Connecting the dots in the migraine brain

Summary: Neuroimaging study reveals altered structural brain connectivity in patients with chronic and episodic migraines.

Source: International Headache Society

A neuroimaging study recently published in the journal Cephalalgia shared more evidence of structural changes in the brain of migraine patients. The study, entitled “Structural connectivity alterations in chronic and episodic migraine: A diffusion magnetic resonance imaging connectomics study”, was conducted by a multidisciplinary team of neurologists and bioengineers, coordinated by Dr. Ángel Luis Guerrero, from the Headache Unit, Department of Neurology, University of Valladolid, Spain.

Migraine is one of the most disabling diseases in the world. To date, it is only diagnosed based on self-reported clinical symptoms, with no overt biomarker identified yet. As a neurological disorder, migraine is known to result from an aberrant central nervous system functioning. On the other hand, it may itself impact brain functioning with increased frequency of headache attacks (e.g., in chronic migraine patients).

Different research groups all around the world are attempting to uncover a brain signature of migraine patients, and nowadays brain connectivity is in the spotlight. Brain connectivity is obtained by neuroimaging techniques capable of mapping a full set of patterns of anatomical links in the brain and the strengths of these links (connectomes). The interpretation of these interactions follows the functional characteristics of each brain structure linked.

Dr. Guerrero’s team assessed brain images from 160 volunteers; fifty healthy participants, 54 episodic migraine patients, and 56 chronic migraine patients. Migraine patients were assessed in the interictal period (headache-free days). Using a whole-brain tractography approach from diffusion magnetic resonance imaging (dMRI) and diffusion tensor imaging (DTI) techniques, a total of 620 connections between 84 cortical and subcortical gray matter regions were analyzed.

The researchers found structural brain connectivity changes between migraine patients and healthy volunteers, as well as between episodic and chronic migraine patients. Based on the number of streamlines from the anatomically-constrained tractography analysis and DTI descriptors, they found the following main patterns of structural changes:

Migraine Patients vs Controls

Simultaneous higher and lower number of streamlines in migraine patients, suggesting respectively coexistent strengthening and weakening structural connectivity changes in migraine. Strengthening connectivity was observed in many areas deeply implicated in migraine’s pathophysiology, such as the caudate nucleus, thalamus and hippocampus, and other regions such as the insula, the superior frontal gyrus, and the precentral gyrus. The authors contextualized the role of the thalamus in the symptomatology of migraine such as photophobia, allodynia, and central sensitization processes, and the role of insula as the “hub of activity” in migraine. Strengthening connectivity in the hippocampus is akin to its role in pain processing and pain-related attention and anxiety.

For weakening connectivity patterns, the authors underscore the changes in the temporal lobe of migraine patients, which may represent a feature of interictal malfunctioning with other pain processing areas in these patients.

Episodic vs Chronic Migraine

Compared to episodic migraine patients, chronic migraine showed more streamlines, but decreased DTI descriptors (in axial and radial diffusivity), suggesting two different mechanisms connectivity alteration; more streamlines meaning potential adaptation to painful stimuli, and reduced diffusivity meaning possible axonal disturbance.

This shows a head with swirly lights
Different research groups all around the world are attempting to uncover a brain signature of migraine patients, and nowadays brain connectivity is in the spotlight. Image is in the public domain.

Moreover, in chronic migraine patients, DTI descriptors were positively correlated with the time from migraine onset, suggesting white matter plastic adaptation to highly recurrent painful stimuli. When adding the history of chronic migraine (the duration of chronic migraine) as a covariate in the statistical analyses, they found reduced streamlines of connections with the insula and thalamus, which was interpreted as indicative of temporal changes in pain processing areas throughout the course of migraine, resulting in plastic maladaptive changes.

According to Álvaro Planchuelo-Gómez, a bioengineer and the first author of the study, “This kind of study is very important to further investigate other aspects of the disease, such as identifying patterns of changes in patients who revert from the chronic to the episodic form of the disease, and treatment effects”. Finally, another relevant aspect of this research is underscored by Dr. David García-Azorín, a neurologist and co-author of the study, “Migraine has no biomarker yet, therefore, more studies engaging the effort of a multidisciplinary team are needed to better understand the complexity of this disease, and, hopefully, establish a brain signature of migraine patients”.

[divider]About this neurology research article[/divider]

Source:
International Headache Society
Media Contacts:
Arão Belitardo de Oliveira – International Headache Society
Image Source:
The image is in the public domain.

Original Research: Closed access
“Structural connectivity alterations in chronic and episodic migraine: A diffusion magnetic resonance imaging connectomics study”. Ángel Luis Guerrero et al.
Cephalalgia doi:10.1177/0333102419885392.

Abstract

Structural connectivity alterations in chronic and episodic migraine: A diffusion magnetic resonance imaging connectomics study

Objective
To identify possible structural connectivity alterations in patients with episodic and chronic migraine using magnetic resonance imaging data.

Methods
Fifty-four episodic migraine, 56 chronic migraine patients and 50 controls underwent T1-weighted and diffusion-weighted magnetic resonance imaging acquisitions. Number of streamlines (trajectories of estimated fiber-tracts), mean fractional anisotropy, axial diffusivity and radial diffusivity were the connectome measures. Correlation analysis between connectome measures and duration and frequency of migraine was performed.

Results
Higher and lower number of streamlines were found in connections involving regions like the superior frontal gyrus when comparing episodic and chronic migraineurs with controls (p < .05 false discovery rate). Between the left caudal anterior cingulate and right superior frontal gyri, more streamlines were found in chronic compared to episodic migraine. Higher and lower fractional anisotropy, axial diffusivity, and radial diffusivity were found between migraine groups and controls in connections involving regions like the hippocampus. Lower radial diffusivity and axial diffusivity were found in chronic compared to episodic migraine in connections involving regions like the putamen. In chronic migraine, duration of migraine was positively correlated with fractional anisotropy and axial diffusivity.

Conclusions
Structural strengthening of connections involving subcortical regions associated with pain processing and weakening in connections involving cortical regions associated with hyperexcitability may coexist in migraine.

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