Altered functional connectivity of the insula in a rat model of recurrent headache

Abstract

Migraine is a pain disorder accompanied by various symptoms. The insula, a “cortical hub,” is involved in many functions. Few studies have focused on the insula in migraine. We explored the resting-state functional connectivity between the insula and other brain areas in rats subjected to repeated meningeal nociception which was commonly used as animal model of migraine. Inflammatory soup was infused through supradural catheters in conscious rats. The rats were subdivided based on the frequency of the inflammatory soup infusions. Magnetic resonance imaging data were acquired on rats 21 days after inflammatory soup infusion and functional connectivity seeded on the insula was analyzed. In the low-frequency inflammatory soup group, magnetic resonance imaging was performed again 1 h after the glyceryl trinitrate injection following baseline scanning. The cerebellum showed increased functional connectivity with the insula in the inflammatory soup groups. The insula showed increased functional connectivity with the medulla and thalamus in the ictal period in the low-frequency inflammatory soup rats. In the high-frequency inflammatory soup group, several areas showed increased functional connectivity with the insula, including the pons, midbrain, thalamus, temporal association cortex, and retrosplenial, visual, and sensory cortices. Our findings support the hypothesis that the headache phase of migraine depends on the activation and sensitization of the trigeminovascular system, and that the chronification of migraine may be related to higher brain centers and limbic cortices. The insula may be a new target for treatment of migraine.

Disrupted Dynamic Functional Connectivity of the Visual Network in Episodic Patients with Migraine without Aura

“…The insula is often referred to as a core region of SN, a pivotal large-scale network that is associated with task processing, attention processing, and integrating of external and internal stimuli [ 28 , 29 ], as well as gating pain processing [ 30 , 31 ]. In accordance with the present results, some clinical and animal model studies have concluded that the insula is involved in regulation of headache intensity and attack frequency of migraine and other neuropathic pain [ 32 – 34 ]. However, a prior study [ 35 ] demonstrated contrary results in female MwoA patients during a headache-free period.…”

Detecting Abnormal Neuronal Activity in a Chronic Migraine Model by Egr1-EGFP Transgenic Mice

“…Mental imagery is a process that integrates multisensory perception to generate a vivid mental image or experience (Di Corrado et al, 2019). TEa was found to have an increased functional connection with insula in a migraine rat model recently, which also suggested the important role of it (Jia et al, 2020). In our study, the enhanced neuronal activity in LA and TEa could not be completely reversed by topiramate.…”

The Characteristics of White Matter Hyperintensities in Patients With Migraine

“…Similar to our results, Xiu reported WMH to be most prevalent in the frontal lobe (74.9%) followed by the parietal lobes. In our study, 14% of individuals (n = 21) with frontal lobe hyperintensities had WMH located in the insula which is an intriguing nding as the insula is a known 'cortical hub' and a key region of the salience network (17) involved in cognitive and interoceptive components of the pain experience (18) and an area known in migraine to demonstrate alterations brain functional connectivity using resting-state imaging (19)(20)(21). Furthermore, using positron emission tomography [ 11 C]HOwe(9) PBR28 imaging, Hadjikhani and collegues found increased binding of the 18 kDa translocator protein, a marker of glial activation, in individuals with migraine with aura in the bilateral insula (22).…”