Default mode network changes in multiple sclerosis: a link between depression and cognitive impairment? S. Bonavita a,b , R. Sacco a , S. Esposito a , A. d’Ambrosio a , M. Della Corte b , D. Corbo b , R. Docimo a , A. Gallo a , L. Lavorgna a , M. Cirillo c , A. Bisecco a , F. Esposito d and G. Tedeschi a,b a Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples; b MRI Center ‘SUN FISM’, Neurological Institute for Diagnosis and Care ‘Hermitage Capodimonte’, Naples; c Neuroradiology Service, Department of Radiology, Second University of Naples, Naples; and d Department of Medicine Surgery and Dentistry, University of Salerno, Salerno, Italy Keywords: cognitive impairment, default mode network, depression, multiple sclerosis, resting state f-MRI Received 25 January 2016 Accepted 27 June 2016 European Journal of Neurology 2017, 24: 27–36 doi:10.1111/ene.13112 Background and purpose: In multiple sclerosis (MS), depression is a common disorder whose pathophysiology is still debated. To gain insights into the pathophysiology of depression in MS, resting-state (RS) functional connectiv- ity (FC) changes of the default mode network (DMN), salience network (SN) and executive control network (ECN) were assessed in a group of depressed MS (D-MS) patients and in appropriately matched control groups. Methods: Sixteen D-MS patients, 17 non-depressed MS (ND-MS) patients, 17 non-depressed healthy controls and 15 depressed subjects (D-S), age, sex and education matched, cognitively preserved and non-fatigued, were enrolled. All participants underwent a neuropsychological evaluation and RS functional magnetic resonance imaging study. Results: Comparing D-MS patients with D-S, within the DMN, a significant RS-FC suppression was found in the posterior cingulate cortex (PCC); com- paring D-MS with ND-MS, FC was significantly increased in the anterior cin- gulate cortex and significantly reduced in the PCC. Within the SN increased FC in the right supramarginal gyrus and right middle frontal gyrus was found in D-MS patients compared to D-S and to ND-MS; within the ECN increased FC in the right inferior parietal cortex was found in D-MS patients compared to ND-MS patients. Conclusions: In cognitively preserved D-MS patients, FC derangement occurs in the SN, ECN and DMN. In the latter, changes occurring both in the ante- rior cingulate cortex and PCC suggest that depression in MS may be linked to MS itself and, in particular, to a peculiar pattern of network abnormalities favored by MS pathology through disconnection mechanisms. Reduced FC in the PCC, similar to MS patients with cognitive impairment, suggests a func- tional link between depression and cognitive impairment in MS. Introduction The most common psychiatric syndrome in multiple sclerosis (MS) is depression, with a lifetime prevalence of 40%–60%, a figure three to 10 times more than the general population [1]. Neuroimaging studies with advanced magnetic reso- nance imaging (MRI) techniques have revealed associ- ations between a number of brain abnormalities and depression in MS, suggesting that depression in MS is mainly linked to damage of fronto-temporal areas in the form of atrophy, discrete white matter (WM) lesions and subtle normal appearing WM (NAWM) abnormalities. However, these studies have produced conflicting results, mostly explainable by differences in study design and sample characteristics, particularly Correspondence: S. Bonavita, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Piazza Miraglia 2, 80138 Naples, Italy (tel./fax: +39 081 56655095; e-mail: simona.bonavita@unina2.it). © 2016 EAN 27 ORIGINALARTICLE EUROPEANJOURNALOFNEUROLOGY