Probing Context-Dependent Modulations of Ipsilateral Premotor-Motor Connectivity in Relapsing-Remitting Multiple Sclerosis
Objective: We employed dual-site TMS to test whether ipsilateral functional premotor-motor connectivity is altered in relapsing-remitting Multiple Sclerosis (RR-MS) and is related to central fatigue.Methods: Twelve patients with RR-MS and 12 healthy controls performed a visually cued Pinch-NoPinch t...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-05-01
|
| Series: | Frontiers in Neurology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fneur.2020.00193/full |
| _version_ | 1818542386229280768 |
|---|---|
| author | Elisa Ruiu Elisa Ruiu Raffaele Dubbioso Raffaele Dubbioso Kristoffer Hougaard Madsen Kristoffer Hougaard Madsen Olivia Svolgaard Estelle Raffin Estelle Raffin Kasper Winther Andersen Anke Ninija Karabanov Anke Ninija Karabanov Hartwig Roman Siebner Hartwig Roman Siebner Hartwig Roman Siebner |
| author_facet | Elisa Ruiu Elisa Ruiu Raffaele Dubbioso Raffaele Dubbioso Kristoffer Hougaard Madsen Kristoffer Hougaard Madsen Olivia Svolgaard Estelle Raffin Estelle Raffin Kasper Winther Andersen Anke Ninija Karabanov Anke Ninija Karabanov Hartwig Roman Siebner Hartwig Roman Siebner Hartwig Roman Siebner |
| author_sort | Elisa Ruiu |
| collection | DOAJ |
| description | Objective: We employed dual-site TMS to test whether ipsilateral functional premotor-motor connectivity is altered in relapsing-remitting Multiple Sclerosis (RR-MS) and is related to central fatigue.Methods: Twelve patients with RR-MS and 12 healthy controls performed a visually cued Pinch-NoPinch task with their right hand. During the reaction time (RT) period of Pinch and No-Pinch trials, single-site TMS was applied to the left primary motor cortex (M1) or dual-site TMS was applied to the ipsilateral dorsal premotor cortex (PMd) and to M1. We traced context-dependent changes of corticospinal excitability and premotor–motor connectivity by measuring Motor-Evoked Potentials (MEPs) in the right first dorsal interosseus muscle. Central fatigue was evaluated with the Fatigue Scale for Motor and Cognitive Functions (FSMS).Results: In both groups, single-pulse TMS revealed a consistent increase in mean MEP amplitude during the Reaction Time (RT) period relative to a resting condition. Task-related corticospinal facilitation increased toward the end of the RT period in Pinch trials, while it decreased in No-Pinch trials. Again, this modulation of MEP facilitation by trial type was comparable in patients and controls. Dual-site TMS showed no significant effect of a conditioning PMd pulse on ipsilateral corticospinal excitability during the RT period in either group. However, patients showed a trend toward a relative attenuation in functional PMd-M1 connectivity at the end of the RT period in No-Pinch trials, which correlated positively with the severity of motor fatigue (r = 0.69; p = 0.007).Conclusions: Dynamic regulation of corticospinal excitability and ipsilateral PMd-M1 connectivity is preserved in patients with RR-MS. MS-related fatigue scales positively with an attenuation of premotor-to-motor functional connectivity during cued motor inhibition.Significance: The temporal, context-dependent modulation of ipsilateral premotor-motor connectivity, as revealed by dual-site TMS of ipsilateral PMd and M1, constitutes a promising neurophysiological marker of fatigue in MS. |
| first_indexed | 2024-12-11T22:21:23Z |
| format | Article |
| id | doaj.art-243fbbce035a4754a84efe3ee7c216bb |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-11T22:21:23Z |
