Dopaminergic brainstem disconnection is common to pharmacological and pathological consciousness perturbation.
Proc Natl Acad Sci U S A
; 118(30)2021 07 27.
Article
en En
| MEDLINE
| ID: mdl-34301891
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Vigilia
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Tronco Encefálico
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Dopamina
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Propofol
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Área Tegmental Ventral
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Trastornos de la Conciencia
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Conectoma
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Lesiones Traumáticas del Encéfalo
Tipo de estudio:
Etiology_studies
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Observational_studies
/
Risk_factors_studies
Límite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2021
Tipo del documento:
Article