Chewing is necessary for digestion and absorption of various nutrients. In addition to these functions, chewing is tightly linked to the emotional centers of the brain (Deiss et al., 2009). Eating behavior depends on the self-perception of the flavor of food involving the sense of taste, smell, temperature, mechanoreception, and masticatory movement. Sensory signals are individually processed in the gustatory and olfactory neural circuits of the brain and then integrated as a sensation of taste in the insular and orbitofrontal cortical areas (Kringelbach, 2005; Shepherd, 2006). Information on flavors from the cortical areas is further transmitted to the brain reward system, including the nucleus accumbens, midbrain dopamine areas, amygdala, and hypothalamus (Shepherd, 2006; Haber and Knutson, 2010). Hedonic (pleasure–displeasure) responses represent the first level of emotional experiences (Hoffman, 1986). Emotional modulation of the hypothalamus affects the autonomic and motor functions of the body. Moreover, delicious meals relieve muscle tension and relax the mind and the body (Nakamura, 2005).

We previously showed that prefrontal cerebral blood flow during palatable gum chewing was higher than during unpalatable gum chewing (Hasegawa et al., 2013). The food-related stimuli, including flavor and taste, caused consistent activation of the prefrontal cortex, suggesting its active involvement in the emotional change during eating (Hasegawa et al., 2013). Stress causing changes in blood circulation and endocrine system is also known to alter eating behavior and contribute to the persistence of unpleasant emotions (Levine and Morley, 1981). We showed that the emotional changes due to taste and odor influenced the hemodynamic responses and the endocrine system functions (Hasegawa et al., 2017). Negative emotions reduce prefrontal cortex activity (Kim and Hamann, 2007). Previous research has shown that emotional changes are closely related to eating behavior, and pleasant/unpleasant memory is also strongly linked to eating behavior (Hernández Ruiz de Eguilaz et al., 2018). However, previous studies failed to compare the cortical activation between pleasant and unpleasant emotions during chewing.

Functional near-infrared spectroscopy (fNIRS) uses surface-mounted optodes to detect changes in the spectral absorbance of both oxyhemoglobin (oxy-Hb) and deoxyhemoglobin (deoxy-Hb) (Wyatt et al., 1990; Villringer and Chance, 1997; Strangman et al., 2002; Cui et al., 2011; Scholkmann et al., 2014). The principle of operation of fNIRS involves hemodynamic signals that serve as a proxy for neural activity, similar to hemodynamic signals acquired by functional magnetic resonance imaging (f-MRI) (Ferrari and Quaresima, 2012; Boas et al., 2014; Noah et al., 2015). For the hemodynamic response measured by fNIRS, the signal source is registered to standard brain coordinates, as in f-MRI. The fNIRS can also quantitatively evaluate neural activity with high temporal resolution on a channel set-up. This device is compact and exhibits no restrictions with respect to the measurement location. As the constraints during measurement are small, the fNIRS enables experiments in a real-world setting with limited body movement as during chewing (Okamoto et al., 2011; Tachibana et al., 2019; Nagashima et al., 2020). This method can omit head movements during the analysis. Therefore, the fNIRS is suitable for measuring brain activity during chewing.

Thus, this crossover study aimed to clarify whether cortical activity is related by emotional states triggered by chewing gums of different flavors. In particular, we focused on whether changes in the activity of the prefrontal cortex were affected by the emotions (palatable-unpalatable) during eating experience. We used the fNIRS to elucidate the cortical activity during palatable or unpalatable gum chewing related to positive/negative emotions.

The study protocol was approved by the Ethics Committee of the Hyogo College of Medicine (approve num-2209). The study protocol was registered with the UMIN CTR Japan Primary Registries Network (UMIN00025567). This study was conducted in compliance with the Declaration of Helsinki and the ethical guidelines for medical and health research involving human subjects established by the Ministry of Health, Labor, and Welfare in Japan. Written informed consent was obtained from all participants.

