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Introduction to Neuroimaging and the Brain–Stomatognathic Axis
1.1 Why Do Dentists Need to Understand the Brain?
1.1.1 Introduction
If we look into any textbook of clinical dentistry – be it oral pathology, prosthodontics, periodontics or orthodontics – we may not feel surprised that the word ‘brain’ would appear just very few times in the whole book. Traditionally, dentists are trained as an expert in treating oral diseases and the topics related to the brain, and its relevant disorders are usually categorized as systemic issues. The dichotomy of ‘dental vs. systemic’ suggests that the brain and behaviour issues are beyond the spotlight of dentists. Such alienation is even pronounced if we hold a ‘pathological perspective’ on the association between the brain and dentistry: oral diseases are usually not the primary aetiology of neurological/mental disorders, cardiovascular, gastrointestinal or endocrinal diseases (Figure 1.1). Therefore, there is no urgent need for dentists to learn the knowledge of the human brain.
However, the association between the brain and dentistry may show a different story if we adopt a ‘functional perspective’. Here, the brain, behaviour and oral health are directly linked if we consider that the brain plays a crucial role in maintaining oral functions, and the integrity of mental functions is critical to maintaining oral health. If we adopt the view that the brain and mental functions guided by the brain are essential to all human behaviours (e.g. from eating to toothbrushing), we may find that the brain has an essential and more dominant role in oral health (Figure 1.1).
In the following sections, we elaborate on this functional perspective by revisiting three lines of evidence. Historically, we see that dentistry and brain science are the ‘old alliance’ for more than 100 years. Educationally, we discuss the role of neuroscience in the curriculum of dental education. Finally, the new engagement between dentistry and the brain via neuroimaging methods is highlighted.
1.1.2 The ‘Old Alliance’ Between Dentistry and Brain Science
The first evidence of the alliance between dentistry and brain science exists in an article published 130 years ago entitled Reflex Neurosis in Relation to Dental Pathology. The author mentioned that ‘… pain in a tooth is not indicative of the source of trouble, … The cause may be remote or in another tooth’ (Hayes 1889), a phenomenon now we may consider as heterotopic pain. Subsequently, the author put forward some insightful speculation on orofacial pain:
Figure 1.1 The association between the brain and the stomatognathic system. The traditional perspective highlights the brain as a ‘systemic factor’ associated with oral health, just like the factors related to other body systems. The functional perspective highlights that the brain and mental functions guided by the brain play an essential role in stomatognathic functions.
Cerebral diseases, for example, insanity, softening of the brain, tumors and inflammation may produce odontalgia, but clinical reports reveal comparatively few, inasmuch owing to their obscurity positive diagnosis is often rendered difficult.
(Hayes 1889)
Though not scientifically accurate from the modern view, the statement points out the complex association between the brain and orofacial pain, which has confused dentists for more than one century. The alliance becomes cemented due to the challenge of treating orofacial pain, and new technologies, including neuroimaging, have provided new insights into this field (see Chapter 6). Our second evidence comes from the issues of infection control, especially the brain abscess secondary to dental infection. At present, dentists have been highly aware of infection control within the oral cavity. However, new challenges have emerged, such as the recent debates on the neuroinflammatory mechanisms that may underlie the link between neurodegenerative disorders and periodontal diseases (see Chapter 7). Finally, the third evidence of the old alliance has an even longer history. Back in 1790, when the terms ‘brain science’ and ‘dentistry’ have not yet popularized, in an article entitled ‘Pathological Observations on the Brain’, the author reported a potential association between epileptic signs and symptoms and irregular behaviour in eating and drinking (Anderson 1790). The finding echoes the link between the brain and oral sensorimotor functions, extensively studied in animal research (Lund 1991). New issues have emerged in modern days. For example, can older individuals be benefited from oral functional training to improve mastication and swallowing (Sessle 2019)? Can patients with neurodegenerative disorders, who have deficits in mental functions, also improve their oral functions? There are more challenges to meet for the old alliance between dentistry and brain science.
1.1.3 Dental Education: The Role of Neuroscience and the Brain
In the previous section, we have briefly discussed how the research of the brain has been linked to issues of oral health. However, the discussion may not be complete without looking into dental education for the following questions: has the role of brain science been recognized in dental education?
