Effect of Bi-/Unilateral Masticatory Training on Memory and Concentration - Assessor-blind, Cross-over, Randomized Controlled Clinical Trial

Article information

J Korean Med. 2022;43(2):61-74
Publication date (electronic) : 2022 June 1
doi : https://doi.org/10.13048/jkm.22020
Department of Clinical Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University
Correspondence to: Won-Seok Chung, Department of Rehabilitation Medicine of Korean Medicine, Kyung Hee University Medical Center, Tel : +82-2-958-9225, Fax : +82-2-958-9104, E-mail : omdluke@naver.com

Contributed equally to this study and should be considered the joint first author.

Received 2022 April 20; Revised 2022 May 25; Accepted 2022 May 25.



This study aimed to explore the short-term effects of bilateral masticatory training using an intraoral device on memory and concentration, which is an advanced form of Gochi, compared to the unilateral form with gum.


Thirty young healthy participants (age, 16–30 years) were screened and randomly assigned to one of two sequences in a crossover design. The participants assigned to sequence A (n=15) performed bilateral mastication using an intraoral device with a total of 300 taps, followed by unilateral mastication using gum with the same number of repetitions and frequency, separated by a 7-day washout period. A reverse order was used for sequence B. The primary and secondary outcomes were the digit span test result and the symbol digit modality test and the word list recallresults, respectively, which were conducted before and after each intervention.


Symbol digit modality test scores increased by 12.03±8.33 with bilateral mastication, which was significantly higher than that obtained with chewing gum (5.17 points;95% confidence interval: 0.99, 9.34; p<0.05). Changes in the digit span test and word list recall scores were not significantly different between the two groups. In the digit span test forward, symbol digit modality test, and word list recall test, bilateral mastication was not inferior to unilateral mastication in improving memory and concentration.


Bilateral masticatory exercises using an intraoral device are not inferior to unilateral mastication with gum for improving memory in healthy young individuals. Further research is needed to determine the efficacy of bilateral masticatory training on cognitive function.


Working memory, which comprises both short-term memory and attentional control1), is the cognitive process of holding and manipulating task-related information2). It is an essential part of cognitive function in humans and is involved in nearly all activities of everyday life. Similarly, concentration, which is the ability to focus attention on a particular subject without being distracted, is also necessary for daily life, and underlies the speed and capacity of recalling memories. Both working memory and concentration are major constituents of cognitive function, and human beings can learn new knowledge with these abilities3).

Masticatory activity has been shown to improve memory in an in vivo study that investigated the hippocampus of mice4) and in review articles involving humans5,6), as well as reinforce concentration6). The known mechanism of action for this improvement is that mastication activates the hippocampus indirectly through neuronal and humoral pathways7) and changes the activity of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in a decrease in corticosterone levels. In addition, it blocks the activation of c-Fos, which is related to learning ability in the hippocampus5). These processes allow masticatory movement to influence working and spatial memory, as well as the storage and information recall.

The masticatory process involves the movement of both the jaws; however, people tend to chew mainly on one side8). Unilateral mastication has been demonstrated to be inferior to bilateral mastication in terms of muscular activation around the jaw and the range of movement of the temporomandibular joint9); it also results in worse masticatory performance10). To our knowledge, no study has compared bilateral mastication with unilateral mastication in relation to cognitive or masticatory function.

In traditional Korean medicine, there is a form of jaw tapping training called Gochi, which means ‘tapping teeth.’ It is a traditional Korean medicinal method of chattering teeth by repeatedly contacting the upper and lower teeth with the biting force of provoking tapping sounds. It has been used as preventive therapy to enhance cognitive function, and even overall human health, in traditional Korean medicine11). Recently, a study using functional magnetic resonance imaging (fMRI) proved that Gochi increased blood oxygen level-dependent signals in brain areas controlling memory and cognitive function12); another fMRI study showed that it activated similar brain areas just as clenching and chewing gum13). Although jaw tapping is a type of bilateral mastication, the absence of normal occlusion can reduce neural effects14) and memory15). Thus, in this study, a specially designed intraoral device that used the concept of Gochi as a motif was utilized to allow efficient bilateral masticatory training regardless of occlusal conditions16).

