Article Figures & Data
Figures
- Cover Figure
Migraine patients (Pts) show widespread structural and functional brain changes that are associated with symptoms and increased pain catastrophizing A, Migraine patients showed (i) increased gray matter volume (GMV) in the left (L) hippocampus and (ii) decreased cortical thickness in the L anterior midcingulate cortex (aMCC) compared to healthy control subjects. B, Pain catastrophizing correlated with GMV reductions in the (i) L primary somatosensory cortex (S1) and (ii) L medial prefrontal cortex (mPFC), and cortical thinning in the (iii) L dorsolateral prefrontal cortex (DLPFC) and middle temporal gyrus (MTG) in migraine patients. C, GMV reductions correlated with (i) disease duration (ii), attack frequency, and (iii) migraine pain intensity in patients. D, Whole-brain overlay maps for migraine patients and healthy controls for the (i) L PCC, (ii) L aINS, and (iii) aMCC seed regions rendered onto inflated brains. Red represents resting-state functional connectivity for healthy controls and green represents the same maps in migraine patients. Yellow represents areas showing overlap in functional connectivity in controls and migraineurs. Images are thresholded at T = 4.5 (cluster extent = 25) for visualization purposes. The schematic illustrates the relationship between disease severity measures and pain catastrophizing and disruptions in functional connectivity between the default mode network (DMN), central executive network (CEN), and salience network (SN) in migraine patients. In patients, pain catastrophizing correlated with increased coupling between DMN and CEN nodes (PCC-DLPFC), whereas disease duration and migraine pain intensity correlated with SN-DMN network decoupling (aINS/aMCC-mPFC), and increased SN-CEN (aMCC-aINS) network coupling, respectively.
- Figure 1.
Statistical maps for the voxel-based morphometric analysis overlaid onto the averaged ch2bet brain template in MRIcron. A, Patients showed significant increased GMV in the left hippocampus, which extended into the parahippocampal gyrus, compared with controls. L, Left hemisphere; R, right hemisphere. B, Cortical areas showing significant group × pain catastrophizing interactions for GMV and corresponding scatter plots showing correlations between GMV and catastrophizing in migraine patients (orange circles) and healthy controls (blue circles). C−E, Regions showing significant reductions in GMV that correlated with longer disease durations (C), greater attack frequency (D), and migraine pain intensity in patients (E).
- Figure 2.
Statistical maps for the surface-based analysis rendered onto the inflated averaged brain template using Freesurfer’s QDEC graphical user interface software. A, Group differences in cortical thickness were found; migraine patients showed significant reductions in cortical thickness in the left aMCC compared with healthy controls. B, Cortical areas showing significant group × pain catastrophizing interactions for cortical thickness measures and corresponding scatter plots displaying correlations between cortical thickness and catastrophizing in migraine patients (orange circles) and healthy controls (blue circles). C−E, Cortical areas showing significant cortical thinning (blue) and thickening (red) in migraine patients that were associated with longer disease durations (C), greater migraine attack frequency (D), and migraine pain intensity in patients (E).
- Figure 3.
Whole-brain overlay maps for patients and controls for the left PCC, left aINS, and aMCC seed regions, rendered onto inflated brains in SPM8. Teal represents RS-FC for healthy controls and purple represents the same maps in migraine patients. Light violet represents areas showing overlap in RS-FC in controls and patients. Images are thresholded at T = 4.5 (cluster extent = 25) for visualization purposes. The PCC seed showed a connectivity map consistent with the DMN, whereas the aINS and aMCC seeds connectivity patterns were consistent with the SN.
- Figure 4.
Group differences in RS-FC for the aINS and aMCC seeds (SN) and PCC seed (DMN) overlaid onto the average ch2bet brain template in MRIcron. A, Patients showed significant enhancement in aINS and aMCC connectivity with the L cuneus and R lingual gyrus, respectively, and B, reduced connectivity between the PCC seed and bilateral DLPFC, S1, R PPC, R IFG, R ITG, and R mPFC. C, D, RS-FC group differences associated with pain catastrophizing for the aINS and PCC seeds. C, Patients high in catastrophizing showed enhanced RS-FC between the aINS and the L hippocampus, L SMA, and bilateral thalami. D, Significant increases in RS-FC were also identified between the PCC and the bilateral DLPFC in patients with greater pain catastrophizing scores. PAT, Patients; CTL, controls.
Tables
- Table 1.
