Brain Advance Access originally published online on May 23, 2008
Brain 2008 131(7):1783-1792; doi:10.1093/brain/awn087
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Intra-cortical connectivity in multiple sclerosis: a neurophysiological approach
1Istituto Scienze e Tecnologie della Cognizione—CNR, Unità MEG, Roma, 2Casa di Cura San Raffaele Cassino e IRCCS San Raffaele Pisana, 3Dipartimento di Neuroscienze ed Unità Operativa Complessa Radiologia Diagnostica ed Interventistica, AFaR, Ospedale Fatebenefratelli and 4Neurologia Clinica, Universitá Campus Biomedico, Roma, Italy
Correspondence to: Dr ssa Franca Tecchio, Unità MEG, Dipartimento di Neuroscienze, Ospedale Fatebenefratelli, Isola Tiberina, 00186 Rome, Italy E-mail: franca.tecchio{at}istc.cnr.it
Multiple sclerosis is an autoimmune disease predominantly affecting the white matter of the CNS, causing—among functional sequelae—cortico-cortical partial or total disconnection. Since functional connectivity linking cerebral regions is reliably reflected by synchronization of their neuronal firing, in this study an electrophysiological parameter measured by magnetoencephalography was used to quantify an intra-cortical connectivity (ICC) index focused on the primary somatosensory cortical areas (S1). Twenty-one patients affected by mild (Extended Disability Scale Score, median 1,5) relapsing-remitting (RR) multiple sclerosis in the remitting phase without clinically evident sensory impairment were evaluated. Three dimensional MRI was used to quantify the lesion load, discriminating black hole and non-black hole portions, normalized by individual brain volumes. When matched with a control population, multiple sclerosis patients showed a reduced ICC combined with the complete loss of the finger-dependent functional specialization in S1 cortex of the dominant hemisphere. No association was found between ICC impairment and disease duration, or prolongation of the central sensory conduction time, presence of spinal cord lesions and ongoing disease modifying therapy. The ICC index slightly correlated with the lesion load. A local index of ICC in a circumscribed brain primary area was altered in mildly disabled RR-multiple sclerosis patients, also in absence of any impairment of central sensory conduction. In conclusion, the diffuse damage influencing the multi-nodal network subtending complex cerebral functions also affects intrinsic cortical connectivity. The S1 ICC index is proposed as a highly sensitive and simple-to-test functional measure for the evaluation of intra-cortical synchronization mechanisms in RR-multiple sclerosis.
Key Words: magnetoencephalography; cerebral connectivity; primary sensorimotor cortex; lesion load black holes
Abbreviations: BHV, black hole volume; CCT, central conduction time; EDSS, Extended Disability Scale Score; EEG, electroencephalography; FSS, functional source separation; ICC, intra-cortical connectivity; LrF, lesion relative fraction; MEG, magnetoencephalography; PD, proton density; S1, primary somatosensory cortical areas; RR, relapsing-remitting; TLV, total lesion volume; WMHy, white matter hyperintensities
Received December 3, 2007. Revised April 11, 2008. Accepted April 15, 2008.
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