Modifications of resting state networks in spinocerebellar ataxia type 2

Cocozza, Sirio; Saccà, Francesco; Cervo, Amedeo; Marsili, Angela; Russo, Cinzia Valeria; Giorgio, Sara Maria delle Acque; Michele, Giuseppe De; Filla, Alessandro; Brunetti, Arturo; Quarantelli, Mario

doi:10.1002/mds.26284

Cited by 22 publications

(27 citation statements)

References 54 publications

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“…Cerebellar clusters of significantly reduced functional connectivity have been recently reported by Cocozza et al (2015) only in the default mode network, executive control network and right fronto-parietal network in patients with SCA2. However, this study used a different resting-state approach (i.e.…”

Section: Discussionmentioning

confidence: 98%

“…However, this study used a different resting-state approach (i.e. ICA) limited to investigate connectivity within specific functional networks (Cocozza et al, 2015). In the present study, by using a whole-brain approach, we provide additional evidence that extensive and segregated functional brain changes may occur as the result of the SCA2 degenerative process.…”

Section: Discussionmentioning

confidence: 99%

“…While structural patterns associated with cerebellum and cerebral cortex have been largely investigated in SCA2, the few studies, that addressed FC, have used resting-state fMRI approaches limited to investigate specific structures using regions chosen a priori through seed-based analysis (Hernandez-Castillo et al, 2015a) or meaningful functional networks through independent component analysis (ICA) (Hernandez-Castillo et al, 2015a, Cocozza et al, 2015). Indeed, the analysis of pre-defined seed regions or specific networks only represents a small proportion of the brain, thus they may not be able to provide a complete picture of how the connectome is affected in by SCA2.…”

Section: Introductionmentioning

confidence: 99%

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Neural substrates of motor and cognitive dysfunctions in SCA2 patients: A network based statistics analysis

Olivito

Cercignani

Lupo

et al. 2017

NeuroImage: Clinical

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Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease characterized by a progressive cerebellar syndrome, which can be isolated or associated with extracerebellar signs. It has been shown that patients affected by SCA2 present also cognitive impairments and psychiatric symptoms.The cerebellum is known to modulate cortical activity and to contribute to distinct functional networks related to higher-level functions beyond motor control. It is therefore conceivable that one or more networks, rather than isolated regions, may be dysfunctional in cerebellar degenerative diseases and that an abnormal connectivity within specific cerebello-cortical regions might explain the widespread deficits typically observed in patients.In the present study, the network-based statistics (NBS) approach was used to assess differences in functional connectivity between specific cerebellar and cerebral “nodes” in SCA2 patients. Altered inter-nodal connectivity was found between more posterior regions in the cerebellum and regions in the cerebral cortex clearly related to cognition and emotion. Furthermore, more anterior cerebellar lobules showed altered inter-nodal connectivity with motor and somatosensory cerebral regions. The present data suggest that in SCA2 a cerebellar dysfunction affects long-distance cerebral regions and that the clinical symptoms may be specifically related with connectivity changes between motor and non-motor cerebello-cortical nodes.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Neural substrates of motor and cognitive dysfunctions in SCA2 patients: A network based statistics analysis

Olivito

Cercignani

Lupo

et al. 2017

NeuroImage: Clinical

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“…Similarly, microstructural abnormalities measured by diffusion weighted imaging have been detected in the cerebellum and the pons28 as well as cortical alterations in SCA2 patients 10, 11, 29. Functional MRI in resting‐state modus further shows changes of cerebellar but also fronto‐ and parietal connectivity networks related to cognitive and motor performance 30, 31. No multimodal MRI data other than macroanatomical measurements exist for the preclinical stage of the disease.…”