It can be speculated that simultaneous bilateral masticatory exercises may have a stronger effect than unilateral masticatory exercises and masticatory movements in improving brain function. We designed a crossover randomized trial to explore the feasibility by comparing bilateral masticatory training using an intraoral device with those of unilateral mastication training with gum chewing, which we used as an active control to improve cognition17), memory, and concentration in healthy young volunteers.

Materials and Methods

The current study was conducted according to the Consolidated Standards of Reporting Trials (CONSORT). A detailed description of the study protocol has been published elsewhere18). Participants were recruited through offline posters and online homepages. Thirty healthy participants were enrolled in the study after screening using the inclusion and exclusion criteria (Figure 1).

Fig. 1

Flowchart for the study.

DST, digit span test; SDMT, symbol digit modalities test; WLR, word list recall; NSE, No-sick Exerciser®.

Only right-handed individuals were included because brain activation differs with handedness19). The design was an assessor-blinded, crossover, randomized controlled trial. Half of the participants (n=15) were assigned to sequence A, and half to sequence B. Participants assigned to sequence A first underwent bilateral mastication training with the intraoral appliance, followed by a 1-week interval after which they underwent unilateral mastication training involving gum chewing. The participants assigned to sequence B received the training in the opposite order, beginning with gum chewing, followed by the use of the appliance. The interventions were performed between 3 and 5 p.m., with at least 2 h of fasting. All procedures were reviewed and approved by the institutional review board (IRB) of Kyung Hee University Korean Medicine Hospital (approval number: KOMCIRB-2018-09-003).

All participants provided written informed consent. Participants under 19 years of age were considered vulnerable, and their legal guardians signed informed consent according to the Korean Good Clinical Practice (KGCP). This study adhered to the principles of the World Medical Association Declaration of Helsinki.

1. Participants

The inclusion criteria were as follows. 1) Healthy population between 16 and 30 years of age, 2) Right-handed, 3) Capable of mastication by moving the temporomandibular joints, 4) No pain during mastication, and 5) No severe dysfunction in memory or concentration

The exclusion criteria were as follows. 1) Use of dentures, implants, or braces within the last 3 months, 2) Having oral conditions of inflammatory disease, lacerations, wounds, etc., 3) History of orofacial surgery, 4) Change in oral medication within the last 3 months, 5) Unable to provide consent for participation or obtain consent through a legal representative, 6) Unable to complete questionnaires or tests, and 7) Considered as inappropriate for the study by the investigators.

After screening, the participants were provided with a description of the study procedures and their legal rights and responsibilities during a one-on-one interview with a study investigator. The investigator verified that the participant understood the process and willingly signed a consent form. After obtaining consent, the investigator collected demographic information.

2. Sample size calculation, allocation, and blinding

This was an exploratory pilot study to compare bilateral mastication with unilateral mastication. A pilot study was required to have at least 12 participants20). This study recruited 30 participants (dropout rate, 60%). A block randomized allocation method was used to assign participants to sequence A or B, with block sizes of 2, 4, or 6, using R 3.2.5 for Windows (R Core Team, Vienna, Austria). The assignment information was transferred to an enclosed envelope and given to the evaluator and statistician.

3. Interventions

A specially manufactured device, the No-Sick Exerciser® (Hifeelworld, Inc., Seoul, Korea) (Figure 2), was used for simultaneous bilateral mastication exercises.

Fig. 2

The intraoral appliance: No-sick exerciser®.

(A) Anterior view. (B) Lateral view. (C) and (D) A person training with the intraoral device. Each trial of chewing starts from (C) without force to (D) with a biting force. (A) and (B) had been published in Integrative Medicine Research 8 (2019) 247–251.

It has been approved as a first-class medical device by the Ministry of Food and Drug Safety of Korea and has been used in chewing training to restore muscular function around the jaw. The main body of the device was made of resin and there were three stainless steel elastic springs, all of which are known to be safe for use in humans. These springs enable the use of both sides of the jaw muscles simultaneously. The participants placed the device in the mouth between the upper and lower teeth and tapped it lightly up and down 100 times. Subsequently, they relaxed their jaw and rested for one minute without any movement or force of the jaw. They repeated this exercise for three rounds, with one-minute rest between rounds. A total of 300 taps were performed per session21,22). This process was conducted around noon, before lunch, to maintain the surrounding conditions in the same manner.

