Diagnosis of occlusal dysesthesia utilizing prefrontal
hemodynamic activity with slight occlusal interference
Yumie Ono1, Yu Ishikawa1, Motohiro Munakata2, Tomoaki Shibuya3,4, Atsushi Shimada3,4,
Hideo Miyachi5, Hiroyuki Wake3,4 & Katsushi Tamaki3,4
1

Health Science and Medical Engineering Laboratory, Department of Electronics and Bioinformatics, School of Science and Technology, Meiji University,
Kawasaki, Japan2
Department of Oral Implantology, Kanagawa Dental University Hospital, Yokosuka, Japan3
Department of Prosthodontic Dentistry for Function of TMJ and Occlusion, Kanagawa Dental University, Yokosuka, Japan
4
Department of Special Denture and Occlusion & Liaison, Kanagawa Dental University Hospital, Yokosuka, Japan
5
Department of Psychiatry, Kitasato University School of Medicine, Sagamihara, Japan

Keywords
diagnostic criteria, near-infrared spectroscopy,
occlusal discomfort syndrome, occlusal
dysesthesia, phantom bite syndrome,
somatoform disorder.
Correspondence
Yumie Ono, Health Science and Medical
Engineering Laboratory, Department ofElectronics and Bioinformatics, School of
Science and Technology, Meiji University, Room
A806, 1-1-1 Higashi-Mita, Tama-ku, Kawasaki,
Kanagawa 214-8571, Japan.
Tel: +81449347302 Fax: +81449347883
E-mail: yumie@meiji.ac.jp
Received: 28 January 2016; Revised:
27 March 2016; Accepted: 30 March 2016
doi: 10.1002/cre2.32

Clinical diagnosis of occlusal dysesthesia (OD), also referred to as phantom bite syndrome, is currently based on the absence of objective occlusal discrepancy despite thepersistent complaint of uncomfortable bite sensation. We previously demonstrated
that the subjective feeling of occlusal discomfort generated by artiﬁcial occlusal interference can be objectively evaluated using prefrontal hemodynamic activity in young
healthy individuals. The aim of this study was to investigate whether dental patientswith and without OD show distinct prefrontal activity during grinding behavior withan occlusal interference. Six dental patients with OD (OD group) and eight patients
without OD (control group) grinded piled occlusal strips placed between their ﬁrst
molars and reported their perception and discomfort thresholds during continuous
monitoring of prefrontal hemodynamic activity with a portable functional nearinfrared spectroscopy. Although patients without OD showed the typical hemodynamic pattern of increased oxyhemoglobin and reduced deoxyhemoglobin (HHb)
concentration, those with OD showed persistent incremental increases of HHb concentration that began at the loading of occlusal strips on their molars before they
executed grinding. The intensities of the task-related HHb activities showed statistically signiﬁcant differences between OD and control groups, particularly at channel
3, arranged over the left frontal pole cortex. When the discrimination criterion was
set using the intensity values of channel 3 from both groups, the overall accuracy of
the OD discrimination was 92.9%. Although physiological interpretation has yet tobe elucidated, the task-related response of an increase in HHb may be a usefulneuronal signature to characterize dental patients with OD.

Introduction
Occlusal dysesthesia (OD) (Clark & Simmons, 2003), also referred to as phantom bite syndrome (Marbach, 1976) or anarrow sense of occlusal discomfort syndrome (Tamaki
et al., 2016), is a symptom characterized by “a persistentcomplaint of uncomfortable bite sensation with no obvious
occlusal discrepancy” (Hara et al., 2012; Melis & Zawawi,2015). Currently, OD is accepted as a derived form of thesomatoform disorder in which the symptom is mostly
expressed in the oral area, and history of dental occlusal
procedures may trigger the symptom (Hara et al., 2012; Melis& Zawawi, 2015). Dental therapy, such as occlusal adjustment,
fails to relieve discomfort in OD patients; therefore, it isnecessary to diagnose patients with OD from other dental
patients early to avoid unnecessary dental treatment and to
improve patient quality of life.
We have previously shown that the intensity of prefrontal
hemodynamic activity accurately reﬂects the subjective intensity of simulated occlusal discomfort in healthy individuals(Ono et al., 2015). In the present study, we adopt a similarparadigm of the combined use of simulated bite rise andfunctional near-infrared spectroscopy (fNIRS) to investigate
whether prefrontal hemodynamic activity under slight occlusal interference differs between OD patients and age-matchedand gender-matched control dental patients without OD.
With its unique feature of tolerance to body movement,
fNIRS has been used to investigate regional cortical activity©2016 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.
1This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original
work is properly cited.

