Lip closure training improves eating behaviors and prefrontal cortical hemodynamic activity and decreases daytime sleep in elderly persons

Accepted Manuscript Lip closure training improves eating behaviors and prefrontal cortical hemodynamic activity and decreases daytime sleep in elderly persons Kouich Takamoto, Tsuyoshi Saitoh, Toru Taguchi, Hiroshi Nishimaru, Susumu Urakawa, Shigekazu Sakai, Taketoshi Ono, Hisao Nishijo PII:

S1360-8592(17)30226-7

DOI:

10.1016/j.jbmt.2017.09.002

Reference:

YJBMT 1589

To appear in:

Journal of Bodywork & Movement Therapies

Received Date: 24 March 2017 Revised Date:

24 August 2017

Accepted Date: 1 September 2017

Please cite this article as: Takamoto, K., Saitoh, T., Taguchi, T., Nishimaru, H., Urakawa, S., Sakai, S., Ono, T., Nishijo, H., Lip closure training improves eating behaviors and prefrontal cortical hemodynamic activity and decreases daytime sleep in elderly persons, Journal of Bodywork & Movement Therapies (2017), doi: 10.1016/j.jbmt.2017.09.002. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT

Lip closure training improves eating behaviors and prefrontal cortical hemodynamic activity and decreases daytime sleep in elderly persons

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Kouich Takamoto, PhD1a, Tsuyoshi Saitoh, MS2a, Toru Taguchi, PhD1#, Hiroshi Nishimaru, MD, PhD2, Susumu Urakawa, PhD1*, Shigekazu Sakai, PhD1, Taketoshi Ono, MD, PhD1, Hisao Nishijo, MD, PhD2

Department of Judo Neurophysiotherapy and 2System Emotional Science, Graduate School

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of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan

*Present address: Department of Musculoskeletal Functional Research and Regeneration, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan

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#Present address: Department of Physical Therapy, Niigata University of Health and Welfare, 1398 Shimami-cho, Kita-ku, Niigata-shi, Niigata, 950-3198, Japan

These authors contributed equally.

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Correspondence to: Dr. Hisao Nishijo System Emotional Science Graduate school of Medicine and Pharmaceutical Sciences University of Toyama, Sugitani 2630, Toyama 930-0194, Japan E-mail: [email protected] Tel: +81-76-434-7215; Fax: +81-76-434-5012

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ACCEPTED MANUSCRIPT Abstract Previous research suggests that aging-related deterioration of oral functions causes not only eating/swallowing disorders but also various conditions such as sleep disorders and

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higher-order brain dysfunction. The aim of the present study was to examine the effects of lip closure training on eating behavior, sleep, and brain function in elderly persons residing in an elder care facility. The 20 elderly subjects (mean age, 86.3 ± 1.0 years) were assigned to a

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control group or a lip closure training (LCT) group, in which an oral rehabilitation device was used for daily LCT sessions over a 4-week period. Before and after the 4-week intervention

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period, maximal lip closure force was measured, and prefrontal cortical hemodynamic activity (changes in oxygenated hemoglobin concentration) during lip closure movements was measured with (LCT group) or without (control group) use of the oral rehabilitation device. We also analyzed eating behavior and daytime sleep before and after the intervention period. Compared with the control group, the LCT group showed improved maximal lip closure

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force, shortened eating time, decreased food spill rates, and decreased daytime sleeping. Furthermore, compared with the control group, the LCT group showed a significant increase

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in prefrontal cortical activity during lip closure. In addition, the increase rate in the right dorsolateral prefrontal cortical activity after the intervention period was significantly

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correlated with the increase rate in the maximal lip closure force after the intervention period. These findings suggest that LCT is useful in elderly individuals with decreased eating/oral and cognitive functions without the risk of pulmonary aspiration during training.

Key words: Lip closure training, eating behavior, circadian rest-activity rhythm, prefrontal cortex, elderly.