| publishDate | 2020-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-243fbbce035a4754a84efe3ee7c216bb2022-12-22T00:48:25ZengFrontiers Media S.A.Frontiers in Neurology1664-22952020-05-011110.3389/fneur.2020.00193519432Probing Context-Dependent Modulations of Ipsilateral Premotor-Motor Connectivity in Relapsing-Remitting Multiple SclerosisElisa Ruiu0Elisa Ruiu1Raffaele Dubbioso2Raffaele Dubbioso3Kristoffer Hougaard Madsen4Kristoffer Hougaard Madsen5Olivia Svolgaard6Estelle Raffin7Estelle Raffin8Kasper Winther Andersen9Anke Ninija Karabanov10Anke Ninija Karabanov11Hartwig Roman Siebner12Hartwig Roman Siebner13Hartwig Roman Siebner14Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Section 714, Hvidovre, DenmarkDepartment of Neurology, University Hospital of Sassari, Sassari, ItalyDanish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Section 714, Hvidovre, DenmarkDepartment of Neurosciences, Reproductive Sciences and Odontostomatology, University Federico II of Naples, Naples, ItalyDanish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Section 714, Hvidovre, DenmarkSection for Cognitive Systems, Department of Applied Mathematics and Computer Science, Technical University of Denmark, Lyngby, DenmarkDanish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Section 714, Hvidovre, DenmarkDanish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Section 714, Hvidovre, DenmarkBrain Mind Institute and Centre of Neuroprosthetics, Swiss Federal Institute of Technology (EPFL), Geneva, SwitzerlandDanish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Section 714, Hvidovre, DenmarkDanish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Section 714, Hvidovre, DenmarkDepartment of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, DenmarkDanish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Section 714, Hvidovre, DenmarkDepartment of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, DenmarkFaculty of Medical and Health Sciences, Institute for Clinical Medicine, University of Copenhagen, Copenhagen, DenmarkObjective: We employed dual-site TMS to test whether ipsilateral functional premotor-motor connectivity is altered in relapsing-remitting Multiple Sclerosis (RR-MS) and is related to central fatigue.Methods: Twelve patients with RR-MS and 12 healthy controls performed a visually cued Pinch-NoPinch task with their right hand. During the reaction time (RT) period of Pinch and No-Pinch trials, single-site TMS was applied to the left primary motor cortex (M1) or dual-site TMS was applied to the ipsilateral dorsal premotor cortex (PMd) and to M1. We traced context-dependent changes of corticospinal excitability and premotor–motor connectivity by measuring Motor-Evoked Potentials (MEPs) in the right first dorsal interosseus muscle. Central fatigue was evaluated with the Fatigue Scale for Motor and Cognitive Functions (FSMS).Results: In both groups, single-pulse TMS revealed a consistent increase in mean MEP amplitude during the Reaction Time (RT) period relative to a resting condition. Task-related corticospinal facilitation increased toward the end of the RT period in Pinch trials, while it decreased in No-Pinch trials. Again, this modulation of MEP facilitation by trial type was comparable in patients and controls. Dual-site TMS showed no significant effect of a conditioning PMd pulse on ipsilateral corticospinal excitability during the RT period in either group. However, patients showed a trend toward a relative attenuation in functional PMd-M1 connectivity at the end of the RT period in No-Pinch trials, which correlated positively with the severity of motor fatigue (r = 0.69; p = 0.007).Conclusions: Dynamic regulation of corticospinal excitability and ipsilateral PMd-M1 connectivity is preserved in patients with RR-MS. MS-related fatigue scales positively with an attenuation of premotor-to-motor functional connectivity during cued motor inhibition.Significance: The temporal, context-dependent modulation of ipsilateral premotor-motor connectivity, as revealed by dual-site TMS of ipsilateral PMd and M1, constitutes a promising neurophysiological marker of fatigue in MS.https://www.frontiersin.org/article/10.3389/fneur.2020.00193/fullmultiple sclerosisdual-site TMSfatiguemovement preparationdorsal premotor cortexprimary motor cortex |
