Effects of oropharyngeal exercises / myofunctional therapy on orofacial function and corticomotor excitability in healthy individuals – implications for obstructive sleep apnea?

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Dongxiang Mi, Eduardo Castrillon, Mohit Kothari, Taro Arima, Peter Svensson This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8664438/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Oropharyngeal exercises / myofunctional therapy (OE/MT) offer complimentary beneficial effects on obstructive sleep apnea. However, the complex nature of intervention impedes the understanding of underlying mechanisms related to sensorimotor function and corticomotor control of involved muscles. This study explored the sensorimotor rehabilitation effects of OE/MT tasks in twenty-two healthy adults (24.1 ± 3.1 years) using a cross-over design to better understand the normal physiology of tongue before and after these different tasks. Sessions involved breathing training (BT), tongue training (TT), or a no-training control (CT). Transcranial magnetic stimulation (TMS) evaluated motor-evoked potentials (MEPs) of the tongue and first dorsal interosseous (FDI, internal control) muscles before and after each session. Secondary outcomes included orofacial muscular pressure/force, peak expiratory flow rate (PEFR), oral stereognosis ability, and subjective ratings. Results showed TT significantly increased tongue MEP amplitude (P < 0.001) and volume (P 0.050). No significant differences were observed in orofacial pressure, PEFR, stereognosis, or subjective ratings (P > 0.050). These findings demonstrate that TT elicits unique corticomotor plasticity in tongue motor control, supporting the therapeutic potential of OE/MT. BT may need further development and be tested longer before functional effects can be observed. Health sciences/Health care Health sciences/Medical research Health sciences/Neurology Biological sciences/Neuroscience Biological sciences/Physiology Myofunctional therapy Oropharyngeal exercise Obstructive Sleep Apnea Neuroplasticity Transcranial Magnetic Stimulation Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction In the past two decades, dental sleep medicine has witnessed empirical evidence indicating that oral healthcare professionals can contribute to evaluating and managing obstructive sleep apnea (OSA) through multidisciplinary collaboration 1 . OSA is characterized by the recurring occurrence of complete or partial obstructions in the upper airway, commonly accompanied by snoring, compromised sleep quality, and cardio-metabolic diseases 2 . Globally, 425 million adults have moderate to severe OSA 3 . Multiple community-based studies revealed that the prevalence of OSA in individuals aged 60 years and older varies between 27% and 80% 4 . Moreover, as individuals age, there is a gradual rise in the collapse of the oropharyngeal muscles 5 . The correlation between muscle strength and OSA suggested the potential involvement of sarcopenia in the pathophysiology of OSA in elderly adults 6 . There is an increasing acceptance of the presence of neurologic factors: inadequate upper-airway sensory responsiveness or motor nerve function may contribute to OSA's pathogenesis 7 . Recently, beyond the oral appliances such as mandibular advancement devices (MAD) and continues positive airway pressure (CPAP), several new treatment strategies have emerged targeting oropharyngeal muscle responsiveness and control: oropharyngeal exercise / myofunctional therapy (OE/MT), hypoglossal nerve stimulation, and daytime transoral electric stimulation 8 . OE/MT comprises a series of exercises designed to improve tongue position and function, the lip seal, and nasal breathing 9 . Although evidence has confirmed that OE/MT may improve upper airway stability and reduce daytime sleepiness 10 , 11 , the underlying mechanisms of OE/MT are not yet well understood. It is generally theorized via increased muscle tone or improved control of oropharyngeal or upper airway muscles 9 . Rodríguez-Alcalá et al. proposed a new name for OE/MT when treating OSA as 'sensorimotor muscle rehabilitation (SMR)', as some OSA patients had mainly hypotony and gnosis-praxis deficit 12 , and the training appears to provide a therapeutic tool for improving motor tongue function and oral stereognosis ability 13 . Recent animal research has provided evidence suggesting that OE/MT (tongue training) may enhance upper airway stability by potentially augmenting the corticomotor excitability of the genioglossus muscle measured by transcranial magnetic stimulation (TMS) 14 . Human studies have reported abnormalities in cortical excitability in OSA patients, characterized by elevated resting motor threshold (RMT) and cortical silent period 15 , as well as diminished neural plasticity 16 . The functional significance of training-induced plasticity in corticomotor control of the orofacial muscles are extrapolated to be associated with oral motor function enhancement 17 . The limitations of OE/MT as an integrated training modality are that, the non-standardized training regimens makes it challenging to draw solid conclusions from the available evidence and determine the effects of each specific exercise on the overall result 8 , 9 . To our knowledge, no studies have investigated the sensorimotor effect of the different training subsets of OE/MT on corticomotor excitability in tongue muscles by TMS. Therefore, this study aimed to explore the sensorimotor rehabilitation effects of OE/MT tasks in healthy humans to better understand normal physiology of the tongue before and after these different tasks. We hypothesized that the OE/MT intervention influences corticomotor excitability and oral stereognosis as well as other measures of oropharyngeal function compared to a control task (no training). Results Of the 27 participants screened for the study, 22 (11 men,11 women, mean age 23.9 ± 3.2 years, range from 20 to 31 years) completed all sessions. Five participants were excluded due to discomfort with the tongue electrode or TMS. Corticomotor Excitability There was a significant interaction between group and time (F 2,63 = 6.559, P = 0.003), where the participants in the TT group increased the tongue MEP amplitude after training (Sidak: P < 0.001); the MEPs at 120% and 160% MT were significantly higher after training (Sidak: P 0.050, Fig. 1 a, c). In addition, there was a significant main effect of time and intensity of stimulation on the MEP amplitude (F 1,63 = 7.565, P = 0.008 and F 3.189 = 71.191, P < 0.001, respectively) but no main effect of training was observed in TT group (F 2,63 = 1.068, P = 0.350). There was a significant main effect of stimulus intensity (F 3,189 = 77.914, P < 0.001), however, no effect of time and group (F 1,63 = 0.557, P = 0.458 and F 2,63 = 0.004; P = 0.996, respectively) and no interaction between these factors for FDI MEPs (Figs. 1 d-f). There were no significant effects of training on MT for any of the tested muscles (tongue: F 2,63 =1.885; P = 0.160 and FDI: F 2,63 = 1.336; P = 0.270, Tables 1 and 2 ). Table 1 Mean and standard error of the mean (SE) of the tongue corticomotor map area, volume, RMT, and center of gravity (CoG) measures pre- and post-training in BT, TT, and CT groups. Different lowercase letters in the same row indicate significant within-group differences. *Repeated-measure ANOVA, following pairwise post hoc comparisons (P 10 µV (cm 2 ) 6.6 ± 0.5 6.6 ± 0.5 Volume (µV × cm 2 ) 66.6 ± 15.7 73.1 ± 17.3 RMT 39.8 ± 1.5 39.5 ± 1.5 CoG ant-post (cm) 2.9 ± 0.1 2.9 ± 0.1 CoG med-lat (cm) 10.0 ± 0.1 10.0 ± 0.1 Tongue training (n = 22) Area > 10 µV (cm 2 ) 6.6 ± 0.4 7.5 ± 0.4 Volume (µV × cm 2 ) 52.7 ± 8.2 98.6 ± 12.7* RMT 39.5 ± 1.6 38.9 ± 1.6 CoG ant-post (cm) 3.0 ± 0.1 2.9 ± 0.1 CoG med-lat (cm) 10.1 ± 0.02 10.0 ± 0.1 Control training (n = 22) Area > 10 µV (cm 2 ) 6.5 ± 0.5 6.8 ± 0.4 Volume (µV × cm 2 ) 53.6 ± 6.6 52.0 ± 7.2 RMT 38.9 ± 1.7 38.9 ± 1.7 CoG ant-post (cm) 3.0 ± 0.1 2.9 ± 0.1 CoG med-lat (cm) 10.1 ± 0.1 10.1 ± 0.1 Table 2 Mean and standard error of the mean (SE) of the FDI corticomotor map area, volume, RMT, and center of gravity (CoG) measures pre- and post-training in BT, TT, and CT groups. Outcome Pre-training Post-training Breathing training (n = 22) Area > 10 µV (cm 2 ) 6.8 ± 0.4 7.2 ± 0.4 Volume (µV × cm 2 ) 346.4 ± 66.1 367.7 ± 73.4 RMT 36.6 ± 1.9 36.6 ± 1.9 CoG ant-post (cm) 1.0 ± 0.1 0.9 ± 0.1 CoG med-lat (cm) 6.0 ± 0.1 6.0 ± 0.1 Tongue training (n = 22) Area > 50 µV (cm 2 ) 6.5 ± 0.5 6.9 ± 0.5 Volume (µV × cm 2 ) 356.5 ± 77.2 369.0 ± 82.0 RMT 37.7 ± 1.7 36.6 ± 1.7 CoG ant-post (cm) 0.9 ± 0.1 0.8 ± 0.1 CoG med-lat (cm) 6.0 ± 0.1 6.0. ± 0.1 Control training (n = 22) Area > 50 µV (cm 2 ) 6.4 ± 0.6 7.0 ± 0.4 Volume (µV × cm 2 ) 335.8 ± 64.1 338.1 ± 64.2 RMT 36.6 ± 1.9 36.6 ± 1.9 CoG ant-post (cm) 0.9 ± 0.1 0.9 ± 0.1 CoG med-lat (cm) 6.0 ± 0.1 6.0 ± 0.1 Figure 2 shows the training effects on the tongue muscle corticomotor mapping. For the mapping area, there was no significant interaction between group and time (F 2,63 = 1.623, P = 0.205), and no main effect of training was observed (F 2,63 = 0.401, P = 0.671); nevertheless, the mapping volume presented a significant interaction between group and time (F 2,63 = 5.164, P = 0.008), where the mapping volume was increased after the training when compared to the pre-training values only in the TT group (Sidak: P < 0.001, Table 2 and Fig. 1 ). In addition, a main effect of time was presented for the mapping volume (F 1,63 = 14.625, P < 0.001), where the values after training were larger than pre-training (Sidak: P < 0.001). The mapping area and volume for FDI muscle were not significantly dependent on the interaction between group and time and training (area: F 2,63 = 0.183 P = 0.833; volume: F 2,63 = 0.065, P = 0.937, Fig. 3 ). There were no significant changes among sessions for any COG outcomes (P > 0.050, Tables 1 and 2 ). Functional Assessment of Orofacial Muscular Pressure and Force, PEFR and Oral Stereognosis Ability Table 3 presents the secondary outcomes of the assessment pre- and post-training. RM-ANOVA showed no significant interaction effects of group and time on any of the secondary outcomes: tongue lifting pressure (F 2,63 = 1.56, P = 0.218); tongue protrusion pressure (F 2.63 = 1.308, P = 0.277); left cheek pressure (F 2,63 = 0.785, P = 0.461); right cheek pressure (F 2,63 = 0.663, P = 0.534); lip closure pressure (F 2,63 = 0.525, P = 0.594); PEFR (F 2,63 = 0.999, P = 0.374); and oral stereognosis ability (F 2,63 = 0.170, P = 0.844). In addition, there was also no main effect of time and group on secondary outcomes (P > 0.007). Table 3 Assessment of secondary outcomes pre- and post-training in BT, TT and CT groups. Outcome Pre-training Post-training Breathing training (n = 22) Tongue lifting pressure (kPa) 33.2 ± 2.2 33.7 ± 2.3 Tongue protrusion pressure (kPa) 27.7 ± 1.9 28.0 ± 1.9 Cheek pressure left (kPa) 14.6 ± 0.8 15.1 ± 0.7 Cheek pressure right (kPa) 15.5 ± 0.7 16.0 ± 0.6 Lip closure pressure (kPa) 6.4 ± 0.6 6.7 ± 0.6 Peak expiratory flow rate (L / min) 458.0 ± 24.6 464.5 ± 24.2 Oral stereognosis test score 20.5 ± 0.5 21.0 ± 0.5 Tongue training (n = 22) Tongue lifting pressure (kPa) 32.8 ± 2.2 34.2 ± 2.6 Tongue protrusion pressure (kPa) 28.0 ± 2.1 29.2 ± 2.4 Cheek pressure left (kPa) 15.1 ± 0.8 15.1 ± 0.9 Cheek pressure right (kPa) 15.7 ± 0.8 15.8 ± 0.8 Lip closure pressure (kPa) 6.3 ± 0.5 6.4 ± 0.6 Peak expiratory flow rate (L / min) 459.2 ± 25.6 460.9 ± 25.4 Oral stereognosis test score 20.5 ± 0.7 20.9 ± 0.5 Control training (n = 22) Tongue lifting pressure (kPa) 31.9 ± 2.3 32.1 ± 2.3 Tongue protrusion pressure (kPa) 27.7 ± 2.0 27.9 ± 2.0 Cheek pressure left (kPa) 14.7 ± 0.8 15.0 ± 0.8 Cheek pressure right (kPa) 15.8 ± 0.7 16.3 ± 0.7 Lip closure pressure (kPa) 6.4 ± 0.6 6.5 ± 0.6 Peak expiratory flow rate (L / min) 464.1 ± 23.2 464.0 ± 23.8 Oral stereognosis test score 20.7 ± 0.6 21.0 ± 0.5 Table 4. Mean and standard error of the mean (SE) of self-reported 0-100 NRS motivation, fun, pain, fatigue, and difficulty scores pre- and post-training in BT, TT, and CT groups. Different lowercase letters in the same row indicate significant within-group differences. *Repeated-measure ANOVA, following pairwise post hoc comparisons (P < 0.050). Outcome Pre-training Post-training Breathing training (n = 22) Motivation 63.2 ± 4.3 62.0 ± 4.0 Fun 53.9 ± 4.1 53.4 ± 3.9 Pain 0.0 0.9 ± 0.9 Fatigue 4.5 ± 2.7 14.1 ± 3.7* Difficulty 18.0 ± 5.1 18.4 ± 5.2 Tongue training (n = 22) Motivation 66.4 ± 3.9 66.0 ± 4.5 Fun 61.1 ± 5.1 59.1 ± 5.5 Pain 0.0 0.5 ± 0.5 Fatigue 4.5 ± 2.6 16.6 ± 3.9* Difficulty 14.1 ± 3.5 18.0 ± 3.5 Control training (n = 22) Motivation 66.1 ± 4.5 63.4 ± 4.6 Fun 60.7 ± 4.2 58.9 ± 4.2 Pain 0.0 0.5 ± 0.5 Fatigue 5.0 ± 2.6 17.5 ± 4.8* Difficulty 18.2 ± 5.7 18.6 ± 5.3 Self-Reported NRS Table 4 shows that there were no significant effects of training on motivation, fun, pain, and difficulty NRS (P > 0.050), and all groups showed significantly higher fatigue score post-training than that of pre-training (F 1,63 = 28.536, P < 0.001). Discussion This mechanistic study provides novel evidence that a single session of tongue training (TT), but not breathing training (BT), can elicit neuroplastic changes in the corticomotor regulation of the tongue musculature in healthy individuals. The MEP amplitude and cortical motor map volume substantially increased following a single 40-minute session of multidirectional