Changes in each index were evaluated using the AUC (Hasegawa et al., 2007, 2009, 2013). Using the median values 5 min before gum chewing as the baseline, variations during and after gum chewing were calculated for each index. Changes in each AUC due to the tasks were evaluated using a one-sample Kolmogorov–Smirnov test. In order to assess those regions, the average AUC of the channels included in the two pairs of bilateral ROIs were calculated, and two-way ANOVA with the main effects of the ROI (FPC or DLPFC/SMA) and condition (palatable or unpalatable) and the first-order interaction effect between them were analyzed. The multiple comparisons with Wilcoxon signed-rank test (p-values were Bonferroni-adjusted) were applied to determine whether there was a statistically significant difference in the oxy-Hb change in each ROI during palatable and unpalatable gum chewing (p < 0.05).

To evaluate temporal changes, representative values were calculated every 30 s. A repeated analysis of variance was performed to investigate changes in each index between baseline (median value for 5 min before chewing started) and each 30-s interval after chewing. If a difference was significant, comparisons were made between values before gum chewing and those at other intervals using Dunnett’s test. To compare two samples (palatable gum vs. unpalatable gum and left vs. right for the same position channel), the paired t-tests (normal distributions) or Wilcoxon signed-rank tests (non-normal distributions) were performed. Pearson correlation coefficient (normal distributions) or Spearman’s rank correlation (non-normal distributions) was used to analyze the correlation between the AUC of oxy-Hb and the sensory evaluation.

All statistical analyses were performed using a commercially available software package (IBM SPSS Statistics, version 22.0.0 for Windows; SPSS, Armonk, NY, USA). The level of significance was set at 5%.

This study was conducted to understand the cortical hemodynamic responses related to chewing of gums with different tastes/odors using the fNIRS system. Hemodynamic responses were significantly increased in the bilateral primary sensorimotor cortex during gum chewing compared to the resting conditions. In addition, unpalatable gum chewing showed an increased hemodynamic response in the left frontal channel. There were significant differences in the hemodynamic responses in BA10, corresponding to the frontopolar cortex, between the palatable and unpalatable gum types during the 5 min of chewing.

It is known that the anterior insula and adjoining frontal opercula cortex constitute the primary taste cortex, and the caudal parts of the orbitofrontal cortex constitute the secondary taste cortex (Ogawa et al., 1989; Baylis et al., 1995). These two cortical areas have been shown to be activated by taste in human neuroimaging studies using positron emission tomography (PET) and f-MRI (Small et al., 2001; Del Parigi et al., 2002; Zald et al., 2002; Kringelbach et al., 2004; Small and Prescott, 2005; Mihara et al., 2008). We previously evaluated the effects of taste and flavor on blood flow changes in the frontal cortex (Hasegawa et al., 2013). In this study, we evaluated the grand and time-binned averages of oxy-Hb concentration changes to compare cortical activity during chewing palatable and unpalatable food. The former was employed to evaluate overall activity changes with the chewing experience with pleasant and unpleasant emotions, and the latter was to determine the transient changes in the cortical activity during chewing a flavored gum, whose intensity of taste and odor stimuli lose over time. There was a trend toward greater oxy-Hb change for the unpalatable gum than for the palatable gum, and the difference in oxy-Hb change between gums was significant only in the left FPC among all ROIs. In the frontopolar and DLPFC/SEF, after 0–150 s from the start of gum chewing, the oxy-Hb value during chewing of unpalatable gum was higher than during palatable gum chewing.

We found that when participants chewed palatable gum, hemodynamic responses were significantly higher than those obtained when they chewed gum without any taste and odor or just sweet, even though the masseter muscle activity was not significantly different among the three gum chews. No significant hemodynamic changes were observed when the same taste and flavor samples as those of the palatable gum were placed in the mouth. The results suggest that taste and odor influence brain activity during mastication in sensory, cognitive, and motivational processes, rather than in the motor control (Hasegawa et al., 2013). Therefore, in the present study, only palatable and unpalatable gum chewing was performed, not tasteless and odorless gum chewing, which served as a control.

