Experiments with animals have shown that occlusal dysfunction
affects brain function. (1-4) These studies indicate that occlusal
dysfunction affects the stress response via brain function and leads to
non-oral health problems. Experiments with human subjects have shown
that posterior mandibular displacement significantly activates the
limbic system, (5) indicating that occlusal dysfunction causes various
somatic symptoms. Functional MRI is a useful noninvasive tool for
testing specific hypotheses regarding the anatomical regions that
process sensory and motor signals in the brain. (6) In our recent
experiments, a particular type of fMRI was used to detect small changes
in blood oxygen levels related to the change in the magnetization of
protons within the blood. (7) These fMRI contrast images have high
spatial and temporal resolution. (8) In this study, fMRI was used to
examine two types of malocclusion models using several custom-made
splints that either forced the mandible to one of two retrusive
positions or, as a control, allowed the mandible to remain in its normal
or centric position. Subjects performed a clenching task at the two
different retrusive positions and at normal position. Brain regional
BOLD signals were recorded at all positions both during the clenching
task, as well as during a resting period at the corresponding position.
We compared these in order to investigate how the amount of
TMJ-displacement affects brain activation.
Material and Methods
The fMRI data were obtained from 12 healthy subjects (6 males and 6
females, aged 22 to 45 years, mean age 33.4) with no history of
psychiatric or neurological disease. And according to sagittal skeletal
and occlusal features, they are all dentoskeletal Class I relationships
without missing teeth. Each subject gave written informed consent after
receiving an explanation of the aims and method of the study, which was
approved by the Committee for Research Ethics of Medical University
Hospital, Bonn, Germany. After clinically examining the subjects and
producing electronic condylographic tracings of mandibular/condylar
movement using CADIAX (Computer Aided Axis Recording; GAMMA-DENTAL,
Klosterneuburg, Austria), plaster models (Type IV stone plaster; Fuji
Rock) were mounted, each with an individual hinge axis, on a fully
adjustable articulator (SL, GAMMA-DENTAL, Klosterneuburg, Austria)
(Figure 1, Upper left). The articulator programming was written using
[FIGURE 1 OMITTED]
We took impressions and made maxillary and mandibular dental casts
for each subject. Splints were fabricated by vacuum-pressing a 0.5 mm
thick, polyvinylchloride sheet over the maxillary dental cast (Figure
la). A control splint and two retrusive-forcing splints were made for
each subject. The two retrusive-forcing splints were made by applying a
mound of light-curing resin (Tetric, Vivadent Co., Germany), one 0.5 mm
thick and the other 0.7 mm thick, in the premolar region of the
vacuumpressed sheet. Another vacuum-pressed sheet was used without
modification as a control splint. The splints were checked using a
cross-mounting technique in which the casts could be aligned at
pre-programmed positions with a Mandibular Position Variator (MPV,
GAMMA-DENTAL, Klosterneuburg, Austria), and an analysis using the CADIAX
confirmed that the condylar position along the sagittal condylar path
was bilaterally shifted by 0.5 mm in the postero-retrusive direction for
one experimental splint and by 0.7 mm for the other experimental splint
(Figure 1, b and e). We also verified that the condyles did not shift to
postero-retrusive direction while the subjects were clenching with the
control splint. In order to minimize measurement error, an experienced
dentist tested each subject three times.
The clenching task consisted of five cycles of a 30-sec. clenching
period followed by a 30-sec. resting period, during which the subject
relaxed the jaw-closing muscles and applied only enough force to keep
the mandibular teeth in contact with the maxillary teeth. The five
clenching cycles lasted a total of five min. Each subject performed the
clenching task three times, once with each of the two retrusive splints
(0.5 mm, 0.7 mm) and once with the control splint. After completing one
of the clenching tasks, subjects waited at least 30 minutes before
performing another of the clenching tasks. This waiting interval
prevented one task from influencing the next.
Functional (T2* weighted) images and anatomical (T1 weighted)
images were acquired with a MAGNETOM Avanto 1.5T MRI system (Siemens,
Erlangen, Germany). The functional images consisted of echo-planar image
volumes sensitive to BOLD contrast in the axial orientation (TE=45 ms,
TR=3000 ms). The volume included the entire brain with a 64 x 64 matrix
and 34 slices (voxel size=3.75 mmx 3.75 mm x 4 mm, slice thickness=3 mm,
gap=0.3 mm). Images with 108 volumes were acquired for each experimental
condition (two mandibular retrusive positions and the control position).