TT. Furthermore, the observed alterations seemed to be limited to training-specific muscles, as there was no indication, based on cortical and MEP characteristics, of any plasticity in the FDI muscle linked with the learning of the different training movements. Our previous research has shown that standardized tongue protrusion training (TPT) can induce corticomotor neuroplasticity 18 . To investigate the underlying mechanisms of the therapeutic benefits of TT as part of a OE/MT for patients with OSA, we deviated from our previously established TPT paradigm. Instead, we provided participants with a clinical and commonly employed TT task for OSA. The observed increase in the stimulus-response MEP induced by TMS immediately after the training session aligns with findings from other investigations on short-term TPT ranging between 15 minutes and 1 hour 19 , 20 . Furthermore, one study reported that 41 minutes of tongue lifting training (TLT) increased the tongue's corticomotor excitability and in addition also the excitability of the masseter muscle 21 . In a subsequent study from our group, an interesting but rationale finding was that jaw protrusion training in turn promoted neuroplasticity of corticomotor control of tongue muscles 22 , leading to more attention on the possible effects of mandibular advancement devices (MAD) in patients with OSA. It suggested that the efficacy of these devices may not solely be attributed to anatomical factors, such as the opening of the upper airway through the forward repositioning of the genioglossus muscle 23 . Matsuzaki and Costa et al. demonstrated that the use of MAD resulted in the induction of neuroplasticity within the corticomotor circuit associated with the muscles of the tongue and masseter in both healthy individuals and in patients with OSA, respectively 24 , 25 The observed outcomes might be ascribed to the convergence of the motor cortical region responsible for controlling the tongue and jaw muscles. This convergence is likely due to the close physical proximity of these muscles and the need for their motor activities to be coordinated 22 . In addition, a notable augmentation in the amplitude of MEPs was detected, accompanied by a substantial rise in cortical map volume after TT. In contrast, the mapping outcomes in the BT and CT groups exhibited no changes. The RMT, mapping area (> 10 µV), and CoG of tongue muscle before and after BT, TT, and CT did not change. The findings presented in this research align with the outcomes of a prior survey on short-term TT 20 . In that earlier study, no significant expansion of the tongue motor map region was seen, and there were no discernible changes in the CoG coordinates for tongue skill, strength, and passive training paradigm 20 . Compared to the expansion of the mapping area in the relative long-term training studies 21 , 26 , it seems that changes in MEP and the extension of the map area do not occur at a parallel pace with improvement in motor performance. This finding is consistent with a previous study that reported a lack of cortical expansions but did find significant associations between improvements in success rate and increased facilitation of the MEP amplitudes after a one-hour TPT session 27 . It is possible that the expansion of the map area may not exhibit a linear correlation with enhancements in motor performance due to its manifestation in the later, gradual stage of training. Furthermore, distinct stages of training may be facilitated by various mechanisms of neuroplasticity 28 . Costa et al. proposed the inclusion of additional map features in the assessment of cortical representations, specifically in areas that are typically determined by a threshold of 5 µV or 10 µV. These additional features, such as volume and areas ≥ 50% max, allow for a more comprehensive evaluation of the topography of cortical representations 29 . Incorporating these features takes into account the natural variation in the individuals' excitability at baseline and enhances the sensitivity to detect even minor changes in cortical maps resulting from short-term interventions. In the current study, we decided to utilize orofacial musculature pressure as the primary measure of performance data rather than task accuracy. This decision was based on previous research findings, which have demonstrated that various training subtypes of OE/MT can improve respiratory muscle tone and strength, thereby enhancing upper airway stability 30 . Additionally, OE/MT has been shown to increase tongue strength, facilitate forward tongue repositioning 13 , and augment labial closure force to ameliorate mouth breathing 31 . No significant changes were seen in any of the orofacial musculature pressure outcomes after the interventions of BT and TT in the present study. This lack of significant change may be attributed to the relatively short period of the training session, which lasted for 40 minutes, compared to the studies conducted on patients with OSA, which typically spanned at least for two weeks. The findings of this study are consistent with previous research, which also found no statistically significant change in electromyographic (EMG) root-mean-square and tongue protrusion pressure following either 40 minutes or 5 days of TLT 21 . One of the notable discoveries in recent animal studies is that an 8-week tongue strength and skill training regimen has been found to have several significant effects. These include increased EMG activity, maximum voluntary force, and corticomotor excitability of the tongue muscle. Additionally, this training has been shown to enhance the stability of the upper airway, as measured by critical pressure 14 . The findings from prior research investigating the influence of various training regimens on neuroplasticity have shown inconclusive results 32 , 33 . The TT paradigm used in this research was a combination of skill training, which consisted of random sequenced and multidirectional exercises and endurance training. Previous studies on TT in humans utilizing an oral typing keyboard have shown that multidirectional training leads to a greater functional engagement of motor cortical neurons than bidirectional training. Multidirectional training has been found to induce neuroplasticity, characterized by both positive and negative change sites on the motor map 34 . A study conducted on nonhuman primates has demonstrated that training in three different directions of tongue protrusion increases the firing rate of direction-sensitive neurons. This increase in firing rate is observed not only in the tongue-MI but also in the tongue-SI. In the tongue-SI, individual neurons exhibit significant changes in spiking activity that correspond to the direction of tongue protrusion 35 . Improvements in the monkeys' behavioral performance were accompanied by neuronal changes occurring in parallel in face-MI and face-SI over short (within minutes) and long (over days) time scales 36 . Sessle et al. also reported an increased number of face-SI and face-MI neurons showing tongue protrusion-related activity and lingual mechanosensory receptive fields after weeks of tongue-task training in monkeys 37 , and increased sensory inputs caused by training or stimulation can also induce face MI neuroplasticity in humans 38 . In addition to its involvement in orofacial motor control, the face-SI also plays a significant role in touch localization and stereognosis. One retrospective study reported that 11–18% of pediatric and adult patients with OSA exhibited atypical tongue stereognosis and praxis abilities 12 . That study revealed that impairments in the cortical imprinting processing of tongue stereognosis and praxis abilities during early development may persist as dysfunctions into adulthood 12 . Likewise, Wallace et al. suggested that individuals with OSA have diminished upper airway sensation, which may play a role in OSA's pathogenesis and might serve as a therapeutic intervention target 39 . A pilot study discovered that people with OSA showed improvements in tongue strength and oral stereognosis ability after smartphone-guided OE/MT treatment, and the authors suggest that the sensory muscle rehabilitation may be attributed to brain stimulation through proprioceptive training 13 . The present study found that the oral stereognosis score exhibited no significant changes following a short-term TT and BT session. This outcome can be attributed to the fact that the participants were in good health and predominantly in their early twenties. The average accuracy in the current research, around 85%, aligns with the findings of a previous study examining young, healthy individuals, which reported accuracy rates ranging around 87% 40 . The current study requires acknowledgment of certain limitations. Initially, it should be noted that the duration of the training was relatively brief. Further studies are needed to evaluate the effect of TT in an OE/MT on motor cortex neuroplasticity from a long-term perspective. Furthermore, monitoring the specific training effects (accuracy, precision) was not conducted. Several studies have conducted additional observations to monitor TT outcomes 20 , 41 . Considering the inherent features of the present cross-over study approach, the corresponding wash-out period and overall study duration will be multiplied if the training duration is prolonged and the subsequent changes are monitored. Nevertheless, the present study represents a feasible model to examine such parameters before clinical studies are designed. Second, only tongue muscle TMS-related outcomes were measured. Other oropharyngeal muscle TMS measurements were not conducted due to technological limitations. Specifically, participants would have required a trans-nasally intraluminal catheter with electrodes to record MEP over the pharyngeal motor cortex. Thirdly, the distinction between the impact of cortical and hypoglossal neurons on MEP alterations was not made in our study. Fourth, while OMT is commonly recommended for individuals with mild to moderate OSA or those who cannot tolerate CPAP therapy, there is currently a lack of research investigating the impact of various subtypes of OE/MT on the central nervous system in human participants. Therefore, this study aimed to assess the effects of different subtypes of OE/MT on the central nervous system in healthy participants, as no previous studies have explored this aspect. Hence, further research is warranted to explore the neurophysiological impact of OE/MT in individuals diagnosed with OSA. This includes examining the potential correlation between neuroplastic alterations and enhancements in tongue strength, upper airway stability, and sensory function. In conclusion, this study offers additional support for the potential therapeutic mechanisms of OE/MT by demonstrating that performing a clinically feasible TT can elicit a unique plasticity of corticomotor excitability associated with tongue motor control. Further investigation is warranted to determine the neurophysiological and therapeutic effects of OE/MT in a long-term perspective in patients diagnosed with OSA. The present study has helped to determine the feasibility and necessity for multi-dimensional assessment of OE/MT in order to better understand mechanisms associated to OSA and its management. Methods Participants Twenty-seven healthy individuals (40.7% women; mean age 24.1 ± 3.1 years) were recruited for preliminary screening. The volunteers were recruited by advertising on a webpage of the Section for Orofacial Pain and Jaw Function, Aarhus University, Denmark ( http://odont.au.dk/om-odontologi/sektioner/kof/ ) and other social media platforms. Inclusion criteria were defined as age > 18 years, right-handedness and no ongoing orofacial pain or other types of chronic pain in the last 6 months (pain-related TMD symptoms were excluded using the TMD pain screener) 42 . Exclusion criteria included the presence of possible OSA issues (STOP-BANG score ≥ 3) 43 , neuromuscular diseases, significant craniofacial abnormalities, a short tongue frenum, extensive nasal obstruction, or a history of oropharyngeal surgery, the presence of contraindications to TMS, such as metal implants in the cranium, history of epilepsy, and pregnancy 44 . The study was conducted in accordance with the second version of the Helsinki Declaration and with regional ethics committee approval (1-10-72-9-23, Aarhus University). All participants were allowed to be accompanied with family or acquaintances while explaining the procedure. Study design This mechanistic study was conducted utilizing a cross-over design comprising three sessions, with a minimum of one week gap between the sessions to avoid any carry-over effects following the previous studies 26 , 45 . Each session entailed one of the three different training tasks: breathing training (BT), tongue training (TT), or control training (CT: no training). The allocation of tasks to participants was randomized (Fig. 4 A). Before and immediately after each training session, corticomotor excitability was assessed by TMS. At the same time, the assessments of orofacial muscular pressure and force, peak expiratory flow rate (PEFR), oral stereognosis ability, and self-reported numerical rating scales (NRS) questionnaire were conducted to evaluate the impact of the interventions. Training Tasks The BT and TT were derived from the evidence-based systematic and literature review on myofunctional