INTRODUÇÃO: O zumbido é um sintoma muito freqüente e de difícil tratamento. Atualmente, algumas evidências mostraram que o zumbido está associado a alterações funcionais do sistema nervoso central. Nos últimos anos, a modulação da atividade cortical relacionada ao zumbido por meio da estimulação magnética transcraniana repetitiva (EMT) tem sido proposta como um tratamento promissor. Entretanto, nenhum estudo avaliou sua eficácia no controle do zumbido em pacientes sem perda auditiva concomitante, nem seu efeito de longa duração. O objetivo do trabalho foi investigar os efeitos imediatos e a longo prazo da estimulação magnética transcraniana repetitiva de baixa freqüência (1 Hz) em pacientes com zumbido e audiometria normal. MÉTODOS: Utilizando um ensaio clínico aleatorizado, duplo cego e paralelo, foram randomizados 20 pacientes para receber a EMT ativa ou placebo. A estimulação foi aplicada no córtex têmporo-parietal esquerdo por cinco dias consecutivos. A avaliação clínica foi feita por meio do Tinnitus Handicap Inventory e da escala análogo-visual. A avaliação por neuroimagem foi feita por meio do SPECT, o qual foi realizado antes e 14 dias após o período de estimulação. RESULTADOS: Clinicamente, o grupo submetido à estimulação magnética transcraniana ativa apresentou uma melhora significativa do zumbido, mantida por até seis meses, quando comparado ao grupo que recebeu a estimulação placebo. A avaliação por SPECT demonstrou redução do fluxo sanguíneo no lobo temporal esquerdo após o período de estimulação ativa. CONCLUSÃO: Os resultados revelam o potencial terapêutico da estimulação magnética transcraniana como nova ferramenta no tratamento do zumbido, proporcionando redução significativa do incômodo provocado pelo zumbido por até seis meses e reduzindo a atividade neuronal no córtex temporal. / INTRODUCTION: Tinnitus is a frequent disorder which is very difficult to treat. There is compelling evidence that tinnitus is associated with functional alterations in the central nervous system. Recently, the targeted modulation of tinnitus-related cortical activity through repetitive transcranial magnetic stimulation (rTMS) has been proposed as a promising new treatment approach. However, its efficacy in patients without hearing loss has never been studied, as well as the long-term duration of its effect. The objective of this study was to investigate both immediate and long-term effect of low frequency (1 Hz) rTMS in patients with tinnitus and normal hearing. METHODS: Using a randomized double-blind and parallel clinical trial, 20 patients were divided to receive either active or placebo transcranial magnetic stimulation over the left temporoparietal cortex for 5 consecutive days. The clinical evaluation was performed by using the Tinnitus Handicap Inventory and the visual analogue scale. The neuroimage evaluation included and ECD-SPECT imaging, which was performed before and 14 days after rTMS. RESULTS: From the clinical point of view, the group submitted to active rTMS presented significant improvement of the tinnitus score, which was sustained up to six months, when compared to the group that received the sham rTMS. SPECT measurements demonstrated a reduction of metabolic activity in the left temporal lobe after active rTMS. CONCLUSION: These results support the potential of rTMS as a new therapeutic tool for the treatment of chronic tinnitus, by demonstrating a significant reduction of tinnitus complaints over a period of at least six months and a significant reduction of neural activity in the temporal cortex.

