Peripherally derived macrophages infiltrate the brain after bone marrow transplantation and during central nervous system (CNS) inflammation. It was initially suggested that these engrafting cells ...were newly derived microglia and that irradiation was essential for engraftment to occur. However, it remains unclear whether brain-engrafting macrophages (beMφs) acquire a unique phenotype in the brain, whether long-term engraftment may occur without irradiation, and whether brain function is affected by the engrafted cells. In this study, we demonstrate that chronic, partial microglia depletion is sufficient for beMφs to populate the niche and that the presence of beMφs does not alter behavior. Furthermore, beMφs maintain a unique functional and transcriptional identity as compared with microglia. Overall, this study establishes beMφs as a unique CNS cell type and demonstrates that therapeutic engraftment of beMφs may be possible with irradiation-free conditioning regimens.
Immune dysfunction is commonly associated with several neurological and mental disorders. Although the mechanisms by which peripheral immunity may influence neuronal function are largely unknown, ...recent findings implicate meningeal immunity influencing behaviour, such as spatial learning and memory. Here we show that meningeal immunity is also critical for social behaviour; mice deficient in adaptive immunity exhibit social deficits and hyper-connectivity of fronto-cortical brain regions. Associations between rodent transcriptomes from brain and cellular transcriptomes in response to T-cell-derived cytokines suggest a strong interaction between social behaviour and interferon-γ (IFN-γ)-driven responses. Concordantly, we demonstrate that inhibitory neurons respond to IFN-γ and increase GABAergic (γ-aminobutyric-acid) currents in projection neurons, suggesting that IFN-γ is a molecular link between meningeal immunity and neural circuits recruited for social behaviour. Meta-analysis of the transcriptomes of a range of organisms reveals that rodents, fish, and flies elevate IFN-γ/JAK-STAT-dependent gene signatures in a social context, suggesting that the IFN-γ signalling pathway could mediate a co-evolutionary link between social/aggregation behaviour and an efficient anti-pathogen response. This study implicates adaptive immune dysfunction, in particular IFN-γ, in disorders characterized by social dysfunction and suggests a co-evolutionary link between social behaviour and an anti-pathogen immune response driven by IFN-γ signalling.
Bulimia nervosa (BN) is characterized by both recurrent episodes of binge eating that are, in part, defined by a sense of loss of control and compensatory behaviors to avoid weight gain. Impulsive ...behaviors are also common in individuals with BN, indicating more pervasive difficulties in behavioral self-regulation. Findings from functional and anatomical neuroimaging studies of individuals with BN suggest dysfunction in the dorsal frontostriatal circuits that support self-regulatory capacities and habit learning and in overlapping ventral circuits that support reward processing and reward-based learning. In this review, we describe the normal development of frontostriatal circuits and then present behavioral and neuroimaging data from adolescents and adults with BN. These data suggest that the abnormal maturation of frontostriatal circuits may contribute to the habitual binge-eating and purging behaviors of BN. Future longitudinal imaging studies will improve understanding of how these circuits contribute to the developmental trajectory of BN and will inform novel interventions that could target or prevent the impulsive and habit-like features of this disorder.
Objective:
Neuroimaging studies of healthy individuals inform us about the normative maturation of the frontostriatal circuits that subserve self-regulatory control processes. Findings from these ...studies can be used as a reference frame against which to compare the aberrant development of these processes in individuals across a wide range of childhood psychopathologies.
Method:
The authors reviewed extensive neuroimaging evidence for the presence of abnormalities in frontostriatal circuits in children and adults with Tourette's syndrome and obsessive-compulsive disorder (OCD) as well as a more limited number of imaging studies of adolescents and adults with anorexia nervosa or bulimia nervosa that, together, implicate dysregulation of frontostriatal control systems in the pathogenesis of these eating disorders.
Results:
The presence of an impaired capacity for self-regulatory control that derives from abnormal development of frontostriatal circuits likely interacts in similar ways with normally occurring somatic sensations and motor urges, intrusive thoughts, sensations of hunger, and preoccupation with body shape and weight to contribute, respectively, to the development of the tics of Tourette's syndrome, the obsessions of OCD, the binge eating behaviors of bulimia, and the self-starvation of anorexia.
Conclusions:
Analogous brain mechanisms in parallel frontostriatal circuits, or even in differing portions of the same frontostriatal circuit, may underlie the differing behavioral disturbances in these multiple disorders, although further research is needed to confirm this hypothesis.
Neuroimaging findings which identify normal brain development trajectories are presented. Results show that early brain development begins with the neural tube formation and ends with myelintation. ...How disturbances in brain development patterns are related to childhood psychiatric disorders is examined.
Background
Based on findings from adults with obsessive‐compulsive disorder (OCD), this study examined alterations in resting‐state functional connectivity (rs‐fc) between the basolateral amygdala ...(BLA) and the ventromedial prefrontal cortex (vmPFC) in children and adolescents with OCD. We also assessed whether such BLA‐vmPFC connectivity changed with or predicted response to exposure and response prevention (E/RP), the first‐line treatment for pediatric OCD, given the involvement of these regions in fear processing, regulation, and extinction learning—a probable mechanism of action of E/RP.
Methods
Resting state functional magnetic resonance imaging scans were acquired from 25 unmedicated, treatment‐naïve pediatric patients with OCD (12.8 ± 2.9 years) and 23 age‐ and sex‐matched healthy controls (HCs; 11.0 ± 3.3 years). Patients completed a 12–16‐week E/RP intervention for OCD. Participants were rescanned after the 12–16‐week period. ANCOVAs tested group differences in baseline rs‐fc. Cross‐lagged panel models examined relationships between BLA‐vmPFC rs‐fc and OCD symptoms pre‐ and posttreatment. All tests were adjusted for participants' age, sex, and head motion.