therapy for OSA 9 , 10 . Detailed information on training task modalities and examples are shown in (Figs. 4 B and 5 ). Each task was accompanied by a PowerPoint file that counted the time and instructed the participant to perform the corresponding training maneuver. BT consisted of three exercises (Fig. 5 -a, b, and c): BT1. Breathe in maximally through the nose and exhale maximally through the mouth using a straw placed in a glass of water and make bubbles whenever possible (Fig. 5 a); BT2. Inhale maximally through the nostril and exhale through the mouth with sufficient force to inflate a balloon. Repeat without removing the balloon from the mouth (Fig. 5 b); BT3. Breathe in maximally through one nostril and exhale maximally through the other while closing the other nostril with the subject’s thumb (Fig. 5 c). A 30-second interval was permitted between each task. The total duration of the BT session was 40 minutes. TT series consisted of six exercises (Fig. 5 d, e, f, g, h, and i): TT1. Press the entire tongue against the front of the palate as firmly as possible for four seconds and slide the tongue backward (Fig. 5 d); TT2. Protrude the tongue tip forward as far as possible and maintain this position for four seconds (Fig. 5 e); TT3 and TT4. Move the tongue to the left and right corner of the mouth as far as possible and maintain this position for four seconds (Fig. 5 f and j). TT5. Stick out the tongue, reach the chin with the tongue tip as far as possible, and maintain this position for four seconds (Fig. 5 h); TT6. Stick out the tongue to reach the nose with the tip as far as possible and maintain this position for four seconds (Fig. 5 i). There was a 30-second break between each series (= TT1–TT6). The total duration of the TT was 40 minutes. CT (sham therapy) consisted of 40 minutes of exercises without therapeutic function (relaxation and stretching of the neck muscles). Corticomotor Excitability assessed by Transcranial Magnetic Stimulation (TMS) The TMS technique was used to trigger motor-evoked potentials (MEP) in order to assess the corticomotor excitability and the possible effects of the training tasks. The participants were seated on a dental chair in a reclined position supported by headrest. An elastic silicone cap was placed over the head, standardized based on anatomical markers and following the International 10–20 Electrode Placement System guidelines 46 . The electromyographic (EMG) activity was recorded from the right side of the tongue dorsum and FDI (First Dorsal Interosseous) muscle by placing disposable self-adhesive silver chloride electrodes (ALMEVAN, Myotrace, Spain) on the right dorsal surface of the tongue (2–3 mm from midline, 10 mm from tongue tip) with an inter-electrode distance of 20 mm 20 , while disposable surface electrodes (Ambu, Neuroline 720, Denmark) were placed over the right FDI 19 . The sampling rate was 4 kHz and the EMG signals were amplified, filtered (10–3,000 kHz) and stored in an electrodiagnostic system (Sierra Summit, CADWELL, USA). TMS (Magstim 200, The Magstim Co. Ltd., UK) pulses were delivered with a 5 cm diameter focal figure–of–eight stimulating coil to the left side of the scalp. The coil of the stimulator was oriented 45° obliquely to the sagittal midline so that the induced current flowed perpendicular to the estimated alignment of the central sulcus 41 . Following previous studies, MEPs in the right tongue musculature could be evoked by stimulation of discrete areas of the left scalp, approximately 2–3 cm anterior to the vertex (Cz) and 7–10 cm lateral to the midsagittal plane. The MEPs from the FDI (control) were evoked by stimulation of the scalp about 1 cm anterior to the Cz line and about 6 cm lateral to the midsagittal plane 20 , 41 . Markings on the coil and reference lines on the cap helped identify the position related to the scalp sites. The cranium locations ('hot spots') at which EMG responses were elicited in the tongue or FDI muscles at the weakest stimulus amplitude were identified and used for subsequent stimulations. The motor threshold (MT) was determined in the relaxed muscles using a descending and ascending method and was defined as the minimum stimulus intensity that elicited 5 out of 10 discrete MEPs that were distinguishable from the background EMG activity (tongue MEP > 5 µV and FDI MEP > 50 µV) 41 . The MEPs were recorded using a stimulus–response (S-R) curve, followed by a corticomotor mapping evaluation. Peak-to-peak amplitudes were measured for 0.9, 1.0, 1.2, and 1.6 times the MT, where MT was measured each time the S–R curve was created 45 . The MEP amplitude (µV) was the mean of 12 stimuli administered at each stimulus level with a 10–15 s interval between stimuli. For corticomotor mapping, each grid site received 8 stimuli at 1.2 times the MT. The grid was stimulated in a fixed pattern, beginning in the center of the hotspot and moving anteriorly and posteriorly at increasing and decreasing latitudes (the sites typically covered 3 cm from Cz and 3 cm anterior and posterior to the interaural line, which corresponded to a total of 9 grids with 1 cm steps) 25 . When the amplitude of MEPs exceeded 5 µV (tongue) and 50 µV (FDI), the grid point was counted as positive and analyzed. In addition, the volume of the map was computed by averaging the MEP amplitudes at each grid point 29 . Following Ridding et al., the center of gravity (CoG) was calculated to identify potential alterations in each muscle's representation on the motor cortex maps 47 . Orofacial Muscular Pressure and Force Measurements of tongue lifting and protrusion pressure; lip and cheek closure pressure were recorded in kilopascals (kPa) with the use of a pressure measurement device (TPM-01, JMS Co.Ltd., Japan), by pressing a disposable standardized air-filled bulb connected to a probe. To measure anterior tongue lifting pressure, the bulb was positioned on the anterior part of the palate with the lips closed. The participants then raised their tongues and compressed the bulb onto the palate. Tongue protrusion pressure was measured with the bulb positioned behind the upper and lower incisors; the probe was placed horizontally in the cuspid and premolar region, lightly bitten and held in position. Participants were instructed to protrude the tongue as hard as possible against the lingual surface of the anterior teeth 48 . For lip pressure, the bulb was centered in front of the upper central incisors. The participants were instructed to purse their lips and compress the bulb between the lips and the labial surface of the anterior teeth while maintaining the teeth occluded. To measure cheek pressure, the bulb was positioned in the space between the upper and lower first molars and the buccal mucosa on both sides; the participants then closed their lips and compressed the bulb against the buccal surface of the molars 49 . Three measurements were taken, with the maximum value being recorded. Peak Expiratory Flow Rate (PEFR) PEFR measurements were recommended over respiratory muscle strength (RMS) measurements to assess respiratory function without lung disorders. Direct evidence of a correlation between PEFR and RMS has been reported in a previous study 50 . PEFR was measured by a digital peak flow meter (asma-1, Vitalograph, UK) with a disposable mouthpiece. Volunteers were instructed to take a maximum inhalation, followed by a maximum rapid and intense exhalation. Three measurements were taken, with the maximum value being recorded. Oral Stereognosis Ability Six small test pieces with the most extended side length or diameters equal to 10 mm were used and combined into three pairings of related shapes, such as a) circle and ellipse, b) square and rectangle, and c) triangle and semicircle 40 . The test pieces were constructed from 3D-printed and sterilizable materials to allow free oral manipulation (VOVO V-Print SG, VOCO GmbH, Germany), and dental floss was affixed to prevent aspiration. A chart depicting the enlarged forms of the test pieces was used as an identification aid to illustrate the procedure. After the explanation, participants had to wear a blindfold and were not informed of the test results. Each test piece was placed on the tongue of the participants in a random order, which was the same for all participants. The participants were free to manipulate the test piece in their mouths without using their teeth to help. The participants raised their hands when they could provide a distinguishable result, and after the examiner removed the test piece, the participant provided their responses. Using a three-point scale, each response was graded. The correct, partially correct, and incorrect responses were awarded 2, 1, and 0 points, respectively. If the response was not precise but fell within the group shape, it is partially correct. The test was carried out twice, and the cumulative score ranged from zero to twenty-four points. Self-Reported Numeric Rating Scales Participants reported perceived levels of motivation, fun, pain, fatigue, and difficulty before and after the training tasks. These were reported using separate 0–100 numerical rating scales (NRS). On the scale, ‘0’ indicated no motivation, fun, pain, fatigue, or difficulty, and ‘100’ indicated the highest level of motivation, fun, pain, fatigue, or difficulty 25 . Statistical Analysis The following outcome variables were evaluated: (a) MEP and corticomotor mapping of the tongue and FDI muscles (primary outcomes); (b) functional assessment of Orofacial Muscular Pressure and Force, Peak Expiratory Flow Rate (PEFR), Oral Stereognosis Ability; and c) Self-Reported NRS (secondary outcomes). All outcome variables were reported as means and standard error of means (SE) unless otherwise noticed. Normal distribution was assessed with Q-Q plots, and Ln transformations were applied to the continuous variables when needed. Based on previous studies 25 , 45 , it was expected that a medium effect size of 0.2 for the differences in corticomotor excitability would be possible to detect considering the within-between interactions from ANOVA with a power of 80% and a significance level of 5%. Therefore, the sample size estimation was considered to include at least 22 participants. One between-subject factor, i.e., group—3 levels (BT, TT and CT), and two within-subject factors, i.e., time—2 levels (pre- and post-training) and stimulus intensity—4 levels (0.9, 1.0, 1.2 and 1.6 times the MT), were considered in a mixed ANOVA to assess differences in the tongue and FDI MEP amplitude. In addition, repeated-measure ANOVA was performed to assess differences in the MT, map area, volume (Ln transformed values), and CoG, orofacial muscular pressure, PEFR, oral stereognosis ability and NRS scores between the groups (between-subject factor—3 levels), with time—2 levels (pre and post training) serving as the within-subject factor. When appropriate, post hoc analyses using the Sidak test were conducted. The significance level was established at 5% (P = 0.050). The adjustment was made to account for these outcomes (N = 7) due to the multiple comparisons in the secondary outcome analyses. Therefore, we implemented the Bonferroni correction and established the significance level at 0.05/7 (P = 0.007). Declarations Competing interest The authors declare no competing interests. Informed consent An informed and written consent form agreeing to participate was obtained from each patient. Additional information Correspondence and requests for materials should be addressed to T.A. Author Contributions Dongxiang Mi : Methodology; Investigation; data curation; formal analysis; writing – original draft. Eduardo Castrillon : Conceptualization; methodology; project administration; formal analysis; writing – review and editing. Mohit Kothari : Conceptualization; methodology; project administration; formal analysis; writing – review and editing. Taro Arima : Conceptualization; methodology; writing – review and editing; funding acquisition; supervision. Peter Svensson : Conceptualization; methodology; project administration; formal analysis; writing – review and editing; funding acquisition; supervision. Funding Open access funding provided by Suzhou Vocational Health College. The study was funded by the Danish Dental Association and Japan Science and Technology Agency SPRING, Grant Number JPMJSP2119. Data Availability Statement The data supporting the findings of this study are available from the corresponding author upon reasonable request. Due to ethical considerations, access to the data is subject to restrictions. References Huang, Z. et al. Dental sleep-related conditions and the role of oral healthcare providers: A scoping review. Sleep. Med. Rev. 67 10.1016/j.smrv.2022.101721 (2023). Gottlieb, D. J. & Punjabi, N. M. Diagnosis and Management of Obstructive Sleep Apnea: A Review. JAMA 323 , 1389–1400. 10.1001/jama.2020.3514 (2020). Benjafield, A. V. et al. