Dysphagia is a major complication that occurs in 37%-78% of stroke patients [1]. Typical complications of dysphagia include dehydration and malnutrition, aspiration pneumonia, and asphyxia, which can lead to death. Therefore, proper treatment after early diagnosis is critical [2,3,4,5]. Current dysphagia treatment goals include preventing aspiration through changes in food and water protocols, compensatory techniques, and rehabilitative exercise [6]. Reorganization in the swallowing cortical area occurs after a stroke, which is known to be related to recovery from dysphagia.

Noninvasive brain stimulation techniques are expected to change brain plasticity during recovery from poststroke dysphagia [7]. Studies using repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation reported the role of noninvasive brain stimulation techniques in dysphagia recovery. Recent studies confirmed the positive effects of rTMS in treating dysphagia [8]. Khedr et al. [9] and Khedr and Abo-Elfetoh [10] applied rTMS over the esophageal cortical area of the affected hemisphere in acute dysphagic stroke patients for 2 months, and improvements in dysphagia and motor disability were observed. Verin and Lerio [11] applied rTMS over the mylohyoid cortical area of the healthy hemisphere in patients with chronic post-stroke dysphagia and detected improvements in swallowing coordination and a decrease in the aspiration score for liquids. In previous studies, rTMS was performed mostly over the cortical lesions of the swallowing muscle, from which improvements of dysphagia were observed.

However, an increasing number of functional magnetic resonance imaging (fMRI) studies have implicated multiple regions of the cerebral cortex and subcortex in the process of swallowing [12,13,14,15]. Bestmann et al. [16] showed that right-hand finger tapping led to pronounced activation in bilateral M1/S1 and supplementary motor area (SMA) lesion, which are also activated during in voluntary swallowing. This indicates that there is a possibility of interconnection between both cortical areas. In a review of studies on transcranial magnetic stimulation (TMS) and fMRI, Reithler et al. [17] showed that TMS over a particular cortical site not only results in focal effects but also affects other brain regions. Furthermore, there is evidence that rTMS modulates remote areas in actual clinical settings. Triggs et al. [18] performed rTMS over the left prefrontal area and observed clinical improvements in depressed mood; they concluded that left prefrontal rTMS is capable of modulating not only the corticospinal motor system but also the orbitofrontal limbic structures, i.e., brain activities in remote areas.

A number of studies indicate that rTMS is a good treatment option for post-stroke patients. However, to the best of our knowledge, none of the studies have compared the clinical effects of rTMS applied directly over the swallowing-related cortex and the interconnected sites in poststroke dysphagia patients.

Hence, in this study, we categorized subacute stroke patients with dysphagia who underwent rTMS over specific sites of dysphagia and the interconnected site by stimulation of the cortex representing the motor hand area. Treatments were administered, after which their efficacies were compared.

A total of 24 subjects with subacute ischemic stroke were recruited; the mean ages of patients in groups A and B were 66.1±11.2 years and 60.9±11.4 years, respectively. No significant differences in demographics or disease-related characteristics were observed between the two groups (Table 1).

In repeated measures ANOVA test, all dysphagia scores (FDS, PAS, DOSS) were improved over time up to 4 weeks after rTMS in group A and only the FDS score was improved in group B. There was no significant group-time interaction in all dysphagia scores (FDS, PAS, DOSS) (Fig. 2). K-MBI was improved over time up to 4 weeks after rTMS, while there was no significant group-time interaction. The MMSE score was not significantly improved over time up to 4 weeks after rTMS, and there was no significant group-time interaction (Fig. 3).

When the treatment effects from baseline to immediately after rTMS were compared between the two groups, there were no statistically significant differences in the degree of improvement in FDS or PAS scores; however, group A showed a statistically significant improvement in the DOSS score. Similarly, when the treatment effects from baseline to 4 weeks after rTMS were compared between the two groups, there were no statistically significant differences in the degree of improvement in FDS or PAS scores; however, group A showed a statistically significant improvement in the DOSS score (Fig. 4).

With respect to MMSE and K-MBI, the degree of improvement from baseline to immediately after rTMS and from baseline to 4 weeks after rTMS showed no difference between the two groups (Fig. 5).

No side effects such as seizure or uncontrollable headaches were reported in either group.

