Circadian Variation of Migraine Attack Onset Affects fMRI Brain Response to Fearful Faces

Daniel Baksa; Edina Szabo; Natalia Kocsel; Attila Galambos; Andrea Edit Edes; Dorottya Pap; Terezia Zsombok; Mate Magyar; Kinga Gecse; Dora Dobos; Lajos Rudolf Kozak; Gyorgy Bagdy; Gyongyi Kokonyei; Gabriella Juhasz

doi:10.3389/fnhum.2022.842426

Circadian Variation of Migraine Attack Onset Affects fMRI Brain Response to Fearful Faces

Front Hum Neurosci. 2022 Mar 9:16:842426. doi: 10.3389/fnhum.2022.842426. eCollection 2022.

Authors

Daniel Baksa^{1

2

3}, Edina Szabo^{1

4

5}, Natalia Kocsel^{1

5}, Attila Galambos^{1

5}, Andrea Edit Edes^{1

2}, Dorottya Pap¹, Terezia Zsombok¹, Mate Magyar^{1

6

7}, Kinga Gecse^{1

2}, Dora Dobos^{1

2}, Lajos Rudolf Kozak⁷, Gyorgy Bagdy^{2

8

9}, Gyongyi Kokonyei^{1

2

5}, Gabriella Juhasz^{1

2

8

9}

Affiliations

¹ SE-NAP2 Genetic Brain Imaging Migraine Research Group, Hungarian Brain Research Program, Semmelweis University, Budapest, Hungary.
² Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary.
³ Department of Personality and Clinical Psychology, Institute of Psychology, Faculty of Humanities and Social Sciences, Pázmány Péter Catholic University, Budapest, Hungary.
⁴ Center for Pain and the Brain (PAIN Research Group), Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital and Harvard Medical School, Boston, MA, United States.
⁵ Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary.
⁶ János Szentágothai Doctoral School of Neurosciences, Semmelweis University, Budapest, Hungary.
⁷ Department of Neuroradiology, Medical Imaging Centre, Semmelweis University, Budapest, Hungary.
⁸ NAP-2-SE New Antidepressant Target Research Group, Hungarian Brain Research Program, Semmelweis University, Budapest, Hungary.
⁹ MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary.

Abstract

Background: Previous studies suggested a circadian variation of migraine attack onset, although, with contradictory results - possibly because of the existence of migraine subgroups with different circadian attack onset peaks. Migraine is primarily a brain disorder, and if the diversity in daily distribution of migraine attack onset reflects an important aspect of migraine, it may also associate with interictal brain activity. Our goal was to assess brain activity differences in episodic migraine subgroups who were classified according to their typical circadian peak of attack onset.

Methods: Two fMRI studies were conducted with migraine without aura patients (n = 31 in Study 1, n = 48 in Study 2). Among them, three subgroups emerged with typical Morning, Evening, and Varying start of attack onset. Whole brain activity was compared between the groups in an implicit emotional processing fMRI task, comparing fearful, sad, and happy facial stimuli to neutral ones.

Results: In both studies, significantly increased neural activation was detected to fearful (but not sad or happy) faces. In Study 1, the Evening start group showed increased activation compared to the Morning start group in regions involved in emotional, self-referential (left posterior cingulate gyrus, right precuneus), pain (including left middle cingulate, left postcentral, left supramarginal gyri, right Rolandic operculum) and sensory (including bilateral superior temporal gyrus, right Heschl's gyrus) processing. While in Study 2, the Morning start group showed increased activation compared to the Varying start group at a nominally significant level in regions with pain (right precentral gyrus, right supplementary motor area) and sensory processing (bilateral paracentral lobule) functions.

Conclusion: Our fMRI studies suggest that different circadian attack onset peaks are associated with interictal brain activity differences indicating heterogeneity within migraine patients and alterations in sensitivity to threatening fearful stimuli. Circadian variation of migraine attack onset may be an important characteristic to address in future studies and migraine prophylaxis.

Keywords: brain imaging; circadian rhythm; emotional faces task; emotional processing; headache onset; pain.