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8664438","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":587550887,"identity":"3919ef5b-a962-4a58-a4f0-143a4f2a56dc","order_by":0,"name":"Dongxiang Mi","email":"","orcid":"","institution":"Hokkaido University","correspondingAuthor":false,"prefix":"","firstName":"Dongxiang","middleName":"","lastName":"Mi","suffix":""},{"id":587550889,"identity":"89ab2ea0-e36e-4e4f-9470-7929599a6efd","order_by":1,"name":"Eduardo Castrillon","email":"","orcid":"","institution":"Aarhus University","correspondingAuthor":false,"prefix":"","firstName":"Eduardo","middleName":"","lastName":"Castrillon","suffix":""},{"id":587550891,"identity":"d52103a8-fc7b-4299-b58f-b6e485ae16ab","order_by":2,"name":"Mohit Kothari","email":"","orcid":"","institution":"Hammel Neurorehabilitation Centre and University Research Clinic, Aarhus University","correspondingAuthor":false,"prefix":"","firstName":"Mohit","middleName":"","lastName":"Kothari","suffix":""},{"id":587550896,"identity":"14911422-872d-4e58-8b7f-80a80e4c57e2","order_by":3,"name":"Taro Arima","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA50lEQVRIiWNgGAWjYHACxgc8QNKAgY2BgYdBAixkgE89UDWzAcla2CSQtBAB7NnPPqt4U3GHwZy9LU3iTY0FA3/7AYbiAny28KSb3Zxz5hmDZc+xY5JzjkkwSJxJYDCegddhaWy3edsOMxjcSG+T5mED+uUGA4MxPhfy8D9jK+b9B9PyT4JBnqAWiTQ2Zt4GkJa0Y9K8bRJABiEtN54xA71wmMfgzLFky7l9EjyGZxIb8PqFvT+N8cObmsNyBsfbDG+8+VYnJ3f88DFjfCEGtw2JwdhmTIQOVMD8mGQto2AUjIJRMJwBALpVQp7/gG+wAAAAAElFTkSuQmCC","orcid":"","institution":"Hokkaido University","correspondingAuthor":true,"prefix":"","firstName":"Taro","middleName":"","lastName":"Arima","suffix":""},{"id":587550901,"identity":"f20c16ec-2328-4b5e-9016-abe1fbf8c214","order_by":4,"name":"Peter Svensson","email":"","orcid":"","institution":"National University of Singapore","correspondingAuthor":false,"prefix":"","firstName":"Peter","middleName":"","lastName":"Svensson","suffix":""}],"badges":[],"createdAt":"2026-01-22 02:38:04","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8664438/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8664438/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102397667,"identity":"9f946206-bf41-41c3-ac41-233f1851c461","added_by":"auto","created_at":"2026-02-11 10:18:50","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":8444190,"visible":true,"origin":"","legend":"\u003cp\u003eStimulus–response MEP obtained by TMS of the tongue and FDI area of the motor cortex pre and post BT (\u003cstrong\u003ea, d\u003c/strong\u003e), TT (\u003cstrong\u003eb, e\u003c/strong\u003e), and CT (\u003cstrong\u003ec, f\u003c/strong\u003e) *Significantly higher MEP post- training than pre- training (Sidak, P \u0026lt; 0.001). BT, breathing training; TT, tongue training; CT, control training. MT. motor threshold. MEP, motor evoked potential.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8664438/v1/5191f347b977244f8ed3c0a8.png"},{"id":102331026,"identity":"a82becd8-28cc-4f88-a945-0d7e632d72aa","added_by":"auto","created_at":"2026-02-10 15:14:31","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":15634415,"visible":true,"origin":"","legend":"\u003cp\u003ePre- and post- training motor cortex representation of the tongue area in BT (\u003cstrong\u003ea\u003c/strong\u003e), TT (\u003cstrong\u003eb\u003c/strong\u003e), and CT (\u003cstrong\u003ec\u003c/strong\u003e) generated by TMS of multiple scalp sites arranged in a 1×1cm2 grid. Arrows indicate directions (A anterior, L lateral, M medial, P posterior). BT, breathing training; TT, tongue training; CT, control training.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-8664438/v1/46b5a3ee048db23970d07e67.png"},{"id":102331027,"identity":"36e9e0ad-a968-4135-b56c-c9071d7c49b6","added_by":"auto","created_at":"2026-02-10 15:14:31","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":21520421,"visible":true,"origin":"","legend":"\u003cp\u003ePre- and post- training motor cortex representation of the FDI area in BT (\u003cstrong\u003ea\u003c/strong\u003e), TT (\u003cstrong\u003eb\u003c/strong\u003e), and CT (\u003cstrong\u003ec\u003c/strong\u003e) generated by TMS of multiple scalp sites arranged in a 1×1cm2 grid. Arrows indicate directions (A anterior, L lateral, M medial, P posterior). BT, breathing training; TT, tongue training; CT, control training\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-8664438/v1/bb7be56ecc132259b2f6c1b3.png"},{"id":102331028,"identity":"30699490-58f4-48fa-b8ae-c5820ce78d5f","added_by":"auto","created_at":"2026-02-10 15:14:31","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":8202438,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea\u003c/strong\u003e. Overview of the study design. Each participant was randomly assigned to one of six counterbalanced sequences (#1–6). A washout period of at least one week was allocated between sessions (BT: Breathing Training; TT: Tongue Training; CT: Control Training) to prevent carry-over effects. \u003cstrong\u003eb\u003c/strong\u003e. Timeline and protocols for the BT (Breathing Training) and TT (Tongue Training) sessions. Top panel (BT Session): Three different breathing exercises were performed in cycles: BT1; breathe in maximally through the nose and exhale maximally through the mouth using a straw placed in a glass of water and make bubbles whenever possible; BT2; breathe in maximally through the nostril and exhale through the mouth with sufficient force to inflate a balloon and repeat it without removing the balloon from the mouth, and BT3; breath in maximally through one nostril and exhale maximally through the other while closing the other nostril with the subject’s thumb. These three tasks were repeated in 9 cycles (3 tasks [BT1–3] × 9 cycles = 27 total tasks). Bottom panel (TT Session): A set of six multidirectional tongue exercises (TT1–6) constituted one task unit, which was repeated 27 times (1 unit [TT1–6] × 27 repetitions = 27 total tasks). The total duration for each session (BT, TT, and CT) was 40 minutes. Before and immediately after each training session, the assessments of corticomotor excitability, orofacial muscular pressure and force, peak expiratory flow rate (PEFR), oral stereognosis ability, and self-reported NRS (numerical rating scales) questionnaire were conducted (\u003cstrong\u003e↑\u003c/strong\u003e).\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-8664438/v1/807f53c1c42041b154164809.png"},{"id":102331030,"identity":"672a2084-f0be-4ab5-bbd0-091859224448","added_by":"auto","created_at":"2026-02-10 15:14:32","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":85125353,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea-c\u003c/strong\u003e. Examples of breathing training exercises BT1-BT3; \u003cstrong\u003ed-i\u003c/strong\u003e: Examples of tongue training exercises TT1-TT6.\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-8664438/v1/a7733bf70d6295094f122c93.png"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effects of oropharyngeal exercises / myofunctional therapy on orofacial function and corticomotor excitability in healthy individuals – implications for obstructive sleep apnea?","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIn the past two decades, dental sleep medicine has witnessed empirical evidence indicating that oral healthcare professionals can contribute to evaluating and managing obstructive sleep apnea (OSA) through multidisciplinary collaboration\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. OSA is characterized by the recurring occurrence of complete or partial obstructions in the upper airway, commonly accompanied by snoring, compromised sleep quality, and cardio-metabolic diseases\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Globally, 425\u0026nbsp;million adults have moderate to severe OSA\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Multiple community-based studies revealed that the prevalence of OSA in individuals aged 60 years and older varies between 27% and 80%\u003csup\u003e4\u003c/sup\u003e. Moreover, as individuals age, there is a gradual rise in the collapse of the oropharyngeal muscles\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. The correlation between muscle strength and OSA suggested the potential involvement of sarcopenia in the pathophysiology of OSA in elderly adults\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. There is an increasing acceptance of the presence of neurologic factors: inadequate upper-airway sensory responsiveness or motor nerve function may contribute to OSA's pathogenesis\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eRecently, beyond the oral appliances such as mandibular advancement devices (MAD) and continues positive airway pressure (CPAP), several new treatment strategies have emerged targeting oropharyngeal muscle responsiveness and control: oropharyngeal exercise / myofunctional therapy (OE/MT), hypoglossal nerve stimulation, and daytime transoral electric stimulation\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. OE/MT comprises a series of exercises designed to improve tongue position and function, the lip seal, and nasal breathing\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Although evidence has confirmed that OE/MT may improve upper airway stability and reduce daytime sleepiness\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e, the underlying mechanisms of OE/MT are not yet well understood. It is generally theorized via increased muscle tone or improved control of oropharyngeal or upper airway muscles\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Rodr\u0026iacute;guez-Alcal\u0026aacute; et al. proposed a new name for OE/MT when treating OSA as 'sensorimotor muscle rehabilitation (SMR)', as some OSA patients had mainly hypotony and gnosis-praxis deficit\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e, and the training appears to provide a therapeutic tool for improving motor tongue function and oral stereognosis ability\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Recent animal research has provided evidence suggesting that OE/MT (tongue training) may enhance upper airway stability by potentially augmenting the corticomotor excitability of the genioglossus muscle measured by transcranial magnetic stimulation (TMS)\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Human studies have reported abnormalities in cortical excitability in OSA patients, characterized by elevated resting motor threshold (RMT) and cortical silent period\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e, as well as diminished neural plasticity\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe functional significance of training-induced plasticity in corticomotor control of the orofacial muscles are extrapolated to be associated with oral motor function enhancement\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. The limitations of OE/MT as an integrated training modality are that, the non-standardized training regimens makes it challenging to draw solid conclusions from the available evidence and determine the effects of each specific exercise on the overall result\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. To our knowledge, no studies have investigated the sensorimotor effect of the different training subsets of OE/MT on corticomotor excitability in tongue muscles by TMS.\u003c/p\u003e \u003cp\u003eTherefore, this study aimed to explore the sensorimotor rehabilitation effects of OE/MT tasks in healthy humans to better understand normal physiology of the tongue before and after these different tasks. We hypothesized that the OE/MT intervention influences corticomotor excitability and oral stereognosis as well as other measures of oropharyngeal function compared to a control task (no training).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eOf the 27 participants screened for the study, 22 (11 men,11 women, mean age 23.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2 years, range from 20 to 31 years) completed all sessions. Five participants were excluded due to discomfort with the tongue electrode or TMS.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eCorticomotor Excitability\u003c/h2\u003e \u003cp\u003eThere was a significant interaction between group and time (F\u003csub\u003e2,63\u003c/sub\u003e = 6.559, P\u0026thinsp;=\u0026thinsp;0.003), where the participants in the TT group increased the tongue MEP amplitude after training (Sidak: P\u0026thinsp;\u0026lt;\u0026thinsp;0.001); the MEPs at 120% and 160% MT were significantly higher after training (Sidak: P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb). However, the BT and CT groups showed no significant difference after training (P\u0026thinsp;\u0026gt;\u0026thinsp;0.050, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea, c). In addition, there was a significant main effect of time and intensity of stimulation on the MEP amplitude (F\u003csub\u003e1,63\u003c/sub\u003e = 7.565, P\u0026thinsp;=\u0026thinsp;0.008 and F\u003csub\u003e3.189\u003c/sub\u003e = 71.191, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, respectively) but no main effect of training was observed in TT group (F\u003csub\u003e2,63\u003c/sub\u003e = 1.068, P\u0026thinsp;=\u0026thinsp;0.350). There was a significant main effect of stimulus intensity (F \u003csub\u003e3,189\u003c/sub\u003e = 77.914, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), however, no effect of time and group (F\u003csub\u003e1,63\u003c/sub\u003e = 0.557, P\u0026thinsp;=\u0026thinsp;0.458 and F\u003csub\u003e2,63\u003c/sub\u003e = 0.004; P\u0026thinsp;=\u0026thinsp;0.996, respectively) and no interaction between these factors for FDI MEPs (Figs.