Results
Right BLA‐vmPFC rs‐fc was significantly reduced (more negative) in patients with OCD relative to HCs at baseline, and increased following treatment. In patients, more positive (less negative) right BLA‐vmPFC rs‐fc pretreatment predicted greater OCD symptoms reduction posttreatment. Changes in BLA‐vmPFC rs‐fc was unassociated with change in OCD symptoms pre‐ to posttreatment.
Conclusions
These results provide further evidence of the BLA‐vmPFC pathway as a potential target for novel treatments or prevention strategies aimed at facilitating adaptive learning and fear extinction in children with OCD or subclinical OCD symptoms.
Anticorrelated resting state connectivity between task-positive and task-negative networks in adults supports flexible shifting between externally focused attention and internal thought. Findings ...suggest that children show positive correlations between task-positive (frontoparietal; FP) and task-negative (default mode; DMN) networks. FP-DMN connectivity also associates with intellectual functioning across the lifespan. We investigated whether FP-DMN connectivity in healthy children varied with age and intelligence quotient (IQ).
We utilized network-based statistics (NBS) to examine resting state functional connectivity between FP and DMN seeds in N = 133 7−25-year-olds (Mage = 15.80). Linear regression evaluated FP-DMN associations with IQ.
We detected NBS subnetworks containing both within- and between-network connections that were inversely associated with age. Four FP-DMN connections showed more negative connectivity between FP (inferior frontal gyrus and precentral gyrus) and DMN regions (frontal medial cortex, precuneus, and frontal pole) among older participants. Frontal pole-precentral gyrus connectivity inversely associated with IQ.
FP-DMN connectivity was more anticorrelated at older ages, potentially indicating dynamic network segregation of these circuits from childhood to early adulthood. Youth with more mature (i.e., anticorrelated) FP-DMN connectivity demonstrated higher IQ. Our findings add to the growing body of literature examining neural network development and its association with IQ.
•Prenatal environmental tobacco smoke (ETS) increases risk for attention problems.•The neurobiological effects of prenatal ETS are unknown.•Prenatal ETS alters the structure and function of ...frontostriatal control circuitry.•Smaller thalamic volume mediated effects of exposure on attention problems.•ETS and smoking in pregnancy confer similar risk on brain structure and behavior.
Prenatal exposure to environmental tobacco smoke (ETS) is associated with increased attention problems in children, however, the effects of such exposure on children’s brain structure and function have not been studied. Herein, we probed effects of prenatal ETS on children’s cognitive control circuitry and behavior.
Forty-one children (7–9 years) recruited from a prospective longitudinal birth cohort of non-smoking mothers completed structural and task-functional magnetic resonance imaging to evaluate effects of maternal ETS exposure, measured by maternal prenatal urinary cotinine. Attention problems and externalizing behaviors were measured by parent report on the Child Behavior Checklist.
Compared to non-exposed children, exposed children had smaller left and right thalamic and inferior frontal gyrus (IFG) volumes, with large effect sizes (p-FDR < .05, Cohen’s D range from 0.79 to 1.07), and increased activation in IFG during the resolution of cognitive conflict measured with the Simon Spatial Incompatibility Task (38 voxels; peak t(25) = 5.25, p-FWE = .005). Reduced thalamic volume was associated with increased IFG activation and attention problems, reflecting poor cognitive control. Mediation analyses showed a trend toward left thalamic volume mediating the association between exposure and attention problems (p = .05).
Our findings suggest that maternal ETS exposure during pregnancy has deleterious effects on the structure and function of cognitive control circuitry which in turn affects attentional capacity in school-age children. These findings are consistent with prior findings documenting the effects of active maternal smoking on chidlren’s neurodevleoment, pointing to the neurotixicity of nicotine regardless of exposure pathway.
Psoriasis is associated with hepatic steatosis, fibrosis, and methotrexate-associated liver injury. There is a need for reliable methods to monitor liver disease in psoriasis. Transient elastography ...(TE) is a validated non-invasive method for assessing hepatic steatosis and fibrosis. Psoriasis-specific TE studies have been limited until recently. Here, we review the utility and limitations of TE to detect and monitor liver disease in the context of psoriasis.
A comprehensive search using OVID, PubMed, and gray literature was conducted (2005-November 2019) to identify studies of TE use in psoriasis for assessment of hepatic steatosis and fibrosis.
Fifteen studies met inclusion criteria. A total of 1,536 patients with psoriasis or psoriatic arthritis were represented. TE-detected liver fibrosis is associated with age, diabetes, obesity, and severity of psoriasis. TE successfully evaluates hepatic steatosis and fibrosis. Elastography has a high negative predictive value and specificity in the context of methotrexate-associated liver fibrosis in psoriasis; however, reported associations between abnormal elastography results and cumulative methotrexate dose varied significantly despite methotrexate's association with hepatotoxicity and fibrosis. The presence of central adiposity is associated with increased TE failure rate.
The TE studies included in this review date from 2007 to 2019, which could contribute to publication bias, as the technique of TE has improved over this time period.
TE is a useful and non-invasive modality to detect hepatic steatosis and fibrosis in psoriasis. Dermatologists might consider TE in psoriatic patients and concomitant risk factors for fibrosis with the understanding that failure rates may be higher in patients with central adiposity.
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