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Experimental Brain Research

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01.06.2024 | Research Article

Interhemispheric inhibition and gait adaptation associations in people with multiple sclerosis

verfasst von: Andrew C. Hagen, Jordan S. Acosta, Clayton W. Swanson, Brett W. Fling

Erschienen in: Experimental Brain Research | Ausgabe 7/2024

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Abstract

Background

Multiple sclerosis is a neurodegenerative disease that damages the myelin sheath within the central nervous system. Axonal demyelination, particularly in the corpus callosum, impacts communication between the brain’s hemispheres in persons with multiple sclerosis (PwMS). Changes in interhemispheric communication may impair gait coordination which is modulated by communication across the corpus callosum to excite and inhibit specific muscle groups. To further evaluate the functional role of interhemispheric communication in gait and mobility, this study assessed the ipsilateral silent period (iSP), an indirect marker of interhemispheric inhibition and how it relates to gait adaptation in PwMS.

Methods

Using transcranial magnetic stimulation (TMS), we assessed interhemispheric inhibition differences between the more affected and less affected hemisphere in the primary motor cortices in 29 PwMS. In addition, these same PwMS underwent a split-belt treadmill walking paradigm, with the faster paced belt moving under their more affected limb. Step length asymmetry (SLA) was the primary outcome measure used to assess gait adaptability during split-belt treadmill walking. We hypothesized that PwMS would exhibit differences in iSP inhibitory metrics between the more affected and less affected hemispheres and that increased interhemispheric inhibition would be associated with greater gait adaptability in PwMS.

Results

No statistically significant differences in interhemispheric inhibition or conduction time were found between the more affected and less affected hemisphere. Furthermore, SLA aftereffect was negatively correlated with both average percent depth of silent period (dSP%_AVE) (r = -0.40, p = 0.07) and max percent depth of silent period (dSP%_MAX) r = -0.40, p = 0.07), indicating that reduced interhemispheric inhibition was associated with greater gait adaptability in PwMS.

Conclusion

The lack of differences between the more affected and less affected hemisphere indicates that PwMS have similar interhemispheric inhibitory capacity irrespective of the more affected hemisphere. Additionally, we identified a moderate correlation between reduced interhemispheric inhibition and greater gait adaptability. These findings may indicate that interhemispheric inhibition may in part influence responsiveness to motor adaptation paradigms and the need for further research evaluating the neural mechanisms underlying the relationship between interhemispheric inhibition and motor adaptability.

Bonzano L, Tacchino A, Roccatagliata L, Abbruzzese G, Mancardi GL, Bove M (2008) Callosal contributions to simultaneous bimanual finger movements. J Neurosci 28(12):3227–3233. https://doi.org/10.1523/jneurosci.4076-07.2008CrossRefPubMedPubMedCentral

Boroojerdi B, Hungs M, Mull M, Töpper R, Noth J (1998) Interhemispheric inhibition in patients with multiple sclerosis. Electroencephalogr Clin Neurophysiology/Electromyography Motor Control 109(3):230–237. https://doi.org/10.1016/s0924-980x(98)00013-7CrossRef

Carson RG (2020) Inter-hemispheric inhibition sculpts the output of neural circuits by co-opting the two cerebral hemispheres. J Physiol 598(21):4781–4802. https://doi.org/10.1113/JP279793CrossRefPubMed

Cash R, Udupa K, Gunraj C, Mazzella F, Daskalakis ZJ, Wong AH, Kennedy JL, Fitzgerald PB, Chen R (2017) Influence of the BDNF VAL66MET polymorphism on the balance of excitatory and inhibitory neurotransmission and relationship to plasticity in human cortex. Brain Stimul 10(2):502. https://doi.org/10.1016/j.brs.2017.01.469CrossRef

Charil A, Zijdenbos AP, Taylor J, Boelman C, Worsley KJ, Evans AC, Dagher A (2003) Statistical mapping analysis of lesion location and neurological disability in multiple sclerosis: application to 452 patient data sets. NeuroImage 19(3):532–544. https://doi.org/10.1016/s1053-8119(03)00117-4CrossRefPubMed

Chieffo R, Straffi L, Inuggi A, Coppi E, Moiola L, Martinelli V, Comi G, Leocani L (2019) Changes in cortical motor outputs after a motor relapse of multiple sclerosis. Multiple Scler J - Experimental Translational Clin 5(3):2055217319866480. https://doi.org/10.1177/2055217319866480CrossRef

