Behavioural Studies

6.1.1 Incidence, Aetiology and Pathophysiology of Pharyngeal Mis-sequencing in Dysphagic Patients with Neurologic Impairment

Research question: Recent clinical experience has identified a group of patients presenting

with an atypical and sometimes profound dysphagia characterized by mis-sequenced pharyngeal pressure when swallowing (Huckabee et al., 2014). The incidence and natural history of pharyngeal mis-sequencing in patients with neurological disorders was not known. What were the defining characteristics of pharyngeal mis-sequencing and in which cohort(s) of neurologic impairment is pharyngeal mis-sequencing observed? Was the temporal development of pharyngeal mis-sequencing the same across cohorts, or variable between or within cohorts?

Objective: To observe the incidence and pattern of development of pharyngeal mis-

sequencing with pharyngeal manometry in patients with cortical stroke, brainstem stroke, PD and base-of-skull surgery.

Hypothesis: Two plausible, yet contrasting, hypotheses could be justified by existing

knowledge. If pharyngeal mis-sequencing was a result of direct neurologic deficit itself, it was hypothesized that pharyngeal mis-sequencing would be evident at the initial and subsequent data collection sessions in patients with brainstem stroke and base-of-skull surgery which directly affect neural structures responsible for swallowing motor programming. It would not expected to see mis-sequencing in the cortical stroke or PD groups. Conversely, if pharyngeal mis-sequencing was a consequence of a maladaptive response to chronic dysphagia, it was hypothesized pharyngeal mis-sequencing would be evident in all patients with swallowing impairment, irrespective of aetiology, at the 3- and 6- month data collection sessions, with no evidence of mis-sequencing immediately post-onset.

Significance: A prospective incidence study was needed to not only further identify specific

patient groups who exhibit pharyngeal mis-sequencing, but also to explore the patterns of development of pharyngeal sequencing itself. Pharyngeal mis-sequencing in dysphagia was not easily observable on VFSS. Therefore, this project would provide important information

to encourage the use of more accurate diagnostic tools, such as pharyngeal manometry, in appropriate patients to prevent misdiagnosis of swallowing problems. Further, this this study was needed to provide researchers a full report of pharyngeal mis-sequencing, detailing much needed information regarding the nature of underlying neural control of swallowing. Thus, the results of this project would likely translate immediately to improved patient care and greater scientific understanding of the complex neural control of swallowing.

Proposed Study (see Chapter 7): The pilot study evaluated patients with dysphagia as a

sequela of four brain disorders (n = 7): base-of-skull surgery, brainstem stroke, cortical stroke and PD. This represents initial data from a larger, ongoing study recruiting a larger sample of the same cohorts (n = 100). Their swallowing was evaluated with manofluoroscopy, combined VFSS and pharyngeal manometry. Each subject was asked to perform 5 dry swallows, three 10 ml liquid trials and three 10 ml puree trials. Follow-up evaluations were completed at 1, 3 and 6 months post-onset (see section 7.2.3 for further details).

6.1.2 Volitional Control of Pharyngeal Swallowing in Healthy Adults

Research question: 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 was a commonly held belief that the sequence of pharyngeal pressure remains constant (Ertekin, 2011). It was unclear to what capacity of healthy humans can volitionally alter the ‘reflexive’ components of the pharyngeal swallow.

Objective: To examine if healthy adults could volitionally produce altered latency of

pharyngeal closure in isolation following intensive training using pharyngeal manometry as visual biofeedback, thereby evaluating the capacity for pharyngeal adaptation in a healthy system.

Hypothesis: Normal healthy adults would be able to adopt a motor plan which recruits

pharyngeal pressure in both the proximal and distal pharynx, with substantially reduced peak- to-peak separation between pharyngeal manometric sensors following two weeks of daily biofeedback training. This would be accomplished without a simultaneous reduction in total swallowing duration, suggesting that the adaptation was one of volitional temporal shift of a

specific component of swallowing rather than a more synergistic reduction in overall swallowing duration.

Significance: Successful modulation of the sequence of pharyngeal pressure by cortical

voluntary mechanisms would provide evidence to challenge the assumption that the sequence of pharyngeal pressure generation is a fixed and patterned reflexive response, unable to be cortically modulated. The ability to gain volitional modulatory control over targeted aspects of the pharyngeal swallow may serve an important avenue for rehabilitative treatment.

Proposed Study (see Chapter 8): Participants were seen for intensive training with the goal

of producing simultaneous pharyngeal pressure when swallowing using low-resolution manometry as a visual biofeedback modality. The temporal separation of peak proximal and distal pharyngeal pressure at baseline, during training with biofeedback and following training without biofeedback were compared with Friedman’s tests and post-hoc pair-wise comparisons with Wilcoxon signed-rank test (see section 8.2.3 for further details).

6.1.3 Pharyngeal Swallowing during Wake and Sleep States

Research question: Sleep has been associated with stages of relative cortical quiescence

(Orr, Heading, Johnson, & Kryger, 2004), enabling evaluation of swallowing under periods of reduced volition and awareness (Kelly, Huckabee, & Cooke, 2006). What were the biomechanical characteristics of reflexive pharyngeal swallowing in humans?

Objective: To evaluate parameters of reflexive pharyngeal swallowing responses during

sleep, which would inform on the role of volition and arousal in control of pharyngeal swallowing.

Hypothesis: It was hypothesized that normal healthy adults and patients with dysphagia

would demonstrate a significant difference between baseline and sleep swallow parameters as measured by HRM, with shorter total pharyngeal duration and lower amplitude when asleep. Further, the latency between maximal superior and inferior pharyngeal pressure would be significantly reduced during sleep as compared to wake states.

Significance: This was the first study to compare pharyngeal pressure during sleep with

wake conditions in healthy adults and patients with dysphagia using manometry. Changes in pharyngeal pressure measures when asleep, as compared to wake states, would suggest a significant role of cortical modulation of the pharyngeal swallowing response. This may provide additional data regarding the debate or the role of volition in swallowing motor control. This was of interest when considering understanding of pharyngeal swallowing and development of novel rehabilitation protocols.

Proposed Study (see Chapter 9): Pharyngeal swallowing was evaluated with pharyngeal

HRM in wake upright, wake supine and sleep conditions. Slope and latency of superior-to- inferior pharyngeal pressure, as well as maximal amplitude of pharyngeal pressure, were analysed. Comparisons were made between the three sleep and two wake conditions using paired t-tests and one-way analysis of variance with post hoc testing (see section 9.2.3 for further details).