Cerebellum and cognition in progressive MS patients: functional changes beyond atrophy?

Cocozza, Sirio; Pontillo, Giuseppe; Russo, Camilla; Russo, Cinzia Valeria; Costabile, Teresa; Pepe, Alessio; Tedeschi, Enrico; Lanzillo, Roberta; Morra, Vincenzo Brescia; Brunetti, Arturo; Inglese, Matilde; Petracca, Maria

doi:10.1007/s00415-018-8985-6

Cited by 22 publications

(28 citation statements)

References 32 publications

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“…We found that the correlation between the FC of both cerebellar compartments and PASAT performance was influenced by the severity of cerebellar structural damage, that is, infratentorial lesion burden and cerebellar volume loss. The relationship between cerebellar structural and functional alterations has recently been investigated, 17 and revealed to be only partially independent of each other in a sample of patients with progressive MS. However, the more advanced clinical stage and more severe tissue damage in those patients could explain a different effect of structural damage on FC and cognitive impairment with respect to our results.…”

Section: Discussionmentioning

confidence: 99%

“…19 fMRI studies have shown an association between attention-task performances and increased activity in the posterior cerebellar lobe, 20 particularly between lobules VI and VII and language, memory, and executive function tasks. 17,18 Furthermore, lobule VIII was found to be activated during hand/arm and lower limb movement. 5,21…”

Section: Introductionmentioning

confidence: 97%

“…12 Indeed, altered functional connectivity (FC) has been repeatedly reported in MS, 13 and more specifically, altered cerebellar FC correlates with disability in MS patients. 14–17…”

Section: Introductionmentioning

confidence: 99%

“…Other studies investigated FC changes of each cerebellar lobule individually 16 or FC changes of only the cCb. 17…”

Section: Introductionmentioning

confidence: 99%

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Resting-state functional connectivity of anterior and posterior cerebellar lobes is altered in multiple sclerosis

et al. 2020

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Background: Damage to the cerebellar sensorimotor and cognitive domains may underlie physical and cognitive disability. Objective: To investigate resting-state functional connectivity (FC) of sensorimotor and cognitive cerebellum, and clinical correlates in multiple sclerosis (MS). Methods: A total of 119 patients with MS and 42 healthy subjects underwent multimodal 3T-magnetic resonance imaging (MRI). Patients were evaluated using the Expanded Disability Status Scale and Multiple Sclerosis Functional Composite Scale. After parcellation of sensorimotor (lobules I–V + VIII) and cognitive cerebellum (lobules VI, VII, IX, X), we calculated cerebellar resting-state FC using a seed-based approach. Results: In patients with MS, the sensorimotor cerebellum showed increased FC mainly with cerebellar, thalamic, and cortical (frontal, parietal, temporal) areas and decreased FC with insular areas; the cognitive cerebellum showed increased FC mainly with thalamic and cortical (temporal-occipital) areas, and decreased FC with frontal-insular areas. Both sensorimotor and cognitive cerebellar FC negatively correlated with disability, and positively with cognitive scores. Cerebellar structural damage only partially influenced results. Conclusion: The two neocerebellar circuits showed altered FC with subcortical and cortical areas. The association between increased sensorimotor and cognitive cerebellar FC and low levels of physical and cognitive disability suggests that altered FC might modulate the effects of cerebellar structural damage on clinical condition.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

“…12 Indeed, altered functional connectivity (FC) has been repeatedly reported in MS, 13 and more specifically, altered cerebellar FC correlates with disability in MS patients. 14–17…”

Section: Introductionmentioning

confidence: 99%

“…Other studies investigated FC changes of each cerebellar lobule individually 16 or FC changes of only the cCb. 17…”

Section: Introductionmentioning

confidence: 99%

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Resting-state functional connectivity of anterior and posterior cerebellar lobes is altered in multiple sclerosis

et al. 2020

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“…Eventually, during the last years, the great interest regarding cerebellum involvement across different neurological diseases has been confirmed by the growing body of methodology to achieve a fine segmentation of this tiny structure (34). However, even though some newer cerebellar segmentation methods have shown higher accuracy (35) than SUIT, the latest has extensively proved to be valid in demonstrating differences between patients with MS and controls, as evidenced by a series of works published in the field (13,14,36), with the advantage of being more user friendly and less time-consuming (35). Despite these limitations, our findings indicate that regional atrophy in the cerebellum along with disruption of afferent and efferent pathways to this structure encompasses a pathological substrate of physical deficits seen in patients with MS and evaluated by measures of balance, EDSS, and 25-FWT.…”

