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Table 1 Summary of functional MRI studies on TMD, MRI techniques including rs-fMRI, ts-fMRI, ASL, and MRS

From: The neuro-pathophysiology of temporomandibular disorders-related pain: a systematic review of structural and functional MRI studies

StudiesModalityAnalysis methodPatientsControlsMain findings in TMD patients compared to HC
CharacteristicsNumber and ageaDurationaMedication (n)Clinical assessmentsNumber and agea
rs-fMRI (n = 4)
Kucyi et al.
[46]
rs-fMRIVoxel-wise FCTMD (RDC/TMD)17F; 33.1 ± 11.9 y9.3 ± 8.3 (0.75–30) y8NPS1, Pain Catastrophizing Scale [44]17F; 32.2 ± 10.2 yIn TMD:
• Increased mPFC FC with other DMN regions, including PCC/PCu, retrosplenial cortex and areas within visual cortex
• Pain rumination scores positively correlated to mPFC FC with the PCC/PCu, retrosplenial cortex, medial thalamus and PAG
He et al.
[47]
rs-fMRIWhole brain fALFFTMD (RDC/TMD)9M, 14F; 22.4 ± 3.6 y; 11/23 received 3-month splint therapy14.8 ± 20.7 months0SCL-90, GCPS [83], Helkimo indices [78], CR–MI discrepancy index [76]9M, 11F; 23.1 ± 2.4 yIn TMD:
• Decreased fALFF in left precentral gyrus, SMA, middle frontal gyrus, and right OFC
• Negative correlation between fALFF in left precentral gyrus and vertical CR-MI discrepancy
• Improved symptoms and signs after treatment, with increased fALFF in left precentral gyrus and left posterior insula compared with pretreatment
He et al. [48]rs-fMRIVoxel-wise FCTMD (RDC/TMD)11M, 19F; 22.1 ± 3.8 (15–29) y; 16/30 had myofascial pain17.3 ± 22.4 months0SCL-90, GCPS [83], Helkimo indices [78]9M, 11F; 23.1 ± 2.4 (20–30) yIn TMD:
• Decreased FC in ventral corticostriatal circuitry, between ventral striatum and ventral frontal cortices, including ACC and anterior IC
• Decreased FC in dorsal corticostriatal circuitry, between dorsal striatum and dorsal cortices, including precentral gyrus and supramarginal gyrus
• Decreased FC within striatum
• Decreased corticostriatal FC correlated with clinical measurements including Di and pain intensity
Zhang et al. [49]rs-fMRIReHo and voxel-wise FCTMD synovitis (RDC/TMD)8F; 33.5 ± 8.7 yNA0VAS210F; 33.9 ± 7.3 yIn TMD:
• Decreased regional homogeneity in right anterior IC
• Decreased positive FC between right anterior IC and MCC
• Decreased negative FC between right anterior IC and the precuneus
ts-fMRI (n = 9)
Nebel et al. [52]ts-fMRIBrain activationTMD (RDC/TMD)13F; 28.7 ± 7.6 yNANASF-MPQ [33]12F; 28.8 ± 7.9 yIn TMD:
• Distinct subregions of contralateral S1, S2 and IC responded maximally for TMD and HC
• Primary auditory cortex activation
• Greater activations bilaterally in ACC and contralaterally in the amygdala
 Ichesco et al. [51]rs-fMRI and ts-fMRIVoxel-wise FCMyofascial TMD (RDC/TMD)8F; 23–31 yNANAbVAS2, SF-MPQ [33], STPI [34]8F; 22–27 yIn TMD:
• Increased FC between left anterior IC and pgACC during both resting state and applied pressure pain
• Negative correlation between anterior IC-ACC connectivity and clinical pain intensity by VAS
 Wessman et al. [54]ts-fMRIBrain activation and ROI-wise FCTMD (RDC/TMD)17F; 35.2 ± 11.6 y9.3 ± 8.3 (0.75–30) y8NRS317F; 34 ± 9.9 yIn TMD:
• Slow reaction times for all Stroop tasks
• Increased task-evoked responses in brain areas implicated in attention (lateral prefrontal, inferior parietal), emotional processes (amygdala, pgACC), motor planning and performance (SMA and M1), and activations of the DMN (mPFC and PCC)
