fMRI Study Reveals Altered Thalamic Functional Connectivity in Migraineurs

According to authors of a cross-sectional study, abnormalities in thalamic functional connectivity are a likely mechanism for migraine development.

Migraineurs had altered voxel-mirrored homotopic connectivity (VMHC) in the bilateral thalamus and abnormal functional connectivity (FC) of bilateral thalamus and other brain regions compared with healthy controls, according to the results of a resting-state functional MRI (rs-fMRI) study.

According to the authors, the findings indicate abnormalities in thalamic FC are likely a mechanism for migraine development.

Migraine affects approximately 1.25 billion people worldwide, yet the condition’s pathogenesis remains unclear. Previous research has utilized rs-fMRI to elucidate the neurophysiological mechanisms of migraine. However, results on brain FC vary, and past studies lacked correction of false positives.

Using VMHC to measure resting-state FC between each voxel in one hemisphere and its mirror counterpart in the other hemisphere, the researchers set out to address this knowledge gap, collecting data from both migraineurs without aura (n = 30) and healthy controls (n = 40).

All participants were recruited from a single hospital in China between August 2020 and June 2021. There were no significant differences in age, gender, or education level between the 2 cohorts and all participants were right-handed.

Any migraineur who used prophylactic, antiepileptic, or antidepressant treatments within the last month was excluded from the study. Patients with migraine also competed a visual analogue scale (VAS) and Migraine-Specific Quality of Life Questionnaire, while all participants completed the Self-rating Anxiety Scale and Self-rating Depression Scale.

“Homotopic resting-state FC was calculated as the resting-state FC between any pair of symmetrical voxels between hemispheres,” the researchers explained. “The seed-based FC was performed using a time-dependent process.”

Mean (SD) migraineur age was 36.17 (13.28) years and 24 migraineurs were women.

Analyses revealed:

  • In comparison with the control group, patients showed enhanced VMHC in the bilateral thalamus (false discover rate [FDR] corrected P < .05)
  • Enhanced FC between the left thalamus and the left superior frontal gyrus was observed (FDR corrected P < .05), along with increased FC between the right thalamus and the left middle frontal gyrus (Brodmann area 45 and Brodmann area 8) (FDR corrected P < .05) in patients
  • FC values in the left superior frontal gyrus (SFG) and left middle frontal gyrus were negatively corrected with VAS scores or attack times for headaches

“The current findings suggest significantly increased VMHC values and enhanced FC between the bilateral thalamus, indicating a reduction in functional pain pathways in the thalamus, which may be associated with disruptions in projection, pain processing, perception, and regulation due to recurrent pain episodes,” the authors wrote.

The thalamus is one of the most important regions for transmission of sensory information and plays a key role in the development of pain. Past research has shown blood flow and functional structural changes of the thalamus in migraineurs.

Furthermore, results showed the SFG—a region responsible for emotion regulation—may also play a role in the production of migraine.

The cross-sectional nature and small sample size of the study mark limitations, and future investigations could further validate results. In addition, because different subregions of the thalamus could have particular functions, more research is needed to better understand the correlation between these regions and migraine causation.

Overall, “the present results reveal that abnormalities in thalamic functional connectivity are a likely mechanism for the development of migraine,” the researchers wrote.

“Resting-state fMRI may be an essential diagnostic modality for differentiating migraine from other types of headaches,” they concluded.


Cao Z-M, Chen Y-C, Liu G-Y, et al. Abnormalities of thalamic functional connectivity in patients with migraine: a resting-state fMRI study. Pain Ther. Published online February 27, 2022. doi:10.1007/s40122-022-00365-1