Imaging Brain Glx Dynamics in Response to Pressure Pain Stimulation: A 1H-fMRS Study.

Luke A Jelen,Jade B Jackson,Matthew A Howard,Alice Egerton,David J Lythgoe,James M Stone

doi:10.3389/fpsyt.2021.681419

Abstract

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.

Highlights

Glutamate, a major excitatory neurotransmitter, is fundamentally involved in normal and abnormal brain function [1]
Two-way repeated measures ANOVA demonstrated a significant main effect of CONDITION for Glx/tCr in the dorsal ACC (dACC) (ROI2) [F(1,17) = 6.075, p = 0.025], with higher Glx/tCr during PAIN compared to REST
There was no significant main effect of SESSION [F(1,17) = 0.672, p = 0.424] and no significant CONDITION ∗ SESSION interaction [F(1,17) = 0.028, p = 0.870] for dACC Glx/tCr (Table 2). dACC Glx/tCr during REST and PAIN is presented in Table 3 and Figure 4

Summary

Introduction

A major excitatory neurotransmitter, is fundamentally involved in normal and abnormal brain function [1]. Glutamate plays a central role in a number of pathologies including psychiatric [2], neurological [3], neurodevelopmental [4] and pain disorders [5]. Proton magnetic resonance spectroscopy (1H-MRS) is a non-invasive in vivo technique that allows the measurement of regional concentrations of brain metabolites, including glutamate, and has proved integral in furthering our understanding of the role of glutamate in health and disease [6]. Functional 1H-MRS (1H-fMRS) is a technique where sequential 1H-MRS scans are acquired to measure dynamic changes in metabolite concentrations. There has been particular interest in using 1H-fMRS methods to investigate changes in glutamate induced by tasks and other stimuli

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