Enhancement of Sensorimotor Cortical Adaptation after Dental Implantation in Comparison to the Conventional Denture — Demonstration by Functional MRI at 1-5T
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.317239
Source of Support: None, Conflict of Interest: None
Keywords: Blood oxygen level dependent, BOLD MRI, complete denture, fMRI-functional MRI, intra-oral dental implantationKey Messages: Placement of Intraoral dental implantation can lead to enhanced Blood oxygen level-dependent (BOLD) activity in the brain.
Loss of tooth has been shown to be one of the important factors contributing toward a reduction in all domains of cognition including behavioral control, learning, memory, attention/sleep, language, intelligence, perception, and visceral/sexual activities as well as functional independence and social relationships., However, cortical areas tend to acquire new target organs after the loss of the primary peripheral organ which they represent, a fact proven in studies with limb amputation and tooth extraction. Origin of new stimulus from the peripheral regions once connected to a specific cortical area may train and recruit newer cortical representative areas, even after the critical developmental period of the brain has expired. Cortical adaptive changes after hand or thumb replantation/transplantation have been well demonstrated by functional MRI (fMRI) but only a few such attempts have been made after dental implantation in patients with the chronic edentulous state. In the present study, we test this hypothesis using blood oxygen level-dependent (BOLD) activity on fMRI as a bio-surrogate.
In this prospective observational “before and after study,” a cohort consisting of 12 consecutive edentulous subjects (mean age = 59.2 years; range 40–70 years) were recruited. The study was duly approved by the institutional ethics committee on 31.1.2014 (Approval no ECR/526/Inst/UP/2014) and written informed consent was obtained from each patient.
A complete denture (CD) was fabricated for the edentulous arches and the subjects were asked to wear it for 3 months. After a period of 3 months, the first fMRI was done. The scanning was done in a supine position with the head immobilized and eyes closed during the examination. Earplugs were provided to avoid auditory discomfort, and the subject was pre-trained for performing the intercuspal clenching tasks while counting the scanning pulses so that he/she could clench and release as when required on his/her own. The task paradigm consisted of a block-design in which activation tasks were alternated with a period of rest, accordingly an initial 10 s of resting phase (labeled as “off”) followed by 10 s of clenching (labeled as “on”), with “off-on” procedure being repeated 10 times in each run. After the first fMRI scan, two implants overdenture (IOD) (Adin Dental Implants, AlonTavor, Israel) were surgically placed bilaterally in the canine region according to the standard Branemark-system protocol. The subjects were recalled after 3 months whereby the loading of the implants was performed. After 3 months of loading of implants, the second fMRI was done following the same protocol as in the first scan.
The MRI scans were performed on a 1.5 Tesla actively shielded whole body superconducting system (Magnatom Avanto; Siemens Medical Systems, Erlangen, Germany) using an 8-channel bird-cage quadrature head coil. An initial fast spin-echo (FSE) T2-weighted (T2W) axial imaging (25 contiguous axial slices each 3 mm thick, with no gaps) were acquired [TR = 3,560 ms, TE = 50 ms, FA = 90°, field of view (FOV) = 192 mm). For the display of fused-BOLD images, a high-resolution T1-weighted structural MRI was acquired for each subject using a three-dimensional fast-spoiled gradient sequence (1 mm thick, 30% overlap, TR/TE/FA = 1900 ms/3.37 ms/15, FOV = 256 mm). Monitoring of head alignment and jaw movement was done during imaging to ensure the absence of significant noise from motor activation of facial muscles and neck movement.
Two radiologists with 5 and 15 years of experience evaluated the images on Neuro3D (Siemens medical system, Erlangen, Germany) software. The global linear models of the BOLD signal were fused with the high-resolution fast-spoiled gradient images to obtain the fusion map of the BOLD signal. The BOLD signal for six anatomical regions, that is, sensory cortex, motor cortex, hippocampus, insula, frontal and temporal lobes on both sides was measured to assess the dominant side for each region. Subsequent analysis was done with the data from the dominant side only. BOLD MR signal was subjectively rated using a 3-point scale (0 = no signal, 1 = mild signal, 2 = strong signal) [Figure 1]. The radiologists were blinded to the information about the dental implantation status of the patients. The BOLD signal as measured from the final fused images on the screenshot images was tabulated with the CD in-site (i.e., pre-implant) and post-implant placement.
The results were expressed as mean with standard deviation. A comparison between this ordinal data was performed using the Wilcoxon sign rank test. The data were considered significant if the P value was equal to or less than 0.05 and highly significant if P value was less than 0.01. The statistical analysis was performed with the aid of SPSS version 16.0 (SPSS, Inc., Chicago, IL, USA).
The mean BOLD MR signal scores were calculated in each patient for six different anatomical regions where significant signal generation and alteration were noted. The differences in score among the pre-implant and post-implant images followed a nonparametric distribution, hence, the significance was tested using the Wilcoxon's signed-rank test after the assignment of ranks to each of the values and the results are summarized in [Table 1]. Analysis for each anatomical region revealed that the BOLD signal was significantly higher in patients 3 months after the placement of the implant in all the locations analyzed [Figure 1] and [Figure 2]. The sensory and motor cortex demonstrated the most significant change in the BOLD MR signal.
