Failure of repetitive TMS over the supplementary motor area or the primary motor cortex to alleviate experimental dyspnea in healthy humans: A randomized sham-controlled physiological study - 17/02/23

Doi : 10.1016/j.rmr.2022.11.077 
J. Hagenburg 1, 2, C. Le Fol 1, A. Sieye 1, J. Voutsa 1, M. Raux 1, 4, C. Morélot-Panzini 1, 3, T. Similowski 1, 3, M.C. Niérat 1,
1 Sorbonne université, Inserm, UMRS1158 neurophysiologie respiratoire expérimentale et clinique, Paris, France 
2 Service des maladies respiratoires, CHU Reims, Reims, France 
3 AP–HP, groupe hospitalier universitaire AP–HP-Sorbonne université, site Pitié-Salpêtrière, département R3S, 75013 Paris, France 
4 AP–HP, groupe hospitalier universitaire AP–HP-Sorbonne université, site Pitié-Salpêtrière, département d’anesthésie-réanimation, Paris, France 

Corresponding author.



Dyspnea, the conscious and unpleasant perception of breathing, is the common manifestation of respiratory, cardiac and neuromuscular disorders, and a life-altering experience. Addressing dyspnea is therefore a central clinical problem. When “lung approaches” cannot be used because of irreversible lesions, “brain approaches” can be useful [1].

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) allows manipulation of the excitability of cortical networks and, can be used to modify motor behaviors or sensory experiences such as chronic neuropathic pain [2]. We hypothesized that modulating the cortical networks involved in the “excessive respiratory effort” type of dyspnea (Supplementary Motor Area – SMA or Primary Motor cortex - M1) that results from experimental inspiratory threshold loading (ITL) by means of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) would attenuate an experimentally induced dyspnea.


A double-blind crossover design including thirty-one healthy subjects (median age: 25 years; 73,33% men) was used to compare the effects of 20Hz HF-rTMS and sham stimulation on experimental “work/effort” dyspnea (ITL). rTMS was applied over the supplementary motor area (SMA) in 12 subjects and over the primary motor cortex (M1) in 19 subjects.

Dyspnea was assessed continuously during hte dyspnogenic challenge by the mean of visual analog scales for sensory and affective dimensions (S-VAS and A-VAS, respectively) and at the end of each session using the Multidimensional Dyspnea Profile (MDP).

First, the level of inspiratory loading was determined to induce a dyspnea intensity of about 50% of the full-scale VAS. Dyspnea and breathing pattern were then measured during 3 5-min sessions of ITL in the following order: at baseline, 5min and 20min after the conditioning by active or sham rTMS (according to randomization).


Contrary to our hypothesis, Work/Effort dyspnea, evaluated by S-VAS, A-VAS and MDP, was not attenuated by either active HF-rTMS over the SMA or over M1. Furthermore, no effect on breathing pattern was observed.

Conclusions and perspectives

HF-rTMS over the SMA or over M1 does not appear to relieve experimentally induced acute dyspnea in healthy subjects. Future studies in healthy subjects should consider other cortical conditioning targets (e.g., limbic areas and insular cortex) and/or other experimental models (e.g., clinical dyspnea in patients with chronic respiratory diseases).

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© 2022  Publicado por Elsevier Masson SAS.

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