An energy costly architecture of neuromodulators for human brain evolution and cognition.

In comparison to other species, the human brain exhibits one of the highest energy demands relative to body metabolism. It remains unclear whether this heightened energy demand uniformly supports an enlarged brain or if specific signaling mechanisms necessitate greater energy. We hypothesized that the regional distribution of energy demands will reveal signaling strategies that have contributed to human cognitive development. We measured the energy distribution within the brain functional connectome using multimodal brain imaging and found that signaling pathways in evolutionarily expanded regions have up to 67% higher energetic costs than those in sensory-motor regions. Additionally, histology, transcriptomic data, and molecular imaging independently reveal an up-regulation of signaling at G-protein-coupled receptors in energy-demanding regions. Our findings indicate that neuromodulator activity is predominantly involved in cognitive functions, such as reading or memory processing. This study suggests that an up-regulation of neuromodulator activity, alongside increased brain size, is a crucial aspect of human brain evolution.

Fully Integrated PET/MR Imaging for the Assessment of the Relationship Between Functional Connectivity and Glucose Metabolic Rate.

In the past, determination of absolute values of cerebral metabolic rate of glucose (CMRGlc) in clinical routine was rarely carried out due to the invasive nature of arterial sampling. With the advent of combined PET/MR imaging technology, CMRGlc values can be obtained non-invasively, thereby providing the opportunity to take advantage of fully quantitative data in clinical routine. However, CMRGlc values display high physiological variability, presumably due to fluctuations in the intrinsic activity of the brain at rest. To reduce CMRGlc variability associated with these fluctuations, the objective of this study was to determine whether functional connectivity measures derived from resting-state fMRI (rs-fMRI) could be used to correct for these fluctuations in intrinsic brain activity. METHODS: We studied 10 healthy volunteers who underwent a test-retest dynamic [18F]FDG-PET study using a fully integrated PET/MR system (Siemens Biograph mMR). To validate the non-invasive derivation of an image-derived input function based on combined analysis of PET and MR data, arterial blood samples were obtained. Using the arterial input function (AIF), parametric images representing CMRGlc were determined using the Patlak graphical approach. Both directed functional connectivity (dFC) and undirected functional connectivity (uFC) were determined between nodes in six major networks (Default mode network, Salience, L/R Executive, Attention, and Sensory-motor network) using either a bivariate-correlation (R coefficient) or a Multi-Variate AutoRegressive (MVAR) model. In addition, the performance of a regional connectivity measure, the fractional amplitude of low frequency fluctuations (fALFF), was also investigated. RESULTS: The average intrasubject variability for CMRGlc values between test and retest was determined as (14 ±8%) with an average inter-subject variability of 25% at test and 15% at retest. The average CMRGlc value (umol/100 g/min) across all networks was 39 ±10 at test and increased slightly to 43 ±6 at retest. The R, MVAR and fALFF coefficients showed relatively large test-retest variability in comparison to the inter-subjects variability, resulting in poor reliability (intraclass correlation in the range of 0.11-0.65). More importantly, no significant relationship was found between the R coefficients (for uFC), MVAR coefficients (for dFC) or fALFF and corresponding CMRGlc values for any of the six major networks. DISCUSSION: Measurement of functional connectivity within established brain networks did not provide a means to decrease the inter- or intrasubject variability of CMRGlc values. As such, our results indicate that connectivity measured derived from rs-fMRI acquired contemporaneously with PET imaging are not suited for correction of CMRGlc variability associated with intrinsic fluctuations of resting-state brain activity. Thus, given the observed substantial inter- and intrasubject variability of CMRGlc values, the relevance of absolute quantification for clinical routine is presently uncertain.

Assessment of the kidney function parameters split function, mean transit time, and outflow efficiency using dynamic FDG-PET/MRI in healthy subjects.

BACKGROUND: Traditionally, isotope nephrography is considered as the method of choice to assess kidney function parameters in nuclear medicine. We propose a novel approach to determine the split function (SF), mean transit time (MTT), and outflow efficiency (OE) with 2-deoxy-2-[18F]fluoro-D-glucose (FDG) dynamic positron emission tomography (PET). MATERIALS AND METHODS: Healthy adult subjects underwent dynamic simultaneous FDG-PET and magnetic resonance imaging (PET/MRI). Time-activity curves (TACs) of total kidneys, renal cortices, and the aorta were prospectively obtained from dynamic PET series. MRI images were used for anatomical correlation. The same individuals were subjected to dynamic renal Technetium-99 m-mercaptoacetyltriglycine (MAG3) scintigraphy and TACs of kidneys; the perirenal background and the left ventricle were determined. SF was calculated on the basis of integrals over the TACs, MTT was determined from renal retention functions after deconvolution analysis, and OE was determined from MTT. Values obtained from PET series were compared with scintigraphic parameters, which served as the reference. RESULTS: Twenty-four subjects underwent both examinations. Total kidney SF, MTT, and OE as estimated by dynamic PET/MRI correlated to their reference values by r = 0.75, r = 0.74 and r = 0.81, respectively, with significant difference (p < 0.0001) between the means of MTT and OE. No correlations were found for cortex FDG values. CONCLUSIONS: The study proofs the concept that SF, MTT, and OE can be estimated with dynamic FDG PET/MRI scans in healthy kidneys. This has advantages for patients receiving a routine PET/MRI scan, as kidney parameters can be estimated simultaneously to functional and morphological imaging with high accuracy.