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Glutamate signalling is increasingly implicated across a range of psychiatric, neurological and pain disorders. Reliable methodologies are needed to probe the glutamate system and understand glutamate dynamics in vivo. Functional magnetic resonance spectroscopy (1H-fMRS) is a technique that allows measurement of glutamatergic metabolites over time in response to task conditions including painful stimuli. In this study, 18 healthy volunteers underwent 1H-fMRS during a pressure-pain paradigm (8 blocks of REST and 8 blocks of PAIN) across two separate sessions. During each session, estimates of glutamate + glutamine (Glx), scaled to total creatine (tCr = creatine + phosphocreatine) were determined for averaged REST and PAIN conditions within two separate regions of interest: the anterior cingulate cortex (ACC) and dorsal ACC (dACC). A two-way repeated measures analysis of variance determined a significant main effect of CONDITION (p = 0.025), with higher Glx/tCr during PAIN compared to REST across combined sessions, in the dACC ROI only. However, increases in dACC Glx/tCr during PAIN compared to REST showed limited reliability and reproducibility across sessions. Future test-retest 1H-fMRS studies should examine modified or alternative paradigms to determine more reliable methodologies to challenge the glutamate system that may then be applied in patient groups and experimental medicine studies.

Glutamate signalling is increasingly implicated across a range of psychiatric, neurological and pain disorders. Reliable methodologies are needed to probe the glutamate system and understand glutamate dynamics in vivo. Functional magnetic resonance spectroscopy (1H-fMRS) is a technique that allows measurement of glutamatergic metabolites over time in response to task conditions including painful stimuli. In this study, 18 healthy volunteers underwent 1H-fMRS during a pressure-pain paradigm (8 blocks of REST and 8 blocks of PAIN) across two separate sessions. During each session, estimates of glutamate + glutamine (Glx), scaled to total creatine (tCr = creatine + phosphocreatine) were determined for averaged REST and PAIN conditions within two separate regions of interest: the anterior cingulate cortex (ACC) and dorsal ACC (dACC). A two-way repeated measures analysis of variance determined a significant main effect of CONDITION (p = 0.025), with higher Glx/tCr during PAIN compared to REST across combined sessions, in the dACC ROI only. However, increases in dACC Glx/tCr during PAIN compared to REST showed limited reliability and reproducibility across sessions. Future test-retest 1H-fMRS studies should examine modified or alternative paradigms to determine more reliable methodologies to challenge the glutamate system that may then be applied in patient groups and experimental medicine studies.

Glutamate signalling is increasingly implicated across a range of psychiatric, neurological and pain disorders. Reliable methodologies are needed to probe the glutamate system and understand glutamate dynamics in vivo. Functional magnetic resonance spectroscopy (1H-fMRS) is a technique that allows measurement of glutamatergic metabolites over time in response to task conditions including painful stimuli. In this study, 18 healthy volunteers underwent 1H-fMRS during a pressure-pain paradigm (8 blocks of REST and 8 blocks of PAIN) across two separate sessions. During each session, estimates of glutamate + glutamine (Glx), scaled to total creatine (tCr = creatine + phosphocreatine) were determined for averaged REST and PAIN conditions within two separate regions of interest: the anterior cingulate cortex (ACC) and dorsal ACC (dACC). A two-way repeated measures analysis of variance determined a significant main effect of CONDITION (p = 0.025), with higher Glx/tCr during PAIN compared to REST across combined sessions, in the dACC ROI only. However, increases in dACC Glx/tCr during PAIN compared to REST showed limited reliability and reproducibility across sessions. Future test-retest 1H-fMRS studies should examine modified or alternative paradigms to determine more reliable methodologies to challenge the glutamate system that may then be applied in patient groups and experimental medicine studies.

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