Introdução: Muitos estudos veem sendo realizados com a finalidade de identificar agentes que possam ter efeito benéfico no tratamento ou prevenção das lesões causadas nos neurônios devido à isquemia. A hipotermia já demonstrou resultados consistentes em estudos experimentais e a Estimulação Magnética Transcraniana (EMTr) já foi usada visando reduzir danos em neurônios hipocampais de animais submetidos a isquemia cerebral. Com a propriedade de aumentar ou diminuir a excitabilidade cortical a partir do estímulo magnético, estima-se que ocorra uma interferência na produção de alguns neurotransmissores e receptores de membrana, que promoveriam efeito protetor a estas células. Neste estudo avaliamos a capacidade da EMTr de proteger os neurônios de uma lesão por hipóxia, e sua possível interferência no efeito protetor da hipotermia, tentando identificar alguns mecanismos que possivelmente estariam envolvidos neste fenômeno. Métodos: Como modelo de isquemia, foram utilizados Gerbils previamente submetidos a uma avaliação de comportamento e memória por meio do teste de esquiva. O protocolo de EMTr foi a partir de sessões diárias com 25 séries de 5 segundo a 25Hz, com um intervalo de 45 segundos entre as séries, por sete dias consecutivos, com um total de 21 875 pulsos com uma intensidade de 100% do limiar motor, e sendo realizada a indução da isquemia logo após o término da última sessão, ou na isquemia após a EMTr, em sessões diárias com 25 séries de 5 segundos a 25Hz, com um intervalo de 45 segundos entre as séries, durante 3 dias consecutivos, começando imediatamente após a cirurgia. Foi mantida a temperatura de 36 °C durante o período de oclusão do vaso e os 30 minutos consecutivos, ou 31 a 32 °C quando em hipotermia. O preparo das lâminas teve cortes envolvendo a região do hipocampo, corados com hematoxilina e eosina, além de outros preparos, a marcação de TUNEL e Caspase, que visam evidenciar a ocorrência de apoptose. Resultados: Embora sem significância estatística, os animais que receberam EMTr aparentemente tiveram uma melhor performance no teste da esquiva, principalmente se aplicado após a indução da isquemia. A hipotermia demonstrou uma eficiência significativa, tanto na análise histológica quanto no teste da esquiva, associado ou não à EMTr, e nestes animais submetidos a isquemia durante a hipotermia, os que receberam EMTr tiveram área de sobrevida no hipocampo significativamente maior na análise histológica com hematoxilina e eosina. Nos animais submetidos à isquemia durante a temperatura normal, a EMTr não demonstrou aumentar a área de sobrevida das células do hipocampo. Conclusões: A EMTr (ativa ou placebo, prévia ou posterior à isquemia) pareceu ter um efeito positivo no teste de esquiva. O procedimento de estimulação pareceu bastante traumático e estressante para os animais, tendo ocorrido alguns óbitos durante a imobilização, provavelmente por asfixia. A EMTr apresentou efeito protetor significativo apenas nos animais submetidos a isquemia durante hipotermia / Introduction: Over the time many researches have been conducted with the aim of identifying agents that may have beneficial effects in the treatment or prevention of cerebral ischemia, hypothermia has shown consistent results in experimental trials and Repetitive Trans Cranial Magnetic Stimulation (rTMS) has been used in a study attempting to reduce damage in hippocampal neurons. With the property to increase or decrease cortical excitability from the repetitive magnetic stimulus, it is estimated that an interference occurs in the production of some neurotransmitters and receptors of neuronal membrane, which therefore protects these cells from hypoxia. In this study we evaluated the ability of rTMS to protect neurons from injury due to hypoxia, and its possible interference in the protective effect of hypothermia and we tried to identify some mechanisms that possibly are involved in this phenomenon. Methods: Ischemia model was performed using Gerbil that was subsequently submitted to an evaluation of behavior and memory through passive avoidance task. The rTMS protocol was daily sessions with 25 series of 5 seconds at 25Hz with an interval of 45 seconds between series, for 7 consecutive days, with a total of 21 875 pulses with an intensity of 100% of motor threshold, and being carried through the induction of ischemia soon after the end of the last session, or rTMS after ischemia, in daily sessions with 25 series of 5 seconds at 25Hz with an interval of 45 seconds between series, for 3 consecutive days, starting immediately after surgery. The temperature of 36 °C was maintained during the period of vessel occlusion and subsequent 30 minutes, or 31 °C to 32 °C when in hypothermia. The preparation of the slices had sections of the region involving the hippocampus, stained with hematoxylin and