Enhancing ALS Research with the DuoMAG MP Dual TMS System

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterised by the degeneration of both upper and lower motor neurons. While changes in electromyography (EMG) serve as objective biomarkers for lower motor neuron degeneration, the challenge has been to find universally accepted quantitative biomarkers for upper motor neuron dysfunction. This is where transcranial magnetic stimulation (TMS) comes into play.

TMS involves the non-invasive application of a brief magnetic pulse over the scalp to activate upper motor neurons indirectly, leading to motor unit action potentials recorded via EMG as motor evoked potentials (MEPs).

Paired pulse TMS protocols, which apply a conditioning stimulus (CS) before a test stimulus (TS), can measure cortical excitability changes in the motor cortex. Specifically, short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) are used to assess inhibitory and facilitatory influences on upper motor neurons. Previous studies have demonstrated that these measures can help discriminate between ALS patients and healthy controls.

 

The Role of the DuoMAG MP Dual TMS System

McMackin et al. (2024) utilised the DuoMAG MP Dual TMS system, an advanced and versatile stimulator, which significantly aided the study by providing precise and consistent stimulation capabilities. Here’s how the DuoMAG MP Dual TMS system facilitated the research:

  1. High Precision and Control: The DuoMAG MP Dual TMS system offers precise control over the magnetic pulse's intensity and timing. This precision is crucial when conducting paired pulse TMS protocols to measure SICI and ICF. The system's ability to deliver monophasic magnetic stimuli with high accuracy ensured reliable data collection.

  2. Automated Threshold Tracking: The system's fully automated parameter estimation by sequential testing (PEST) for determining resting motor thresholds (RMT) and threshold hunting targets (THT) streamlined the process. This automation reduced the variability and potential for human error, leading to more consistent and reproducible results.

  3. Flexible Coil Orientation: The study explored the use of different coil orientations, specifically posterior-to-anterior (PA) and anterior-to-posterior (AP), to determine which provided better sensitivity in detecting ALS-related cortical abnormalities. The DuoMAG MP Dual TMS system’s flexibility in coil positioning was vital for comparing these orientations effectively.

  4. User-Friendly Interface: The DuoMAG system's interface allowed researchers to easily switch between different stimulation protocols and adjust parameters in real-time. This adaptability was essential for conducting the varied and complex protocols required in the study.

  5. Enhanced Data Collection: By ensuring that TMS pulses were consistently delivered to the same scalp location, the DuoMAG system helped maintain the accuracy and reliability of the data collected. This consistency is especially important when dealing with a sensitive and variable measure like MEP amplitude.

Participants in the study included 35 ALS patients and 39 healthy controls. The DuoMAG MP Dual TMS system delivered monophasic magnetic stimuli via a 50 mm mid-diameter figure-of-eight coil. Researchers measured SICI at 1 ms and 3 ms intervals using both PA and AP coil orientations and ICF at a 10 ms interval using the PA orientation. The precision and flexibility of the DuoMAG system were instrumental in these measurements.

Key Findings

  1. Motor Thresholds: ALS patients exhibited higher motor thresholds (in terms of %MSO) compared to controls when using the PA orientation, indicating cortical motor neuron dysfunction.
  2. SICI Measurements: Significant differences in SICI were observed between ALS patients and controls. SICI was lower in ALS patients, indicating reduced cortical inhibition. The DuoMag system's ability to measure SICI with high precision at different ISIs and orientations was crucial in identifying these differences.
  3. Discrimination Ability: The study found that averaging SICI values across different ISIs and orientations improved the discrimination of ALS patients from controls. The DuoMAG system's flexibility in coil orientation and precise control over stimulation parameters were key to obtaining these nuanced measurements.

The DuoMAG MP Dual TMS system was integral to the success of this research, providing the precision, flexibility, and automation needed to explore complex TMS protocols effectively. By enabling accurate and consistent measurement of motor cortical excitability, the DuoMAG system contributed significantly to advancing our understanding of ALS-related cortical dysfunction. This research underscores the potential of advanced TMS technology in developing reliable biomarkers for neurodegenerative diseases like ALS, ultimately aiding in better diagnosis and monitoring of these conditions.