1.1.3.1 The Tradition of ‘Dentists as Surgeons’
A discussion of early dental education will not be complete without mentioning the contribution from Pierre Fauchard, widely recognized as the Father of Modern Dentistry, with the first textbook of dentistry Le Chirurgien Dentiste (‘The Surgeon Dentist’) published in 1728. As the name suggests, dentistry is the discipline of managing dental diseases with a surgeon’s training. Notably, in this book, Fauchard has extended the professional domain of dentists from ‘teeth’ to the oral cavity (including the soft tissue). The new profession, a ‘surgeon dentist’, is different from a ‘toothpuller’ in the seventeenth to eighteenth centuries (Lynch et al. 2006). Though he also emphasized the relationship between oral and systemic diseases (Lynch et al. 2006), the primary task for dentists is to fix the structural deficits of the oral cavity, such as restoring a decayed tooth or replacing the missing teeth with a denture. All the jobs require dentists to be capable of performing complicated surgical skills.
An over‐focus on the surgical skills of dental treatment, however, had gradually received criticism since the early days when dental education became an independent discipline. As pointed by Eugene Talbot early in 1900:
The result is that study of the general diseases which affect the mouth, jaws and teeth have been neglected. Limitations of a dental education have prevented the dentist from associating local diseases with systemic causes.
(Talbot 1900)
The statement corresponds to the degree delivered for this new profession, namely Doctor of Dental Surgery (DDS), at Talbot’s time. He further showed the concern that ‘… the graduate of dental surgery is not competent to associate systemic diseases with their effects on the teeth, nor is he capable of appreciating systemic lesions due to overtreatment of pathologic conditions of the teeth’ (Talbot 1900). The gap between a dentist and medical knowledge would make dentists ignore the systemic condition of patients – moreover, the ignorance may further exacerbate systemic health when dentists ‘overtreat’ patients (Talbot 1900).
1.1.3.2 Brain and Neuroscience: Is It Neglected in Dental School?
According to the Basic Science Survey Series of the American Dental Education Association (ADEA), neuroscience is widely taught in most dental schools in North American. In 2014, among 66 dental schools, 31 (47%) offered neuroscience as a standalone course, with the others integrated the neuroscience topics into other courses (Gould et al. 2014). It is also noteworthy that in most dental schools, the course was delivered by teachers from medical schools, who may not tailor‐make the course for dental students (Gould et al. 2014). The average year of teaching of the teachers is relatively high (23.1 years), suggesting fewer younger teachers are involved in the field (Gould et al. 2014). Critically, the topics to be delivered significantly varied between courses. Some topics, such as the knowledge of cranial nerves, were taught averagely for three hours. In contrast, issues of the neuropathic mechanisms of pain, including nerve regeneration, neuralgia, allodynia and hyperalgesia, were taught less than half an hour (Gould et al. 2014). Topics related to the human brain were taught in most of the courses. Nevertheless, among the 31 independent neuroscience courses, almost half of them focused on neuroanatomy, which emphasizes the knowledge of brain structure rather than the link between the brain and oral functions. This alienation reflects that many courses were taught by personnel outside the dental schools and may not provide what dentists need to know for their clinical careers.
Therefore, for teaching neuroscience and brain science in dental schools, the real challenge is not the time and classes allocated for teaching, but how these materials are taught. Non‐dental school faculties mainly taught the courses, and the topics were less tailored for dentistry. For example, in some syllabi of the neuroscience courses, the issue ‘pain’ is taught alongside somatosensation. Nowadays, we have much evidence showing that pain, as a more generalized cognitive–affective experience, is associated with the brain mechanisms of attention, emotional and cognitive processing (see Chapter 6). In this case, a focus on the brain and mental functions, such as the modulatory effect of attention and cognitive appraisal on pain, should be tailored for dental students since it is highly associated with the clinical management of patients.
