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Introduction: The cerebellum has been showed by numerous studies to be active during the process of swallowing. Cortically targeted repetitive transcranial magnetic stimulation (rTMS) is a technique which has been shown to result in beneficial electrophysiological and behavioral changes in healthy participants and patients with post stroke dysphagia. Cerebellar rTMS is a relatively unstudied area of this emerging field. Here we apply cerebellar targeted rTMS to a patient with post stroke dysphagia in an attempt to improve their swallowing., Methods: A 67-year-old woman with post stroke dysphagia was recruited to undergo a crossover active rTMS vs sham rTMS study. Outcome measures were pharyngeal motor evoked potential (PMEP) amplitude and cumulative penetration-aspiration score (cPAS). The patient attended the laboratory on two occasions. During each attendance, baseline PMEP and cPAS measurements were acquired followed by either active or sham rTMS. Following this, PMEP and cPAS measurements were repeated at 30 minutes., Results: Active cerebellar rTMS was able to increase both PMEP amplitude (55% over baseline) and improve swallowing safety (17% below baseline). Sham rTMS did not result in any beneficial PMEP or cPAS changes., Conclusion: Our results suggest that cerebellar rTMS has plausible therapeutic potential for post stroke dysphagia., (© 2019 John Wiley & Sons Ltd.)

Background Pharyngeal electrical stimulation (PES) appears to promote cortical plasticity and swallowing recovery poststroke. Objective We aimed to assess clinical effectiveness with longer follow-up. Methods Dysphagic patients (n = 36; median = 71 years; 61% male) recruited from 3 trial centers within 6 weeks of stroke, received active or sham PES in a single-blinded randomized design via an intraluminal pharyngeal catheter (10 minutes, for 3days). The primary outcome measure was the Dysphagia Severity Rating (DSR) scale (<4, no-mild; ≥4, moderate-severe). Secondary outcomes included unsafe swallows on the Penetration-Aspiration Scale (PAS ≥ 3), times to hospital discharge, and nasogastric tube (NGT) removal. Data were analyzed using logistic regression. Odds/hazard ratios (ORs/HRs) >1 for DSR <4, hospital discharge, and NGT removal and OR <1 for PAS ≥3, indicated favorable outcomes for active PES. Results Two weeks post-active PES, 11/18 (61%) had DSR <4: OR (95% CI) = 2.5 (0.52, 14). Effects of active versus sham for secondary outcomes included the following: PAS ≥3 at 2 weeks, OR (95% CI) = 0.61 (0.27, 1.4); times to hospital discharge, 39 days versus 52 days, HR (95% CI) = 1.2 (0.55, 2.5); NGT removal 8 versus 14 days, HR (95% CI) = 2.0 (0.51, 7.9); and DSR <4 at 3 months, OR (95% CI) = 0.97 (0.13, 7.0). PES was well tolerated, without adverse effects or associations with serious complications (chest infections/death). Conclusions Although the direction of observed differences were consistent with PES accelerating swallowing recovery over the first 2 weeks postintervention, suboptimal recruitment prevents definitive conclusions. Our study design experience and outcome data are essential to inform a definitive, multicenter randomized trial., (© The Author(s) 2016.)

Key points: Despite evidence that the human cerebellum has an important role in swallowing neurophysiology, the effects of cerebellar stimulation on swallowing in the disrupted brain have not been explored.In this study, for the first time, the application of cerebellar neurostimulation is characterized in a human model of disrupted swallowing (using a cortical virtual lesion).It is demonstrated that cerebellar stimulation can reverse the suppressed activity in the cortical swallowing system and restore swallowing function in a challenging behavioural task, suggesting the findings may have important therapeutic implications. Repetitive transcranial magnetic stimulation (rTMS) can alter neuronal activity within the brain with therapeutic potential. Low frequency stimulation to the 'dominant' cortical swallowing projection induces a 'virtual‐lesion' transiently suppressing cortical excitability and disrupting swallowing behaviour. Here, we compared the ability of ipsi‐lesional, contra‐lesional and sham cerebellar rTMS to reverse the effects of a 'virtual‐lesion' in health. Two groups of healthy participants (n = 15/group) were intubated with pharyngeal catheters. Baseline pharyngeal motor evoked potentials (PMEPs) and swallowing performance (reaction task) were measured. Participants received 10 min of 1 Hz rTMS to the pharyngeal motor cortex which elicited the largest PMEPs to suppress cortical activity and disrupt swallowing behaviour. Over six visits, participants were randomized to receive 250 pulses of 10 Hz cerebellar rTMS to the ipsi‐lesional side, contra‐lesional side or sham while assessing PMEP amplitude or swallowing performance for an hour afterwards. Compared to sham, active cerebellar rTMS, whether administered ipsi‐lesionally (P = 0.011) or contra‐lesionally (P = 0.005), reversed the inhibitory effects of the cortical 'virtual‐lesion' on PMEPs and swallowing accuracy (ipsi‐lesional, P < 0.001, contra‐lesional, P < 0.001). Cerebellar rTMS was able to reverse the disruptive effects of a 'virtual lesion'. These findings provide evidence for developing cerebellar rTMS into a treatment for post‐stroke dysphagia. Key points: Despite evidence that the human cerebellum has an important role in swallowing neurophysiology, the effects of cerebellar stimulation on swallowing in the disrupted brain have not been explored.In this study, for the first time, the application of cerebellar neurostimulation is characterized in a human model of disrupted swallowing (using a cortical virtual lesion).It is demonstrated that cerebellar stimulation can reverse the suppressed activity in the cortical swallowing system and restore swallowing function in a challenging behavioural task, suggesting the findings may have important therapeutic implications. [ABSTRACT FROM AUTHOR]