eosin in addition to other preparations, TUNEL and caspase, which aim to evidence the occurrence of apoptosis. Results: Although not statistically significant, animals that received rTMS, apparently had better performance in passive avoidance task especially when applied after ischemia. The hypothermia demonstrated a significant efficiency, both in the histological analysis and in the passive avoidance task, associated or not to applications of rTMS and, in these animals undergoing ischemia during hypothermia, the ones who received rTMS had survival area in hippocampus significantly higher in histological analysis with hematoxylin and eosin. In animals undergone to ischemia during normal temperature, the rTMS has not shown to increase the area of hippocampal cell survival. Conclusions: rTMS (placebo or active, after or before the ischemia) seems to have a positive effect on passive avoidance task. The stimulation procedure appeared to be very traumatic and stressful for the animal, in which a few deaths occurred during the procedure, probably from asphyxiation due to restraint. The rTMS had a significant protective effect only in animals undergoing ischemia during hypothermia, as demonstrated in the histological analysis with hematoxylin and eosin

INTRODUÇÃO: O zumbido é um sintoma muito freqüente e de difícil tratamento. Atualmente, algumas evidências mostraram que o zumbido está associado a alterações funcionais do sistema nervoso central. Nos últimos anos, a modulação da atividade cortical relacionada ao zumbido por meio da estimulação magnética transcraniana repetitiva (EMT) tem sido proposta como um tratamento promissor. Entretanto, nenhum estudo avaliou sua eficácia no controle do zumbido em pacientes sem perda auditiva concomitante, nem seu efeito de longa duração. O objetivo do trabalho foi investigar os efeitos imediatos e a longo prazo da estimulação magnética transcraniana repetitiva de baixa freqüência (1 Hz) em pacientes com zumbido e audiometria normal. MÉTODOS: Utilizando um ensaio clínico aleatorizado, duplo cego e paralelo, foram randomizados 20 pacientes para receber a EMT ativa ou placebo. A estimulação foi aplicada no córtex têmporo-parietal esquerdo por cinco dias consecutivos. A avaliação clínica foi feita por meio do Tinnitus Handicap Inventory e da escala análogo-visual. A avaliação por neuroimagem foi feita por meio do SPECT, o qual foi realizado antes e 14 dias após o período de estimulação. RESULTADOS: Clinicamente, o grupo submetido à estimulação magnética transcraniana ativa apresentou uma melhora significativa do zumbido, mantida por até seis meses, quando comparado ao grupo que recebeu a estimulação placebo. A avaliação por SPECT demonstrou redução do fluxo sanguíneo no lobo temporal esquerdo após o período de estimulação ativa. CONCLUSÃO: Os resultados revelam o potencial terapêutico da estimulação magnética transcraniana como nova ferramenta no tratamento do zumbido, proporcionando redução significativa do incômodo provocado pelo zumbido por até seis meses e reduzindo a atividade neuronal no córtex temporal. / INTRODUCTION: Tinnitus is a frequent disorder which is very difficult to treat. There is compelling evidence that tinnitus is associated with functional alterations in the central nervous system. Recently, the targeted modulation of tinnitus-related cortical activity through repetitive transcranial magnetic stimulation (rTMS) has been proposed as a promising new treatment approach. However, its efficacy in patients without hearing loss has never been studied, as well as the long-term duration of its effect. The objective of this study was to investigate both immediate and long-term effect of low frequency (1 Hz) rTMS in patients with tinnitus and normal hearing. METHODS: Using a randomized double-blind and parallel clinical trial, 20 patients were divided to receive either active or placebo transcranial magnetic stimulation over the left temporoparietal cortex for 5 consecutive days. The clinical evaluation was performed by using the Tinnitus Handicap Inventory and the visual analogue scale. The neuroimage evaluation included and ECD-SPECT imaging, which was performed before and 14 days after rTMS. RESULTS: From the clinical point of view, the group submitted to active rTMS presented significant improvement of the tinnitus score, which was sustained up to six months, when compared to the group that received the sham rTMS. SPECT measurements demonstrated a reduction of metabolic activity in the left temporal lobe after active rTMS. CONCLUSION: These results support the potential of rTMS as a new therapeutic tool for the treatment of chronic tinnitus, by demonstrating a significant reduction of tinnitus complaints over a period of at least six months and a significant reduction of neural activity in the temporal cortex.

