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.

Die transkranielle Magnetstimulation (TMS) ist ein nichtinvasives Hirnstimulationsverfahren, mit welchem sowohl die funktionelle Untersuchung umschriebener kortikaler Regionen als auch die Modulation der Erregbarkeit ebendieser sowie die Induktion neuroplastischer Phänomene möglich ist. Sie wurde in der Vergangenheit insbesondere bei der Erforschung des humanen zentralmotorischen Systems angewandt. Dabei zeigte sich, dass ein einzelner über dem primärmotorischen Areal (M1) applizierter TMS-Puls multiple deszendierende Erregungswellen im Kortikospinaltrakt induzieren kann. Von diesen Undulationen besitzt die D-Welle (direkte Welle) die kürzeste Latenz und sie rekurriert auf eine direkte Aktivierung kortikospinaler Neurone, wohingegen I-Wellen (indirekte Wellen) längere Latenzen besitzen und durch transsynaptische Aktivierung dieser Zellen entstehen. Bemerkenswert ist das periodische Auftreten der letztgenannten Erregungswellen mit einer Periodendauer von etwa 1,5 ms. Zwar sind die genauen Mechanismen noch unbekannt, welche der Entstehung dieser I-Wellen sowie dem Phänomen der I-Wellen-Fazilitierung, das sich in geeigneten TMS-Doppelpulsprotokollen offenbart, zugrunde liegen, jedoch existieren hierzu verschiedene Erklärungsmodelle. Im Mittelpunkt der vorliegenden Arbeit steht die repetitive Anwendung eines TMS-Doppelpulsprotokolls, bei dem das Interpulsintervall (IPI) im Bereich der I-Wellen-Periodizität liegt (iTMS) und das gleichsam durch eine Implementierung der I-Wellen-Fazilitierung in der repetitiven TMS charakterisiert ist. Da gezeigt werden konnte, dass iTMS mit einem IPI von 1,5 ms (iTMS_1,5ms) die kortikospinale Erregbarkeit signifikant intra- und postinterventionell zu steigern vermag, und die I-Wellen-Periodizität interindividuellen Schwankungen unterliegt, wurde in der hier vorgestellten Studie an Normalprobanden der Einfluss einer individuellen Anpassung des IPIs (resultierend in der iTMS_adj) auf die intrainterventionelle kortikospinale Erregbarkeit untersucht. In der Tat stellte sich heraus, dass die iTMS_adj der iTMS_1,5ms diesbezüglich überlegen ist. Dieses Ergebnis unterstreicht das Potential einer Individualisierung der interventionellen TMS für erregbarkeitsmodulierende Effekte und macht dasjenige der ohnehin auf physiologische Prozesse abgestimmten iTMS explizit, was insbesondere für klinische Anwendungen relevant sein mag.

Die transkranielle Magnetstimulation (TMS) ist ein nichtinvasives Hirnstimulationsverfahren, mit welchem sowohl die funktionelle Untersuchung umschriebener kortikaler Regionen als auch die Modulation der Erregbarkeit ebendieser sowie die Induktion neuroplastischer Phänomene möglich ist. Sie wurde in der Vergangenheit insbesondere bei der Erforschung des humanen zentralmotorischen Systems angewandt. Dabei zeigte sich, dass ein einzelner über dem primärmotorischen Areal (M1) applizierter TMS-Puls multiple deszendierende Erregungswellen im Kortikospinaltrakt induzieren kann. Von diesen Undulationen besitzt die D-Welle (direkte Welle) die kürzeste Latenz und sie rekurriert auf eine direkte Aktivierung kortikospinaler Neurone, wohingegen I-Wellen (indirekte Wellen) längere Latenzen besitzen und durch transsynaptische Aktivierung dieser Zellen entstehen. Bemerkenswert ist das periodische Auftreten der letztgenannten Erregungswellen mit einer Periodendauer von etwa 1,5 ms. Zwar sind die genauen Mechanismen noch unbekannt, welche der Entstehung dieser I-Wellen sowie dem Phänomen der I-Wellen-Fazilitierung, das sich in geeigneten TMS-Doppelpulsprotokollen offenbart, zugrunde liegen, jedoch existieren hierzu verschiedene Erklärungsmodelle. Im Mittelpunkt der vorliegenden Arbeit steht die repetitive Anwendung eines TMS-Doppelpulsprotokolls, bei dem das Interpulsintervall (IPI) im Bereich der I-Wellen-Periodizität liegt (iTMS) und das gleichsam durch eine Implementierung der I-Wellen-Fazilitierung in der repetitiven TMS charakterisiert ist. Da gezeigt werden konnte, dass iTMS mit einem IPI von 1,5 ms (iTMS_1,5ms) die kortikospinale Erregbarkeit signifikant intra- und postinterventionell zu steigern vermag, und die I-Wellen-Periodizität interindividuellen Schwankungen unterliegt, wurde in der hier vorgestellten Studie an Normalprobanden der Einfluss einer individuellen Anpassung des IPIs (resultierend in der iTMS_adj) auf die intrainterventionelle kortikospinale Erregbarkeit untersucht. In der Tat stellte sich heraus, dass die iTMS_adj der iTMS_1,5ms diesbezüglich überlegen ist. Dieses Ergebnis unterstreicht das Potential einer Individualisierung der interventionellen TMS für erregbarkeitsmodulierende Effekte und macht dasjenige der ohnehin auf physiologische Prozesse abgestimmten iTMS explizit, was insbesondere für klinische Anwendungen relevant sein mag.