**4. Discussion**

We analysed right pupillary reflex data from eight normal subjects, as shown in Figure 5. D1 was 6.15 ± 0.64 mm under the resting condition and 5.20 ± 1.12 mm under the 89 Hz-S condi‐ tion (*p*< 0.01: Wilcoxon signed-rank test, two-tailed). D2 was 4.03 ± 0.79 mm under the rest‐ ing condition and 3.47 ± 0.84 mm under the 89 Hz-S condition (*p*< 0.01). CR was 0.37 ± 0.10 ms under rest and 0.35 ± 0.09 under the 89 Hz-S condition. T3 was 1.089 ± 0.094 ms under rest and 0.973 ± 0.175 ms under the 89 Hz-S condition (*p*< 0.05). VC was 4.90 ± 0.95 mm/s under rest and 5.03 ± 0.89 mm/s under the 89 Hz-S condition. AC was 52.4 ± 16.8 mm/s2

D1, D2, and T3 showed an absolute decrease between the resting state and 89 Hz-S stimula‐ tion, and AC increased between the resting and 89 Hz-S conditions. CR and VC did not

We recorded typical heart rate changes and performed a power-spectral analysis (HRV module, AD Instruments, Japan) under the following six conditions: (1) resting state; (2) 89 Hz-S face; (3) listening to Mozart (Mozart); (4) Mozart + 89 Hz-S face; (5) 89 Hz-S neck; and (6) listening to noise (Noise), as shown in Figure 6. For example, Mozart + 89 Hz-S face "pulse (+)" indicates that participants were listening to Mozart classical music while receiv‐ ing 89 Hz-S vibrotactile stimulation on the face. When comparing heart rates between the rest state and under various stimuli, we used the RR interval peak value from the powerspectral analysis (Fig. 6A and 6C). RR interval peak values (ms) from the power-spectral analysis were compared. The values were as follows: resting state, 757.5 ± 57.0 ms; 89 Hz-S face, 905.1 ± 189.5 ms, Mozart, 771.7 ± 86.7 ms; Mozart + 89 Hz-S face, 875.3 ± 188.3 ms; 89 Hz-S neck, 901.7 ± 188.4 ms; and Noise, 831.7 ± 114.6 ms (Fig. 6C). Significant differen‐ ces were observed between resting state and 89 Hz-S face (paired *t*-test, *P*< 0.01) and be‐ tween resting state and Mozart + 89 Hz-S face, 89 Hz-S neck, and Noise (paired *t*-test, *P*<

The resting-state peak value had the lowest frequency. The Mozart-listening peak value was closest to the resting-state value, which might be because the majority of subjects disliked listening to classical music (three subjects favourite music was classical, and seven people reported classical music was not their favourite), as shown in Figure 6C. The 89 Hz-S stimu‐ lation led to the highest heart-beat frequency in comparison with the resting condition, as shown in Figures 6A and 6C. However, 89 Hz-S face stimulation was effective in many sub‐ jects, as 89 Hz-S face had the smallest SD, as shown in Figure 6C. On the other hand, heart rates during the resting condition and while listening to noise were similar. We generated noise with fractioned foam polystyrene. Many subjects may have felt discomfort due to the

noise; however, we believe that discomfort induced by this noise was unlikely.

change between the resting and 89 Hz-S conditions, as shown in Figure 5.

**3.5. Analysis of HRV during vibrotactile stimulation**

under the 89 Hz-S condition (*p*< 0.05). Of particular note,

under rest and 56.7 ± 17.0 mm/s2

362 Advances in Vibration Engineering and Structural Dynamics

0.05; Fig. 6C).

### **4.1. Relaxation produced by 89 Hz-S vibrotactile stimulation**

We reported that 89 Hz-S vibrotactile stimulation evoked rest and increased salivation, as shown in previous papers (Hiraba et al. 2008, 2011). We further investigated increased sali‐ vation during 89 Hz-S. We were the first to show that increased salivation during 89 Hz-S stimulation was due to increased salivation from the submandibular and sublingual glands but not from the parotid glands, as shown in Figure 3. We knew that the amylase-rich paro‐ tid glands were principally responsible for the increased salivation. Salivation also occurs during mechanical stimulation during mastication when eating (Matuo, 2003). In addition to hunger- and mastication-induced salivation, salivation was also increased through 89 Hz-S vibrotactile stimulation of the facial and intraoral structures. This increased salivation may be different from salivation produced by hunger, as increased salivation during 89 Hz-S caused salivation in the submandibular and sublingual glands. In particular, increased sali‐ vation evoked by 89 Hz-S vibrotactile stimulation may be due to somatosensory input from the facial skin and intraoral cavity. Vibrotactile stimulation at 89 Hz-S may evoke a different perception from masticatory mechanical stimuli.

