The dynamics of the resting brain exhibit transitions between a small number of discrete networks, each remaining stable for tens to hundreds of milliseconds. These functional microstates are thought to be the building blocks of spontaneous consciousness. The electroencephalogram (EEG) is a useful tool for imaging microstates, and EEG microstate analysis can potentially give insight into altered brain dynamics underpinning cognitive impairment in disorders such as Alzheimer’s disease (AD). Since EEG is non-invasive and relatively inexpensive, EEG microstates have the potential to be useful clinical tools for aiding early diagnosis of AD. In this study, EEG was collected from two independent cohorts of probable AD and cognitively healthy control participants, and a cohort of mild cognitive impairment (MCI) patients with four-year clinical follow-up. The microstate associated with the frontoparietal working-memory/attention network was altered in AD due to parietal inactivation. Using a novel measure of complexity, we found microstate transitioning was slower and less complex in AD. When combined with a spectral EEG measure, microstate complexity could classify AD with sensitivity and specificity > 80%, which was tested on an independent cohort, and could predict progression from MCI to AD in a small preliminary test cohort of 11 participants. EEG microstates therefore have potential to be a non-invasive functional biomarker of AD.

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The ␣7 nicotinic acetylcholine receptor (nAChR) has been implicated in Alzheimer's disease and schizophrenia, leading to efforts targeted toward discovering agonists and positive allosteric modulators (PAMs) of this receptor. In a Ca 2ϩ flux fluorometric imaging plate reader assay, SB-206553 (3,5-dihydro -5 -methyl -N -3 -pyridinylbenzo [1, 2 -b : 4, 5 -bЈ] -di pyrrole-1(2H)-carboxamide), a compound known as a 5-hydroxytryptamine 2B/2C receptor antagonist, produced an 8-fold potentiation of the evoked calcium signal in the presence of an EC 20 concentration of nicotine and a corresponding EC 50 of 1.5 M for potentiation of EC 20 nicotine responses in GH4C1 cells expressing the ␣7 receptor. SB-206553 was devoid of direct ␣7 receptor agonist activity and selective against other nicotinic receptors. Confirmation of the PAM activity of SB-206553 on the ␣7 nAChR was obtained in patch-clamp electrophysiological experiments in GH4C1 cells, where it failed to evoke any detectable currents when applied alone, yet dramatically potentiated the currents evoked by an EC 20 (17 M) and EC 100 (124 M) of acetylcholine (ACh). Native nicotinic receptors in CA1 stratum radiatum interneurons of rat hippocampal slices could also be activated by ACh (200 M), an effect that was entirely blocked by the ␣7-selective antagonist methyllycaconitine (MLA). These ACh currents were potentiated by SB-206553, which increased the area of the current response significantly, resulting in a 40-fold enhancement at 100 M. In behavioral experiments in rats, SB-206553 reversed an MK-801 (dizocilpine maleate)-induced deficit in the prepulse inhibition of acoustic startle response, an effect attenuated in the presence of MLA. This latter observation provides further evidence in support of the potential therapeutic utility of ␣7 nAChR PAMs in schizophrenia.Nicotinic acetylcholine receptors (nAChRs) are formed of pentameric combinations of ␣ and non-␣ subunits with a high degree of complexity conferred by 10 different ␣ subunits (␣1-␣10) and seven different non-␣ subunits (␤1-␤4, ␥␦, ε)Article, publication date, and citation information can be found at

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Table of contentsA1 Functional advantages of cell-type heterogeneity in neural circuitsTatyana O. SharpeeA2 Mesoscopic modeling of propagating waves in visual cortexAlain DestexheA3 Dynamics and biomarkers of mental disordersMitsuo KawatoF1 Precise recruitment of spiking output at theta frequencies requires dendritic h-channels in multi-compartment models of oriens-lacunosum/moleculare hippocampal interneuronsVladislav Sekulić, Frances K. SkinnerF2 Kernel methods in reconstruction of current sources from extracellular potentials for single cells and the whole brainsDaniel K. Wójcik, Chaitanya Chintaluri, Dorottya Cserpán, Zoltán SomogyváriF3 The synchronized periods depend on intracellular transcriptional repression mechanisms in circadian clocks.Jae Kyoung Kim, Zachary P. Kilpatrick, Matthew R. Bennett, Kresimir JosićO1 Assessing irregularity and coordination of spiking-bursting rhythms in central pattern generatorsIrene Elices, David Arroyo, Rafael Levi, Francisco B. Rodriguez, Pablo VaronaO2 Regulation of top-down processing by cortically-projecting parvalbumin positive neurons in basal forebrainEunjin Hwang, Bowon Kim, Hio-Been Han, Tae Kim, James T. McKenna, Ritchie E. Brown, Robert W. McCarley, Jee Hyun ChoiO3 Modeling auditory stream segregation, build-up and bistabilityJames Rankin, Pamela Osborn Popp, John RinzelO4 Strong competition between tonotopic neural ensembles explains pitch-related dynamics of auditory cortex evoked fieldsAlejandro Tabas, André Rupp, Emili Balaguer-BallesterO5 A simple model of retinal response to multi-electrode stimulationMatias I. Maturana, David B. Grayden, Shaun L. Cloherty, Tatiana Kameneva, Michael R. Ibbotson, Hamish MeffinO6 Noise correlations in V4 area correlate with behavioral performance in visual discrimination taskVeronika Koren, Timm Lochmann, Valentin Dragoi, Klaus ObermayerO7 Input-location dependent gain modulation in cerebellar nucleus neuronsMaria Psarrou, Maria Schilstra, Neil Davey, Benjamin Torben-Nielsen, Volker SteuberO8 Analytic solution of cable energy function for cortical axons and dendritesHuiwen Ju, Jiao Yu, Michael L. Hines, Liang Chen, Yuguo YuO9 C. elegans interactome: interactive visualization of Caenorhabditis elegans worm neuronal networkJimin Kim, Will Leahy, Eli ShlizermanO10 Is the model any good? Objective criteria for computational neuroscience model selectionJustas Birgiolas, Richard C. Gerkin, Sharon M. CrookO11 Cooperation and competition of gamma oscillation mechanismsAtthaphon Viriyopase, Raoul-Martin Memmesheimer, Stan GielenO12 A discrete structure of the brain wavesYuri Dabaghian, Justin DeVito, Luca PerottiO13 Direction-specific silencing of the Drosophila gaze stabilization systemAnmo J. Kim, Lisa M. Fenk, Cheng Lyu, Gaby MaimonO14 What does the fruit fly think about values? A model of olfactory associative learningChang Zhao, Yves Widmer, Simon Sprecher,Walter SennO15 Effects of ionic diffusion on power spectra of local field potentials (LFP)Geir Halnes, Tuomo Mäki-Marttunen, Daniel Keller, Klas H. Pettersen,Ole A. Andreassen...