Descriptive and inferential statistics for demographic and behavioral measures in migraine patients and healthy controls
Variable Healthy controls Migraine patients Test statistic p Gender (F/M) a 14/4 13/4 0.008 0.930 Handedness (R/L) a 16/2 16/1 0.305 0.581 Age (years) 38.89 ± 11.25 41.71 ± 12.20 0.505 0.482 Education levela 0.369 0.985 High school 1 (5.6%) 1 (5.9%) - - Some college 2 (11.1%) 2 (11.8%) - - Bachelors 8 (44.4%) 6 (35.3%) - - Masters 4 (22.2%) 5 (29.4%) - - Doctorate 3 (16.7%) 3 (17.6%) - - POMS (Total) 37.11 ± 10.27 59.18 ± 16.79 22.28 <0.001 Depress/Deject 15.61 ± 1.14 17.35 ± 2.50 7.17 0.011 Tension/Anxiety 12.94 ± 2.21 16.59 ± 4.18 10.55 0.003 Anger/Hostility 12.72 ± 1.45 13.00 ± 1.87 0.243 0.625 Confusion/Bewilderment 10.50 ± 1.79 13.00 ± 3.89 6.082 0.019 Fatigue/Inertia 9.56 ± 2.62 14.82 ± 4.90 15.984 <0.001 Vigor/Activity 24.22 ± 6.91 15.59 ± 4.89 18.025 <0.001 PCS (Total) 7.94 ± 9.43 18.47 ± 8.62 11.835 0.002 MIDAS (Total) 0.56 ± 1.20 71.71 ± 73.89 16.716 <0.001 SFMPQ (Total) 0.00 ± 0.00 7.53 ± 7.60 17.697 <0.001 Descriptive statistical values are represented as percentages (%) or means ± SD for the healthy control and migraine patient groups. In cases where inferential statistics were also performed, the test statistic and corresponding p value for the one-way ANOVA (F statistic) or Pearson’s chi-square test (χ2 statistic; indicated by a ) are shown. The p values for test statistics that reached significance are bolded. Abbreviations are as defined in the text.
M, Males; F, females.
- Table 2.
Summary of significant clusters for voxel- and surface-based morphometric group effects, group × pain catastrophizing interactions, and migraine disease characteristics
Measure Region Clusterextent MNI coordinates t/F valuecluster p valuecluster Partial corr CTL Partial corr PAT x y z r p r p GMV PAT > CTL L Hippo. 1048 −22 −15 −15 4.23 0.011 − − − − PCS: CTL > PAT L S1 1240 −42 −27 54 4.62 0.007 0.64 0.008 −0.72 0.002 L mPFC 1131 −8 56 16 4.39 0.009 0.23 0.390 −0.71 0.003 L aMCC 893 −3 30 16 4.52 0.018 0.58 0.018 −0.43 0.110 Disease duration L pINS 2334 −34 −16 22 −6.80 <0.001 − − − − R pINS 545 44 −12 24 −4.13 0.029 − − − − L IFG 519 −27 47 −17 −9.05 0.032 − − − − Attack frequency L IFG 602 −38 54 12 −6.08 0.022 − − − − L Lingual 642 −18 −63 −2 −5.08 0.019 − − − − R PCC 1025 3 −52 30 −4.26 0.004 − − − − L PPC 665 −32 −75 30 −4.74 0.017 − − − − R S1 1107 38 −33 60 −6.40 0.003 − − − − Pain intensity L aINS 918 −36 14 −23 −9.20 0.006 − − − − L PCC 2919 −8 −46 27 −9.90 <0.001 − − − − L Cerebellum 2756 −8 −42 −17 −6.69 <0.001 − − − − R Cerebellum 705 51 −73 −32 −3.83 0.014 − − − − Cortical thickness CTL > PAT L aMCC 140 −3 29 20 3.53 <0.005 − − − − PCS: CTL > PAT L DLPFC 273 −36 42 24 3.74 <0.005 0.56 0.026 −0.70 0.003 L MTG 174 −67 −24 −21 2.87 <0.005 0.56 0.026 −0.53 0.041 R IFG 160 54 20 2 4.07 <0.005 0.53 0.034 −0.74 0.002 Disease duration L DLPFC 144 −20 42 31 −3.26 <0.005 − − − − R DLPFC 138 45 52 8 −3.05 <0.005 − − − − Attack frequency L Lingual 101 −33 −44 −8 −5.16 <0.005 − − − − L Lingual 116 −21 −66 −9 −3.21 <0.005 − − − − R Lingual 363 16 −68 −8 −4.33 <0.005 − − − − L Supramarg. 139 −53 −35 43 −3.56 <0.005 − − − − L DLPFC 105 −24 16 43 3.01 <0.005 − − − − R S1 248 38 −32 63 −4.20 <0.005 − − − − Pain intensity L PCC 120 −9 −33 42 −4.43 <0.005 − − − − L M1 108 −46 −8 53 −3.43 <0.005 − − − − L IFG 117 −55 13 11 −3.18 <0.005 − − − − L Fusiform 104 −32 −70 −9 −3.05 <0.005 − − − − R mPFC 133 11 59 −11 −3.40 <0.005 − − − − R Lingual 116 13 −81 −10 −3.30 <0.005 − − − − Hippo., Hippocampus; corr, correlations; M1, primary motor cortex; PPC, posterior parietal cortex; Supramarg., supramarginal gyrus; PAT, migraine patients; CTL, healthy controls. Other abbreviations are as defined in the text.
