Emilia Michou

Cortical input in control of swallowing.

Purpose of reviewThis review presents a current synopsis of newer research in cortical control of swallowing and its relationship to advancing knowledge in the field of human swallowing neurophysiology. The intent is to highlight recent findings and to stimulate potential research questions not yet investigated. Recent findingsAdvances in human brain imaging have led to a wealth of newer insights into the cortical and subcortical control of human swallowing. This includes a better understanding of the hemispheric contributions to swallowing control and the mechanisms that underlie recovery or compensation after neurological injury. SummaryThrough advances in imaging and neuroimaging techniques, our knowledge of the neuroanatomy and physiology of swallowing has increased dramatically over the last decade. Integration and interconnection of the diverse swallowing cortical network and how sensory input influences swallowing cortical activation has started to provide a better understanding of the physiological mechanisms that underpin this exquisite yet fundamental sensorimotor function. Experimental paradigms for swallowing neural reorganization have begun to provide evidence for their translation into clinical practice for dysphagia rehabilitation.

Adjunctive functional pharyngeal electrical stimulation reverses swallowing disability after brain lesions.

BACKGROUND & AIMS Oropharyngeal dysphagia is an important disability that occurs after stroke; it contributes to aspiration pneumonia and death, and current modalities for rehabilitation of dysphagia have uncertain efficacy. We therefore examined the role of pharyngeal electrical stimulation (PES) in expediting human swallowing recovery after experimental (virtual) and actual (stroke) brain lesions. METHODS First, healthy subjects (n = 13) were given 1-Hz repetitive transcranial magnetic stimulation to induce a unilateral virtual lesion in pharyngeal motor cortex followed by active or sham (control) PES. Motor-evoked potentials and swallow accuracy were recorded before and after the lesion to assess PES response. Thereafter, 50 acute dysphagic stroke patients underwent either a dose-response study, to determine optimal parameters for PES (n = 22), or were assigned randomly to groups given either active or sham (control) PES (n = 28). The primary end point was the reduction of airway aspiration at 2 weeks postintervention. RESULTS In contrast to sham PES, active PES reversed the cortical suppression induced by the virtual lesion (F(7,70) = 2.7; P = .015) and was associated with improvement in swallowing behavior (F(3,42) = 5; P = .02). After stroke, 1 PES treatment each day (U = 8.0; P = .043) for 3 days (U = 10.0) produced improved airway protection compared with controls (P = .038). Active PES also reduced aspiration (U = 54.0; P = .049), improved feeding status (U = 58.0; P = .040), and resulted in a shorter time to hospital discharge (Mantel-Cox log-rank test, P = 0.038). CONCLUSIONS This pilot study of PES confirms that it is a safe neurostimulation intervention that reverses swallowing disability after virtual lesion or stroke.

Targeting Unlesioned Pharyngeal Motor Cortex Improves Swallowing in Healthy Individuals and After Dysphagic Stroke

BACKGROUND & AIMS Patients with stroke experience swallowing problems (dysphagia); increased risk of aspiration pneumonia, malnutrition, and dehydration; and have increased mortality. We investigated the behavioral and neurophysiological effects of a new neurostimulation technique (paired associative stimulation [PAS]), applied to the pharyngeal motor cortex, on swallowing function in healthy individuals and patients with dysphagia from stroke. METHODS We examined the optimal parameters of PAS to promote plasticity by combining peripheral pharyngeal (electrical) with cortical stimulation. A virtual lesion was used as an experimental model of stroke, created with 1-Hz repetitive transcranial magnetic stimulation over the pharyngeal cortex in 12 healthy individuals. We tested whether hemispheric targeting of PAS altered swallowing performance before applying the technique to 6 patients with severe, chronic dysphagia from stroke (mean of 38.8 ± 24.4 weeks poststroke). RESULTS Ten minutes of PAS to the unlesioned pharyngeal cortex reversed (bilaterally) the cortical suppression induced by virtual lesion (lesioned: F(1,9) = 21.347, P = .001; contralesional: F(1,9) = 9.648, P = .013; repeated-measures analysis of variance) compared with sham PAS. It promoted changes in behavior responses measured with a swallowing reaction time task (F(1,7) = 21.02, P = .003; repeated-measures analysis of variance). In patients with chronic dysphagia, real PAS induced short-term bilateral changes in the brain; the unaffected pharyngeal cortex had increased excitability (P = .001; 95% confidence interval, 0.21-0.05; post hoc paired t test) with reduced penetration-aspiration scores and changes in swallowing biomechanics determined by videofluoroscopy. CONCLUSIONS The beneficial neurophysiological and behavioral properties of PAS, when applied to unlesioned brain, provide the foundation for further investigation into the use of neurostimulation as a rehabilitative approach for patients with dysphagia from stroke.

