HIGH-TEMPORAL RESOLUTION PET/MRIREVEALS DISTINCT METABOLIC AND HEMODYNAMIC WORKING MEMORY RESPONSES IN HUMAN POSTERIOR CINGULATE CORTEX

Abstract Background Previous studies have reported spatial dissociations between glucose metabolism and BOLD responses in the human posterior cingulate cortex (PCC)1, with an opposite influence of the fronto-parietal network (FPN) and the dorsal attention network (DAN) metabolism onto the PCC2. Until recently, a truly synchronized assessment of these influences in the temporal domain was limited due to the inherently low temporal resolution of positron emission tomography (PET) when compared to functional magnetic resonance imaging (fMRI). Aims & Objectives We employed high temporal resolution functional PET (fPET) to synchronously investigate dynamic metabolic and hemodynamic responses during working memory performance in the PCC. Methods Thirty-five participants underwent either a simultaneous fPET/fMRI (n=19) or separate fPET and fMRI scans (n=16). During the scan, an n-back working memory paradigm was completed while acquiring [18 F]FDG fPET and BOLD fMRI data. fPET data were reconstructed to 3 s temporal resolution, whereas BOLD fMRI acquisition had a repetition time of 2 s. Participants were divided into three distinct groups based on the mentioned difference in task-specific metabolism between the FPN and DAN: low (metabolism of FPN <DAN, 25% of participants), balanced (FPN = DAN, 50%) and high (FPN >DAN, 25%). [18F]FDG and BOLD time series were extracted from the PCC region2 and these parameters were compared between the three groups using repeated measures ANOVA (groups-by-time interaction). Results In the spatial domain, the PCC exhibited a negative BOLD response, while no change in metabolic demands was found during task performance (p<0.05 FWE-corrected cluster level following p<0.001 uncorrected voxel level). Temporal profile assessment of the PCC between the defined groups revealed an interaction effect (p = 0.0016) for the metabolic signal, with significant post-hoc differences between high vs. low participants (p <10-5) and low vs. balanced (p = 0.025). While the low group showed a constant decrease in PCC metabolism, followed by a subsequent increase, the high group exhibited a delayed increase. At the same time, the balanced group showed almost no variation in their metabolic response. BOLD time series of the PCC revealed robust decreases for all three groups without significant difference (interaction p = 0.9). Discussion & Conclusion Simultaneous BOLD fMRI and high resolution [18F]FDG fPET provide deeper insight into the divergence between glucose metabolism and BOLD deactivations in the PCC1 during working memory performance. Confirming the previous results of a dependence of PCC metabolic time course on energy demands of the corresponding task-positive networks2, the high-resolution dynamic assessment of the presented approach enabled distinguishing group differences with decreased vs. increased PCC metabolism. Given the involvement of impaired neurovascular coupling3 and widespread decreased metabolism4 in diseases like Alzheimer’ s, synchronous multimodal imaging at high temporal resolution could benefit the diagnosis of neuropsychiatric disorders at early stages by detecting minor deviations. References 1.Stiernman, L. J. et al. Dissociations between glucose metabolism and blood oxygenation in the human default mode network revealed by simultaneous PET-fMRI. Proc. Natl. Acad. Sci. 118, (2021). 2.Godbersen, G. M. et al. Task-evoked metabolic demands of the posteromedial default mode network are shaped by dorsal attention and frontoparietal control networks. eLife 12, e84683 (2023). 3.Tarantini, S., Tran, C. H. T., Gordon, G. R., Ungvari, Z. &Csiszar, A. Impaired neurovascular coupling in aging and Alzheimer’ s disease: Contribution of astrocyte dysfunction and endothelial impairment to cognitive decline. Exp. Gerontol. 94, 52–58 (2017). 4.Teipel, S. et al. Multimodal imaging in Alzheimer’ s disease: validity and usefulness for early detection. Lancet Neurol. 14, 1037–1053 (2015).