Clark DJ (2015) Automaticity of walking: functional significance, mechanisms, measurement and rehabilitation strategies. Front Hum Neurosci 9:246. https://doi.org/10.3389/fnhum.2015.00246CrossRefPubMedPubMedCentral

Confavreux C, Vukusic S, Moreau T, Adeleine P (2000) Relapses and progression of disability in multiple sclerosis. N Engl J Med 343(20):1430–1438. https://doi.org/10.1056/nejm200011163432001CrossRefPubMed

Davidson T, Tremblay F (2013) Age and hemispheric differences in transcallosal inhibition between motor cortices: an Ispsilateral Silent period study. BMC Neurosci 14(1). https://doi.org/10.1186/1471-2202-14-62

Dietz V (2002) Do human bipeds use quadrupedal coordination? Trends Neurosci 25(9):462–467. https://doi.org/10.1016/s0166-2236(02)02229-4CrossRefPubMed

Ferbert A, Priori A, Rothwell JC, Day BL, Colebatch JG, Marsden CD (1992) Interhemispheric inhibition of the human motor cortex. J Physiol 453(1):525–546. https://doi.org/10.1113/jphysiol.1992.sp019243

Finley JM, Long A, Bastian AJ, Torres-Oviedo G (2015) Spatial and temporal control contribute to step length asymmetry during Split-Belt Adaptation and Hemiparetic Gait. Neurorehabilit Neural Repair 29(8):786–795. https://doi.org/10.1177/1545968314567149CrossRef

Fleming MK, Newham DJ (2017) Reliability of transcallosal inhibition in healthy adults. Frontiers in Human Neuroscience, 10. https://doi.org/10.3389/fnhum.2016.00681

Fling BW, Seidler RD (2011) Fundamental differences in callosal structure, neurophysiologic function, and bimanual control in young and older adults. Cereb Cortex 22(11):2643–2652. https://doi.org/10.1093/cercor/bhr349CrossRefPubMedPubMedCentral

Fling BW, Walsh CM, Bangert AS, Reuter-Lorenz PA, Welsh RC, Seidler RD (2011) Differential Callosal contributions to bimanual control in young and older adults. J Cogn Neurosci 23(9):2171–2185. https://doi.org/10.1162/jocn.2010.21600CrossRefPubMed

Fling BW, Benson BL, Seidler RD (2013) Transcallosal sensorimotor fiber tract structure-function relationships. Hum Brain Mapp 34(2):384–395. https://doi.org/10.1002/hbm.21437CrossRefPubMed

Fling BW, Dutta GG, Schlueter H, Cameron MH, Horak FB (2014) Associations between Proprioceptive Neural Pathway Structural Connectivity and balance in people with multiple sclerosis. Front Hum Neurosci 8:814. https://doi.org/10.3389/fnhum.2014.00814CrossRefPubMedPubMedCentral

Gandolfi M, Geroin C, Picelli A, Munari D, Waldner A, Tamburin S, Marchioretto F, Smania N (2014) Robot-assisted vs. sensory integration training in treating gait and balance dysfunctions in patients with multiple sclerosis: a randomized controlled trial. Front Hum Neurosci 8:318. https://doi.org/10.3389/fnhum.2014.00318CrossRefPubMedPubMedCentral

Ghasemi N, Razavi S, Nikzad E (2017) Multiple sclerosis: Pathogenesis, symptoms, diagnoses and Cell-based therapy. Cell J 19(1):1–10. https://doi.org/10.22074/cellj.2016.4867CrossRefPubMed

Giovannelli F, Borgheresi A, Balestrieri F, Zaccara G, Viggiano MP, Cincotta M, Ziemann U (2009) Modulation of interhemispheric inhibition by volitional motor activity: an ipsilateral silent period study. J Physiol 587(Pt 22):5393–5410. https://doi.org/10.1113/jphysiol.2009.175885CrossRefPubMedPubMedCentral

Gooijers J, Swinnen SP (2014) Interactions between brain structure and behavior: the corpus callosum and bimanual coordination. Neurosci Biobehav Rev 43:1–19. https://doi.org/10.1016/j.neubiorev.2014.03.008CrossRefPubMed

Hagen AC, Acosta JS, Geltser CS, Fling BW (2023) Split-belt Treadmill Adaptation improves spatial and temporal gait symmetry in people with multiple sclerosis. Sensors 23(12):5456. https://doi.org/10.3390/s23125456CrossRefPubMedPubMedCentral

