Dysfunction of bulbar central pattern generator in ALS patients with dysphagia during sequential deglutition Ibrahim Aydogdu a,b,⇑ , Zeynep Tanriverdi a , Cumhur Ertekin a,b a Department of Neurology, Ege University Medical School Hospital, Bornova, Izmir 35100, Turkey b Clinical Neurophysiology, Ege University Medical School Hospital, Bornova, Izmir 35100, Turkey article info Article history: Accepted 1 November 2010 Available online 15 December 2010 Keywords: Sequential swallowing Respiration Central pattern generator Motor neuron disease Electrophysiology Submental EMG abstract Objective: The aim of this study is to investigate a probable dysfunction of the central pattern generator (CPG) in dysphagic patients with ALS. Methods: We investigated 58 patients with ALS, 23 patients with PD, and 33 normal subjects. The laryn- geal movements and EMG of the submental muscles were recorded during sequential water swallowing (SWS) of 100 ml of water. The coordination of SWS and respiration was also studied in some normal cases and ALS patients. Results: Normal subjects could complete the SWS optimally within 10 s using 7 swallows, while in dys- phagic ALS patients, the total duration and the number of swallows were significantly increased. The novel finding was that the regularity and rhythmicity of the swallowing pattern during SWS was disor- ganized to irregular and arhythmic pattern in 43% of the ALS patients. The duration and speed of swal- lowing were the most sensitive parameters for the disturbed oropharyngeal motility during SWS. Conclusions: The corticobulbar control of swallowing is insufficient in ALS, and the swallowing CPG can- not work very well to produce segmental muscle activation and sequential swallowing. CPG dysfunction can result in irregular and arhythmical sequential swallowing in ALS patients with bulbar plus pseudo- bulbar types. Significance: The arhythmical SWS pattern can be considered as a kind of dysfunction of CPG in human ALS cases with dysphagia. Ó 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. 1. Introduction It has been shown that the ‘‘voluntary-induced’’ swallows are initiated by the convergence of the cortical descending inputs and sensory inputs coming from the oropharynx to the swallowing central pattern generator (CPG) network, while the ‘‘spontaneous’’ or ‘‘reflexive’’ swallows are initiated only by the sensory inputs and the CPG of pontobulbar origin (Miller, 1982, 2008; Jean, 2001; Jean and Dallaporta, 2006; Ertekin et al., 2001; Ertekin, 2004). A striking characteristic of swallowing in experimental animals is that the whole motor sequence can be readily initiated by the stimulus of the superior laryngeal nerve (SLN) (Jean, 2001; Miller, 1972). Interestingly, long-lasting repetitive stimulation of the SLN can elicit a pattern of ‘‘rhythmic’’ motor activities of swallowing (Jean, 2001; Roman and Car, 1970; Nakamura et al.,2004; German et al., 2009). The sequential and rhythmic patterns of swallowing are formed and organized by a CPG (Bariohay et al., 2008; Felix et al., 2006; Wang and Bieger, 1991). The bulbar CPG has been de- scribed as swallowing center (Jean, 1990, 2001). In humans, the method of investigation of the oropharyngeal swallowing has been mostly carried out with a single or discrete bolus analysis. Single swallow can be expected and demonstrated to trigger the swallowing at the oropharynx, either voluntarily (Ertekin et al., 1995, 1998) or spontaneously (Ertekin et al., 2001). However, the continuous sequential cup/straw swallowing or drinking in humans have recently been understood as a more logical approach to test the sequential and rhythmic swallowing of the CPG (Daniels and Foundas, 2001; Daniels et al., 2004). In- deed, after the first swallow, the subsequent swallows and their rhythmicity demonstrate that the subsequent swallows could be mostly initiated at the hypopharynx in normal subjects. Such a sequential swallowing rhythmicity in human could also be similar to the fictive swallowing produced by the stimulation of SLN. In sequential swallowing, hypopharyngeal stimulation of the bolus sequences initiates the sensory inputs to the NTS (Nucleus Tractus Solitarius) at first via shorter afferent circuit and also going up to the cortex (Miller, 1972, 1999). The subsequent swallows can be 1388-2457/$36.00 Ó 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.clinph.2010.11.002 ⇑ Corresponding author at: Department of Neurology, Ege University Medical School Hospital, Bornova, Izmir 35100, Turkey. Tel.: +90 232 3903851; fax: +90 232 3880980. E-mail address: ibrahim.aydogdu@ege.edu.tr (I. Aydogdu). Clinical Neurophysiology 122 (2011) 1219–1228 Contents lists available at ScienceDirect Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph