This research programme was inspired by a desire to understand the neural underpinnings of an interesting patient cohort with an atypical presentation of dysphagia (Huckabee, Lamvik, & Jones, 2014). These patients presented with mis-sequenced, rather than weakened, pharyngeal constriction when swallowing. As a result, they were unable to coordinate streamlined food or liquid transfer from the pharynx into the oesophagus. This cohort gave rise to a series of studies to explore the nature of underlying neural control of swallowing and mis-swallowing, behavioural modulation of volitional and spontaneous swallowing, and methodological limitations of existing diagnostic techniques. A prospective incidence study is currently ongoing to identify specific patient groups who exhibit pharyngeal mis-sequencing and to further explore mechanisms of pharyngeal sequencing itself. This study is evaluating swallowing in patients with dysphagia as a sequela of four brain disorders (n = 100): base of skull surgery, brainstem stroke, cortical stroke and Parkinson’s disease. Manofluoroscopic results from current participants (n = 7) are reported in this thesis. Completion of this project will likely translate immediately to improved patient care and greater scientific understanding of the complex neural control of swallowing. Previous research has documented that pressure and duration of brainstem-generated pharyngeal swallowing can be cortically modulated (Bülow et al., 2001; Fukuoka et al., 2013; Wheeler-Hegland et al., 2008; Witte et al., 2008). But there is a commonly held belief that the sequence of pharyngeal pressure remains constant (Ertekin, 2011). Intensive training was provided to healthy adults (n = 6) to determine if participants can volitionally alter latency of pharyngeal closure, thereby evaluating the capacity for pharyngeal adaptation in a healthy system. Following training, participants were able to reduce temporal separation of peak pressure between the proximal and distal pharyngeal sensors from a baseline median of 188 ms (interquartile range (IQR) = 231 ms) to 68 ms (IQR = 92 ms; p = 0.002). However, there was a contemporaneous reduction in swallowing duration post-training (p = 0.03). Participants may have achieved a reduced peak-to-peak latency through optimizing a reduction in overall swallowing duration, suggesting volitional modulation cannot alter the reflexive pharyngeal sequence to a pathologic level. Sleep has been associated with periods of relative cortical quiescence (Orr, Johnson, & Robinson, 1984), enabling evaluation of volitional and automatic swallowing conditions. Pharyngeal swallowing was analysed with low and high-resolution manometry in healthy participants (n = 20) and patients with dysphagia (n = 3). Results indicated sleep swallows were of lower amplitude than supine awake swallows (p < 0.01), with no significant difference between awake and supine swallows in terms of latency (p = 0.11) or slope (p = 0.73). This contrasts to findings of patients with dysphagia, who presented with a clear pattern of mis-sequenced pressure during sleep, even in the two patients who were able to sequence pressure adequately to enable functional swallowing when awake. This may provide additional data regarding the debate or the role of volition and arousal in swallowing motor control. Advancements in circumferential sensor technology now enable comparison of manometric catheters with similar diameter (2.1 mm unidirectional diameter to 2.75 mm circumferential diameter). Understanding differences in measurement between these two intraluminal pressure measurement devices is critical to explain the variability in normative data collected by similar intraluminal instruments. A comparison of low- and high-resolution manometry found significant differences in measurement of temporal and amplitude characteristics. Further, in-vivo and in-vitro studies were completed with low- and high-resolution manometry, with stable measurement in low-resolution manometry contrasting to unstable high-resolution manometry measurement, varying both between studies (p < 0.01) and within sensors (p < 0.01). Further, this measurement error is not corrected via the standard operating instructions. Topical nasal anaesthetic is used in research and clinical examinations with pharyngeal highresolution manometry and recommended in clinical protocols (Knigge, Thibeault, & McCulloch, 2013). However, it is unclear if desensitizing the nasal mucosa improves procedure tolerability or affects pharyngeal swallowing. Results indicate topical nasal anaesthetic provides no improvement in procedure comfort (p = 0.23), with potential alterations in pharyngeal swallowing as compared to placebo conditions. Lastly, Knigge et al. (2014) provide the only published clinical protocol for analysis of high-resolution manometry spatiotemporal plots using existing system-based technologies (e.g., ManoScan™ high-resolution manometry systems). Results indicate that, following training, intra-rater reliability was 0.99 (range = 0.97 – 1.0; SD = 0.01) while inter-rater reliability was variable across measures (range = 0.11-0.95; SD=0.32). While this will likely have an impact on current best practice, further research is needed to standardize measurement of pharyngeal swallowing using high-resolution manometry. The studies included in this programme of research contribute to shortcomings in the literature regarding best practice in diagnostic methodology and the nature of underlying neural control of pharyngeal swallowing.