Contemporary research has been examining potential links existing among sensory, motor and attentional systems. Previous studies using TMS have shown that the abrupt onset of sounds can both capture attention and modulate motor cortex excitability, which may reflect the potential need for a behavioral response to the attended event. TMS, however, only quantifies motor cortex excitability immediately following the deliverance of a TMS pulse. Therefore, the temporal development of how the motor cortex is modulated by sounds can’t be quantified using TMS. Thus, the purpose of the present study is to use time frequency analysis of EEG to identify the time course of cortical mechanisms underlying increased motor cortex excitability after sound onset. Subjects sat in a sound attenuated booth with their hands outstretched at 45-degree angles while frequency modulated sounds were intermittently presented from a speaker either in the left and right hemispace. Our results indicated a transient reduction in EEG power from 18-24 Hz (300-600 ms latency) and then a long lasting increase in EEG power that began at ~800 ms and continued until at least 1.7 sec. The latency of EEG power changes was shorter for sounds presented from the right speaker at both time periods. When sounds were presented from the right speaker the contralateral hemisphere over motor regions also showed greater power increases after 800 ms relative to the ipsilateral hemisphere. In addition, power increases were greater in the left-handed subjects (8-12 Hz). Results showed that sounds increased EEG power at the time of a previously observed increase in motor cortex excitability. Findings also suggest an increased attentional salience to the right hemispace in neurologically normal subjects and asymmetrical hemispheric activations in right and left-handers. / acase@tulane.edu

This thesis describes a series of experiments in human observers using neurophysiological and behavioural approaches to investigate the effects of varying haptic stimuli, attentional demand and age on motor control and perception during haptic sensing (i.e., using the hand to seek sensory information by touch). In Experiments I-IV, transcranial magnetic stimulation (TMS) was used to explore changes in corticomotor excitability when participants were actively engaged in haptic sensing tasks. These studies showed that corticospinal excitability, as reflected in motor evoked potential (MEP) amplitude, was greatly enhanced when participants were engaged in different forms of haptic sensing. Interestingly, this extra corticomotor facilitation was absent when participants performed finger movements without haptic sensing or when attention was diverted away from haptic input by a concurrent cognitive task (Exp I). This provided strong evidence that the observed corticomotor facilitation was likely central in origin and related to haptic attention. Neuroimaging has shown activation of the parieto-frontal network likely subserves this aspect of haptic perception. Further, this haptic-specific corticomotor facilitation was finely modulated depending on whether participants focused attention on identifying material (texture) as opposed to geometric properties of scanned surfaces (Exp II). With regards to aging effects, haptic-related corticomotor facilitation was associated with higher recognition accuracy in seniors (Exp III). In line with this, seniors exhibited similar levels of haptic-related corticomotor facilitation to young adults when task demands were adjusted for age (Exp IV). Interestingly, both young and senior adults also showed substantial corticomotor facilitation in the ‘resting’ hand when the ipsilateral hand was engaged in haptic sensing (Exp IV). Simply touching the stimulus without being required to identify its properties (no attentional task demands) produced no extra corticomotor facilitation in either hand or age group, attesting again to the specificity of the effects with regards to haptic attention. In Experiments V-VI, the ability to recognise 2-D letters by touch was investigated using kinematic and psychophysical measures. In Experiment V, we characterized how age affected contact forces deployed at the fingertip. This investigation showed that older adults exhibited lower normal force and increased letter-to-letter variability in normal force when compared to young adults. This difference in contact force likely contributed to longer contact times and lower recognition accuracy in older adults, suggesting a central contribution to age-related declines in haptic perception. Consistent with this interpretation, Experiment VI showed that haptic letter recognition in older adults was characterized not only by lower recognition accuracy but also by substantial increases in response times and specific patterns of confusion between letters. All in all, these investigations highlight the critical interaction of central factors such as attentional demand with aging effects on motor and perceptual aspects of haptic sensing. Of particular significance is the clear demonstration that corticomotor excitability is greatly enhanced when a haptic sensing component (i.e., attending to specific haptic features) is added to simple finger movements performed at minimal voluntary effort levels (typically <15 % of the maximal effort). These observations underline the therapeutic potential of active sensory training strategies based on haptic sensing tasks for the re-education of motor and perceptual deficits in hand function (e.g., subsequent to a stroke). The importance of adjusting attentional demands and stimuli is highlighted, particularly with regards to special considerations in the aging population.