• Decreased FC between prefrontal and cingulate cortices and between amygdala and cingulate cortex
Zhao et al. [53]ts-fMRIBrain activationTMD synovitis with unilateral biting pain (RDC/TMD)3M, 11F; 33.7 ± 13.2 y; contralateral (n = 8) and ipsilateral (n = 6) TMD biting painNANAVAS2, SCL-907M, 7F; 23.7 ± 0.9 yTMJ synovitis patients with contralateral or ipsilateral biting pain showed activations in inferior frontal gyrus, superior temporal gyrus, medium frontal gyrus, M1, and ACC; of these ACC was not activated in HC
Gustin et al. [50]ts-fMRI; DTI; ASLBrain activation, FA, and CBFTMD (RDC/TMD)4M, 13F; 44 ± 3 y10.7 ± 2.9 y13VAS2, MPQ [36]26M, 27F; 41 ± 2 yPositive results for PTN patients, but not TMD:
• Showed S1 functional reorganization
• Showed reduced CBF in contralateral S1
• Showed decreased FA in contralateral S1
Lickteig et al. [60]ts-fMRIBrain activationTMD (RDC/TMD)1M, 13F; 25.7 ± 8.7 (21–53) yNANAGCPS [83], Mandibular Function Impairment Questionnaire [131]No control groupIn TMD:
• Subjective pain ratings decreased, and symmetry of condylar movements increased during therapy
• fMRI during occlusion showed activation decrease in right anterior IC and right cerebellum during therapy
• Correlation analysis between pain score and fMRI activation decrease identified right anterior IC, left posterior IC, and left cerebellar hemisphere
• Left cerebellar and right M1 activation magnitude negatively associated with symmetry of the condylar movements
He et al. [57]ts-fMRIBrain activationTMD (RDC/TMD)11M, 19F; 22.1 ± 3.8 (15–29) y; 16/30 with myofascial pain17.3 ± 22.4 months0SCL-90, GCPS [83], Helkimo indices [78]9M, 11F; 23.1 ± 2.4 (20–30) y• TMD showed decreased positive activity in left M1, right and left inferior temporal gyrus, and left cerebellum, and increased negative activations in the right mPFC during teeth clench
• For the 11 TMD after splint treatment, these areas returned to normal neural activity
Harper et al. [56]ts-fMRIBrain activationMyofascial TMD (RDC/TMD)1M, 9F; 24.9 ± 1.2 y2.3 ± 2.0 yNAbVAS2, SF-MPQ [33]10F; 26.9 ± 4.4 y• SVM could determine location of pain evoked from pressure on temporalis and thumb in TMD, but not in HC
• Differences in TMD included decreased responses to temporalis-evoked pain in the left OFC, ACC, and operculum
• No significant difference in pain-evoked BOLD response for a location remote from the TMJ (the thumb)
Roy et al. [55]ts-fMRIBrain activationTMD with jaw pain (TMD pain screening questionnaire [132])6M, 10F; 36.56 (18–68) y≥ 6 monthsNAGCPS [83], VAS26M, 9F; 30.5 (18–58) y• For controlled grip-force task, SVM separated the groups according to the functional activity in regions including the PFC, IC, and thalamus
• For controlled pain-eliciting stimulus on forearm, SVM separated the groups according to functional activity in brain regions including dlPFC, rostral ventral premotor cortex, and inferior parietal lobule
ASL and MRS (n = 3)
 Gerstner et al. [58]MRSMetabolite levelsMyofascial TMD (RDC/TMD)1M, 10F; 25.8 ± 2.33 y6 months to 7 yearsNAbSF-MPQ [33], STPI [34]1M, 10F; 24.8 ± 1.2 y• Glu levels lower in all individuals after pain testing
• In TMD:
- Left-insular Gln levels were related to reported pain
