Regional variations in cingulate cortex glutamate levels: a magnetic resonance spectroscopy study at 3 T

Regional variations in glutamate levels across the cingulate cortex, decreasing rostral to caudal, have been observed previously in healthy volunteers with proton magnetic resonance spectroscopy (¹H-MRS) at 7 T. This study sought to explore cingulate cortex glutamate trends further by investigating whether a similar gradient could be detected at 3 T, the effect of sex, as well as whether individual variations gave rise to more than one regional glutamate pattern. ¹H-MRS at 3 T [Phillips Elition; semi-localization by adiabatic selective refocusing, echo time (TE)/repetition time (TR) = 32/5,000] was acquired in four cingulate regions: the anterior, midanterior, midposterior, and posterior cortices, in 50 healthy participants (26 F) scanned at a fixed time of day and with controlled food intake. <i>K</i>-means clustering was used to characterize the presence of distinct regional patterns, which were then compared between sex and clusters. In addition, cortical thickness was compared between clusters and in relation to glutamate. Aligned with 7 T findings, we demonstrated that average glutamate levels decreased rostral to caudal in the healthy cingulate cortex. No effect of sex was found, suggesting similar resting glutamate levels in both sexes. Interestingly, the majority of participants were characterized by glutamate levels that did not significantly change across the cingulate (65%). Different regional patterns in cortical thickness between clusters offer further evidence into these distinct glutamate variations and suggest that both a neuroanatomical and a functional role may lead to these findings. This study provides a much-needed foundation for further research to determine the implications of neurotransmission patterns in health and disease.<b>NEW & NOTEWORTHY</b> In a large, sex-balanced sample of healthy individuals, we demonstrate that average regional differences (rostral to caudal) in cingulate cortex glutamate exist, using optimized experimental conditions and 3 T magnetic resonance spectroscopy techniques. Results align with observations from 7 T. A novel clustering approach was introduced to determine the number of patterns for glutamate in the healthy adult brain for the first time. These findings demonstrate that regional differences are detectable at 3 T when present and suggest the occurrence of multiple glutamate metabolism patterns in the cingulate.