Fig 1.
Flowchart showing the sequence of patient inclusion.
Table 1.
Demographic and clinical characteristics of the migraine patients.
Fig 2.
Change in the pain tolerance thresholds.
Allodynia state was determined according to the changes in the pain tolerance thresholds between interictal and ictal visits on face and hand. If the pain tolerance change was >3°C on both face and hand the patient was categorized as having generalized allodynia. Localized allodynia was defined if >3°C change was observed on face but not hand. If there was no change or if the change was < 3°C on face and hand that was considered no allodynia. In total there were 7 patients who experienced generalized allodynia and 8 who were categorized as having no allodynia with the remaining 4 experiencing localized allodynia.
Fig 3.
Brain activation for ictal vs. interictal state.
Contrast analysis of the ictal visit vs. interictal visit in response to noxious thermal stimulation on the left hand is presented. Hot colors (yellow to red colors) indicate stronger activation during the ictal state. The results are based on longitudinal data of 19 migraine patients, and non-noxious heat vs. noxious heat contrast maps. Statistical maps were thresholded and corrected for multiple comparisons using Gaussian mixture modeling (GMM) approach. Coordinates are in Montreal Neurological Institute (MNI) space.
Fig 4.
Brain activation in generalized allodynia vs. no allodynia.
Contrast analysis of the ictal vs. interictal visits in response to noxious thermal stimulation on the left hand is presented for patients with generalized allodynia vs. patients with no allodynia. Hot colors (yellow to red colors) indicate stronger activation during the ictal state. The results are based on longitudinal data of 7 patients with generalized allodynia and 8 patients with no allodynia. Statistical maps were thresholded and corrected for multiple comparisons using Gaussian mixture modeling (GMM) approach. Coordinates are in Montreal Neurological Institute (MNI) space.
Fig 5.
Signal change differences along the trigeminal pathway based on Region of Interest (ROI) analysis.
Signal change values were extracted using Featquery. For those patients who received thermal stimulation on the right side, the brains were flipped along the y-axis so that all images were in accordance regarding the site of the migraine (and the stimulation side). The left side is the ipsilateral stimulation side and the right is the contralateral stimulation side. The group average results for percentage signal change between generalized and no allodynia groups are shown for the left thalamus and left trigeminal nucleus ipsilateral to the side of stimulation. For the trigeminal ganglion, the signal change is reported for the contralateral region (right side). Error bars represent standard deviations. The * symbol indicates group differences at a significant level of p < 0.05.
Fig 6.
Region of Interest (ROI) based comparison results for percentage (%) signal change in various thalamic regions according to the cortical connectivity in ictal vs. interictal scans.
Signal change values were extracted using Featquery. Thalamic sub-regions (indicated by different colors) were segmented based on the white-matter connectivity between the thalamus and cortex. The label for each color is listed in the x-axis. Bars represent changes in the percentage of the average signal change between ictal vs. interictal activation in response to noxious heat applied to the dorsum of the hand for patients with generalized allodynia and with no allodynia. The main differences are in the thalamic regions that have connections with temporal and prefrontal cortical regions with an increased signal change in generalzied allodynia patients. In contrast, thalamic regions with connectivity to the posterior parietal regions showed stronger signal change in the no allodynia group. Error bars represent standard deviations. The * symbol indicates group differences at a significant level of p < 0.05.
Table 2.
a. Whole brain contrast results in ictal vs. interictal scans (ictal > interictal). b. Whole brain contrast results in ictal vs. interictal scans (interictal > ictal).