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ed-f). There were no significant effects of training on MT for any of the tested muscles (tongue: F\u003csub\u003e2,63\u003c/sub\u003e =1.885; P\u0026thinsp;=\u0026thinsp;0.160 and FDI: F\u003csub\u003e2,63\u003c/sub\u003e = 1.336; P\u0026thinsp;=\u0026thinsp;0.270, Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMean and standard error of the mean (SE) of the tongue corticomotor map area, volume, RMT, and center of gravity (CoG) measures pre- and post-training in BT, TT, and CT groups. Different lowercase letters in the same row indicate significant within-group differences. *Repeated-measure ANOVA, following pairwise post hoc comparisons (P\u0026thinsp;\u0026lt;\u0026thinsp;0.050).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePre-training\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePost-training\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBreathing training (n\u0026thinsp;=\u0026thinsp;22)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArea\u0026thinsp;\u0026gt;\u0026thinsp;10 \u0026micro;V (cm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e6.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e6.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume (\u0026micro;V \u0026times; cm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e66.6\u0026thinsp;\u0026plusmn;\u0026thinsp;15.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e73.1\u0026thinsp;\u0026plusmn;\u0026thinsp;17.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRMT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e39.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e39.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoG ant-post (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e2.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoG med-lat (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e10.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e10.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eTongue training (n\u0026thinsp;=\u0026thinsp;22)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArea\u0026thinsp;\u0026gt;\u0026thinsp;10 \u0026micro;V (cm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e6.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e7.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume (\u0026micro;V \u0026times; cm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e52.7\u0026thinsp;\u0026plusmn;\u0026thinsp;8.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e98.6\u0026thinsp;\u0026plusmn;\u0026thinsp;12.7*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRMT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e39.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e38.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoG ant-post (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoG med-lat (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e10.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e10.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eControl training (n\u0026thinsp;=\u0026thinsp;22)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArea\u0026thinsp;\u0026gt;\u0026thinsp;10 \u0026micro;V (cm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e6.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e6.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume (\u0026micro;V \u0026times; cm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e53.6\u0026thinsp;\u0026plusmn;\u0026thinsp;6.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e52.0\u0026thinsp;\u0026plusmn;\u0026thinsp;7.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRMT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e38.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e38.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoG ant-post (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoG med-lat (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e10.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e10.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMean and standard error of the mean (SE) of the FDI corticomotor map area, volume, RMT, and center of gravity (CoG) measures pre- and post-training in BT, TT, and CT groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePre-training\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePost-training\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBreathing training (n\u0026thinsp;=\u0026thinsp;22)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArea\u0026thinsp;\u0026gt;\u0026thinsp;10 \u0026micro;V (cm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e6.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e7.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume (\u0026micro;V \u0026times; cm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e346.4\u0026thinsp;\u0026plusmn;\u0026thinsp;66.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e367.7\u0026thinsp;\u0026plusmn;\u0026thinsp;73.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRMT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e36.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e36.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoG ant-post (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoG med-lat (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e6.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e6.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eTongue training (n\u0026thinsp;=\u0026thinsp;22)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArea\u0026thinsp;\u0026gt;\u0026thinsp;50 \u0026micro;V (cm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e6.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e6.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume (\u0026micro;V \u0026times; cm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e356.5\u0026thinsp;\u0026plusmn;\u0026thinsp;77.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e369.0\u0026thinsp;\u0026plusmn;\u0026thinsp;82.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRMT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e37.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e36.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoG ant-post (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoG med-lat (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e6.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e6.0. \u0026plusmn; 0.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eControl training (n\u0026thinsp;=\u0026thinsp;22)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArea\u0026thinsp;\u0026gt;\u0026thinsp;50 \u0026micro;V (cm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e6.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e7.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume (\u0026micro;V \u0026times; cm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e335.8\u0026thinsp;\u0026plusmn;\u0026thinsp;64.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e338.1\u0026thinsp;\u0026plusmn;\u0026thinsp;64.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRMT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e36.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e36.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoG ant-post (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoG med-lat (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e6.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e6.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows the training effects on the tongue muscle corticomotor mapping. For the mapping area, there was no significant interaction between group and time (F\u003csub\u003e2,63\u003c/sub\u003e = 1.623, P\u0026thinsp;=\u0026thinsp;0.205), and no main effect of training was observed (F\u003csub\u003e2,63\u003c/sub\u003e = 0.401, P\u0026thinsp;=\u0026thinsp;0.671); nevertheless, the mapping volume presented a significant interaction between group and time (F\u003csub\u003e2,63\u003c/sub\u003e = 5.164, P\u0026thinsp;=\u0026thinsp;0.008), where the mapping volume was increased after the training when compared to the pre-training values only in the TT group (Sidak: P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In addition, a main effect of time was presented for the mapping volume (F\u003csub\u003e1,63\u003c/sub\u003e = 14.625, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), where the values after training were larger than pre-training (Sidak: P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The mapping area and volume for FDI muscle were not significantly dependent on the interaction between group and time and training (area: F\u003csub\u003e2,63\u003c/sub\u003e = 0.183 P\u0026thinsp;=\u0026thinsp;0.833; volume: F\u003csub\u003e2,63\u003c/sub\u003e = 0.065, P\u0026thinsp;=\u0026thinsp;0.937, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). There were no significant changes among sessions for any COG outcomes (P\u0026thinsp;\u0026gt;\u0026thinsp;0.050, Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eFunctional Assessment of Orofacial Muscular Pressure and Force, PEFR and Oral Stereognosis Ability\u003c/h3\u003e\n\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e presents the secondary outcomes of the assessment pre- and post-training. RM-ANOVA showed no significant interaction effects of group and time on any of the secondary outcomes: tongue lifting pressure (F\u003csub\u003e2,63\u003c/sub\u003e = 1.56, P\u0026thinsp;=\u0026thinsp;0.218); tongue protrusion pressure (F\u003csub\u003e2.63\u003c/sub\u003e = 1.308, P\u0026thinsp;=\u0026thinsp;0.277); left cheek pressure (F\u003csub\u003e2,63\u003c/sub\u003e = 0.785, P\u0026thinsp;=\u0026thinsp;0.461); right cheek pressure (F\u003csub\u003e2,63\u003c/sub\u003e = 0.663, P\u0026thinsp;=\u0026thinsp;0.534); lip closure pressure (F\u003csub\u003e2,63\u003c/sub\u003e = 0.525, P\u0026thinsp;=\u0026thinsp;0.594); PEFR (F\u003csub\u003e2,63\u003c/sub\u003e = 0.999, P\u0026thinsp;=\u0026thinsp;0.374); and oral stereognosis ability (F\u003csub\u003e2,63\u003c/sub\u003e = 0.170, P\u0026thinsp;=\u0026thinsp;0.844). In addition, there was also no main effect of time and group on secondary outcomes (P\u0026thinsp;\u0026gt;\u0026thinsp;0.007).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssessment of secondary outcomes pre- and post-training in BT, TT and CT groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePre-training\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePost-training\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBreathing training (n\u0026thinsp;=\u0026thinsp;22)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTongue lifting pressure (kPa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e33.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e33.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTongue protrusion pressure (kPa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e27.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e28.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCheek pressure left (kPa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e14.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e15.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCheek pressure right (kPa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e15.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e16.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLip closure pressure (kPa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e6.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak expiratory flow rate (L / min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e458.0\u0026thinsp;\u0026plusmn;\u0026thinsp;24.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e464.5\u0026thinsp;\u0026plusmn;\u0026thinsp;24.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral stereognosis test score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e20.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e21.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eTongue training (n\u0026thinsp;=\u0026thinsp;22)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTongue lifting pressure (kPa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e32.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e34.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTongue protrusion pressure (kPa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e28.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e29.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCheek pressure left (kPa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e15.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e15.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCheek pressure right (kPa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e15.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e15.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLip closure pressure (kPa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e6.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e6.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak expiratory flow rate (L / min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e459.2\u0026thinsp;\u0026plusmn;\u0026thinsp;25.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e460.9\u0026thinsp;\u0026plusmn;\u0026thinsp;25.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral stereognosis test score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e20.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e20.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eControl training (n\u0026thinsp;=\u0026thinsp;22)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTongue lifting pressure (kPa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e31.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e32.