Generative models of neuroimaging and electrophysiological data present new opportunities for accessing hidden or latent brain states. Dynamic causal modeling (DCM) uses Bayesian model inversion and selection to infer the synaptic mechanisms underlying empirically observed brain responses. DCM for electrophysiological data, in particular, aims to estimate the relative strength of synaptic transmission at different cell types and via specific neurotransmitters. Here, we report a DCM validation study concerning inference on excitatory and inhibitory synaptic transmission, using different doses of a volatile anaesthetic agent (isoflurane) to parametrically modify excitatory and inhibitory synaptic processing while recording local field potentials (LFPs) from primary auditory cortex (A1) and the posterior auditory field (PAF) in the auditory belt region in rodents. We test whether DCM can infer, from the LFP measurements, the expected drug-induced changes in synaptic transmission mediated via fast ionotropic receptors; i.e., excitatory (glutamatergic) AMPA and inhibitory GABA_A receptors. Cross- and auto-spectra from the two regions were used to optimise three DCMs based on biologically plausible neural mass models and specific network architectures. Consistent with known extrinsic connectivity patterns in sensory hierarchies, we found that a model comprising forward connections from A1 to PAF and backward connections from PAF to A1 outperformed a model with forward connections from PAF to A1 and backward connections from A1 to PAF and a model with reciprocal lateral connections. The parameter estimates from the most plausible model indicated that the amplitude of fast glutamatergic excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) behaved as predicted by previous neurophysiological studies. Specifically, with increasing levels of anaesthesia, glutamatergic EPSPs decreased linearly, whereas fast GABAergic IPSPs displayed a nonlinear (saturating) increase. The consistency of our model-based in vivo results with experimental in vitro results lends further validity to the capacity of DCM to infer on synaptic processes using macroscopic neurophysiological data.

¹⁸F-Prostate-specific membrane antigen (PSMA)-1007 is mainly excreted through the liver. We benchmarked the performance of ¹⁸F-PSMA-1007 against three renally excreted PSMA-tracers. Methods: Among 668 patients we selected 27 patients in whom the PET/CT with ⁶⁸Ga-PSMA-11, ¹⁸F-DCFPyL, or ¹⁸F-JK-PSMA-7 was interpreted as equivocal or negative or as oligometastatic disease (PET-1). Within <3 weeks, a second PET scan with ¹⁸F-PSMA-1007 was performed (PET-2). The confidence in the interpretation of PSMA-positive loco-regional findings was scored on a 5-point scale, first in routine diagnostics (reader 1), then by an independent second evaluation (reader 2). Discordant PSMA-positive skeletal findings were examined by contrast enhanced MRI. Results: For both readers, ¹⁸F-PSMA-1007 facilitated the interpretability of 27 loco-regional lesions. In PET-2, the clinical read-out led to a significantly lower number of equivocal loco-regional lesions (P = 0.024), reader 2 reported a significantly higher rate of suspicious lesions that were falsely interpreted as probably benign in PET-1 (P = 0.023). Exclusively on PET-2, we observed a total of 15 PSMA-positive PSMA-spots in the bone marrow of 6 patients (= 22%). None of the 15 discordant spots had a morphological correlate on the corresponding CT or on the subsequent MRI. Thus, ¹⁸F-PSMA-1007 exhibits a significantly higher rate of unspecific medullary spots (P = 0.0006). Conclusion: ¹⁸F-PSMA-1007 may increase confidence to interpret small loco-regional lesions adjacent to the urinary tract. However, it may decrease the interpretability of skeletal lesions.

Decision making refers to the process by which subjects choose between competing courses of action based on the expected costs and benefits of their consequences. Lesion studies in rats suggest that the anterior cingulate cortex and the nucleus accumbens are key structures of a neural system that subserves effort-based decision making. Little is known about brain activation associated with effort-based decisions in intact rats. Using an open hypothesis approach, we used 2-deoxy-2[¹⁸F]fluoro-d-glucose positron emission tomography (FDG-PET) to assess regional metabolic changes in two conditions of an effort-based decision making task. In the “same effort” condition, male rats could choose between two response options associated with the same effort but different reward sizes, i.e., decision making was simply a function of reward size. By contrast, in the “different effort” condition, an integration of different efforts and reward sizes associated with the two response options was necessary before making a decision. Separate PET scans were performed from each condition. Subtractive analysis revealed that metabolic activity was increased in the different effort relative to the same effort condition in the left anterior cingulate, left orbitofrontal and prelimbic cortex region. Metabolic activity was decreased in the infralimbic cortex and septum region. Our findings suggest that making decisions on how much effort to invest to obtain greater rewards evokes changes of metabolic activity in multiple brain areas associated with cognitive, limbic, motor and autonomic functions. This study demonstrates that FDG-PET provides a tool to determine in rats regional brain metabolic activity in cognitive tasks.