients with disorders of consciousness (DoC). However, optimal subcortical targets for therapeutic stimulation are not well established. Here, we leveraged 7 Tesla resting-state functional MRI (rs-fMRI) data from 168 healthy subjects from the Human Connectome Project to map the subcortical connectivity of six canonical cortical networks that modulate higher-order cognition and function: the default mode, executive control, salience, dorsal attention, visual, and somatomotor networks. Based on spatiotemporally overlapped networks generated by the Nadam-Accelerated SCAlable and Robust (NASCAR) tensor decomposition method, our goal was to identify subcortical hubs that are functionally connected to multiple cortical networks. We found that the ventral tegmental area (VTA) in the midbrain and the central lateral and parafascicular nuclei of the thalamus-regions that have historically been targeted by neuromodulatory therapies to restore consciousness-are subcortical hubs widely connected to multiple cortical networks. Further, we identified a subcortical hub in the pontomesencephalic tegmentum that overlapped with multiple reticular and extrareticular arousal nuclei and that encompassed a well-established "hot spot" for coma-causing brainstem lesions. Multiple hubs within the brainstem arousal nuclei and thalamic intralaminar nuclei were functionally connected to both the default mode and salience networks, emphasizing the importance of these cortical networks in integrative subcortico-cortical signaling. Additional subcortical connectivity hubs were observed within the caudate head, putamen, amygdala, hippocampus, and bed nucleus of the stria terminalis, regions classically associated with modulation of cognition, behavior, and sensorimotor function. Collectively, these results suggest that multiple subcortical hubs in the brainstem tegmentum, thalamus, basal ganglia, and medial temporal lobe modulate cortical function in the human brain. Our findings strengthen the evidence for targeting subcortical hubs in the VTA, thalamic intralaminar nuclei, and pontomesencephalic tegmentum to restore consciousness in patients with DoC. We release the subcortical connectivity maps to support ongoing efforts at therapeutic neuromodulation of consciousness.

Indexed as

BrainCerebral CortexConnectomeConsciousnessNerve NetThalamusVentral Tegmental AreaAdultFemaleHumansMagnetic Resonance ImagingMaleYoung Adult

Identifiers

PMID41074653
PMCPMC12514454

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.