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ACCEPTED MANUSCRIPT Introduction

Oral function gradually decreases with age. The risk of pulmonary aspiration increases

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owing to poor oral movements such as mastication, food spillage, or increased pharyngeal residue due to decreased lip closure force, and may result in dehydration, malnutrition, or even asphyxial death (Robbins et al, 2001; Mioche et al, 2004; Hägg & Anniko, 2008; Steele

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et al, 2009; Weijenberg et al, 2011). In addition, skeletal muscle mass and muscle motor units decrease due to aging (Doherty et al, 1993, 2003; Erim et al, 1999), which might decrease

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muscular strength of the swallowing-related muscles and impair swallowing (Kawashima et al, 2004; Maeda et al, 2016). Further, decreased lip closure force due to aging leads to mouth breathing and a tendency for the mouth to remain open, thereby leading to onset of 1) sleep apnea due to glossoptosis and 2) sleep-wake rhythm disorders such as increased daytime sleepiness (Bachour & Maasilta, 2004; Ramar & Guilleminault, 2006; Enoz, 2007; Lee et al,

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2007; Yoshimura et al, 2016). It has also been reported that various oral functional disorders induce cognitive deficits and that brain function improves by ameliorating such disorders

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(Grabe et al, 2009; Narita et al, 2009). The above findings suggest that aging-related deterioration of oral function causes eating/swallowing disorders as well as sleep disorder and

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deficits in higher brain functions.

Various oral training/rehabilitation methods have been attempted to improve the oral and brain functions. Mastication exercises improved working memory and activated the prefrontal

cortex

(Hirano

et

al,

2008,

2013)

and

decreased

behavioral

and

electroencephalogram reaction time to sensory stimuli (Sakamoto et al, 2009) in healthy adults. Furthermore, a study of elderly persons has reported that masticatory movements activated the prefrontal cortex (Onozuka et al, 2003). Recently, a few studies focused on training the orbicularis oris muscle in the lip; lip closure training using the orbicularis oris

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ACCEPTED MANUSCRIPT muscle increased lip closure force and activated the prefrontal cortex in healthy young subjects (Nakada et al, 2013a; Kaede et al, 2016) and improved lip closure force, saliva swallowing, and circadian rhythm in elderly subjects (Nakada et al, 2013b). A recent

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noninvasive imaging study reported an involvement of the prefrontal cortex in motor learning; activity of the prefrontal cortex, in particular the anterior medial part of the prefrontal cortex (Area 10), was correlated to performance improvement during repeated motor learning

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(Ishikuro et al., 2014). Furthermore, activity of this area was correlated to activity in the sensorimotor cortical areas including the dorsal premotor, primary motor and primary

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somatosensory areas (Ishikuro et al., 2014). Therefore, we hypothesized that lip closure training would activate the prefrontal cortex.

The above findings suggest that lip closure training might improve eating behavior and prefrontal cortical activity, and ameliorate daytime sleepiness in elderly subjects. In the present study, we examined the effects of lip closure training on eating behavior, sleep in the

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daytime, and prefrontal cortical activity in elderly subjects in an elder care facility. Prefrontal cortical activation was measured using Near-infrared spectroscopy (NIRS). NIRS is a

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non-invasive neuro-monitoring technique that requires less body and head restriction in a limited space than functional magnetic resonance imaging (fMRI) and positron emission

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tomography (PET), and can be applied to more natural conditions than the other non-invasive methods including fMRI and PET. Furthermore, we analyzed the relationships between lip closure force improvement by training and prefrontal activation.

Materials and methods Subjects The subjects were 20 elderly residents of an elder care facility in Toyama, Japan (2 men and 18 women; mean age, 86.3 ± 1.0 years) (Table 1). To assess eating behaviors, we

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ACCEPTED MANUSCRIPT recruited subjects who had no hemiplegia nor facial nerve palsy due to cerebrovascular diseases, and used subjects who could eat foods using their own hands regardless of denture status. The following 10 items of the Barthel index (BI; Mahoney & Barthel, 1965) were used

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to comprehensively evaluate activities of daily living (ADLs): 1) eating, 2) transfer between wheelchair/bed, 3) grooming activities, 4) toilet movements, 5) bathing, 6) horizontal walking/wheelchair movement, 7) climbing up and down stairs, 8) changing clothes, 9)

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defecation control, and 10) urination control. All patients were treated in strict compliance with the Declaration of Helsinki and the U.S. code of Federal Regulations for the Protection

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of Human Subjects. The present study was approved by the Institutional Review Board of the University of Toyama, an explanation was given to all subjects and their family members before implementation of the experiment, and signed consent was obtained from all subjects prior to participating.