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related to jaw movement as a reliable functional brain imaging
modality in the ﬁeld of dentistry (Shibusawa et al., 2009;
Narita et al., 2009; Iida et al., 2012). The current hypothesisis that the hemodynamic response from the frontal polecortex (FPC), the most anterior part of the prefrontal cortex,
may show a distinct response pattern in OD patients. Although the primary role of the FPC in a variety of human cognitive functions is still debated, Christoff and Gabrieli (2000)
suggested that an activation of FPC indicates “monitoringand manipulation of internally represented information” thathas been previously or originally experienced, to assist thecognitive processing of “externally generated,” ongoing information in the dorsolateral prefrontal cortex (DLPFC). Participants in the current study were instructed to judge if the
thickness of their raised bite was at their perception or discomfort threshold in order to compare altered proprioceptive
occlusal perceptions with intrinsic occlusal perceptions. Consequently, the activation of FPC and the concomitant increaseof blood ﬂow signal in fNIRS are expected in this paradigm.
We aimed to determine whether the FPC area of OD patients,
whose self-body image of their dental occlusion had been altered, exhibited a hemodynamic response pattern required
to judge occlusal vertical dimension. An additional aim was
to investigate the utilization of different hemodynamic
response patterns between patients with and without OD toclassify these two patient groups given their distinct hemodynamic time courses.

Materials and Methods
Participants
Six patients with OD (one man, ﬁve women; mean age± standard deviation [SD] 49.5 ± 7.5 years; OD group)and eight age-matched dental patients without OD (allwomen, mean age ± SD 59.3 ± 8.0 years; control group)participated in the experiment. Mean patient age and gender distribution conformed to those in a previous reportof 37 cases (51.7 ± 10.6 years, male/female ratio: 1/5.1)(Hara et al., 2012). OD was diagnosed by one psychiatrist
and three dental clinicians based on criteria proposed by
Melis and Zawawi (2015). Brieﬂy, the criteria for OD
patients comprised complaint of uncomfortable bite sensation for at least 6 months in the absence of dental occlusal discrepancies or disproportional to the complaint.
Control group participants were patients who regularly
visited the Kanagawa Dental University Hospital for prosthodontic apparatus maintenance. Inclusion criteria forcontrol group comprised no complaint of uncomfortable
bite sensation for at least 6 months and remaining natural
mandibular ﬁrst molar and its opposing teeth of the habitual chewing side. Clinicians interviewed all participants
and assessed their stomatognathic function upon arrival at2

the clinic to ensure that they were free from psychiatric
symptoms and any objective stomatognathic symptoms
that required treatment such as caries, periodontal
disease, and temporomandibular dysfunction. Exclusion
criteria therefore comprised (i) existence of prosthetic
apparatus (bridge, removable denture, and/or tooth
implant) and (ii) caries and/or severe periodontal diseasearound the mandibular ﬁrst molar and its opposing teethof the habitual chewing side. Occlusal contact between thetested teeth was conﬁrmed in all participants with 12-μmthick occlusal paper. This study followed the protocol forthe use of human participants and was approved by the
Ethics Committee of the Kanagawa Dental University
Hospital (approval no. 214). All participants provided
written informed consent after full explanation of theexperiment was provided.