The participants on the trial of unilateral mastication were instructed to chew a gum (Xylitol®, 70 × 20 mm, 3.0 g; Lotte, Japan) on one side of the mouth. Similar to the bilateral mastication sequence, the participants performed light chewing 100 times, followed by a minute of rest. The chew/rest sequence was repeated two more times for a total of 300 unilateral chews.

4. Outcome measurements

Participants in the current study completed three tests in regular order immediately before and after each intervention, as conducted in previous studies measuring the short-term effects of masticatory movement, with questionnaires given immediately after interventions23,24). Each participant completed the test four times. All tests were administered and scored according to standard instructions.

The digit span test (DST) was the primary outcome of this study. It is a neuropsychological test to evaluate memory and concentration and has been used to assess memory improvement in healthy young populations25,26), as well as memory impairment in older adults and patients with cognitive symptoms27). It can be administered in two forms: DST forward, characterized by memorization in a forward order, and DST backward, characterized by memorizing in a backward order. DST forward measures concentration ability, while DST backward evaluates working memory. A tester tells the numbers at an interval of one second for three to nine digits at a time, and a testee memorizes the sequence. The length of the digits of the correct answer and the longest digit equals the test score.

The secondary outcomes are symbol digit modalities test (SDMT) and Wordlist recall (WLR). SDMT is a common instrument used to assess cognitive function and concentration. It contains 75 questions, which are scored based on the standardized numbers assigned to the participant’s sex, age, and educational background. It is used to assess the cognitive effects of computer games28) and gum chewing29).

WLR is a type of free recall test that uses 10 common words. The participants were instructed to read the 10 words aloud and to recall as many words as possible from the list. The task was performed three times, and the order of the words was randomized in each trial. This test evaluates working memory in various age groups30).

5. Data management, safety monitoring, analysis

Data from the tasks were entered into Excel and given to the statistician without any information on the sequence of each participant. The data file was protected using a password. Monitoring was performed before, during, and after the study by the internal institutional monitoring staff.

All data analyses in this study were conducted using SPSS for Windows Version 18.0 (SPSS Inc., Chicago, IL, USA). This study used a crossover design, and a mixed model was used to correct crossover sequences and identify participants as random variables to analyze the differences between the two interventions. General characteristics and test scores were converted to percentages (%) and standardized z-scores. Continuous data are presented as means and standard deviations (SD), medians, interquartile ranges (IQR), as well as minimum and maximum values. Both paired sample t-tests and Wilcoxon rank-sum tests were used to compare the differences between the changes following the two interventions. Statistical significance was set at P < 0.05. Non-inferiority was verified by setting the tolerance to 10%.


1. General demographic characteristics of the participants

A total of 30 people participated in this study, with no dropouts during the trial. The study included 13 male (43.3%) and 17 female (56.7%) participants (age range, 19–29 years; mean age, 25.7 years). Seven males and eight females were assigned to sequence A, and six males and nine females were assigned to sequence B. The mean ages of the participants were as follows: sequence A, 26.5 years; sequence B, 26.3 years.

2. Changes in DST score

The average score for the forward condition of the DST increased by 0.40 ± 1.22 after masticatory exercise with the intraoral device, whereas it decreased by 0.04 ± 1.16 after mastication with chewing gum. However, the difference between the changes in bilateral and unilateral mastication was not significant (P > 0.05) (Table 1). The average score for the backward condition of the DST increased by 0.33 ± 1.45 after bilateral mastication and by 0.60 ± 1.48 after unilateral mastication. The difference between these changes was not statistically significant (p > 0.05).

Changes in Digit Span Test, Symbol Digit Modalities Test, and Wordlist Recall Scores Before and After Bilateral and Unilateral Mastication

3. Changes in SDMT score

The SDMT score increased by 12.03 ± 8.33 after bilateral mastication and 6.87 ± 7.45 after unilateral mastication; the change was significantly higher in the bilateral mastication group than in the unilateral mastication group (P < 0.05) (Table 1).