Test procedure

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PLACE TABLE 1

The subjects were randomly assigned to a lip closure training (LCT) group that received

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lip closure training (n = 10; two men and eight women; mean age, 87.3 ± 1.6 years) or a control group (n = 10; 10 women; mean age, 85.3 ± 1.4 years). An experimenter, who was not

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involved in the data collection and analyses, conducted random assignment of the subjects using random allocation software. Under the guidance of the facility staff, subjects in the LCT group were instructed to perform lip closure training using an oral rehabilitation device (Lip Trainer Patakara®; PATAKARA Co., Ltd., Tokyo, Japan) for 3 minutes, three times a day (before breakfast/before lunch/before dinner) for 4 consecutive weeks. Lip closure training was not performed in the control group. The facility staff confirmed that each subject performed the training according to the treatment protocol in each occasion. Four items (maximal lip closure force, eating behavior, rest-activity rhythm, and

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ACCEPTED MANUSCRIPT cerebral hemodynamic activity during the lip closure movement) were measured twice in both groups before (0 w) and after (4 w) the intervention period. These measurements were performed between 10:00 AM and 11:00 AM in a room at 26 ± 1°C, except for eating

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behaviors, which were measured at lunch time. All results were assessed by an independent experimenter, who was not the facility staff and blinded to the treatment groups in this study.

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Lip closure training device

The body of the Patakara oral cavity rehabilitation device is made of polyester

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elastomer and is 74 mm × 59 mm in size (Fig. 1). The individuals in the LCT group set the Patakara between the upper and lower lips, which loaded a force expanding these lips, and were asked to perform isometric contractions of the orbicularis oris muscle by maintaining lip closure. The subjects performed isometric contractions of the orbicularis oris muscle to maintain lip closure for 3 minutes against the load of the device (4.0 N). HERE

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PLACE FIGURE 1

Measurement of maximal lip closure force

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A digital measurement device (LIP DE CUM; Cosmo Instruments Co., Ltd., Tokyo, Japan) was used to measure maximal lip closure force. Subjects were asked to rest in a chair,

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and a plastic cap with pressure sensor was attached to the lips. The subjects were instructed to perform lip closure with maximal muscle force for 30 seconds while confirming lip closure force displayed in real time on a monitor, and maximal lip closure force was recorded. Maximal lip closure force before and after the 4-week intervention period was determined, and the rate of change (4 w/0 w) after the intervention period was calculated for each subject. The mean values of the rates were compared between the LCT and control groups using Student’s t-test.

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ACCEPTED MANUSCRIPT Evaluation of eating behavior Eating behavior was recorded using two digital video cameras (Everio GZ-MG275; Victor, Kanagawa, Japan) (iVIS HFM32; Canon, Tokyo, Japan) twice before the intervention

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(0 w) and twice after the intervention period (4 w). Four items (eating time from the start to the end of the meal, number of chews, number of food spills per mouthful, and number of choking experiences) were analyzed by slow motion review (0.5 speed) using a GOMPLAYR

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(Gretech Corporation, Korea). The number of food spills from the start to the end of eating and the total number of times food brought to the mouth were counted. Then, the total number

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of food spills/total number of mouthfuls was computed as the “number of food spills per mouthful.” The time needed to process one mouthful (eating time per mouthful) was defined as “total eating time/total number of mouthfuls.” With respect to the above parameters, the mean value of the data measured twice each before intervention (0 w) and after intervention (4 w) was calculated, and the mean of the rate of change after 4 weeks (4 w/0 w) was

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analysis.