- Left posterior insular NAA and Cho levels higher at baseline
- Left insular NAA levels positively correlated with pain symptom duration
 Youssef et al. [23]ASLCBF and brain stem blood flowTMD (RDC/TMD)3M, 12F; mean ± SEM, 44.9 ± 3.1 (25–67) y11.4 ± 3.3 y5VAS2, MPQ [36]13M, 41F; mean ± SEM, 46.9 ± 2.1 (20–80) y• TNP had CBF decreases in several regions, including thalamus, S1 and cerebellar cortices
• TMD had CBF increases in regions associated with higher-order cognitive and emotional functions, such as ACC, dlPFC and precuneus
• In TMD, blood flow increased in motor-related regions and within spinal trigeminal nucleus
 Harfeldt et al. [59]MRSMetabolite levelsrTMD and gTMD (DC/TMD)rTMD: 17F, median age, 40 (30–44) y;
gTMD: 19F, median age, 43 (40–56) y
≥3 monthsNANRS310F; median age, 36 (26–51) y• Only tCr level was higher in TMD than HC
• Cho negatively correlated to maximum mouth opening capacity with or without pain, as well as PPT at the hand
• Glu positively correlated to temporal summation and the rTMD and gTMD pain groups showed more pronounced temporal summation
• gTMD pain group had lower PPT than rTMD
  1. aAge and disease duration give as mean ± SD (range), unless stated otherwise (e.g. mean ± SEM, median)
  2. bThe study did not report the details of individual medication status but asked patients to be free of medication before MRI scanning
  3. 1Numerical pain scale (range 0–10, 0 = “no pain”, 10 = “the worst pain imaginable”)
  4. 2Visual analogue scale (range 0–10, 0 = “no pain”, 10 = “the worst pain imaginable”)
  5. 3Numerical rating scale (range 0–10, 0 = “no pain”, 10 = “most possible pain”)
  6. Abbreviations:n number; M male; F female; SD standard deviation; SEM standard error of the mean; y year (s); NA not applicable; VAS visual analog scale; SF-MPQ short-form McGill Pain Questionnaire; MPQ McGill Pain Questionnaire; NRS numerical rating scale; NPS numeric pain scale; SCL-90 Symptom Check List-90; Di dysfunction index; GCPS Graded Chronic Pain Scale; TMD temporomandibular disorders; RDC/TMD (diagnosed using) Research Diagnostic Criteria for TMD; DC/TMD (diagnosed using) Diagnostic Criteria for TMD; HC healthy controls; MRI magnetic resonance imaging; fMRI functional MRI; MRS magnetic resonance spectroscopy; rs-fMRI resting-state fMRI; ts-fMRI task-state fMRI; ASL arterial spin labeling; mPFC medial prefrontal cortex; DMN default mode network; PCu precuneus; PAG periaqueductal gray; fALFF fractional amplitude of low-frequency fluctuation; SMA supplementary motor areas; SVM support vector machine; OFC orbitofrontal cortex; CR-MI centric relation-maximum intercuspation; ACC anterior cingulate cortex; FC functional connectivity; IC insular cortex; Di disable index; S1 primary somatosensory cortex; S2 secondary somatosensory cortex; pgACC pregenual ACC; M1 primary motor cortex; PCC posterior cingulate cortex; PTN painful trigeminal neuropathy; FA fractional anisotropy; BOLD signal blood-oxygen-level-dependent signal; TMJ temporomandibular joint; PFC prefrontal cortex; dlPFC dorsolateral PFC; Gln Glutamine; NAA N-acetyl aspartate; Cho choline; CBF cerebral blood flow; tCr total creatine; PPT pressure-pain threshold; rTMD regional TMD pain; gTMD generalized pain including TMD pain
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