气候变化领域集成服务门户(CCPortal): Dopaminergic brainstem disconnection is common to pharmacological and pathological consciousness perturbation

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DOI	10.1073/pnas.2026289118
	Dopaminergic brainstem disconnection is common to pharmacological and pathological consciousness perturbation
	Spindler L.R.B.; Luppi A.I.; Adapa R.M.; Craig M.M.; Coppola P.; Peattie A.R.D.; Manktelow A.E.; Finoia P.; Sahakian B.J.; Williams G.B.; Allanson J.; Pickard J.D.; Menon D.K.; Stamatakis E.A.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:30
英文摘要	Clinical research into consciousness has long focused on cortical macroscopic networks and their disruption in pathological or pharmacological consciousness perturbation. Despite demonstrating diagnostic utility in disorders of consciousness (DoC) and monitoring anesthetic depth, these cortico-centric approaches have been unable to characterize which neurochemical systems may underpin consciousness alterations. Instead, preclinical experiments have long implicated the dopaminergic ventral tegmental area (VTA) in the brainstem. Despite dopaminergic agonist efficacy in DoC patients equally pointing to dopamine, the VTA has not been studied in human perturbed consciousness. To bridge this translational gap between preclinical subcortical and clinical cortico-centric perspectives, we assessed functional connectivity changes of a histologically characterized VTA using functional MRI recordings of pharmacologically (propofol sedation) and pathologically perturbed consciousness (DoC patients). Both cohorts demonstrated VTA disconnection from the precuneus and posterior cingulate (PCu/PCC), a main default mode network node widely implicated in consciousness. Strikingly, the stronger VTA–PCu/PCC connectivity was, the more the PCu/PCC functional connectome resembled its awake configuration, suggesting a possible neuromodulatory relationship. VTA-PCu/PCC connectivity increased toward healthy control levels only in DoC patients who behaviorally improved at follow-up assessment. To test whether VTA–PCu/PCC connectivity can be affected by a dopaminergic agonist, we demonstrated in a separate set of traumatic brain injury patients without DoC that methylphenidate significantly increased this connectivity. Together, our results characterize an in vivo dopaminergic connectivity deficit common to reversible and chronic consciousness perturbation. This noninvasive assessment of the dopaminergic system bridges preclinical and clinical work, associating dopaminergic VTA function with macroscopic network alterations, thereby elucidating a critical aspect of brainstem–cortical interplay for consciousness. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Brainstem; Consciousness; Disorders of consciousness; Dopamine; Neurotransmitter
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238850
作者单位	University Division of Anaesthesia, Addenbrooke’s Hospital, University of Cambridge, Cambridge, CB2 0SP, United Kingdom; Department of Clinical Neurosciences, Addenbrooke’s Hospital, University of Cambridge, Cambridge, CB2 0SP, United Kingdom; Division of Neurosurgery, School of Clinical Medicine, Addenbrooke’s Hospital, University of Cambridge, Cambridge, CB2 0SP, United Kingdom; Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge, CB2 0SZ, United Kingdom; Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, CB2 3EB, United Kingdom; Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, CB2 0QQ, United Kingdom; Department of Neurosciences, Addenbrooke’s Hospital, Cambridge University Hospitals National Health Service Foundation, Cambridge, CB2 0SP, United Kingdom
推荐引用方式 GB/T 7714	Spindler L.R.B.,Luppi A.I.,Adapa R.M.,et al. Dopaminergic brainstem disconnection is common to pharmacological and pathological consciousness perturbation[J],2021,118(30).
APA	Spindler L.R.B..,Luppi A.I..,Adapa R.M..,Craig M.M..,Coppola P..,...&Stamatakis E.A..(2021).Dopaminergic brainstem disconnection is common to pharmacological and pathological consciousness perturbation.Proceedings of the National Academy of Sciences of the United States of America,118(30).
MLA	Spindler L.R.B.,et al."Dopaminergic brainstem disconnection is common to pharmacological and pathological consciousness perturbation".Proceedings of the National Academy of Sciences of the United States of America 118.30(2021).