Brain connectivity changes in autosomal recessive Parkinson disease: A model for the sporadic form

Elena Makovac, Mara Cercignani, Laura Serra, Mario Torso, Barbara Spano', Simona Petrucci, Lucia Ricciardi, Monia Ginevrino, Carlo Caltagirone, A. Bentivoglio, Enza Maria Valente, Marco Bozzali

Research output: Contribution to journalArticle

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 (RSfMRI), 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 RSfMRI 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.

Original languageEnglish
Article numbere0163980
JournalPLoS One
Volume11
Issue number10
DOIs
Publication statusPublished - Oct 1 2016

Fingerprint

Parkinson disease
Parkinson Disease
Brain
mutation
brain
Mutation
Magnetic Resonance Imaging
Short-Term Memory
signs and symptoms (animals and humans)
Data storage equipment
Independent component analysis
Neurobehavioral Manifestations
Heterozygote
Genes
heterozygosity
Networks (circuits)
genes
Spatial Memory

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Brain connectivity changes in autosomal recessive Parkinson disease : A model for the sporadic form. / Makovac, Elena; Cercignani, Mara; Serra, Laura; Torso, Mario; Spano', Barbara; Petrucci, Simona; Ricciardi, Lucia; Ginevrino, Monia; Caltagirone, Carlo; Bentivoglio, A.; Valente, Enza Maria; Bozzali, Marco.

In: PLoS One, Vol. 11, No. 10, e0163980, 01.10.2016.

Research output: Contribution to journalArticle

Makovac, E, Cercignani, M, Serra, L, Torso, M, Spano', B, Petrucci, S, Ricciardi, L, Ginevrino, M, Caltagirone, C, Bentivoglio, A, Valente, EM & Bozzali, M 2016, 'Brain connectivity changes in autosomal recessive Parkinson disease: A model for the sporadic form', PLoS One, vol. 11, no. 10, e0163980. https://doi.org/10.1371/journal.pone.0163980
Makovac, Elena ; Cercignani, Mara ; Serra, Laura ; Torso, Mario ; Spano', Barbara ; Petrucci, Simona ; Ricciardi, Lucia ; Ginevrino, Monia ; Caltagirone, Carlo ; Bentivoglio, A. ; Valente, Enza Maria ; Bozzali, Marco. / Brain connectivity changes in autosomal recessive Parkinson disease : A model for the sporadic form. In: PLoS One. 2016 ; Vol. 11, No. 10.
@article{ad1977c767264a038500a361e0c0d6ce,
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 (RSfMRI), 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 RSfMRI 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.",
author = "Elena Makovac and Mara Cercignani and Laura Serra and Mario Torso and Barbara Spano' and Simona Petrucci and Lucia Ricciardi and Monia Ginevrino and Carlo Caltagirone and A. Bentivoglio and Valente, {Enza Maria} and Marco Bozzali",
year = "2016",
month = "10",
day = "1",
doi = "10.1371/journal.pone.0163980",
language = "English",
volume = "11",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "10",

}

TY - JOUR

T1 - Brain connectivity changes in autosomal recessive Parkinson disease

T2 - A model for the sporadic form

AU - Makovac, Elena

AU - Cercignani, Mara

AU - Serra, Laura

AU - Torso, Mario

AU - Spano', Barbara

AU - Petrucci, Simona

AU - Ricciardi, Lucia

AU - Ginevrino, Monia

AU - Caltagirone, Carlo

AU - Bentivoglio, A.

AU - Valente, Enza Maria

AU - Bozzali, Marco

PY - 2016/10/1

Y1 - 2016/10/1

N2 - 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 (RSfMRI), 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 RSfMRI 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.

AB - 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 (RSfMRI), 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 RSfMRI 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.

UR - http://www.scopus.com/inward/record.url?scp=84992756733&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84992756733&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0163980

DO - 10.1371/journal.pone.0163980

M3 - Article

VL - 11

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 10

M1 - e0163980

ER -