Changes In Brain Architecture Research Articles

Difficulties during delivery, brain ventricle enlargement and cognitive impairment in first episode psychosis.

Patients with a first episode of psychosis (FEP) display clinical, cognitive, and structural brain abnormalities at illness onset. Ventricular enlargement has been identified in schizophrenia since the initial development of neuroimaging techniques. Obstetric abnormalities have been associated with an increased risk of developing psychosis but also with cognitive impairment and brain structure abnormalities. Difficulties during delivery are associated with a higher risk of birth asphyxia leading to brain structural abnormalities, such as ventriculomegaly, which has been related to cognitive disturbances. We examined differences in ventricular size between 142 FEP patients and 123 healthy control participants using magnetic resonance imaging. Obstetric complications were evaluated using the Lewis-Murray scale. We examined the impact of obstetric difficulties during delivery on ventricle size as well as the possible relationship between ventricle size and cognitive impairment in both groups. FEP patients displayed significantly larger third ventricle size compared with healthy controls. Third ventricle enlargement was associated with diagnosis (higher volume in patients), with difficulties during delivery (higher volume in subjects with difficulties), and was highest in patients with difficulties during delivery. Verbal memory was significantly associated with third ventricle to brain ratio. Our results suggest that difficulties during delivery might be significant contributors to the ventricular enlargement historically described in schizophrenia. Thus, obstetric complications may contribute to the development of psychosis through changes in brain architecture.

Interrelated effects of age and parenthood on whole-brain controllability: protective effects of parenthood in mothers.

Controllability is a measure of the brain's ability to orchestrate neural activity which can be quantified in terms of properties of the brain's network connectivity. Evidence from the literature suggests that aging can exert a general effect on whole-brain controllability. Mounting evidence, on the other hand, suggests that parenthood and motherhood in particular lead to long-lasting changes in brain architecture that effectively slow down brain aging. We hypothesize that parenthood might preserve brain controllability properties from aging. In a sample of 814 healthy individuals (aged 33.9 ± 12.7 years, 522 females), we estimate whole-brain controllability and compare the aging effects in subjects with vs. those without children. We use diffusion tensor imaging (DTI) to estimate the brain structural connectome. The level of brain control is then calculated from the connectomic properties of the brain structure. Specifically, we measure the network control over many low-energy state transitions (average controllability) and the network control over difficult-to-reach states (modal controllability). In nulliparous females, whole-brain average controllability increases, and modal controllability decreases with age, a trend that we do not observe in parous females. Statistical comparison of the controllability metrics shows that modal controllability is higher and average controllability is lower in parous females compared to nulliparous females. In men, we observed the same trend, but the difference between nulliparous and parous males do not reach statistical significance. Our results provide strong evidence that parenthood contradicts aging effects on brain controllability and the effect is stronger in mothers.

Abnormal static and dynamic functional network connectivity of the whole-brain in children with generalized tonic-clonic seizures.

Generalized tonic-clonic seizures (GTCS) are a subtype of generalized seizures exhibiting bursts of bilaterally synchronous generalized spike-wave discharges. Numerous neuroimaging studies have reported aberrant functional activity and topological organization of brain network in epilepsy patients with GTCS, but most studies have focused on adults. However, the effect of GTCS on the spatial and temporal properties of brain function in children remains unclear. The present study aimed to explore whole-brain static (sFC) and dynamic functional connectivity (dFC) in children with GTCS. Twenty-three children with GTCS and 32 matched healthy controls (HCs) were recruited for the present study. Resting-state functional magnetic resonance imaging (MRI) data were collected for each subject. The group independent component analysis method was used to obtain independent components (ICs). Then, sFC and dFC methods were applied and the differences in functional connectivity (FC) were compared between the children with GTCS and the HCs. Additionally, we investigated the correlations between the dFC indicators and epilepsy duration. Compared to HCs, GTCS patients exhibited a significant decrease in sFC strengths among most networks. The K-means clustering method was implemented for dFC analysis, and the optimal number of clusters was estimated: two discrete connectivity configurations, State 1 (strong connection) and State 2 (weak connection). The decreased dFC mainly occurred in State 1, especially the dFC between the visual network (VIS) and somatomotor network (SMN); but the increased dFC mainly occurred in State 2 among most networks in GTCS children. In addition, GTCS children showed significantly shorter mean dwell time and lower fractional windows in stronger connected State 1, while GTCS children showed significantly longer mean dwell time in weaker connected State 2. In addition, the dFC properties, including mean dwell time and fractional windows, were significantly correlated with epilepsy duration. Our results indicated that GTCS epilepsy not only alters the connectivity strength but also changes the temporal properties of connectivity in networks in the whole brain. These findings also emphasized the differences in sFC and dFC in children with GTCS. Combining sFC and dFC methods may provide more comprehensive understanding of the abnormal changes in brain architecture in children with GTCS.

