Journal Article

Brain Connectivity Changes in Autosomal Recessive Parkinson Disease: A Model for the Sporadic Form

Makovac, Elena, Cercignani, Mara, Serra, Laura, Valente, Enza Maria, Petrucci, Simona, Bentivoglio, Anna Rita, Ginevrino, Monia, Caltagirone, Carlo, Ricciardi, Lucia, Torso, Mario, Spanò, Barbara, Bozzali, Marco

2016

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Biology and Life Sciences / Brain / Brain - diagnostic imaging / Brain - pathology / Brain - physiopathology / Brain damage / Brain Mapping / Carriers / Cognitive ability / Computer and Information Sciences / Data processing / Dementia / Female / Functional magnetic resonance imaging / Functional morphology / Gene mutation / Genetic aspects / Heterozygote / Heterozygotes / Homozygote / Humans / Impairment / Independent component analysis / Laboratories / Magnetic Resonance Imaging / Male / Medical imaging / Medicine and Health Sciences / Memory / Middle Aged / Movement disorders / Mutation / Nerve Net - pathology / Nerve Net - physiopathology / Networks / Neural networks / Neurodegenerative diseases / Neurology / Neurons / Neuropsychological Tests / Neurosciences / Parkinson disease / Parkinson Disease - diagnostic imaging / Parkinson Disease - genetics / Parkinson Disease - pathology / Parkinson Disease - physiopathology / Parkinson's disease / Parkinsons disease / PTEN-induced putative kinase / Research and Analysis Methods / Rest - physiology / Short term memory / Social Sciences / Spatial distribution / Spatial memory