| spellingShingle | Elisa Ruiu Elisa Ruiu Raffaele Dubbioso Raffaele Dubbioso Kristoffer Hougaard Madsen Kristoffer Hougaard Madsen Olivia Svolgaard Estelle Raffin Estelle Raffin Kasper Winther Andersen Anke Ninija Karabanov Anke Ninija Karabanov Hartwig Roman Siebner Hartwig Roman Siebner Hartwig Roman Siebner Probing Context-Dependent Modulations of Ipsilateral Premotor-Motor Connectivity in Relapsing-Remitting Multiple Sclerosis Frontiers in Neurology multiple sclerosis dual-site TMS fatigue movement preparation dorsal premotor cortex primary motor cortex |
| title | Probing Context-Dependent Modulations of Ipsilateral Premotor-Motor Connectivity in Relapsing-Remitting Multiple Sclerosis |
| title_full | Probing Context-Dependent Modulations of Ipsilateral Premotor-Motor Connectivity in Relapsing-Remitting Multiple Sclerosis |
| title_fullStr | Probing Context-Dependent Modulations of Ipsilateral Premotor-Motor Connectivity in Relapsing-Remitting Multiple Sclerosis |
| title_full_unstemmed | Probing Context-Dependent Modulations of Ipsilateral Premotor-Motor Connectivity in Relapsing-Remitting Multiple Sclerosis |
| title_short | Probing Context-Dependent Modulations of Ipsilateral Premotor-Motor Connectivity in Relapsing-Remitting Multiple Sclerosis |
| title_sort | probing context dependent modulations of ipsilateral premotor motor connectivity in relapsing remitting multiple sclerosis |
| topic | multiple sclerosis dual-site TMS fatigue movement preparation dorsal premotor cortex primary motor cortex |
| url | https://www.frontiersin.org/article/10.3389/fneur.2020.00193/full |
| work_keys_str_mv | AT elisaruiu probingcontextdependentmodulationsofipsilateralpremotormotorconnectivityinrelapsingremittingmultiplesclerosis AT elisaruiu probingcontextdependentmodulationsofipsilateralpremotormotorconnectivityinrelapsingremittingmultiplesclerosis AT raffaeledubbioso probingcontextdependentmodulationsofipsilateralpremotormotorconnectivityinrelapsingremittingmultiplesclerosis AT raffaeledubbioso probingcontextdependentmodulationsofipsilateralpremotormotorconnectivityinrelapsingremittingmultiplesclerosis AT kristofferhougaardmadsen probingcontextdependentmodulationsofipsilateralpremotormotorconnectivityinrelapsingremittingmultiplesclerosis AT kristofferhougaardmadsen probingcontextdependentmodulationsofipsilateralpremotormotorconnectivityinrelapsingremittingmultiplesclerosis AT oliviasvolgaard probingcontextdependentmodulationsofipsilateralpremotormotorconnectivityinrelapsingremittingmultiplesclerosis AT estelleraffin probingcontextdependentmodulationsofipsilateralpremotormotorconnectivityinrelapsingremittingmultiplesclerosis AT estelleraffin probingcontextdependentmodulationsofipsilateralpremotormotorconnectivityinrelapsingremittingmultiplesclerosis AT kasperwintherandersen probingcontextdependentmodulationsofipsilateralpremotormotorconnectivityinrelapsingremittingmultiplesclerosis AT ankeninijakarabanov probingcontextdependentmodulationsofipsilateralpremotormotorconnectivityinrelapsingremittingmultiplesclerosis AT ankeninijakarabanov probingcontextdependentmodulationsofipsilateralpremotormotorconnectivityinrelapsingremittingmultiplesclerosis AT hartwigromansiebner probingcontextdependentmodulationsofipsilateralpremotormotorconnectivityinrelapsingremittingmultiplesclerosis AT hartwigromansiebner probingcontextdependentmodulationsofipsilateralpremotormotorconnectivityinrelapsingremittingmultiplesclerosis AT hartwigromansiebner probingcontextdependentmodulationsofipsilateralpremotormotorconnectivityinrelapsingremittingmultiplesclerosis |