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Claustral structural connectivity and cognitive impairment in drug naïve Parkinson’s disease

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The claustrum is a thin grey matter structure which is involved in a wide brain network. Previous studies suggested a link between claustrum and Parkinson’s Disease (PD), showing how α-synuclein pathology may affect claustral neurons as well as how α-synuclein immunoreactivity may correlate with the onset of cognitive dysfunctions. Our aim is to investigate, via diffusion MRI, claustral structural network changes in drug naïve PD patients, with the goal to understand whether such changes may contribute to cognitive decline in PD. 15 drug naïve PD patients and 15 age-matched controls were enrolled; MR protocol was performed on a 3T scanner. Whole brain probabilistic tractography was obtained using Constrained Spherical Deconvolution (CSD) diffusion model. Connectivity matrices were estimated based on a robust anatomical parcellation of structural T1w images. In PD group, impaired subnetworks were correlated with psychological examinations. We found decreased claustral connectivity in PD patients compared to controls, especially with areas mainly involved in visuomotor and attentional systems. Moreover, we found a positive correlation between MoCA and density of pathways connecting ipsilaterally claustrum to left (r = 0.578, p = 0.021) and right (r = 0.640, p = 0.020) Pars Orbitalis. Our results support the hypothesis of claustral involvement in cognitive decline in drug naïve PD patients.
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ORIGINAL RESEARCH
Claustral structural connectivity and cognitive impairment in drug naïve
Parkinsons disease
Alessandro Arrigo
1
&Alessandro Calamuneri
2,3
&Demetrio Milardi
2,4
&Enricomaria Mormina
3,4
&Michele Gaeta
4
&
Francesco Corallo
2
&Viviana Lo Buono
2
&Gaetana Chillemi
2
&Silvia Marino
2
&Alberto Cacciola
2,4
&
Giuseppe Di Lorenzo
2
&Giuseppina Rizzo
4
&Giuseppe Pio Anastasi
4
&Angelo Quartarone
2,4,5,6
Published online: 18 June 2018
#Springer Science+Business Media, LLC, part of Springer Nature 2018
Abstract
The claustrum is a thin grey matter structure which is involved in a wide brain network. Previous studies suggested a link between
claustrum and Parkinsons Disease (PD), showing how α-synuclein pathology may affect claustral neurons as well as how α-
synuclein immunoreactivity may correlate with the onset of cognitive dysfunctions. Our aim is to investigate, via diffusion MRI,
claustral structural network changes in drug naïve PD patients, with the goal to understand whether such changes may contribute to
cognitive decline in PD. 15 drug naïve PD patients and 15 age-matched controls were enrolled; MR protocol was performed on a 3T
scanner. Whole brain probabilistic tractography was obtained using Constrained Spherical Deconvolution (CSD) diffusion model.
Connectivity matrices were estimated based on a robust anatomical parcellation of structural T1w images. In PD group, impaired
subnetworks were correlated with psychological examinations. We found decreased claustral connectivity in PD patients compared
to controls, especially with areas mainly involved in visuomotor and attentional systems. Moreover, we found a positive correlation
between MoCA and density of pathways connecting ipsilaterally claustrum to left (r=0.578,p= 0.021) and right (r=0.640,p=
0.020) Pars Orbitalis. Our results support the hypothesis of claustral involvement in cognitive decline in drug naïve PD patients.
Keywords Claustrum .Connectivity .Diffusion MRI .Parkinsons disease .Cognitive assessment; Tractography
Introduction
The histopathological hallmark of both Parkinsons disease
(PD) and Lewy Body Dementia (LBD) is the presence of
alpha-synuclein (alpha-Syn) positive intraneuronal inclusions
known as Lewy bodies and Lewy neurites. Although their
presence in the substantia nigra is pathognomonic for PD,
alpha-Syn pathological lesions have been reported in several
extranigral regions as well. In a very elegant study Kalaitzakis
and associates have evaluated the alpha-Syn, tau and
amyloid-βeta (Aβ) pathologies in claustrum of 20 PD cases
without dementia, 12 PD cases with dementia (PDD) and 7
cases with dementia with LBD (Kalaitzakis et al. 2009). An
alpha-Syn positivity has been observed in 75% of PD cases
without dementia and in 100% of PDD and LBD cases. On the
other hand, Aβpathology has been observed in claustrum in
25% of PD, 58% of PDD and 100% of LBD cases. The au-
thors concluded that pathology in the claustrum was strongly
related to the presence of dementia in PD and LBD.
Claustrum is a thin layer of subcortical gray matter (GM)
placed in the deep part of both the cerebral lobes.
Alessandro Arrigo and Alessandro Calamuneri PhD equally contributed
to the present work and are considered co-first authors.
Electronic supplementary material The online version of this article
(https://doi.org/10.1007/s11682-018-9907-z) contains supplementary
material, which is available to authorized users.
*Alessandro Calamuneri
alecalamuneri@gmail.com
1
Department of Ophthalmology, IRCCS Ospedale San Raffaele,
University Vita-Salute San Raffaele, Milan, Italy
2
IRCCS Centro Neurolesi Bonino Pulejo, S.S. 113 Contrada
Casazza, 98124 Messina, Italy
3
Department of Clinical and Experimental Medicine, University of
Messina, Messina, Italy
4
Department of Biomedical Sciences and Morphological and
Functional Images, University of Messina, Messina, Italy
5
NYU-Langone School of Medicine, New York, NY, USA
6
The Fresco Institute for Parkinsons & Movement Disorders, New
York, NY, USA
Brain Imaging and Behavior (2019) 13:933944
https://doi.org/10.1007/s11682-018-9907-z
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... In patients with Parkinson's disease, there is a decrease in claustral connectivity with cortical regions involved in visual-motor and auditory processing. There is a decrease in the density of connections with the parietal, upper temporal and postcentral cortical regions as well as the middle temporal gyrus, pars opercularis, pars triangularis, and pars orbitalis of the frontal gyrus [75]. Functional and anatomical disorders in claustrum are therefore associated with progressive dementia in Parkinson's disease [75]. ...
... There is a decrease in the density of connections with the parietal, upper temporal and postcentral cortical regions as well as the middle temporal gyrus, pars opercularis, pars triangularis, and pars orbitalis of the frontal gyrus [75]. Functional and anatomical disorders in claustrum are therefore associated with progressive dementia in Parkinson's disease [75]. Atrophic lesions in the claustrum may be a manifestation of pathophysiological changes in patients with Parkinson's disease [76,77]. ...
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