4. Changes in WLR average score

The average increase in the total number of items recalled during the WLR was 0.69 ± 1.01 in the bilateral mastication group and 0.77 ± 0.75 in the unilateral mastication group, which was not significantly different (P > 0.05) (Table 1).

5. Results of non-inferiority of bilateral mastication with a medical device compared with unilateral mastication with gum

Bilateral mastication with the exercising device was not inferior to unilateral mastication with gum based on the test of non-inferiority during DST forward, SDMT, and WLR (Table 2) (Figure 3).

Non-inferiority Margin Scores for Each Outcome

Fig. 3

Non-inferiority test of the DST, SDMT, and WLR.

DST, digit span test; SDMT, symbol digit modality test; WLR, word list recal

However, this was not proven during DST backward. The margin of the non-inferiority tolerance limit was set to 10%31).

6. Adverse events after the intervention

No adverse events were observed for the bilateral or unilateral interventions.


Based on the hypothesis that bilateral mastication is more effective than unilateral mastication based on its effects on memory and concentration, mastication with a specially manufactured intraoral device and gum was compared to investigate the feasibility in this study.

The results of the current study shows that bilateral masticatory movement was not inferior to unilateral movement during the two tasks that assessed concentration (DST forward) and working memory (WLR). Additionally, on the secondary outcome, bilateral mastication was more effective than unilateral mastication in SDMT—a concentration test. This indicates that exercising with the device is not inferior to the widely accepted method of chewing gum and it improves the ability to focus within a shorter period than gum.

These results are important for several reasons. First, bilateral masticatory exercises using the device allows both jaw joints to be activated sufficiently at the same time, which may contribute to the activation of more areas of the brain by stimulating the masticatory muscles bilaterally19,22). Generally, people tend to masticate unilaterally31), which causes unbalanced facilitation of soft tissues around the temporomandibular joints32) and osseous morphology33), resulting in less activation of the hippocampus and amygdala34). Second, bilateral masticatory training using the intraoral device is relatively safe for healthy volunteers because no adverse events were reported in this study. Therefore, bilateral mastication training using this device is likely to increase brain activity better than that with chewing gum. In addition, the springs inserted between the upper and lower bodies of the device facilitate the standardization and quantification of chewing exercises.

Formerly, other researchers have studied jaw tapping (Gochi) without any apparatus in the mouth to investigate its effect on cognitive function12). However, a training device was employed in this study to embody bilateral masticatory training by activating the muscles of both sides equally. Generally, individuals have individual intercuspal positions (ICPs) to obtain maximal occlusal contact35), which causes an imbalance in muscular activation during mastication. The intraoral appliance, however, resolves the imbalance developed from the unique ICP and enables balanced masticatory movement with three springs between the upper and lower parts of the apparatus. In addition, the springs produce resistance during chewing movement, followed by increased activation of the surrounding muscles without any side effects.

The mechanism of improvement in memory and concentration from bilateral and unilateral mastication can be inferred based on previous research. In an animal study, mice with incomplete mastication due to dental problems had learning impairments and eventually underwent memory deficits. Loss of chewing movement affects CA1 and CA3—a sub-area of the hippocampus—and inhibits c-Fos expression36). This phenomenon impedes the synthesis of acetylcholine and accelerates the inflammatory response, resulting in the aging of the hippocampus. Masticatory movement increases cerebral blood flow37), with simultaneous bilateral jaw movement possibly contributing to a bilateral increase in inflow, as investigated in an fMRI study38). Neuronal and humoral pathways are also considered to be activated during mastication, with the stimulation of both sides able to enhance this mechanism. In addition, when people use the other side of the body rather than the preferred side, new neuroanatomic connections are more likely to be generated39).

