Corticomotoneuronal activity in ALS: changes in the peristimulus time histogram over time

Area of Science:

• Neuroscience
• Neurology
• Motor Neuron Diseases

Background:

• The primary peak in peristimulus time histograms (PSTH) reflects the excitatory post-synaptic potential (EPSP) in anterior horn cells.
• In amyotrophic lateral sclerosis (ALS), this peak is known to be delayed, prolonged, and desynchronized, indicating corticomotoneuron dysfunction.
• It remains unclear if these motor pathway abnormalities evolve over time in ALS patients.

Purpose of the Study:

• To investigate the temporal changes in PSTH abnormalities of motor units in patients with ALS.
• To determine if the observed desynchronization and other abnormalities in the corticomotoneuronal pathway progress over time.

Main Methods:

• Peristimulus time histograms (PSTHs) were generated by analyzing the firing probability of single motor units during voluntary activation.
• Subthreshold transcranial magnetic stimulation was used to evoke responses in 58 motor units from 12 ALS patients across two separate visits (average 10.6 months apart).
• Data from ALS patients were compared to 49 motor units in 11 age-matched healthy controls.

Main Results:

• Significant differences were observed between ALS patients and controls in all PSTH parameters except amplitude.
• The primary peak in ALS was frequently complex, desynchronized, and sometimes presented as a double peak.
• These abnormalities persisted or worsened at follow-up, characterized by increased excess bins, longer duration and latency, and reduced synchrony.

Conclusions:

• The progressive desynchronization of the primary peak over time in ALS suggests ongoing dysfunction of the monosynaptic corticomotoneuronal pathway.
• These findings may also indicate the recruitment of additional, slower-conducting, and/or polysynaptic corticomotoneuronal connections as the disease progresses.