HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Figures Only Full Text (PDF) Services Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Ettlin, D.A. Articles by Palla, S. Search for Related Content PubMed PubMed Citation Articles by Ettlin, D.A. Articles by Palla, S.

Cortical Activation Resulting from Painless Vibrotactile Dental Stimulation Measured by Functional Magnetic Resonance Imaging (fMRI)

¹ Center for Dental and Oral Medicine and Cranio-maxillofacial Surgery, Clinic for Masticatory Disorders and Complete Dentures, ³ University Hospital Balgrist and ⁴ Institute of Neuropsychology, University of Zürich, Plattenstrasse 11, CH-8028 Zürich, Switzerland; ² Department of Surgery, Northwestern University, Chicago, IL, USA; and ⁵ Institute of Biomedical Engineering, ETH & University of Zürich, Switzerland;

^* corresponding author, ettlin{at}zzmk.unizh.ch

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS & METHODS RESULTS DISCUSSION REFERENCES

 
There have been few investigations on hemodynamic responses in the human cortex resulting from dental stimulation. Identification of cortical areas involved in stimulus perception may offer new targets for pain treatment. This initial study aimed at establishing a cortical map of dental representation, based on non-invasive fMRI measurements. Five right-handed subjects were studied. Eight maxillary and 8 mandibular teeth were stimulated after the vibratory perception threshold was determined for each tooth. Suprathreshold stimulation was repeated thrice per session, in a total of three sessions performed on three consecutive days. Statistical inference on cluster level identified increased blood-oxygen-level-dependent signal during vibratory dental stimulation, primarily in the insular cortex bilaterally and in the supplementary motor cortex. No significant brain activation was observed in the somatosensory cortex with this stimulation protocol. These results agree with previous findings obtained from invasive direct electrical cortical stimulation of the human insula.

KEY WORDS: cerebral cortex/anatomy and histology • echo-planar imaging/methods • tooth • physical stimulation/methods • perception/physiology

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERIALS & METHODS RESULTS DISCUSSION REFERENCES

 
Trigeminal processing beyond the brainstem and trigeminal cortical representation in humans have not been extensively studied (Sessle, 2000). By applying electrical cortical stimulation, Penfield and colleagues (Penfield and Boldrey, 1937; Penfield and Jasper, 1954) discovered a medial-to-lateral representation in the somatosensory cortex of the upper lip, lower lip, tongue, and intra-oral cavity, the upper teeth and gums being represented between the lips and tongue. Peripheral tissue stimulation in animals and humans thus far has not revealed consistent results regarding cortical representation of oral structures (Cusick et al., 1986; Krubitzer et al., 1995; Allison et al., 1996). More dental-specific experiments provided some evidence that there is a difference between painful vs. non-painful surface cortical representation. Magneto-encephalographic recordings of noxious tooth pulp stimulation in man revealed activation in the upper bank of the Sylvian Fissure, corresponding to the anterior end of the secondary somatosensory cortex (Hari et al., 1983). In contrast, only very small responses were recorded in this cortical area when the teeth were tapped (Hari and Kaukoranta, 1985). Presently, investigations applying positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) techniques allow investigators to assess functional-anatomical concordances bilaterally and three-dimensionally and therefore promise to offer further insight into dental cortical representation.

The aim of this study was to establish a three-dimensional human cortical map of dental representation, based on painless vibrotactile stimulation of teeth and resulting increases in blood-oxygen-level-dependent (BOLD) responses measured by fMRI.

	MATERIALS & METHODS

TOP ABSTRACT INTRODUCTION MATERIALS & METHODS RESULTS DISCUSSION REFERENCES

 
Subjects
Five healthy subjects (three females, two males; from 19 to 32 yrs of age), all right-handed by self-report, were recruited between April, 2002, and May, 2002. Inclusion into the study required a full dentition with vital teeth, no attachment loss, no increased tooth mobility, no periodontal pockets greater than 3 mm, and no caries lesions. Pregnancy and the usual MRI contra-indications led to exclusion from the study. The number of subjects was limited due to high labor and costs associated with the technically demanding set-up and the protocol execution. All subjects read and signed an informed consent prior to the scan. The study was approved by the local ethics committee.

