title: Neuroimaging brainstem circuitry supporting cardiovagal response to pain: a combined heart rate variability/ultrahigh-field (7 T) functional magnetic resonance imaging study.
abstract: Central autonomic control nuclei in the brainstem have been difficult to evaluate non-invasively in humans. We applied ultrahigh-field (7 T) functional magnetic resonance imaging (fMRI), and the improved spatial resolution it affords (1.2 mm isotropic), to evaluate putative brainstem nuclei that control and/or sense pain-evoked cardiovagal modulation (high-frequency heart rate variability (HF-HRV) instantaneously estimated through a point-process approach). The time-variant HF-HRV signal was used to guide the general linear model analysis of neuroimaging data. Sustained (6 min) pain stimulation reduced cardiovagal modulation, with the most prominent reduction evident in the first 2 min. Brainstem nuclei associated with pain-evoked HF-HRV reduction were previously implicated in both autonomic regulation and pain processing. Specifically, clusters consistent with the rostral ventromedial medulla, ventral nucleus reticularis (Rt)/nucleus ambiguus (NAmb) and pontine nuclei (Pn) were found when contrasting sustained pain versus rest. Analysis of the initial 2-min period identified Rt/NAmb and Pn, in addition to clusters consistent with the dorsal motor nucleus of the vagus/nucleus of the solitary tract and locus coeruleus. Combining high spatial resolution fMRI and high temporal resolution HF-HRV allowed for a non-invasive characterization of brainstem nuclei, suggesting that nociceptive afference induces pain-processing brainstem nuclei to function in concert with known premotor autonomic nuclei in order to affect the cardiovagal response to pain.
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milano, Italy Department of Radiology, Logan University, Chesterfield, MO, USA roberta@nmr.mgh.harvard.edu.
authors.forename: Roberta
authors.identifier: http://orcid.org/0000-0001-8837-5218
authors.initials: R
authors.lastname: Sclocco
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA Somatosensory and Autonomic Therapy Research, Institute of Neuroradiology, Hannover Medical School, Hannover, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Beissner
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
authors.forename: Gaelle
authors.initials: G
authors.lastname: Desbordes
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Polimeni
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
authors.forename: Lawrence L
authors.initials: LL
authors.lastname: Wald
authors.affiliation: Department of Radiology, Logan University, Chesterfield, MO, USA.
authors.forename: Norman W
authors.initials: NW
authors.lastname: Kettner
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA Clinical Research Division, Korea Institute of Oriental Medicine, Daejeon, South Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA Masira Research Institute, School of Medicine, Universidad de Santander, Bucaramanga, Colombia.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Garcia
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland.
authors.forename: Ville
authors.initials: V
authors.lastname: Renvall
authors.affiliation: Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milano, Italy.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Bianchi
authors.affiliation: Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milano, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Cerutti
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA Department of Radiology, Logan University, Chesterfield, MO, USA.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Napadow
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milano, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Barbieri
mesh_terms: D006339:Heart Rate / Q000502:physiology*
keywords: autonomic nervous system; brainstem; cardiovagal; functional magnetic resonance imaging; pain; ultrahigh field