Palatable gum has been marketed for many years in Japan and is known to have a popular taste and odor; thus, the majority of participants might be able to chew this gum with minimal attention, such as during semi-voluntary exercise (e.g., walking) for 300 s. Conversely, unpalatable gum has a displeasing flavor and is not delicious for most Japanese individuals. Moreover, the participants were under stressful/negative-emotion conditions when they were asked to chew according to the metronome’s rhythm. Thus, the participants had to exert greater effort with respect to the act of chewing in comparison to that of palatable gum. As a result, chewing unpalatable gum was an exercise requiring more voluntary and intentional awareness than chewing palatable gum. Cortical activity in the left frontopolar cortex and DLPFC, which we defined as ROIs in this study, showed a higher value when chewing unpalatable gum than palatable gum.

In this study, cortical activity in the left prefrontal cortex, corresponding to the frontopolar cortex, DLPFC, and supplementary eye fields (BA 8, 9, 10, 46, 44, 45, lateral 47) increased during unpalatable gum chewing compared to that during palatable gum chewing. BA 4, 6, 9, 8 collect sensory information from all modalities undergoing higher-order processing via bidirectional nerve fiber connections between the temporal and parietal association areas. At the same time, BA10 receives inputs of emotional and arousal states through nerve fiber connections with the limbic system, including the hippocampus, cingulate cortex, and amygdala, as well as with the brainstem (Ono et al., 2015a,b). BA10 is also known to be the highest-order cognitive processing area that integrates and controls information from other prefrontal cortex areas. The prefrontal cortex (the frontal pole is part of the prefrontal cortex) and the striatum are involved in the reward prediction process, and anatomically the prefrontal cortex and striatum are closely connected (Ono et al., 2015a,b). Pan et al. (2014) suggested that striatal neurons may only be able to predict reward for novel stimuli. In the present study, it is possible that the striatal neurons were excited by the novel stimuli because the taste of the unpalatable gum was unknown, resulting in increased FPC activity, whereas the known and learned palatable gum did not excite the striatal neurons.

The prefrontal cortex, responsible for appetite control, is thought to be the center of cognitive functions such as attention, learning, thought, memory, and action. In addition, the DLPFC is a critical brain area associated with appetitive control, food craving, and executive functioning, and controls the executive function, which is deeply related to memory, attention, learning, and behavior (Goldman-Rakic, 1996; Miller, 1999; Rowe et al., 2000); PET studies have found that changes in the DLPFC are related to reward value, and regulation of limbic reward regions (Small et al., 2001; Del Parigi et al., 2002). Kringelbach et al. (2004) showed that activation of the left DLPFC region was associated with taste or taste-odor combinations (Gluck et al., 2017). The prefrontal cortex, including the DLPFC, is also known to be responsive to exercise (Colcombe et al., 2006). During low-intensity exercise, the left DLPFC activity is evoked (Byun et al., 2014). In addition, young adults typically demonstrate left-lateralized frontal activation during light-intensity exercise (Hyodo et al., 2016). Notably, chewing movement is a light-intensity exercise; therefore, our results are consistent with those of previous studies. It has been reported that occlusal discomfort, an unpleasant emotion of oral movement origin, increased hemodynamic response in the frontopolar cortex and DLPFC (Ono et al., 2015a), and the present results also implicate the DLPFC in the regulation of emotion. Lorenz et al. reported that DLPFC activity was negatively correlated with perceived intensity and unpleasant emotion (Lorenz et al., 2003), and Minematsu et al. (2018) showed that hedonically positive stimuli decreased oxy-Hb and hedonically negative stimuli increased oxy-Hb in the anterior prefrontal cortex, which is consistent with our results. The valence-lateralization theory, f-MRI studies in healthy subjects demonstrated linear or parametric dependence of negative and positive emotional judgments on neural activity in left and right DLPFC (Grimm et al., 2006). Grimm et al. (2008) reported that healthy subjects showed a negative correlation between left DLPFC neural activity and positive emotional valence by f-MRI study. This report is consistent with our results and may reflect the processing of emotions by chewing at DLPFC. Our result supposed that unpleasurable negative valence may cause greater cortical activity in the frontopolar cortex and DLPFC than pleasant positive valence.

