title: Human brain functional network changes associated with enhanced and impaired attentional task performance.
abstract: How is the cognitive performance of the human brain related to its topological and spatial organization as a complex network embedded in anatomical space? To address this question, we used nicotine replacement and duration of attentionally demanding task performance (time-on-task), as experimental factors expected, respectively, to enhance and impair cognitive function. We measured resting-state fMRI data, performance and brain activation on a go/no-go task demanding sustained attention, and subjective fatigue in n = 18 healthy, briefly abstinent, cigarette smokers scanned repeatedly in a placebo-controlled, crossover design. We tested the main effects of drug (placebo vs Nicorette gum) and time-on-task on behavioral performance and brain functional network metrics measured in binary graphs of 477 regional nodes (efficiency, measure of integrative topology; clustering, a measure of segregated topology; and the Euclidean physical distance between connected nodes, a proxy marker of wiring cost). Nicotine enhanced attentional task performance behaviorally and increased efficiency, decreased clustering, and increased connection distance of brain networks. Greater behavioral benefits of nicotine were correlated with stronger drug effects on integrative and distributed network configuration and with greater frequency of cigarette smoking. Greater time-on-task had opposite effects: it impaired attentional accuracy, decreased efficiency, increased clustering, and decreased connection distance of networks. These results are consistent with hypothetical predictions that superior cognitive performance should be supported by more efficient, integrated (high capacity) brain network topology at greater connection distance (high cost). They also demonstrate that brain network analysis can provide novel and theoretically principled pharmacodynamic biomarkers of pro-cognitive drug effects in humans.
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, United Kingdom. carsten.giessing@uni-oldenburg.de
authors.forename: Carsten
authors.initials: C
authors.lastname: Giessing
authors.forename: Christiane M
authors.initials: CM
authors.lastname: Thiel
authors.forename: Aaron F
authors.initials: AF
authors.lastname: Alexander-Bloch
authors.forename: Ameera X
authors.initials: AX
authors.lastname: Patel
authors.forename: Edward T
authors.initials: ET
authors.lastname: Bullmore
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001288:Attention / Q000187:drug effects*; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D001931:Brain Mapping; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D009483:Neuropsychological Tests; D009538:Nicotine / Q000009:adverse effects*; D018722:Nicotinic Agonists / Q000009:adverse effects; D010100:Oxygen / Q000097:blood; D012146:Rest / Q000502:physiology; D057566:Self Report; D012890:Sleep / Q000502:physiology; D012907:Smoking / Q000188:drug therapy / Q000473:pathology*; D013997:Time Factors; D055815:Young Adult
chemical_list: D018722:Nicotinic Agonists; D009538:Nicotine; D010100:Oxygen
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