Materials
Rigid removable bite splints made of clear acrylic were fabricated for each quadrant of the dentition. Holes (4 mm) were drilled into the splint on the buccal aspect of each test tooth. These were the central incisor, canine, second premolar, and second molar of each jaw quadrant, forming a series of non-neighboring teeth. Clear plastic tubes (diameter, 4 mm) were inserted into each of the splint holes and permanently attached with GC acrylic resin (GC Europe N.V., B-3001 Heverlee, Belgium). The individual tubes were long enough to extend extra-orally beyond the foot-end of the MRI patient table. A solid plastic rod (diameter, 3 mm) was inserted into the tube. The rod was 5 cm longer than the tube when in contact with the dental surface of the test tooth (Fig. 1). The retractable rod served as a plastic mandrel for transmitting a vibratory impulse from the stimulation device (described below) to the test tooth. A pneumatically driven piston (Power-Pillo, Renfert GmbH, D-78247 Hilzingen, Germany), normally used in the dental laboratory to carve stone models, served for mechanical vibratory tooth stimulation. We modified this device for MRI compatibility by replacing the metal chisel with an acrylic connector that tightly fit the stimulation rod. This instrument was powered by compressed air, set at 5 bars. Air movement regulated the stroke intensity, and air flow was controllable by rotation of the end of the piston which opened/closed the spring-loaded valve. Frequency and intensity of the vibratory stimulus were measured by means of a piezo-resistive force transducer (mod. Briforce 806, Bricon AG, CH-8954 Geroldswil, Switzerland). The fundamental frequency of the stimulation was 80 Hz; the maximum force value was 4.0 N.

View larger version (97K): [in this window] [in a new window]   Figure 1. Stimulation device. Clear plastic tubes (1) attached to the dental splint (2) with red GC acrylic resin (3) for guidance of the orange stimulation rod (4), which was connected to the pneumatically driven stimulation device (not shown).

Stimulus Application in the MRI Scanner
Each subject was comfortably placed on the scanner table in a supine position. The removable splint with the 4 attached plastic tubes was inserted. The subject’s head was immobilized by vacuum pads. A trial run to confirm the stimulus perception in all test teeth preceded the actual experiment. Four single teeth in each jaw quadrant, selected as described above, were then stimulated sequentially. The maxillary teeth were tested first, whereas the initial stimulation quadrant was assigned randomly. When starting on the right side, we sequentially tested the quadrants in clockwise rotation, whereas the opposite rotation was chosen otherwise. The stimulus was presented thrice to each tooth for alternating periods of 9 sec ‘ON’, followed by 9 sec ‘OFF’, totaling 54 sec before the next tooth was stimulated after a pause of, minimally, 10 sec. After complete stimulation of the 4 teeth in one jaw quadrant, the subject was moved out of the scanner. The splint was removed and replaced by a splint for the next quadrant. The same stimulation protocol was followed for each jaw quadrant, so that 16 teeth were stimulated during one session. The same procedure was repeated on three consecutive days to optimize reliability of the results, with the initial stimulation quadrant altered each day. The paradigm for each day is depicted in Fig. 2.

View larger version (18K): [in this window] [in a new window]   Figure 2. Schematic representation of paradigm. The Fig. depicts one day as an example. Four quadrants were stimulated consecutively. Within each quadrant, 4 different teeth were stimulated, as shown. Duration of the stimulation and rest epochs was 9 sec each.

Post-processing and Statistical Analysis
Our first step in data analysis was to apply motion correction of the time series data, using the statistical parametric mapping software SPM99 (http://www.fil.ion.ucl.ac.uk/spm). To transform the data into a standardized coordinate system, we used linear and non-linear transformations (Ashburner et al., 2000). Smoothing of the data was accomplished by convolution with a Gaussian kernel of 8 mm full width at half-maximum (FWHM) before statistical mapping by SPM99. Data were scaled to the global mean signal intensity. To remove non-physiologic effects, we removed fast signal changes by applying a Gaussian smoothing kernel of 4 s FWHM in the temporal domain and, for the same reason, removed frequency components lower than 1/36 Hz. A general linear model (GLM) was formulated by incorporation of the data from all subjects (fixed-effects model) so that brain activation could be described for the sample of subjects studied (Worsley and Friston, 1995), as implemented in SPM99. On the calculated maps, the differences between the stimulation and the resting conditions of the signal intensity were transformed into a color-coded T-map for each voxel. The resulting statistical maps are shown, superimposed onto coronal sections, through a representative brain of the series provided by the Montreal Neurological Institute (MNI-Brain). We analyzed the data on a fixed-effects basis, since the small sample size does not allow for valid inferences to the general population. Hence, we list the p-values as effect sizes for the group under investigation and did not correct for multiple comparisons.