Section: Discussionmentioning

confidence: 99%

A Comprehensive Approach to Disentangle the Effect of Cerebellar Damage on Physical Disability in Multiple Sclerosis

et al. 2020

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Cerebellar damage occurs frequently in multiple sclerosis (MS) patients, with a wide exhibition of symptoms particularly as impairments of balance and gait. Recent studies implementing new postprocessing magnetic resonance imaging (MRI) techniques showed how cerebellar subregional atrophy provides an explanation of disability in MS. The aim of this work was to evaluate the relationship between quantitative measures of physical disability, cerebellar subregional atrophy, and cerebellar peduncle disruption. Forty-nine MS patients and 32 healthy subjects as controls (HS) underwent a 3-Tesla MRI including 3D T1-weighted and diffusion tensor imaging. Patients underwent static posturography to calculate the body's center of pressure (COP) displacement, Expanded Disability Status Scale (EDSS), and 25-ft walking test (25-FWT). Cerebellar lobular volumes were automatically calculated using the Spatially Unbiased Infratentorial Toolbox. Tract-based spatial statistics (TBSS) in FSL was used to process diffusion tensor imaging (DTI) Fit-generated fractional anisotropy (FA) maps to assess structural connectivity of cerebellar peduncles. Stepwise multivariate linear regression analyses were used to explore relationships between variables. Cerebellar volumes (anterior and posterior, as well as lobular volumes from I to X) were significantly lower in patients with MS than HS (p < 0.05). FA in all cerebellar peduncles was lower in MS patients than in HS (p < 0.05). EDSS and 25-FWT showed an association with atrophy of lobule VIIIb (β = −0.37, p < 0.01, and β = −0.45, p < 0.001, respectively) COP measures inversely correlated with volume of lobules I-IV (β = −0.37, p < 0.01, and β = −0.36, p < 0.01). Lower FA in the three cerebellar peduncles of MS patients positively correlated with cerebellar lobular volumes. Our findings show how sensorimotor cerebellum atrophy and disruption of both afferent and efferent cerebellar connections contribute to physical disability in MS patients.

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Resting‐state functional magnetic resonance imaging reveals functional connectivity alteration in the experimental autoimmune encephalomyelitis model of multiple sclerosis

Bontempi,

Piccolantonio,

Busato

et al. 2024

NMR in Biomedicine

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Multiple sclerosis (MS) is an autoimmune degenerative disease targeting white matter in the central nervous system. The most common animal model that mimics MS is experimental autoimmune encephalomyelitis (EAE) and it plays a crucial role in pharmacological research, from the identification of a therapeutic target to the in vivo validation of efficacy. Magnetic resonance imaging (MRI) is largely used to detect MS lesions, and resting‐state functional MRI (rsfMRI) to investigate alterations in the brain functional connectivity (FC). MRI was mainly used in EAE studies to detect lesions in the spinal cord and brain. The current longitudinal MRI study aims to validate rsfMRI as a biomarker of the disease progression in the myelin oligodendrocyte glycoprotein 35–55 induced EAE animal model of MS. MR images were acquired 14, 25, and 50 days postimmunization. Seed‐based analysis was used to investigate the whole‐brain FC with some predefined areas, such as the thalamic regions, cerebellum, motor and somatosensory cortex. When compared with the control group, the EAE group exhibited a slightly altered FC and a decreasing trend in the total number of activated voxels along the disease progression. The most interesting result regards the whole‐brain FC with the cerebellum. A hyperconnectivity behavior was found at an early phase and a significant reduced connectivity at a late phase. Moreover, we found a negative correlation between the total number of activated voxels during the late phase and the cumulative disease index. The results obtained provide a clinically relevant experimental platform that may be pivotal for the elucidation of the key mechanisms of accumulation of irreversible disability, as well as the development of innovative therapies for MS. Moreover, the negative correlation between the disease severity and the size of the activated area suggests a possible research pathway to follow for the resolution of the clinico‐radiological paradox.

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Cerebellum and cognition in progressive MS patients: functional changes beyond atrophy?

Abstract: PMS patients show cerebellar FC rearrangements that are partially independent from cerebellar structural damage, and are likely expression of a maladaptive functional rewiring.

Cited by 22 publications

References 32 publications

Resting-state functional connectivity of anterior and posterior cerebellar lobes is altered in multiple sclerosis

Resting-state functional connectivity of anterior and posterior cerebellar lobes is altered in multiple sclerosis

A Comprehensive Approach to Disentangle the Effect of Cerebellar Damage on Physical Disability in Multiple Sclerosis

Resting‐state functional magnetic resonance imaging reveals functional connectivity alteration in the experimental autoimmune encephalomyelitis model of multiple sclerosis

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