Because unstable magnetization routinely degraded the quality of the
first eight volumes, the start of the first cycle of clenching was timed
to coincide with the beginning of the ninth image volume. Immediately
following each fMRI run (five cycles, 108 image volumes), subjects
quantified the subjective discomfort they felt during clenching by
marking a visual analog rating scale (VAS) (9) ranging from 0 to 5 (0 =
no discomfort, 5 = extreme discomfort) and verbally expressed how they
felt during clenching to an interviewer.
Head motion was corrected using SPM5 (University College London,
London). A total of 324 functional images (three runs, 108 image volumes
per run) obtained from each subject were normalized to the MNI template
(10) and spatially smoothed by an 8-mm Gaussian kernel. The data were
statistically analyzed by the general linear model approach (11) using
SPM5. Proportional scaling removed global changes in the BOLD signals.
Statistical contrast images of all subjects for group analysis were used
(paired t-test, uncorrected for multiple comparisons) with a
random-effects model. A value of p<0.01 is considered statistically
significant. For each region of the brain, Tukey's HSD test was
used to compare the BOLD signal changes associated with clenching in the
three different positions. BOLD signal changes were also analyzed by
ANOVA. Statistical significance was established at p<0.05. In the
same way as the BOLD signal changes, the VAS scores were analyzed with
Tukey's HSD test. Statistical significance was established at
A random-effect analysis (n=12) showed that all clenching increased
the BOLD signals in the sensory and motor areas of the oral region,
cerebellum, and the insula (data not shown). All voxel in an activated
area were assigned a value equal to the voxel in that area that had the
peak value (statistically significant at p<0.01, Figure 2).
Control-position clenching activated the PFA. However, it did not
activate the amygdala (Figure 2a). Clenching at the two mandibular
retrusive positions (0.5 mm, 0.7 mm) significantly activated both the
amygdala and the PFA (Figure 2, b and e). The highest threshold T for
statistical significance was 2.76.
In the amygdala, the BOLD signal was greatest when the retrusion
distance was 0.5 mm (statistically significant at * p < 0.01, ** p
< 0.001, Figure 3A). In the PFA, the BOLD signal was greatest when
the retrusion distance was 0.7 mm (statistically significant at * p <
0.01, ** p < 0.001, Figure 3B). The mean VAS score after
retrusive-clenching was higher than it was after controlclenching
(statistically significant at * p < 0.01, ** p < 0.001, Figure 4).
The subjective feeling of discomfort tended to increase as the
mandibular position moved backward.
A previous study (5) had simply manipulated the mandible to the
retrusive position; however, in the present study, the clenching task in
two mandibular retrusive positions calculated on the mounted cast
activated the amygdala and the PFA. These results corroborate a previous
study. (5) However, unlike that previous study, clenching did not
activate the anterior cingulate cortex (ACC) in the present study. This
discrepancy is due to a difference in the clenching task. In the present
experiment, the retrusive splints were produced by adding self-curing
dental resin to the posterior regions (from 1st premolar to 2nd molar on
both sides) of the maxillary splint. These splints force the mandible to
a retrusive position because of contact between upper and lower
posterior teeth (from 1st premolar to 2nd molar on both sides). In
contrast, the retrusive splint in the previous study (5) was produced by
adding self-curing dental resin to the anterior regions (from right
canine to left canine) of the maxillary splint. This splint forced the
mandible to a retrusive position because of contact between upper and
lower anterior teeth (from right canine to left canine). There is
substantial difference between posterior teeth and anterior teeth with
regard to the amount of sensory information transmitted. (12.13)
Therefore, the disappearance of activity in the ACC in this study is
attributed to the difference of sensory input from different regions of
the dental arches. However these two types of mandibular retrusion could
be possible in usual dental practice.