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No description available.

Swallowing is a complex sensorimotor behaviour that includes precisely-timed bilateral activation and relaxation of muscles of the face, lips, tongue, cheeks, palate, larynx, pharynx and oesophagus. These events of activation and inhibition are controlled by many structures of the brain and are executed by cranial nerves that carry motor and sensory information to and from the swallowing muscles. Swallowing disorders are common sequelae of many neurological and structural disorders, including stroke, Parkinson’s disease, and head and neck cancer. Changes to swallowing physiology are also prevalent in older individuals, but these changes do not necessarily translate to dysphagia. Decreased muscle strength, changes to motor unit properties, and hypotrophic changes in skeletal muscles can result in age-related changes in swallowing physiology. In addition to muscular changes, neural changes might also change swallowing function in older subjects. The motor-learning literature presents a clear distinction between the differential applications and effects of skill- and strength-training approaches for rehabilitation of limb movement. In contrast to limb-movement rehabilitation, swallowing rehabilitation approaches consist mainly of strength training, although the pathophysiological basis for dysphagia is not always weakness. Therefore, this Phase I clinical-trial critically evaluated a unique swallowing skill training protocol in which the goal of intervention is to increase precision of motor control during swallowing. A Phase I clinical-trial was necessary to identify the appropriate protocol for inducing neurophysiological, biomechanical, and structural adaptations, to estimate effect sizes, and to identify adverse effects. The first and primary question addressed in this thesis was whether swallowing skill training would produce greater physiological effects in healthy subjects than a traditional swallowing strength training approach. In order to answer this question, three levels of assessment were included. Neurophysiological assessment consisted of delivering single-pulse transcranial magnetic stimulation (TMS) over the M1 area that sends efferent projections to the submental muscle group during a functional task of volitional saliva swallowing, and during a non-functional task of submental muscle group contraction. Biomechanical assessments consisted of pharyngeal and upper esophageal sphincter (UES) pressure measurements using pharyngeal manometry during effortful and non-effortful swallowing tasks, submental muscle activation measurements using surface electromyography (sEMG) during effortful and non-effortful swallowing tasks, and hyoid displacement using ultrasonography. Structural assessment consisted of measuring the cross sectional area of the submental muscle group. Finally, motor performance during training, and subjective ratings of the training protocols were assessed. Two skill training protocols were developed to assess the use of immediate versus delayed visual feedback in swallowing skill training. In addition, a pilot study aimed at examining the effects of increased dosage of training sessions was conducted. Forty healthy subjects (20 young, and 20 old; 20 females and 20 males) were allocated to skill and strength training groups in a counterbalanced manner. Strength training consisted of execution of the effortful swallowing technique targeting increased demand for strength. Skill training targeted precise timing and force execution during swallowing execution. Several motor-learning principles were considered in devising the training protocols, including the principles of task specificity and high intensity of training. Biofeedback was included to promote motor learning. Since the submental muscle group plays an important role in hyolaryngeal excursion, the current study utilized submental sEMG biofeedback using custom-made training software. The training protocols consisted of 1000 repetition of swallowing over a 2-week period. Subjects trained for an hour, five days a week, for 2 weeks (i.e., 10 training sessions). The extended dosage protocol included 10 subjects and comprised an additional eight sessions. The results indicated that there was a significant difference in submental activation following training, with strength training having an increase in sEMG peak amplitude in comparison to skill training. There were no other differences between groups at the 5% error level. Patterns of change were revealed when marginally significant results (0.05 < p ≤ 0.10) were investigated as well. Strength training resulted in a trend towards increased neural drive for volitional effortful-type tasks (i.e., effortful saliva swallowing, effortful