Abnormal connectivity of the sensorimotor network in patients with MS: A multicenter fMRI study

In this multicenter study, we used dynamic causal modeling to characterize the abnormalities of effective connectivity of the sensorimotor network in 61 patients with multiple sclerosis (MS) compared with 74 age‐matched healthy subjects. We also investigated the correlation of such abnormalities with findings derived from structural MRI. In a subgroup of subjects, diffusion tensor (DT) MRI metrics of the corpus callosum and the left corticospinal tract (CST) were also assessed. MS patients showed increased effective connectivity relative to controls between: (a) the left primary SMC and the left dorsal premotor cortex (PMd), (b) the left PMd and the supplementary motor areas (SMA), (c) the left secondary sensorimotor cortex (SII) and the SMA, (d) the right SII and the SMA, (e) the left SII and the right SII, and (f) the right SMC and the SMA. MS patients had relatively reduced effective connectivity between the left SMC and the right cerebellum. No interaction was found between disease group and center. Coefficients of altered connectivity were weakly correlated with brain T2 LV, but moderately correlated with DT MRI‐measured damage of the left CST. In conclusion, large multicenter fMRI studies of effective connectivity changes in diseased people are feasible and can facilitate studies with sample size large enough for robust outcomes. Increased effective connectivity in the patients for the simple motor task suggests local network modulation contributing to enhanced long‐distance effective connectivity in MS patients. This extends and generalizes previous evidence that enhancement of effective connectivity may provide an important compensatory mechanism in MS. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.

[1]  R. C. Oldfield.  The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[2]  J. Kurtzke.  Rating neurologic impairment in multiple sclerosis , 1983, Neurology.

[3]  A. P. Georgopoulos,et al.  Functional magnetic resonance imaging of motor cortex: hemispheric asymmetry and handedness. , 1993, Science.

[4]  P. Basser,et al.  Estimation of the effective self-diffusion tensor from the NMR spin echo. , 1994, Journal of magnetic resonance. Series B.

[5]  M Requardt,et al.  Functional cooperativity of human cortical motor areas during self-paced simple finger movements. A high-resolution MRI study. , 1994, Brain : a journal of neurology.

[6]  Karl J. Friston,et al.  Analysis of fMRI Time-Series Revisited , 1995, NeuroImage.

[7]  Karl J. Friston,et al.  Analysis of fMRI Time-Series Revisited—Again , 1995, NeuroImage.

[8]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[9]  N. Sadato,et al.  Role of the Supplementary Motor Area and the Right Premotor Cortex in the Coordination of Bimanual Finger Movements , 1997, The Journal of Neuroscience.

[10]  P. Skudlarski,et al.  An fMRI study of the human cortical motor system response to increasing functional demands. , 1997, Magnetic resonance imaging.

[11]  S. Scott,et al.  Reaching movements with similar hand paths but different arm orientations. II. Activity of individual cells in dorsal premotor cortex and parietal area 5. , 1997, Journal of neurophysiology.

[12]  S. Röricht,et al.  Topography of fibers in the human corpus callosum mediating interhemispheric inhibition between the motor cortices , 1998, Annals of neurology.

[13]  Scott T. Grafton,et al.  Dorsal premotor cortex and conditional movement selection: A PET functional mapping study. , 1998, Journal of neurophysiology.

[14]  Jonathan D. Cohen,et al.  Reproducibility of fMRI Results across Four Institutions Using a Spatial Working Memory Task , 1998, NeuroImage.

[15]  S Takahashi,et al.  Functional MR imaging of cortical activation of the cerebral hemispheres during motor tasks. , 1998, AJNR. American journal of neuroradiology.

[16]  R. Passingham,et al.  Temporary interference in human lateral premotor cortex suggests dominance for the selection of movements. A study using transcranial magnetic stimulation. , 1998, Brain : a journal of neurology.

[17]  Karl J. Friston,et al.  Multisubject fMRI Studies and Conjunction Analyses , 1999, NeuroImage.

