Brain Metabolism in Pre-frontal Cortex and Insula Areas in Patients With Occlusal Splint for Temporomandibular Muscle Disorders

doi:10.21203/rs.3.rs-4846295/v1

Background: There is a relationship between anxiety/depression and the development of disorders in the temporomandibular joint (TMJ), but it is unknown whether treatment for these conditions could have any effect on emotional symptoms. The aim of the present study was to compare brain metabolism in the prefrontal cortex and insula before and after occlusal splint placement in patients with TMJ muscle disorders with anxiety and/or depression. Methods: An experimental study evaluated 23 patients with anxiety and/or depression confirmed by the Hospital Anxiety and Depression Scale (HADS) questionnaire and with TMJ muscle disorders diagnosed by means of clinical examination and the Research Diagnostic Criteria for Temporomandibular Disorders questionnaire. (RDC/TMD), an occlusal splint was then made for condylar decompression 2 mm greater than the mandibular rest space, as confirmed by panoramic radiography before and after the placement of the occlusal splint. Brain metabolism in response to a positive or negative stimulus was evaluated by functional magnetic resonance imaging (fMRI), both with and without occlusal splints.

Results: In both the prefrontal cortex and insula, a statistically significant difference (p <0.001 Wilcoxon test) was found between the stimulus reading without a splint and the stimulus reading with an occlusal splint.

Conclusion: There was a significant difference in brain metabolism in both the prefrontal cortex and insula area, either with positive or negative stimulation before and after occlusal splint placement, between patients with TMJ muscle disorders.

Temporomandibular Joint Disorders

Magnetic Resonance Imaging

Test Anxiety Scale

Occlusal Splints.

People of all ages have been shown to develop stress, anxiety, and depression as well as signs and symptoms of temporomandibular dysfunction [1]. Stress and anxiety are the result of personal and social experiences that normally arise in response to the demands of everyday life; they act as signals to seek adaptation, they are usually transitory, and they can be perceived by affected people as nervousness, frustration and restlessness. Depression is an emotional disorder that affects millions of people every year and is a social and economic burden for nations [2]. Psychosocial stress is a predisposing factor for anxiety and depression and alters the secretion of adrenocorticotropic hormone and cortisol, which modifies the structure of the temporomandibular joint and generates inflammation [1, 3].

Currently, stress, anxiety and depression are considered the most common precursors for the development of TMDs because they promote strong parafunctional muscle activity [4].

Temporomandibular disorders constitute a complex group of pathologies that involve the masticatory musculature, the temporomandibular joint and other structures associated with the stomatognathic system [2, 5, 6]. Epidemiological studies show that 50–70% of the population has these pathologies, mainly in adults between the second and fourth decades of life, preferably in females whose etiology is associated with stress and/or altered psychological states. such as anxiety and depression [7–11].

The most common symptom of temporomandibular disorders is pain [9], which appears as a result of mandibular activity when speaking or chewing, and painful sensations are located in the masticatory muscles, in the atrial prearea and in the joint itself [7, 10]. Individuals with stress, anxiety and depression are associated with pain syndrome,[7] which is related to the presence of acute muscle disorders [9]. A strong relationship has been found between acute pain and stress and anxiety and between chronic pain and depression [7, 8]. Occlusal splint therapy is the most effective therapeutic modality because it significantly improves the signs and symptoms of temporomandibular disorders, positively affecting the masticatory musculature [7, 8, 11, 12].

Stress, anxiety and depression have direct effects on the brain’s emotional reaction centers, that is, on the hypothalamus, the amygdala and the reticular system, producing activation and therefore transmitting excitation to the muscles [6]. The overall effect is an increase in muscle tone (hypertonicity), which produces muscle spasms and increases the amount of inflammation in the temporomandibular joint, leading to muscle parafunction and orofacial pain [6, 8]. Currently, functional magnetic resonance imaging (MR) is the most promising imaging technique for measuring hemodynamic changes in the brain and mapping neurophysiological responses to sensory, motor, and cognitive stimuli [13]. The origin of the changes in the functional magnetic resonance signal is local alterations in tissue oxygenation related to variations in neuronal activity, which are monitored by rapid acquisition sequences, which make it possible to measure these brain changes using the images obtained [13, 14].

This led us to investigate the changes in brain metabolism observed via functional magnetic resonance imaging before and after occlusal splint placement in patients with temporomandibular joint dysfunction.