1.1.4 The ‘New Engagement’: Modern Cross‐Disciplinary Research of Dentistry and Brain Science
Instead of being a comprehensive textbook on the neurobiology of dentistry, this book aims to outline the ‘new engagement’ between dentistry and brain science, with neuroimaging as a critical approach to bridge the two fields. Here, we discuss the trend of cross‐disciplinary research between dentistry and brain science, according to two brief bibliometric surveys. Firstly, a survey based on PubMed was performed by the keywords ‘dental’ and ‘brain’ and the search was limited to titles and abstracts of the literature (tooth[mesh] OR oral[mesh] OR dental[mesh] OR dentistry[mesh] OR teeth[tiab] OR tooth[tiab] OR oral[tiab] OR dental[tiab] OR dentistry[tiab] AND brain[tiab]). The findings revealed that by December 2020, 20261 research papers had been documented in PubMed. The number of publications shows a pronounced rise in recent years, which almost doubled within 10 years. For example, between 1980 and 1989, the number of publications n = 1566. This number rose from 1990 to 1999 (n = 2684) and almost doubled from 2000 to 2009 (n = 4721). From 2010 to 2019, the number doubled again to n = 9331. As discussed in Section 1.2, the increasing number of publications on the brain topic corresponds to the increasing number of publications on neuroimaging, which has become a pivotal method in studying the human brain.
A second survey was conducted by searching for the past and current research projects funded by the National Institutes of Health (NIH), USA, using the online platform of Research Portfolio Online Reporting Tools (RePORT) report. From 2020 to February 2021, the keywords ‘dental’ and ‘brain’ have led to 106 projects, with 39 projects funded by the National Institute of Dental and Craniofacial Research (NIDCR). This number is almost twice the number of sponsored projects (53) in the whole 1990s when the NIDCR funded 29 projects. The results suggest an increasing trend of cross‐disciplinary research between oral and brain sciences. Critically, not all the projects were granted by the NIDCR, which specializes in orofacial medicine. Several projects were supported by the National Institute of Mental Health and the National Institute on Aging, highlighting the importance of oral issues in cognitive deficits and aging.
1.1.5 Summary
- From a functional perspective, the brain, behaviour and oral health are directly linked because the brain plays a crucial role in maintaining oral functions, and the integrity of mental functions is critical to maintaining oral health.
- The alliance between the research on dentistry and the brain has a long history. It contributes to tackling unsolved challenges (e.g. orofacial pain) and new challenges (e.g. aging and oral functions).
- Topics of neuroscience and the brain are not neglected in dental education. However, many courses are taught by non‐dental school faculties, and the topics were less tailored for dentistry.
- Recently, cross‐disciplinary research on oral and brain sciences has quickly emerged in the number of publications and research grants.
1.2 What Is Neuroimaging?
1.2.1 Introduction
In Section 1.1, we have highlighted a significant overlap between dentistry and brain science. Though the two fields are closely linked from a functional perspective, there exists a vast difference between research approaches of the oral cavity and those of the brain. Dentists can visually examine the oral structure, and oral functions can be quantified with a chairside set of assessments. In contrast, brain functions and mental status, sometimes metaphorized as a ‘black box’, can hardly be examined directly at the chairside. Therefore, a pivotal step to facilitate the investigation of the brain is to develop the technology for quantifying brain structure and functions. Neuroimaging, defined as a non‐invasive approach of ‘visualizing the central nervous system, especially the brain, by various imaging modalities’ (MeSH 2012), is such a technological breakthrough that revolutionizes the research approaches of the brain.
A common myth is that neuroimaging or ‘brain scan’ would be a kind of ‘modern magic’. The impression is strengthened by some sci‐fi movies, where ‘peeking into the brain’ is taken as an icon of something futuristic. Contrary to the popular myth, the term ‘neuroimaging’ has been adopted as a common method for regular clinical investigation and research. In the following sections, we outline the primary methods of neuroimaging approaches in brain science, and their roles in brain science and practical implications in dentistry are highlighted.