A few limitations of this study must be addressed. First, the number of participants were insufficient to verify the superiority of the experimental group compared to the other groups. After power analysis, it was suggested that 50 or more participants would be required. This is an important point that future follow-up studies should address. Second, the time points for evaluation after the intervention were comparatively short. A study design for a long-term setup is necessary for a follow-up trial to investigate durational effects. The current exploratory pilot study focused on short-term effects, as suggested by a previous study in which masticatory movement was shown to activate the primary sensorimotor cortex immediately after the intervention38). Future long-term studies should be conducted based on the current study, with a short-term evaluation. Third, many preceding factors related to oral function, such as chewing habits and bruxism, were not considered before conducting the study. These factors need to be explored in future studies to understand the correlation between the factors and the results of the study. Fourth, the participants were limited to healthy young populations. As a pilot study, we tried to investigate if bilateral mastication affects memory and concentration of healthy participants. In the follow-up study, patients with mild cognitive impairment should be included. Fifth, the cross-over design may have caused recall bias for the outcomes because the measurements can be learned by participants. Sixth, two groups of participants could not have been blinded because using the intraoral device and chewing gum are impossible to be blinded. Lastly, the outcomes used in this study were limited to responses to a questionnaire for assessing task performance on cognitive tasks. Additional techniques, such as fMRI and near-infrared spectroscopy, must be used to identify the multidirectional analysis of the effects. Electromyography can also be used to compare bilateral muscular activation around the temporomandibular joint. Despite these limitations, this study is valuable in that it is the first exploratory study to demonstrate the effects of bilateral and unilateral masticatory training.

This pilot study investigated the effects of bilateral chewing training on young, healthy volunteers. The current study is only the beginning of an extensive investigation to verify traditional Korean medicine theory. A wide spectrum of participants, from healthy young people to aged populations or patients with cognitive impairment, which covers hyperfunctioning to hypo-functioning individuals, should be surveyed in the future with a more upgraded method with various measurement tools such as functional magnetic resonance imaging to assess the contribution of bilateral masticatory training with the device.


Bilateral masticatory exercise using an oral apparatus manufactured based on Gochi, the traditional Korean medicinal rehabilitative method, is not inferior to unilateral mastication using gum based on its effects on short-term memory in healthy young populations. In addition, it was beneficial for short-term concentration. The bilateral masticatory training conducted in this study was safe and demonstrated no adverse events. Limitations described above should be avoided in the future study. Additional clinical studies involving a broader category of participants, longer period of evaluation, and additional measurement techniques are required to prove the efficacy of bilateral masticatory training.


This study was funded by Hifeelworld, Inc. We would like to thank Editage (www.editage.co.kr) for English language editing.


Data Availability

The data from this study will be distributed when requested from the corresponding author via e-mail.

Conflicts of Interest

This study was funded by Hifeelworld, Inc. However, the funder had no role in the study design, data collection and analysis, or preparation of the manuscript.

Funding Statement

This study was funded by Hifeelworld, Inc., which develops and manufactures medical devices for various Korean medicine applications.