The role of brain oscillations in post-stroke motor recovery: An overview.

Stroke is the second cause of disability and death worldwide, highly impacting patient’s quality of life. Several changes in brain architecture and function led by stroke can be disclosed by neurophysiological techniques. Specifically, electroencephalogram (EEG) can disclose brain oscillatory rhythms, which can be considered as a possible outcome measure for stroke recovery, and potentially shaped by neuromodulation techniques. We performed a review of randomized controlled trials on the role of brain oscillations in patients with post-stroke searching the following databases: Pubmed, Scopus, and the Web of Science, from 2012 to 2022. Thirteen studies involving 346 patients in total were included. Patients in the control groups received various treatments (sham or different stimulation modalities) in different post-stroke phases. This review describes the state of the art in the existing randomized controlled trials evaluating post-stroke motor function recovery after conventional rehabilitation treatment associated with neuromodulation techniques. Moreover, the role of brain pattern rhythms to modulate cortical excitability has been analyzed. To date, neuromodulation approaches could be considered a valid tool to improve stroke rehabilitation outcomes, despite more high-quality, and homogeneous randomized clinical trials are needed to determine to which extent motor functional impairment after stroke can be improved by neuromodulation approaches and which one could provide better functional outcomes. However, the high reproducibility of brain oscillatory rhythms could be considered a promising predictive outcome measure applicable to evaluate patients with stroke recovery after rehabilitation.

Voluntary alcohol binge-drinking in adolescent C57Bl6 mice induces delayed appearance of behavioural defects in both males and females.

Adolescence is a developmental period characterized by significant changes in brain architecture and behaviour. The immaturity of the adolescent brain is associated with heightened vulnerability to exogenous agents, including alcohol. Alcohol is the most consumed drug among teenagers, and binge‐drinking during adolescence is a major public health concern. Studies have suggested that adolescent alcohol exposure may interfere with the maturation of frontal brain regions and lead to long‐lasting behavioural consequences. In this study, by using a slightly modified version of the Drinking in the Dark paradigm, adolescent C57Bl6 mice reach high blood alcohol concentration after voluntary binge‐drinking. In order to assess short‐ and long‐term consequences of adolescent alcohol exposure (AAE), a battery of behavioural tests was performed during late adolescence and during adulthood. We showed that AAE had no short‐term effect on young mice behaviour but rather increased anxiety‐ and depressive‐like behaviours, as well as alcohol consumption during adulthood. Moreover, alcohol binge‐drinking during adolescence dramatically decreased recognition memory performances and behavioural flexibility in both adult males and females. Furthermore, we showed that voluntary consumption of alcohol during adolescence did not trigger any major activation of the innate immune system in the prefrontal cortex. Together, our data suggest that voluntary alcohol binge‐drinking in adolescent mice induces a delayed appearance of behavioural impairments in adulthood.

