Independent and Interactive Impacts of Prenatal Exposure to Legal Substances and Childhood Trauma on Emotion Processing in Pre-Adolescents: Preliminary Findings From the ABCD Study.

Objective: This paper investigated the effects of prenatal drug exposure (PDE), childhood trauma (CT), and their interactions on the neurobiological markers for emotion processing.

Method: Here, in a non-clinical sample of pre-adolescents (9-10 years of age) from the Adolescent Brain Cognitive Development (ABCD) Study (N = 6,146), we investigate the impact of PDE to commonly used substances (ie, alcohol, cigarettes, and marijuana), CT, and their interaction on emotion processing. From the Emotional N-back functional magnetic resonance imaging task data, we selected 26 regions of interests, previously implicated in emotion processing, and conducted separate linear mixed models (108 total) and accounted for available environmental risk factors.

Dynamic Functional Connectivity Correlates of Trait Mindfulness in Early Adolescence.

Background: Trait mindfulness-the tendency to attend to present-moment experiences without judgment-is negatively correlated with adolescent anxiety and depression. Understanding the neural mechanisms that underlie trait mindfulness may inform the neural basis of psychiatric disorders. However, few studies have identified brain connectivity states that are correlated with trait mindfulness in adolescence, and they have not assessed the reliability of such states.

Dynamic functional connectivity correlates of trait mindfulness in early adolescence.

Background: Trait mindfulness, the tendency to attend to present-moment experiences without judgement, is negatively correlated with adolescent anxiety and depression. Understanding the neural mechanisms underlying trait mindfulness may inform the neural basis of psychiatric disorders. However, few studies have identified brain connectivity states that correlate with trait mindfulness in adolescence, nor have they assessed the reliability of such states.

RIPK1: Inflamed if you do, inflamed if you don't.

RIPK1 is known as a driver of cell death and inflammation. In this issue of Immunity, Imai et al. and Mannion et al.

Striatal and Behavioral Responses to Reward Vary by Socioeconomic Status in Adolescents.

Disparities in socioeconomic status (SES) lead to unequal access to financial and social support. These disparities are believed to influence reward sensitivity, which in turn are hypothesized to shape how individuals respond to and pursue rewarding experiences. However, surprisingly little is known about how SES shapes reward sensitivity in adolescence.

LITAF protects against pore-forming protein-induced cell death by promoting membrane repair.

Pore-forming toxins (PFTs) are the largest class of bacterial toxins and contribute to virulence by triggering host cell death. Vertebrates also express endogenous pore-forming proteins that induce cell death as part of host defense. To mitigate damage and promote survival, cells mobilize membrane repair mechanisms to neutralize and counteract pores, but how these pathways are activated is poorly understood.

Evaluating instrumental learning and striatal-cortical functional connectivity in adolescent alcohol and cannabis use.

Adolescence is a vulnerable time for the acquisition of substance use disorders, potentially relating to ongoing development of neural circuits supporting instrumental learning. Striatal-cortical circuits undergo dynamic changes during instrumental learning and are implicated in contemporary addiction theory. Human studies have not yet investigated these dynamic changes in relation to adolescent substance use.

Contrasting dose-dependent effects of acute intravenous methamphetamine on lateral hypothalamic extracellular glucose dynamics in male and female rats.

Glucose is the brain's primary energetic resource. The brain's use of glucose is dynamic, balancing delivery from the neurovasculature with local metabolism. Although glucose metabolism is known to differ in humans with and without methamphetamine use disorder (MUD), it is unknown how central glucose regulation changes with acute methamphetamine experience.

Altered linear coupling between stimulus-evoked blood flow and oxygen metabolism in the aging human brain.

Neural-vascular coupling (NVC) is the process by which oxygen and nutrients are delivered to metabolically active neurons by blood vessels. Murine models of NVC disruption have revealed its critical role in healthy neural function. We hypothesized that, in humans, aging exerts detrimental effects upon the integrity of the neural-glial-vascular system that underlies NVC.

Cutting Edge: DOCK8 Regulates a Subset of Dendritic Cells That Is Critical for the Development of Experimental Autoimmune Encephalomyelitis.

Dedicator of cytokinesis 8 (DOCK8) is a guanine nucleotide exchange factor with an essential role in cytoskeletal rearrangement, cell migration, and survival of various immune cells. Interestingly, DOCK8-deficient mice are resistant to the development of experimental autoimmune encephalomyelitis (EAE). To understand if EAE resistance in these mice results from an alteration in dendritic cell (DC) functions, we generated mice with conditional deletion of DOCK8 in DCs and observed attenuated EAE in these mice compared with control mice.

Reward-Related Neural Circuitry in Depressed and Anxious Adolescents: A Human Connectome Project.

Objective: Although depression and anxiety often have distinct etiologies, they frequently co-occur in adolescence. Recent initiatives have underscored the importance of developing new ways of classifying mental illness based on underlying neural dimensions that cut across traditional diagnostic boundaries. Accordingly, the aim of the study was to clarify reward-related neural circuitry that may characterize depressed-anxious youth.

Resting cerebral oxygen metabolism exhibits archetypal network features.

Standard magnetic resonance imaging approaches offer high-resolution but indirect measures of neural activity, limiting understanding of the physiological processes associated with imaging findings. Here, we used calibrated functional magnetic resonance imaging during the resting state to recover low-frequency fluctuations of the cerebral metabolic rate of oxygen (CMRO ). We tested whether functional connections derived from these fluctuations exhibited organization properties similar to those established by previous standard functional and anatomical connectivity studies.

