Deep brain stimulation of the motor thalamus relieves experimentally induced air hunger

Eur Respir J. 2024 Oct 28:2401156. doi: 10.1183/13993003.01156-2024. Online ahead of print.

Abstract

Research question: We previously reported that Deep Brain Stimulation (DBS) of motor thalamus (MT), in a patient with post-stroke tremor, relieved breathlessness associated with chronic obstructive pulmonary disease. This raised the question of whether MT DBS mitigates the ascending dyspnoea signal. We therefore sought to conduct a fully powered cohort study of experimentally induced air hunger (AH), an uncomfortable urge to breathe in patients with MT DBS ON and OFF.

Methods: 16 patients (3 females) with DBS of the ventral intermediate nucleus (VIM) as treatment for tremor, underwent hypercapnic AH tests, with DBS "ON" and "OFF". Patients rated AH on a visual analogue scale (VAS) every 15 s. Hypercapnia and ventilation were matched for ON and OFF states (mean±sd 43±4 and 43±4 mmHg for end-tidal PCO2, 13.7 and 13.4 L·min-1 for ventilation). Participants ventilation was constrained to baseline levels by breathing from a 3-litre inspiratory reservoir with fixed flow of fresh gas while targeting their resting breathing frequency to a metronome.

Results: Overall steady state AH was 52±28%VAS for "ON" and 67±20%VAS for "OFF" (p=0.002; two-tailed paired t-test). The mean reduction in AH during VIM DBS was -14.4%VAS. MT DBS relieved AH in thirteen patients, heightened AH in two and caused no change in one.

Conclusion: MT DBS for tremor relief also mitigates the AH component of dyspnoea. We posit that DBS of the MT heightens the gating control of the thalamus modulating the ascending air hunger signal. Extent of relief suggests that thalamic DBS may prove to be a viable therapy for intractable dyspnoea.