The aim of this investigation was to compare the effect of an occlusal splint on brain metabolism in the prefrontal cortex and insula before and after the placement of an occlusal splint in patients with TMJ muscle disorders with anxiety and/or depression using functional magnetic resonance imaging.

Participants

The study was approved by the ethics committee of the Cayetano Heredia University of Lima, Peru, with the code 000006645. Each participant signed the informed consent form. The analysis unit was composed of patients who were treated at the Dental Clinic of the San Francisco University of Quito and at the Cabezas Dental Clinic in Quito, Ecuador. The sample size was determined by means of the statistical comparison formula of two proportions, determining the number of samples in 23 (n = 23). Patients who presented with anxiety and/or depression (Hospital Anxiety and Depression Scale”, HADS original version Zigmond and Snaith 1983) were included; had temporomandibular disorders, specifically muscle disorders according to the Research Diagnostic Criteria for Temporomandibular Disorders [RDC/TMD] Dworkin and LeResche, 1992]; were undergoing treatment for temporomandibular disorders for the first time with an occlusal splint; had no systemic diseases; and were not taking any type of medication. Likewise, it was considered that the selected patients did not have pacemakers, brackets, or any metallic objects that could interfere with the quality of the magnetic resonance image and that they did not suffer from claustrophobia.Three patients were excluded for presenting evidence of brain pathology at the initial MRI scan.

Clinical measurements

The psychosocial assessment of anxiety and depression was performed using the "Hospital Scale of Anxiety and Depression" (HADS) [15], where the conditions of anxiety and depression in the study subjects were assessed.

Temporomandibular disorders were evaluated according to the diagnostic criteria for temporomandibular dysfunctions [16], where only muscle disorders of the temporomandibular joint were considered.

Occlusal splint

The 23 patients underwent preparation of an occlusal splint of the superior complete type by means of their individual bite registration via the direct technique, in which acrylic was placed to perform occlusal registration; the thickness was 2 mm greater than the value of the free space in the jaw’s resting position, yielding a vertical thickness of 4 mm. Then, panoramic X-ray was performed with maximum occlusion and with a splint placed in the mouth to confirm condylar decompression.

The splint was worn for the first time in the study at the time of the second functional MRI scan.

Functional magnetic resonance imaging study

The analysis consisted of two functional magnetic resonance imaging methods, the first without prior placement of the occlusal splint and the second immediately after the first resonance recording, in which the occlusal splint was used for the first time after its preparation.

During the study, in both shots, the patients were subjected to visualization of emotional images, some joy (positive stimulation) and others sadness (negative stimulation) at different time intervals, during which memories and images of their life were evoked to produce those feelings. MR imaging started with a complete brain scan in which all brain areas were evaluated for pathologies and/or resonance findings not previously reported. Once the radiologist determined that no pathologies were present, we proceeded with specific functional magnetic resonance imaging to study the prefrontal cortex and insular brain areas, capturing their metabolic activity before and after the placement of the occlusal splint. In the scanning phase, functional magnetic resonance imaging was performed without the placement of the occlusal splint. Seven analysis sequences of 10 seconds each were performed, alternating rest with eyes closed and activation with eyes open. When opening their eyes, patients were instructed to observe the images of people with facial gestures that denoted sadness, panic, terror, or anger (negative emotions) and to think about unpleasant situations that they had experienced during their life.

The same procedure was subsequently performed, with seven analysis sequences of 10 seconds each, alternating rest with eyes closed and activation with eyes open. When opening their eyes, the patients were instructed to observe the images that were shown people with facial gestures that denoted joy, happiness, and enthusiasm (positive emotions) and to think about pleasant situations that they had in their life. In the next phase of the study, the same procedures described above were performed but with the placement of the occlusal splint, and the areas were evaluated in the same way to subsequently establish the difference. (Figs. 1 & 2)

Image acquisition

The functional magnetic resonance imaging data were obtained using a 3T Phillips Healthcare, Best, N. H. An MRI scanner (Netherlands) located at the Axxis Hospital Imaging Center, located in Quito, Ecuador, was used. To characterize the discriminative pattern of brain regions, the percentage oxygen metabolism method was used. The magnetic resonance study was carried out by Dr. P.F., a medical specialist in Radiology with more than 10 years of experience.

During the scan, the subjects received specific instructions; in the first scan, they were maintained with maximum occlusion, and in the second scan, the splint was placed in the mouth for the first time.