water swallowing, and submental muscle contraction) as indicated by increased MEP magnitude (p = 0.07) which was consistent with significantly increased peak amplitude of submental activity measures (p < 0.001). This finding supports the task specificity principle of motor learning. Skill training resulted in no changes in MEP magnitude. There was a trend (p = 0.06) towards increased submental muscles activity during functional swallowing tasks (i.e., non-effortful swallowing) in young subjects,. Males in skill training had decreased duration of UES opening in 10 mL water effortful swallowing task (p = 0.02), a trend towards increased UES pressure in non-effortful saliva swallowing task (p = 0.07), and reduced hyoid displacement following training (p < 0.001). Changes in pharyngeal pressures were detected for skill training with delayed visual feedback that resulted in decreased pressure at mid-pharynx in effortful and non-effortful tasks (p < 0.05). No difference in submental CSA changes was detected in either training group. Both groups improved motor performance measured by data collected during the session (target hit-rate and muscle activity). The results of the pilot study that examined the effects of an extended dosage of training were difficult to interpret due to the small sample size. However, there were significant and marginally significant effects of skill training on mid-pharyngeal and UES pressure duration events. Dysphagia is common in patients with Parkinson’s disease, but no specific training programme exists for these patients, leading to the second question addressed through this research. Since movement planning is compromised due to dysfunction of the basal ganglia, providing external information for planning and executing swallowing was hypothesized to alleviate dysphagic symptoms. Ten subjects were recruited. Swallowing skill training with immediate feedback was administered for one hour every day, five days a week, for 2 weeks, similar to the training dosage and frequency in the healthy group. Biomechanical and structural changes were assessed. Swallowing skill training with immediate feedback led to an increase in submental activity in effortful swallowing tasks but not non-effortful tasks. In addition, it was found that individuals with dysphagia secondary to Parkinson’s disease have deceased submental muscle reserve relative to healthy subjects. Preliminary analysis of MEP data led to exploration of submental MEP measures between younger and older subjects. This ‘discovery’ research shed light on the third topic addressed in this thesis. There are contradicting results in the literature regarding age-related brain activity during swallowing. Since submental MEPs were included as an outcome measure in the main study, it was important to evaluate them at baseline in order to understand and interpret changes in this measure. Unlike other measures, such as pharyngeal pressure and hyoid displacement that have been documented in the literature to change with age, no similar study has been conducted to assess for differences in swallowing-related MEPs. Baseline data from the main study were analysed. Older subjects produced larger MEP magnitude in comparison to young in volitional saliva swallowing and volitional submental contraction. This finding raised some questions regarding the use of MEPs as an outcome measure, since it is not clear what constitutes a ‘positive’ change. This study documented, for the first time, the application of skill training in swallowing in a healthy and dysphagic population. Positive effects of treatment were found in the dysphagic group; an indication of negative effects was identified in the healthy group. In addition, this is the first study to compare skill to strength training in swallowing. The only significant difference between the two was significantly greater submental activation in effortful swallowing tasks following strength training in comparison to skill training; although there were some significant interactions between age and training type and gender and training type. This project represents the first Phase I clinical-trial of an innovative approach for addressing swallowing impairments. Achieving the ultimate aim of finding the most appropriate training protocol for treating individuals with a specific pathophysiological basis of dysphagia, requires the implementation of a long-term on-going research programme characterized by a staged process. This research programme sets an initial reference framework from which further projects can estimate the sample size required to answer specific questions, control for effects of age and gender and their interaction with training, increase precision in choosing assessment tools, and test new specific questions.