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTongue protrusion pressure (kPa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e27.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e27.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCheek pressure left (kPa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e14.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e15.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCheek pressure right (kPa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e15.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e16.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLip closure pressure (kPa)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e6.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e6.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak expiratory flow rate (L / min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e464.1\u0026thinsp;\u0026plusmn;\u0026thinsp;23.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e464.0\u0026thinsp;\u0026plusmn;\u0026thinsp;23.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral stereognosis test score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e20.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e21.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003cdiv align=\"char\" class=\"colspec\"\u003e\u003cstrong\u003eTable 4.\u003c/strong\u003e Mean and standard error of the mean (SE) of self-reported 0-100 NRS motivation, fun, pain, fatigue, and difficulty scores pre- and post-training in BT, TT, and CT groups. Different lowercase letters in the same row indicate significant within-group differences. *Repeated-measure ANOVA, following pairwise post hoc comparisons (P \u0026lt; 0.050).\u003c/div\u003e\u0026nbsp;\u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOutcome\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePre-training\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePost-training\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eBreathing training (n\u0026thinsp;=\u0026thinsp;22)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMotivation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e62.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFun\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e53.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFatigue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDifficulty\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.0\u0026thinsp;\u0026plusmn;\u0026thinsp;5.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18.4\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eTongue training (n\u0026thinsp;=\u0026thinsp;22)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMotivation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e66.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFun\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e61.1\u0026thinsp;\u0026plusmn;\u0026thinsp;5.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e59.1\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFatigue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDifficulty\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eControl training (n\u0026thinsp;=\u0026thinsp;22)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMotivation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e63.4\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFun\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e58.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFatigue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDifficulty\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003ch3\u003eSelf-Reported NRS\u003c/h3\u003e\n\u003cp\u003eTable 4 shows that there were no significant effects of training on motivation, fun, pain, and difficulty NRS (P \u0026gt; 0.050), and all groups showed significantly higher fatigue score post-training than that of pre-training (F\u003csub\u003e1,63\u0026nbsp;\u003c/sub\u003e= 28.536, P \u0026lt; 0.001).\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis mechanistic study provides novel evidence that a single session of tongue training (TT), but not breathing training (BT), can elicit neuroplastic changes in the corticomotor regulation of the tongue musculature in healthy individuals. The MEP amplitude and cortical motor map volume substantially increased following a single 40-minute session of multidirectional TT. Furthermore, the observed alterations seemed to be limited to training-specific muscles, as there was no indication, based on cortical and MEP characteristics, of any plasticity in the FDI muscle linked with the learning of the different training movements.\u003c/p\u003e \u003cp\u003eOur previous research has shown that standardized tongue protrusion training (TPT) can induce corticomotor neuroplasticity\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. To investigate the underlying mechanisms of the therapeutic benefits of TT as part of a OE/MT for patients with OSA, we deviated from our previously established TPT paradigm. Instead, we provided participants with a clinical and commonly employed TT task for OSA. The observed increase in the stimulus-response MEP induced by TMS immediately after the training session aligns with findings from other investigations on short-term TPT ranging between 15 minutes and 1 hour\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Furthermore, one study reported that 41 minutes of tongue lifting training (TLT) increased the tongue's corticomotor excitability and in addition also the excitability of the masseter muscle\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. In a subsequent study from our group, an interesting but rationale finding was that jaw protrusion training in turn promoted neuroplasticity of corticomotor control of tongue muscles\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e, leading to more attention on the possible effects of mandibular advancement devices (MAD) in patients with OSA. It suggested that the efficacy of these devices may not solely be attributed to anatomical factors, such as the opening of the upper airway through the forward repositioning of the genioglossus muscle\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. Matsuzaki and Costa et al. demonstrated that the use of MAD resulted in the induction of neuroplasticity within the corticomotor circuit associated with the muscles of the tongue and masseter in both healthy individuals and in patients with OSA, respectively\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e The observed outcomes might be ascribed to the convergence of the motor cortical region responsible for controlling the tongue and jaw muscles. This convergence is likely due to the close physical proximity of these muscles and the need for their motor activities to be coordinated\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn addition, a notable augmentation in the amplitude of MEPs was detected, accompanied by a substantial rise in cortical map volume after TT. In contrast, the mapping outcomes in the BT and CT groups exhibited no changes. The RMT, mapping area (\u0026gt;\u0026thinsp;10 \u0026micro;V), and CoG of tongue muscle before and after BT, TT, and CT did not change. The findings presented in this research align with the outcomes of a prior survey on short-term TT\u003csup\u003e20\u003c/sup\u003e. In that earlier study, no significant expansion of the tongue motor map region was seen, and there were no discernible changes in the CoG coordinates for tongue skill, strength, and passive training paradigm\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Compared to the expansion of the mapping area in the relative long-term training studies\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e, it seems that changes in MEP and the extension of the map area do not occur at a parallel pace with improvement in motor performance. This finding is consistent with a previous study that reported a lack of cortical expansions but did find significant associations between improvements in success rate and increased facilitation of the MEP amplitudes after a one-hour TPT session\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. It is possible that the expansion of the map area may not exhibit a linear correlation with enhancements in motor performance due to its manifestation in the later, gradual stage of training. Furthermore, distinct stages of training may be facilitated by various mechanisms of neuroplasticity\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. Costa et al. proposed the inclusion of additional map features in the assessment of cortical representations, specifically in areas that are typically determined by a threshold of 5 \u0026micro;V or 10 \u0026micro;V. These additional features, such as volume and areas\u0026thinsp;\u0026ge;\u0026thinsp;50% max, allow for a more comprehensive evaluation of the topography of cortical representations\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. Incorporating these features takes into account the natural variation in the individuals' excitability at baseline and enhances the sensitivity to detect even minor changes in cortical maps resulting from short-term interventions.\u003c/p\u003e \u003cp\u003eIn the current study, we decided to utilize orofacial musculature pressure as the primary measure of performance data rather than task accuracy. This decision was based on previous research findings, which have demonstrated that various training subtypes of OE/MT can improve respiratory muscle tone and strength, thereby enhancing upper airway stability\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. Additionally, OE/MT has been shown to increase tongue strength, facilitate forward tongue repositioning\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e, and augment labial closure force to ameliorate mouth breathing\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. No significant changes were seen in any of the orofacial musculature pressure outcomes after the interventions of BT and TT in the present study. This lack of significant change may be attributed to the relatively short period of the training session, which lasted for 40 minutes, compared to the studies conducted on patients with OSA, which typically spanned at least for two weeks. The findings of this study are consistent with previous research, which also found no statistically significant change in electromyographic (EMG) root-mean-square and tongue protrusion pressure following either 40 minutes or 5 days of TLT\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. One of the notable discoveries in recent animal studies is that an 8-week tongue strength and skill training regimen has been found to have several significant effects. These include increased EMG activity, maximum voluntary force, and corticomotor excitability of the tongue muscle. Additionally, this training has been shown to enhance the stability of the upper airway, as measured by critical pressure\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe findings from prior research investigating the influence of various training regimens on neuroplasticity have shown inconclusive results\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e,\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e. The TT paradigm used in this research was a combination of skill training, which consisted of random sequenced and multidirectional exercises and endurance training. Previous studies on TT in humans utilizing an oral typing keyboard have shown that multidirectional training leads to a greater functional engagement of motor cortical neurons than bidirectional training. Multidirectional training has been found to induce neuroplasticity, characterized by both positive and negative change sites on the motor map\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e. A study conducted on nonhuman primates has demonstrated that training in three different directions of tongue protrusion increases the firing rate of direction-sensitive neurons. This increase in firing rate is observed not only in the tongue-MI but also in the tongue-SI. In the tongue-SI, individual neurons exhibit significant changes in spiking activity that correspond to the direction of tongue protrusion\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e. Improvements in the monkeys' behavioral performance were accompanied by neuronal changes occurring in parallel in face-MI and face-SI over short (within minutes) and long (over days) time scales\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e. Sessle et al. also reported an increased number of face-SI and face-MI neurons showing tongue protrusion-related activity and lingual mechanosensory receptive fields after weeks of tongue-task training in monkeys\u003csup\u003e\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e, and increased sensory inputs caused by training or stimulation can also induce face MI neuroplasticity in humans\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e. In addition to its involvement in orofacial motor control, the face-SI also plays a significant role in touch localization and stereognosis.