Superconditioning TMS for examining upper motor neuron function in MND.

Area of Science:

• Neuroscience
• Neurology
• Clinical Neurophysiology

Background:

• Motor neuron disease (MND), including amyotrophic lateral sclerosis (ALS), affects upper motor neurons.
• Cortical hyperexcitability and reduced short-interval intracortical inhibition (SICI) are potential biomarkers in MND.
• Assessing upper motor neuron function changes over time is crucial for understanding MND progression.

Purpose of the Study:

• To investigate cortical excitability, specifically SICI, in subjects with MND using transcranial magnetic stimulation (TMS).
• To evaluate the utility of a novel four-pulse superconditioning TMS (TMSsc) paradigm for quantifying upper motor neuron function during MND progression.
• To compare TMS measures between MND subjects and healthy controls.

Main Methods:

• Repeated TMS examinations of motor-evoked potentials (MEPs) in eight MND subjects (seven with ALS) and 15 controls over two years.
• Testing involved abductor pollicis brevis (APB) and tibialis anterior (TA) muscles bilaterally.
• A novel four-pulse superconditioning TMS (TMSsc) paradigm was employed alongside standard TMS protocols.

Main Results:

• No significant difference in SICI was found between MND subjects and controls for APB or TA muscles.
• Other cortical excitability measures (TMS threshold, MEP amplitude) suggested lowered cortical excitability in MND subjects.
• TMSsc demonstrated enhanced inhibition or facilitation compared to dual-pulse TMS and could elicit MEPs in muscles unresponsive to single-pulse TMS.

Conclusions:

• Reduced SICI was not a prominent feature of cortical hyperexcitability in this MND cohort.
• The TMSsc paradigm shows promise for detecting subtle changes in upper motor neuron function and excitability in MND.
• A multi-faceted neurophysiologic protocol including TMSsc may be beneficial for monitoring MND progression.