[18]  K. Chang,et al.  Subregions within the Supplementary Motor Area Activated at Different Stages of Movement Preparation and Execution , 1999, NeuroImage.

[19]  B R Rosen,et al.  Activation of distinct motor cortex regions during ipsilateral and contralateral finger movements. , 1999, Journal of neurophysiology.

[20]  J. Karhu,et al.  Simultaneous early processing of sensory input in human primary (SI) and secondary (SII) somatosensory cortices. , 1999, Journal of neurophysiology.

[21]  H Hämäläinen,et al.  fMRI activations of SI and SII cortices during tactile stimulation depend on attention , 2000, Neuroreport.

[22]  G. B. Pike,et al.  Relating axonal injury to functional recovery in MS , 2000, Neurology.

[23]  H. Shibasaki,et al.  Movement-related change of electrocorticographic activity in human supplementary motor area proper. , 2000, Brain : a journal of neurology.

[24]  R. Johansson,et al.  Cortical activity in precision- versus power-grip tasks: an fMRI study. , 2000, Journal of neurophysiology.

[25]  P. Matthews,et al.  Normalized Accurate Measurement of Longitudinal Brain Change , 2001, Journal of computer assisted tomography.

[26]  R. E Passingham,et al.  Cerebral dominance for action in the human brain: the selection of actions , 2001, Neuropsychologia.

[27]  J. Callicott,et al.  Neurophysiological correlates of age-related changes in human motor function , 2002, Neurology.

[28]  Michael Alexander,et al.  Age-Related Differences in Movement Representation , 2002, NeuroImage.

[29]  J. Lurito,et al.  Multiple sclerosis: low-frequency temporal blood oxygen level-dependent fluctuations indicate reduced functional connectivity initial results. , 2002, Radiology.

[30]  Gian Domenico Iannetti,et al.  Contribution of Corticospinal Tract Damage to Cortical Motor Reorganization after a Single Clinical Attack of Multiple Sclerosis , 2002, NeuroImage.

[31]  P. Morgan,et al.  Pyramidal tract mapping by diffusion tensor magnetic resonance imaging in multiple sclerosis: improving correlations with disability , 2003, Journal of neurology, neurosurgery, and psychiatry.

[32]  Karl J. Friston,et al.  Dynamic causal modelling , 2003, NeuroImage.

[33]  R. Caminiti,et al.  Callosal connections of dorso‐lateral premotor cortex , 2003, The European journal of neuroscience.

[34]  C. Calautti,et al.  Functional Neuroimaging Studies of Motor Recovery After Stroke in Adults: A Review , 2003, Stroke.

[35]  Karl J. Friston,et al.  Comparing dynamic causal models , 2004, NeuroImage.

[36]  Giuseppe Scotti,et al.  Pyramidal tract lesions and movement-associated cortical recruitment in patients with MS , 2004, NeuroImage.

[37]  P. Matthews,et al.  Altered cerebellar functional connectivity mediates potential adaptive plasticity in patients with multiple sclerosis , 2004, Journal of Neurology, Neurosurgery & Psychiatry.

[38]  M. Wiesendanger,et al.  Transcallosal connections of the distal forelimb representations of the primary and supplementary motor cortical areas in macaque monkeys , 2004, Experimental Brain Research.

[39]  Bertrand Audoin,et al.  Modulation of effective connectivity inside the working memory network in patients at the earliest stage of multiple sclerosis , 2005, NeuroImage.

[40]  Gregory G. Brown,et al.  Reproducibility of functional MR imaging: preliminary results of prospective multi-institutional study performed by Biomedical Informatics Research Network. , 2005, Radiology.

[41]  P. Morgan,et al.  ‘Importance sampling’ in MS: Use of diffusion tensor tractography to quantify pathology related to specific impairment , 2005, Journal of the Neurological Sciences.

