title: Brain Connectivity Changes in Autosomal Recessive Parkinson Disease: A Model for the Sporadic Form.
abstract: Biallelic genetic mutations in the Park2 and PINK1 genes are frequent causes of autosomal recessive PD. Carriers of single heterozygous mutations may manifest subtle signs of disease, thus providing a unique model of preclinical PD. One emerging hypothesis suggests that non-motor symptom of PD, such as cognitive impairment may be due to a distributed functional disruption of various neuronal circuits. Using resting-state functional MRI (RS-fMRI), we tested the hypothesis that abnormal connectivity within and between brain networks may account for the patients' cognitive status. Eight homozygous and 12 heterozygous carriers of either PINK1 or Park2 mutation and 22 healthy controls underwent RS-fMRI and cognitive assessment. RS-fMRI data underwent independent component analysis to identify five networks of interest: default-mode network, salience network, executive network, right and left fronto-parietal networks. Functional connectivity within and between each network was assessed and compared between groups. All mutation carriers were cognitively impaired, with the homozygous group reporting a more prominent impairment in visuo-spatial working memory. Changes in functional connectivity were evident within all networks between homozygous carriers and controls. Also heterozygotes reported areas of reduced connectivity when compared to controls within two networks. Additionally, increased inter-network connectivity was observed in both groups of mutation carriers, which correlated with their spatial working memory performance, and could thus be interpreted as compensatory. We conclude that both homozygous and heterozygous carriers exhibit pathophysiological changes unveiled by RS-fMRI, which can account for the presence/severity of cognitive symptoms.
authors: Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.
authors: Elena
authors: E
authors: Makovac
authors: Clinical Imaging Sciences Centre, Brighton & Sussex Medical School, Falmer, Brighton, United Kingdom.
authors: Mara
authors: M
authors: Cercignani
authors: Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.
authors: Laura
authors: L
authors: Serra
authors: Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.
authors: Mario
authors: M
authors: Torso
authors: Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.
authors: Barbara
authors: B
authors: Spanò
authors: IRCCS Casa Sollievo della Sofferenza, CSS-Mendel laboratory, San Giovanni Rotondo, Italy.|Dept. of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
authors: Simona
authors: S
authors: Petrucci
authors: Sobell Dept. of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, London, United Kingdom.
authors: Lucia
authors: L
authors: Ricciardi
authors: IRCCS Casa Sollievo della Sofferenza, CSS-Mendel laboratory, San Giovanni Rotondo, Italy.
authors: Monia
authors: M
authors: Ginevrino
authors: Dept. of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, Rome, Italy.|Dept. of Neuroscience, University of Rome 'Tor Vergata', Rome, Italy.
authors: Carlo
authors: C
authors: Caltagirone
authors: Dept. of Neurosciences, Catholic University, Rome, Italy.
authors: Anna Rita
authors: AR
authors: Bentivoglio
authors: IRCCS Casa Sollievo della Sofferenza, CSS-Mendel laboratory, San Giovanni Rotondo, Italy.|Section of Neurosciences, Dept. of Medicine and Surgery, University of Salerno, Salerno, Italy.
authors: Enza Maria
authors: EM
authors: Valente
authors: Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.
authors: Marco
authors: M
authors: Bozzali
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology; D001931:Brain Mapping; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009415:Nerve Net / Q000473:pathology* / Q000503:physiopathology; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D012146:Rest / Q000502:physiology