Abstract
Neurons in the central nervous system are organized in functional units interconnected to form complex networks. Acute and chronic brain damage disrupts brain connectivity producing neurological signs and/or symptoms. In several neurological diseases, particularly in Multiple Sclerosis (MS), structural imaging studies cannot always demonstrate a clear association between lesion site and clinical disability, originating the “clinico-radiological paradox.” The discrepancy between structural damage and disability can be explained by a complex network perspective. Both brain networks architecture and synaptic plasticity may play important roles in modulating brain networks efficiency after brain damage. In particular, long-term potentiation (LTP) may occur in surviving neurons to compensate network disconnection. In MS, inflammatory cytokines dramatically interfere with synaptic transmission and plasticity. Importantly, in addition to acute and chronic structural damage, inflammation could contribute to reduce brain networks efficiency in MS leading to worse clinical recovery after a relapse and worse disease progression. These evidence suggest that removing inflammation should represent the main therapeutic target in MS; moreover, as synaptic plasticity is particularly altered by inflammation, specific strategies aimed at promoting LTP mechanisms could be effective for enhancing clinical recovery. Modulation of plasticity with different non-invasive brain stimulation (NIBS) techniques has been used to promote recovery of MS symptoms. Better knowledge of features inducing brain disconnection in MS is crucial to design specific strategies to promote recovery and use NIBS with an increasingly tailored approach.
Highlights
Multiple Sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) characterized by white matter demyelinating lesions and gray matter atrophy
The remote effects of a brain lesion on functionally connected regions and the ongoing rearrangement produced by synaptic plasticity in response to brain damage can concur in determining the discrepancy between structural damage and clinical symptoms
A study showed that IL-6 blood levels covaried with connectivity in the default mode network (Marsland et al, 2017). These studies are in line with previous reports showing that peripheral cytokines may modulate central synaptic transmission altering task-based functional MRI (fMRI) (Capuron et al, 2005; Harrison et al, 2009). These data suggest that inflammation in MS, altering synaptic transmission, may represent an additional key feature contributing to network dysfunction
Summary
Multiple Sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) characterized by white matter demyelinating lesions and gray matter atrophy. As inflammatory cytokines alter synaptic functioning, a direct role of neuroinflammation in connectivity dysfunction occurring in MS may be hypothesized To support this view, few studies showed that in patients with clinically isolated syndrome (CIS) significant FC alterations develop even without white matter lesions or brain atrophy. A study showed that IL-6 blood levels covaried with connectivity in the default mode network (Marsland et al, 2017) These studies are in line with previous reports showing that peripheral cytokines may modulate central synaptic transmission altering task-based fMRI (Capuron et al, 2005; Harrison et al, 2009). Overall, these data suggest that inflammation in MS, altering synaptic transmission, may represent an additional key feature contributing to network dysfunction. LTP can be virtually induced in all brain areas and may reduce the clinical
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