\u003c/p\u003e \u003cp\u003eOne retrospective study reported that 11\u0026ndash;18% of pediatric and adult patients with OSA exhibited atypical tongue stereognosis and praxis abilities\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. That study revealed that impairments in the cortical imprinting processing of tongue stereognosis and praxis abilities during early development may persist as dysfunctions into adulthood\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Likewise, Wallace et al. suggested that individuals with OSA have diminished upper airway sensation, which may play a role in OSA's pathogenesis and might serve as a therapeutic intervention target\u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e. A pilot study discovered that people with OSA showed improvements in tongue strength and oral stereognosis ability after smartphone-guided OE/MT treatment, and the authors suggest that the sensory muscle rehabilitation may be attributed to brain stimulation through proprioceptive training\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. The present study found that the oral stereognosis score exhibited no significant changes following a short-term TT and BT session. This outcome can be attributed to the fact that the participants were in good health and predominantly in their early twenties. The average accuracy in the current research, around 85%, aligns with the findings of a previous study examining young, healthy individuals, which reported accuracy rates ranging around 87%\u003csup\u003e40\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe current study requires acknowledgment of certain limitations. Initially, it should be noted that the duration of the training was relatively brief. Further studies are needed to evaluate the effect of TT in an OE/MT on motor cortex neuroplasticity from a long-term perspective. Furthermore, monitoring the specific training effects (accuracy, precision) was not conducted. Several studies have conducted additional observations to monitor TT outcomes\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e. Considering the inherent features of the present cross-over study approach, the corresponding wash-out period and overall study duration will be multiplied if the training duration is prolonged and the subsequent changes are monitored. Nevertheless, the present study represents a feasible model to examine such parameters before clinical studies are designed. Second, only tongue muscle TMS-related outcomes were measured. Other oropharyngeal muscle TMS measurements were not conducted due to technological limitations. Specifically, participants would have required a trans-nasally intraluminal catheter with electrodes to record MEP over the pharyngeal motor cortex. Thirdly, the distinction between the impact of cortical and hypoglossal neurons on MEP alterations was not made in our study. Fourth, while OMT is commonly recommended for individuals with mild to moderate OSA or those who cannot tolerate CPAP therapy, there is currently a lack of research investigating the impact of various subtypes of OE/MT on the central nervous system in human participants. Therefore, this study aimed to assess the effects of different subtypes of OE/MT on the central nervous system in healthy participants, as no previous studies have explored this aspect. Hence, further research is warranted to explore the neurophysiological impact of OE/MT in individuals diagnosed with OSA. This includes examining the potential correlation between neuroplastic alterations and enhancements in tongue strength, upper airway stability, and sensory function.\u003c/p\u003e \u003cp\u003eIn conclusion, this study offers additional support for the potential therapeutic mechanisms of OE/MT by demonstrating that performing a clinically feasible TT can elicit a unique plasticity of corticomotor excitability associated with tongue motor control. Further investigation is warranted to determine the neurophysiological and therapeutic effects of OE/MT in a long-term perspective in patients diagnosed with OSA. The present study has helped to determine the feasibility and necessity for multi-dimensional assessment of OE/MT in order to better understand mechanisms associated to OSA and its management.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eParticipants\u003c/h2\u003e \u003cp\u003eTwenty-seven healthy individuals (40.7% women; mean age 24.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1 years) were recruited for preliminary screening. The volunteers were recruited by advertising on a webpage of the Section for Orofacial Pain and Jaw Function, Aarhus University, Denmark (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://odont.au.dk/om-odontologi/sektioner/kof/\u003c/span\u003e\u003cspan address=\"http://odont.au.dk/om-odontologi/sektioner/kof/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) and other social media platforms. Inclusion criteria were defined as age\u0026thinsp;\u0026gt;\u0026thinsp;18 years, right-handedness and no ongoing orofacial pain or other types of chronic pain in the last 6 months (pain-related TMD symptoms were excluded using the TMD pain screener)\u003csup\u003e\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e. Exclusion criteria included the presence of possible OSA issues (STOP-BANG score\u0026thinsp;\u0026ge;\u0026thinsp;3)\u003csup\u003e43\u003c/sup\u003e, neuromuscular diseases, significant craniofacial abnormalities, a short tongue frenum, extensive nasal obstruction, or a history of oropharyngeal surgery, the presence of contraindications to TMS, such as metal implants in the cranium, history of epilepsy, and pregnancy\u003csup\u003e\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e. The study was conducted in accordance with the second version of the Helsinki Declaration and with regional ethics committee approval (1-10-72-9-23, Aarhus University). All participants were allowed to be accompanied with family or acquaintances while explaining the procedure.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy design\u003c/h3\u003e\n\u003cp\u003eThis mechanistic study was conducted utilizing a cross-over design comprising three sessions, with a minimum of one week gap between the sessions to avoid any carry-over effects following the previous studies\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e,\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u003c/sup\u003e. Each session entailed one of the three different training tasks: breathing training (BT), tongue training (TT), or control training (CT: no training). The allocation of tasks to participants was randomized (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA). Before and immediately after each training session, corticomotor excitability was assessed by TMS. At the same time, the assessments of orofacial muscular pressure and force, peak expiratory flow rate (PEFR), oral stereognosis ability, and self-reported numerical rating scales (NRS) questionnaire were conducted to evaluate the impact of the interventions.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eTraining Tasks\u003c/h3\u003e\n\u003cp\u003eThe BT and TT were derived from the evidence-based systematic and literature review on myofunctional therapy for OSA\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Detailed information on training task modalities and examples are shown in (Figs.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB and \u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Each task was accompanied by a PowerPoint file that counted the time and instructed the participant to perform the corresponding training maneuver.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eBT consisted of three exercises (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e-a, b, and c): BT1. Breathe in maximally through the nose and exhale maximally through the mouth using a straw placed in a glass of water and make bubbles whenever possible (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ea); BT2. Inhale maximally through the nostril and exhale through the mouth with sufficient force to inflate a balloon. Repeat without removing the balloon from the mouth (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eb); BT3. Breathe in maximally through one nostril and exhale maximally through the other while closing the other nostril with the subject\u0026rsquo;s thumb (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ec). A 30-second interval was permitted between each task. The total duration of the BT session was 40 minutes.\u003c/p\u003e \u003cp\u003eTT series consisted of six exercises (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ed, e, f, g, h, and i): TT1. Press the entire tongue against the front of the palate as firmly as possible for four seconds and slide the tongue backward (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ed); TT2. Protrude the tongue tip forward as far as possible and maintain this position for four seconds (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ee); TT3 and TT4. Move the tongue to the left and right corner of the mouth as far as possible and maintain this position for four seconds (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ef and j). TT5. Stick out the tongue, reach the chin with the tongue tip as far as possible, and maintain this position for four seconds (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eh); TT6. Stick out the tongue to reach the nose with the tip as far as possible and maintain this position for four seconds (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ei). There was a 30-second break between each series (=\u0026thinsp;TT1\u0026ndash;TT6). The total duration of the TT was 40 minutes.\u003c/p\u003e \u003cp\u003eCT (sham therapy) consisted of 40 minutes of exercises without therapeutic function (relaxation and stretching of the neck muscles).\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eCorticomotor Excitability assessed by Transcranial Magnetic Stimulation (TMS)\u003c/h2\u003e \u003cp\u003eThe TMS technique was used to trigger motor-evoked potentials (MEP) in order to assess the corticomotor excitability and the possible effects of the training tasks. The participants were seated on a dental chair in a reclined position supported by headrest. An elastic silicone cap was placed over the head, standardized based on anatomical markers and following the International 10\u0026ndash;20 Electrode Placement System guidelines\u003csup\u003e\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e. The electromyographic (EMG) activity was recorded from the right side of the tongue dorsum and FDI (First Dorsal Interosseous) muscle by placing disposable self-adhesive silver chloride electrodes (ALMEVAN, Myotrace, Spain) on the right dorsal surface of the tongue (2\u0026ndash;3 mm from midline, 10 mm from tongue tip) with an inter-electrode distance of 20 mm\u003csup\u003e20\u003c/sup\u003e, while disposable surface electrodes (Ambu, Neuroline 720, Denmark) were placed over the right FDI\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. The sampling rate was 4 kHz and the EMG signals were amplified, filtered (10\u0026ndash;3,000 kHz) and stored in an electrodiagnostic system (Sierra Summit, CADWELL, USA). TMS (Magstim 200, The Magstim Co. Ltd., UK) pulses were delivered with a 5 cm diameter focal figure\u0026ndash;of\u0026ndash;eight stimulating coil to the left side of the scalp. The coil of the stimulator was oriented 45\u0026deg; obliquely to the sagittal midline so that the induced current flowed perpendicular to the estimated alignment of the central sulcus\u003csup\u003e\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e. Following previous studies, MEPs in the right tongue musculature could be evoked by stimulation of discrete areas of the left scalp, approximately 2\u0026ndash;3 cm anterior to the vertex (Cz) and 7\u0026ndash;10 cm lateral to the midsagittal plane. The MEPs from the FDI (control) were evoked by stimulation of the scalp about 1 cm anterior to the Cz line and about 6 cm lateral to the midsagittal plane\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e. Markings on the coil and reference lines on the cap helped identify the position related to the scalp sites. The cranium locations ('hot spots') at which EMG responses were elicited in the tongue or FDI muscles at the weakest stimulus amplitude were identified and used for subsequent stimulations. The motor threshold (MT) was determined in the relaxed muscles using a descending and ascending method and was defined as the minimum stimulus intensity that elicited 5 out of 10 discrete MEPs that were distinguishable from the background EMG activity (tongue MEP\u0026thinsp;\u0026gt;\u0026thinsp;5 \u0026micro;V and FDI MEP\u0026thinsp;\u0026gt;\u0026thinsp;50 \u0026micro;V)\u003csup\u003e41\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe MEPs were recorded using a stimulus\u0026ndash;response (S-R) curve, followed by a corticomotor mapping evaluation. Peak-to-peak amplitudes were measured for 0.9, 1.0, 1.2, and 1.6 times the MT, where MT was measured each time the S\u0026ndash;R curve was created\u003csup\u003e\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u003c/sup\u003e. The MEP amplitude (\u0026micro;V) was the mean of 12 stimuli administered at each stimulus level with a 10\u0026ndash;15 s interval between stimuli. For corticomotor mapping, each grid site received 8 stimuli at 1.2 times the MT. The grid was stimulated in a fixed pattern, beginning in the center of the hotspot and moving anteriorly and posteriorly at increasing and decreasing latitudes (the sites typically covered 3 cm from Cz and 3 cm anterior and posterior to