[42]  My-Van Au Duong,et al.  Altered Functional Connectivity Related to White Matter Changes inside the Working Memory Network at the Very Early Stage of MS , 2005, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[43]  Maria Assunta Rocca,et al.  A method for obtaining tract-specific diffusion tensor MRI measurements in the presence of disease: application to patients with clinically isolated syndromes suggestive of multiple sclerosis , 2005, NeuroImage.

[44]  S. Wakana,et al.  MRI Atlas of Human White Matter , 2005 .

[45]  Gary H. Glover,et al.  Reducing interscanner variability of activation in a multicenter fMRI study: Controlling for signal-to-fluctuation-noise-ratio (SFNR) differences , 2006, NeuroImage.

[46]  Paul M Matthews,et al.  Reduced brain functional reserve and altered functional connectivity in patients with multiple sclerosis. , 2006, Brain : a journal of neurology.

[47]  Lee Friedman,et al.  Report on a multicenter fMRI quality assurance protocol , 2006, Journal of magnetic resonance imaging : JMRI.

[48]  Mark J. Lowe,et al.  Functional pathway-defined MRI diffusion measures reveal increased transverse diffusivity of water in multiple sclerosis , 2006, NeuroImage.

[49]  N. Ward.  Compensatory mechanisms in the aging motor system , 2006, Ageing Research Reviews.

[50]  Katsuya Ogata,et al.  Age-related alterations of the functional interactions within the basal ganglia and cerebellar motor loops in vivo , 2007, NeuroImage.

[51]  U. Habel,et al.  Neural correlates of working memory dysfunction in first-episode schizophrenia patients: An fMRI multi-center study , 2007, Schizophrenia Research.

[52]  E. Sell.  [Functional magnetic resonance]. , 2007, Medicina.

[53]  M. Rushworth,et al.  Functionally Specific Reorganization in Human Premotor Cortex , 2007, Neuron.

[54]  M Filippi,et al.  Altered functional and structural connectivities in patients with MS , 2007, Neurology.

[55]  Bertrand Audoin,et al.  Structure of WM bundles constituting the working memory system in early multiple sclerosis: A quantitative DTI tractography study , 2007, NeuroImage.

[56]  M. Brammer,et al.  Multisite fMRI reproducibility of a motor task using identical MR systems , 2007, Journal of magnetic resonance imaging : JMRI.

[57]  Massimo Filippi,et al.  Functional MRI in Multiple Sclerosis , 2007, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[58]  Giancarlo Zito,et al.  Intra-cortical connectivity in multiple sclerosis: a neurophysiological approach. , 2008, Brain : a journal of neurology.

[59]  Massimo Filippi,et al.  Reproducibility of fMRI in the clinical setting: Implications for trial designs , 2008, NeuroImage.

[60]  M. Lowe,et al.  Resting state sensorimotor functional connectivity in multiple sclerosis inversely correlates with transcallosal motor pathway transverse diffusivity , 2008, Human brain mapping.

[61]  P. Haggard,et al.  Dorsal premotor cortex exerts state-dependent causal influences on activity in contralateral primary motor and dorsal premotor cortex. , 2008, Cerebral cortex.

[62]  Rupert Lanzenberger,et al.  The suppressive influence of SMA on M1 in motor imagery revealed by fMRI and dynamic causal modeling , 2008, NeuroImage.

[63]  Andreas Kleinschmidt,et al.  Recent advances in recording electrophysiological data simultaneously with magnetic resonance imaging , 2008, NeuroImage.

[64]  P M Matthews,et al.  Relating functional changes during hand movement to clinical parameters in patients with multiple sclerosis in a multi‐centre fMRI study , 2008, European journal of neurology.

[65]  M. Filippi,et al.  Structural and functional MRI correlates of Stroop control in benign MS , 2009, Human brain mapping.

[66]  Elizabeth R. Tuminello,et al.  Functional neuroimaging studies in normal aging. , 2012, Current topics in behavioral neurosciences.