Hagen AC, Patrick CM, Bast IE, Fling BW (2024) Propulsive force modulation drives Split-Belt Treadmill Adaptation in people with multiple sclerosis. Sensors 24(4):1067. https://doi.org/10.3390/s24041067CrossRefPubMedPubMedCentral

Hupfeld KE, Swanson CW, Fling BW, Seidler RD (2020) TMS-induced silent periods: a review of methods and call for consistency. J Neurosci Methods 346:108950. https://doi.org/10.1016/j.jneumeth.2020.108950CrossRefPubMedPubMedCentral

Jung P, Beyerle A, Humpich M, Neumann-Haefelin T, Lanfermann H, Ziemann U (2006) Ipsilateral silent period: a marker of callosal conduction abnormality in early relapsing–remitting multiple sclerosis? J Neurol Sci 250(1–2):133–139. https://doi.org/10.1016/j.jns.2006.08.008CrossRefPubMed

Kolasinski J, Hinson EL, Zand D, Rizov AP, Emir A, U. E., Stagg CJ (2019) The dynamics of cortical GABA in human motor learning. J Physiol 597(1):271–282. https://doi.org/10.1113/JP276626CrossRefPubMed

Krakauer JW, Hadjiosif AM, Xu J, Wong AL, Haith AM (2019) Motor Learning. Compr Physiol 9(2):613–663. https://doi.org/10.1002/cphy.c170043CrossRefPubMed

Kujirai T, Caramia MD, Rothwell JC, Day BL, Thompson PD, Ferbert A, Wroe S, Asselman P, Marsden CD (1993) Corticocortical inhibition in human motor cortex. J Physiol 471:501–519. https://doi.org/10.1113/jphysiol.1993.sp019912CrossRefPubMedPubMedCentral

Kuo YL, Dubuc T, Boufadel DF, Fisher BE (2017) Measuring ipsilateral silent period: effects of muscle contraction levels and quantification methods. Brain Res 1674:77–83. https://doi.org/10.1016/j.brainres.2017.08.015CrossRefPubMed

Lazzaro VD, Restuccia D, Oliviero A, Profice P, Ferrara L, Insola A, Mazzone P, Tonali P, Rothwell JC (1998) Magnetic transcranial stimulation at intensities below active motor threshold activates intracortical inhibitory circuits. Exp Brain Res 119(2):265–268. https://doi.org/10.1007/s002210050341CrossRefPubMed

Lemon RN (2008) Descending pathways in motor control. Annu Rev Neurosci 31(1):195–218. https://doi.org/10.1146/annurev.neuro.31.060407.125547CrossRefPubMed

Lenzi D, Conte A, Mainero C, Frasca V, Fubelli F, Totaro P, Caramia F, Inghilleri M, Pozzilli C, Pantano P (2007) Effect of corpus callosum damage on ipsilateral motor activation in patients with multiple sclerosis: a functional and anatomical study. Hum Brain Bapping 28(7):636–644. https://doi.org/10.1002/hbm.20305CrossRef

Llufriu S, Blanco Y, Martinez-Heras E, Casanova-Molla J, Gabilondo I, Sepulveda M, Falcon C, Berenguer J, Bargallo N, Villoslada P, Graus F, Valls-Sole J, Saiz A (2012) Influence of corpus callosum damage on cognition and physical disability in multiple sclerosis: a multimodal study. PLoS ONE 7(5):e37167. https://doi.org/10.1371/journal.pone.0037167CrossRefPubMedPubMedCentral

Madhavan S, Rogers LM, Stinear JW (2010) A paradox: after stroke, the non-lesioned lower limb motor cortex may be maladaptive. Eur J Neurosci 32:1032–1039. https://doi.org/10.1111/j.1460-9568.2010.07364.xCrossRefPubMedPubMedCentral

Malcom M, Triggs W, Light K, Schechtman O, Khandekar G, Gonzalezrothi L (2006) Reliability of motor cortex transcranial magnetic stimulation in four muscle representations. Clin Neurophysiol 117(5):1037–1046. https://doi.org/10.1016/j.clinph.2006.02.005CrossRef

Malone LA, Bastian AJ (2010) Thinking about walking: effects of conscious correction versus distraction on locomotor adaptation. J Neurophysiol 103(4):1954–1962. https://doi.org/10.1152/jn.00832.2009CrossRefPubMedPubMedCentral