Image processing and analysis

The system used for the processing and analysis of computer images was the Exterder Mr. Work Station Philips platform with the Iview Bold (blood oxygen level determination) program, which specifically assesses tissue oxygenation levels related to variations in neuronal activity and is monitored by rapid acquisition sequences establishing quantitative consumption levels with scales ranging from 0 to + 40 (binary system) by means of which comparative values will be established. The functional magnetic resonance analysis sequences of each patient consisted of 18 brain sections. For each cut, 70 activation dynamics were processed and divided into 4 sets of rest and 3 activation sets (of 10 activation dynamics for each). Once the first two shots were taken (flairing and diffusing), with the participants to whom no pathology or abnormal findings were found, the raw functional sequence was taken, with maximum occlusion and a splint placed for the first time, where we visualized and recorded the raw images in real time, analyzing the brain behavior of oxygen consumption with the established paradigms for the activation and deactivation phases. Finally, each specific brain area of the study was evaluated, where the levels of cellular oxygen consumption were analyzed, and comparisons of consumption percentages were made in the activation and deactivation phases with each paradigm used to obtain the results of the study. The information was stored and managed in DICOM format. Simple raw data were stored in an IMPAX System. A backup copy was made on CD (physical medium support) as a routine procedure of the hospital center, where the confidentiality of the protocol was maintained after receiving the permission of the institutional ethics committee. Each specific analysis image (8 shots per patient) encoded with the respective patient number and paradigm was printed without reference to the patient's personal data. These codes are numbered from 001 to 023 for individual study subject codes and subsequent scoring for each corresponding paradigm and brain area as follows:

1.- Negative paradigm, without splint, prefrontal;

2.- Negative paradigm, with splint, prefrontal;

3.- Negative paradigm, without splint, insula;

4.- Negative paradigm, with splint, insula;

5.-Positive paradigm, without splint, prefrontal;

6.- Positive paradigm, with splint, prefrontal,

7.- Positive paradigm, without splint, insula;

8.- Positive paradigm, with splint, insula.

Statistical analysis

Descriptive statistics (mean, median, mode, and standard deviation) of the continuous variables in the study (anxiety and depression) and the frequency and percentages were obtained for the qualitative variable sex. Furthermore, it was determined that the sample did not have a normal distribution using the Shapiro‒Wilk test. For the bivariate analysis, the Mann‒Whitney U test was used because the data were not normally distributed. The Wilcoxon test was used for analysis between groups. For multivariable analysis, multiple regression analysis was used. SPSS (Statistical Package for Social Sciences) version 16.0 software was used for all the statistical analyses.

Of the 23 patients, 78.23% were female and 21.7% were male. The average age was 36 ± 11.8 years for women and 38 ± 10.9 years for men; these two age groups did not significantly differ (p = 0.857 U according to the Mann‒Whitney test). Regarding the depression scale score, the women had an average of 8.88 ±1.49 points, while the men had a score of 9.60 ±2.96 points; these two groups were not significantly different (p= 0.459 Student's t test for the independent groups).

Regarding the anxiety score, the group of women obtained a score of 12.11 ±2.44, while the group of men had an average of 13.2 ±3.34; these two groups did not significantly differ (p = 0.424; Student's t test for independent groups). Therefore, the group was homogeneous in terms of anxiety and depression in both sexes. Regarding the psychological diagnosis, 78.3% of patients had depression and anxiety, 17.4% had only anxiety, and 4.3% had only depression. (Table 1)

PREFRONTAL CORTEX AREA WITH POSITIVE STIMULATION WITH OCCLUSAL SPLINT AND WITHOUT OCCLUSAL SPLINT

The variations in oxygen metabolism in the prefrontal cortex area after exposure to a positive stimulus without the use of an occlusal splint ranged from 30.0% to 48.0%, with an average of 11.6% ± 10.8%, while after the use of the occlusal splint, the values ranged from 1% to 10%, with an average of 3.9% ± 2.8%, which indicated a decrease in cerebral hyperactivity in the studied area (Table 2). A graphical representation of the magnitude of this difference is shown in Figure 3.

