mGluR₅ and GABA_A receptor‐specific parametric PET atlas construction—PET/MR data processing pipeline, validation, and application

Abstract

The glutamate and γ-aminobutyric acid neuroreceptor subtypes mGluR 5 and GABA A are hypothesized to be involved in the development of a variety of psychiatric diseases.However, detailed information relating to their in vivo distribution is generally unavailable. Maps of such distributions could potentially aid clinical studies by providing a reference for the normal distribution of neuroreceptors and may also be useful as covariates in advanced functional magnetic resonance imaging (MR) studies. In this study, we propose a comprehensive processing pipeline for the construction of standard space, in vivo distributions of non-displaceable binding potential (BP ND ), and total distribution volume (V T ) based on simultaneously acquired bolus-infusion positron emission tomography (PET) and MR data. The pipeline was applied to [ 11 C]ABP688-PET/MR (13 healthy male non-smokers, 26.6 ± 7.0 years) and [ 11 C]Flumazenil-PET/MR (10 healthy males, 25.8 ± 3.0 years) data. Activity concentration templates, as well as V T and BP ND atlases of mGluR 5 and GABA A , were generated from these data. The maps were validated by assessing the percent error δ from warped space to native space in a selection of brain regions. We verified that the average δ ABP = 3.0 ± 1.0% and δ FMZ = 3.8 ± 1.4% were lower than the expected variabilities σ of the tracers (σ ABP = 4.0%-16.0%, σ FMZ = 3.9%-9.5%). An evaluation of PET-to-PET registrations based on the new maps showed higher registration accuracy compared to registrations based on the commonly used [ 15 O]H 2 O-template distributed with SPM12. Thus, we conclude that the resulting maps can be used for further research and the proposed pipeline is a viable tool for the construction of standardized PET data distributions.

Temporal dissociation between local and global functional adaptations of the maternal brain to childbirth: A longitudinal assessment

“…All post-hoc statistical analyses were conducted with statsmodels (0.13.5) and pingouin (0.5.3) [24,25]. Brain gene expression and nuclear imaging data were obtained with abagen (0.1.3) [26], neuromaps (0.0.3) [27], and from author sources [28,29]. Visualizations were created with matplotlib (3.5.2) [30], seaborn (0.12.1) [31], and nilearn.…”

“…We therefore examined if postpartum rsfMRI changes and their normalization patterns after childbirth were distributed across the brain following spatial distributions of pregnancy-related hormonal receptors (progesterone: PGR, estrogen: ESR1/ESR2, cortisol: NR3C1/NR3C2) and functionally close neurotransmitter receptors (oxytocin: OXTR, GABA: GABAA, glutamate: mGluR5). Maps of receptor distributions were obtained from Allen Brain Atlas postmortem gene expression 45 (PGR, ESR1/ESR2, NR3C1/NR3C2, and OXTR) and in-vivo nuclear imaging data [46][47][48] (GABAA and mGluR5; Supplement 1.7). We first assessed if the mean spatial colocalization between receptor distributions and baseline rsfMRI alterations in postpartum women relative to controls exceeded those of permutated data.…”

“…We therefore examined if postpartum rsfMRI changes and their normalization patterns after birth were distributed across the brain following spatial distributions of pregnancy-related hormonal receptors (progesterone: PGR, estrogen: ESR1/ESR2, cortisol: NR3C1/NR3C2) and functionally close neurotransmitter receptors (oxytocin: OXTR, GABA: GABAA, glutamate: mGluR5). In-vivo maps of GABAA and mGluR5 distributions were obtained with positron emission tomography imaging in independent healthy adult subjects 28,29 , all other maps were derived from postmortem Allen Brain Atlas data 30 (Figure 3, left). We tested for colocalization between (i) parcellated rsfMRI maps of each postpartum mother relative to the control group as a reference and (ii) independent receptor maps using Spearman correlations 31 .…”

Regional patterns of human cortex development correlate with underlying neurobiology

“…The neuroimaging ("ni-") dataset consisted of group-average nuclear imaging atlases (neurotransmitter receptors, brain metabolism and immunity, synaptic density, and transcriptomic activity) and an MRI-based marker of cortical microstructure (T1/T2 ratio; Text S1.1.1) 28,29,35,[78][79][80][81] .…”

Fluoxetine degrades luminance perceptual thresholds while enhancing motivation and reward sensitivity

“…In addition, fluoxetine decreases extracellular GABA levels ( Santana et al, 2004 ; Vetencourt et al, 2008 ; Baroncelli et al, 2011 ; Beshara et al, 2016 ) thus leading to enhanced cortical excitability through a reduction of global inhibition. Relevant to the study of the effects of serotonin on top-down and bottom-up visual processes, GABAa receptor concentrations are higher in the visual cortex than in the rest of the brain and higher in the ventral part of the striate and extrastriate cortex than in its dorsal part ( Kaulen et al, 2022 ). All this taken together indicates complex interactions between serotonin circulating levels and behavioral and cognitive markers of visual perception.…”