Eric Verin

Unilateral suppression of pharyngeal motor cortex to repetitive transcranial magnetic stimulation reveals functional asymmetry in the hemispheric projections to human swallowing

Inhibitory patterns of repetitive transcranial magnetic stimulation (rTMS) were applied to pharyngeal motor cortex in order to establish its role in modulating swallowing activity and provide evidence for functionally relevant hemispheric asymmetry. Healthy volunteers underwent single pulse TMS before and for 60 min after differing intensities of 1 Hz rTMS (n= 9, 6 male, 3 female, mean age 34 ± 3 years) or theta burst stimulation (TBS) (n= 9, 6 male, 3 female, mean age 37 ± 4 years). Electromyographic responses recorded from pharynx and hand were used as a measure of cortico‐motor pathway excitability. Swallowing behaviour was then examined with a reaction time protocol, before and for up to 60 min after the most effective inhibitory protocol (1 Hz) applied to each hemisphere. Interventions were conducted on separate days and compared to sham using ANOVA. Only high intensity 1 Hz rTMS consistently suppressed pharyngeal motor cortex immediately and for up to 45 min (−34 ± 7%, P≤ 0.001). Adjacent hand and contralateral pharyngeal motor cortex showed no change in response (−15 ± 12%, P= 0.14 and 15 ± 12%, P= 0.45, respectively). When used to unilaterally disrupt each hemisphere, rTMS to pharyngeal motor cortex with the stronger responses altered normal (−12 ± 3%, P≤ 0.001) and fast (−9 ± 4%, P≤ 0.009) swallow times, not seen following rTMS to the contralateral cortex or after sham. Thus, suppression of pharyngeal motor cortex to rTMS is intensity and frequency dependent, which when applied to each hemisphere reveals functionally relevant asymmetry in the motor control of human swallowing.

Comparison between anatomy and resistance of upper airway in normal subjects, snorers and OSAS patients

Upper airway (UA) anatomical abnormalities are frequently observed in obstructive sleep apnea syndrome (OSAS). The correspondence between UA anatomical modifications and UA resistance (UAR) had not been studied. We aimed to determine if cephalometric characteristics could be related to segmental UAR. In twenty-five patients (21 males) (15 OSAS patients, 10 snorers) and 10 control subjects (8 males), segmental UAR were measured in supine position and cephalometry was performed. Inspiratory and expiratory UAR were calculated at peak flow. Length of the soft palate (LP), posterior airway space (PAS), distance from hyoid bone to mandibular plane and to posterior pharyngeal wall were different between the groups (P<0.01). Inspiratory and expiratory, total and segmental, UAR were higher in OSAS (P<0.001). Segmental UAR were correlated with PAS and distance from hyoid bone to mandibular plane and to pharyngeal posterior wall (P<0.05). In conclusion, OSAS patients had higher UAR depending on anatomical variables, especially the place of the hyoid bone.

Mylohyoid motor‐evoked potentials relate to swallowing function after chronic stroke dysphagia

Abstract   This work aimed to study mylohyoid motor‐evoked potentials (MHMEPs) and examined if it is related to chronic stroke dysphagia. Conduction time (CT) and amplitudes of the right and left MHMEPs in response to focal cortical magnetic stimulations over affected and unaffected hemispheres were recorded in 16 stroke patients with aspiration (n = 9) or residue (n = 7) and compared with eight control patients. In control group, MHMEPs were present on ipsilateral and contralateral sides after stimulation of both hemispheres and permitted to determine a dominant hemisphere. In stroke patients, after stimulation of the affected hemisphere, ipsilateral MEPs had a longer CT and lower amplitudes in patients with aspiration compared with patients with residue or control patients (P < 0.05). Contralateral CT was not different between the three groups, but amplitudes were lower in patients with residue and aspiration than in control patients (P < 0.01). In the unaffected hemisphere, MHMEPs were present, and not different between the three groups for the ipsilateral side and amplitudes were decreased in contralateral side in patients with residue. In conclusion, MHMEP alterations of the affected hemisphere related to chronic stroke dysphagia severity and were closed to normal in the unaffected hemisphere.

Ventilatory responses to hypercapnia in divers and non-divers: effects of posture and immersion.