Background and aims: The primary motor cortex (M1) controls voluntary motor behaviours. M1 has been identified to play a major role in the execution of voluntary corticospinal tasks as well as self-initiated corticobulbar tasks. However, the involvement of M1 in more complex corticubulbar tasks, such as swallowing, is not yet fully understood. Swallowing is quite different from other voluntary motor tasks as it has both voluntary and reflexive components. The degree of M1 involvement in the pharyngeal, or more reflexive, component of swallowing is unclear. Studies investigating the role of M1 in swallowing have yielded contradictory findings regarding the specific functional contribution of M1 to swallowing. Therefore, further investigation is warranted to clarify the role of M1 in pharyngeal swallowing. Discrete saliva or water swallowing has been utilized in most studies investigating neurophysiology of swallowing in health and disease. However, individuals most frequently complete multiple, consecutive swallows during the ingestion of liquid. Biomechanical differences between discrete and continuous water swallows have been identified using videofluoroscopic swallowing study (VFSS). However, no studies have investigated the pharyngeal pressure differences between these two swallowing tasks. Additional insights into task differences may be revealed through evaluation of pharyngeal pressure utilizing pharyngeal manometry. This research programme sought to clarify the role of M1 in reflexively and volitionally initiated pharyngeal swallowing. In order to understand M1 involvement in the execution of swallowing, comparative tasks that require known dependence on M1 were also included in this research programme. This research programme addressed the biomechanical changes in motor behaviours as a result of neural disruption during the performance of a number of motor tasks. This neural disruption was intrinsically generated through application of dual task (DT) paradigm and extrinsically generated using single pulse transcranial magnetic stimulation (TMS). A secondary aim of this research programme was to identify the differences in pharyngeal pressure generation between discrete and continuous swallowing. Methods: Twenty-four right handed participants (12 males, average age= 24.4, SD= 6.3) were recruited to this research programme. A number of motor tasks that vary in complexity were tested. These tasks included: volitional swallowing, reflexive swallowing, eyebrow movement, jaw movement and finger tapping with right, left, or bilateral index fingers. Participants performed multiple trials of several tasks in each study. Repetitions of tasks during a single session may affect performance due to factors such as fatigue or practice. A baseline study was undertaken to determine within-participant variability of measures across repeated trials. Following the baseline study, the role of M1 in pharyngeal swallowing was investigated in two main studies in counter balanced order. The role of M1 in pharyngeal swallowing was evaluated by investigating swallowing parameters during neural disruption using a DT paradigm. Participants performed tasks in isolation (baseline) and with interference that consisted of pairing swallowing with comparative task that activates M1 (fingers tapping and eyebrow movement tasks). In the other study, single pulse TMS was utilized to create an electrophysiological disruption to the areas of M1 associated with muscular representation of a number of motor behaviours (swallowing tasks, jaw movement and fingers tapping tasks). Stimulation was provided to both hemispheres in random order to evaluate laterality effects. Swallowing parameters and the performance of the other motor tasks were evaluated when performed with and without electrophysiological disruption. Differences in pharyngeal pressure generation between discrete and continuous swallowing were investigated using pharyngeal manometry. Pharyngeal pressures were recorded at three locations: upper pharynx, mid-pharynx and upper esophageal sphincter (UES) during four swallowing types: discrete saliva swallowing, discrete 10 ml swallowing, volitional continuous swallowing, and reflexive continuous swallowing. The research paradigm used in this research programme identified the effect of experimental conditions on the rate and regularity of task performance. In addition, pharyngeal manometry was utilised to measure the effect of experimental conditions on the pattern of the pharyngeal pressure generation during swallowing. Within subject differences from baseline were identified by means of Repeated Measures Analyses of Variance (RM-ANOVA). Results: Initial analysis of the data revealed that repetition of tasks within a session did not affect the rate and regularity of voluntary corticospinal tasks, voluntary corticiobulbar tasks nor swallowing tasks. In addition, repeating the swallowing tasks during a session did not affect pharyngeal pressure as measured by pharyngeal manometry. When motor tasks were performed concurrently in the DT paradigm, rate and regularity of eyebrow movements were significantly decreased when paired with swallowing tasks, whereas rate and regularity of swallowing were significantly decreased when paired with left finger