Mayo Foundation for Medical Education and Research (2022) Multiple sclerosis. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/symptoms-causes/syc-20350269

Morris R, Stuart S, McBarron G, Fino PC, Mancini M, Curtze C (2019) Validity of mobility lab (version 2) for gait assessment in young adults, older adults and Parkinson’s disease. Physiol Meas 40(9):095003. https://doi.org/10.1088/1361-6579/ab4023CrossRefPubMedPubMedCentral

Mrachacz-Kersting N, Stevenson AJT, Ziemann U (2021) Short-interval intracortical inhibition and facilitation targeting upper and lower limb muscles. Sci Rep 11(1):21993. https://doi.org/10.1038/s41598-021-01348-6CrossRefPubMedPubMedCentral

Murase N, Duque J, Mazzocchio R, Cohen LG (2004) Influence of interhemispheric interactions on motor function in chronic stroke. Ann Neurol 55(3):400–409. https://doi.org/10.1002/ana.10848CrossRefPubMed

Neva JL, Lakhani B, Brown KE, Wadden KP, Mang CS, Ledwell NH, Borich MR, Vavasour IM, Laule C, Traboulsee AL, MacKay AL, Boyd LA (2016) Multiple measures of corticospinal excitability are associated with clinical features of multiple sclerosis. Behav Brain Res 297:187–195. https://doi.org/10.1016/j.bbr.2015.10.015CrossRefPubMed

Ozturk A, Smith S, Gordon-Lipkin E, Harrison D, Shiee N, Pham D, Caffo B, Calabresi P, Reich D (2010) MRI of the Corpus Callosum in multiple sclerosis: Association with disability. Multiple Scler J 16(2):166–177. https://doi.org/10.1177/1352458509353649CrossRef

Paparella G, De Riggi M, Cannavacciuolo A, Colella D, Costa D, Birreci D, Passaretti M, Angelini L, Guerra A, Berardelli A, Bologna M (2023) Relationship between the interlimb transfer of a visuomotor learning task and interhemispheric inhibition in healthy humans. Cereb Cortex 33(12):7335–7346. https://doi.org/10.1093/cercor/bhad042CrossRefPubMed

Plotnik M, Wagner JM, Adusumilli G, Gottlieb A, Naismith RT (2020) Gait asymmetry, and bilateral coordination of gait during a six-minute walk test in persons with multiple sclerosis. Sci Rep 10(1):12382. https://doi.org/10.1038/s41598-020-68263-0CrossRefPubMedPubMedCentral

Proessl F, Ketelhut NB, Rudroff T (2018) No association of leg strength asymmetry with walking ability, fatigability, and fatigue in multiple sclerosis. Int J Rehabil Res 41(3):267–269. https://doi.org/10.1097/MRR.0000000000000278CrossRefPubMed

R Core Team (2022) R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/.

Reisman DS, Wityk R, Silver K, Bastian AJ (2007) Locomotor adaptation on a split-belt treadmill can improve walking symmetry post-stroke. Brain 130(7):1861–1872. https://doi.org/10.1093/brain/awm035CrossRefPubMed

Reisman DS, Wityk R, Silver K, Bastian AJ (2009) Split-belt treadmill adaptation transfers to overground walking in persons poststroke. Neurorehabilit Neural Repair 23(7):735–744. https://doi.org/10.1177/1545968309332880CrossRef

Richmond SB, Fling BW (2019) Transcallosal control of bilateral actions. Exerc Sport Sci Rev 47(4):251–257. https://doi.org/10.1249/jes.0000000000000202CrossRefPubMed

Richmond SB, Swanson CW, Peterson DS, Fling BW (2020) A temporal analysis of bilateral gait coordination in people with multiple sclerosis. Multiple Scler Relat Disorders 45:102445. https://doi.org/10.1016/j.msard.2020.102445CrossRef

Richmond SB, Peterson DS, Fling BW (2022) Bridging the callosal gap in gait: Corpus callosum white matter integrity’s role in Lower Limb Coordination. Brain Imaging Behav 16(4):1552–1562. https://doi.org/10.1007/s11682-021-00612-7CrossRefPubMed

Rudroff T, Proessl F (2018) Effects of muscle function and limb loading asymmetries on Gait and Balance in people with multiple sclerosis. Front Physiol 9:531. https://doi.org/10.3389/fphys.2018.00531CrossRefPubMedPubMedCentral