The frontal cortex is associated with cognitive function, including memory, attention, ab‐ stract reasoning, and higher cognitive processes (Principles of Neural Science, 2000a). We re‐ corded changes in frontal cortex BBF to examine typical changes in fNIRS parameters based on increased oxyHb and totalHb and decreased deoxyHb, as reported by Sakatani et al. (2006). The effect of 89 Hz-S vibrotactile stimulation was almost zero for oxyHb, deoxyHb, and totalHb, as shown in a previous paper (Hiraba et al. 2011). The fNIRS activity focuses on excitatory behaviours that increase oxyHb. In animal experiments, changes in oxyHb and BBF are related, and fNIRS activity changes in oxyHb are used as a marker of neuronal ac‐ tivity (Hoshi et al. 2001). Thus, changes in oxyHb produced by 89 Hz-S vibrotactile stimula‐ tion may indicate mental stability. This may be due to the trend in oxyHb concentration between the 89 Hz-S vibrotactile stimulation in subjects who liked to listen to classical music (Fig. 6B). People relax when they listen to classical music, so we think that 89 Hz-S vibrotac‐ tile stimulation elicits excitation of the parasympathetic system. In particular, although the 89 Hz-S vibrotactile stimulation always led to parasympathetic excitation, listening to classi‐ cal music caused different activity depending on music preference (Fig. 6B). Those subjects who enjoyed Mozart classical music found it relaxing, whereas those who disliked it per‐ ceived it as noise. However, 89 Hz-S vibrotactile stimulation may lead to a balanced mental condition, regardless of preference. This phenomenon suggests that the effect caused by the 89 Hz-S vibrotactile stimulation and the feeling experienced by those listening to Mozart who enjoyed it may be the same. Thus, we suggest that these feelings were produced by parasympathetic activity. We further investigated pupillary reflex and heart rate during 89 Hz-S stimulation.

the resting and the 89 Hz-S conditions (*P*< 0.05). These results suggested that the 89 Hz-S vibrotactile stimulation may elicit parasympathetic activity and greater pupil acceleration. This is likely because parasympathetic activity was stimulated by the 89 Hz-S face stimula‐ tion. Furthermore, vibrotactile stimulation at 89 Hz-S also led to parasympathetic activity.

Optimal Vibrotactile Stimulation Activates the Parasympathetic Nervous System

http://dx.doi.org/10.5772/51156

365

We examined parasympathetic activity in three organs. Autonomic function must ultimate‐ ly be coordinated for adaptation to environmental changes. The autonomic nervous system is composed of visceral sensory and motor system; the visceral reflexes are controlled by vari‐ ous local circuits in the brainstem and spinal cord. These reflexes are regulated by networks of central autonomic control nuclei in the brainstem, hypothalamus, and forebrain and are not under voluntary control, nor do they impinge on consciousness, with a few exceptions (Principles of Neural Science, 2000b). The pupillodilator muscle in the iris (pupil diameter), salivary glands, and heart rate are driven by sympathetic and parasympathetic nerves. Pupil diameter con‐ tracts, heart rate elongates, and salivation increases due to parasympathetic nerve activity. We also believe that changes in the frontal cortex BBF may represent autonomic activity. This coordination is carried out by a highly interconnected set of structures in the brainstem and forebrain that form a central autonomic network. The key component of this network is initiated by integrated information from the parabrachial nucleus of the solitary tract and trigeminal sensory complex in the brainstem. These nuclei receive inputs from somatosensory and vis‐ ceral afferents of the trigeminal, facial, glossopharyngeal, and vagus nerves and then use the information to modulate autonomic function. The somatosensory and visceral sensory out‐ puts from the trigeminal and solitary nuclei are relayed to the forebrain and amygdala by the parabrachial nucleus, which is important for behavioural responses to somatosensory, taste, and other visceral sensations (Principles of Neural Science, 2000b). Information arriving in the amygdala leads to sensations of pleasure and pain. In contrast, the parabrachial nucleus is a taste-sensation relay nucleus in rats (Scott and Small, 2009), and the rodent parabrachial nucleus sends integral limbic and reward system information (Yamamoto et al. 2009). Although their functions in humans are unknown, we think that these nuclei may play roles as relay nuclei of the autonomic system. On the other hand, we showed that a projection from the trigemi‐ nal sensory complex (e.g., the parabrachial nucleus) can also record the response to tactile stimuli from facial skin (Chiang et al. 1994). Furthermore, somatosensory information projects to the primary somatosensory cortex and is then relayed to the frontal cortex via the parietal

