title: Spatial heterogeneity of the relation between resting-state connectivity and blood flow: an important consideration for pharmacological studies.
abstract: Resting state fMRI (RSfMRI) and arterial spin labeling (ASL) provide the field of pharmacological Neuroimaging tool for investigating states of brain activity in terms of functional connectivity or cerebral blood flow (CBF). Functional connectivity reflects the degree of synchrony or correlation of spontaneous fluctuations--mostly in the blood oxygen level dependent (BOLD) signal--across brain networks; but CBF reflects mean delivery of arterial blood to the brain tissue over time. The BOLD and CBF signals are linked to common neurovascular and hemodynamic mechanisms that necessitate increased oxygen transportation to the site of neuronal activation; however, the scale and the sources of variation in static CBF and spatiotemporal BOLD correlations are likely different. We tested this hypothesis by examining the relation between CBF and resting-state-network consistency (RSNC)--representing average intranetwork connectivity, determined from dual regression analysis with eight standard networks of interest (NOIs)--in a crossover placebo-controlled study of morphine and alcohol. Overall, we observed spatially heterogeneous relations between RSNC and CBF, and between the experimental factors (drug-by-time, time, drug and physiological rates) and each of these metrics. The drug-by-time effects on CBF were significant in all networks, but significant RSNC changes were limited to the sensorimotor, the executive/salience and the working memory networks. The post-hoc voxel-wise statistics revealed similar dissociations, perhaps suggesting differential sensitivity of RSNC and CBF to neuronal and vascular endpoints of drug actions. The spatial heterogeneity of RSNC/CBF relations encourages further investigation into the role of neuroreceptor distribution and cerebrovascular anatomy in predicting spontaneous fluctuations under drugs.
authors.affiliation: Institute of Psychology, Leiden University, Leiden, The Netherlands; Department of Radiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands; Leiden Institute for Brain and Cognition (LIBC), Leiden University, Leiden, The Netherlands.
authors.forename: Najmeh
authors.initials: N
authors.lastname: Khalili-Mahani
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: van Osch
authors.forename: Mark
authors.initials: M
authors.lastname: de Rooij
authors.forename: Christian F
authors.initials: CF
authors.lastname: Beckmann
authors.forename: Mark A
authors.initials: MA
authors.lastname: van Buchem
authors.forename: Albert
authors.initials: A
authors.lastname: Dahan
authors.forename: Johannes M
authors.initials: JM
authors.lastname: van Gerven
authors.forename: Serge A R B
authors.initials: SA
authors.lastname: Rombouts
mesh_terms: D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D001921:Brain / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology*; D001944:Breath Tests; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D063132:Connectome / Q000379:methods*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology*; D010919:Placebos; D012146:Rest / Q000502:physiology; D013113:Spin Labels; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D002492:Central Nervous System Depressants; D010919:Placebos; D013113:Spin Labels; D000431:Ethanol; D009020:Morphine
keywords: arterial spin labeling; cerebral blood flow; cerebral perfusion; drug research; functional brain connectivity; pharmacological fMRI; resting state; resting-state networks