Resting-state BOLD functional connectivity depends on the heterogeneity of capillary transit times in the human brain A combined lesion and simulation study about the influence of blood flow response timing
Sebastian C. Schneider,
Mario E. Archila-Meléndez,
Jens Göttler,
Stephan Kaczmarz,
Benedikt Zott,
Josef Priller,
Michael Kallmayer,
Claus Zimmer,
Christian Sorg,
Christine Preibisch
Affiliations
Sebastian C. Schneider
Department of Diagnostic and Interventional Neuroradiology, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Ismaningerstr. 22, 81675 Munich, Germany; TUM Neuroimaging Center, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Ismaningerstr. 22, 81675 Munich, Germany; Department of Psychiatry, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Ismaningerstr. 22, 81675 Munich, Germany
Mario E. Archila-Meléndez
Department of Diagnostic and Interventional Neuroradiology, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Ismaningerstr. 22, 81675 Munich, Germany; TUM Neuroimaging Center, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Ismaningerstr. 22, 81675 Munich, Germany
Jens Göttler
Department of Diagnostic and Interventional Neuroradiology, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Ismaningerstr. 22, 81675 Munich, Germany; TUM Neuroimaging Center, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Ismaningerstr. 22, 81675 Munich, Germany
Stephan Kaczmarz
Department of Diagnostic and Interventional Neuroradiology, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Ismaningerstr. 22, 81675 Munich, Germany; TUM Neuroimaging Center, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Ismaningerstr. 22, 81675 Munich, Germany; Philips GmbH Market DACH, Hamburg, Germany
Benedikt Zott
Department of Diagnostic and Interventional Neuroradiology, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Ismaningerstr. 22, 81675 Munich, Germany; TUM Neuroimaging Center, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Ismaningerstr. 22, 81675 Munich, Germany
Josef Priller
Department of Psychiatry, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Ismaningerstr. 22, 81675 Munich, Germany
Michael Kallmayer
Department of Vascular and Endovascular Surgery, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Ismaningerstr. 22, 81675 Munich, Germany
Claus Zimmer
Department of Diagnostic and Interventional Neuroradiology, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Ismaningerstr. 22, 81675 Munich, Germany
Christian Sorg
Department of Diagnostic and Interventional Neuroradiology, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Ismaningerstr. 22, 81675 Munich, Germany; TUM Neuroimaging Center, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Ismaningerstr. 22, 81675 Munich, Germany; Department of Psychiatry, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Ismaningerstr. 22, 81675 Munich, Germany
Christine Preibisch
Department of Diagnostic and Interventional Neuroradiology, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Ismaningerstr. 22, 81675 Munich, Germany; TUM Neuroimaging Center, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Ismaningerstr. 22, 81675 Munich, Germany; Department of Neurology, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Ismaningerstr. 22, 81675 Munich, Germany; Corresponding author at: Department of Diagnostic and Interventional Neuroradiology, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Ismaningerstr. 22, 81675 Munich, Germany
Functional connectivity (FC) derived from blood oxygenation level dependent (BOLD) functional magnetic resonance imaging at rest (rs-fMRI), is commonly interpreted as indicator of neuronal connectivity. In a number of brain disorders, however, metabolic, vascular, and hemodynamic impairments can be expected to alter BOLD-FC independently from neuronal activity. By means of a neurovascular coupling (NVC) model of BOLD-FC, we recently demonstrated that aberrant timing of cerebral blood flow (CBF) responses may influence BOLD-FC. In the current work, we support and extend this finding by empirically linking BOLD-FC with capillary transit time heterogeneity (CTH), which we consider as an indicator of delayed and broadened CBF responses. We assessed 28 asymptomatic patients with unilateral high-grade internal carotid artery stenosis (ICAS) as a hemodynamic lesion model with largely preserved neurocognitive functioning and 27 age-matched healthy controls. For each participant, we obtained rs-fMRI, arterial spin labeling, and dynamic susceptibility contrast MRI to study the dependence of left-right homotopic BOLD-FC on local perfusion parameters. Additionally, we investigated the dependency of BOLD-FC on CBF response timing by detailed simulations. Homotopic BOLD-FC was negatively associated with increasing CTH differences between homotopic brain areas. This relation was more pronounced in asymptomatic ICAS patients even after controlling for baseline CBF and relative cerebral blood volume influences. These findings match simulation results that predict an influence of delayed and broadened CBF responses on BOLD-FC. Results demonstrate that increasing CTH differences between homotopic brain areas lead to BOLD-FC reductions. Simulations suggest that CTH increases correspond to broadened and delayed CBF responses to fluctuations in ongoing neuronal activity.