What does BBF activity in the frontal cortex indicate? We think that the information transmit‐ ted via the parabrachial nucleus dominates by way of the parietal association area. Thus, information in the frontal cortex is assumed to arrive via the parabrachial nucleus. The hypo‐ thalamus is the centre of the autonomic system. We perceive emotional experiences such as fear, pleasure, and contentment, and these perceptions reflect the interplay between higher brain centres and sub-cortical regions such as the hypothalamus and amygdala (Principles of Neural Science, 2000a). Patients in whom the prefrontal cortex or the cingulate gyrus has been removed are no longer bothered by pain but exhibit appropriate autonomic reactions; howev‐

**4.3. Autonomic activity and anatomical projections in the central nervous system**

association area (Handbook of Neuropsychology, 1994).

## **4.2. Parasympathetic effect produced by 89 Hz-S vibrotactile stimulation**

Our heartbeat increases when we are frightened (Principles of Neural Science, 2000b). The parasympathetic nervous system is responsible for rest, digestion, basal heart rate mainte‐ nance, respiration, and metabolism under normal resting conditions (Principles of Neural Science, 2000b). We examined parasympathetic effects by observing changes in the amount of salivation, HRV modulation of heart rate, and pupillary reflex induced by light stimula‐ tion during various stimuli.

We verified increased salivation induced by 89 Hz-S vibrotactile stimulation; the higher RR frequency was induced by the 89 Hz-S neck stimulation (Fig. 6C), and the greatest pupil contraction following light stimulation was induced by 89 Hz-S vibrotactile stimulation (Fig. 5). Furthermore, the 89 Hz-S face stimulation increased salivation the most (Fig. 3). Specifi‐ cally, increased salivation was due to saliva secretion by the submandibular and sublingual glands but not the parotid glands. This was likely not due to hunger because the amount of salivation in the parotid glands did not increase. From these results, as for 89Hz-S neck, the relaxation effect might be big, however the salivated promotion effect was very weak. Con‐ versely, the difference between pupil diameter before (D1) and after (D2) light stimulation during the resting condition was great, but the difference between pupil diameter before (a-D1) and after (a-D2) light stimulation during 89 Hz-S face was small, as shown in Figure 4. Furthermore, as shown in Figure 5, the AC (acceleration) was significantly different between the resting and the 89 Hz-S conditions (*P*< 0.05). These results suggested that the 89 Hz-S vibrotactile stimulation may elicit parasympathetic activity and greater pupil acceleration. This is likely because parasympathetic activity was stimulated by the 89 Hz-S face stimula‐ tion. Furthermore, vibrotactile stimulation at 89 Hz-S also led to parasympathetic activity.

## **4.3. Autonomic activity and anatomical projections in the central nervous system**

The frontal cortex is associated with cognitive function, including memory, attention, ab‐ stract reasoning, and higher cognitive processes (Principles of Neural Science, 2000a). We re‐ corded changes in frontal cortex BBF to examine typical changes in fNIRS parameters based on increased oxyHb and totalHb and decreased deoxyHb, as reported by Sakatani et al. (2006). The effect of 89 Hz-S vibrotactile stimulation was almost zero for oxyHb, deoxyHb, and totalHb, as shown in a previous paper (Hiraba et al. 2011). The fNIRS activity focuses on excitatory behaviours that increase oxyHb. In animal experiments, changes in oxyHb and BBF are related, and fNIRS activity changes in oxyHb are used as a marker of neuronal ac‐ tivity (Hoshi et al. 2001). Thus, changes in oxyHb produced by 89 Hz-S vibrotactile stimula‐ tion may indicate mental stability. This may be due to the trend in oxyHb concentration between the 89 Hz-S vibrotactile stimulation in subjects who liked to listen to classical music (Fig. 6B). People relax when they listen to classical music, so we think that 89 Hz-S vibrotac‐ tile stimulation elicits excitation of the parasympathetic system. In particular, although the 89 Hz-S vibrotactile stimulation always led to parasympathetic excitation, listening to classi‐ cal music caused different activity depending on music preference (Fig. 6B). Those subjects who enjoyed Mozart classical music found it relaxing, whereas those who disliked it per‐ ceived it as noise. However, 89 Hz-S vibrotactile stimulation may lead to a balanced mental condition, regardless of preference. This phenomenon suggests that the effect caused by the 89 Hz-S vibrotactile stimulation and the feeling experienced by those listening to Mozart who enjoyed it may be the same. Thus, we suggest that these feelings were produced by parasympathetic activity. We further investigated pupillary reflex and heart rate during 89

