An exploration of non-invasive brain stimulation and its effects on swallowing behaviour and oropharyngeal dysphagia

UoM administered thesis: Phd

Abstract

Dysphagia can occur if damage is done to the muscles and soft tissues which carry out swallowing or any of the neuronal centres or pathways which control it. Neurogenic dysphagia occurs secondary to neurological pathology such as strokes or Parkinson’s disease (PD). Functional imaging studies performed during swallowing have shown areas of the motor cortex and cerebellum display increased activity, although the cerebellum has not been extensively studied. These brain regions or ‘swallowing centres’ act to control the process of swallowing. Most of what is known about swallowing in health and disease pertains to cerebral cortical swallowing centres and post stroke dysphagia. Over the cerebral cortex, swallowing centres are known to be asymmetrically active with a ‘dominant’ or more active hemisphere and a ‘non-dominant’ or less active hemisphere. Hemispheric strokes are more likely to cause dysphagia if the patient’s dominant swallowing hemisphere is affected. Recovery of dysphagia is associated with neuroplastic changes over the undamaged hemispheric swallowing centre. Failure to recover is associated with a lack of compensatory neuroplasticity. Studies have shown neuro-stimulatory techniques such as repetitive transcranial magnetic stimulation (rTMS) and pharyngeal electrical stimulation (PES) can modulate neuronal activity within the brain and act to encourage plastic changes. Cerebellar rTMS is a new rTMS approach which could be as efficacious as traditional cortical targeted rTMS while being safer and easier to administer. More work needs to be done to refine neuro-stimulatory techniques such as cerebellar rTMS before investigating their effects in patients with neurogenic dysphagia. Addressing these needs, for refinement and more dysphagic patient studies, were the overarching aims of this thesis.
The first study was a two-part cerebellar rTMS healthy participant (n = 15) ‘virtual lesion’ reversal study. Cortical virtual lesions were administered to the dominant pharyngeal motor area following which each participant had uni-hemispheric ipsi-lesional, contra-lesional cerebellar pharyngeal area rTMS or sham in a crossover manner. Measurements of pharyngeal motor evoked potential (PMEP) amplitudes and swallowing behaviour (measured using a behaviour timing task) were taken at baseline and at 15-minute intervals for 1 hour. Cerebellar rTMS fully reversed suppressed PMEP amplitudes and disrupted swallowing behaviour following the cortical virtual lesion.
In the second study (n = 13), the PMEP and swallowing behavioural effects of uni-hemispheric were compared to bi-hemispheric cerebellar rTMS. This three-part study involved first comparing the abilities of these techniques to excite cerebral motor cortical pharyngeal areas before assessing their effects on a virtual lesion. Bi-hemispheric cerebellar rTMS was found to be significantly more effective than uni-hemispheric cerebellar rTMS in causing cortical excitation and reversing the disrupted PMEP and behavioural virtual lesion after-effects.
The third study involved the exploration of the PMEP and swallowing behavioural effects of vermis cerebellar rTMS. In this two-part crossover study, healthy participants (n = 13) were first randomly allocated to either vermis cerebellar rTMS, uni-hemispheric cerebral rTMS or sham cerebellar rTMS. The PMEP amplitude effects of these interventions were then compared against each other. In the second part of the study the swallowing effects of vermis cerebellar RTMS were compared against sham. Surprisingly, cerebellar vermis rTMS was found to suppress cortical PMEP amplitudes and disrupt swallowing behaviour in a similar manner to the often-used cortical virtual lesion protocol.
The fourth study comprises a protocol paper of an ongoing cerebellar rTMS in post stroke dysphagia (PSD) study. The study is designed as a two-part crossover study. The first part aims to investigate the cortical PMEP and swallowing effects of uni-hemispheric cerebellar rTMS. Swallowing is being assessed using videofluoroscopy (VFS) and the penetration aspiration scale (PAS). The second part is a dose response study involving high dose cerebellar rTMS (Administered twice daily for 5 days) being compared to low intensity (once daily for 3 days) and sham.
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The final study is a comparison of the effects of three different types of neurostimulation, 5 Hz (excitatory) cortical rTMS, 1 Hz (inhibitory) cortical rTMS and pharyngeal electrical stimulation (PES) in patients with Parkinson’s disease (PD) and dysphagia (n = 12). Each intervention was compared against sham. PMEP amplitudes and VFS PAS measurements were recorded. Challenges with recruitment resulted in the study being underpowered. No significant differences from sham were seen for all three interventions. However, following post-hoc analysis wherein data from the two excitatory interventions (5 Hz rTMS and PES) were combined, a significant improvement in PAS scores for thin fluids (IDDSI 0) was observed.
In my thesis I have illustrated how human cerebellar rTMS stimulation can reverse a virtual lesion; refined the technique of cerebellar rTMS thereby making it more effective and shown, for the first time, site specificity of neurological response with regards to vermis and hemispheric cerebellar rTMS. Furthermore, the patient studies I have designed and performed aim to provide translational data regarding the effectiveness of neurostimulation in patients with PSD and PD dysphagia. Despite sub-optimal recruitment, post-hoc analysis of combined excitatory data (5 Hz rTMS and PES) showed that neurostimulation can lead to swallowing improvements in patients with PD dysphagia. My findings are in keeping with my overarching aims and support the translation of promising neuro-stimulatory techniques from the bench to the ward.

Details

Original languageEnglish
Awarding Institution
Supervisors/Advisors
Thesis sponsors
  • Medical Research Council (MRC)
Award date5 Mar 2021