Section: Discussionmentioning

confidence: 99%

Brain atrophy measures in preclinical and manifest spinocerebellar ataxia type 2

Reetz

Rodríguez‐Labrada²,

Dogan

et al. 2018

Ann Clin Transl Neurol

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ObjectiveSpinocerebellar ataxia type 2 (SCA2) is an autosomal dominantly inherited neurodegenerative disease mainly affecting the cerebellum and brainstem. In this Cuban‐German research collaboration, we aimed to characterize atrophy patterns and associations with clinical measures in preclinical and manifest SCA2.MethodsIn this study, 16 nonmanifest SCA2 mutation carriers, 26 manifest patients with SCA2, and 18 healthy control subjects underwent magnetic resonance imaging, as well as genetic and clinical characterization including assessment of ataxia (Scale for the Assessment and Rating of Ataxia) and saccade velocity in Cuba were enrolled. Semiautomated quantitative volumetry of the cerebellum and brainstem, subdivided into the medulla oblongata, the pontine brainstem, and mesencephalon was performed. Additionally, the anteroposterior diameter of the pontine brainstem was measured.ResultsAnalysis of volumetric data revealed degeneration of the cerebellum and brainstem, in particular of pontine volumes and the anteroposterior diameter of the pons, in both manifest SCA2 patients and individuals at risk for SCA2 compared to controls. Comparing patients with nonataxic preclinical SCA2 mutation carriers, we found more pronounced reductions of the pontine brainstem and cerebellum in manifest SCA2. Volumetric data further showed associations with CAG repeat length and predicted age of onset in preclinical SCA2 individuals, and by trend with ataxia signs in patients. Although saccade velocity was associated with reduction in the pontine brainstem in preclinical and manifest SCA2, reduced ability to suppress interfering stimuli measured by the Stroop task was related to cerebellar volume loss in patients.InterpretationPreclinical SCA2 mutation carriers exhibit brain abnormalities, which could be targeted as surrogate parameters for disease progression and in future preventive trials.

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“…Proton magnetic resonance spectrometry showed a decreased of NAA in the pons and cerebellar hemispheres 50, 51. Finally, a resting state functional magnetic resonance imaging study, corrected for atrophy, showed, besides disruption of the cerebellar component of the major resting state networks, supratentorial involvement for the default‐mode network 52. Dopaminergic transmission studied by beta‐CIT, a presynaptic dopamine reuptake site ligand, and iodobenzamide (IBZM), a postsynaptic dopamine D2 receptor ligand, was found to be abnormal even in patients without parkinsonian features 53, 54.…”

Section: Imagingmentioning

confidence: 93%

The Multiple Faces of Spinocerebellar Ataxia type 2

Antenora

Rinaldi

Roca

et al. 2017

Ann Clin Transl Neurol

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Spinocerebellar ataxia type 2 (SCA2) is among the most common forms of autosomal dominant ataxias, accounting for 15% of the total families. Occurrence is higher in specific populations such as the Cuban and Southern Italian. The disease is caused by a CAG expansion in ATXN2 gene, leading to abnormal accumulation of the mutant protein, ataxin‐2, in intracellular inclusions. The clinical picture is mainly dominated by cerebellar ataxia, although a number of other neurological signs have been described, ranging from parkinsonism to motor neuron involvement, making the diagnosis frequently challenging for neurologists, particularly when information about the family history is not available. Although the functions of ataxin‐2 have not been completely elucidated, the protein is involved in mRNA processing and control of translation. Recently, it has also been shown that the size of the CAG repeat in normal alleles represents a risk factor for ALS, suggesting that ataxin‐2 plays a fundamental role in maintenance of neuronal homeostasis.

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Modifications of resting state networks in spinocerebellar ataxia type 2

Cited by 22 publications

References 54 publications

Neural substrates of motor and cognitive dysfunctions in SCA2 patients: A network based statistics analysis

Neural substrates of motor and cognitive dysfunctions in SCA2 patients: A network based statistics analysis

Brain atrophy measures in preclinical and manifest spinocerebellar ataxia type 2

The Multiple Faces of Spinocerebellar Ataxia type 2

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