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Encephalography cross-frequency coupling and brain alteration in amyotrophic lateral sclerosis
Cristina Benetton1, Arnaud Preuilh1, Mohammed Khamaysa1
1Sorbonne Université, Inserm, CNRS, Laboratoire d'Imagerie Biomédicale, LIB, Paris 75006, France.
Brain Communications
|June 9, 2025
Summary
Altered theta-gamma phase-amplitude coupling (PAC) in the dominant hemisphere of patients with amyotrophic lateral sclerosis (ALS) may indicate cortical dysfunction. This EEG marker shows higher diagnostic accuracy than MRI for ALS detection.
Area of Science:
- Neuroscience
- Neurology
- Biophysics
Background:
- Diagnosing amyotrophic lateral sclerosis (ALS) requires identifying degeneration in both brain and bulbospinal motor neurons, but detecting cortical dysfunction is challenging.
- Peripheral symptoms in ALS often overshadow upper motor neuron signs, and current tools like transcranial magnetic stimulation (TMS) and MRI have limitations in early or progressive stages.
- There is a need for reliable neuromarkers to detect cortical dysfunction and monitor ALS progression.
Purpose of the Study:
- To explore phase-amplitude coupling (PAC) in theta, alpha, beta, and gamma frequency bands in patients with ALS.
- To investigate the link between PAC alterations, handedness, and brain structure in ALS.
- To assess the diagnostic potential of PAC as a neuromarker for cortical dysfunction in ALS.
Main Methods:
- Resting-state electroencephalography (EEG) and magnetic resonance imaging (MRI) were performed on 26 ALS patients and 26 healthy controls.
- Phase-amplitude coupling (PAC) was calculated between slow and gamma oscillations at sensorimotor electrodes.
- Grey and white matter integrity was assessed using cortical thickness measurements and diffusion metrics along the corticospinal tract.
Main Results:
- Significantly decreased theta-gamma PAC was observed in the dominant hemisphere of ALS patients compared to controls.
- No significant changes were found in other frequency couplings or band powers.
- Diffusion metrics showed alterations in the brainstem segment of the pyramidal tract in the dominant hemisphere of ALS patients, and PAC outperformed MRI in diagnostic accuracy.
Conclusions:
- Lateralized theta-gamma PAC alterations in ALS patients may reflect the greater vulnerability of the dominant hemisphere.
- PAC alterations are likely linked to excitation/inhibition imbalances preceding upper motor neuron degeneration and are particularly affected in patients with cognitive impairments.
- Phase-amplitude coupling shows promise as a sensitive marker for detecting cortical dysfunction in amyotrophic lateral sclerosis, potentially aiding in diagnosis and monitoring.
