Exploring Region-Specific Changes in Brain Glutamate and Gamma-Aminobutyric Acid (GABA) Across the Migraine Cycle in Children and Adolescents

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Migraine is a neurological disorder with multiple phases (i.e., migraine cycle). There is evidence that migraine is associated with excitation-inhibition imbalances and dysregulation of glutamate and gamma-aminobutyric acid (GABA), the primary excitatory and inhibitory neurochemicals, respectively. Magnetic resonance spectroscopy (MRS) is a non-invasive imaging method to quantify brain levels of glutamate and GABA. It has been proposed progressing through the migraine cycle is also related to changes in excitation and inhibition. Few studies have measured glutamate and GABA in adults with migraine, and migraine studies in the pediatric population specifically focusing on glutamate and GABA are very scarce. In this study, children and adolescents with migraine were recruited to have four MRS scans over two weeks to quantify levels of glutamate and GABA in the sensorimotor cortex, thalamus, and occipital cortex. Two approaches were used to determine glutamate and GABA changes across the migraine cycle: (1) binning by migraine cycle phases and (2) time as a continuous metric leading up to or following headache. Analysis of migraine cycle phases showed occipital cortex glutamate was higher in the headache phase and thalamic glutamate was higher in the postdrome phase, both compared to the interictal phase. When using a continuous time metric, glutamate significantly decreased following the onset of the headache phase in the occipital cortex and thalamus, and sensorimotor GABA significantly increased leading up to the headache. I propose that these changes reflect increased excitation in the occipital cortex and thalamus and increased inhibition in the sensorimotor cortex during the migraine attack which may be evidence of thalamocortical dysrhythmia underlying migraine pathophysiology. This study provides insight into the underlying biology of migraine in children and adolescents, and if replicated, may help inform development of future treatments and interventions.
Migraine, Pediatrics, Excitation, Inhibition, Thalamocortical Dysrhythmia, Magnetic Resonance Spectroscopy (MRS), Edited-MRS, Macromolecule-Suppressed GABA-Edited MRS, Glutamate, Gamma-Aminobutyric Acid (GABA)
Cho, L. Y. (2023). Exploring region-specific changes in brain Glutamate and Gamma-Aminobutyric Acid (GABA) across the migraine cycle in children and adolescents (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.