For oxy-Hb changes in the frontal lobe, the left hemisphere level was significantly increased by chewing compared to that in the right hemisphere, possibly because of the presence of a language center in the left hemisphere (Paulesu et al., 1993). Since all the participants in this study were right-handed, the language center was likely located in the left hemisphere. Cortical activity changes in the primary sensorimotor cortex were increased compared to those in the frontal lobe, likely because chewing is considered a semi-voluntary exercise. In the frontal association area, the anterior portion was responsible for higher information processing. For example, the lateral frontal association cortex plays an important role in complicated, abstract cognitive manipulation. In addition, cortical activity in the bilateral hemispheres was the highest approximately 90 s after the start of chewing, and a tendency to maintain such a peak during chewing was also shown in our previous study (Hasegawa et al., 2007). Notably, gum chewing increases oxy-Hb because it is a low-intensity exercise (Hasegawa et al., 2007, 2013). Aoki et al. showed that the prefrontal cortex plays a role in the interaction between mood and cognition in everyday situations (Aoki et al., 2011).

Our results show that blood circulation and chewing muscle activity were comparable between the two gum types. We found weak negative correlations between subjective evaluations and cortical activity changes in the left frontal cortex. Cortical activity increases with brain activity, and right hemisphere superiority is likely related to the stimulation of the taste (Small et al., 1999) and odor (Zatorre et al., 1992; Small et al., 1997)pathways. Stimulation with palatable gum (a familiar flavor for participants) might have caused reduced activation of the left prefrontal cortex. In addition, since the SEF (the anatomical area of the dorsal medial frontal lobe) receives input from DLPFC, and the SEF neurons are known to carry signals related to response evaluation, it is possible that the neural activity in the area was increased during the series of chewing the unfamiliar flavor gum, which elicited negative feelings of not palatable (Stuphorn, 2015).

The present study has some limitations. It is important to note that there is no conclusive evidence to support the hypothesis that emotion or preference is asymmetrically represented in the brain area. Because fNIRS monitors changes in cortical activity on the surface of the cortex, the activity of the areas deeply involved in taste/odor (i.e., gustatory and olfactory neural circuits) cannot be evaluated in this experiment. In the orbital frontal cortex, BA10 was evaluated by many channels, but the cortex corresponding to BA13 and 14 was not covered in this study. To evaluate emotional changes during eating, channel placement targeting the orbitofrontal cortex should be considered in the future. Since Sato et al. (2011) reported that salivary secretion (hemodynamic changes in the arteries around the parotid gland) in response to taste stimuli correlates well with the DLPFC, we should have considered whether there is a difference in salivation between the two gums.

Regardless of gum type, the cortical hemodynamic response was increased in the primary sensory-motor cortex area in both hemispheres during chewing. Emotional changes due to taste and odor modulated the left frontopolar cortex and dorsolateral prefrontal cortex during gum chewing. However, the relationships between such emotional changes and cerebral cortex activity could not be represented by a simple correlation. The palatable/unpalatable emotion during chewing modulated activity in the frontal pole and prefrontal cortex, suggested that the hemodynamic response to chewing with unpleasant emotion was similar to the hemodynamic response that occurs during unpleasant stimuli.

The raw data supporting the conclusions of this article will be made available upon request to the corresponding author YH, cem17150@dent.niigata-u.ac.jp, pending a formal data sharing agreement and approval from the Local Ethics Committee.

The studies involving human participants were reviewed and approved by the Ethics Committee of the Hyogo College of Medicine (approve num-2209). The patients/participants provided their written informed consent to participate in this study.

YH, AS, TS, JS, MS, YO, and TO conceived and designed the research and reviewed the data. YT and HK critically revised the manuscript. YH, AS, TS, JS, and YO collected the data, performed the statistical analysis, and drafted the manuscript. All authors have reviewed the manuscript.