1. Baddeley AD, Hitch G. 1974;Psychology of learning and motivation; Cambridge: Academic Press. Working Memory 8:47–89. https://doi.org/10.1016/S0079-7421(08)60452-1 .
2. Clark CM, Lawlor-Savage L, Goghari VM. 2017;Working memory training in healthy young adults: Support for the null from a randomized comparison to active and passive control groups. PLoS One 12(5):e0177707. https://doi.org/10.1371/journal.pone.0177707 .
3. Lamprecht R, LeDoux J. 2004;Structural plasticity and memory. Nature Reviews Neuroscience 5(1):45–54. https://doi.org/10.1038/nrn1301 .
4. Fukushima-Nakayama Y, Ono T, Hayashi M, Inoue M, Wake H, Ono T, et al. 2017;Reduced mastication impairs memory function. Journal of Dental Research 96(9):1058–1066. https://doi.org/10.1177/0022034517708771 .
5. Krishnamoorthy G, Narayana AI, Balkrishanan D. 2018;Mastication as a tool to prevent cognitive dysfunctions. Japanese Dental Science Review 54(4):169–173. https://doi.org/10.1016/j.jdsr.2018.06.001 .
6. Tada A, Miura H. 2017;Association between mastication and cognitive status: A systematic review. Archives of Gerontology and Geriatrics 70:44–53. https://doi.org/10.1016/j.archger.2016.12.006 .
7. Ono Y, Yamamoto T, Kubo KY, Onozuka M. 2010;Occlusion and brain function: Mastication as a prevention of cognitive dysfunction. Journal of Oral Rehabilitation 37(8):624–640. https://doi.org/10.1111/j.1365-2842.2010.02079.x .
8. Mioche L, Hiiemae KM, Palmer JB. 2002;A postero-anterior videofluorographic study of the intra-oral management of food in man. Archives of Oral Biology 47(4):267–280. https://doi.org/10.1016/s0003-9969(02)00007-9 .
9. Jia L, Wang Y, Wang M. 2016;Characteristics of opening movement in patients with unilateral mastication [Chinese]. Zhong Nan Da Xue Xue Bao Yi Xue Ban 41(8):826–831. https://doi.org/10.11817/j.issn.1672-7347.2016.08.009 .
10. Farias Gomes SG, Custodio W, Moura Jufer JS, Del Bel Cury AA, Rodrigues Garcia RC. 2010;Correlation of mastication and masticatory movements and effect of chewing side preference. Brazilian dental journal 21(4):351–355. https://doi.org/10.1590/s0103-64402010000400011 .
11. Lee Y-J, Lee S-B, Choi G-W, Yin CS. 2014;Intraoral appliances in the medical classics of 12th to 19th centuries [Korean]. Association of TMJ Balancing Medicine 4(1):1–4.
12. Cho SY, Shin AS, Na BJ, Jahng GH, Park SU, Jung WS, et al. 2013;Brain activity associated with memory and cognitive function during jaw-tapping movement in healthy subjects using functional magnetic resonance imaging. Chinese Journal of Integrative Medicine 19(6):409–417. https://doi.org/10.1007/s11655-012-1187-7 .
13. Tamura T, Kanayama T, Yoshida S, Kawasaki T. 2003;Functional magnetic resonance imaging of human jaw movements. Journal of Oral Rehabilitation 30(6):614–622. https://doi.org/10.1046/j.1365-2842.2003.01054.x .
14. Tramonti Fantozzi MP, Diciotti S, Tessa C, Castagna B, Chiesa D, Barresi M, et al. 2019;Unbalanced occlusion modifies the pattern of brain activity during execution of a finger to thumb motor task. Frontiers in Neuroscience 13:499. https://doi.org/10.3389/fnins.2019.00499 .
15. Kubo KY, Yamada Y, Iinuma M, Iwaku F, Tamura Y, Watanabe K, et al. 2007;Occlusal disharmony induces spatial memory impairment and hippocampal neuron degeneration via stress in SAMP8 mice. Neuroscience Letters 414(2):188–191. https://doi.org/10.1016/j.neulet.2006.12.020 .
16. Kim MJ, Hong JY, Lee G, Yoon T, Hwang SH, Kim HH, et al. 2020;Effects of chewing exercises on the occlusal force and masseter muscle thickness in community-dwelling Koreans aged 65 years and older: A randomised assessor-blind trial. Journal of Oral Rehabilitation 47(9):1103–1109. https://doi.org/10.1111/joor.13036 .
17. Johnson AJ, Muneem M, Miles C. 2013;Chewing gum benefits sustained attention in the absence of task degradation. Nutritional Neuroscience 16(4):153–159. https://doi.org/10.1179/1476830512Y.0000000041 .
18. Kim H, Bae JH, Chung WS. 2019;Effects of a chattering teeth training oral appliance for working memory improvement in healthy volunteers: a cross-over randomized trial. Integrative Medicine Research 8(4):247–251. https://doi.org/10.1016/j.imr.2019.09.001 .
19. Jiang H, Liu H, Liu G, Jin Z, Wang L, Ma J, et al. 2015;Analysis of brain activity involved in chewing-side preference during chewing: an fMRI study. Journal of Oral Rehabilitation 42(1):27–33. https://doi.org/10.1111/joor.12224 .
20. Julious SA. 2005;Sample size of 12 per group rule of thumb for a pilot study. Pharmaceutical Statistics 4(4):287–291. https://doi.org/10.1002/pst.185 .
