Adaptive functional changes in the cerebral cortex during multiple sclerosis

Background/Objective. Position sense, defined as the ability to identify joint and limb position in space, is crucial for balance and gait but has received limited attention in patients with multiple sclerosis (MS). We investigated lower limb position sense deficits, their neural correlates, and their effects on standing balance in patients with early MS. Methods. A total of 24 patients with early relapsing-remitting MS and 24 healthy controls performed ipsilateral and contralateral matching tasks with the right foot during functional magnetic resonance imaging. Corpus callosum (CC) integrity was estimated with diffusion tensor imaging. Patients also underwent an assessment of balance during quiet standing. We investigated differences between the 2 groups and the relations among proprioceptive errors, balance performance, and functional/structural correlates. Results. During the contralateral matching task, patients demonstrated a higher matching error than controls, which correlated with the microstructural damage of the CC and with balance ability. In contrast, during the ipsilateral task, the 2 groups showed a similar matching performance, but patients displayed a functional reorganization involving the parietal areas. Neural activity in the frontoparietal regions correlated with the performance during both proprioceptive matching tasks and quiet standing. Conclusion. Patients with early MS had subtle, clinically undetectable, position sense deficits at the lower limbs that, nevertheless, affected standing balance. Functional changes allowed correct proprioception processing during the ipsilateral matching task but not during the more demanding bilateral task, possibly because of damage to the CC. These findings provide new insights into the mechanisms underlying disability in MS and could influence the design of neurorehabilitation protocols.

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Contribution to the Pathological Anatomy of Multiple Sclerosis, with Particular Regard to the Cerebral Cortex [Zur pathologischen Anatomie der multiplen Sklerose mit besonderer Berucksichtigung der Hirnrindenherde]. (Neur. Cbl., Nr. 19, 1908.) Oppenheim, G.

Journal of Mental Science ◽

10.1192/bjp.55.229.377-a ◽

1909 ◽

Vol 55 (229) ◽

pp. 377-378

Author(s):

Hamilton C. Marr

Keyword(s):

Multiple Sclerosis ◽

Cerebral Cortex ◽

Pathological Anatomy

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Changes and variability of proton density and T1 relaxation times in early multiple sclerosis: MRI markers of neuronal damage in the cerebral cortex

European Radiology ◽

10.1007/s00330-015-4072-x ◽

2015 ◽

Vol 26 (8) ◽

pp. 2578-2586 ◽

Cited By ~ 19

Author(s):

René-Maxime Gracien ◽

Sarah C. Reitz ◽

Stephanie Michelle Hof ◽

Vinzenz Fleischer ◽

Hilga Zimmermann ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebral Cortex ◽

Neuronal Damage ◽

Relaxation Times ◽

Proton Density ◽

T1 Relaxation

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Unexpected Microglial “De-activation” Associated With Altered Synaptic Transmission in the Early Stages of an Animal Model of Multiple Sclerosis

Journal of Experimental Neuroscience ◽

10.1177/1179069519825882 ◽

2019 ◽

Vol 13 ◽

pp. 117906951982588 ◽

Cited By ~ 1

Author(s):

Shaona Acharjee ◽

Quentin J Pittman

Keyword(s):

Multiple Sclerosis ◽

Animal Model ◽

Basolateral Amygdala ◽

Demyelinating Disease ◽

Unexpected Finding ◽

Autoimmune Encephalomyelitis ◽

Functional Changes ◽

Functional Relevance ◽

Underlying Mechanisms ◽

Excitatory Drive

Multiple sclerosis, and its animal model—experimental autoimmune encephalomyelitis (EAE), is a demyelinating disease causing motor and sensory dysfunction, as well as behavioral comorbidities. In exploring possible functional changes underlying behavioral comorbidities in EAE, we observed increased excitatory drive onto the major cells of the basolateral amygdala. This was associated with increased numbers of dendritic spines. An unexpected finding was that microglial cells at this time were in a “deactivated” state, and further studies suggested that the microglial deactivation was responsible for the increased excitatory drive. This is the first report of microglial deactivation in an inflammatory disease and raises many questions as to the underlying mechanisms and functional relevance.

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Fronto-limbic disconnection in patients with multiple sclerosis and depression

Multiple Sclerosis Journal ◽

10.1177/1352458518767051 ◽

2018 ◽

Vol 25 (5) ◽

pp. 715-726 ◽

Cited By ~ 9

Author(s):

Quinten van Geest ◽

Rosa E Boeschoten ◽

Matthijs J Keijzer ◽

Martijn D Steenwijk ◽

Petra JW Pouwels ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Duration ◽

Neuropsychological Testing ◽

Uncinate Fasciculus ◽

Resting State Functional Connectivity ◽

Major Depressive ◽

Brain Volumes ◽

Functional Changes ◽

Severity Of Depression ◽

Magnetic Resonance Imaging Mri

Background: The biological mechanism of depression in multiple sclerosis (MS) is not well understood. Based on work in major depressive disorder, fronto-limbic disconnection might be important. Objective: To investigate structural and functional fronto-limbic changes in depressed MS (DMS) and non-depressed MS (nDMS) patients. Methods: In this retrospective study, 22 moderate-to-severe DMS patients (disease duration 8.2 ± 7.7 years), 21 nDMS patients (disease duration 15.3 ± 8.3 years), and 12 healthy controls underwent neuropsychological testing and magnetic resonance imaging (MRI; 1.5 T). Brain volumes (white matter (WM), gray matter, amygdala, hippocampus, thalamus), lesion load, fractional anisotropy (FA) of fronto-limbic tracts, and resting-state functional connectivity (FC) between limbic and frontal areas were measured and compared between groups. Regression analysis was performed to relate MRI measures to the severity of depression. Results: Compared to nDMS patients, DMS patients (shorter disease duration) had lower WM volume ( p < 0.01), decreased FA of the uncinate fasciculus ( p < 0.05), and lower FC between the amygdala and frontal regions ( p < 0.05). Disease duration, FA of the uncinate fasciculus, and FC of the amygdala could explain 48% of variance in the severity of depression. No differences in cognition were found. Conclusion: DMS patients showed more pronounced (MS) damage, that is, structural and functional changes in temporo-frontal regions, compared to nDMS patients, suggestive of fronto-limbic disconnection.

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