Key points Neurostimulation is a rapidly emerging approach to swallowing rehabilitation, but cerebellar stimulation has not been explored as a treatment. Such proposed therapies for post-stroke dysphagia have required confirmation of physiological effects and optimisation of parameters in healthy humans prior to translational progression into patient groups., There is strong evidence for a role of the cerebellum in swallowing physiology, but this relationship has been under-explored., Recently, single pulses of cerebellar magnetic stimulation have been shown to directly evoke responses from pharyngeal musculature and produce short-term enhancement of cortico-pharyngeal motor evoked potentials, suggesting the feasibility of a cerebellar approach to neurostimulation in the swallowing system., We therefore examined multiple parameters of repetitive cerebellar magnetic stimulation and have described the optimal settings to provoke longer-lasting changes in swallowing neurophysiology. Based on evidence from the post-stroke dysphagia neurostimulation literature, these changes may have a therapeutic potential for swallowing rehabilitation., Abstract Brain neurostimulation has been shown to modulate cortical swallowing neurophysiology in post-stroke dysphagia with therapeutic effects which are critically dependent on the stimulation parameters. Cerebellar neurostimulation is, however, a novel, unexplored approach to modulation of swallowing pathways as a prelude to therapy for dysphagia. Here, we randomised healthy human subjects ( n = 17) to receive one of five cerebellar repetitive TMS (rTMS) interventions (Sham, 1 Hz, 5 Hz, 10 Hz and 20 Hz) on separate visits to our laboratory. Additionally, a subset of subjects randomly received each of three different durations (50, 250, 500 pulses) of optimal frequency versus sham cerebellar rTMS. Prior to interventions subjects underwent MRI-guided single-pulse transcranial magnetic stimulation (TMS) to co-localise pharyngeal and thenar representation in the cortex and cerebellum (midline and hemispheric) before acquisition of baseline motor evoked potential (MEP) recordings from each site as a measure of excitability. Post-interventional MEPs were recorded for an hour and compared to sham using repeated measures ANOVA. Only 10 Hz cerebellar rTMS increased cortico-pharyngeal MEP amplitudes (mean bilateral increase 52%, P = 0.007) with effects lasting 30 min post-intervention with an optimal train length of 250 pulses ( P = 0.019). These optimised parameters of cerebellar rTMS can produce sustained increases in corticobulbar excitability and may have clinical translation in future studies of neurogenic dysphagia. [ABSTRACT FROM AUTHOR]

Key points Cortical control of swallowing exhibits functional asymmetry with brain lesions involving the strongest projection being implicated in the pathophysiology of dysphagia after unilateral stroke., Swallowing recovery is associated with neuroplastic adaptation in the unlesioned hemisphere, a process which can be facilitated by excitatory neurostimulation techniques including transcranial direct current stimulation (tDCS)., Unilateral suppression of the strongest pharyngeal motor projection using 1 Hz repetitive transcranial magnetic stimulation (rTMS) can disrupt swallowing neurophysiology and behaviour making it a useful model for trialling novel neurostimulation interventions in healthy subjects., In this healthy participant study we examined the effects of tDCS after unilateral pre-conditioning with 1 Hz rTMS to determine its ability to restore swallowing neurophysiology and behaviour., We show that application of optimised parameters of tDCS (anodal stimulation, 1.5 mA, 10 min) over the unconditioned hemisphere reverses the brain and behavioural consequences of inhibitory pre-conditioning, supporting the use of tDCS in clinical trials., Abstract The human cortical swallowing system exhibits bilateral but functionally asymmetric representation in health and disease as evidenced by both focal cortical inhibition (pre-conditioning with 1 Hz repetitive transcranial magnetic stimulation; rTMS) and unilateral stroke, where disruption of the stronger (dominant) pharyngeal projection alters swallowing neurophysiology and behaviour. Moreover, excitatory neurostimulation protocols capable of reversing the disruptive effects of focal cortical inhibition have demonstrated therapeutic promise in post-stroke dysphagia when applied contralaterally. In healthy participants ( n = 15, 8 males, mean age (±SEM) 35 ± 9 years), optimal parameters of transcranial direct current stimulation (tDCS) (anodal, 1.5 mA, 10 min) were applied contralaterally after 1 Hz rTMS pre-conditioning to the strongest pharyngeal projection. Swallowing neurophysiology was assessed in both hemispheres by intraluminal recordings of pharyngeal motor-evoked responses (PMEPs) to single-pulse TMS as a measure of cortical excitability. Swallowing behaviour was examined using a pressure-based reaction time protocol. Measurements were made before and for up to 60 min post intervention. Subjects were randomised to active or sham tDCS after 1 Hz rTMS on separate days and data were compared using repeated measures ANOVA. Active tDCS increased PMEPs bilaterally ( F1,14 = 7.4, P = 0.017) reversing the inhibitory effects of 1 Hz rTMS in the pre-conditioned hemisphere ( F1,14 = 10.1, P = 0.007). Active tDCS also enhanced swallowing behaviour, increasing the number of correctly timed challenge swallows compared to sham ( F1,14 = 6.3, P = 0.025). Thus, tDCS to the contralateral pharyngeal motor cortex reverses the neurophysiological and behavioural effects of focal cortical inhibition on swallowing in healthy individuals and has therapeutic potential for dysphagia rehabilitation. [ABSTRACT FROM AUTHOR]