	RESULTS

TOP ABSTRACT INTRODUCTION MATERIALS & METHODS RESULTS DISCUSSION REFERENCES

 
The largest clusters of BOLD responses from comparisons between resting conditions and stimulation were found in the supplementary motor area (SMA, 255 voxels), and in the anterior insula bilaterally (right, 65 voxels; left, 53 voxels) (Table, Fig. 3). Small activations were further located in the cuneus, superior occipital gyrus, and post-central sulcus. Since these latter clusters showed a considerably smaller BOLD effect compared with the first two clusters (see p-values in Table), we restricted further discussion of cortical activations to the SMA and the insula, where we recognized a robust effect.

View larger version (129K): [in this window] [in a new window]   Figure 3. fMRI coronal slices. These slices cover the three most activated clusters to depict the distribution and size of the group activation overlaid on a representative brain of the MNI series. The numbers for each slice indicate the y coordinate in reference to the MNI coordinate system.

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERIALS & METHODS RESULTS DISCUSSION REFERENCES

Insula
The insular connections and circuitry are extensive and complex (for a detailed review, see Mesulam and Mufson, 1985). Penfield and Faulk (1955) reported that painful and non-painful sensations were usually elicited in the mid-line structures such as lips, tongue, mouth, and throat by direct electrical stimulation of the anterior (as opposed to posterior) insula. These sensations were usually felt bilaterally. Since then, extensive evidence from primate and human studies indicates that the insula is involved in the processing of painful and non-painful sensations from various body regions, including trigeminal nerve sensations (Penfield and Faulk, 1955; Burton et al., 1993; Schneider et al., 1993; Augustine, 1996; Derbyshire et al., 1997; Ostrowsky et al., 2002).

Recently, Ostrowsky and co-workers (Ostrowsky et al., 2002) also performed stimulations in the human insular cortex, and their findings show remarkable congruence with the data published in 1955 regarding the somatotopic organization. Furthermore, while stimulation sites for extremities triggered sensations allocated to one body side, stimulation of the craniofacial tissue sites was not side-specific. Together, the findings of direct cortical stimulation experiments suggest two features to be characteristic of the human insula: (1) The extremities seem to be represented more posteriorly than orofacial structures, suggesting a certain somatotopic organization of the insula; and (2) orofacial sensations cannot be clearly allocated to one specific hemisphere. Our findings, based on a non-invasive technique, support both hypotheses: (1) The predominant activation resulting from vibrotactile stimulation of the dentition was found in the anterior insula; and (2) vibratory stimulation of one side of the dentition did not lead to activation of one specific hemisphere. However, the lack of side-specific activation could also be the result of the small sample size and the reduced statistical power after the dataset was split in half. Thus, further evidence is needed to show whether activation is equally strong in both hemispheres when only one side of the dentition is stimulated.

In our protocol, the vibratory stimulus applied to individual teeth most likely spread to other teeth via interdental contacts and the transseptal fiber system. Hence, we stimulated neurons with extended receptive fields (Trulsson, 1993). Neurons with such properties have been previously described in the insular cortex of monkeys (Robinson and Burton, 1980; Schneider et al., 1993). Further support that the insula is involved in oral tactile sensation comes from a PET study that demonstrated that injection of pure water into the mouth resulted in large bilateral activations of the insula, as well as the buried frontal operculum (Zald and Pardo, 2000).

The correlation of our findings with data obtained invasively from direct insular stimulation confirms the value of fMRI methodology in functional brain studies (Penfield and Faulk, 1955; Ostrowsky et al., 2002).

Somatosensory Cortex
Remarkably, no significant brain activation was observed in the somatosensory cortex in the fixed-effects group analysis results, indicating that the response in this cortical area is far less dominant and robust than in the other activated areas induced by our stimulation protocol. This confirms findings obtained by magneto-encephalographic methods whereby electrical pulp stimulation results were compared with those obtained from mechanical tapping of teeth (Hari and Kaukoranta, 1985) as well as results from PET studies investigating jaw muscle pain (Kupers et al., 2004). On the other hand, this lack of a BOLD response in the somatosensory cortex could be attributed to the small sample size. Large variations regarding the orofacial somatotopic representation in the somatosensory cortex between different individuals and different species have also been observed in primate studies (Krubitzer et al., 1995). In a recent study in monkeys, many areas were reported to be unresponsive to tactile oral stimulation, while others showed multiple isolated ‘islands’ of activation within the cortex (Jain et al., 2001). Our findings, combined with these reports in animals, suggest that brain areas other than the somatosensory cortex, particularly the insula, may be more responsive to vibrotactile stimulation of the dentition.

