Migraine is associated with structural and functional brain changes that are thought to reflect abnormal circuitry in the brain, specifically neuronal hyperexcitability.1,2 Numerous studies point to increased neuroplasticity (reorganization or changes) of the “migraine brain” which increases with the frequency and intensity of migraine attacks. One of these changes involves cortical thickening in specific regions of the brain that are involved in nociception, which is thought to result from repeated exposure to pain during migraine attacks.1,3 A research group at Harvard Medical School examined whether people with migraine who respond to anti-calcitonin gene-related peptide (CGRP) monoclonal antibody treatment would exhibit reversal of cortical thickening by virtue of the reduced exposure to painful attacks.
Measuring cortical thickness and functional connectivity
To test the hypothesis that responders to anti-CGRP monoclonal antibody (MAb) treatment would show more cortical thinning than non-responders, a cohort of 36 adults with high-frequency episodic and chronic migraine was enrolled in a prospective, observational, open-label study.1 Participants were classified as either responders to anti-CGRP MAb treatment (i.e., ≥50% reduction in monthly migraine days) or non-responders (<50% reduction) after 3 months of treatment. Magnetic resonance imaging (MRI) was used to measure brain structural and functional activity before and after treatment.
MRI can capture changes in cortical thickness as a marker of neuroplasticity
Effective treatment of migraine reduces cortical thickness
As expected, anti-CGRP treatment responders showed a statistically significant reduction in cortical thickness from baseline to 3 months.1 Widespread cortical thinning was observed in the sensorimotor cortex, supramarginal gyrus, prefrontal cortex, and anterior cingulate cortex regions of the brain. These areas are implicated in cognition, pain modulation, and emotional processing. In contrast, anti-CGRP MAb non-responders showed cortical thinning only in the left prefrontal cortex (an area associated with higher cognitive functions).
Anti-CGRP treatment responders showed more cortical thinning than non-responders
Changes in functional connectivity
The research group was also interested in whether the structural changes in response to treatment had an impact on functional connectivity between various brain regions. To test this, a specific type of MRI called functional imaging was used in participants before and after treatment. Anti-CGRP MAb responders showed a reduction in functional connections between the occipital, temporal, and insular cortices, which are implicated in the integration of visual and sensory processing.1 In contrast, treatment non-responders showed no significant changes in functional connectivity.
Treatment responders showed a reduction in functional connectivity in the sensorimotor cortex amongst other brain areas
Changes in cortical structure and function are indicative of recovery
The reductions in cortical thickness and functional connectivity in anti-CGRP MAb responders suggest that the “migraine brain” can recover from maladaptive neuronal activity in the cognitive, visual, sensory, and pain regions of the cortex. Dr. Szabo concluded that effective treatment and prevention of migraine provides the brain with a break from the hyperexcitable neuronal activity and nociceptive signals that occur during migraine episodes. She hypothesized that longer-term treatment may allow normalization of cortical structure and function, but this remains to be demonstrated in future clinical trials.
Prolonged response to treatment may allow the migraine brain to recover
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