Background & Aims
Myogenic temporomandibular disorders (mTMD) are the second most common cause of musculoskeletal pain and chronic facial pain1. Oral behaviors, such as wake-time tooth clenching and grinding, are the strongest predictor of these disorders2. Oral behaviors are also a coping behavior for stress3,4. The amygdala is implicated in modulating limbic activity, including stress-related behaviors5. A recent rodent study identified a brain circuit linking the central nucleus of the amygdala (CeA) to the trigeminal motor nucleus (5M)6, which controls the muscles of mastication. Our lab has resolved the CeA-5M circuit in humans in vivo for the first-time using MRI7; however, the circuit’s functional role in humans has yet to be explored. Here we tested whether a validated stress-inducing tasks elicits a jaw motor-response (i.e., change of masseter activity) and activates the CeA-5M circuit in individuals with mTMD and pain-free controls.
Methods
40 healthy adults (19 F, 21 M) and 31 individuals with TMD (23 F, 8M) completed questionnaires (State-Trait Anxiety Inventory8, and Oral Behaviors Checklist9,10) and performed a validated experimental stress-inducing task11. This stress-inducing task involves presenting neutral and aversive images from the International Affective Picture System (IAPS)12 in separate runs to participants in a laboratory setting, and again while undergoing functional MRI (fMRI). During this stress-inducing task, participants provided self-reported stress ratings on numeric rating scales (0: no stress; 10: most stress they have ever felt) during stress and neutral runs11. Surface electromyography (EMG) was used to assess masseter muscle activity in the laboratory. Task-based fMRI was analyzed using FSL. We tested for whole-brain group differences, and task-based functional connectivity (psychophysiological interaction; PPI) of the CeA to the rest of the brain.
Results
Stress ratings were higher in the stress condition compared to the neutral condition for both groups (p<0.001). Participants with mTMD reported higher stress ratings across all conditions compared to the control group (p<0.05). EMG power was higher in the stress condition compared to the neutral condition in the 100-300Hz range (p<0.001)–thus our task elicited a jaw motor response to stress. During the stress task, we found activation of the CeA, as well as cortical motor regions (cluster-corrected p<0.05) in both groups. We did not, however, see activation of 5M in either group. The PPI did not identify CeA-5M circuit in either group. The mTMD group had stronger functional connectivity between the CeA and premotor cortex (PMC), supplementary motor area (SMA), and subgenual anterior cingulate cortex (sgACC) compared to controls, suggesting that other cortical motor regions are involved in the jaw motor response to stress (uncorrected p<0.001).
Conclusions
Stress ratings were higher in the stress condition compared to the neutral condition for both groups (p<0.001). Participants with mTMD reported higher stress ratings across all conditions compared to the control group (p<0.05). EMG power was higher in the stress condition compared to the neutral condition in the 100-300Hz range (p<0.001)–thus our task elicited a jaw motor response to stress. During the stress task, we found activation of the CeA, as well as cortical motor regions (cluster-corrected p<0.05) in both groups. We did not, however, see activation of 5M in either group. The PPI did not identify CeA-5M circuit in either group. The mTMD group had stronger functional connectivity between the CeA and premotor cortex (PMC), supplementary motor area (SMA), and subgenual anterior cingulate cortex (sgACC) compared to controls, suggesting that other cortical motor regions are involved in the jaw motor response to stress (uncorrected p<0.001).
References
1.Ananthan, S. & Benoliel, R. Chronic orofacial pain. J Neural Transm 127, 575–588 (2020).
2.Ohrbach, R. et al. Clinical orofacial characteristics associated with risk of first-onset TMD: the OPPERA prospective cohort study. J Pain 14, 10.1016/j.jpain.2013.07.018 (2013).
3.Ohrbach, R. & Michelotti, A. The Role of Stress in the Etiology of Oral Parafunction and Myofascial Pain. Oral and Maxillofacial Surgery Clinics of North America 30, 369–379 (2018).
4.Flor, H., Birbaumer, N., Schulte, W. & Roos, R. Stress-related electromyographic responses in patients with chronic temporomandibular pain. Pain 46, 145–152 (1991).
5.Janak, P. H. & Tye, K. M. From circuits to behaviour in the amygdala. Nature 517, 284–292 (2015).
6.Han, W. et al. Integrated Control of Predatory Hunting by the Central Nucleus of the Amygdala. Cell 168, 311-324.e18 (2017).
7.Kaya, B., Geha, P., de Araujo, I., Cioffi, I. & Moayedi, M. Identification of central amygdala and trigeminal motor nucleus connectivity in humans: An ultra-high field diffusion MRI study. Human Brain Mapping 44, 1309–1319 (2023).
8.Spielberger, C. D. State-Trait Anxiety Inventory for Adults. (1983) doi:10.1037/t06496-000.
9.Sullivan, M. J. L., Bishop, S. R. & Pivik, J. The Pain Catastrophizing Scale: Development and validation. Psychological Assessment 7, 524–532 (1995).
10.Nakao, M. & Barsky, A. J. Clinical application of somatosensory amplification in psychosomatic medicine. Biopsychosoc Med 1, 17 (2007).
11.Markiewicz, M. R., Ohrbach, R. & McCall, W. D. Oral behaviors checklist: reliability of performance in targeted waking-state behaviors. J Orofac Pain 20, 306–316 (2006).
12.van der Meulen, M. J., Lobbezoo, F., Aartman, I. H. A. & Naeije, M. Validity of the Oral Behaviours Checklist: correlations between OBC scores and intensity of facial pain. J Oral Rehabil 41, 115–121 (2014).
13.Sinha, R., Lacadie, C. M., Constable, R. T. & Seo, D. Dynamic neural activity during stress signals resilient coping. Proceedings of the National Academy of Sciences 113, 8837–8842 (2016).
14.PJ Lang, Bradley, M. & Cuthbert, B. International Affective Picture System (IAPS): Affective Ratings of Pictures and Instruction Manual. (2008).
Presenting Author
Suha Sagheer
Poster Authors
Suha Sagheer; HBSc
BSc(Hons)
Centre for Multimodal Sensorimotor and Pain Research, Faculty of Dentistry, University of Toronto
Lead Author
Topics
- Pain Imaging