Functional near-infrared spectroscopy dataacquisition
Participants comfortably sat in a dental chair at reclining angleof 100° (Fig. 1A). An investigator (M. Munakata or K.
Tamaki) inserted a 12-μm-thick metal strip (ARTUS;
Englewood, NJ) on the occlusal surface of the mandibular ﬁrst
molar of the habitual chewing side and verbally instructed thetiming for grinding motion. A block design comprising 10 s ofholding the metal strip in the mouth, 15 s of gentle grinding,and 30 s of rest was adopted. Participants closed their jaw with
their least occlusal force to hold the metal strip with theirmaxilla and mandibular molar teeth to perform grinding.
Four-channel wireless fNIRS probes (Hb13; Astem Co. Ltd,
Kanagawa, Japan) were positioned over the prefrontal cortices. Probes were attached above Fp1, Fp2, F7, and F8 according to the international 10–10 system, corresponding tobilateral FPCs and inferior frontal gyri ((Okamoto et al.,2004); Fig. 1B). Each optical probe comprised a single emitterand two detectors with different emitter-detector intervals (4and 35 mm; Fig. 1C) to simultaneously record the skin andcortical blood ﬂow at a sampling rate of 2 Hz. Measurements
were repeated by increasing the thickness of metal strips(12 μm per each strip) through stacking from 0 μm (onlythe strip holder was inserted into the mouth) until the thickness at which the participant perceived occlusal discomfort
was reached. Participants communicated their perception
and discomfort thresholds to the investigator by hand signs after the rest period of each trial.

Data analysis
Previous studies have shown that the occlusal vertical dimensions at perception and discomfort thresholds vary
among participants (Ono et al., 2015). Therefore, we ﬁrst
compared the time course of fNIRS responses between the©2016 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.

Y. Ono et al.

Occlusal Dysesthesia Diagnosis

Figure 1. Schematic image of experimental setup. (A) Portable functional near-infrared spectroscopy (fNIRS) arrangement on a participant sitting in a dental
chair. (B) Four optical probes (channels 1–4) are attached on the forehead of the participant. (C) Magniﬁed image of a single probe (photograph on the top)
containing one emitter and a pair of detectors for simultaneous measurements of cutaneous and cortical hemodynamic responses, respectively.

OD and control group during (i) grinding without metal
strip, and grinding metal strips with thicknesses at their(ii) individual perception and (iii) discomfort threshold.
The fNIRS waveforms of each trial were separately normalized with SD values during 5 sec before initiating holding
motion and were baseline corrected at the onset of holding
motion to enable comparison between participants. The
peak amplitudes of the normalized and baseline-corrected
fNIRS responses were compared among the three conditions
to investigate the difference in fNIRS responses related to
the grinding with different occlusal perceptions. The aforementioned analysis demonstrated that the time course of
these waveforms were almost identical in a single participantgroup at these three conditions, which were almost equal or
below the minimal discomfort threshold. Therefore, fNIRS
waveforms were averaged across all trials for each participant to improve the data’s signal-to-noise ratio. The averaged, normalized, and baseline-corrected data were used
for further analysis.
To conﬁrm that the observed fNIRS response mainly originating from the cortex, we measured the signals obtained
from two different interprobe intervals. Because of the path
length of the near-infrared light, fNIRS signals obtained froman interprobe interval of 4 mm can be considered as signals
mostly reﬂecting skin blood ﬂow, while those obtained froman interprobe interval of 35 mm are those mainly reﬂecting
cerebral blood ﬂow with little skin blood ﬂow contamination(Fig. 1C).
We also performed a regression analysis of the averaged,
normalized, and baseline-corrected waveforms at a selectedchannel to determine the task-dependent activity pattern intensity. A generalized linear model using the hemodynamic
response function (HRF; (Friston et al., 1994)) was applied
accordingly,y ðt Þ ¼ a1 HRF ðt Þ þ a2 t þ b þ ε;where a1, a2 denote HRF and time-course trend coefﬁcientsand b and ε denote baseline and error, respectively. The coefﬁcient a1 corresponding to the HRF was considered the intensity of the task-dependent hemodynamic response aspreviously described (Ye et al., 2009; Ono et al., 2015).
Using the coefﬁcient values of the individual fNIRS signal at
the speciﬁc channel, we further developed the classiﬁer that
could best discriminate the patients with and without OD.
In brief, the linear discrimination analysis algorithm(Krzanowski, 1988) was applied to the coefﬁcient values ofboth groups to determine the discrimination threshold. The
mean accuracy of the classiﬁer was determined using theleave-one-out cross-validation algorithm. We also calculated
the sensitivity, speciﬁcity, positive predictive value, and negative predictive value of the classiﬁer. All analytical procedures
were performed by our in-house developed programs using
MATLAB (Natick, MA).

