Physiopathology of Migraine: What Have We Learned from Functional Imaging?
- 993 Downloads
Purpose of Review
This review aims to provide an overview of the most recent and significant functional neuroimaging studies which have clarified the complex mechanisms underlying migraine pathophysiology.
The recent data allow us to overcome the concept of a migraine generator suggesting that functional networks abnormalities may lead to changes in different brain area activities and consequent reduced migraine thresholds susceptibility, likely associated with higher migraine severity and burden.
Although functional magnetic resonance imaging studies have allowed recognition of several migraine mechanisms, its pathophysiology is not completely understood and is still a matter of research. Nevertheless, in recent years, functional magnetic resonance imaging studies have allowed us to implement our knowledge of migraine pathophysiology. The pivotal role of both the brainstem and the hippocampus in the first phase of a migraine attack, the involvement of limbic pathway in the constitution of a migrainous pain network, the disrupted functional connectivity in cognitive brain networks, as well as the abnormal function of the visual network in patients with migraine with aura are the main milestones in migraine imaging achieved through functional imaging advances. We believe that further studies based on combined functional and structural techniques and the investigation of the different phases of migraine cycle may represent an efficient methodological approach for comprehensively looking into the migrainous brain secrets.
KeywordsMigraine Functional neuroimaging PET fMRI Resting-state network Trigeminal stimulation
Compliance with Ethical Standards
Conflict of Interest
Antonio Russo, Marcello Silvestro, Gioacchino Tedeschi, and Alessandro Tessitore declare no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 13.• Maniyar FH, Sprenger T, Schankin C, et al. The origin of nausea in migraine—a PET study. J Headache Pain. 2014;15:84. The results demonstrate that nausea is a centrally driven symptom in migraine due to activation of brain structures known to be involved in nausea independently from pain and trigeminal activation. CrossRefPubMedPubMedCentralGoogle Scholar
- 18.•• Coppola G, Di Renzo A, Tinelli E, et al. Resting state connectivity between default mode network and insula encodes acute migraine headache. Cephalalgia. 2017;1:333102417715230.The authors demonstrated a reduced DMN-insula connectivity related with an increased pain perception during attacks in migraine, unlike what has been observed in other chronic extra-cephalic pain disorders. Google Scholar
- 22.•• DaSilva AF, Nascimento TD, Love T, et al. 3D-neuronavigation in vivo through a patient’s brain during a spontaneous migraine headache. J Vis Exp. 2014;(88). This study investigated, for the first time, using a novel 3D interactive neuronavigation approach, the endogenous μ-opioid transmission in the brain during a migraine attack.Google Scholar
- 23.Leao AAP. Spreading depression of activity in cerebral cortex. J Neurophysiol. 1944;7(6):359–90.Google Scholar
- 33.•• Schulte LH, Allers A, May A. Hypothalamus as a mediator of chronic migraine: evidence from high-resolution fMRI. Neurology. 2017;88(21):2011–6. The study results confirm the key role of the anterior part of the hypothalamus in the pathophysiology of migraine chronification. CrossRefPubMedGoogle Scholar
- 34.•• Russo A, Esposito F, Conte F, et al. Functional interictal changes of pain processing in migraine with ictal cutaneous allodynia. Cephalalgia. 2017;37(4):305–14. These findings suggest that ictal cutaneous allodynia may be subtended by both a dysfunctional analgesic compensatory mechanism and an abnormal internal representation of pain in migraine patients. CrossRefPubMedGoogle Scholar
- 35.•• Schwedt TJ, Chong CD, Chiang CC, et al. Enhanced pain-induced activity of pain-processing regions in a case-control study of episodic migraine. Cephalalgia. 2014;34(12):947–58. The study underlines that the enhanced cognitive pain processing might reflect cerebral hypersensitivity related to high expectations and hypervigilance for pain in migraine patients. CrossRefPubMedPubMedCentralGoogle Scholar
- 36.•• Schulte LH, May A. The migraine generator revisited: continuous scanning of the migraine cycle over 30 days and three spontaneous attacks. Brain. 2016;139(Pt 7):1987–93. In this elegant study, the hypothalamus shows altered functional coupling with the spinal trigeminal nuclei and the region of the brainstem, suggesting that the real driver of attacks might be the functional changes in hypothalamo-brainstem connectivity. CrossRefPubMedGoogle Scholar
- 38.Martín H, Sánchez del Río M, de Silanes CL, et al. Photoreactivity of the occipital cortex measured by functional magnetic resonance imaging-blood oxygenation level dependent in migraine patients and healthy volunteers: pathophysiological implications. Headache. 2011;51(10):1520–8.CrossRefPubMedGoogle Scholar
- 40.•• Hougaard A, Amin FM, Hoffmann MB, et al. Interhemispheric differences of fMRI responses to visual stimuli in patients with side-fixed migraine aura. Hum Brain Mapp. 2014;35(6):2714–23. These findings suggest that an advanced visual system hyperexcitability characterizes the hemispheres involved in the aura phenomenon also during the interictal phase. CrossRefPubMedGoogle Scholar
- 42.•• Russo A, Marcelli V, Esposito F, et al. Abnormal thalamic function in patients with vestibular migraine. Neurology. 2014;82(23):2120–6. A novel evidence for abnormal thalamic functional response to vestibular stimulation in patients with VM has been demonstrated for the first time, suggesting that functional abnormalities in central vestibular processing may contribute to VM pathophysiology. CrossRefPubMedGoogle Scholar
- 63.•• Tessitore A, Russo A, Conte F, et al. Abnormal connectivity within executive resting-state network in migraine with aura. Headache. 2015;55(6):794–805. The study demonstrates disrupted executive control network functional connectivity in patients with migraine with and without aura, during the interictal period, although in the absence of clinically relevant executive deficits. CrossRefPubMedGoogle Scholar
- 64.•• Tedeschi G, Russo A, Conte F, et al. Increased interictal visual network connectivity in patients with migraine with aura. Cephalalgia. 2016;36(2):139–47. The results support that the increased functional connectivity of the visual network represents a functional biomarker that could differentiate patients experiencing the aura phenomenon from patients with migraine without aura, even between attacks. CrossRefPubMedGoogle Scholar
- 65.Niddam DM, Lai KL, Fuh JL, et al. Reduced functional connectivity between salience and visual networks in migraine with aura. Cephalalgia. 2015;36(1):53–66.Google Scholar