Betamethasone Induces a Unique Transcriptome in Neural Stem Cells

Twelve percent of pregnant women receive glucocorticoids (sGCs) to reduce the risks to reduce morbidity and mortality associated with preterm birth in infants. The two most commonly administered sGC are Dexamethasone (Dex) and Betamethasone (Beta) and they serve to decrease the severity of respiratory distress, intraventricular hemorrhage and necrotizing enterocolitis. However, repeated administration of sGC has been shown to be associated with adverse neurological outcome and depends on the type of sGCs used, dose, timing of sGCs administration and sex. We have previously shown that prenatal exposure to Dex in a murine model lead to sex specific changes in the transcription response and in the biological function of neural stem cells and to long-term changes in brain architecture and behavior. Beta is the predominant sGC used prenatally in the United States, therefore these studies investigated the cellular and molecular responses to beta exposure on the neural stem cells in-vitro and anatomical organization of the brain in-vivo. Murine NSCs were isolated from the E14.5 cerebral cortex and exposed to 10-7 M Dex, 10-7 M Beta, or Vehicle for 4 or 24 hours and the immediate and long-term impact on transcription, proliferation and neuronal, glial and oligodendrocyte differentiation examined. Affymetrix genome transcriptional analyses reveal sex specific responses to Dex vs Beta in 4 hours. In females 682 genes were differentially regulated by Dex compared to 576 by Beta. In contrast, 875 were altered by Dex and 576 by Beta in males (Fold change > +/- 1.5, P< 0.05). Select target genes were independently validated by QPCR. Ingenuity Pathway Analysis was used to identify unique and overlapping pathways that were altered by Dex vs Beta. In males, Dex uniquely altered 34 pathways including, Thyroid Hormone Metabolism, ERK5 Signaling and Opioid Signaling while Bata altered 33 pathways including, Phagasome formation, IL-7 Signaling and JAK STAT signaling. In Females, Dex altered 45 pathways including Calcium Signaling, Serotonin Receptor Signaling and Xenobiotic Signaling, while Beta altered 46 pathways including, FXR/RXR Activation, Tec Kinase Signaling and D-myo-Inositol-5-Phosphate Metabolism. Another 35 pathways were altered by both Dex and Beta but they showed differences in genes activated or repressed. Dex and Beta, both significantly altered genes involved in proliferation and differentiation therefore the biological response of NSC to sGCs stimulation in vitro and the long term consequences of sGC exposure in-vivo was compared. Distinct differences in cell proliferation, glial and oligodendrocyte differentiation were observed. These results reveal gene targets, cellular pathways and processes that are differentially altered by prenatal Dex vs Beta exposure. Our finds may provide insights into the sex specific neurological outcomes observed in children exposed to sGCs in-utero.

Cross-species cortical alignment identifies different types of anatomical reorganization in the primate temporal lobe.

Evolutionary adaptations of temporo-parietal cortex are considered to be a critical specialization of the human brain. Cortical adaptations, however, can affect different aspects of brain architecture, including local expansion of the cortical sheet or changes in connectivity between cortical areas. We distinguish different types of changes in brain architecture using a computational neuroanatomy approach. We investigate the extent to which between-species alignment, based on cortical myelin, can predict changes in connectivity patterns across macaque, chimpanzee, and human. We show that expansion and relocation of brain areas can predict terminations of several white matter tracts in temporo-parietal cortex, including the middle and superior longitudinal fasciculus, but not the arcuate fasciculus. This demonstrates that the arcuate fasciculus underwent additional evolutionary modifications affecting the temporal lobe connectivity pattern. This approach can flexibly be extended to include other features of cortical organization and other species, allowing direct tests of comparative hypotheses of brain organization.

Neurotoxicity and inflammation induced by individual and combined exposure to iron oxide nanoparticles and silver nanoparticles

The present study aimed to investigate the neurotoxicity of iron oxide and silver NPs solely or combined. At the molecular level, the exposure to both NPs induced marked DNA fragmentation, downregulation of mtTFA, and upregulation of PGC-1α expression. Both NPs caused decline in acetylcholine esterase, norepinephrine, serotonin, dopamine, and antioxidants enzymes, while causing an increase in lipid peroxidation, nitric oxide, tumour suppressor gene p53, tumour necrosis factor-α, interleukin-6, acetylcholine, and norepinephrine. NPs exposure was associated with severe histologic changes in brain architecture. The effect of the combined exposure to both NPs was more pronounced than each one alone. This study showed that the mechanism of neurotoxicity may involve different pathways including changes in gene expression of mTFA and PGC-1α, induced DNA fragmentation, deregulated neurotransmitters, oxidative stress and disturbed cytokine production and tumour suppressor protein p53.

Longitudinally consistent estimates of intrinsic functional networks.

Increasing numbers of neuroimaging studies are acquiring data to examine changes in brain architecture by investigating intrinsic functional networks (IFN) from longitudinal resting-state functional MRI (rs-fMRI). At the subject level, these IFNs are determined by cross-sectional procedures, which neglect intra-subject dependencies and result in suboptimal estimates of the networks. Here, a novel longitudinal approach simultaneously extracts subject-specific IFNs across multiple visits by explicitly modeling functional brain development as an essential context for seeking change. On data generated by an innovative simulation based on real rs-fMRI, the method was more accurate in estimating subject-specific IFNs than cross-sectional approaches. Furthermore, only group-analysis based on longitudinally consistent estimates identified significant developmental effects within IFNs of 246 adolescents from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) study. The findings were confirmed by the cross-sectional estimates when the corresponding group analysis was confined to the developmental effects. Those effects also converged with current concepts of neurodevelopment.