Functional Alterations in Cerebellar Functional Connectivity in Anxiety Disorders.

Adolescents with anxiety disorders exhibit excessive emotional and somatic arousal. Neuroimaging studies have shown abnormal cerebral cortical activation and connectivity in this patient population. The specific role of cerebellar output circuitry, specifically the dentate nuclei (DN), in adolescent anxiety disorders remains largely unexplored.

Gene editing to induce FOXP3 expression in human CD4 T cells leads to a stable regulatory phenotype and function.

Thymic regulatory T cells (tT) are potent inhibitors of autoreactive immune responses, and loss of tT function results in fatal autoimmune disease. Defects in tT number or function are also implicated in multiple autoimmune diseases, leading to growing interest in use of T as cell therapies to establish immune tolerance. Because tT are present at low numbers in circulating blood and may be challenging to purify and expand and also inherently defective in some subjects, we designed an alternative strategy to create autologous T-like cells from bulk CD4 T cells.

Reward-Sensitive Basal Ganglia Stabilize the Maintenance of Goal-Relevant Neural Patterns in Adolescents.

Maturation of basal ganglia (BG) and frontoparietal circuitry parallels developmental gains in working memory (WM). Neurobiological models posit that adult WM performance is enhanced by communication between reward-sensitive BG and frontoparietal regions, via increased stability in the maintenance of goal-relevant neural patterns. It is not known whether this reward-driven pattern stability mechanism may have a role in WM development.

Image acquisition and quality assurance in the Boston Adolescent Neuroimaging of Depression and Anxiety study.

The Connectomes Related to Human Diseases (CRHD) initiative was developed with the Human Connectome Project (HCP) to provide high-resolution, open-access, multi-modal MRI data to better understand the neural correlates of human disease. Here, we present an introduction to a CRHD project, the Boston Adolescent Neuroimaging of Depression and Anxiety (BANDA) study, which is collecting multimodal neuroimaging, clinical, and neuropsychological data from 225 adolescents (ages 14-17), 150 of whom are expected to have a diagnosis of depression and/or anxiety. Our transdiagnostic recruitment approach samples the full spectrum of depressed/anxious symptoms and their comorbidity, consistent with NIMH Research Domain Criteria (RDoC).

Fixed and flexible: Dynamic prefrontal activations and working memory capacity relationships vary with memory demand.

Prefrontal cortex (PFC) activation during encoding of memoranda (proactive responses) is associated with better working memory (WM) compared to reactive/retrieval-based activation. This suggests that dynamic PFC activation patterns may be fixed, based upon one's WM ability, with individuals who have greater WM ability relying more on proactive processes and individuals with lesser WM ability relying more on reactive processes. We newly tested whether this heuristic applied when challenging an individual's WM capacity.

Functional Territories of Human Dentate Nucleus.

Anatomical connections link the cerebellar cortex with multiple sensory, motor, association, and paralimbic cerebral areas. The majority of fibers that exit cerebellar cortex synapse in dentate nuclei (DN) before reaching extracerebellar structures such as cerebral cortex, but the functional neuroanatomy of human DN remains largely unmapped. Neuroimaging research has redefined broad categories of functional division in the human brain showing that primary processing, attentional (task positive) processing, and default-mode (task negative) processing are three central poles of neural macroscale functional organization.

Age-differential relationships among dopamine D1 binding potential, fusiform BOLD signal, and face-recognition performance.

Facial recognition ability declines in adult aging, but the neural basis for this decline remains unknown. Cortical areas involved in face recognition exhibit lower dopamine (DA) receptor availability and lower blood-oxygen-level-dependent (BOLD) signal during task performance with advancing adult age. We hypothesized that changes in the relationship between these two neural systems are related to age differences in face-recognition ability.

Intratumoral activation of the necroptotic pathway components RIPK1 and RIPK3 potentiates antitumor immunity.

Although the signaling events that induce different forms of programmed cell death are well defined, the subsequent immune responses to dying cells in the context of cancer remain relatively unexplored. Necroptosis occurs downstream of the receptor-interacting protein kinases RIPK1 and RIPK3, whose activation leads to lytic cell death accompanied by de novo production of proinflammatory mediators. Here, we show that ectopic introduction of necroptotic cells to the tumor microenvironment promotes BATF3 cDC1- and CD8 leukocyte-dependent antitumor immunity accompanied by increased tumor antigen loading by tumor-associated antigen-presenting cells.

Rapid immune reconstitution of SCID-X1 canines after G-CSF/AMD3100 mobilization and in vivo gene therapy.

Hematopoietic stem-cell gene therapy is a promising treatment of X-linked severe combined immunodeficiency disease (SCID-X1), but currently, it requires recipient conditioning, extensive cell manipulation, and sophisticated facilities. With these limitations in mind, we explored a simpler therapeutic approach to SCID-X1 treatment by direct IV administration of foamy virus (FV) vectors in the canine model. FV vectors were used because they have a favorable integration site profile and are resistant to serum inactivation.

Preserved canonicality of the BOLD hemodynamic response reflects healthy cognition: Insights into the healthy brain through the window of Multiple Sclerosis.

The hemodynamic response function (HRF), a model of brain blood-flow changes in response to neural activity, reflects communication between neurons and the vasculature that supplies these neurons in part by means of glial cell intermediaries (e.g., astrocytes).