DOI: 10.19185/maters.201905000001 Maters (ISSN: 2297-8240) | 1 Correspondence Joanes.Grandjean@rad- boudumc.nl  Disciplines Neuroscience  Keywords FMRI Hydrocephalus Resting-State Cerebrospinal Fluid Mouse  Type of Observation Standalone  Type of Link Case study  Submited Mar 13, 2019  Published Jun 10, 2019 3 x Triple Blind Peer Review The handling editor, the re- viewers, and the authors are all blinded during the review process. Full Open Access Supported by the Velux Foundation, the University of Zurich, and the EPFL School of Life Sciences. 4.0 Creative Commons 4.0 This observation is dis- tributed under the terms of the Creative Commons Atribution 4.0 International License. Preserved functional networks in a hydrocephalic mouse Francesca Mandino, Ling Yun Yeow, John Gigg, Malini Olivo, Joanes Grandjean Singapore Bioimaging Consortium (SBIC), Agency for Science, Technology and Research (A*STAR), Faculty of Biology, Medicine and Health, Te University of Manchester, Manchester, United Kingdom; Singapore Bioimaging Consortium (SBIC), Agency for Science, Technology and Research (A*STAR); Faculty of Biology, Medicine and Health, Te University of Manch- ester, Manchester, United Kingdom; Department of Radiology and Nuclear Medicine & Donders Institute for Brain, Cognition, and Behaviour, Donders Institute, Radbound University Medical Centre Abstract Hydrocephalus is a brain condition characterized by enlarged ventricles, due to an ex- cess of cerebrospinal uid. Although it is known to aect cognition, development, gait, and mood, the impact of hydrocephalus on large-scale functional brain organization is poorly documented. Here, we present results on a single spontaneous occurrence of severe hydrocephalus observed in a 3xTgAD mouse, compared to a control cohort of 3xTgAD litermates. Resting-state functional magnetic resonance imaging analy- sis, carried out under light anesthesia, revealed the remarkable presence of functional connectivity (FC) resembling the common mouse resting-state networks (RSNs). Four main components were identied in the hydrocephalic mouse, atributable to the De- fault Mode network, Salience network, and sensorimotor networks. Characteristic fea- tures of the RSNs in the hydrocephalic mouse were found to be well preserved, both in spatial distribution and in FC magnitude, despite the severity of the pathology. Tis is the rst documented case of resting-state fMRI conducted on a mouse aected by severe hydrocephalus. Te surprising presence of resting-state networks was found to be comparable to litermate controls, highlighting a remarkable functional resilience in the hydrocephalic brain. Introduction Cerebrospinal uid (CSF) plays an important role in the regulation of the interstitial uid of the brain parenchyma and in brain development. Compromised CSF dynamics, due either to excess production, reduced resorption, or altered ow of CSF within the ventricles, aect brain development, leading to hydrocephalus. Tis condition is char- acterized by an excess of CSF in the ventricles, impaired cognitive and physical devel- opment or, when appearing later in life, cognitive decline, gait disturbance, and urinary incontinence [1]. Congenital hydrocephalus is one of the most common developmental disorders, aecting nearly 1 in 1000 newly born babies [2]. Magnetic resonance imaging (MRI) is a non-invasive technique for diagnosis of hydro- cephalus, due to its excellent sof tissue contrast and ability to resolve multiple imaging parameters [3]. Beyond anatomical imaging to resolve the extent of CSF distribution and plan for surgeries, diusion tensor imaging studies have reported lesions in the white mater in hydrocephalic patients [4] [5] [B]. While the later provides an insight into the integrity of the structural tracts across the whole brain, the use of functional (f)MRI is an atractive method to assess the functional integrity of underlying neuronal networks. In particular, functional connectivity (FC), estimated in a paradigm-free seting, allows for the imaging of several resting-state networks (RSNs) in parallel across the brain. Tis provides a comprehensive representation of the functional parcellation of healthy and diseased tissue. To date, the extent of FC across RSNs in hydrocephalic conditions has been marginally investigated. Patients with idiopathic normal pressure hydrocephalus were shown to have decreased DMN activity relative to healthy controls [M]. However, the same DMN activity was counterintuitively increased with symptom severity. A more recent clinical study on resting-state fMRI (rs-fMRI) found disrupted interhemispheric FC in hydro- cephalic patients compared to healthy subjects [X]. Currently, there are no established biomarkers for the functional impact of hydrocephalus [X].