Trials / Unknown
UnknownNCT06320444
Non-invasive Spinal, Cortical, and Sensorimotor Biomarkers in Motor Neurone Disease
Developing Novel Non-invasive Electrophysiological Biomarkers of Dysfunction in Spinal and Cortical Pathways and Sensorimotor Impairments in Motor Neurone Disease
- Status
- Unknown
- Phase
- —
- Study type
- Observational
- Enrollment
- 240 (estimated)
- Sponsor
- University of Dublin, Trinity College · Academic / Other
- Sex
- All
- Age
- 18 Years
- Healthy volunteers
- Accepted
Summary
Substantial variability exists in the onset, and rate of degeneration across individuals with Motor Neurone Disease (MND) or Amyotrophic Lateral Sclerosis (ALS). This variability requires biomarkers that accurately classify and reliably track clinical subtypes as the disease progresses. Degeneration occurs in the brain and spinal cord, however, non-invasive diagnosis of spinal cord function remains highly challenging due to its unique alignment in spine. Disruption of complex spinal and cortical circuits that transmit and process neural signals for position sense and movement has not been adequately captured in the neurophysiological profiling of ALS patients. The overarching aim of this study is to reveal and quantify the extent of change in the sensorimotor integration and its potential contribution to network disruption in ALS.
Detailed description
Background: Substantial variability exists in the onset, and rate of degeneration across individuals with Motor Neurone Disease (MND) or Amyotrophic Lateral Sclerosis (ALS). This variability requires biomarkers that accurately classify and reliably track clinical subtypes as the disease progresses. Degeneration occurs in the brain and spinal cord, however, non-invasive diagnosis of spinal cord function remains highly challenging due its unique alignment in the spine. Disruption of complex spinal and cortical circuits that transmit and process neural signals for position sense and movement has not been adequately captured in the neurophysiological profiling of ALS patients. Aim: To develop, test, and employ non-invasive techniques to explore (dys)function between motor, sensory brain, and spinal networks in ALS. The project will address if the electrical activity of the cortical-spinal network by the of use peripheral stimulation (vibration, electrical nerve stimulation) to probe and reveal the normal or abnormal communication between brain and spinal networks. It is expected to reveal novel neurophysiological signatures in ALS patients compared to healthy controls. Study Design \& Data Analysis: Surface electrodes will be mounted over the targeted regions in conjunction with High-Density EEG and High-density Electromyography (EMG). A physical and mathematical model of the underlying sources of electric activity (source localization) will be carried out at rest, during task, and with non-invasive peripheral nerve stimulation (PNS) and TMS. A separate paradigm will augment sensorimotor communication between the primary motor cortex (M1) and the somatosensory cortex (S1). Mild vibration (5N/\< 500 grams) will be applied to the wrist and/or bicep tendon transcutaneously. Vibration in conjunction with non-invasive peripheral nerve stimulation will induce transient changes (30 seconds maximum) in the intrinsic excitability of motor neurons in the spinal cord. Surface EMG will capture altered MN activity at the spinal level and the anticipated augmented communication in cortical networks (S1-M1) will be captured with EEG through connectivity analysis. Non-invasive transcranial magnetic stimulation in conjunction with vibration/nerve stimulation will be recorded to explore upper motor neurone influences on the altered intrinsic excitability of spinal motor neurons. Data collection: EXG-EEG-EMG and TMS/Peripheral Stimulation recordings will be conducted using a BioSemi® ActiveTwo system with 128 active sintered Ag-AgCl electrodes and headcaps (BioSemi B.V., Amsterdam, The Netherlands). The TMS system is a Brainbox DuoMAG (Brainbox Ltd., Cardif, Wales, UK) which can be used with a Digitimer peripheral stimulator.
Conditions
- Motor Neuron Disease, Amyotrophic Lateral Sclerosis
- Motor Neuron Disease Progressive Spinal Muscle Atrophy
- Primary Lateral Sclerosis
- Multiple Sclerosis
- Postpoliomyelitis Syndrome
Interventions
| Type | Name | Description |
|---|---|---|
| PROCEDURE | 232 Electrode Electrophysiology (EEG-ECG-EMG-EXG) | Noninvasive 232 Channel Electrode Electrophysiological signals (EEG-ECG-EMG-EXG) will be recorded from electrodes placed in a montage over the scalp, neck,and upper back along with muscles located on the hand. These signals will be recorded while resting or performing voluntary task. Other Intervention: The 232 electrode noninvasive electrophysiological data will be recorded in response to non-invasive peripheral nerve stimulation or vibration induced stimulation. These sessions are designed to engage specific cortical motor networks of interest for evaluating sensorimotor networks. (Cognitive, behavioural, motor, spinal, and sensory) |
Timeline
- Start date
- 2023-06-15
- Primary completion
- 2024-12-15
- Completion
- 2025-07-15
- First posted
- 2024-03-20
- Last updated
- 2024-03-20
Locations
1 site across 1 country: Ireland
Source: ClinicalTrials.gov record NCT06320444. Inclusion in this directory is not an endorsement.