Network Analysis in Motor Neuron Diseases: A Cortico-Muscular Coherence Study

Abstract

Neurodegenerative conditions are associated with widespread changes in the motor networks. There is preliminary evidence from (f)MRI studies that the structural changes extend beyond the primary motor areas in cortical regions and spinal networks, but it is unclear how the function of these networks are affected in the disease. The recording of joint multi-channel electroencephalogram (EEG) and electromyogram (EMG) for time-series analysis has been found to be instrumental for assessing the communication between cortical brain regions and the periphery by quantifying the oscillatory motor drives to muscles during specified motor tasks; hence, providing direct neuro-electric signatures of network disruption. The overarching aim of the study was to develop corticomuscular coherence-based biomarkers as potential tools for assessing network disruption in selected motor subsystems in MND patient subgroups during functional isometric motor tasks. More specifically, I hypothesized that cortico-muscular coherence (CMC) between EEG- EMG can interrogate disease-specific alterations in the brain s motor networks within and beyond the primary motor cortex in MND. We used high-density 128-channel EEG and 8 bipolar surface electromyographic recordings from extrinsic and intrinsic hand muscles to obtained measures from patients with dominant upper (PLS), lower (Polio/SMA) and mixed upper/lower (ALS) motor neuron degeneration as well as from healthy controls, during isometric precision grip tasks. Our findings showed distinct pathological changes in the patient groups compared to controls, which indicate a pathological increase of cortico-muscular coherence over frontal and parietal brain regions. These include abnormal frequency band changes over parietal regions in PLS, abnormal alpha band coherence in ALS, as well as abnormal gamma-band coherence patterns between APB/FPB muscles and the frontal/parietal regions in the Polio/SMA groups. This work reveals a previously unrecognised functional change in the motor networks. Our results suggest that the EEG-EMG coherence during functional motor tasks mark pathological functional changes in the central-peripheral communication, due to adaptive or compensatory mechanism. I argue that due to disruption in the main corticospinal pathways, alternative communications pathways re-establish with the networks not typically used which may have been pruned in early life. The findings from my experiments illustrate that highly connected areas operate as a network that can be identified using modern neurophysiological methods, and regardless of the point of origin of a lesion (UMN/LMN), my findings support the idea that neuronal circuitry adapts, and communication pathways are re- modelled as individual neurons within the motor circuit degenerate. This remodelling occurs both upstream and downstream of the neuronal injury. These network-level changes have the potential to be used as biomarkers of disease, as well as prospective tools for patient stratifications in the clinical trial settings.