1.2.2 What Is the Role of Neuroimaging Research in Dentistry
1.2.2.1 Trends of Research Publications in Dental Neuroimaging Research
Table 1.1 summarizes the number of dental research publications combined with research on the brain and neuroimaging, according to a PubMed‐based survey. The trend of publication of dental research related to neuroimaging was strikingly similar to that related to the brain. Before 1970, only a few publications were found in these fields. In contrast, after the 1990s, the percentage of these studies showed a pronounced increase. Notably, this trend in publication can be compared with the dental research related to neuroscience in general, as recently reported by Iwata and Sessle (2019). In terms of brain and neuroimaging research, almost half of the dental research on brain and neuroimaging was published last decade (2011–2020) (Table 1.1). This trend is very different from the general field of neuroscience. It is also noteworthy that more than 90% of the dental research on neuroimaging was published after the mid‐1990s, about the same time when functional magnetic resonance imaging (fMRI) came into practice (Bandettini 2012). The trend reflects that technological innovation of biomedical imaging may facilitate cross‐disciplinary research on dentistry and the brain.
Table 1.1 Trends of the academic publicationa in dental research related to brain and neuroimaging.
| Period | Dentistry + Brain | Dentistry + Neuroimaging | ||
|---|---|---|---|---|
| No. of articles | Percentage | No. of articles | Percentage | |
| 2011–2020 | 10004 | 49 | 391 | 65 |
| 2001–2010 | 5119 | 25 | 152 | 25 |
| 1991–2000 | 2773 | 14 | 61 | 10 |
| 1981–1990 | 1719 | 8 | 2 | 0 |
| 1971–1980 | 631 | 3 | 0 | 0 |
| 1961–1970 | 145 | 1 | 0 | 0 |
| 1951–1960 | 53 | 0 | 0 | 0 |
| before 1951 | 11 | 0 | 0 | 0 |
a The number of articles was surveyed using PubMed with the following combination of keywords: ‘tooth[mesh] OR oral[mesh] OR dental[mesh] OR dentistry[mesh] OR teeth[tiab] OR tooth[tiab] OR oral[tiab] OR dental[tiab] OR dentistry[tiab]’ in conjunction with ‘brain[tiab]’ and ‘neuroimaging[tiab]’ for ‘Dentistry + Brain’ and ‘Dentistry + Neuroimaging’, respectively.
1.2.2.2 The ‘Landmark Discoveries or Concepts’: Past and Future
In their article ‘The Evolution of Neuroscience as a Research Field Relevant to Dentistry’ for the Journal of Dental Research (JDR) Centennial Series, Iwata and Sessle enlisted several achievements of orofacial neuroscience in the decades (Iwata and Sessle 2019). Many of these achievements have been made based on clinical, animal and laboratory research. For example, the gate control theory has been widely investigated from the clinical to the molecular levels. Remarkably, animal research has unravelled a complex pattern of bi‐directional projections between the stomatognathic system to the brain (Figure 1.2). Investigation of the human brain may disclose more insights on this topic. While the ‘gating’ mechanism at the spinal level has been gradually elucidated, how the nociceptive processing is translated to pain, a subjective experience, has remained a challenging issue. As noted in Chapter 6, neuroimaging methods may help extend our current knowledge in pain and its management. Another example is the investigation of neural mechanisms of mastication and swallowing, which significantly impact our understanding of oral physiology and the management of oral dysfunctions. Recent neuroimaging findings, on the one hand, confirm the evidence from animal research (e.g. the role of primary sensorimotor cortices in chewing) (Table 1.2 and Figure 1.2). On the other hand, neuroimaging findings disclose new knowledge about the role of learning and cognitive control in oral motor functions (Table 1.3). As shown in Table 1.2, many examples reveal how neuroimaging, as an exploratory tool, broadens the frontier of orofacial neuroscience into the uncharted area.
1.2.3 Methods of Neuroimaging
As an approach to visualize the central nervous system (CNS), neuroimaging consists of various methods to image the brain. The methods can be generally categorized by the degree of invasiveness, by the brain features to be quantified (e.g. brain structure or functions), and by the signals to be detected (e.g. neural activity or cerebral flow). A brief introduction of the methods is summarized in the following sections, and more detailed mechanisms are discussed in Chapter 2.