- Table 3.
Brain regions showing significant resting-state functional connectivity patterns for the group effect, and group × pain catastrophizing interactions
Seed Region Clustersize MNI coordinates t value cluster p value cluster Partial corr CTL Partial corr PAT x y z r p r p PAT > CTL L aINS L Cuneus 1549 −10 −66 2 4.03 <0.001 − − − − aMCC R Lingual 1307 12 −56 −8 4.39 <0.001 − − − − CTL > PAT L PCC L DLPFC 364 −52 16 28 4.98 0.004 − − − − R DLPFC 590 54 10 26 3.96 <0.001 − − − − R PPC 381 34 −62 44 4.09 <0.001 − − − − R IFG 250 36 36 −6 3.54 0.014 − − − − R ITG 281 60 −44 −22 5.37 0.010 − − − − L S1 477 −32 −38 42 5.53 0.001 − − − − R S1 425 44 −32 48 3.79 0.002 − − − − R mPFC 198 2 30 46 3.87 0.025 − − − − PCS: PAT > CTL L aINS L Hippo. 161 −26 −18 −10 3.97 0.034 −0.59 0.014 0.63 0.009 L SMA 135 −36 −14 62 3.76 0.050 −0.47 0.055 0.67 0.004 L Thalamus 235 −12 −18 2 4.55 0.013 −0.51 0.036 0.70 0.003 R Thalamus 190 12 −24 14 4.21 0.023 −0.77 0.001 0.63 0.008 L PCC L DLPFC 215 −36 22 28 3.74 0.020 −0.30 0.250 0.76 0.001 R DLPFC 212 38 22 28 4.15 0.021 −0.52 0.034 0.81 0.001 aMCC L Precuneus 146 −14 −64 28 4.10 0.052 −0.45 0.069 0.63 0.008 R Precuneus 307 8 −66 30 3.84 0.008 −0.34 0.177 0.66 0.006 PCS: CTL > PAT L PCC R Cerebellum 539 14 −56 −36 5.39 0.001 0.63 0.006 −0.78 <0.001 R Cerebellum 187 36 −52 −44 5.00 0.028 0.63 0.007 −0.67 0.004 R Cerebellum 159 24 −78 −26 3.68 0.041 0.70 0.002 −0.59 0.015 L Cerebellum 297 −16 −70 −26 4.36 0.008 0.82 0.001 −0.44 0.091 Hippo., Hippocampus; corr, correlations; PPC, posterior parietal cortex; SMA, supplementary motor area; PAT, migraine patients; CTL, healthy controls. Other abbreviations are as defined in the text.
- Table 4.
Summary of significant correlations between whole-brain resting-state functional connectivity and migraine disease characteristics
Diseasecharacteristics Seed Region Clustersize MNI coordinates t value cluster p value cluster +/−corr x y z Disease duration L aINS R Caudate 133 6 14 6 4.12 0.036 − L PPC 488 −52 −56 50 6.32 <0.001 − L MTG 213 −48 −24 −10 5.58 0.010 − L SFG 139 −16 38 58 5.66 0.032 − L mPFC 1578 −2 42 −14 5.31 <0.001 − L PCC R Pons 181 4 −30 −38 6.63 0.014 + aMCC R mPFC 133 6 34 −16 4.95 0.048 − Attack frequency L aINS L ITG 131 −34 14 −32 5.82 0.038 − L Hippocampus 121 −32 −44 2 5.26 0.045 + L PCC L PPC 136 0 −40 66 5.93 0.028 − aMCC L MTG 148 −52 −4 −34 5.27 0.038 − Pain intensity L PCC R V2 105 54 −68 22 4.21 0.049 + R Fornix 170 20 −40 26 6.24 0.016 − L PPC 399 −36 −38 30 7.20 0.001 + aMCC R aINS 269 32 12 10 9.19 0.038 + PPC; Posterior parietal cortex; SFG, superior frontal gyrus; STG, superior temporal gyrus. +/− corr denotes positive or negative correlation. Other abbreviations are as defined in the text.
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