Somatotopic activation triggered by combined corneal pain and eye blink.

<p>The Pain+Blink condition activated contralateral S1 (Max zstat  = 4.9 at 56, −14, 43) and bilateral M1 (Max zstat  = 9.9 at 52, 2, 31) in regions corresponding to the eye in the Penfield sensory and motor homunculi <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044643#pone.0044643-Penfield2" target="_blank">[19]</a> (p<0.0001, uncorrected for multiple comparisons). The No Pain+Blink condition activated bilateral M1 (Max zstat  = 7.4 at 44, −4, 43), but not S1. Investigations were restricted to the non-shaded areas in the activation maps, which correspond to bilateral pre- (blue) and post-central gyri (red) as highlighted in the underlying brain slices and colored squares (dashed squares denote absent activation). Note that the boundaries of these probabilistic-defined areas overlap with other regions, such as supplementary motor area, middle frontal gyrus, and supramarginal gyrus. Of note, the supplementary motor area has previously been associated with voluntary blinking <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044643#pone.0044643-Chung1" target="_blank">[13]</a>, and was active in both conditions along the midline of coronal slice y = −14 (only shown for Pain+Blink in figure). A = anterior; L = left; P = posterior; R = right.</p

Brain regions with decreased hypothalamic functional connectivity in migraine patients vs. healthy control subjects.

<p><u>Legend:</u> FrPole = frontal pole; ParaCG = paracingulate gyrus; PrCG = precentral gyrus; SFG = superior frontal gyrus.</p

Increased hypothalamic functional connectivity in migraine-healthy controls in parasympathetic and sympathetic nervous system brain structures.

<p>Functional connectivity contrast maps were thresholded at a posterior probability of p>0.5 using GMM. Contrast maps overlay the standard MNI152 whole-brain atlas. PNS = parasympathetic nervous system, SNS = sympathetic nervous system. In reference to coordinates, x = sagittal (posterior-anterior, from left to right of the image), y = coronal (right-left), and z = axial planes (right-left).</p

Subject demographics.

<p><u>Key</u>: “Side” = the laterality of migraine attacks (B = Bilateral, L = Left unilateral, R = Right unilateral, U = Unilateral, alternating sides); “Pain w/o med” = average pain intensity reported during a migraine attack when no abortive medication is taken. Pain intensity was reported using a numeric rating scale from 0–10; “Pain w/med” = the average pain intensity reported during a migraine attack when abortive medication is taken. Freq = headache days per month.</p

Hypothalamus seeds across subjects registered to the MNI152 standard brain.

<p>Anatomical boundaries for each subject were based on Saleem et al., 2007 (see Methods for details).</p

Brain regions with increased hypothalamic functional connectivity in migraine patients vs. healthy control subjects.

<p><u>Legend</u>: Cr I/II = Crus I and II; ITG = inferior temporal gyrus; IX = hemispheric lobule IX; MFG = middle frontal gyrus; PHG = parahippocampal gyrus; PN = pontine nuclei; PrCG = precentral gyrus; SMG = supramarginal gyrus; SPL = superior parietal lobule; STG = superior temporal gyrus; TmP = temporal pole; V = hemispheric lobule V; V/VI = hemispheric lobules V and VI; Verm VIIIa/VIIIb = Vermal lobules VIIIa/VIIIb.</p

Contrast analysis results for painful heat functional MRI activation after sumatriptan administration on the CGRP day.

<p>Contrast analysis results for painful heat functional MRI activation after sumatriptan administration on the CGRP day.</p

Time-to-peak determined from a 2 gamma function fit of the average responses contra/ipsi for VAS of 3 and 7 (see text).

<p>Time-to-peak determined from a 2 gamma function fit of the average responses contra/ipsi for VAS of 3 and 7 (see text).</p

Headache score: Median headache score on the verbal rating scale (VRS) in 27 healthy volunteers.

<p>Black line with squares is the headache score on the CGRP day while gray line with triangles is headache score on the placebo day.</p

Figure 2

<p>(A) Left Panel: Group average response to innocuous thermal stimuli in the contralateral (blue line) and ipsilateral side (red line). (B) Right Panel: Group average response to noxious stimuli for contralateral and ipsilateral sides. Both graphs display changes in oxyhemoglobin concentration. Error bars represent the SEM. Gray block indicates the duration of the applied stimuli.</p