Sasikumar S, Sorrento G, Lang AE, Strafella AP, Fasano A (2023) Cognition affects gait adaptation after split-belt treadmill training in parkinson’s disease. Neurobiol Dis 181:106109. https://doi.org/10.1016/j.nbd.2023.106109CrossRefPubMed

Schmierer K, Irlbacher K, Grosse P, Röricht S, Meyer BU (2002) Correlates of disability in multiple sclerosis detected by transcranial magnetic stimulation. Neurology 59(8):1218–1224. https://doi.org/10.1212/wnl.59.8.1218CrossRefPubMed

Snow NJ, Wadden KP, Chaves AR, Ploughman M (2019) Transcranial Magnetic Stimulation as a Potential Biomarker in Multiple Sclerosis: A Systematic Review with Recommendations for Future Research. Neural Plasticity, 2019, 6430596. https://doi.org/10.1155/2019/6430596

Swanson CW, Fling BW (2018) Associations between gait coordination, variability and motor cortex inhibition in young and older adults. Exp Gerontol 113:163–172. https://doi.org/10.1016/j.exger.2018.10.002CrossRefPubMed

Swanson CW, Fling BW (2023) Links between Neuroanatomy and Neurophysiology with turning performance in people with multiple sclerosis. Sensors 23(17):7629. https://doi.org/10.3390/s23177629CrossRefPubMedPubMedCentral

Swanson CW, Proessl F, Stephens JA, Miravalle AA, Fling BW (2021) Non-invasive brain stimulation to assess neurophysiologic underpinnings of lower limb motor impairment in multiple sclerosis. J Neurosci Methods 356:109143. https://doi.org/10.1016/j.jneumeth.2021.109143CrossRefPubMed

Swinnen SP (2002) Intermanual coordination: from behavioural principles to neural-network interactions. Nat Rev Neurosci 3(5):348–359. https://doi.org/10.1038/nrn807CrossRefPubMed

The Colorado Health Foundation (2015) The Colorado Health Report Card. Colorado Health. https://coloradohealth.org/sites/default/files/documents/2017-01/2015 COHRC Get Active.pdf

Vanderah TW, Gould DJ (2016) Nolte’s the human brain: an introduction to its functional anatomy, 7th edn. Elsevier

Wahl M, Hübers A, Lauterbach-Soon B, Hattingen E, Jung P, Cohen LG, Ziemann U (2010) Motor Callosal disconnection in early relapsing-remitting multiple sclerosis. Hum Brain Mapp 32(6):846–855. https://doi.org/10.1002/hbm.21071CrossRefPubMedPubMedCentral

Wallin MT, Culpepper WJ, Campbell JD, Nelson LM, Langer-Gould A, Marrie RA, Cutter GR, Kaye WE, Wagner L, Tremlett H, Buka SL, Dilokthornsakul P, Topol B, Chen LH, LaRocca NG (2019) The prevalence of MS in the United States. Neurology 92(10). https://doi.org/10.1212/wnl.0000000000007035

Walton C, King R, Rechtman L, Kaye W, Leray E, Marrie RA, Robertson N, La Rocca N, Uitdehaag B, van der Mei I, Wallin M, Helme A, Napier A, Rijke C, N., Baneke P (2020) Rising prevalence of multiple sclerosis worldwide: insights from the atlas of MS, third edition. Multiple Scler J 26(14):1816–1821. https://doi.org/10.1177/1352458520970841CrossRef

Williams JA, Pascual-Leone A, Fregni F (2010) Interhemispheric modulation induced by cortical stimulation and motor training. Phys Ther 90(3):398–410. https://doi.org/10.2522/ptj.20090075CrossRefPubMed

Titel: Interhemispheric inhibition and gait adaptation associations in people with multiple sclerosis
verfasst von: Andrew C. Hagen
Jordan S. Acosta
Clayton W. Swanson
Brett W. Fling
Publikationsdatum: 01.06.2024
Verlag: Springer Berlin Heidelberg
Erschienen in: Experimental Brain Research / Ausgabe 7/2024
Print ISSN: 0014-4819
Elektronische ISSN: 1432-1106
DOI: https://doi.org/10.1007/s00221-024-06860-5

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Interhemispheric inhibition and gait adaptation associations in people with multiple sclerosis