Supplementary Motor Area (SMA)
Various stimulation methods result in activation of the SMA. This has been observed during vibrotactile stimulation of human forearms, hands, and feet (Burton et al., 1993; Coghill et al., 1994). Furthermore, noxious stimulation of the central tongue and hard palate have also resulted in activation of this area (Allison et al., 1996). Many experimental and clinical studies have led to the hypothesis that the SMA is involved in the planning, initiation, and programming of voluntary movements or the urge to move a body part (Halsband et al., 1993; Tanji and Shima, 1994). Even the imagination or preparation of movement without an actual movement can cause blood flow changes in SMA (Yazawa et al., 1998; Maruno et al., 2000). Hence, the SMA activation in our study may be the result of the type of stimulation or simply reflect an interplay between sensory and motor systems, as apparent from previous studies (Fink et al., 1997).

	ACKNOWLEDGMENTS

 
This work was supported by a grant from the Swiss Dental Association. Our gratitude for their valued support goes to H. Eschle, D. Dembski, and S. Erni, all staff members of the Center for Dental and Oral Medicine and Cranio-Maxillofacial Surgery, University of Zürich. In addition, we appreciate the time and efforts of P. Kemppainen, University of Helsinki, Finland, and C. Forster and R. Ringler, University of Erlangen, Germany, for critical review of our manuscript and helpful insights.

Received December 17, 2003; Last revision May 26, 2004; Accepted July 12, 2004

	REFERENCES

TOP ABSTRACT INTRODUCTION MATERIALS & METHODS RESULTS DISCUSSION REFERENCES

 
Allison T, McCarthy G, Luby M, Puce A, Spencer DD (1996). Localization of functional regions of human mesial cortex by somatosensory evoked potential recording and by cortical stimulation. Electroencephalogr Clin Neurophysiol 100:126–140.[Medline]

Ashburner J, Andersson JL, Friston KJ (2000). Image registration using a symmetric prior—in three dimensions. Hum Brain Mapp 9:212–225.[ISI][Medline]

Augustine JR (1996). Circuitry and functional aspects of the insular lobe in primates including humans. Brain Res Rev 22:229–244.[Medline]

Burton H, Videen TO, Raichle ME (1993). Tactile-vibration-activated foci in insular and parietal-opercular cortex studied with positron emission tomography: mapping the second somatosensory area in humans. Somatosens Mot Res 10:297–308.[ISI][Medline]

Coghill RC, Talbot JD, Evans AC, Meyer E, Gjedde A, Bushnell MC, et al. (1994). Distributed processing of pain and vibration by the human brain. J Neurosci 14:4095–4108.[Abstract]

Cusick CG, Wall JT, Kaas JH (1986). Representations of the face, teeth and oral cavity in areas 3b and 1 of somatosensory cortex in squirrel monkeys. Brain Res 370:359–364.[ISI][Medline]

Derbyshire SW, Jones AK, Gyulai F, Clark S, Townsend D, Firestone LL (1997). Pain processing during three levels of noxious stimulation produces differential patterns of central activity. Pain 73:431–445.[ISI][Medline]

Dong WK, Shiwaku T, Kawakami Y, Chudler EH (1993). Static and dynamic responses of periodontal ligament mechanoreceptors and intradental mechanoreceptors. J Neurophysiol 69:1567–1582.[Abstract/Free Full Text]

Fink GR, Frackowiak RSáJ, Pietrzyk U, Passingham RE (1997). Multiple nonprimary motor areas in the human cortex. J Neurophysiol 77:2164–2174.[Abstract/Free Full Text]

Halsband U, Ito N, Tanji J, Freund HJ (1993). The role of premotor cortex and the supplementary motor area in the temporal control of movement in man. Brain 116(Pt 1):243–266.[Abstract/Free Full Text]

Hari R, Kaukoranta E (1985). Neuromagnetic studies of somatosensory system: principles and examples. Prog Neurobiol 24:233–256.[ISI][Medline]

Hari R, Kaukoranta E, Reinikainen K, Huopaniemie T, Mauno J (1983). Neuromagnetic localization of cortical activity evoked by painful dental stimulation in man. Neurosci Lett 42:77–82.[ISI][Medline]

