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Updated: Dec 21, 2025
Measuring and Manipulating Functionally Specific Neural Pathways in the Human Motor System with Transcranial Magnetic Stimulation
Published on: February 23, 2020
Probing Context-Dependent Modulations of Ipsilateral Premotor-Motor Connectivity in Relapsing-Remitting Multiple
Elisa Ruiu1,2, Raffaele Dubbioso1,3, Kristoffer Hougaard Madsen1,4
1Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Section 714, Hvidovre, Denmark.
In relapsing-remitting Multiple Sclerosis (RR-MS), altered premotor-motor connectivity is linked to central fatigue. Specifically, reduced functional connectivity between the dorsal premotor cortex (PMd) and motor cortex (M1) correlated with motor fatigue severity in RR-MS patients.
Area of Science:
- Neuroscience
- Neurophysiology
- Multiple Sclerosis Research
Background:
- Relapsing-remitting Multiple Sclerosis (RR-MS) is a central nervous system disorder impacting motor function.
- Central fatigue is a common and debilitating symptom in MS patients.
- The neural underpinnings of fatigue in MS, particularly involving motor network connectivity, require further elucidation.
Purpose of the Study:
- To investigate alterations in ipsilateral functional premotor-motor connectivity in RR-MS patients using dual-site transcranial magnetic stimulation (TMS).
- To determine if these connectivity changes are associated with central fatigue experienced by individuals with RR-MS.
- To explore the dynamic modulation of corticospinal excitability and premotor-motor pathways during a cued motor task.
Main Methods:
- Employed dual-site TMS targeting the dorsal premotor cortex (PMd) and primary motor cortex (M1) in 12 RR-MS patients and 12 healthy controls.
- Assessed corticospinal excitability and PMd-M1 connectivity by measuring Motor-Evoked Potentials (MEPs) during a visually cued Pinch-NoPinch task.
- Quantified central fatigue using the Fatigue Scale for Motor and Cognitive Functions (FSMS).
Main Results:
- Task-related modulation of corticospinal excitability was comparable between RR-MS patients and controls.
- Dual-site TMS revealed no significant direct effect of PMd stimulation on M1 excitability in either group.
- A trend towards attenuated functional PMd-M1 connectivity was observed in RR-MS patients during motor inhibition (No-Pinch trials), positively correlating with motor fatigue severity (r=0.69, p=0.007).
Conclusions:
- Dynamic regulation of corticospinal excitability and ipsilateral PMd-M1 connectivity appears preserved in RR-MS patients.
- MS-related motor fatigue is associated with a functional attenuation of premotor-to-motor connectivity during cued motor inhibition.
- The temporal modulation of ipsilateral PMd-M1 connectivity, assessed via dual-site TMS, shows potential as a neurophysiological marker for fatigue in MS.
