title: Nicotine restores functional connectivity of the ventral attention network in schizophrenia.
abstract: While previous work has suggested that nicotine may transiently improve attention deficits in schizophrenia, the neuronal mechanisms are poorly understood. This study is the first to examine the effects of nicotine on connectivity within the ventral attention network (VAN) during a selective attention task in schizophrenia. Using a crossover design, 17 nonsmoking patients with schizophrenia and 20 age/gender-matched nonsmoking healthy controls performed a go/no-go task with environmental noise distractors during application of a 7 mg nicotine or placebo patch. Psychophysiological interaction analysis was performed to analyze task-associated changes in connectivity between a ventral parietal cortex (VPC) seed and the inferior frontal gyrus (IFG), key components of the human VAN. Effects of nicotine on resting state VAN connectivity were also examined. A significant diagnosis × drug interaction was observed on task-associated connectivity between the VPC seed and the left IFG (F(1,35) = 8.03, p < 0.01). This effect was driven by decreased connectivity after placebo in patients and greater connectivity after nicotine. Resting state connectivity analysis showed a significant main effect of diagnosis between the seed and right IFG (F = 4.25, p = 0.023) due to increased connectivity in patients during placebo, but no drug × diagnosis interactions or main effects of drug. This study is the first to demonstrate that 1) the VAN is disconnected in schizophrenia during selective attention, and 2) nicotine may normalize this pathological state.
authors.affiliation: Neuroscience Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address: Jason.smucny@ucdenver.edu.
authors.forename: Jason
authors.initials: J
authors.lastname: Smucny
authors.affiliation: Research Service, Denver VA Medical Center, Denver, CO 80220, USA; Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Ann
authors.initials: A
authors.lastname: Olincy
authors.affiliation: Neuroscience Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Research Service, Denver VA Medical Center, Denver, CO 80220, USA; Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Tregellas
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000328:Adult; D001288:Attention / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000008:administration & dosage*; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D016037:Single-Blind Method; D061485:Tobacco Use Cessation Devices
chemical_list: D009538:Nicotine
keywords: Attention; Connectivity; Nicotine; Schizophrenia; Ventral attention network; fMRI