1.2.3.1 Invasive Methods of Neuroimaging
It would be contradictory to talk about an invasive imaging method if we strictly define neuroimaging as a non‐invasive approach. However, some invasive approaches have provided crucial conceptual advancement in neuroimaging. For example, in electrocorticography (ECoG), experimenters detect brain signals using a meshwork that consists of multiple electrodes. This meshwork is overlaid on the dura of the brain, and therefore, the response of the electrodes at different positions can be (though roughly) mapped to the anatomical region of the brain (Gazzaniga et al. 2019). The method was limited to patients who received brain surgery. ECoG reveals the feasibility of brain mapping, i.e. to map the association between the geometric features of the brain and mental functions, a fundamental element of modern neuroimaging.
Figure 1.2 A general view of the neural circuitries of the brain mechanisms of orofacial functions. The circuitries between the central and peripheral sites (i.e. pathways labelled in blue and red) are investigated primarily via animal models. Notably, the circuitries within the brain (i.e. the intracortical pathways labelled in black) have not been fully elucidated.
Source: Avivi‐Arber and Sessle (2018). Reproduced with permission of John Wiley and Sons.
Table 1.2 Selected findings (since 2010)a of neuroimaging research, which are related to the issues of the ‘landmark discoveries or concepts’ of oral neuroscience (Iwata and Sessle 2019), as quoted in field (A) to (G).
Source: Field (A) to (G) based on Iwata and Sessle (2019).
| Source | Participants | Methods | Major findings |
|---|---|---|---|
| (A) ‘Presentation of the gate control theory of pain’ | |||
| Brügger et al. (2012) | Healthy adults | fMRI | ‘Cerebral toothache intensity coding on a group level can thus be attributed to specific subregions within the cortical pain network’. |
| Gustin et al. (2011) | TNP and TMD patients | sMRI, MRS | ‘…neuropathic pain conditions that result from peripheral injuries may be generated and/or maintained by structural changes in regions such as the thalamus’ |
| (B) ‘… the multidimensionality and biopsychosocial aspects of pain and their application to improved diagnosis and management of orofacial pain conditions’ | |||
| Youssef et al. (2014) | Painful TN and TMD patients | ASL‐MRI | ‘… non‐neuropathic pain was associated with significant CBF increases in regions commonly associated with higher‐order cognitive and emotional functions …’ |
| Weissman‐Fogel et al. (2011) | Patients with nontraumatic TMD | fMRI | ‘… the slow behavioural responses in idiopathic TMD may be due to attenuated, slower and/or unsynchronized recruitment of attention/cognition processing areas’. |
| (C) ‘Discovery of trigeminal nociceptive afferents and their modulation by processes within orofacial tissues …’/‘Discovery of the plasticity of the nociceptive neurons …’ | |||
| Gustin et al. (2012) | Patients with painful TN and painful TMD | fMRI, ASL‐MRI | ‘… while human patients with neuropathic pain displayed cortical reorganization and changes in somatosensory cortex activity, patients with non‐neuropathic chronic pain did not’. |
| Moayedi et al. (2012) | TMD patients | DTI | ‘… novel evidence for CNV microstructural abnormalities that may be caused by increased nociceptive activity, accompanied by abnormalities along central WM pathways in TMD’. |
| (D) ‘Discovery of nociceptive neurons in the brain and their modulation by intrinsic CNS circuits and endogenous mediators…’ | |||
| Desouza et al. (2013) | Patients with idiopathic trigeminal neuralgia | sMRI | ‘These findings may reflect increased nociceptive input to the brain, an impaired descending modulation system that does not adequately inhibit pain …’ |
| Abrahamsen et al. (2010) | TMD patients | fMRI | ‘… hypnotic hypoalgesia is associated with a pronounced suppression of cortical activity …’ |
| (E) ‘Definition of the central pattern generators for chewing and swallowing’ | |||
| Lowell et al. (2012) | Healthy adults | fMRI | ‘The greater connectivity from the left hemisphere insula to brain regions within and across hemispheres suggests that the insula is a primary integrative region for volitional swallowing in humans’. |
| Quintero et al. (2013) | Healthy adults | fMRI | ‘… demonstrated that brain activation patterns may dynamically change over the course of chewing sequences’. |
| (F) ‘… discovery of the plasticity of sensorimotor cortex and other CNS regions in relation to orofacial sensorimotor control, learning and adaptation to injury and other changes in orofacial tissues’ | |||
| Kimoto et al. (2011) | Edentulous patients wearing a CD and an IOD | fMRI | |
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