tapping, but not right finger tapping. However, there was no significant effect of any task on the pattern of pharyngeal pressure generation. Extrinsically generated disruption using TMS significantly reduced rate and regularity of finger tapping tasks and regularity of jaw movement and swallowing tasks. In addition, interruption of pharyngeal M1 during the volitional swallowing task produced significant increase in the duration but not the amplitude of the pharyngeal pressure. Pharyngeal pressure generation differed between swallowing types and boluses types, in that saliva swallowing produced longer pharyngeal pressure duration and lower nadir pressure than water swallows. Discrete water bolus swallowing produced longer UES opening compared to both saliva swallowing or continuous water swallowing. Conclusion: The results of this research programme provided valuable methodological information regarding the effect of trials on task performance as well as identifying pharyngeal pressure differences between discrete and continuous swallowing. In addition to the methodological contribution, this research programme expanded on previous knowledge of neural control of swallowing, in that it extended the findings regarding potential role of M1 in pharyngeal swallowing. Given the absent effect of task repetition on the performance of corticospinal and corticobulbar motor tasks, it is speculated that outcomes of research investigating the effect of experimental manipulation on motor tasks performance is due to the experimental tasks, rather than natural variance in the data. The effect of swallowing on the rate and regularity of eyebrow movement, when performed concurrently using DT paradigm, suggest bilateral functional overlapping to a significant degree between neural substrates that control swallowing and orofacial muscles. These results offer partial support of bilateral representation of swallowing in the cortex. In addition, results further revealed potential involvement of right M1 in the regulation of pharyngeal swallowing as evidenced by a disruptive effect of left finger tapping on the rate and regularity of swallowing. The results from the hemispheric TMS disruption study support the active involvement M1 in the execution of voluntary corticospinal and corticobulbar motor tasks. In addition, the current findings extended previous knowledge of neural control of pharyngeal swallowing by documenting the effect of neural disruption on the regularity and pharyngeal pressure measures during volitional and reflexive swallowing. The current programme documented potential role of M1 in the control of pharyngeal swallowing possibly by modulating the motor plan at the swallowing CPG in the brainstem. This project is the first to document pharyngeal pressure differences between discrete and continuous swallowing. These findings contribute valuable information to the swallowing literature as limited number of studies investigated the biomechanical differences between discrete and continuous liquid ingestion. This knowledge will assist clinicians and researchers in identifying the pharyngeal pressure differences between normal and abnormal swallowing in different swallowing types and ultimately guide their rehabilitation decisions. Data from this research programme will add to the existing knowledge of neurophysiology of swallowing, thereby facilitating understanding of swallowing pathophysiology which is crucial for appropriate management of swallowing disorders.

A full-sine (biphasic) pulse waveform is most commonly used for repetitive transcranial magnetic stimulation (TMS), but little is known about how variations in duration or amplitude of distinct pulse segments influence the effectiveness of a single TMS pulse to elicit a corticomotor response. Using a novel TMS device, we systematically varied the configuration of full-sine pulses to assess the impact of configuration changes on resting motor threshold (RMT) as measure of stimulation effectiveness with single-pulse TMS of the non-dominant motor hand area (M1). In young healthy volunteers, we (i) compared monophasic, half-sine, and full-sine pulses, (ii) applied two-segment pulses consisting of two identical half-sines, and (iii) manipulated amplitude, duration, and current direction of the first or second full-sine pulse half-segments. RMT was significantly higher using half-sine or monophasic pulses compared with full-sine. Pulses combining two half-sines of identical polarity and duration were also characterized by higher RMT than fullsine stimuli resulting. For full-sine stimuli, decreasing the amplitude of the halfsegment inducing posterior-anterior oriented current in M1 resulted in considerably higher RMT, whereas varying the amplitude of the half-segment inducing anterior-posterior current had a smaller effect. These findings provide direct experimental evidence that the pulse segment inducing a posterior anterior directed current in M1 contributes most to corticospinal pathway excitation. Preferential excitation of neuronal target cells in the posterior-anterior segment or targeting of different neuronal structures by the two half-segments can explain this result. Thus, our findings help understanding the mechanisms of neural stimulation by full-sine TMS.