Disrupted Spontaneous Neural Activity and Its Interaction With Pain and Emotion in Temporomandibular Disorders

Abstract

Background and PurposeTemporomandibular disorders (TMD), especially pain-related TMD, are closely related to social and psychological factors. We aimed to measure changes in spontaneous brain activity and its related functional connectivity (FC), as well as FC characteristics within the mood-regulating circuits (MRC) in TMD patients by resting-state functional magnetic resonance imaging (RS-fMRI), and to analyze the relationship between these parameters and emotional symptoms.Materials and MethodsTwenty-one adult TMD patients and thirty demographically matched healthy controls (HCs) underwent clinical scale evaluation and RS-fMRI scanning. After processing RS-fMRI data, the values of the amplitude of low-frequency fluctuation (ALFF) between the two groups were compared. Regions with abnormal ALFF values were selected as areas of interest (ROIs) to compare the differences of whole-brain seed-based FC between groups. The FCs between regions within MRC were also analyzed and compared. In addition, the relationships between RS-fMRI characteristics and pain and mood were explored by correlation and mediation analyses.ResultsCompared with HCs, TMD patients showed increased ALFF in the right parahippocampal gyrus (PHG), the right supplementary motor area, and the bilateral precentral gyrus, with decreased ALFF in the right cerebelum_crus2. Patients showed enhanced right PHG-related FC in the vermis and posterior cingulate cortex, orbitofrontal cortex (OFC)-related FC in the striatal-frontal regions, while decreased dorsolateral prefrontal cortex-related FC in the amygdala. In TMD patients, ALFF values in the right PHG and FC values between the right PHG and the vermis were positively correlated with depressive symptoms. Abnormal FCs in the left striatal-orbitofrontal pathway were correlated with pain and depressive symptoms. More importantly, mediation analysis revealed that chronic pain mediates the relationship between FC of right PHG with vermis and depressive symptoms, and abnormal FC in the left striatal-orbitofrontal pathway can mediate the association between pain and depressive symptoms.ConclusionTMD patients have dysregulated spontaneous activity and FC in the default mode network, sensorimotor network and pain-related regions, as well as dysfunction of the fronto-striatal-limbic circuits. The development of negative emotions in TMD may be related to the dysfunction of components within the reward system (especially hippocampus complex, OFC, striatum) due to chronic pain.

Resting state functional connectivity differentiation of neuropathic and nociceptive pain in individuals with chronic spinal cord injury

“… Chen et al, 2018 ). Pain-related alterations in rsFC between the parahippocampal gyrus and amygdala to cortical regions have also been previously identified, with the direction of association reported dependent on the cortical region and population (X. F. Chen et al, 2022 , Desmarteaux et al, 2021 , Mao et al, 2022 , Verriotis et al, 2022 ). In addition to their roles in pain processing, the parahippocampal gyrus and amygdala are involved in processes of emotion, memory, attention, and conditional learning through association of stimuli with positive or negative outcomes ( Aminoff et al, 2013 , Gallagher and Chiba, 1996 ).…”

Determination of pain intensity, pain-related disability, anxiety, depression, and perceived stress in Polish adults with temporomandibular disorders: A prospective cohort study

“…TMD pain in these studies was recognized as a source of peripheral neuropathy causing inflammation in the central nervous system After removing the source of peripheral inflammation, we can see immediate significant changes in brain activity and signal overload during examination by functional magnetic resonance imaging ( Barkhordarian et al, 2020 ). Chen et al (2022) also indicated neurobiological evidence that the occurrence and development of negative emotions in TMD patients may be related to the dysfunction of dopamine pathway components induced by chronic pain. The abnormal dopaminergic functional connection linking orofacial pain and depression may indicate right treatment of TMD comorbidity with negative emotion by the application of serotonin reuptake inhibitor drugs ( Chen et al, 2022 ).…”

“… Chen et al (2022) also indicated neurobiological evidence that the occurrence and development of negative emotions in TMD patients may be related to the dysfunction of dopamine pathway components induced by chronic pain. The abnormal dopaminergic functional connection linking orofacial pain and depression may indicate right treatment of TMD comorbidity with negative emotion by the application of serotonin reuptake inhibitor drugs ( Chen et al, 2022 ). Also studies conducted by Suenaga et al have shown that TMD pain is most often associated with the thalamus, the primary somatosensory cortex, the insula, and the anterior and mid-cingulate cortices ( Suenaga et al, 2016 ).…”

“…In the literature we can find also research with the use of magnetic voxel-based morphometry (VBM). Findings show that TMD, like other chronic pain states are associated with changes in brain morphology ( Gerstner et al, 2011 ; Suenaga et al, 2016 ; Barkhordarian et al, 2020 ; Budd et al, 2022 ; Chen et al, 2022 ).…”

The conscious processing of emotion in depression disorder: a meta-analysis of neuroimaging studies

“…The activation of PHG is related with emotional memory encoding ( 69 ). Chen et al ( 70 ) found a positive correlation between the activation of right PHG and depressive symptoms. The cuneus belongs to the visual areas; the activation of the sensory-related brain areas is a prerequisite to the generation of consciousness ( 8 , 71 ).…”