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compared between the LCT and control groups. Mann-Whitney U test was used for statistical

Evaluation of circadian rest–activity rhythm

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Circadian rest–activity rhythm was measured using a three-axis accelerometer (ActiSleep Monitor; Actigraph, Pensacola, USA). Before (0 w) and after (4 w) the intervention, the device was worn on each subject’s non-dominant hand for 7 days and the movement of the upper arm was recorded. The acceleration axis setting of the ActiSleep Monitor was set to three dimensions, and the low-frequency extension feature was employed for elderly persons. Furthermore, epoch time was set at 1 minute. The device recorded motion that exceeded the upper-arm activity cut point every 0.1 seconds and recorded the total value every minute. Device measurement settings and data were extracted using the software Acti

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ACCEPTED MANUSCRIPT life 5 (Actigraph). Measurement of daytime sleep time was performed from 8:30 AM to 12:00 PM (morning) and from 1:00 PM to 5:00 PM (afternoon), excluding meal times. The Cole-Kripke algorithm in the same software was used for sleep/wake identification. The rate

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of change (4 w/0 w) of the daytime sleeping time in the morning and afternoon was analyzed using repeated-measures two-way analysis of variance (ANOVA) (time period × group).

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Measurement of prefrontal cerebral hemodynamics

Near-infrared spectroscopy (NIRS) (OEG16; Spectratech Inc., Yokohama, Japan) was

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used to measure cerebral hemodynamics. The subjects were asked to sit on an armchair, wear the oral rehabilitation device, and place both hands on the thighs with the eyes open. A probe pad for NIRS measurement of the same device (six light-emitting probes, six light-receiving probes; 16 channels as measuring points) was placed on the head so that the probes at the lower part of the pad were aligned with the Fp1-Fp2 line in the 10-20 system (Fig. 2A). The

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optical fiber output in the device was set to below 0.2 mW/mm2, which is well below 1/15 of the maximum permissible exposure of the skin against laser radiation (Orihuela-Espina et al.,

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2010). Near-infrared light (wavelength, 780–830 nm) permits relatively easy penetration of the skin and bone and is absorbed by oxygenated and deoxygenated hemoglobin. NIRS can

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noninvasively measure changes in hemoglobin concentrations associated with neuronal activity using this near-infrared light. Each probe interval was maintained at a fixed distance (3 cm) by the head pads, and the intermediate points between the light-emitting and light-receiving probes were used as the measurement channels. After the recording, the 3-D locations of the NIRS probes were measured using a digitizer (Shimadzu Co. Ltd., Kyoto, Japan) with reference to the nasion and bilateral external auditory meatus. PLACE FIGURE 2

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The task was as follows: after a 30-second rest period (muscle relaxation baseline

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ACCEPTED MANUSCRIPT period), lip closure was maintained in response to the oral rehabilitation tool for 30 seconds followed by another 30-second rest. The timing above was set as one cycle, and four cycles were continuously repeated. We measured the changes in oxygenated hemoglobin (Oxy-Hb),

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deoxygenated hemoglobin, and total hemoglobin concentrations in each channel. In the present study, we analyzed Oxy-Hb concentration change as an indicator of brain activity, since Oxy-Hb concentration is the most consistent parameter for cortical activity (Okamoto et

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al, 2006). Data were corrected for the baseline (30 seconds before lip closure) prior to analysis.

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To identify the anatomical locations of NIRS channels in each subject, the 3D locations of the NIRS probes and channels in each subject were spatially normalized to a standard coordinate

system

using

NIRS

SPM

software

(statistical

parametric

mapping:

http://bisp.kaist.ac.kr/NIRS-SPM, version3.1) (Ye et al, 2009); the coordinates for each NIRS channel were normalized to MNI (Montreal Neurological Institute) space using virtual

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registration (Tsuzuki et al., 2007). We then identified the Brodmann areas corresponding to the NIRS channels of each subject using MRIcro software (www.mricro.com, version 1.4).

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The measured regions were divided into three regions of interest: the bilateral dorsolateral prefrontal cortex (Brodmann areas 45 and 46) and anterior dorsomedial prefrontal cortex (area

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10) (Fig. 2B).

The data on changes in Oxy-Hb concentration were analyzed using SPM, and activity during the lip closure was calculated as a t-value. The mean t-value in the channels within each region of interest was calculated in each subject, and repeated-measures two-way ANOVA (region of interest × group) was used for the analysis.

Statistical analysis The normality of the data was evaluated using the Shapiro-Wilk test. The homogeneity

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ACCEPTED MANUSCRIPT of variance was evaluated using Levene’s test. Based on the above evaluation, Student’s t-test, repeated-measures two-way ANOVA, or the Mann-Whitney U test were used to analyze the

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data of the two groups. Values of P < 0.05 were considered statistically significant.

