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Cortical glutamate and gamma-aminobutyric acid over the course of a provoked migraine attack, a 7 Tesla magnetic resonance spectroscopy study.

ABSTRACT: Enhanced activity of the glutamatergic system has been linked to migraine pathophysiology. The present study aimed to assess the involvement of the glutamatergic system in the onset of attacks. We provoked attacks by infusion of glyceryl trinitrate (GTN; 0.5 µg/kg/min over 20 min) in 24 female episodic migraineurs without aura and 13 female age-matched healthy controls. Over the course of a single day participants were scanned three times at fixed time slots (baseline before GTN infusion, 90 min and 270 min after start of GTN infusion). Single-volume proton magnetic resonance spectra (1H-MRS) were acquired at 7 Tesla from a volume of interest (VOI, 2x2x3 cm) in the visual cortex. We assessed the concentrations of glutamate, its major precursor glutamine, and its product gamma-aminobutyric acid (GABA) over the course of a provoked attack. The preictal state was defined as the period after GTN infusion until the migraine-like headache started, independent of possible experienced premonitory symptoms, and the ictal state was defined as the period with provoked migraine-like headache. Data were analyzed using a linear mixed-effect model for repeated measures. Glutamate and glutamine levels did not change from interictal to the preictal and ictal state. GABA levels increased from interictal towards the preictal state for migraine patients compared with healthy controls. We conclude that high resolution 7T MRS is able to show changes in the glutamatergic system towards a triggered migraine attack, by revealing an increased GABA concentration associated with the onset of a migraine attack.

SUBMITTER: Onderwater GLJ

PROVIDER: S-EPMC8640106 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe pathogenesis of migraine chronification remains unclear. Functional and structural magnetic resonance imaging studies have shown impaired functional and structural alterations in the brains of patients with chronic migraine. The cerebellum and periaqueductal gray (PAG) play pivotal roles in the neural circuits of pain conduction and analgesia in migraine. However, few neurotransmitter metabolism studies of these migraine-associated regions have been performed. To explore the pathogenesis of migraine chronification, we measured gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx) levels in the dentate nucleus (DN) and PAG of patients with episodic and chronic migraine and healthy subjects.MethodsUsing the MEGA-PRESS sequence and a 3-Tesla magnetic resonance scanner (Signa Premier; GE Healthcare, Chicago, IL, USA), we obtained DN and PAG metabolite concentrations from patients with episodic migraine (n = 25), those with chronic migraine (n = 24), and age-matched and sex-matched healthy subjects (n = 16). Patients with chronic migraine were further divided into those with (n = 12) and without (n = 12) medication overuse headache. All scans were performed at the Beijing Tiantan Hospital, Capital Medical University.ResultsWe found that patients with chronic migraine had significantly lower levels of GABA/water (p = 0.011) and GABA/creatine (Cr) (p = 0.026) in the DN and higher levels of Glx/water (p = 0.049) in the PAG than healthy controls. In all patients with migraine, higher GABA levels in the PAG were significantly associated with poorer sleep quality (GABA/water: r = 0.515, p = 0.017, n = 21; GABA/Cr: r = 0.522, p = 0.015, n = 21). Additionally, a lower Glx/Cr ratio in the DN may be associated with more severe migraine disability (r = -0.425, p = 0.055, n = 20), and lower GABA/water (r = -0.424, p = 0.062, n = 20) and Glx/Water (r = -0.452, p = 0.045, n = 20) may be associated with poorer sleep quality.ConclusionsNeurochemical levels in the DN and PAG may provide evidence of the pathological mechanisms of migraine chronification. Correlations between migraine characteristics and neurochemical levels revealed the pathological mechanisms of the relevant characteristics.

Project description:ImportanceMajor depressive disorder (MDD) is one of the most prevalent illnesses worldwide. Perturbations of the major inhibitory and excitatory neurotransmitters, γ-aminobutyric acid (GABA) and glutamate (Glu), respectively, as well as Glx (Glu or glutamine [Gln]) have been extensively reported in a multitude of brain areas of individuals with depression, but few studies have examined changes in Gln, the metabolic counterpart of synaptic Glu.ObjectiveTo investigate changes in GABA, Glx, Glu, and Gln levels in a voxel in the left dorsolateral prefrontal cortex of participants with no, past, and current MDD using proton magnetic resonance spectroscopy (1H-MRS).Design, setting, and participantsThis community-based study used a cross-sectional design using 3-T 1H-MRS in participants not taking MDD medication recruited from the community. The sample consisted of 251 healthy controls, 98 participants with a history of past MDD, and 47 participants who met the diagnostic criteria for current MDD. Diagnostic groups were comparable regarding age, education, income, and diet. Data were collected from March 2014 to October 2021, and data were analyzed from October 2021 to June 2022.Main outcomes and measuresGABA, Glx, Glu, and Gln concentrations in the left dorsolateral prefrontal cortex.ResultsOf 396 included participants, 258 (65.2%) were female, and the mean (SD) age was 25.0 (4.7) years. Compared with healthy controls, those with past MDD and current MDD had lower GABA concentrations (mean [SEM] concentration: healthy controls, 2.70 [0.03] mmol/L; past MDD, 2.49 [0.05] mmol/L; current MDD, 2.54 [0.07] mmol/L; 92 with past MDD vs 236 healthy controls: r = 0.18; P = .002; 44 with current MDD vs 236 healthy controls: r = 0.13; P = .04). Compared with healthy controls, those with past MDD also had lower Glu concentrations (mean [SEM] concentration: healthy controls, 7.52 [0.06] mmol/L; past MDD, 7.23 [0.11] mmol/L; 93 with past MDD vs 234 healthy controls: r = 0.16; P = .01) and higher Gln concentrations (mean [SEM] concentration: healthy controls, 1.63 [0.04] mmol/L; past MDD, 1.84 [0.07] mmol/L; 66 with past MDD 153 healthy controls: r = 0.17; P = .04).Conclusions and relevanceIn a large, mostly medication-free community sample, reduced prefrontal GABA concentrations were associated with past MDD, consistent with histopathologic studies reporting reduced glial cell and GABA cell density in the prefrontal cortex in individuals with depression. Patients with MDD also demonstrated increased Gln levels, indicative of increased synaptic Glu release, adding to previous evidence for the Glu hypothesis of MDD.

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Cortical glutamate and gamma-aminobutyric acid over the course of a provoked migraine attack, a 7 Tesla magnetic resonance spectroscopy study.

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