Statistical analysis
Occlusal vertical dimensions at perception and discomfort
thresholds were compared between groups using two-sample
t-test, after the Shapiro–Wilk test conﬁrmed the normality ofthe data. The peak amplitudes of the grinding-related fNIRS
responses among different occlusal vertical dimensions thatwere compared using one-way repeated measures analysis ofvariance after the Shapiro–Wilk test conﬁrmed the normalityof the data. We conﬁrmed the signiﬁcance of linear regression
relationships between the fNIRS waveforms and the predictor
responses in all regression models tested using an F-test simultaneously calculated with the regression analysis in MATLAB.
Mean coefﬁcient amplitudes were compared between groups©2016 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.

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Y. Ono et al.

Occlusal Dysesthesia Diagnosis

using the t-test after data normality was conﬁrmed by the
Shapiro–Wilk test.

Results
Perception and discomfort thresholds
Control and OD groups showed comparable occlusal verticaldimensions at perception and discomfort thresholds. Discrimination thresholds were 40.5 ± 6.0 and 32.0 ± 8.0 μm incontrol and OD groups (P = 0.401), and discomfort thresholds were 79.5 ± 9.6 and 76.0 ± 19.5 μm in control and OD
groups, respectively (P = 0.865). There were no statisticallysigniﬁcant differences in mean discrimination and discomfort
thresholds between participant groups.

Task-related increase of deoxyhemoglobin
response in OD patients
The time course of the cortical oxyhemoglobin (HbO) anddeoxyhemoglobin (HHb) concentration change responses in
conditions without bite rise, with occlusal vertical dimension

at perception, and with that at discomfort threshold wereshown in Figure 2. Although there was a tendency of augmented hemodynamic response found at discomfort threshold compared with the other conditions, neither participantgroup showed statistically signiﬁcant differences in the peak
amplitudes of hemodynamic responses among conditions(detailed results of the statistical analysis were shown in Fig. 2).
Time courses of HbO and HHb concentration change
responses averaged across all trials at four cortical (35 mm),and cutaneous (4 mm) fNIRS channels are presented in
Figure 3. Hemodynamic response patterns of cutaneous
HbO and HHb signals were almost identical (Fig. 3B); however, the cortical HbO and, in particular, the HHb signals
showed contrasting pattern between groups. The hemodynamic response of the control group comprised increasing
HbO and decreasing HHb. There was little or no increase in
HbO signals in the OD group; however, there was a strong
task-dependent increase of HHb, particularly at the channels
on the left hemisphere (channels 3 and 4). Furthermore, theincrease in HHb signals began from the time around 0 in all
channels (Fig. 3A), before the actual grinding is performed.
Therefore, the duration of cortical activity in a basal function

Figure 2. Normalized oxyhemoglobin (HbO) and deoxyhemoglobin (HHb) waveforms during the grinding task with different occlusal vertical dimension ofno bite rise (black), perception threshold (green), and discomfort threshold (red) in control group (A) and occlusal dysesthesia (OD) group (B). Shaded areas
indicate standard error of mean. Time zero was set at the loading of a strip holder into the mouth, and participants were instructed to maintain a 10-sec
mandible rest position (indicated as “H”: hold). Following the hold period, participants performed a gentle grinding for 15 sec (indicated as “G”: grind). F
and P values obtained from one-way repeated measures analysis of variance of the peak amplitudes among conditions were also provided.

4©2016 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.