In the prefrontal cortex area, before and after the use of the occlusal splint according to the sex of the patient, when exposed to a positive stimulus, an average of 6.1%± 6.6 was found in the female sex, whereas in the group of males, 13.6± 15.2 was found; these findings showed that there was no statistically significant difference (p= 0.111 U) in the Mann‒Whitney test. (Table 3)

Regarding oxygen metabolism in the prefrontal zone in patients with and without an occlusal splint when a positive stimulus was found, a statistically significant difference was found (p <0.001, Wilcoxon test). (Table 3)

PREFRONTAL CORTEX AREA WITH NEGATIVE STIMULATION WITH OCCLUSAL SPLINT AND WITHOUT OCCLUSAL SPLINT

The variations in oxygen metabolism in the prefrontal cortex area when exposed to a negative stimulus without the use of an occlusal splint ranged from 5.0% to 30.0%, averaging 16.3% + 7.6%, while after the use of the occlusal splint, 2% to 12% of the participants were involved in oxygen metabolism, with an average of 4.7% + 2.7%, which indicated decreased cerebral hyperactivity in the studied area (Table 2). A graphical representation of the magnitude of this difference is shown in Figure 1.

In the prefrontal cortex, before and after the use of the occlusal splint according to the sex of the patient, when exposed to a negative stimulus, there was an average of 10.9 ± 7.3 in the female sex and 14.4 ± 4.4 in the male group; these findings showed that there was no statistically significant difference (p = 0.320 U of the Mann‒Whitney test). (Table 3)

Regarding oxygen metabolism in the prefrontal zone with splints and without occlusal splints when exposed to a negative stimulus, a statistically significant difference was found (p <0.001, Wilcoxon test). (Table 3)

INSULA AREA WITH POSITIVE STIMULATION WITH OCCLUSAL SPLINT AND WITHOUT OCCLUSAL SPLINT

The variations in oxygen metabolism in the insula area before a positive stimulus without the use of an occlusal splint ranged from 2.0% to 22.0%, averaging 7.7% + 5.4%, while after the use of the occlusal splint, the values ranged from 0% to 18% of oxygen metabolism, with an average of 2.3% + 3.5, which indicated a decrease in cerebral hyperactivity in the studied area (Table 2). A graphical representation of the magnitude of this difference is shown in Figure 3.

In the insula, before and after the use of the occlusal splint according to the sex of the patient, when exposed to a positive stimulus, an average of 4.4 ± 3.3 was found, and in the group of males, 8.6 ± 4.4 was found; these findings showed that there was no statistically significant difference (p = 0.067) according to the Mann‒Whitney U test (Table 3).

A statistically significant difference in oxygen metabolism in the insula between patients who were wearing a splint and those who were not wearing an occlusal splint was found (p <0.001, Wilcoxon test). (Table 3)

INSULA AREA WITH NEGATIVE STIMULATION WITH OCCLUSAL SPLINT AND WITHOUT OCCLUSAL SPLINT

The variations in oxygen metabolism in the insula area when exposed to a negative stimulus without the use of an occlusal splint ranged from 1.0% to 22.0%, averaging 7.7% + 5.1%, while after the use of the occlusal splint, the values ranged from 0% to 11% of oxygen metabolism, with an average of 3.2% + 2.7%, which indicated a decrease in cerebral hyperactivity in the studied area (Table 2). A graphical representation of the magnitude of this difference is shown in Figure 2.

In the insula, before and after the use of the occlusal splint according to the sex of the patient, when exposed to a negative stimulus, an average of 4.4 ± 3.3 was observed in the female sex, whereas in the group of males, 5.2 ± 3.6 was observed; these findings showed that there was no statistically significant difference (p = 0.446) in the Mann–Whitney U test (Table 3). Regarding oxygen metabolism in the insula area with splints and without occlusal splints when exposed to a negative stimulus, a statistically significant difference was found (p <0.001, Wilcoxon test). (Table 3)

Table 1.- Sample distribution
	n	%
Gender
Female	18	78,3
Male	5	21,7

Psychological diagnoses
Depression	1	4,3
Anxiety	4	17,4
Depression and anxiety	18	78,3
Total	23	100