Changes in brain architecture are consistent with altered fear processing in domestic rabbits

The most characteristic feature of domestic animals is their change in behavior associated with selection for tameness. Here we show, using high-resolution brain magnetic resonance imaging in wild and domestic rabbits, that domestication reduced amygdala volume and enlarged medial prefrontal cortex volume, supporting that areas driving fear have lost volume while areas modulating negative affect have gained volume during domestication. In contrast to the localized gray matter alterations, white matter anisotropy was reduced in the corona radiata, corpus callosum, and the subcortical white matter. This suggests a compromised white matter structural integrity in projection and association fibers affecting both afferent and efferent neural flow, consistent with reduced neural processing. We propose that compared with their wild ancestors, domestic rabbits are less fearful and have an attenuated flight response because of these changes in brain architecture.

Environmental ritalinization: Brain structural changes after exposition to methylphenidate residues

Methylphenidate, marketed as Ritalin, is an emerged pollutant found in wastewater. Methylphenidate exposure at pharmacological doses can modify brain metabolism, however, the consequences of environmental residues remains to be elucidated. This work presents the results of a chronic exposure to methylphenidate residual levels (0.1875 and 1.875 µg/L) consistent with the amount found in the environment. Animals were exposed to contaminated water during childhood and adolescence. Results evidence significant changes in brain architecture such as decreased cortical and increased striatum relative mass and proteins promoted by methylphenidate. To the best the authors’ knowledge, this is the first time that the interference in synaptic plasticity after chronic exposure to environmental levels of methylphenidate is shown. Key words: Ecotoxicology, emerged pollutants, wastewater, neurotoxicology.

Reproductive parameters of female Wistar rats treated with methylphenidate during development

Methylphenidate (MPH), a psychoactive agent that acts mainly by blocking the uptake of dopamine, is the main drug used to treat Attention Deficit Hyperactivity Disorder in children and adolescents. During development, important changes in brain architecture and plasticity occur, these changes, sensitive to exposure to stimulant drugs, are important in the control of GnRH secretion, influencing the release of sex hormones throughout the ovarian cycle. This study investigated the effects of repeated treatment with MPH during development on reproductive parameters of adult female rats. Wistar rats received MPH 2.5mg/kg, MPH 5.0mg/kg, or tap water (gavage) from postnatal day (PND) 21 to PND 60. From PND 75, one subgroup of females was selected for evaluation of estrous cycle, estradiol levels, weight of sexual organs, and histomorphological analysis of ovary follicles and uterus. In another subgroup, the sexual and maternal behaviors were evaluated at PND 90 and on lactational day 5, respectively. No significant alterations were observed in the MPH groups. This study demonstrated that repeated administration of MPH during the period corresponding to childhood to early adulthood does not interfere in the reproductive function of female rats in adulthood.

Coordinated brain development: exploring the synchrony between changes in grey and white matter during childhood maturation.

Brain development during childhood and early adolescence is characterized by global changes in brain architecture. Neuroimaging studies have revealed overall decreases in cortical thickness (CT) and increases in fractional anisotropy (FA). Furthermore, previous studies have shown that certain cortical regions display coordinated growth during development. However, there is significant heterogeneity in the timing and speed of these developmental transformations, and it is still unclear whether white and grey matter changes are co-localized. In this multimodal neuroimaging study, we investigated the relationship between grey and white matter developmental changes and asynchronous maturation within brain regions in 249 normally developing children between the ages 7-14. We used structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to analyze CT and FA, respectively, as well as their covariance across development. Consistent with previous studies, we observed overall cortical thinning with age, which was accompanied by increased FA. We then compared the coordinated development of grey and white matter as indexed by covariance measures. Covariance between grey matter regions and the microstructure of white matter tracts connecting those regions were highly similar, suggesting that coordinated changes in the cortex were mirrored by coordinated changes in their respective tracts. Examining within-brain divergent trajectories, we found significant structural decoupling (decreased covariance) between several brain regions and tracts in the 9- to 11-year-old group, particularly involving the forceps minor and the regions that it connects to. We argue that this decoupling could reflect a developmental pattern within the prefrontal region in 9- and 11-year-old children, possibly related to the significant changes in cognitive control observed at this age.

Essential Nonredundant Function of the Catalytic Activity of Histone Deacetylase 2 in Mouse Development.