[FIGURE 2 OMITTED]
The amygdala plays a critical role in determining the response to
stress, fear and/or emotion. (14-16) In the current experiment, the
amygdala was significantly activated by clenching at two different
values of mandibular retrusion. In contrast, the amygdala was not
significantly activated by control-position clenching. In this study,
forcing the mandible into a retrusive position promptly caused signals
to be transmitted to the amygdala that gave subjects a feeling that they
described as unpleasant or fear. These results corroborate a previous
study (5); however, the activity in the amygdala associated with
clenching at the 0.5 mm retrusive position was stronger than that at the
0.7 mm retrusive position. This means that the amygdala activity in the
present study probably played a role, not only the unpleasant odor, but
also in the transfer area between neuronal networks related to negative
emotion. The subject could get used to the situation at the mandibular
retrusion and feel a little less fear when clenching at the 0.7 mm
retrusive position. At the same time, there was activity in the PFA for
all of the clenching conditions in this study. The PFA is closely
associated with emotional stress and negative emotional reactions. (17)
The activity in the PFA associated with clenching at the 0.7 mm
retrusive position was strongest among all positions. In this study, the
PFA activity and the VAS score was increasing as the malocclusal level
worsened. This means that the PFA activity in the present study probably
played a role in the scale of unpleasantness.
[FIGURE 3 OMITTED]
The PFA is involved with various higher-level cognitive functions,
(18-21) and imaging studies of this brain region are in progress. Hoshi,
et al., reported that pleasant or unpleasant emotions can be recognized
from cerebral blood flow (CBF), using near-infrared spectroscopy (NIRS).
(22) Because the PFA is located in the cerebral cortex, brain-imaging
techniques that can produce functional images include functional NIRS,
which is a convenient means of imaging the brain. In the future,
malocclusion should be assessed, and its treatment should be designed
objectively via focus on brain activity in the PFA.
[FIGURE 4 OMITTED]
The current study aimed to investigate the correlation between the
severity of malocclusion and brain activation. The study's results
were that the PFA activity and unpleasantness increase as malocclusal
levels worsen. These results indicate that we may be able to objectively
assess the severity of malocclusion by focusing on the brain activity.
However, malocclusions range widely and the sample size is not large
enough to permit a definitive conclusion. Further research is required.
This study was performed at the Life & Brain Institute for
Neuroscience, Medical University of Bonn, Germany, in association with
the Kanagawa Dental College Research Institute of Occlusion Medicine,
Yokosuka, Kanagawa, Japan. We thank Ms. Beate Newport for producing the
functional images and Prof. Rudolf Slavicek of Austria for making this
study possible with his encouragement and expert guidance.
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Markus Greven, D.D.S., Ph.D.; Takero Otsuka, D.D.S., Ph.D.; Leander
Zutz D.D.S.; Bernd Weber, M.D., Ph.D.; Christian Elger M.D., Ph.D.;
Sadao Sato D.D.S., Ph.D.
Manuscript received December 16, 2010; revised manuscript received
May 4, 2011; accepted June 6, 2011
Address for correspondence:
Dr. Takero Otsuka
82 Inaoka-cho, Yokosuka 238-8580 Japan
E-mail: takero @ kdcnet.ac.jp
Dr. Markus Greven is a research student in the Department of
Craniofacial Growth and Development Dentistry, Kanagawa Dental College.
He received his D.D.S. degree from Aachen University in 1994 and a Ph.D.
from Kanagawa Dental College in 2010. His major research interest is
correlation between dysfunction of the masticatory organ and brain
Dr. Takero Otsuka is a special post doctoral researcher of the
Department of Craniofacial Growth and Development Dentistry, Kanagawa
Dental College. He received his D.D.S. from Nihon University in 2003 and
his Ph.D. from Kanagawa Dental College in 2008. His major research
interest is correlation between dysfunction of the masticatory organ and
Dr. Leander Zutz is a dentist and received his D.D.S. from Aachen
University in 2002. His major research interest is function and
dysfunction of the craniomandibular system.
Dr. Bernd Weber is a professor of the biological basis of human
economic decision making at the University of Bonn, sponsored by the DFG
and holds an M.D. degree. His major research interest is in
Dr. Christian Elger is a professor in the Department of
Epileptology at the Medical University of Bonn since 198Z He graduated
from the Medical School of Miinster, Germany in 1976 and received his
D.D.S. degree from the same university in 1978. He received a Ph.D. in
physiology in 1982 and in 1985, he finished his special post doctoral
education in the field of neurology. His major research interests are
brain function in general, epileptological diseases and neuromarketing.
Dr. Sadao Sato is a professor and head of the Department of
Craniofacial Growth and Development dentistry, Kanagawa Dental College.
He received his D.D.S. degree from Kanagawa Dental College in 1971 and a
Ph.D. in 1978 from the same school. Since 1992, he has been a member of
the E.H. Angle Society of Orthodontists. His major research interests
include function and dysfunction of the masticatory organ, the emotional
role of bruxism activity, and craniofacial growth and malocclusion.