Y. Ono et al.

Occlusal Dysesthesia Diagnosis

Figure 3. Normalized and averaged oxyhemoglobin (HbO) and deoxyhemoglobin (HHb) waveforms in control group (black) and occlusal dysesthesia (OD)
group (blue) at interprobe intervals of 35 (A) and 4 mm (B). Shaded areas indicate standard error of mean. Time zero was set at the loading of a strip holder
into the mouth, and participants were instructed to maintain a 10-sec mandible rest position (indicated as “H”: hold). Following the hold period, participants
performed a gentle grinding for 15 sec (indicated as “G”: grind).

for the regression analysis HRF(t) was deﬁned from the loading of occlusal strips (t = 0 sec; Fig. 3) until the end of grinding
period (t = 25 sec; Fig. 3). Regression analyses of cortical HbO
and HHb responses further conﬁrmed the signiﬁcantly larger
task-dependent HHb response in the OD group at channels 3(P = 0.001) and 4 (P = 0.021, Fig. 4).

Classiﬁcation of occlusal dysesthesia patientsdepending on prefrontal deoxyhemoglobin
signals
We calculated threshold values to discriminate the occurrenceof OD using the regression coefﬁcient values of channel 3,
showing the highest statistical signiﬁcance in group comparison. After determining the threshold value in each test andtraining data sets in the leave-one-out cross-validation, themean classiﬁcation accuracy was 92.9%. The overall sensitivity, speciﬁcity, positive predictive value, and negative predictive values were 83.3%, 100%, 100%, and 88.9%, respectively.

Discussion
We measured prefrontal hemodynamic responses during
grinding behavior with slight occlusal interference in dental
patients with and without OD. Patients with OD showed atask-related increase in HHb; however, those without OD
showed a task-related reduction in HHb. This suggests that
prefrontal hemodynamic responses may be a potential marker
for detecting patients with OD. In addition to high discrimination accuracy of OD patients in the regression analysis of
HHb responses, this examination requires minimal stress tothe patient, because the thickness of the occlusal interference
does not exceed the individual discomfort threshold and theportable fNIRS system enables the patient to remain in thedental chair during examination. In addition to the previous
studies (Ono et al., 2015; Shibusawa et al., 2009; Narita
et al., 2009; Iida et al., 2012) that utilized fNIRS under various
jaw movements to understand the cerebral representation of
the periodontal sensory input, our results further encourage©2016 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.

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Occlusal Dysesthesia Diagnosis

Figure 4. Task-dependent hemodynamic response intensity comparisons
between control and occlusal dysesthesia (OD) groups. Asterisks indicate
statistically signiﬁcant increase of the task-dependent deoxyhemoglobin
response in OD group compared with control (two-sample t-test,**P = 0.001 and *0.021 at channel (Ch) 3 and Ch 4, respectively).

the use of fNIRS in the clinical dentistry as a quantitative, noninvasive, and low-cost diagnostic tool for patients with OD.
We observed a distinct pattern of HbO and HHb responses
during the grinding task between patients with and without
OD. Corresponding to our previous fNIRS study applying asimilar bite rise paradigm to healthy young adult volunteers(Ono et al., 2015), hemodynamic responses in control participants comprised increased HbO and reduced HHb activities.
This indicates blood ﬂow increase and the activation of FPC(Scholkmann et al., 2013), suggesting that FPC works to recall
and manipulate the patient’s self-oral image to assist the comparison process in the DLPFC (Christoff & Gabrieli, 2000). In
contrast, participants with OD showed vague, ﬂuctuated HbO
response and a clear, box-car-shaped HHb response. The
HHb response began at the loading of occlusal strips on molars before grinding was executed (t = 0 s) suggesting that this
response is associated with top-down cognitive control, preparing for the upcoming examination of occlusal vertical dimension, as opposed to bottom-up perception processing