This study compared dysphagia treatment effects according to the stimulation site; the cortex, responsible for innervating the suprahyoid muscle, which is related to swallowing, and the motor cortex, responsible for innervating the APB muscle. Dysphagia scores (FDS, PAS, DOSS) started to improve immediately after rTMS and continued to improve over time up to 4 weeks after rTMS. Group A showed greater improvement in the DOSS score than group B in the between-group analysis.

Previous studies also performed rTMS over dysphagia-related specific sites in post-stroke patients with dysphagia [9,10]. However, since sham rTMS was performed for the control group in the aforementioned study, the differences in the effects of rTMS related to the stimulation site could not be determined.

In this study, the suprahyoid muscle was selected as the specific dysphagia-related target. In post-stroke dysphagia, the main cause of dysphagia is problems in the pharyngeal phase (decreased laryngeal elevation due to weakened muscles involved in the swallowing process) rather than in the oral phase [19]. Two studies reported that pharyngeal electrical stimulation to the degree of contracting muscles lowers the hyoid bone by contracting the sternohyoid and omohyoid muscles, thereby interfering with the swallowing process [24,25]. Kim and Han [26] also reported that when the suprahyoid muscle of a normal person is stimulated, the hyoid bone becomes elevated. Kim et al. [27] conducted suprahyoid muscle electrical stimulation in brain-injured patients with dysphagia and reported that this stimulation resulted in superior outcomes compared to those with conventional management.

In this study, to stimulate the interconnected sites, the cortex representing the motor hand area (APB) was stimulated. According to previous brain cortex mapping studies, there are differences in the location of the brain cortex representing the APB muscle (lateral, 6.0-6.2 cm; anterior, 0.1-0.2 cm from Cz) and the submental (suprahyoid) muscle (lateral, 14.3±0.5 cm; anterior, 3.9±0.5 cm from Cz) [20,28]. Despite this, in this study, the group that underwent stimulation of the cortex representing the APB muscle showed improvements in swallowing function. There are two possibilities: 1) first possibility is the natural recovery of subacute stroke patients, or 2) second possibility is stimulation of the interconnected site, when the primary motor cortex is stimulated [12,13,14,15,16,17,29]. This may be because the white matter is interconnected; therefore, when the motor cortex representing the APB is stimulated, regions related to swallowing may have been stimulated.

In this study, only the DOSS score showed a statistically significant degree of improvement, which is due to the unique characteristics of each scale. Three dysphagia scales were used in this study: FDS provides information on the oral and pharyngeal phases that can be used for quantifying dysphagia severity [21]; PAS evaluates whether the material passes through the airway during VFSS [22] (in this study, PAS for fluids was measured); and DOSS documents the functional outcome of swallowing and reflects the diet status based on the objective assessment [23]. The reason why the changes in FDS scores did not show statistical significance in this study is probably that the suprahyoid muscle was selected as the dysphagia-specific area, meaning that the pharyngeal phase was targeted. The FDS also includes an evaluation of the oral phase; thus, it is less sensitive to the degree of improvement in dysphagia. Improvement in the PAS score also did not show statistical significance; in this study, PAS evaluated only the airway invasion of fluids. Clinically, improvement in dysphagia is observed much earlier with solid foods than with fluids. For this reason, the degree of solid food-related dysphagia functional improvement was not well reflected by the PAS score. In comparison, the DOSS score reflected not only the pharyngeal phase but also the degree of improvement with regard to solid food; hence, in this study, it would have shown the highest sensitivity towards the stimulation of a dysphagia-specific area.

This study had a few limitations. First, the sample size was small (n=24). Attempts were made to minimize bias associated with the small sample size using a matched comparative study design, but the limitation remained. Second, the follow-up period was too short. Third, there was no sham rTMS control group, meaning that the improvement in dysphagia after rTMS conducted at an interconnected site could not be distinguished from that during the natural recovery of post-stroke patients in the subacute phase. Hence, future studies that address these issues are required to validate our results.

In conclusion, the results of this study showed that performing rTMS over the cortical area representing the suprahyoid muscle was more effective than performing rTMS over the cortical area representing the APB in patients with post-stroke dysphagia. In conclusion, stimulation of a specific site using rTMS according to the primary purpose or outcome can maximize its effectiveness.