the interaural line, which corresponded to a total of 9 grids with 1 cm steps)\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. When the amplitude of MEPs exceeded 5 \u0026micro;V (tongue) and 50 \u0026micro;V (FDI), the grid point was counted as positive and analyzed. In addition, the volume of the map was computed by averaging the MEP amplitudes at each grid point\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. Following Ridding et al., the center of gravity (CoG) was calculated to identify potential alterations in each muscle's representation on the motor cortex maps\u003csup\u003e\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eOrofacial Muscular Pressure and Force\u003c/h2\u003e \u003cp\u003eMeasurements of tongue lifting and protrusion pressure; lip and cheek closure pressure were recorded in kilopascals (kPa) with the use of a pressure measurement device (TPM-01, JMS Co.Ltd., Japan), by pressing a disposable standardized air-filled bulb connected to a probe. To measure anterior tongue lifting pressure, the bulb was positioned on the anterior part of the palate with the lips closed. The participants then raised their tongues and compressed the bulb onto the palate. Tongue protrusion pressure was measured with the bulb positioned behind the upper and lower incisors; the probe was placed horizontally in the cuspid and premolar region, lightly bitten and held in position. Participants were instructed to protrude the tongue as hard as possible against the lingual surface of the anterior teeth\u003csup\u003e\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u003c/sup\u003e. For lip pressure, the bulb was centered in front of the upper central incisors. The participants were instructed to purse their lips and compress the bulb between the lips and the labial surface of the anterior teeth while maintaining the teeth occluded. To measure cheek pressure, the bulb was positioned in the space between the upper and lower first molars and the buccal mucosa on both sides; the participants then closed their lips and compressed the bulb against the buccal surface of the molars\u003csup\u003e\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e\u003c/sup\u003e. Three measurements were taken, with the maximum value being recorded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003ePeak Expiratory Flow Rate (PEFR)\u003c/h2\u003e \u003cp\u003ePEFR measurements were recommended over respiratory muscle strength (RMS) measurements to assess respiratory function without lung disorders. Direct evidence of a correlation between PEFR and RMS has been reported in a previous study\u003csup\u003e\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e\u003c/sup\u003e. PEFR was measured by a digital peak flow meter (asma-1, Vitalograph, UK) with a disposable mouthpiece. Volunteers were instructed to take a maximum inhalation, followed by a maximum rapid and intense exhalation. Three measurements were taken, with the maximum value being recorded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eOral Stereognosis Ability\u003c/h2\u003e \u003cp\u003eSix small test pieces with the most extended side length or diameters equal to 10 mm were used and combined into three pairings of related shapes, such as a) circle and ellipse, b) square and rectangle, and c) triangle and semicircle\u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e. The test pieces were constructed from 3D-printed and sterilizable materials to allow free oral manipulation (VOVO V-Print SG, VOCO GmbH, Germany), and dental floss was affixed to prevent aspiration. A chart depicting the enlarged forms of the test pieces was used as an identification aid to illustrate the procedure. After the explanation, participants had to wear a blindfold and were not informed of the test results. Each test piece was placed on the tongue of the participants in a random order, which was the same for all participants. The participants were free to manipulate the test piece in their mouths without using their teeth to help. The participants raised their hands when they could provide a distinguishable result, and after the examiner removed the test piece, the participant provided their responses. Using a three-point scale, each response was graded. The correct, partially correct, and incorrect responses were awarded 2, 1, and 0 points, respectively. If the response was not precise but fell within the group shape, it is partially correct. The test was carried out twice, and the cumulative score ranged from zero to twenty-four points.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eSelf-Reported Numeric Rating Scales\u003c/h2\u003e \u003cp\u003eParticipants reported perceived levels of motivation, fun, pain, fatigue, and difficulty before and after the training tasks. These were reported using separate 0\u0026ndash;100 numerical rating scales (NRS). On the scale, \u0026lsquo;0\u0026rsquo; indicated no motivation, fun, pain, fatigue, or difficulty, and \u0026lsquo;100\u0026rsquo; indicated the highest level of motivation, fun, pain, fatigue, or difficulty\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003e The following outcome variables were evaluated: (a) MEP and corticomotor mapping of the tongue and FDI muscles (primary outcomes); (b) functional assessment of Orofacial Muscular Pressure and Force, Peak Expiratory Flow Rate (PEFR), Oral Stereognosis Ability; and c) Self-Reported NRS (secondary outcomes). All outcome variables were reported as means and standard error of means (SE) unless otherwise noticed. Normal distribution was assessed with Q-Q plots, and Ln transformations were applied to the continuous variables when needed.\u003c/p\u003e \u003cp\u003eBased on previous studies\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e,\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u003c/sup\u003e, it was expected that a medium effect size of 0.2 for the differences in corticomotor excitability would be possible to detect considering the within-between interactions from ANOVA with a power of 80% and a significance level of 5%. Therefore, the sample size estimation was considered to include at least 22 participants.\u003c/p\u003e \u003cp\u003eOne between-subject factor, i.e., group\u0026mdash;3 levels (BT, TT and CT), and two within-subject factors, i.e., time\u0026mdash;2 levels (pre- and post-training) and stimulus intensity\u0026mdash;4 levels (0.9, 1.0, 1.2 and 1.6 times the MT), were considered in a mixed ANOVA to assess differences in the tongue and FDI MEP amplitude. In addition, repeated-measure ANOVA was performed to assess differences in the MT, map area, volume (Ln transformed values), and CoG, orofacial muscular pressure, PEFR, oral stereognosis ability and NRS scores between the groups (between-subject factor\u0026mdash;3 levels), with time\u0026mdash;2 levels (pre and post training) serving as the within-subject factor. When appropriate, post hoc analyses using the Sidak test were conducted. The significance level was established at 5% (P\u0026thinsp;=\u0026thinsp;0.050). The adjustment was made to account for these outcomes (N\u0026thinsp;=\u0026thinsp;7) due to the multiple comparisons in the secondary outcome analyses. Therefore, we implemented the Bonferroni correction and established the significance level at 0.05/7 (P\u0026thinsp;=\u0026thinsp;0.007).\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompeting interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAn informed and written consent form agreeing to participate was obtained from each patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdditional information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCorrespondence and requests for materials should be addressed to T.A.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDongxiang Mi\u003c/strong\u003e: Methodology; Investigation; data curation; formal analysis; writing \u0026ndash; original draft. \u003cstrong\u003eEduardo Castrillon\u003c/strong\u003e: Conceptualization; methodology; project administration; formal analysis; writing \u0026ndash; review and editing. \u003cstrong\u003eMohit Kothari\u003c/strong\u003e: Conceptualization; methodology; project administration; formal analysis; writing \u0026ndash; review and editing. \u003cstrong\u003eTaro Arima\u003c/strong\u003e: Conceptualization; methodology; writing \u0026ndash; review and editing; funding acquisition; supervision. \u003cstrong\u003ePeter Svensson\u003c/strong\u003e: Conceptualization; methodology; project administration; formal analysis; writing \u0026ndash; review and editing; funding acquisition; supervision. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOpen access funding provided by Suzhou Vocational Health College. The study was funded by the Danish Dental Association and Japan Science and Technology Agency SPRING, Grant Number JPMJSP2119.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data supporting the findings of this study are available from the corresponding author upon reasonable request. Due to ethical considerations, access to the data is subject to restrictions.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHuang, Z. et al. Dental sleep-related conditions and the role of oral healthcare providers: A scoping review. \u003cem\u003eSleep. Med. 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Res.\u003c/em\u003e \u003cb\u003e30\u003c/b\u003e, 331\u0026ndash;340. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s40520-017-0777-9\u003c/span\u003e\u003cspan address=\"10.1007/s40520-017-0777-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2018).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Myofunctional therapy, Oropharyngeal exercise, Obstructive Sleep Apnea, Neuroplasticity, Transcranial Magnetic Stimulation","lastPublishedDoi":"10.21203/rs.3.rs-8664438/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8664438/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eOropharyngeal exercises / myofunctional therapy (OE/MT) offer complimentary beneficial effects on obstructive sleep apnea. However, the complex nature of intervention impedes the understanding of underlying mechanisms related to sensorimotor function and corticomotor control of involved muscles. This study explored the sensorimotor rehabilitation effects of OE/MT tasks in twenty-two healthy adults (24.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1 years) using a cross-over design to better understand the normal physiology of tongue before and after these different tasks. Sessions involved breathing training (BT), tongue training (TT), or a no-training control (CT). Transcranial magnetic stimulation (TMS) evaluated motor-evoked potentials (MEPs) of the tongue and first dorsal interosseous (FDI, internal control) muscles before and after each session. Secondary outcomes included orofacial muscular pressure/force, peak expiratory flow rate (PEFR), oral stereognosis ability, and subjective ratings. Results showed TT significantly increased tongue MEP amplitude (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and volume (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) compared to BT and CT. Conversely, FDI MEPs were unaffected by any task (P\u0026thinsp;\u0026gt;\u0026thinsp;0.050). No significant differences were observed in orofacial pressure, PEFR, stereognosis, or subjective ratings (P\u0026thinsp;\u0026gt;\u0026thinsp;0.050). These findings demonstrate that TT elicits unique corticomotor plasticity in tongue motor control, supporting the therapeutic potential of OE/MT. BT may need further development and be tested longer before functional effects can be observed.\u003c/p\u003e","manuscriptTitle":"Effects of oropharyngeal exercises / myofunctional therapy on orofacial function and corticomotor excitability in healthy individuals – implications for obstructive sleep apnea?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-10 15:14:26","doi":"10.21203/rs.3.rs-8664438/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-16T08:31:50+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-15T10:01:54+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-26T22:21:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"203937671547969600670517552236396827077","date":"2026-02-07T20:54:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"312341726778152286684965243741976564667","date":"2026-02-06T16:56:16+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-06T09:59:19+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-06T09:58:17+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-04T08:04:30+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-03T08:53:25+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2026-02-03T08:22:09+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"97a50aa6-ad2c-4fd4-9ed0-1b82c2672961","owner":[],"postedDate":"February 10th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":62515742,"name":"Health sciences/Health care"},{"id":62515743,"name":"Health sciences/Medical research"},{"id":62515744,"name":"Health sciences/Neurology"},{"id":62515745,"name":"Biological sciences/Neuroscience"},{"id":62515746,"name":"Biological sciences/Physiology"}],"tags":[],"updatedAt":"2026-05-19T08:24:27+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-10 15:14:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8664438","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8664438","identity":"rs-8664438","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}