Task-based changes in proton MR spectroscopy signal during configural working memory in human medial temporal lobe.

PURPOSE: To detect local cholinergic changes in human medial temporal lobe during configural working memory performance. MATERIALS AND METHODS: Proton magnetic resonance spectroscopy (1 H-MRS) measurements were acquired at 3T from a 2 × 2 × 3 cm voxel in right medial temporal lobe from 36 subjects during performance of a configural visual working memory task (cWMT). In order to compensate for expected task-based blood oxygenation level-dependent (BOLD) T2 * effects, resonance signal changes of unbound choline-containing metabolites (Cho) were referenced to an internal standard of creatine + phosphocreatine metabolites (Cre) and compared between four task blocks: rest, memorization, active memory maintenance, and recognition. An unannounced memory retention test was conducted in 21 subjects. Quality assurance analyses examined task-based Cho and Cre individually as well as referenced to resonance signal from N-acetylaspartate (NAA). RESULTS: Increases from a resting baseline in the Cho/Cre ratio were observed during 60-second blocks of active memory maintenance across the group (P = 0.0042). Behavioral accuracy during task performance correlated with memory retention (r = 0.48, P = 0.027). Quality assurance measures showed task-based changes in Cre resonance signal both individually (P = 0.00099) and when utilized as a noncholinergic internal reference (NAA/Cre, P = 0.00079). CONCLUSION: Increases in human medial temporal lobe 1 H-MRS Cho/Cre ratio occur during the maintenance of configural working memory information. However, interpretation of these results as driven by cholinergic activity cannot be assumed, as NAA, a noncholinergic metabolite, shows similar results when utilizing Cre as a reference. Caution is advised when considering Cre as an internal standard for task-based 1 H-MRS measurements. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:682-691.