Internship proposal: Cortical neural coupling in amyotrophic lateral sclerosis (ALS)


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Internship type

Master 2, neuroscience

Internship duration

6 months


ALS is a debilitating and fatal neurodegenerative disease affecting the motor system in humans, with progressive degeneration of pyramidal cells in motor cortex and bulbo-spinal motoneurons. Among the various mechanisms underlying neurodegeneration, hyperexcitability and excito-toxicity can manifest at early stage of the disease and has also been revealed at presymptomatic stages thanks to studies in preclinical models and in first-degree relatives of patients with familial forms of ALS (about 10% of the cases, 90% being sporadic). In humans, cortical dysfunctions, and more precisely cortical hyperexcitability, has been reported using transcranial magnetic stimulation (TMS). However, this tool cannot be implemented for a long time along the disease course due to the increase in stimulation threshold and the resulting discomfort, and the limitation of the current stimulators. Moreover, even at early stages of the disease, TMS cannot be performed in some patients (about 25-33%). Therefore, there is a crucial need for another tool to evaluate the cortical dysfunctions in patients for diagnosis and follow-up, including clinical trials. Our strategy is to analyse scalp high density EEG and evaluate the crossed coupling frequency i.e., how the phase of a low-frequency signal interferes with the amplitude of an higher-frequency signal since part of this coupling depends on the balance between cortical excitation and inhibition (E/I) which is perturbed in ALS. This way, it has been shown that the theta-gamma coupling is depressed in mice models and we have performed a preliminary analysis in humans giving rise to the same results. Therefore, the modulation index (MI) of theta-gamma coupling might be a potent transversal biomarker in ALS.

Objective and missions

The objective of the internship is to go further into the EEG analysis in a cohort of 26 patients and a group of 23 gender and aged matched healthy controls (data already available). The student will have to use the codes developed in Python-MNE by the PhD student (Alper ER) to extract the MI based on source analysis. Then, she/he will be in charge of the statistical analysis to compare MI between ALS and controls and to evaluate whether the MI in ALS is correlated to clinical phenotype (using JMP software). During the internship, the student will also have the possibility to observe experiments in presymptomatic ALS (EEG recordings, EMG, TMS, Brain-spinal cord MRI etc.) thanks to a new protocol that will start in July 2022. She/he will have thus the opportunity to discover different techniques to investigate the human central nervous system.



Location: Laboratoire d’Imagerie Biomédicale, 1er étage du Service de Rééducation de l’Hôpital Pitié-Salpêtrière, 89 bd de l’Hôpital, 75013 Paris.