Table 2.- Comparison of cerebral activity with and without oclusal splint
	Neg. SP Prefrontal	Neg. CP Prefrontal	Neg. SP Insula	Neg. CP Insula	Pos. SP Prefrontal	Pos. CP Prefrontal	Pos. SP Insula	Pos. CP Insula
N	23.0	23.0	23.0	23.0	23.0	23.0	23.0	23.0
Mean	16.3	4.7	7.7	3.2	11.6	3.9	7.7	2.3
Median	16.0	4.0	6.0	2.0	8.0	4.0	5.0	2.0
Mode	20.0	2.0	4.0a	2.0	5.0	1.0a	5.0	1.0
Est. Desv.	7.6	2.7	5.1	2.7	10.8	2.8	5.4	3.5
Mínimum	5.0	2.0	1.0	0.0	3.0	1.0	2.0	0.0
Máximum	30.0	12.0	22.0	11.0	48.0	10.0	22.0	18.0
Shapiro‒Wilk	0.258	0.006	0.02	0.002	0.0001	0.005	0.011	0.0001
Wilcoxon Comparison	<0.001		<0.001		<0.001		<0.001
Neg. SP: without Split Negative Stimulation Neg. CP: with Split Negative Stimulation/Pos. SP: without Split Positive Stimulation/Pos. CP: with Split Positive Stimulation

Table 3.- Comparison of oxygen metabolism before and after the splint, according to sex
	Prefrontal		Insula
	positive stimulation	negative stimulation	positive stimulation	negative stimulation
Female	6.1	10.9	4.4	4.4
Male	13.6	14.4	8.6	5.2
U Mann-Withney(sig.)	0.111	0.32	0.067	0.446

Occlusal splint therapy, like relaxation techniques, stress management, guided imagery, biofeedback, and cognitive therapies, is important in the combined treatment of temporomandibular disorders [17, 18]. In the present study, the effect of an occlusal splint on the perception of emotions was demonstrated through the use of an occlusal splint, which has an effect on psychological components, and by measuring brain metabolism in the prefrontal cortex and insular brain areas. initiators of temporomandibular dysfunction.

There is a relationship between the time the splint is worn and the health joint results; that is, with the use of the splint, the dysfunction symptoms decrease, and stress levels also decrease [19–22]. In the present study, there was evidence of the mechanism of action of the splint, since statistical tests revealed a relationship between the use of the occlusal splint and decreased brain metabolism in the prefrontal cortex area and in the insula area when exposed to a positive or negative stimulus, respectively. (Table 3)

In all positions of condylar relocation by occlusal splint, there was an improvement in the symptoms presented [20]; adult patients with obstructive sleep apnea evaluated by electromyography and the use of mandibular advancement occlusal splints with vertical thicknesses ranging from 2 to 8 mm reported decreased muscle activity after splint use [23]. In the present study, the use of an occlusal splint improved the neuronal hyperactivity present in patients with anxiety and depression, as indicated by the remarkable results of decreased hyperactivity in all the patients, with respective values of for positive and negative stimuli in the prefrontal cortex area of -7.7% and − 11.6%, respectively, and in the insula area of -5.4% and − 4.5%, respectively, which proves the effectiveness of the use of the occlusal splint in various treatment alternatives.

Occlusal splints with a vertical 4 mm thickness or greater generate an effective change in the condyle’s position for muscle decompression and improvements in the symptoms of temporomandibular dysfunction [19]. In the present study, occlusal splints were made with a vertical thickness greater than 4 mm in the anterior section, which led to condylar decompression greater than 2 mm.

There is a direct relationship between psychological states and temporomandibular disorders not related to dental conditions [24]. In this research, we found an average of 8.88 ± 1.49 on the Depression Scale according to the Hospital Anxiety and Depression Scale (HADS), indicating that this group falls into the category of individuals on the borderline for depression. In contrast, the average anxiety score was 12.11 ± 2.44, which classifies the group as within the installed pathology group regarding anxiety [15].

With respect to the association between sex and acute symptoms of temporomandibular dysfunctions and psychosocial disorders, women develop chronic temporomandibular dysfunction and present significantly greater anxieties and psychosocial disorders than women who do not present chronic temporomandibular dysfunction or men, where the same results were found [25]. According to the statistical results of the present investigation, all the study subjects, both female and male, presented chronic temporomandibular dysfunction of a muscular type and psychosocial alterations of anxiety, with suggestive values for the presence of the condition in patients of both sexes and borderline values of depression. These findings were statistically verified (78.3% of patients with depression and anxiety, 17.4% with only anxiety and 4.3% with only depression).

