Functional Connectivity of the Motor System in Dystonia Due to PKAN

Overview

Journal eNeurologicalSci

Specialty Neurology

Date 2021 Feb 4

PMID 33537468

Authors

Peter Stoeter

Pedro Roa

Pamela Bido

Herwin Speckter

Jairo Oviedo

Rea Rodriguez-Raecke

Affiliations

Soon will be listed here.

Abstract

Purpose: To demonstrate deviations of functional connectivity within the motor system in dystonic patients suffering from Pantothenate Kinase Associated Neurodegeneration, a genetic and metabolic disease, which is characterized by a primary lesion in the globus pallidus.

Material And Methods: Functional Magnetic Resonance Imaging data were measured during resting state in 12 patients suffering from a confirmed mutation of the PANK2 gene. In this region-of-interest based analysis, data were evaluated in respect to correlation of signal time course between basal ganglia, motor-related cortical regions and cerebellum, were related to clinical data and were compared to a control group of 20 healthy volunteers.

Results: During resting state, correlation coefficients within the motor system were significantly lower in patients than in controls (0.025 vs. 0.133, < 0.05). Network analysis by Network Based Statistics showed that these differences mainly affected the connectivity between a sub-network consisting of the basal ganglia and another one, the motor system-related cortical areas ( < 0.05). 6 out of 12 connections, which correlated significantly to duration of disease, were connections between both sub-networks.

Conclusion: The finding of a reduced functional connectivity within the motor network, between the basal ganglia and cortical motor-related areas, fits well into the concept of a general functional disturbance of the motor system in PKAN.

References

Delnooz C, Pasman J, Beckmann C, van de Warrenburg B . Altered striatal and pallidal connectivity in cervical dystonia. Brain Struct Funct. 2013; 220(1):513-23. DOI: 10.1007/s00429-013-0671-y. View

Mink J . The Basal Ganglia and involuntary movements: impaired inhibition of competing motor patterns. Arch Neurol. 2003; 60(10):1365-8. DOI: 10.1001/archneur.60.10.1365. View

Trujillo J, Gerrits N, Veltman D, Berendse H, van der Werf Y, van den Heuvel O . Reduced neural connectivity but increased task-related activity during working memory in de novo Parkinson patients. Hum Brain Mapp. 2015; 36(4):1554-66. PMC: 6869711. DOI: 10.1002/hbm.22723. View

Zalesky A, Fornito A, Bullmore E . Network-based statistic: identifying differences in brain networks. Neuroimage. 2010; 53(4):1197-207. DOI: 10.1016/j.neuroimage.2010.06.041. View

Leoni V, Strittmatter L, Zorzi G, Zibordi F, Dusi S, Garavaglia B . Metabolic consequences of mitochondrial coenzyme A deficiency in patients with PANK2 mutations. Mol Genet Metab. 2012; 105(3):463-71. PMC: 3487396. DOI: 10.1016/j.ymgme.2011.12.005. View

Mantel T, Meindl T, Li Y, Jochim A, Gora-Stahlberg G, Kraenbring J . Network-specific resting-state connectivity changes in the premotor-parietal axis in writer's cramp. Neuroimage Clin. 2017; 17:137-144. PMC: 5650679. DOI: 10.1016/j.nicl.2017.10.001. View

Quartarone A, Cacciola A, Milardi D, Ghilardi M, Calamuneri A, Chillemi G . New insights into cortico-basal-cerebellar connectome: clinical and physiological considerations. Brain. 2019; 143(2):396-406. DOI: 10.1093/brain/awz310. View

Hayflick S, Westaway S, Levinson B, Zhou B, Johnson M, Ching K . Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome. N Engl J Med. 2003; 348(1):33-40. DOI: 10.1056/NEJMoa020817. View

Carbon M, Eidelberg D . Abnormal structure-function relationships in hereditary dystonia. Neuroscience. 2009; 164(1):220-9. PMC: 2760608. DOI: 10.1016/j.neuroscience.2008.12.041. View

10.

Rodriguez-Raecke R, Roa-Sanchez P, Speckter H, Fermin-Delgado R, Perez-Then E, Oviedo J . Grey matter alterations in patients with Pantothenate Kinase-Associated Neurodegeneration (PKAN). Parkinsonism Relat Disord. 2014; 20(9):975-9. DOI: 10.1016/j.parkreldis.2014.06.005. View

11.

Mayka M, Corcos D, Leurgans S, Vaillancourt D . Three-dimensional locations and boundaries of motor and premotor cortices as defined by functional brain imaging: a meta-analysis. Neuroimage. 2006; 31(4):1453-74. PMC: 2034289. DOI: 10.1016/j.neuroimage.2006.02.004. View

12.

Stoeter P, Rodriguez-Raecke R, Vilchez C, Perez-Then E, Speckter H, Oviedo J . Motor activation in patients with Pantothenate-Kinase Associated Neurodegeneration: a functional magnetic resonance imaging study. Parkinsonism Relat Disord. 2012; 18(9):1007-10. DOI: 10.1016/j.parkreldis.2012.05.009. View

13.

Kruer M, Hiken M, Gregory A, Malandrini A, Clark D, Hogarth P . Novel histopathologic findings in molecularly-confirmed pantothenate kinase-associated neurodegeneration. Brain. 2011; 134(Pt 4):947-58. PMC: 3105492. DOI: 10.1093/brain/awr042. View

14.

Battistella G, Fuertinger S, Fleysher L, Ozelius L, Simonyan K . Cortical sensorimotor alterations classify clinical phenotype and putative genotype of spasmodic dysphonia. Eur J Neurol. 2016; 23(10):1517-27. PMC: 5308055. DOI: 10.1111/ene.13067. View

15.

Bullmore E, Sporns O . Complex brain networks: graph theoretical analysis of structural and functional systems. Nat Rev Neurosci. 2009; 10(3):186-98. DOI: 10.1038/nrn2575. View

16.

Milardi D, Quartarone A, Bramanti A, Anastasi G, Bertino S, Basile G . The Cortico-Basal Ganglia-Cerebellar Network: Past, Present and Future Perspectives. Front Syst Neurosci. 2019; 13:61. PMC: 6831548. DOI: 10.3389/fnsys.2019.00061. View

17.

Stoeter P, Roa-Sanchez P, Speckter H, Perez-Then E, Foerster B, Vilchez C . Changes of cerebral white matter in patients suffering from Pantothenate Kinase-Associated Neurodegeneration (PKAN): A diffusion tensor imaging (DTI) study. Parkinsonism Relat Disord. 2015; 21(6):577-81. DOI: 10.1016/j.parkreldis.2015.03.009. View

18.

Zhan C, Chen H, Gao Y, Zou T . Functional Network-Based Statistics Reveal Abnormal Resting-State Functional Connectivity in Minimal Hepatic Encephalopathy. Front Neurol. 2019; 10:33. PMC: 6362410. DOI: 10.3389/fneur.2019.00033. View

19.

Murphy K, Fox M . Towards a consensus regarding global signal regression for resting state functional connectivity MRI. Neuroimage. 2016; 154:169-173. PMC: 5489207. DOI: 10.1016/j.neuroimage.2016.11.052. View

20.

Hayflick S, Hartman M, Coryell J, Gitschier J, Rowley H . Brain MRI in neurodegeneration with brain iron accumulation with and without PANK2 mutations. AJNR Am J Neuroradiol. 2006; 27(6):1230-3. PMC: 2099458. View