**4.2. Parasympathetic effect produced by 89 Hz-S vibrotactile stimulation**

Our heartbeat increases when we are frightened (Principles of Neural Science, 2000b). The parasympathetic nervous system is responsible for rest, digestion, basal heart rate mainte‐ nance, respiration, and metabolism under normal resting conditions (Principles of Neural Science, 2000b). We examined parasympathetic effects by observing changes in the amount of salivation, HRV modulation of heart rate, and pupillary reflex induced by light stimula‐

We verified increased salivation induced by 89 Hz-S vibrotactile stimulation; the higher RR frequency was induced by the 89 Hz-S neck stimulation (Fig. 6C), and the greatest pupil contraction following light stimulation was induced by 89 Hz-S vibrotactile stimulation (Fig. 5). Furthermore, the 89 Hz-S face stimulation increased salivation the most (Fig. 3). Specifi‐ cally, increased salivation was due to saliva secretion by the submandibular and sublingual glands but not the parotid glands. This was likely not due to hunger because the amount of salivation in the parotid glands did not increase. From these results, as for 89Hz-S neck, the relaxation effect might be big, however the salivated promotion effect was very weak. Con‐ versely, the difference between pupil diameter before (D1) and after (D2) light stimulation during the resting condition was great, but the difference between pupil diameter before (a-D1) and after (a-D2) light stimulation during 89 Hz-S face was small, as shown in Figure 4. Furthermore, as shown in Figure 5, the AC (acceleration) was significantly different between

Hz-S stimulation.

364 Advances in Vibration Engineering and Structural Dynamics

tion during various stimuli.

We examined parasympathetic activity in three organs. Autonomic function must ultimate‐ ly be coordinated for adaptation to environmental changes. The autonomic nervous system is composed of visceral sensory and motor system; the visceral reflexes are controlled by vari‐ ous local circuits in the brainstem and spinal cord. These reflexes are regulated by networks of central autonomic control nuclei in the brainstem, hypothalamus, and forebrain and are not under voluntary control, nor do they impinge on consciousness, with a few exceptions (Principles of Neural Science, 2000b). The pupillodilator muscle in the iris (pupil diameter), salivary glands, and heart rate are driven by sympathetic and parasympathetic nerves. Pupil diameter con‐ tracts, heart rate elongates, and salivation increases due to parasympathetic nerve activity. We also believe that changes in the frontal cortex BBF may represent autonomic activity. This coordination is carried out by a highly interconnected set of structures in the brainstem and forebrain that form a central autonomic network. The key component of this network is initiated by integrated information from the parabrachial nucleus of the solitary tract and trigeminal sensory complex in the brainstem. These nuclei receive inputs from somatosensory and vis‐ ceral afferents of the trigeminal, facial, glossopharyngeal, and vagus nerves and then use the information to modulate autonomic function. The somatosensory and visceral sensory out‐ puts from the trigeminal and solitary nuclei are relayed to the forebrain and amygdala by the parabrachial nucleus, which is important for behavioural responses to somatosensory, taste, and other visceral sensations (Principles of Neural Science, 2000b). Information arriving in the amygdala leads to sensations of pleasure and pain. In contrast, the parabrachial nucleus is a taste-sensation relay nucleus in rats (Scott and Small, 2009), and the rodent parabrachial nucleus sends integral limbic and reward system information (Yamamoto et al. 2009). Although their functions in humans are unknown, we think that these nuclei may play roles as relay nuclei of the autonomic system. On the other hand, we showed that a projection from the trigemi‐ nal sensory complex (e.g., the parabrachial nucleus) can also record the response to tactile stimuli from facial skin (Chiang et al. 1994). Furthermore, somatosensory information projects to the primary somatosensory cortex and is then relayed to the frontal cortex via the parietal association area (Handbook of Neuropsychology, 1994).

What does BBF activity in the frontal cortex indicate? We think that the information transmit‐ ted via the parabrachial nucleus dominates by way of the parietal association area. Thus, information in the frontal cortex is assumed to arrive via the parabrachial nucleus. The hypo‐ thalamus is the centre of the autonomic system. We perceive emotional experiences such as fear, pleasure, and contentment, and these perceptions reflect the interplay between higher brain centres and sub-cortical regions such as the hypothalamus and amygdala (Principles of Neural Science, 2000a). Patients in whom the prefrontal cortex or the cingulate gyrus has been removed are no longer bothered by pain but exhibit appropriate autonomic reactions; howev‐ er, the sensation is not perceived as a powerfully unpleasant experience (Principles of Neu‐ ral Science, 2000a). Furthermore, the anatomical connections between the amygdala and the temporal (cingulate gyrus) and frontal (prefrontal) association cortices provide the means by which visceral and somatosensory sensations trigger a rich assortment of associations or the cognitive interpretation of emotional states (Principles of Neural Science, 2000b).