Results Subjects’ general condition

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Table 1 shows the ADLs of the subjects by age, sex, and BI. No significant differences

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between the LCT and control groups were noted in age or BI (Student’s t-test, P > 0.05).

Maximal lip closure

In the LCT group, maximal lip closure force was significantly greater after the intervention period (6.77±1.01 N) than before the intervention period (4.66±0.69 N) (paired t-test, P < 0.05). In the control group, there was no significant difference in the maximal lip

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closure force between before (6.52±0.93 N) and after (4.91±0.56 N) the intervention period (paired t test, P > 0.05). Figure 3 shows the rate of change in maximal lip closure force in the

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LCT group (10 subjects) and control group (10 subjects) after the intervention period. The mean rate of change in the LCT group (1.66 ± 0.10) was significantly increased compared

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with the control group (0.93 ± 0.14) (Student’s t-test, P < 0.05). PLACE FIGURE 3

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Eating behavior

In the LCT group, eating time per mouthful was significantly shorter after the intervention period (12.60±1.23 sec) than before the intervention period (14.90±1.95 sec) (paired t-test, P < 0.05). In the control group, there was no significant difference in eating time per mouthful between before (13.27±1.02 sec) and after (13.55±0.77 sec) the intervention period (Wilcoxon signed-rank test, P < 0.05). Figure 4A shows the rate of change in eating

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ACCEPTED MANUSCRIPT time per mouthful after the intervention period. Compared with the control group, the rate of change significantly decreased in the LCT group (Mann-Whitney U test, P < 0.05). The number of food spills per mouthful in the LCT group was significantly lower after

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the intervention period (1.44±0.39 times) than before the intervention period (3.47±0.87 times) (paired t-test, P < 0.05). In the control group, there was no significant difference in the number of food spills per mouthful between before (2.46±0.84 times) and after (3.50±0.95

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times) the intervention period (paired t-test, P > 0.05). Figure 4B shows the rate of change in the number of food spills per mouthful in the LCT and control groups. Compared with the

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control group, the LCT group had a significantly smaller mean rate of change in food spilling per mouthful (Mann-Whitney U test, P < 0.05). These findings indicate that eating time was faster and food spilling occurred less in the LCT group. PLACE FIGURE 4

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Circadian rest-activity rhythm

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In the LCT group, daytime sleep time in the morning before and after the intervention period was 122.20±13.81 and 117.93±16.35 min, respectively, while daytime sleep time in the

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afternoon before and after the intervention period was 128.52±18.54 and 122.72±20.61, respectively. A statistical comparison by repeated measures two-way ANOVA (sleep time ×

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intervention) indicated no significant main effect of sleep time [F (1, 9) = 0.62, P > 0.05], nor significant main effect of intervention [F (1, 9) = 1.44, P > 0.05]. In the control group, daytime sleep time in the morning before and after the intervention period was 83.59±14.21 and 88.70±15.85 min, respectively, while daytime sleep time in the afternoon before and after the intervention period was 85.57±15.92 and 95.03±20.61 min, respectively. A statistical comparison by repeated measures two-way ANOVA indicated no significant main effect of sleep time [F(1, 9) = 0.51, P > 0.05], nor significant main effect of intervention period [F(1, 9) = 3.19, P > 0.05]. However, we found a significant effect of lip closure training when the data

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ACCEPTED MANUSCRIPT were normalized by computing rate of change (4 w/0 w) of the daytime sleeping time. Figure 5 shows the rate of change in daytime sleep time after the intervention period. The results of analysis using repeated-measures two-way ANOVA (time period × group) did not reveal any

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significant main effect for time period (F(1,18) = 0.168, P > 0.05). In contrast, a significant main effect was noted for group (F(1,18) = 6.341, P < 0.05). The above findings indicate that daytime sleep time significantly decreased in the LCT group compared with the control

PLACE FIGURE 5

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group. HERE

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Cerebral hemodynamics

Figure 6 shows changes in t-values calculated by SPM analysis. A statistical analysis by repeated-measures two-way ANOVA (region of interest × group) revealed no significant main effect for region of interest [F(1,18) = 3.401, P > 0.05], but a significant main effect for group was noted [F(1,18) = 4.452, P < 0.05]. These findings indicate that Oxy-Hb concentration

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changes significantly increased in the prefrontal cortex in the LCT group compared with the control group. Furthermore, we analyzed the correlation between the rate of change in

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maximal lip closure force and changes in t-values in the three regions of interest to clarify the effect of lip closure training on the activity of the prefrontal cortex. The results revealed a

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significant positive correlation between the rate of change of the maximal lip closure force and changes in t-values in the right dorsolateral prefrontal cortex (Spearman’s correlation, ρ = 0.448; P < 0.05).