The class I histone deacetylases (HDACs) HDAC1 and HDAC2 play partially redundant roles in the regulation of gene expression and mouse development. As part of multisubunit corepressor complexes, these two deacetylases exhibit both enzymatic and nonenzymatic functions. To examine the impact of the catalytic activities of HDAC1 and HDAC2, we generated knock-in mice expressing catalytically inactive isoforms, which are still incorporated into the HDAC1/HDAC2 corepressor complexes. Surprisingly, heterozygous mice expressing catalytically inactive HDAC2 die within a few hours after birth, while heterozygous HDAC1 mutant mice are indistinguishable from wild-type littermates. Heterozygous HDAC2 mutant mice show an unaltered composition but reduced associated deacetylase activity of corepressor complexes and exhibit a more severe phenotype than HDAC2-null mice. They display changes in brain architecture accompanied by premature expression of the key regulator protein kinase C delta. Our study reveals a dominant negative effect of catalytically inactive HDAC2 on specific corepressor complexes resulting in histone hyperacetylation, transcriptional derepression, and, ultimately, perinatal lethality.

Annual Research Review: Neural contributions to risk-taking in adolescence--developmental changes and individual differences.

Risk-taking, which involves voluntary choices for behaviors where outcomes remain uncertain, undergoes considerable developmental changes during childhood, adolescence, and early adulthood. In addition, risk-taking is thought to be a key element of many externalizing disorders, such as ADHD, delinquency, conduct disorder, and substance abuse. In this review, we will discuss the potential adaptive and nonadaptive properties of risk-taking in childhood and adolescence. We propose that the changes in brain architecture and function are a crucial element underlying these developmental trajectories. We first identify how subcortical and cortical interactions are important for understanding risk-taking behavior in adults. Next, we show how developmental changes in this network underlie changes in risk-taking behavior. Finally, we explore how these differences can be important for understanding externalizing behavioral disorders in childhood and adolescence. We conclude that longitudinal studies are of crucial importance for understanding these developmental trajectories, and many of these studies are currently underway.

The PTEN/mTOR pathway in autism spectrum disorders

Event Abstract Back to Event The PTEN/mTOR pathway in autism spectrum disorders Jason Howitt1* 1 The University of Melbourne, Florey Institute of Neuroscience and Mental Health, Australia Autism spectrum disorders (ASDs) are a common cause of neurodevelopmental disability and are presumed secondary to abnormal early brain development. Recent evidence implicates several hundred genes as risk factors for the disorder. This large genetic heterogeneity for ASD presents a substantial obstacle to developing therapies. To overcome this hurdle we have investigated a single gene variant syndrome involving PTEN, which causes autism with macrocephaly. PTEN negatively regulates the PI3K/AKT/mTOR signalling pathway which is centrally important to both normal brain development and human neurological disorders. We have created a new mouse model of PTEN loss during development (PTEN-ASD) that results in brain overgrowth, as well as a number of phenotypes associated with comorbidities observed in autism with macrocephaly patients. Behavioural testing indicated that developmental deletion of PTEN resulted in a loss of motor coordination and somatosensory reflexes. The PTEN-ASD mouse model was further investigated to understand the prenatal development of ASD and the changes in brain architecture that result in behavioural deficits. We demonstrate that this PTEN-ASD mouse model can be used for pre-clinical testing of drugs to rescue phenotypes of PTEN loss related to ASD. Keywords: autism, neurodevelopment, Pten, ASD, mTOR, single gene polymorphism Conference: 14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016. Presentation Type: Symposium 8: Molecular Pathways in Autism Spectrum Disorders Topic: 14th Meeting of the Asian-Pacific Society for Neurochemistry Citation: Howitt J (2016). The PTEN/mTOR pathway in autism spectrum disorders. Conference Abstract: 14th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00033 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 26 Jul 2016; Published Online: 11 Aug 2016. * Correspondence: Dr. Jason Howitt, The University of Melbourne, Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia, jason.howitt@florey.edu.au Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Jason Howitt Google Jason Howitt Google Scholar Jason Howitt PubMed Jason Howitt Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Toxic levels of ammonia in human brain abscess.