The 89 Hz-S stimulation evokes parasympathetic activity. This conclusion was based on increased salivation and heart rate and decreased pupil diameter during 89 Hz-S vibrotac‐ tile stimulation. Increased parotid gland salivation may be due to appetite, and increased salivation in the submandibular and sublingual glands may be associated with feelings of calm. On the other hand, we examined changes in the HRV module (RR intervals) be‐ tween the resting state and exposure to various stimuli, and we showed increased heart rates during 89 Hz-S stimulation in comparison with the resting state (Billman, 2011). Further‐ more, we think that the pupillary light-reflex test (Brashow, 1968) and heart rate HRV module (Billman, 2011) are the best tests for examining autonomic nervous system function (Gad‐

Optimal Vibrotactile Stimulation Activates the Parasympathetic Nervous System

http://dx.doi.org/10.5772/51156

367

We showed that the most effective changes in salivation, pupil contraction, and HRV modu‐ lation (RR interval) were elicited by 89 Hz-S vibrotactile stimulation on the face. We thus conclude that 89 Hz-S vibrotactile stimulation affected parasympathetic activity based on changes observed in three organs. We also investigated autonomic activity by observing fNIRS waves. Because increased salivation was only observed in the submandibular and sublingual glands, it was likely not due to hunger. Furthermore, pupil constriction due to 89 Hz-S stimulation was less than that due to light following the resting condition. This likely indicated parasympathetic activity induced by 89 Hz-S stimulation. Changes in heart rate (RR intervals) during various stimuli were as effective as changes due to various stimuli combined with the 89 Hz-S stimulation. BBF oxyHb concentrations in the frontal cortex dur‐ ing 89 Hz-S vibrotactile stimulation were the same as those in subjects who preferred listen‐ ing to classical music. Thus, 89 Hz-S vibrotactile stimulation may produce relaxation; salivation increases, pupil diameter constricts, and the heart rate (RR interval) is prolonged due to parasympathetic excitation. Thus, we believe that fNIRS in the frontal cortex reflects

This work was supported by a Sogoshigaku research grant and the Sato Fund, as well grants

, Takako Sato2

, Katuko Ebihara1

, Satoshi Nishimura2

, Hisako Ishii1

, Masaru Yamao‐

and Koichiro Ueda1

from the Ministry of Education and a Grant-in-Aid for Scientific Research (21592539).

ner and Martin, 2000).

**5. Conclusion**

autonomic activity.

**Author details**

, Takaya Shimano1

ka3

Nelcy Hisao Hiraba1\*, Motoharu Inoue1

, Ryuichi Sampei1

\*Address all correspondence to: hiraba@dent.nihon-u.ac.jp

**Acknowledgements**

**Figure 7.** Pathways responsible for somatosensory information in the brain. Somatosensory information evoked by vibrotactile stimulation is relayed by the trigeminal sensory complex and solitary and parabrachial nuclei, which arrive at the hypothalamus, thalamus, amygdala, and frontal cortex, respectively. The autonomic system (particularly the parasympathetic nervous system) produces increased salivation. The lateral branch of the trigeminal sensory nucleus projects to the parabrachial nucleus. Information from the parabrachial nucleus is received by the amygdala and fron‐ tal cortex. Furthermore, somatosensory information is projected to the primary somatosensory cortex and relayed to the frontal cortex via the parietal association area. Thus, this information finally leads to a relaxed feeling, and BBF waves reflect parasympathetic activity (modified from schemas in Principles of Neural Science 2000b and Handbook of Neuropsychology 1994).

The 89 Hz-S stimulation evokes parasympathetic activity. This conclusion was based on increased salivation and heart rate and decreased pupil diameter during 89 Hz-S vibrotac‐ tile stimulation. Increased parotid gland salivation may be due to appetite, and increased salivation in the submandibular and sublingual glands may be associated with feelings of calm. On the other hand, we examined changes in the HRV module (RR intervals) be‐ tween the resting state and exposure to various stimuli, and we showed increased heart rates during 89 Hz-S stimulation in comparison with the resting state (Billman, 2011). Further‐ more, we think that the pupillary light-reflex test (Brashow, 1968) and heart rate HRV module (Billman, 2011) are the best tests for examining autonomic nervous system function (Gad‐ ner and Martin, 2000).
