title: Globally conditioned Granger causality in brain-brain and brain-heart interactions: a combined heart rate variability/ultra-high-field (7 T) functional magnetic resonance imaging study.
abstract: The causal, directed interactions between brain regions at rest (brain-brain networks) and between resting-state brain activity and autonomic nervous system (ANS) outflow (brain-heart links) have not been completely elucidated. We collected 7 T resting-state functional magnetic resonance imaging (fMRI) data with simultaneous respiration and heartbeat recordings in nine healthy volunteers to investigate (i) the causal interactions between cortical and subcortical brain regions at rest and (ii) the causal interactions between resting-state brain activity and the ANS as quantified through a probabilistic, point-process-based heartbeat model which generates dynamical estimates for sympathetic and parasympathetic activity as well as sympathovagal balance. Given the high amount of information shared between brain-derived signals, we compared the results of traditional bivariate Granger causality (GC) with a globally conditioned approach which evaluated the additional influence of each brain region on the causal target while factoring out effects concomitantly mediated by other brain regions. The bivariate approach resulted in a large number of possibly spurious causal brain-brain links, while, using the globally conditioned approach, we demonstrated the existence of significant selective causal links between cortical/subcortical brain regions and sympathetic and parasympathetic modulation as well as sympathovagal balance. In particular, we demonstrated a causal role of the amygdala, hypothalamus, brainstem and, among others, medial, middle and superior frontal gyri, superior temporal pole, paracentral lobule and cerebellar regions in modulating the so-called central autonomic network (CAN). In summary, we show that, provided proper conditioning is employed to eliminate spurious causalities, ultra-high-field functional imaging coupled with physiological signal acquisition and GC analysis is able to quantify directed brain-brain and brain-heart interactions reflecting central modulation of ANS outflow.
authors.affiliation: Medical Physics Section, Department of Biomedicine and Prevention, University of Rome 'Tor Vergata', Rome, Italy duggento@med.uniroma2.it.
authors.forename: Andrea
authors.identifier: http://orcid.org/0000-0001-6030-5269
authors.initials: A
authors.lastname: Duggento
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
authors.forename: Marta
authors.identifier: http://orcid.org/0000-0001-9606-6853
authors.initials: M
authors.lastname: Bianciardi
authors.affiliation: Istituto di Bioimmagini e Fisiologia Molecolare, Consiglio Nazionale delle Richerche, Catanzaro, Italy Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
authors.forename: Luca
authors.initials: L
authors.lastname: Passamonti
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: Medical Physics Section, Department of Biomedicine and Prevention, University of Rome 'Tor Vergata', Rome, Italy.
authors.forename: Maria
authors.identifier: http://orcid.org/0000-0002-7456-4349
authors.initials: M
authors.lastname: Guerrisi
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
authors.affiliation: Medical Physics Section, Department of Biomedicine and Prevention, University of Rome 'Tor Vergata', Rome, Italy Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
authors.forename: Nicola
authors.identifier: http://orcid.org/0000-0003-1929-5833
authors.initials: N
authors.lastname: Toschi
mesh_terms: D008279:Magnetic Resonance Imaging / Q000379:methods*
keywords: Granger causality; blood-oxygen-level dependent; brain–heart interactions; heart rate variability; ultra-high-field functional magnetic resonance imaging