21. Hirano Y, Obata T, Kashikura K, Nonaka H, Tachibana A, Ikehira H, et al. 2008;Effects of chewing in working memory processing. Neuroscience Letters 436(2):189–192. https://doi.org/10.1016/j.neulet.2008.03.033 .
22. Hasegawa Y, Ono T, Hori K, Nokubi T. 2007;Influence of human jaw movement on cerebral blood flow. Journal of Dental Research 86(1):64–68. https://doi.org/10.1177/154405910708600110 .
23. Wilkinson L, Scholey A, Wesnes K. 2002;Chewing gum selectively improves aspects of memory in healthy volunteers. Appetite 38(3):235–236. https://doi.org/10.1006/appe.2002.0473 .
24. Baker JR, Bezance JB, Zellaby E, Aggleton JP. 2004;Chewing gum can produce context-dependent effects upon memory. Appetite 43(2):207–210. https://doi.org/10.1016/j.appet.2004.06.004 .
25. Prastowo NA, Kristanto S, Sasmita PK. 2015;Dark chocolate administration improves working memory in students. Universa Medicina 34(3):229–236. https://doi.org/10.18051/UnivMed.2015.v34.229-236 .
26. Guo X, Ohsawa C, Suzuki A, Sekiyama K. 2017;Improved digit Span in children after a 6-week intervention of playing a musical instrument: An exploratory randomized controlled trial. Frontiers in Psychology 8:2303. https://doi.org/10.3389/fpsyg.2017.02303 .
27. Zimmermann N, Cardoso CO, Trentini CM, Grassi-Oliveira R, Fonseca RP. 2015;Brazilian preliminary norms and investigation of age and education effects on the Modified Wisconsin Card Sorting Test, Stroop Color and Word test and Digit Span test in adults. Dementia & Neuropsychologia 9(2):120–127. https://doi.org/10.1590/1980-57642015DN92000006 .
28. Patel V, Walker L, Feinstein A. 2017;Deconstructing the symbol digit modalities test in multiple sclerosis: The role of memory. Multiple Sclerosis and Related Disorders 17:184–189. https://doi.org/10.1016/j.msard.2017.08.006 .
29. Onyper SV, Carr TL, Farrar JS, Floyd BR. 2011;Cognitive advantages of chewing gum. Now you see them, now you don’t. Appetite 57(2):321–328. https://doi.org/10.1016/j.appet.2011.05.313 .
30. Khosravizadeh P, Gerami S. 2010;Word list recall in youngsters and older adults. Brain (Bacau) 2(1):5–10.
31. Serel Arslan S, Demir N, Karaduman AA. 2017;Chewing side preference is associated with hemispheric laterality in healthy adults. Somatosensory and Motor Research 34(2):92–95. https://doi.org/10.1080/08990220.2017.1308923 .
32. Yamasaki Y, Kuwatsuru R, Tsukiyama Y, Matsumoto H, Oki K, Koyano K. 2015;Objective assessment of actual chewing side by measurement of bilateral masseter muscle electromyography. Archives of Oral Biology 60(12):1756–1762. https://doi.org/10.1016/j.archoralbio.2015.09.010 .
33. Jiang H, Li C, Wang Z, Cao J, Shi X, Ma J, et al. 2015;Assessment of osseous morphology of temporomandibular joint in asymptomatic participants with chewing-side preference. Journal of Oral Rehabilitation 42(2):105–112. https://doi.org/10.1111/joor.12240 .
34. Lee SM, Oh S, Yu SJ, Lee KM, Son SA, Kwon YH, et al. 2017;Association between brain lateralization and mixing ability of chewing side. Journal of Dental Sciences 12(2):133–138. https://doi.org/10.1016/j.jds.2016.09.004 .
35. Nishigawa K, Suzuki Y, Ishikawa T, Bando E. 2012;Effect of occlusal contact stability on the jaw closing point during tapping movements. Journal of Prosthodontic Research 56(2):130–135. https://doi.org/10.1016/j.jpor.2011.04.005 .
36. Watanabe K, Ozono S, Nishiyama K, Saito S, Tonosaki K, Fujita M, et al. 2002;The molarless condition in aged SAMP8 mice attenuates hippocampal Fos induction linked to water maze performance. Behavioural Brain Research 128(1):19–25. https://doi.org/10.1016/s0166-4328(01)00268-6 .
37. Miyake S, Wada-Takahashi S, Honda H, Takahashi SS, Sasaguri K, Sato S, et al. 2012;Stress and chewing affect blood flow and oxygen levels in the rat brain. Archives of Oral Biology 57(11):1491–1497. https://doi.org/10.1016/j.archoralbio.2012.06.008 .
38. Shinagawa H, Ono T, Honda E, Sasaki T, Taira M, Iriki A, et al. 2004;Chewing-side preference is involved in differential cortical activation patterns during tongue movements after bilateral gum-chewing: A functional magnetic resonance imaging study. Journal of Dental Research 83(10):762–766. https://doi.org/10.1177/154405910408301005 .
39. Liepert J, Terborg C, Weiller C. 1999;Motor plasticity induced by synchronized thumb and foot movements. Experimental Brain Research 125(4):435–439. https://doi.org/10.1007/s002210050700 .