After studying 23 patients with temporomandibular disorders who were treated with an occlusal splint, a decrease in regional brain function in the frontal cortex was found to be related to motor and cognitive function; additionally, the areas of left precentral cerebral convolution were negatively correlated with patients with vertical discrepancy. Likewise, after eliminating discrepancies and stabilizing the occlusion with occlusal splint treatment, the altered brain functions recover [21]. In both studies, a decrease in brain function was found after placing the occlusal splint, which validates the findings of this research. The most notable difference from the findings of this study are that when the frontal zone (linked to motor and cognitive activity) was evaluated, the areas of left precentral cerebral convolution were also evaluated; however, in the present study, the prefrontal cortex area and insula, which are related to emotions, were evaluated. Another important difference is that the patients treated by TMD[21] were not psychologically pathological, unlike the patients in the present study, who, as a condition for their selection, had some degree of anxiety or depression[21]. We found no statistically significant difference between the use of the anterior deprogramming splint before and immediately after use, but only 3 months later, they managed to find statistically significant differences, which led us to consider that the variable of splint wear time may have affected the results. It is also important to note that in the study by He et al. [21]. Neither positive nor negative paradigms were used.

Chronic stress-related psychiatric illnesses such as major depression, posttraumatic stress disorder, and schizophrenia are characterized by poor organizational adaptation. Current evidence suggests functional disability in the prefrontal cortex, which leads to the hypothesis that chronic stress is related to neuropathological disorders and that these mechanisms involve the neurofunctional connectivity of the prefrontal cortex [26]. In the present study, we found that the prefrontal cortex has a direct function in the brain’s mechanism of emotions, both for emotions in the negative paradigm and for emotions in the positive paradigm, as evidenced by the variations and decreases in brain metabolism.

The negative paradigms vs. positive paradigms showed a statistically significant increase in brain activity in hyperactivity ranges in these areas, which proves that they are centers of brain management of emotions, mostly fear emotions and subjective experiences [27]. These findings are consistent with the present study because the values in the insular zone also presented hyperactivity in both the negative and positive paradigms, with averages of 7.7.% ± 5.1 and 7.7%± 5.4, respectively, and with a notable decrease in hyperactivity after the use of the occlusal splint, with negative paradigm values of 3.2% ± 2.7 and a positive paradigm of 2.3% ± 3.5, respectively, showing that in negative emotions, the values are slightly greater.

A promising finding of the present study is the decrease in brain hyperactivity against negative stimuli, which could lead to the possibility of new studies regarding brain plasticity resulting from decompression of the articular disc because this compressed disc in dysfunctional conditions functions as a bullying (stressful) agent.

Finally, it is important to highlight that the findings of this research demonstrated the interrelationship between the brain and each part of the human body. The bone, muscle and ligament structures that make up the temporomandibular joint are closely linked with the management of psychosocial conditions that have repercussions on psychological disorders; therefore, it is necessary to advance the scientific understanding of this interrelationship to establish new protocols for medical-dental care based on updated evidence.

After comparing before and after the use of the occlusal splint in patients with TMJ muscle disorders, anxiety and/or depression and using functional nuclear magnetic resonance images, it was shown that there was a significant difference in both the prefrontal and insula areas, both for positive and negative stimulation.

TMJ temporomandibular joint

HADS Hospital Anxiety and Depression Scale

RDC/TMD Research Diagnostic Criteria for Temporomandibular Disorders questionnaire

MRI magnetic resonance imaging

DICOM Digital Imaging and Communication in Medicine

CD Compact disk

SPSS Statistical Package for Social Sciences

Neg. SP: without Split Negative Stimulation

Neg. CP: with Split Negative Stimulation

Pos. SP: without Split Positive Stimulation

Pos. CP: with Split Positive Stimulation

Acknowledgements

The authors wish to thank The PhD Program at Universidad Peruana Cayetano Heredia for their support given to this study.

Author contributions

G.C.B; E.V.C. and Y.T.Ch. designed the study; GCB take data from the MRI studies reports. E.V.C. performed the statistical analysis of the data. All authors wrote the main text of the manuscript and revised the manuscript.

Ethics approval and consent to participate

The present study was approved and performed following the regulations of the institutional Ethics Committee of The Universidad Peruana Cayetano Heredia (code number 000006645). Each participant signed the informed consent.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests

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No competing interests reported.

Brain Metabolism in Pre-frontal Cortex and Insula Areas in Patients With Occlusal Splint for Temporomandibular Muscle Disorders

Status:

Version 1

Abstract

Figures

INTRODUCTION

METHODS

Participants

Clinical measurements

Occlusal splint

Functional magnetic resonance imaging study

Image acquisition

Image processing and analysis

Statistical analysis

RESULTS

DISCUSSION

Conclusion

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1