PLACE FIGURE 6

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Effects on lip closure force The present results indicate that maximal lip closure force in elderly persons increased after lip closure training. Previous studies also reported that lip closure training increased lip

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ACCEPTED MANUSCRIPT closure force in elderly and healthy young adults (Nakada et al, 2013a,b; Kaede et al, 2016). Furthermore, the results of our previous study demonstrated that the same lip closure training increased the number of repetitive saliva swallows (Nakada et al, 2013b). The orbicularis oris

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muscle is involved in: 1) lip closure during masticatory movements so the bolus does not fall out of the mouth; 2) swallowing pressure formation in the swallowing movement to transfer the bolus to the pharynx during the oral cavity phase; and 3) lip formation during articulation

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(Wohlert & Hammen 2000; Secil et al, 2002; Ertekin & Aydogdu 2003; Ertekin et al, 2013). Studies of elderly outpatients in nursing care facilities reported that mouth exercises including

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lip movements increased lip closure force and ameliorated articulation and swallowing dysfunction (Ishikawa et al, 2006; Ooka et al, 2008). These findings suggest that enhancing lip closure force through lip closure training is useful for improving eating and swallowing as well as articulation. Consistent with this idea, lip closure training improved eating behavior

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(see below) and swallowing (Nakada et al, 2013b).

Effects on eating behavior

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The present results indicated that lip closure training decreased eating time per mouthful and decreased food spills per mouthful, suggesting improvement of eating/oral function.

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Malnutrition is often observed in elderly persons requiring nursing care due to decreased eating/oral function, and there is an increased risk of morbidity and mortality associated with malnutrition in such patients (Sullivan et al, 1990; Robbins et al, 2002; Weijenberg et al, 2011). Furthermore, meals are adjusted for most elderly residents in facilities for patients requiring intensive nursing cares (e.g., rice porridge, food blending). Improvement of eating behavior by lip closure training might not only ameliorate malnutrition, but also improve quality of life of elderly persons residing in such facilities since they can accept a wider variety of foods due to improvement of eating/oral function.

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ACCEPTED MANUSCRIPT It has been reported that elderly persons take compensatory actions such as avoiding foods that they find difficult to chew, and preferring soft foods in response to decreased eating/oral function (Horwath, 1989; Mioche et al, 2004). In studies using rats and

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senescence-accelerated mice, soft diet feeding and cutting off of molar crowns decreased the number of cholinergic neurons in the diagonal band/medial septal nucleus, decreased acetylcholine concentration, decreased synaptic density in the cerebral cortex and

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hippocampus, and decreased spatial memory compared with control animals (Terasawa et al, 2002; Onozuka et al, 1999; Yamamoto et al, 2001). These findings suggest that eating/oral

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dysfunction may negatively affect cognition and memory, which could be ameliorated by lip closure training.

Effects on daytime sleep

Daytime sleepiness is associated with sleep apnea. The prevalence of sleep apnea with

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apnea-hypopnea index (AHI) ≥ 5 in elderly persons is extremely high (20-50%) (Krieger et al, 1983; Ancoli-Israel et al, 1991; Dickel et al, 1990; Bixler et al, 1998). Mouth breathing, one

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of the causes of sleep apnea in elderly persons, tends to be induced by lip closure dysfunction (De Menezes et al, 2006), and may promote airway obstruction due to glossoptosis and sleep

