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Table 2 Summary of structural MRI studies on TMD, MRI techniques including sMRI and DTI

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

Studies (n = 9)ModalityAnalysis methodPatientControlsMain findings in TMD patients compared to HC
CharacteristicsNumber and age*Duration*Medication (n)Clinical assessmentsNumber and age*
Younger et al. [31]3D T1Whole brain VBMMyofascial TMD
(RDC/TMD)
14F; 38 ± 13.7 (23–61) y4.4 ± 2.9 (1–11) y9NRS315F, individually age-matched to patients• No overall difference in GMV between TMD and HC
• In TMD:
- Decreased or increased GMV in several areas of trigemino-thalamo-cortical pathway, including brainstem trigeminal sensory nuclei, thalamus and S1
- Increased GMV in limbic regions such as posterior putamen, globus pallidus, and anterior IC
- Self-reported pain severity was associated with increased GMV in pgACC and PCC
Gerstner et al. [32]3D T1Whole brain VBMMyofascial TMD (RDC/TMD)9F; 25.4 ± 2.5 (23–31) y2.5 ± 2.1 (0.5–4) yNA**VAS2, SF-MPQ [33], STPI [34]9F; 24.8 ± 1.4 (24–27) y• No differences in global GMV or WMV
• In TMD:
- Decreased GMV in left ACC, right PCC, right anterior IC, left inferior frontal gyrus, and superior temporal gyrus
- Decreased regional WMV in medial prefrontal cortex bilaterally
Gustin et al. [35]3D T1 and MRSWhole brain VBM and metabolite levelsTMD (RDC/TMD)4M, 16F; mean ± SEM, 45.7 ± 2.9 (28–70) y11.4 ± 3.3 y14VAS2, MPQ [36], BDI [37], STATE [38]6M, 25F; mean ± SEM, 46.8 ± 3.3 (21–87) y• VBM revealed no change in regional GMV in TMD compared to HC, while TNP had significant regional GMV changes in a number of brain regions
• No significant change in NAA/Cr in thalami of TMD compared with HC, while NAA/Cr was decreased in the thalamus in TNP
• Regional GMV and thalamic NAA/Cr was negatively correlated to diary pain scores in TNP but not TMD
Moayedi et al. [39]3D T1CTA and VBM (ROI)TMD (RDC/TMD)17F; 33.1 ± 11.9 y9.8 ± 8.25 (0.75–30) y11NPS1, NEO-FFI [40]17F; 32.2 ± 10.1 (20–50) y• TMD patients had cortical thickening in S1 and PFC
• TMD clinical characteristics were related to brain structure:
- GMV in sensory thalamus positively correlated to TMD duration
- Cortical thickness in M1 and aMCC negatively correlated to pain intensity
- Pain unpleasantness negatively correlated to cortical thickness in OFC
- Positive correlation between neuroticism and OFC thickness
Moayedi et al. [41]3D T1CTA and VBM (ROI)DittoDittoDittoDittoNPS1Ditto• TMD had accelerated whole-brain GMV loss compared to HC, but TMD duration was not correlated to GMV
• Three types of aberrant relationships between GM and age in five focal brain regions:
- TMD had age-related GMV increases in thalamus whereas GM in HC was relatively sustained
- TMD had age-related cortical thinning in aMCC/pgACC, while HC had age-related cortical thickening
- TMD patients maintained cortical thickness in dorsal striatum and PMC with age, as opposed to age-related GMV decrease in HC.
• TMD duration was related to cortical thinning in PMC
Moayedi et al. [42]DTIFA, MD, and RD (ROI)DittoDittoDittoDittoNPS1DittoIn TMD:
• Decreased FA in right and left trigeminal nerves, and FA in right trigeminal nerve negatively correlated with TMD duration
• Widespread microstructure alterations of WM tracts related to sensory, motor, cognitive and pain functions, including a focal area of the corpus callosum
• Corpus callosum had higher connection probability to frontal pole and lower connection probability to dlPFC
• FA correlated with TMD clinical characteristics
- FA in tracts adjacent to vlPFC and tracts coursing through thalamus negatively correlated with pain intensity
- FA in internal capsule negatively correlated with pain intensity and unpleasantness
Salomons et al. [43]3D T1 and DTICTA (ROI) and FA (TBSS)DittoDittoDittoDittoNPS1, Pain Catastrophizing Scale [44]DittoIn TMD:
• Magnitude of self-reported helplessness correlated with cortical thickness in SMA and MCC, regions implicated in cognitive aspects of motor behavior
• FA of connected white matter tracts along corticospinal tract was associated with helplessness and mediated the relationship between SMA cortical thickness and helplessness
Wilcox et al. [45]3D T1 and DTIVBM (ROI), FA and MDTMD (RDC/TMD)4M, 16F; mean ± SEM, 45.7 ± 2.9 (20–78) ymean ± SEM: 9.15 ± 8.78 (1.5–30) y14VAS2, MPQ [36]5M, 21F; mean ± SEM, 52.3 ± 2.95 y• Trigeminal neuralgia displayed 47% decrease in trigeminal nerve root volume but no change in DTI values
• TNP had 40% increase in nerve volume but no change in DTI values
• TMD had no change in volume or DTI values
Wilcox et al. [22]3D T1 and DTIVBM (ROI), FA and MDTMD (RDC/TMD)4M, 18F; mean ± SEM, 46.5 ± 2.6ymedian: 9.7 y15VAS2, MPQ [36]7M, 33F; mean ± SEM, 48.3 ± 2.1 yIn TMD:
• Regional GMV decrease in medullary dorsal horn, in conjunction with an increase in MD
• Volumetric and MD changes in regions of the descending pain modulation system, including the PAG and nucleus raphe magnus
• Decreased FA in root entry zone of trigeminal nerve, spinal trigeminal tract and ventral trigemino-thalamic tracts
  1. *Age and disease duration represented as mean ± SD (range), unless stated otherwise (e.g. mean ± SEM, median)
  2. **The 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 0–11, 0 = “no pain”, 11 = “most possible pain”)
  6. Abbreviations:n number; M male; F female; SD standard deviation; SEM standard error of the mean; y years; NA not applicable; VAS visual analog scale; SF-MPQ short-form McGill Pain Questionnaire; MPQ McGill Pain Questionnaire; BDI Beck Depression Inventory; STATE State Anxiety Index; NRS numerical rating scale; NPS numeric pain scale; TMD temporomandibular disorders; RDC/TMD (diagnosed using) Research Diagnostic Criteria for TMD; HC healthy controls; MRI magnetic resonance imaging; sMRI structural MRI; DTI diffusion tensor imaging; MRS magnetic resonance spectroscopy; GM gray matter; GMV gray matter volume; WM white matter; WMV white matter volume; ACC anterior cingulate cortex; pgACC pregenual ACC; PCC posterior cingulate cortex; IC cingulate cortex; VBM voxel-based morphometry; NAA N-acetyl aspartate; NEO Neuroticism-Extraversion-Openness Five Factor Inventory; Cr creatine; CTA cortical thickness analysis; TNP trigeminal neuropathic pain; S1 primary somatosensory cortex; PFC prefrontal cortex; M1 primary motor cortex; aMCC anterior mid cingulate cortex; OFC orbitofrontal cortex; PMC premotor cortex; FA fractional anisotropy; MD mean diffusivity; RD radial diffusivity; dlPFC dorsolateral PFC; vlPFC ventrolateral PFC; SMA supplementary motor areas; PAG periaqueductal gray
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