Attentional bias to threat is a key endophenotype that contributes to the chronicity of trauma-related psychopathology. However, little is known about the neurobiology of this endophenotype and no known in vivo molecular imaging study has been conducted to evaluate candidate receptor systems that may be implicated in this endophenotype or the phenotypic expression of trauma-related psychopathology that comprises threat (ie, re-experiencing, avoidance, and hyperarousal) and loss (ie, emotional numbing, depression/dysphoria, generalized anxiety) symptomatology. Using the radioligand [(11)C]OMAR and positron emission tomography (PET), we evaluated the relationship between in vivo cannabinoid receptor type 1 (CB1) receptor availability in the amygdala, and performance on a dot-probe measure of attentional bias to threat, and clinician interview-based measures of trauma-related psychopathology. The sample comprised adults presenting with a broad spectrum of trauma-related psychopathology, ranging from nontrauma-exposed, psychiatrically healthy adults to trauma-exposed adults with severe trauma-related psychopathology. Results revealed that increased CB1 receptor availability in the amygdala was associated with increased attentional bias to threat, as well as increased severity of threat, but not loss, symptomatology; greater peripheral anandamide levels were associated with decreased attentional bias to threat. A mediation analysis further suggested that attentional bias to threat mediated the relationship between CB1 receptor availability in the amygdala and severity of threat symptomatology. These data substantiate a key role for compromised endocannabinoid function in mediating both the endophenotypic and phenotypic expression of threat symptomatology in humans. They further suggest that novel pharmacotherapies that target the CB1 system may provide a more focused, mechanism-based approach to mitigating this core aspect of trauma-related psychopathology.

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Purpose

Exploring synaptic density changes during brain growth is crucial to understanding brain development. Previous studies in nonhuman primates report a rapid increase in synapse number between the late gestational period and the early neonatal period, such that synaptic density approaches adult levels by birth. Prenatal synaptic development may have an enduring impact on postnatal brain development, but precisely how synaptic density changes in utero are unknown because current methods to quantify synaptic density are invasive and require post-mortem brain tissue.

Methods

We used synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) radioligands [¹¹C]UCB-J and [¹⁸F]Syn-VesT-1 to conduct the first assessment of synaptic density in the developing fetal brain in gravid rhesus monkeys. Eight pregnant monkeys were scanned twice during the third trimester at two imaging sites. Fetal post-mortem samples were collected near term in a subset of subjects to quantify SV2A density by Western blot.

Results

Image-derived fetal brain SV2A measures increased during the third trimester. SV2A concentrations were greater in subcortical regions than in cortical regions at both gestational ages. Near term, SV2A density was higher in primary motor and visual areas than respective associative regions. Post-mortem quantification of SV2A density was significantly correlated with regional SV2A PET measures.

Conclusion

While further study is needed to determine the exact relationship of SV2A and synaptic density, the imaging paradigm developed in the current study allows for the effective in vivo study of SV2A development in the fetal brain.

Since the last IAEA-FEC in 2021, significant progress on the development of long pulse steady state scenario and its related key physics and technologies have been achieved, including the reproducible 403 s long-pulse steady-state H-mode plasma with pure radio frequency (RF) power heating. A thousand-second time scale (∼1056 s) fully non-inductive plasma with high injected energy up to 1.73 GJ has also been achieved. The EAST operational regime of high βP has been significantly extended (H98y2 > 1.3, βP ∼ 4.0, βN ∼ 2.4 and ne/nGW ∼ 1.0) using RF and neutral beam injection (NBI). The full edge localized mode suppression using the n = 4 resonant magnetic perturbations has been achieved in ITER-like standard type-I ELMy H-mode plasmas with q95 ≈ 3.1 on EAST, extrapolating favorably to the ITER baseline scenario. The sustained large ELM control and stable partial detachment have been achieved with Ne seeding. The underlying physics of plasma-beta effect for error field penetration, where toroidal effect dominates, is disclosed by comparing the results in cylindrical theory and MARS-Q simulation in EAST. Breakdown and plasma initiation at low toroidal electric fields (<0.3 V m−1) with EC pre-ionization is developed. A beneficial role on the lower hybrid wave injection to control the tungsten concentration in the NBI discharge is observed for the first time in EAST suggesting a potential way toward steady-state H-mode NBI operation.