title: Directional connectivity between frontal and posterior brain regions is altered with increasing concentrations of propofol.
abstract: Recent studies using electroencephalography (EEG) suggest that alteration of coherent activity between the anterior and posterior brain regions might be used as a neurophysiologic correlate of anesthetic-induced unconsciousness. One way to assess causal relationships between brain regions is given by renormalized partial directed coherence (rPDC). Importantly, directional connectivity is evaluated in the frequency domain by taking into account the whole multichannel EEG, as opposed to time domain or two channel approaches. rPDC was applied here in order to investigate propofol induced changes in causal connectivity between four states of consciousness: awake (AWA), deep sedation (SED), loss (LOC) and return of consciousness (ROC) by gathering full 10/20 system human EEG data in ten healthy male subjects. The target-controlled drug infusion was started at low rate with subsequent gradual stepwise increases at 10 min intervals in order to carefully approach LOC (defined as loss of motor responsiveness to a verbal stimulus). The direction of the causal EEG-network connections clearly changed from AWA to SED and LOC. Propofol induced a decrease (p = 0.002-0.004) in occipital-to-frontal rPDC of 8-16 Hz EEG activity and an increase (p = 0.001-0.040) in frontal-to-occipital rPDC of 10-20 Hz activity on both sides of the brain during SED and LOC. In addition, frontal-to-parietal rPDC within 1-12 Hz increased in the left hemisphere at LOC compared to AWA (p = 0.003). However, no significant changes were detected between the SED and the LOC states. The observed decrease in back-to-front EEG connectivity appears compatible with impaired information flow from the posterior sensory and association cortices to the executive prefrontal areas, possibly related to decreased ability to perceive the surrounding world during sedation. The observed increase in the opposite (front-to-back) connectivity suggests a propofol concentration dependent association and is not directly related to the level of consciousness per se.
authors.affiliation: Department of Perioperative Services, Intensive Care and Pain Medicine, Turku University Hospital, Turku, Finland; Turku PET Centre, University of Turku, Turku, Finland.
authors.forename: Anu
authors.initials: A
authors.lastname: Maksimow
authors.affiliation: Department of Computer Science and Engineering, University of Oulu, Oulu, Finland.
authors.forename: Minna
authors.initials: M
authors.lastname: Silfverhuth
authors.affiliation: Turku PET Centre, University of Turku, Turku, Finland; Intensive Care Unit, Tampere University Hospital, Tampere, Finland.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Långsjö
authors.affiliation: Department of Perioperative Services, Intensive Care and Pain Medicine, Turku University Hospital, Turku, Finland; Turku PET Centre, University of Turku, Turku, Finland.
authors.forename: Kimmo
authors.initials: K
authors.lastname: Kaskinoro
authors.affiliation: Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
authors.forename: Stefanos
authors.initials: S
authors.lastname: Georgiadis
authors.affiliation: Department of Clinical Neurophysiology, Turku University Hospital, Turku, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Jääskeläinen
authors.affiliation: Turku PET Centre, University of Turku, Turku, Finland; Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.
authors.forename: Harry
authors.initials: H
authors.lastname: Scheinin
mesh_terms: D000328:Adult; D000465:Algorithms; D000704:Analysis of Variance; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D003243:Consciousness; D054810:Deep Sedation; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008959:Models, Neurological; D009434:Neural Pathways / Q000187:drug effects* / Q000502:physiology; D015742:Propofol / Q000008:administration & dosage / Q000494:pharmacology*; D014474:Unconsciousness; D014851:Wakefulness; D055815:Young Adult
chemical_list: D018686:Anesthetics, Intravenous; D015742:Propofol