SHORT TITLE: Neonatal Esophageal Dysmotility Mechanisms

46 Aims: To define the sensorimotor characteristics of aero-digestive reflexes evoked 47 upon mid-esophageal provocations in neuropathology infants. Methods: Provocative 48 esophageal motility testing was performed in 20 neuropathology infants and 10 controls 49 at 42.3±0.6 and 38.9±0.9 wk postmenstrual age. Data from 1,073 infusions were 50 examined for the sensory thresholds, response frequencies, response magnitude of 51 upper esophageal sphincter (UES) contractile reflexes, lower esophageal sphincter 52 (LES) relaxation reflexes, and peristaltic reflexes using mixed statistical models. 53 Results: Threshold volumes for air and liquid in neuropathology and control infants 54 were similar for all reflexes. Graded air and liquid volume-dependent UES contractile 55 reflex, LES relaxation reflex, and peristaltic reflex frequencies recruitment were present 56 in neuropathology and control subjects for the media (P<0.0001) and the reflexes 57 (P<0.0001). In neuropathology infants (vs. controls): UES contractile magnitude is 58 higher (P<0.0001); LES relaxation reflex occurred earlier (P=0.008); LES nadir duration 59 lasted longer (P=0.006); secondary peristalsis is the chief method of esophageal 60 clearance (P<0.0001); pharyngeal swallows and deglutition apneas are less frequent 61 (P=0.001); proximal, mid-esophageal waveform magnitudes and duration are 62 exaggerated (P<0.008). UES contractile reflex was longer with liquid than air in both 63 groups (P=0.03). Conclusions: 1) Perception to mid-esophageal provocation remains 64 preserved in neuropathology neonates. 2) Sustained and exaggerated myogenic 65 response from afferent activation is evident by: a) increased excitatory efferent outputs 66 to the UES and esophageal body, b) increased inhibitory efferent outputs to the LES. 3) 67 Dysfunctional regulation of pharyngeal swallowing and infrequent deglutition responses 68