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apnea during sleeping (Bachour & Maasilta, 2004; Ramar & Guilleminault, 2006; Enoz, 2007; Lee et al, 2007; Yoshimura et al, 2016), eventually leading to cognitive impairments from obstructive sleep apnea (Lal et al, 2012; da Silva, 2015). Thus, lip closure dysfunction is one of peripheral causes of obstructive sleep apnea. Central (brain–related) impairments could also induce obstructive sleep apnea. A brain morphological study of patients with obstructive sleep apnea revealed atrophy of brain regions including the frontal lobe; the atrophy was unilateral and was found in well-perfused areas, suggesting that it may be the cause rather than the result of sleep apnea (Macey et al, 2002). These findings suggest that elderly persons

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ACCEPTED MANUSCRIPT are likely to have sleep disorders, which might increase daytime sleep due to obstructive sleep apnea with peripheral and/or central causes, although the symptoms are not severe in elderly persons (Bixler et al, 1998).

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In the present study, daytime sleep duration decreased by lip closure training. A previous study reported that lip closure training ameliorated apnea-hypopnea index (AHI) and increased saturation of peripheral oxygen (SpO2) during sleep (Suzuki et al, 2013). These

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findings suggest that lip closure training might ameliorate sleep apnea, in turn reducing daytime sleep, through 1) amelioration of lip closure dysfunction (amelioration of obstructive

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sleep apnea) and 2) activation of the brain including the prefrontal cortex (see below).

Effects on the prefrontal cortical hemodynamic activity

The results of the present study revealed that the dorsolateral prefrontal cortex was activated during lip closure in the LCT group performing lip closure training. Furthermore,

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activation in the prefrontal cortex was correlated with the improvement of maximal lip closure force by training. Consistent with the present results, the dorsolateral prefrontal cortex is

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implicated in motor control; activity of the dorsolateral prefrontal cortex was increased during production of static precision grip force (Neely et al., 2013). Furthermore, repetitive

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transcranial magnetic stimulation at the dorsolateral prefrontal cortex improved fine motor control of the hand (Baeken et al., 2011). The dorsolateral prefrontal cortex plays a central role in cognitive functions such as working memory, executive function, and attention, but such activity declines due to aging and dementia (Neary et al, 1988; Imran et al, 1999; Nyberg et al, 2010). Previous studies have suggested a link between oral function and cognitive/memory function; an fMRI study reported that the subjects’ task response latency (healthy adults) was shortened by pre-task gum chewing and that the anterior cingulate cortex and left prefrontal cortex were activated

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ACCEPTED MANUSCRIPT during the task (Hirano et al, 2013). Studies using mouse models of eating disorders reported that a decrease in chewing ability and change to soft diet feeding decreased synaptic and neuronal density in the hippocampus and cerebral cortex, causing memory and cognitive

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impairments (Onozuka et al, 1999; Yamamoto et al, 2001). These findings suggest that sensory feedback signals from the orofacial region is important to maintain prefrontal activity and its function, and that lip closure training enhanced prefrontal cortical activity by

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improving eating/oral function, through enhancement of sensory feedback signals from the orofacial region (see below). It has been reported that the mesencephalic nucleus of the

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trigeminal nerve, which receives inputs from the masticatory muscular receptors and orofacial somatosensory receptors, projects to the superior colliculus (Ndiaye et al, 2000), forming a system that plays an important role in masticatory movements (Adachi et al, 2003). Furthermore, the superior colliculus projects directly to the prefrontal cortex in humans (Leh et

al,

2005).

These

findings

suggest

that

sensory

signals

from

various

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mechanical/somatosensory receptors in the orofacial region during masticatory movements stimulate the brain including the prefrontal cortex (Ono et al, 2010). Thus, lip closure training

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Conclusions

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might improve orofacial sensory feedback system, thereby activating the prefrontal cortex.

Our results demonstrated that lip closure training ameliorated eating dysfunction, decreased daytime sleep, and activated the prefrontal cortex in elderly persons. These findings suggest that lip closure training improves not only ADLs but also higher-brain function, suggesting its usefulness in elderly individuals with decreased oral/eating and cognitive functions. It is noted that implementation of oral function training using food involves the risk of pulmonary aspiration. However, the present training method to improve oral function can be implemented daily without such risk, further raising the usefulness of lip closure training in

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ACCEPTED MANUSCRIPT elderly persons.

Acknowledgments

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This work was supported partly by a research grant from Japan Judo Therapist

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Association.

