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However, optimal subcortical targets for therapeutic stimulation are not well established. Here, we leveraged 7 Tesla resting\u2010state functional MRI (rs\u2010fMRI) data from 168 healthy subjects from the Human Connectome Project to map the subcortical connectivity of six canonical cortical networks that modulate higher\u2010order cognition and function: the default mode, executive control, salience, dorsal attention, visual, and somatomotor networks. Based on spatiotemporally overlapped networks generated by the Nadam\u2010Accelerated 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\u2014regions that have historically been targeted by neuromodulatory therapies to restore consciousness\u2014are 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\u2010established \u201chot spot\u201d for coma\u2010causing 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\u2010cortical 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.<\/jats:p>","DOI":"10.1002\/hbm.70352","type":"journal-article","created":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:05:02Z","timestamp":1760173502000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Subcortical Hubs of Brain Networks Sustaining Human Consciousness"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9179-461X","authenticated-orcid":false,"given":"Morgan K.","family":"Cambareri","sequence":"first","affiliation":[{"name":"Department of Neurology Center for Neurotechnology and Neurorecovery, Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Biomedical Engineering Boston University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Horn","sequence":"additional","affiliation":[{"name":"Department of Neurology Center for Neurotechnology and Neurorecovery, Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Center for Brain Circuit Therapeutics, Brigham and Women's Hospital, Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Institute for Network Stimulation, Department of Stereotactic and Functional Neurosurgery University Hospital Cologne  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura D.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology  Cambridge Massachusetts USA"},{"name":"Institute for Medical Engineering and Science, Massachusetts Institute of Technology  Boston Massachusetts USA"},{"name":"Department of Radiology Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology Center for Neurotechnology and Neurorecovery, Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Radiology Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Edlow","sequence":"additional","affiliation":[{"name":"Department of Neurology Center for Neurotechnology and Neurorecovery, Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Radiology Athinoula A. 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