Characterizing the Mechanisms of Central and Peripheral Forms of Neurostimulation in Chronic Dysphagic Stroke Patients

Background Swallowing problems following stroke may result in increased risk of aspiration pneumonia, malnutrition, and dehydration. Objective/hypothesis Our hypothesis was that three neurostimulation techniques would produce beneficial effects on chronic dysphagia following stroke through a common brain mechanism that would predict behavioral response. Methods In 18 dysphagic stroke patients (mean age: 66 ± 3 years, 3 female, time-post-stroke: 63 ± 15 weeks [±SD]), pharyngeal electromyographic responses were recorded after single-pulse transcranial magnetic stimulation (TMS) over the pharyngeal motor cortex, to measure corticobulbar excitability before, immediately, and 30 min, after real and sham applications of neurostimulation. Patients were randomized to a single session of either: pharyngeal electrical stimulation (PES), paired associative stimulation (PAS) or repetitive TMS (rTMS). Penetration-aspiration scores and bolus transfer timings were assessed before and after both real and sham interventions using videofluoroscopy. Results Corticobulbar excitability of pharyngeal motor cortex was beneficially modulated by PES, PAS and to a lesser extent by rTMS, with functionally relevant changes in the unaffected hemisphere. Following combining the results of real neurostimulation, an overall increase in corticobulbar excitability in the unaffected hemisphere (P = .005, F1,17 = 10.6, ANOVA) with an associated 15% reduction in aspiration (P = .005, z = −2.79) was observed compared to sham. Conclusions In this mechanistic study, an increase in corticobulbar excitability the unaffected projection was correlated with the improvement in swallowing safety (P = .001, rho = −.732), but modality-specific differences were observed. Paradigms providing peripheral input favored change in neurophysiological and behavioral outcome measures in chronic dysphagia patients. Further larger cohort studies of neurostimulation in chronic dysphagic stroke are imperative.

Examining the Role of Carbonation and Temperature on Water Swallowing Performance: A Swallowing Reaction-Time Study

Various therapeutic approaches for dysphagia management are based on modifications of bolus properties to change swallowing biomechanics and increase swallowing safety. Limited evidence exists for the effects of carbonation and bolus temperature on swallowing behavior. Here, we investigated the effects of carbonation and temperature on swallowing behavior using a novel automated and complex swallowing reaction time task via pressure signal recordings in the hypopharynx. Healthy participants (n = 39, 27.7±5 years old) were randomized in two different experiments and asked to perform 10 normal-paced swallows, 10 fast-paced swallows, and 10 challenged swallows within a predetermined time-window of carbonated versus still water (experiment 1) and of cold (4 °C) versus hot (45 °C) versus room temperature (21 °C) water (experiment 2). Quantitative measurements of latencies and percentage of successful challenged swallows were collected and analyzed nonparametrically. An increase in successfully performed challenged swallowing task was observed with carbonated water versus still water (P = 0.021), whereas only cold water shortened the latencies of normally paced swallows compared with room (P = 0.001) and hot (P = 0.004) temperatures. Therefore, it appears that chemothermal stimulation with carbonation and cold are most effective at modulating water swallowing, which in part is likely to be driven by central swallowing afferent activity.

Val66Met in Brain-Derived Neurotrophic Factor Affects Stimulus-Induced Plasticity in the Human Pharyngeal Motor Cortex

BACKGROUND & AIMS Polymorphisms in brain-derived neurotrophic factor (BDNF) can affect brain and behavioral responses. However, little is known about the effects of a single nucleotide polymorphism (SNP) in BDNF, at codon 66 (the Val-Met substitution, detected in approximately 33% of the Caucasian population) on stimulation-induced plasticity in the cortico-bulbar system. We examined whether this SNP influenced outcomes of different forms of neurostimulation applied to the pharyngeal motor cortex. METHODS Thirty-eight healthy volunteers were assessed for corticobulbar excitability after single-pulse, transcranial magnetic stimulation of induced pharyngeal electromyographic responses, recorded from a swallowed intraluminal catheter. Thereafter, volunteers were conditioned with pharyngeal electrical stimulation, or 2 forms of repetitive (1 and 5 Hz) transcranial magnetic stimulation (rTMS). Repeated measurements of pharyngeal motor-evoked potentials were assessed with transcranial magnetic stimulation for as long as 1 hour after the 3 forms of neurostimulation and correlated with SNPs at codon 66 of BDNF (encoding Val or Met). RESULTS Pharyngeal electrical stimulation significantly increased the amplitude of motor-evoked potentials in individuals with the SNP that encoded Val66, compared to those that encoded Met66, with a strong GENOTYPE*TIME interaction (F₈,₁₁₂ = 2.4; P = .018). By contrast, there was a significant reduction in latencies of subjects with the SNP that encoded Met66 after 5-Hz rTMS (F₃,₆₀ = 4.9; P = .04). In addition, the expected inhibitory effect of 1-Hz rTMS on amplitude was not observed in subjects with the SNP that encoded Met66 in BDNF (F₇,₁₄₀ = 2.23; P = .035). CONCLUSIONS An SNP in human BDNF at codon 66 affects plasticity of the pharyngeal cortex to different forms of neurostimulation. Genetic analysis might help select specific forms of neurostimulation as therapeutics for patients with disorders such as dysphagic stroke.