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ACCEPTED MANUSCRIPT training improves halitosis and obstructive sleep apnea syndrome: a case report. Journal

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ACCEPTED MANUSCRIPT Figure legends

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Fig. 1. Lip closure training device.

Fig. 2. Probe position using near-infrared spectroscopy (NIRS) to measure cerebral hemodynamics.

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A: Placement diagram of the light-emitting and -receiving probes. The light-emitting and -receiving probes (six each) were alternately placed and the measurement channels were set at

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16 points at the midpoints between them. The inter-probe space was 3 cm.

B: The prefrontal cortex was divided into three regions: channels 1–3 were placed on the right dorsolateral prefrontal cortex (a), channels 4–13 on the anterior dorsomedial prefrontal cortex (b), and channels 14–16 on the left dorsolateral prefrontal cortex (c).

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Fig. 3. Changes in maximal lip closure force before versus after intervention. The rate of change in maximal lip closure force significantly increased in the lip closure

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training (LCT) group compared with the control group (Student’s t-test, P < 0.05). The

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vertical axis shows the rate of change in maximal lip closure force (4 weeks/0 weeks).

Fig. 4. Changes in eating behavior. A: Post-intervention rate of change in eating time per mouthful significantly decreased in the lip closure training (LCT) group compared with the control group (Mann-Whitney U test, P < 0.05). The vertical axis shows the rate of change (4 weeks/0 weeks). B: Post-intervention rate of change in food spills per mouthful significantly decreased in the LCT group compared with the control group (Mann-Whitney U test, P < 0.05). The vertical axis shows the rate of change in the rate of food spills per mouthful (4 weeks/0 weeks).

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Fig. 5. Changes in daytime sleep hours before versus after the intervention period. The rates of change in sleep time in the morning (8:30 AM–12:00 PM) and afternoon (1:00

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PM–5:00 PM) before and after intervention were analyzed by repeated-measures two-way analysis of variance (time period × group). The results indicate that the rate of change in sleep time significantly decreased in the lip closure training (LCT) group compared to the control

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group (P < 0.05). The vertical axis shows the rate of change in daytime sleep time (4 weeks/0

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weeks).

Fig. 6. Changes in cerebral hemodynamic activity in the prefrontal cortex before versus after the intervention period.

A repeated measures two-way ANOVA (region of interest × group) of changes in t-values between before and after the intervention period indicated that changes in t-values

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significantly increased in the lip closure training (LCT) group compared with the control group (P < 0.05). The vertical axis shows changes in Oxy-Hb t-values (4 weeks - 0 week).

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DLPFC, dorsolateral prefrontal cortex; DMPFC, dorsomedial prefrontal cortex.

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Table 1. General conditions of the subjects.

Women Age (± SE)

LCT group

10

2

8

87.3 ± 1.6

Control group

10

0

10

85.3 ± 1.4

Barthel Index (± SE)

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Men

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Total

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53.5 ± 8.3

48.5 ± 5.9

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Fig. 1

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A.

Light-emitting probes

Channels

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Light-receiving probes

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NIRS 16 ch

Fig. 2

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B.

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Rate of change in lip closure force (4 weeks/0 weeks) 1.0

0.5

0

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1.5

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2.0

*

Fig. 3

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(N = 10)

(N = 10)

Control

LCT

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A. Eating behavior (time)

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1.0

* 0.8

0.6

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Rate of change in eating time per mouthful (4 weeks/0 weeks)

1.2

(N = 10) 0.4

(N = 10)

Control

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LCT

B. Eating behavior (food spilling)

1.0

0.5

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1.5

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Rate of change in food spills per mouthful (4 weeks/0 weeks)

2.0

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0

*

(N = 10)

(N = 10)

Control

LCT

Fig. 4

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1.2

1.0

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Rate of change of sleep duration

LCT (N = 10)

1.4

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Control (N = 10) *

0.8

0

Morning

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Afternoon

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Fig. 5

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Control (N = 10)

4

LCT (N = 10)

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2

0

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Changes in Oxy-Hb t-values (4 weeks - 0 week)

*

DMPFC

-2

DLPFC (left)

DLPFC (right)

Fig. 6

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-4

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