Article information Continued

Fig. 1

Flowchart for the study.

DST, digit span test; SDMT, symbol digit modalities test; WLR, word list recall; NSE, No-sick Exerciser®.

Fig. 2

The intraoral appliance: No-sick exerciser®.

(A) Anterior view. (B) Lateral view. (C) and (D) A person training with the intraoral device. Each trial of chewing starts from (C) without force to (D) with a biting force. (A) and (B) had been published in Integrative Medicine Research 8 (2019) 247–251.

Fig. 3

Non-inferiority test of the DST, SDMT, and WLR.

DST, digit span test; SDMT, symbol digit modality test; WLR, word list recal

Table 1

Changes in Digit Span Test, Symbol Digit Modalities Test, and Wordlist Recall Scores Before and After Bilateral and Unilateral Mastication

Variable Bilateral mastication (n=30) Unilateral mastication (n=30) Difference P-value (Paired t-test) P-value (Wilcoxon test)

Mean SD Median IQR Mean SD Median IQR Mean 95% CI
DST forward Pre-mastication 6.27 1.14 7 1 6.57 1.07 7 0 −0.30 −0.83 0.23 0.2560 0.3151
Post-mastication 6.67 0.55 7 1 6.53 0.78 7 1 0.13 −0.16 0.42 0.3545 0.3667
Difference 0.40 1.22 0 0 −0.04 1.16 0 0 0.43 −0.12 0.99 0.1192 0.1494

DST backward Pre-mastication 5.70 1.18 6 2 5.40 1.57 6 3 0.30 −0.30 0.90 0.3131 0.2984
Post-mastication 6.03 1.25 7 2 6.00 1.23 6.5 2 0.03 −0.49 0.56 0.8973 0.9041
Difference 0.33 1.45 0 1 0.60 1.48 0 2 −0.27 −1.01 0.48 0.4708 0.6521

SDMT Pre-mastication 83.67 12.95 84.5 19 87.43 14.42 92.5 25 −3.77 −9.13 1.59 0.1614 0.1791
Post-mastication 95.70 7.50 96.5 10 94.30 9.45 100.5 13 1.40 −1.27 4.07 0.2921 0.3091
Difference 12.03 8.33 11.5 10 6.87 7.45 6 12 5.17 0.99 9.34 0.017* 0.0202*

WLR average Pre-mastication 8.72 1.11 9.00 1.67 8.62 0.99 8.83 1.33 0.10 −0.46 0.66 0.7170 0.6013
Post-mastication 9.41 0.76 9.67 1.00 9.39 0.77 9.67 1.00 0.02 −0.17 0.22 0.8157 0.6033
Difference 0.69 1.01 0.50 1.33 0.77 0.75 0.67 1.00 −0.08 −0.54 0.39 0.7343 0.6648

DST, digit span test; SDMT, symbol digit modalities test; WLR, word list recall; SD, standard deviation; IQR, interquartile range; CI, confidence interval;


, P < 0.05.

Table 2

Non-inferiority Margin Scores for Each Outcome

Variable Difference (bilateral – unilateral) Total Margin

Mean 95% CI
DST forward Difference (post-pre) 0.43 −0.12 0.99 7 −0.7
DST backward Difference (post-pre) −0.27 −1.01 0.48 7 −0.7
SDMT Difference (post-pre) 5.17 0.99 9.34 102 −10.2
WLR Difference (post-pre) −0.08 −0.54 0.39 10 −1.0

DST, digit span test; SDMT, symbol digit modality test; WLR, wordlist recall; CI, confidence interval.