Jain N, Qi HX, Catania KC, Kaas JH (2001). Anatomic correlates of the face and oral cavity representations in the somatosensory cortical area 3b of monkeys. J Comp Neurol 429:455–468.[ISI][Medline]

Krubitzer L, Clarey J, Tweedale R, Elston G, Calford M (1995). A redefinition of somatosensory areas in the lateral sulcus of macaque monkeys. J Neurosci 15(5 Pt 2):3821–3839.[Abstract]

Kupers RC, Svensson P, Jensen TS (2004). Central representation of muscle pain and mechanical hyperesthesia in the orofacial region: a positron emission tomography study. Pain 108:284–293.[ISI][Medline]

Maruno N, Kaminaga T, Mikami M, Furui S (2000). Activation of supplementary motor area during imaginary movement of phantom toes. Neurorehabil Neural Repair 14:345–349.

Mesulam MM, Mufson EJ (1985). The insula of Reil in man and monkey: architectonics, connectivity, and function. In: Cerebral cortex. Vol. 4. Association and auditory cortices. Peters A, Jones GE, editors. New York: Plenum Press, pp. 179–226.

Ostrowsky K, Magnin M, Ryvlin P, Isnard J, Guenot M, Mauguiere F (2002). Representation of pain and somatic sensation in the human insula: a study of responses to direct electrical cortical stimulation. Cereb Cortex 12:376–385.[Abstract/Free Full Text]

Penfield W, Boldrey E (1937). Somatic motor and sensory representation in the cerebral cortex of man as studied by electrical stimulation. Brain 60:389–443.[Free Full Text]

Penfield W, Faulk M (1955). The insula; further observations on its function. Brain 78:445–470.[Free Full Text]

Penfield W, Jasper H (1954). Epilepsy and functional anatomy of the human brain. Boston, MA: Little, Brown and Co.

Robertson LT, Levy JH, Petrisor D, Lilly DJ, Dong WK (2003). Vibration perception thresholds of human maxillary and mandibular central incisors. Arch Oral Biol 48:309–316.[ISI][Medline]

Robinson CJ, Burton H (1980). Somatic submodality distribution within the second somatosensory (SII), 7b, retroinsular, postauditory, and granular insular cortical areas of M. fascicularis. J Comp Neurol 192:93–108.[ISI][Medline]

Schneider RJ, Friedman DP, Mishkin M (1993). A modality-specific somatosensory area within the insula of the rhesus monkey. Brain Res 621:116–120.[ISI][Medline]

Sessle BJ (2000). Acute and chronic craniofacial pain: brainstem mechanisms of nociceptive transmission and neuroplasticity, and their clinical correlates. Crit Rev Oral Biol Med 11:57–91.[Abstract]

Tanji J, Shima K (1994). Role for supplementary motor area cells in planning several movements ahead. Nature 371:413–416.[Medline]

Trulsson M (1993). Multiple-tooth receptive fields of single human periodontal mechanoreceptive afferents. J Neurophysiol 69:474–481.[Abstract/Free Full Text]

Trulsson M, Johansson RS (1996). Encoding of tooth loads by human periodontal afferents and their role in jaw motor control. Prog Neurobiol 49:267–284.[ISI][Medline]

Worsley KJ, Friston KJ (1995). Analysis of fMRI time-series revisited—again. Neuroimage 3:173–181.

Yazawa S, Ikeda A, Kunieda T, Mima T, Nagamine T, Ohara S, et al. (1998). Human supplementary motor area is active in preparation for both voluntary muscle relaxation and contraction: subdural recording of Bereitschaftspotential. Neurosci Lett 244:145–148.[ISI][Medline]

Zald DH, Pardo JV (2000). Cortical activation induced by intraoral stimulation with water in humans. Chem Senses 25:267–275.[Abstract/Free Full Text]

This article has been cited by other articles:

				J. J. Miyamoto, M. Honda, D. N. Saito, T. Okada, T. Ono, K. Ohyama, and N. Sadato The Representation of the Human Oral Area in the Somatosensory Cortex: a Functional MRI Study Cereb Cortex, May 1, 2006; 16(5): 669 - 675. [Abstract] [Full Text] [PDF]

This Article Abstract Figures Only Full Text (PDF) Services Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Ettlin, D.A. Articles by Palla, S. Search for Related Content PubMed PubMed Citation Articles by Ettlin, D.A. Articles by Palla, S.