The loss of stimulus from a peripheral organ like a limb or a tooth causes the cortical representative area in the human brain to deactivate itself by a complex cascading mechanism. Once deactivated, the region may or may not be able to support the same activity again in the event of a new organ being implanted or transplanted but the brain as such has been shown to support the incumbent implant. This has been explained by the phenomenon of neuroplasticity whereby newer cortical areas of the brain are recruited to support functions that were once performed by another area., The present study utilizes fMRI to demonstrate the existence of such a phenomenon after placement of an IOD in edentulous patients where an initial scan confirms the absence of any significant cortical masticatory activation even with a CD.
The results in this study demonstrate an unequivocal increase of the BOLD signal on performing the functional MRI described above. Similar results have been shown in a smaller cohort of four patients in an earlier study where chewing gum was used instead of controlled tooth clenching. Though in agreement with our findings, the paradigm used in the above study may not be appropriate, as the actual chewing is a complex muscular activity that may cause more widespread activation both in terms of a number of areas activated and the intensity of activation. Further, confounding noise due to random head movement may also be a drawback with such a paradigm. However, tooth clenching to chewing which one is better for evaluation is still not clear in the current literature, simply clenching can cause activation in certain new areas of the brain, which might be evaluated by further research.
The activation of the primary sensorimotor cortex was noted in 91.67% subjects. Certain studies using techniques such as cortical surface electrical stimulation, intracortical microstimulation, cortical neural recordings in animals, electrical stimulation, transcranial magnetic stimulation (TMS) in humans have demonstrated a major role of motor cortex, not only in the initiation, control, and execution of orofacial movements but also in learning of new motor skills., The primary sensory area contributes to the masticatory action by processing the somatosensory afferents and sending requisite corticofugal modulation of such activity through the interconnections with the motor cortex. Accordingly, in our dataset, though there was an activation of these areas with CD, a statistically significant increase in the BOLD signal was noted with IOD. This not only indicates toward a regaining of the lost function during the process of neuroplasticity but also supports the fact that an IOD enhances the brain activity by the process of osseoperception, a fact that has significance in avoiding the onset of dementia. Bilateral frontal cortices were activated in all patients with an IOD while only 66.7% of subjects with a CD showed activation in this area. The activation in the latter group was unilateral and much milder. A recent citation has found bilateral prefrontal cortex (PFC) activation in patients with fixed implant-supported prosthesis. The PFC, especially the dorsolateral part, is observed to play a key role in learning and memory. It was proved that this part of the brain may contribute to long-term memory through its role in the active processing of relationships during encoding, whereas the ventrolateral PFC may have a more general role in promoting successful long-term memory formation. The dorsolateral circuit is also associated with cognitive-habit learning. Thus, we are under the impression that bilateral PFC might take part in the adaptive changes occurring as a result of some masticatory function which is related to long-term memory and skill learning. An increase in BOLD signals was seen in all individuals in the hippocampus and temporal cortex. The dominant hippocampal cortex region had a marked increase in half of the subjects with IOD while those with CD did not show any significant pre-implant activation. The dominant temporal cortex showed mild activation in 58.3% of the subjects with a CD in situ which increased to activation in 75% of the subject with an IOD. The intensity of activation in the latter group was also higher. These results were similar to activation pattern in a previous study where the hippocampal gyrus was activated in 5 of 12 (almost 50%) patients with an IOD but in only one of eight patients with CD. The relationship between hippocampus and memory has been demonstrated in many studies,, and decreased activation secondary to reduced mastication may lead to an impairment of spatial memory and degeneration of hippocampal neurons in aged mice. Another study has demonstrated activation in superior temporal gyrus after the installation of the new CD in old denture wearers. Studies have shown that both temporal and hippocampus are associated with memory function in individuals. Thus, a suggestion that an increase in activity in these areas can lead to better memory function in senile individuals, seems reasonable and may be evaluated in further systematic studies.,, Activation was also noted in the insular cortex in 41.7% subjects with a CD which increased to 66.7% subjects with an IOD. Again, an increase in BOLD signal intensity was also noted in all these subjects. The phenomenon is in agreement with similar observations made by unrelated groups previously. A suggestion that the insular cortex is involved in memory and emotional expressions also gives strength to the suggestion of a possible association of dementia with the BOLD signal seen on fMRI in edentulous and in subjects with dental implants. Though the present study suffers from a limitation of stopping short of validating the actual cognitive effects of intra-oral dental implantation on clinical dementia scales, the demonstration of the fMRI effect may be convincing toward the suggestion. Further, a limited sample size precludes the application of advanced statistical methods. Also, the subjective assessment of BOLD activity may be a source of observer bias though adequate blinding methods were applied to address the same. Another limitation of our study was a lack of control group receiving the only CD with sequential MRI which could have been compared to the patients with IOD. The comparison of two different sets of patients, one with CD only and the other undergoing IOD would more emphatically demonstrate the cortical regeneration associated with IOD.
fMRI is a powerful tool for translational neuroscience research. In this study, it has been used to test the hypothesis that placement of an IOD may lead to activation of the hitherto deactivated primary sensorimotor cortical representation of tooth as a result of a subject becoming edentulous. Apart from demonstrating the above, it was also noted that certain newer areas (viz. hippocampi, insular cortex, and basifrontal cortex) may be recruited after an IOD placement.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
The authors wish to express their gratitude towards the seven patients who funded their own scans after due informed consent and to the head of the department of radiodiagnosis of this institute for waiving off the charges for the other five patients as per academic protocol. We also express our gratitude to all patients for having given informed consent for being included in this study. The first author Aparajita Singh expressed gratitude towards Raichelamma Luyees for cooperation in performing all scans.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
[Figure 1], [Figure 2]