Dysphagia in Parkinson's disease: a therapeutic challenge?

This article focuses on the current status and research directions on swallowing disorders (dysphagia) in patients with Parkinson’s disease (PD). Although epidemiological data are scarce, increased incidence of dysphagia in patients with PD leads to increased risk of mortality, secondary to aspiration pneumonia. Although studies show that aspiration pneumonia is a common cause of death in this group of patients, clinical practice lacks an evidence base and there is an increased need for randomized clinical trials. Importantly, the underlying mechanisms accounting for the progression of dysphagia in PD are still unclear. Furthermore, evidence shows that dopaminergic medication does not affect swallowing performance. Future research in the field is urgently needed and may result in improved management of dysphagia in patients with PD.

Transcranial direct current stimulation reverses neurophysiological and behavioural effects of focal inhibition of human pharyngeal motor cortex on swallowing

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.

Priming Pharyngeal Motor Cortex by Repeated Paired Associative Stimulation Implications for Dysphagia Neurorehabilitation

Background. Several stimulation parameters can influence the neurophysiological and behavioral effects of paired associative stimulation (PAS), a neurostimulation paradigm that repeatedly pairs a peripheral electrical with a central cortical (transcranial magnetic stimulation [TMS]) stimulus. This also appears to be the case when PAS is applied to the pharyngeal motor cortex (MI), with some variability in excitatory responses, questioning its translation into a useful therapy for patients with brain injury. Objective. To investigate whether repeated PAS in both “responders” and “nonresponders” could enhance cortical excitability in pharyngeal MI more robustly. Methods. Based on their responses after single PAS, healthy participants were stratified into 2 groups of “responders” and “nonresponders” and underwent 2 periods (60 minutes inter-PAS interval) of active and sham PAS in a randomized order. Neurophysiological measurements with single TMS pulses from pharyngeal motor representation were collected up to 90 minutes after the second PAS period. Results. Repeated PAS increased cortical excitability up to 95% at 60 minutes following the second PAS in both the “responders” and “nonresponders.” Moreover, cortical excitability in the “nonresponders” was significantly different after repeated PAS compared with single and sham application (P = .02; z = −2.2). Conclusions. Double dose PAS switched “nonresponders” to “responders.” These results are important for PAS application to dysphagic stroke patients who do not initially respond to a single application.

Characterization of Corticobulbar Pharyngeal Neurophysiology in Dysphagic Patients With Parkinson's Disease

BACKGROUND & AIMS Dysphagia in patients with Parkinsons disease, persisting despite dopaminergic treatment, affects intake of nutrients and medication, and reduces quality of life (QOL). We investigated the neurophysiologic mechanisms that contribute to dysphagia in these patients, on and off L-3,4-dihydroxyphenylalanine (levodopa), using transcranial magnetic stimulation. METHODS We studied 26 patients with Parkinsons disease (age, 65 ± 9 y; 10 men). Dysphagia and QOL were first assessed with qualitative questionnaires. Twelve hours after patients were taken off levodopa, they underwent cortical transcranial magnetic stimulation mapping of the pharyngeal musculature and trigeminal (bulbar) transcranial magnetic stimulation, as well as videofluoroscopy to examine swallowing. The analyses were repeated after administration of levodopa. RESULTS Eleven patients initially reported dysphagia and reduced QOL scores. Videofluoroscopy identified 10 patients with swallowing impairments on and off levodopa, and 6 patients with swallowing impairments only on levodopa; the remaining 10 subjects showed no swallowing impairments, on or off the drug. While patients were on levodopa, those with swallowing impairments had bilateral increases in pharyngeal cortical excitability compared with those with no swallowing impairment (P < .05). By contrast, with medication, amplitudes of brainstem reflexes were altered only in patients with swallowing impairments on levodopa; these were decreased compared with when the patients were off levodopa. CONCLUSIONS In patients with Parkinsons disease, dopaminergic medications such as levodopa can negatively affect swallowing. The increased cortical excitability observed in dysphagic patients after they begin taking levodopa likely results from compensatory mechanisms, perhaps secondary to subcortical disease, because we observed associated inhibition of brainstem reflexes in patients with affected swallowing on medication. UK clinical trials registration no., 9882.