Resting-state functional connectivity changes in the cerebellum in multiple sclerosis. A review.
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1
University College of London, Neuroinflammation, United Kingdom
Background: Dysfunction of the cerebellum in multiple sclerosis (MS) patients is frequent and can be caused by demyelinating lesions, cortical lesions, atrophy and damage in the white matter (WM) tracts in the peduncles (1). Cerebellar involvement in MS contributes not only to physical disability, but also to cognitive impairment (2). Therefore, there has been a growing interest in studying the role of cerebellum connectivity changes in cognitive function in MS patients. Resting state fMRI (rs-fMRI) is an MRI technique that can be used to evaluate regional interactions that occur when a subject is not performing a task. Rs-fMRI allows the investigation of changes within and across multiple functional networks without bias of task performance, adherence or subject effort (3).
Objective: This review aims to determine if rs-fMRI changes in cerebellum functional connectivity (FC) are associated with cognitive dysfunction in MS patients.
Methods: We conducted a systematic search on Medline including all published original studies in MS patients with rs-fMRI investigating the role of cerebellum functional connectivity changes in cognitive dysfunction. We found 6 observational cross-sectional case-control studies. A total of 236 patients with MS were studied (221 relapsing-remitting; 10 clinically isolated syndrome; 5 secondary progressive). Only 1 study did not include age and gender matched healthy controls (HCs). The cognitive test most used was the Paced Auditory Serial Addition Test (PASAT). All studies assessed the cerebellum white matter damage calculating the lesion load on T2/FLAIR sequences and 2 studies evaluated the WM tract integrity with DTI. Only 1 study used DIR to evaluate the presence of cerebellar cortical lesions.
Results: Three studies showed an inverse correlation between resting state functional connectivity (RS-FC) in the cerebellum and the PASAT score (higher scores correspond to better cognitive performance) (4-6). Particularly, in one study (4) greater FC between the dentate nucleus and frontal and parietal cortical areas inversely correlated with PASAT scores. One study found reduced FC in the dorsal attentional network, connected with the ventral cerebellum (7). One study did not show a correlation between PASAT performance and cerebellar RS-FC (8). Finally, one study did not find local FC alterations in the cerebellum, irrespective of structural damage (9). (Table 1)
Conclusions: A few rs-fMRI studies have been conducted so far to investigate the role of the cerebellum in cognition in MS. Most of them are consistent with the results from previous task-fMRI studies concerning an alteration in the cerebellum circuits, locally or in connection with other cortical areas, associated with performance at the cognitive tests. Cross-sectional rs-fMRI studies in patients with MS suggest that prominent functional changes can be detected in cerebellar networks and correlate with clinical measures Therefore, rs-fMRI could have the potential to monitor the impact of possible therapeutic interventions. Interestingly, an association between increased RS-FC and higher cognitive test score was observed in the only study conducted in patients with early MS, although patients and controls showed a similar range of scores. This observation is in concordant with the lack of major cognitive deficits in early MS and could suggest an initial compensatory neuroplasticity. Future, comprehensive longitudinal studies could assess the associations between the evolution over time of the cognitive function, evolution of the disease and cerebellum connectivity metrics.
References
1) Weier et al., “The Role of the Cerebellum in Multiple Sclerosis”. Cerebellum 2015; 14 (3) : 364-374.
2) Ruet et al., “Information processing speed impairment and cerebellar dysfunction in relapsing–remitting multiple sclerosis”. Journal of the Neurological Sciences 2014; 347: 246–250
3) Pinter et al., “Reproducibility of Resting State Connectivity in Patients with Stable Multiple Sclerosis.” PLoS One 2016;11(3): e0152158.
4) Sbardella et al., “Dentate nucleus connectivity in adult patients with multiple sclerosis: functional changes at rest and correlation with clinical features.” Mult Scler. 2016; Vol. 13.
5) Loitfelder et al., “Abnormalities of Resting State FunctionalConnectivityAre Related to Sustained Attention Deficits in MS.” PLoS One 2012; 7 (8): e42862.
6) Tona et al., “Multiple Sclerosis: Altered Thalamic Resting-State Functional Connectivity and Its Effect on Cognitive Function.” Radiology 2014; 271 (3): 814-821.
7) Louapre et al., “Brain Networks Disconnection in Early Multiple Sclerosis Cognitive Deficits: An Anatomofunctional Study” Human Brain Mapping 2014; 35: 4706–4717.
8) Sbardella et al., “Functional connectivity changes and their relationship with clinical disability and white matter integrity in patients with relapsing–remitting multiple sclerosis.” Mult Scler. 2015, Vol. 21(13) 1681–1692
9) Romascano et al., “Multicontrast Connectometry: A New Tool to Assess Cerebellum Alterations in Early Relapsing-Remitting Multiple Sclerosis.” Human Brain Mapping 2015; 36:1609–1619
Keywords:
resting state fMRI,
Cerebellum,
Multiple Sclerosis,
Adult,
Cognition
Conference:
The Cerebellum inside out: cells, circuits and functions
, ERICE (Trapani), Italy, 1 Dec - 5 Dec, 2016.
Presentation Type:
poster
Topic:
Integrative nuroscience and MRI
Citation:
Collorone
S and
Toosy
A
(2019). Resting-state functional connectivity changes in the cerebellum in multiple sclerosis. A review..
Conference Abstract:
The Cerebellum inside out: cells, circuits and functions
.
doi: 10.3389/conf.fncel.2017.37.000019
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Received:
29 Nov 2016;
Published Online:
25 Jan 2019.
*
Correspondence:
MD. Sara Collorone, University College of London, Neuroinflammation, London, WC1N 3BG, United Kingdom, s.collorone@ucl.ac.uk