Abstract. The aim of this study was to determine the effects on respiratory drive of two factors, one mechanical (lung volume) and one chemical (sensitivity to hypercapnia), that are involved in determining the breath-hold duration (BHD). Functional residual capacity was measured by helium dilution with the subject seated in air, seated in water and in the prone position in water. Hyperoxic hypercapnia rebreathing (Reads method) was carried out under identical environmental conditions to assess the effects of CO2 pressure on respiratory centre output by measuring ventilation, mean inspiratory flow and occlusion pressure. Sixteen healthy volunteers were tested, 8 trained divers and 8 non-divers. Functional residual capacity decreased for the postures seated in water (30.8%–34.8%) and for prone position in water (20.3%–20.9%) when compared to the posture seated in air (P<0.0001), all subjects pooled. No difference was found between groups. The slopes of the linear regression, which characterised the sensitivity to CO2 and were determined with the rebreathing tests, revealed differences between the two populations (ventilation: P<0.0001; mean inspiratory flow: P<0.05). No difference was found for occlusion pressure or between the different postures. These results confirmed a lower sensitivity to CO2 for trained divers. This adaptation was shown to decrease respiratory centre activity at the origin of the breath-hold breaking point. The immersion, did not influence respiratory drive, despite a decrease in lung volumes. The authors suggest that these findings may be explained by a specific apnoea training and a pronounced bradycardia in immersion.

Intracortical inhibition and facilitation of the response of the diaphragm to transcranial magnetic stimulation

&NA; Respiratory muscles respond to a subcortical automatic command and to a neocortical voluntary command. In diseases such as stroke or motor neurone disease, an abnormal diaphragmatic response to single transcranial magnetic stimuli can identify a central source for respiratory disorders, but this is not likely to be the case in disorders affecting intracortical inhibitory and facilitatory mechanisms. This study describes the response of the diaphragm to paired transcranial magnetic stimulation. Thirteen normal subjects were studied (age range, 22 to 43 years; 7 men; phrenic conduction, <6.8 msec; latency of diaphragmatic motor evoked potential, <20.5 msec). Motor evoked potentials in response to paired stimulation were obtained in eight subjects only, with the motor threshold in the remaining five subjects too high to absorb the loss of power inherent in the double‐stimulation montage. Interstimulus intervals less than 5 msec resulted in a statistically significant inhibition (p < 0.01 for interstimulus intervals of 1 and 3 ms), whereas intervals longer than 6 msec were facilitatory (maximal, 15 msec). The diaphragmatic pattern matched that of the biceps brachii. The authors conclude that it is possible to study intracortical inhibition and facilitation of diaphragmatic control, although not in all subjects. Technical improvement should alleviate current limitations and make paired transcranial magnetic stimulation a tool to study respiratory muscle abnormalities in settings in which intracortical interactions are important, such as movement disorders.

Submental sensitive transcutaneous electrical stimulation (SSTES) at home in neurogenic oropharyngeal dysphagia: a pilot study.

OBJECTIVE Oropharyngeal dysphagia is frequent in chronic neurological disorders and increases mortality, mainly due to pulmonary complications. Our aim was to show that submental sensitive transcutaneous electrical stimulation (SSTES) applied during swallowing at home can improve swallowing function in patients with chronic neurological disorders. METHODS Thirteen patients were recruited for the study (4 f, 68 ± 12 years). They all suffered from neurogenic oropharyngeal dysphagia. We first compared the swallowing of paste and liquid with and without SSTES. Thereafter, the patients were asked to perform SSTES at home with each meal. Swallowing was evaluated before and after six weeks of SSTES using the SWAL-QoL questionnaire. RESULTS With the stimulator switch turned on, swallowing coordination improved, with a decrease in swallow reaction time for the liquid (P<0.05) and paste boluses (P<0.01). Aspiration scores also decreased significantly with the electrical stimulations (P<0.05), with no change in stasis. At-home compliance was excellent and most patients tolerated the electrical stimulations with no discomfort. A comparison of the SWAL-QoL questionnaires after 6 weeks revealed an improvement in the burden (P=0.001), fatigue (P<0.05), and pharyngeal symptom (P<0.001) scales. CONCLUSION The present study demonstrated that SSTES is easy to use at home and improves oropharyngeal dysphagia quality of life.

