Association between migraine frequency and neural response to emotional faces: An fMRI study

Previous studies have demonstrated that migraine is associated with enhanced perception and altered cerebralprocessing of sensory stimuli. More recently, it has been suggested that this sensory hypersensitivity mightreflect a more general enhanced response to aversive emotional stimuli. Using functional magnetic resonanceimaging and emotional face stimuli (fearful, happy and sad faces), we compared whole-brain activation between41 migraine patients without aura in interictal period and 49 healthy controls. Migraine patients showed in-creased neural activation to fearful faces compared to neutral faces in the right middle frontal gyrus and frontalpole relative to healthy controls. We also found that higher attack frequency in migraine patients was related toincreased activation mainly in the right primary somatosensory cortex (corresponding to the face area) to fearfulexpressions and in the right dorsal striatal regions to happy faces. In both analyses, activation differences re-mained significant after controlling for anxiety and depressive symptoms. Thesefindings indicate that enhancedresponse to emotional stimuli might explain the migraine trigger effect of psychosocial stressors that graduallyleads to increased somatosensory response to emotional clues and thus contributes to the progression orchronification of migrain

Increased activation of the pregenual anterior cingulate cortex to citalopram challenge in migraine: an fMRI study

Background: The anterior cingulate cortex (ACC) is a key structure of the pain processing network. Several structural and functional alterations of this brain area have been found in migraine. In addition, altered serotonergic neurotransmission has been repeatedly implicated in the pathophysiology of migraine, although the exact mechanism is not known. Thus, our aim was to investigate the relationship between acute increase of brain serotonin (5-HT) level and the activation changes of the ACC using pharmacological challenge MRI (phMRI) in migraine patients and healthy controls. Methods: Twenty-seven pain-free healthy controls and six migraine without aura patients participated in the study. All participant attended to two phMRI sessions during which intravenous citalopram, a selective serotonin reuptake inhibitor (SSRI), or placebo (normal saline) was administered. We used region of interest analysis of ACC to compere the citalopram evoked activation changes of this area between patients and healthy participants. Results: Significant difference in ACC activation was found between control and patient groups in the right pregenual ACC (pgACC) during and after citalopram infusion compared to placebo. The extracted time-series showed that pgACC activation increased in migraine patients compared to controls, especially in the first 8–10 min of citalopram infusion. Conclusions: Our results demonstrate that a small increase in 5-HT levels can lead to increased phMRI signal in the pregenual part of the ACC that is involved in processing emotional aspects of pain. This increased sensitivity of the pgACC to increased 5-HT in migraine may contribute to recurring headache attacks and increased stress-sensitivity in migraine

ASSOCIATION ANALYSIS OF 5-HTTLPR VARIANTS, 5-HT2A RECEPTOR GENE 102T/C POLYMORPHISM AND MIGRAINE

It is well known that migraine has a strong genetic component, although the type and number of genes involved is not yet clear. There is evidence to suggest that serotonin-related genes participate in the pathogenesis of migraine. Previous studies have shown that gender differences influence the serotonergic neurotransmission and, in addition, the migraine prevalence is higher in females than males. Therefore, we investigated the functional polymorphism in the upstream regulatory region of the serotonin transporter gene (5-HTTLPR) and the 102T/C polymorphism of the 5-HT2A receptor gene in the Hungarian female population. These genes were analysed in 126 migraine sufferers (with or without aura)and 101 unrelated healthy controls using case control design. A borderline association (chi2 = 3.84, df = 1, p = 0.049; OR = 1.45, 95% CI = 1.00-2.12) between 5-HTTLPR short (S) allele and migraine was found. No significant difference between migraine sufferers and controls was observed for the 102T/C polymorphism of 5-HT2A receptor gene. Furthermore, there was no significant interaction between5-HTTLPR and 102T/C polymorphisms in our study population. In conclusion, our results support that the genetic susceptibility of migraine may be associated with a locus at or near the 5-HT transporter gene