Stimulating ideas for disorders of breathing, speech and swallowing

The pharynx is a multifunctional passageway. It serves as a shared conduit of the respiratory airways and the alimentary tract. Motor control of the pharynx is complex. In humans, the highly compliant muscular structure sub-serves critical roles in phonation, swallowing and resistance to airflow. Pharyngeal dysfunction can result in swallowing disturbances and sleep-related recurrent airway obstruction, which adversely affect health and quality of life. Ageing is a risk factor for dysphagia and obstructive sleep apnoea. Moreover, the incidence of neuromuscular dysfunction affecting speech, swallowing and breathing during sleep increases in neurological conditions, including stroke, and in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. Non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) can, through electromagnetic induction, evoke changes in neural excitability that influence a variety of behaviours, extending to corticomotor control. Neuromodulation has proved an effective strategy in the treatment of a wide variety of conditions. TMS and repetitive TMS (rTMS) protocols have been used in studies of people with sleep disorders, sleep apnoea, dysphagia and dysarthria (Kwon et al. 2015; Pisegna et al. 2016; Nardone et al. 2020). Not surprisingly, in light of the heterogeneous nature of disease states and the inherent complexity in the neural circuitries, there are considerable challenges in determining the optimal site(s), durations and intensities of stimulation for effective functional outcomes. In this issue of The Journal of Physiology, Cheng et al. (2020) explore the efficacy of rTMS protocols in modulating pharyngeal motor evoked potentials and swallowing accuracy. The major focus of the study, in healthy participants, was to determine whether rTMS conditioning of the pharyngeal motor cortex could prime responses to a subsequent rTMS protocol, drawing from evidence for the capacity for such ‘metaplasticity’ in studies of motor control of the hand (Iyer et al. 2003). The central premise of the proof-of-concept study in the context of the pharyngeal motor cortex was that neural responses to rTMS protocols evoking plasticity (i.e. lasting changes in excitability) are dependent upon antecedent activity in neural networks, which can be manipulated by rTMS. The authors reasoned that suppression of basal neural activity would lead to a potentiated response to subsequent excitation, whereas enhancement of neural activity would potentiate the response to subsequent inhibition. Indeed, this proved to be the case, with the application of optimal successive stimulus intensities separated by an optimal inter-rTMS interval resulting in potentiation of pharyngeal motor cortex excitability and improved swallowing reaction time or suppression of pharyngeal motor cortex excitability and functional impairment depending upon the stimulation strategy used by the investigators. The effects elaborated by stimulation protocols that followed a pre-conditioning protocol were greater than those evoked by the same stimulation protocols without pre-conditioning. The study is a significant step forward for the field and the potential application of rTMS for the treatment of dysphagia. In utilizing a new twist on the application of conventional rTMS, the authors provide a powerful experimental tool for the study of the physiology and pathophysiology of swallowing. Suppression of cortical excitability with rTMS provides researchers with a reproducible capacity to create ‘virtual lesions’ relevant to neurogenic stroke. In addition, Cheng et al. (2020) highlight the capacity to evoke and manipulate plasticity in neural circuits underpinning corticomotor control. This widens considerably the vista of opportunities that can now be pursued in studies of normal and aberrant swallowing. Moreover, the study should serve to encourage renewed enthusiasm for the potential application of de novo rTMS protocols in the study of sleep, speech and breathing in health and disease. How exciting!