Potential of Olfactory Ensheathing Cells from Different Sources for Spinal Cord Repair

Spinal cord injury (SCI) induces a permanent disability in patients. To this day no curative treatment can be proposed to restore lost functions. Therefore, extensive experimental studies have been conducted to induce recovery after SCI. One of the most promising therapies is based on the use of olfactory ensheathing cells (OECs). OECs can be obtained from either the olfactory bulbs (OB-OECs) or from olfactory mucosa (OM-OECs), involving a less invasive approach for autotransplantation. However the vast majority of experimental transplantations have been focusing on OB-OECs although the OM represents a more accessible source of OECs. Importantly, the ability of OM-OECs in comparison to OB-OECs to induce spinal cord recovery in the same lesion paradigm has never been described. We here present data using a multiparametric approach, based on electrophysiological, behavioral, histological and magnetic resonance imaging experiments on the repair potential of OB-OECs and OM-OECs from either primary or purified cultures after a severe model of SCI. Our data demonstrate that transplantation of OECs obtained from OB or OM induces electrophysiological and functional recovery, reduces astrocyte reactivity and glial scar formation and improves axonal regrowth. We also show that the purification step is essential for OM-OECs while not required for OB-OECs. Altogether, our study strongly indicates that transplantation of OECs from OM represents the best benefit/risk ratio according to the safety of access of OM and the results induced by transplantations of OM-OECs. Indeed, purified OM-OECs in addition to induce recovery can integrate and survive up to 60 days into the spinal cord. Therefore, our results provide strong support for these cells as a viable therapy for SCI.

Upper airway resistance during progressive hypercapnia and progressive hypoxia in normal awake subjects

Ventilatory motor output is known to influence the upper airway. Although inspiratory upper airway resistance decreases during progressive hypoxia or hypercapnia, the effects of hypoxia and hypercapnia on expiratory upper airway resistance remain unknown. In the present study, we attempted to examine whether the expiratory and the inspiratory upper airway resistances were modified in the same way by progressive hyperoxic hypercapnia or by progressive normocapnic hypoxia. Nine healthy subjects (five males, four females, 33+/-9 years) participated in the study. Inspiratory upper airway (iUAR) and expiratory upper airway resistances (eUAR) were calculated at flow 300 ml x s(-1). Both resistances were obtained during a baseline period and during progressive hyperoxic hypercapnia or progressive normocapnic hypoxia. In all subjects, iUAR and eUAR decreased significantly during hypercapnic or hypoxic challenge (P<0.05). eUAR was always lower than iUAR during hypercapnic challenge (P<0.0001) and during hypoxic challenge (P<0.0001). The authors conclude that expiratory upper airway resistance, as with inspiratory resistance, decreases during progressive hypercapnia or during progressive hypoxia. Pharyngeal dilator or constrictor muscle activities may be implicated.

Cartography of human diaphragmatic innervation: preliminary data.

In humans, anatomy indicates that the phrenic nerve mainly arises from the C4 cervical root, with variable C3 and C5 contributions. How this translates into functional innervation is unknown. The diaphragm response to electrical stimulation of C3, C4 and C5 was described in three patients undergoing surgical laryngeal reinnervation with an upper phrenic root (surface chest electrodes at anterior, lateral and posterior sites; oesophageal and gastric pressures (Pes and Pga) to derive transdiaphragmatic pressure (Pdi)). Anatomically, the phrenic nerve predominantly originated from C4. Phrenic stimulation elicited motor responses at the three sites in the three patients, as did C4 stimulation. It produced Pdi values of 9, 11, and 14cmH(2)O in the three patients, respectively, vs. 9, 9, and 7cmH(2)O for C4. C3 stimulation produced modest Pdi responses, whereas C5 stimulation could produce Pdi responses close to those observed with C4 stimulation. These singular observations confirm the dominance of C4 in diaphragm innervation but suggest than C5 can be of importance.

Impact of deep brain stimulation on pharyngo‐esophageal motility: a randomized cross‐over study

Bilateral subthalamic nucleus (STN) stimulation is used to alleviate Parkinsons disease (PD) motor symptoms. Recently, it has been shown that this therapeutic also increased gut cholinergic contractions. We therefore investigated the effect of STN stimulation on esophageal motility in an interventional randomized study.