Brain abscesses could lead to cerebral symptoms through tissue destruction, edema, changes in brain architecture, and increased intracranial pressure. However, the possibility that the pus itself could contribute to symptoms has received little attention. Brain abscesses are areas of tissue destruction, proteolysis, and formation of free amino acids, which are energy substrates for bacteria and possible sources of ammonia. Ammonia is neurotoxic, may cause brain edema, and could contribute to the symptoms of brain abscesses. The authors analyzed the extracellular phase of pus from 14 patients with brain abscesses with respect to ammonia and amino acids. For comparison, CSF from 10 patients undergoing external ventricular drainage was included. The ammonia-forming ability of Streptococcus intermedius and Staphylococcus aureus, two common microbial isolates in brain abscesses, was studied in vitro. In brain abscesses ammonia was 15.5 mmol/L (median value; range 1.7-69.2 mmol/L). In CSF ammonia was 29 μmol/L (range 17-55 μmol/L; difference from value in pus: p < 0.001). The total concentration of amino acids in brain abscesses was 1.12-16 times higher than the ammonia concentration (p = 0.011). The median glucose value in pus was 0 mmol/L (range 0-2.1 mmol/L), lactate was 21 mmol/L (range 3.3-26.5 mmol/L), and pH was 6.8 (range 6.2-7.3). In vitro, S. intermedius and S. aureus formed ammonia at 6-7 mmol/L in 24 hours when incubated with 20 proteinogenic amino acids plus g-aminobutyric acid (GABA), taurine, and glutathione at 1 mmol/L. Intracerebral abscesses contain toxic levels of ammonia. At the concentrations found in pus, ammonia could contribute to the brain edema and the symptoms of brain abscesses.

Exposure to sublethal concentrations of a pesticide or predator cues induces changes in brain architecture in larval amphibians.

Naturally occurring environmental factors shape developmental trajectories to produce variable phenotypes. Such developmental phenotypic plasticity can have important effects on fitness, and has been demonstrated for numerous behavioral and morphological traits. However, surprisingly few studies have examined developmental plasticity of the nervous system in response to naturally occurring environmental variation, despite accumulating evidence for neuroplasticity in a variety of organisms. Here, we asked whether the brain is developmentally plastic by exposing larval amphibians to natural and anthropogenic factors. Leopard frog tadpoles were exposed to predator cues, reduced food availability, or sublethal concentrations of the pesticide chlorpyrifos in semi-natural enclosures. Mass, growth, survival, activity, larval period, external morphology, brain mass, and brain morphology were measured in tadpoles and after metamorphosis. Tadpoles in the experimental treatments had lower masses than controls, although developmental rates and survival were similar. Tadpoles exposed to predator cues or a high dose of chlorpyrifos had altered body shapes compared to controls. In addition, brains from tadpoles exposed to predator cues or a low dose of chlorpyrifos were narrower and shorter in several dimensions compared to control tadpoles and tadpoles with low food availability. Interestingly, the changes in brain morphology present at the tadpole stage did not persist in the metamorphs. Our results show that brain morphology is a developmentally plastic trait that is responsive to ecologically relevant natural and anthropogenic factors. Whether these effects on brain morphology are linked to performance or fitness is unknown.

Effects of Cannabis on the Adolescent Brain

This article reviews neuroimaging, neurocognitive, and preclinical findings on the effects of cannabis on the adolescent brain. Marijuana is the second most widely used intoxicant in adolescence, and teens who engage in heavy marijuana use often show disadvantages in neurocognitive performance, macrostructural and microstructural brain development, and alterations in brain functioning. It remains unclear whether such disadvantages reflect pre-existing differences that lead to increased substances use and further changes in brain architecture and behavioral outcomes. Future work should focus on prospective investigations to help disentangle dose-dependent effects from pre-existing effects, and to better understand the interactive relationships with other commonly abused substances (e.g., alcohol) to better understand the role of regular cannabis use on neurodevelopmental trajectories.

Multisite neuroimaging trials

The intent of this study is to review trends in multicenter neuroimaging trials and their value for research and implications for clinical treatment. The rise in availability of MRI for detecting disorders in the living brain has made it an attractive technology for assessing neural structure and function in a number of prominent diseases. Geographic factors underlying diseased populations coupled with complementary neuroimaging research programs have led to an increase in multicenter neuroimaging trials and consortia. Neuroimaging has become a major focus for multiinstitutional research in progressive changes in brain architecture, proxy biomarkers of treatment response, and the effects of disease on patterns of cognitive activation and connectivity. Notable consortia and research trial studies have focused on Alzheimer's disease, pediatric brain cancer, and fetal alcohol syndrome, in addition to multiinstitutional collaborative programs for mapping the normal brain. Such large-scale efforts necessitate close coordination of image data collection protocols, ontology development, computational requirements, concerted data archiving, and sharing. Multicenter neuroimaging trials, consortia, and collaboratives enable the acquisition of large-scale, purpose-driven datasets that can then be used by the broader community to model and predict clinical outcomes as well as guide clinicians in selecting treatment options for neurological disease.