Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Extinction learning alters the neural representation of conditioned fear

Extinction learning is a primary means by which conditioned associations to threats are controlled and is a model system for emotion dysregulation in anxiety disorders. Recent work has called for new approaches to track extinction-related changes in conditioned stimulus (CS) representations. We applied a multivariate analysis to previously -collected functional magnetic resonance imaging data on extinction learning, in which healthy young adult participants (N = 43; 21 males, 22 females) encountered dynamic snake and spider CSs while passively navigating 3D virtual environments. We used representational similarity analysis to compare voxel-wise activation t-statistic maps for the shock-reinforced CS (CS+) from the late phase of fear acquisition to the early and late phases of extinction learning within subjects. These patterns became more dissimilar from early to late extinction in a priori regions of interest: subgenual and dorsal anterior cingulate gyrus, amygdala and hippocampus. A whole-brain searchlight analysis revealed similar findings in the insula, mid-cingulate cortex, ventrolateral prefrontal cortex, somatosensory cortex, cerebellum, and visual cortex. High state anxiety attenuated extinction-related changes to the CS+ patterning in the amygdala, which suggests an enduring threat representation. None of these effects generalized to an unreinforced control cue, nor were they evident in traditional univariate analyses. Our approach extends previous neuroimaging work by emphasizing how evoked neural patterns change from late acquisition through phases of extinction learning, including those in brain regions not traditionally implicated in animal models. Finally, the findings provide additional support for a role of the amygdala in anxiety-related persistence of conditioned fears

Functional MRI in the investigation of blast-related traumatic brain injury

This review focuses on the application of functional magnetic resonance imaging (fMRI) to the investigation of blast-related traumatic brain injury (bTBI). Relatively little is known about the exact mechanisms of neurophysiological injury and pathological and functional sequelae of bTBI. Furthermore, in mild bTBI, standard anatomical imaging techniques (MRI and CT) generally fail to show focal lesions and most of the symptoms present as subjective clinical functional deficits. Therefore, an objective test of brain functionality has great potential to aid in patient diagnosis and provide a sensitive measurement to monitor disease progression and treatment. The goal of this review is to highlight the relevant body of blast-related TBI literature and present suggestions and considerations in the development of fMRI studies for the investigation of bTBI. The review begins with a summary of recent bTBI publications followed by discussions of various elements of blast-related injury. Brief reviews of some fMRI techniques that focus on mental processes commonly disrupted by bTBI, including working memory, selective attention, and emotional processing, are presented in addition to a brief review of resting state fMRI. Potential strengths and weaknesses of these approaches as regards bTBI are discussed. Finally, this review presents considerations that must be made when designing fMRI studies for bTBI populations, given the heterogeneous nature of bTBI and its high rate of comorbidity with other physical and psychological injuries

Fetal dopamine receptor characteristics assessed in utero

Any tracer in fetal tissue comes from maternal arterial blood. Provided steady state is achieved and intermediate compartments are reversible, the Logan graphical methods should be applicable to the assessment of binding parameters in the fetal brain. Two pregnant rhesus macaques were studied with fallypride and the Logan method was used to assess dopamine receptor distribution volume ratios (DVRs) in both maternal and fetal striatum. The agreement between fetal striatal DVRs using maternal arterial blood and maternal and fetal cerebellum as input functions strongly supports our hypothesis that the conditions necessary for graphical analysis have been met

Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa: A Coordinated Analysis by the ENIGMA Eating Disorders Working Group

The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood. While several studies report substantial deficits in gray matter volume and cortical thickness in acutely underweight patients, others find no differences, or even increases in patients compared with healthy control subjects. Recent weight regain before scanning may explain some of this heterogeneity. To clarify the extent, magnitude, and dependencies of gray matter changes in AN, we conducted a prospective, coordinated meta-analysis of multicenter neuroimaging data