6

based on ongoing motor/proprioceptive afferent information.
The potential contamination of the motion artifact and theautonomic change in the cutaneous blood ﬂow can be excluded because cortical HbO and HHb behaved differently,
and the time course of the cutaneous blood ﬂow response differed from those of the cortical. Alongside the fact that the
HHb responses are less affected by systemic responses, suchas breathing cycles and blood pressure changes (Kirilina
et al., 2012), we consider that the HHb signal increase in
OD patients indicates reduced blood ﬂow in the FPC and cerebral blood ﬂow reallocation to the other part of the cortex.
This may imply the suppression of FPC activity during discrimination of occlusal vertical dimension that may accountfor the variability in an individual’s inappropriate occlusal vertical dimension claims due to the suppressed ability of maintaining self-oral image. This is also supported by the tendency
for larger discomfort threshold variance in patients with OD
than in controls, although the discrimination threshold mean
and variance between these two groups were comparable.
The time course of the hemodynamic responses at discomfort threshold tended to show larger amplitudes comparedwith those in the other conditions in both participant groups,
although the peak amplitudes were not statistically different
among the conditions (Fig. 2). The discrepancy in the different subjective sense of occlusion and the comparable prefrontal blood ﬂow responses may arise from a lack of the statisticalpower to differentiate the minor perceptual differences among
the conditions, which were almost equal or below the minimal
discomfort threshold. However, we could observe distinct differences between participant groups, even from the single-trial
fNIRS signals such as decreasing and increasing patterns of
HHb responses between control and OD groups, respectively,
showing the usefulness of the fNIRS examination under the
proposed grinding paradigm for characterizing patients withand without OD.
In addition to the averaged hemodynamic responses obtained through all bite rise conditions, we also examined discrimination accuracy using regression coefﬁcient values
from hemodynamic responses in the individual trial at no biterise, discrimination threshold, and discomfort threshold. The
best discrimination accuracy was obtained when we utilized
the averaged hemodynamic responses. This suggests that averaging responses may be useful to suppress artifacts that are nottime-locked with the grinding task.
There were several limitations to the current study. First,
the sample size was small because of the relatively rare occurrence of OD. Accumulating more cases could help determine
the general diagnostic criteria of OD via intensity of taskdependent HHb responses. Second, measured cortical areas
were limited to the anterior prefrontal region. The portable
fNIRS system utilizes light-emitting diodes as a light source,
and therefore, we were unable to detect signals from corticalareas covered with hair, such as somatosensory cortices and©2016 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.

Y. Ono et al.

DLPFCs, because of the absorption of near-infrared light byblack hair and hair roots in the Asian participants. Wholehead fNIRS imaging using a system equipped with highpower laser diodes as a light source should be utilized to investigate whether the increased HHb response in the FPC is associated with reallocation of blood ﬂow. However, the FPC
activity well characterized dental patients with and without
OD and is therefore potentially useful for OD diagnosis. The
comparable perception and discomfort thresholds between
patients with and without OD found in the current study support a previous report (Baba et al., 2005) that indicated thecomparative ability of oral sensory perception between OD
patients and healthy controls. Our results suggest that theorofacial area of the somatosensory cortices, which receives
primary sensory information from peripheral nerves to initiate oral sensory processes in the cerebrum (Trulsson et al.,2010), may be intact in patients with OD and that the alteredocclusal perception in the patients with OD may arise fromthe difference in the cortical activity in the higher cognitiveprocessing centers such as the prefrontal cortices. Further
comparison of the somatosensory and prefrontal hemodynamic activities with grinding behavior in patients with andwithout OD would be necessary to elucidate the underlying
neural mechanism of OD, although it is beyond the scope ofthe current study.
In conclusion, we propose a regression analysis of fNIRS
signals during grinding behavior to diagnose OD. Our results
suggest that HHb response coefﬁcients from the left FPC are
signiﬁcantly different between patients with and without OD
and are therefore potentially useful to discriminate the occurrence of OD.

Acknowledgments
This work was supported by Grants-in-Aid for Scientiﬁc Research from the Ministry of Education, Science and Cultureof Japan (KAKENHI grant number 24592938).

Conﬂict of Interest
None declared.
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