Brain charts for the human lifespan.

Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data ( http://www.brainchart.io/ ). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.

Maternal immune activation dysregulation of the fetal brain transcriptome and relevance to the pathophysiology of autism spectrum disorder.

Maternal immune activation (MIA) via infection during pregnancy is known to increase risk for autism spectrum disorder (ASD). However, it is unclear how MIA disrupts fetal brain gene expression in ways that may explain this increased risk. Here we examine how MIA dysregulates rat fetal brain gene expression (at a time point analogous to the end of the first trimester of human gestation) in ways relevant to ASD-associated pathophysiology. MIA downregulates expression of ASD-associated genes, with the largest enrichments in genes known to harbor rare highly penetrant mutations. MIA also downregulates expression of many genes also known to be persistently downregulated in the ASD cortex later in life and which are canonically known for roles in affecting prenatally late developmental processes at the synapse. Transcriptional and translational programs that are downstream targets of highly ASD-penetrant FMR1 and CHD8 genes are also heavily affected by MIA. MIA strongly upregulates expression of a large number of genes involved in translation initiation, cell cycle, DNA damage and proteolysis processes that affect multiple key neural developmental functions. Upregulation of translation initiation is common to and preserved in gene network structure with the ASD cortical transcriptome throughout life and has downstream impact on cell cycle processes. The cap-dependent translation initiation gene, EIF4E, is one of the most MIA-dysregulated of all ASD-associated genes and targeted network analyses demonstrate prominent MIA-induced transcriptional dysregulation of mTOR and EIF4E-dependent signaling. This dysregulation of translation initiation via alteration of the Tsc2-mTor-Eif4e axis was further validated across MIA rodent models. MIA may confer increased risk for ASD by dysregulating key aspects of fetal brain gene expression that are highly relevant to pathophysiology affecting ASD.

Bandwidth and Electron Correlation-Tuned Superconductivity in Rb_{0.8}Fe_{2}(Se_{1-z}S_{z})_{2}.

We present a systematic angle-resolved photoemission spectroscopy study of the substitution dependence of the electronic structure of Rb_{0.8}Fe_{2}(Se_{1-z}S_{z})_{2} (z=0, 0.5, 1), where superconductivity is continuously suppressed into a metallic phase. Going from the nonsuperconducting Rb_{0.8}Fe_{2}S_{2} to superconducting Rb_{0.8}Fe_{2}Se_{2}, we observe little change of the Fermi surface topology, but a reduction of the overall bandwidth by a factor of 2. Hence, for these heavily electron-doped iron chalcogenides, we have identified electron correlation as explicitly manifested in the quasiparticle bandwidth to be the important tuning parameter for superconductivity, and that moderate correlation is essential to achieving high T_{C}.

Effect of electron correlations on magnetic excitations in the isovalently doped iron-based superconductor Ba(Fe(1-x)Ru(x))(2)As(2).

Magnetic correlations in isovalently doped Ba(Fe(1-x)Ru(x))(2)As(2) (x = 0.25, T(c) = 14.5 K; x = 0.35, T(c) = 20 K) are studied by elastic and inelastic neutron scattering techniques. A relatively large superconducting spin gap accompanied by a weak resonance mode is observed in the superconducting state in both samples. In the normal state, the magnetic excitation intensity is dramatically reduced with increasing Ru doping toward the optimally doped regime. Our results favor that the weakening of the electron-electron correlations by Ru doping is responsible for the dampening of the resonance mode, as well as the suppression of the normal state antiferromagnetic correlations near the optimally doped regime in this system.

Neutron-diffraction measurements of an antiferromagnetic semiconducting phase in the vicinity of the high-temperature superconducting state of K(x)Fe(2-y)Se2.

The recently discovered K-Fe-Se high-temperature superconductor has caused heated debate regarding the nature of its parent compound. Transport, angle-resolved photoemission spectroscopy, and STM measurements have suggested that its parent compound could be insulating, semiconducting, or even metallic [M. H. Fang, H.-D. Wang, C.-H. Dong, Z.-J. Li, C.-M. Feng, J. Chen, and H. Q. Yuan, Europhys. Lett. 94, 27009 (2011); F. Chen et al., Phys. Rev. X 1, 021020 (2011); and W. Li et al., Phys. Rev. Lett. 109, 057003 (2012)]. Because the magnetic ground states associated with these different phases have not yet been identified and the relationship between magnetism and superconductivity is not fully understood, the real parent compound of this system remains elusive. Here, we report neutron-diffraction experiments that reveal a semiconducting antiferromagnetic (AFM) phase with rhombus iron vacancy order. The magnetic order of the semiconducting phase is the same as the stripe AFM order of the iron pnictide parent compounds. Moreover, while the sqrt[5]×sqrt[5] block AFM phase coexists with superconductivity, the stripe AFM order is suppressed by it. This leads us to conjecture that the new semiconducting magnetic ordered phase is the true parent phase of this superconductor.

Maternal transmission of a rare GABRB3 signal peptide variant is associated with autism.

Maternal 15q11-q13 duplication is the most common copy number variant in autism, accounting for ∼1-3% of cases. The 15q11-q13 region is subject to epigenetic regulation, and genomic copy number losses and gains cause genomic disorders in a parent-of-origin-specific manner. One 15q11-q13 locus encodes the GABA(A) receptor ß3 subunit gene (GABRB3), which has been implicated by several studies in both autism and absence epilepsy, and the co-morbidity of epilepsy in autism is well established. We report that maternal transmission of a GABRB3 signal peptide variant (P11S), previously implicated in childhood absence epilepsy, is associated with autism. An analysis of wild-type and mutant ß3 subunit-containing α1ß3γ2 or α3ß3γ2 GABA(A) receptors shows reduced whole-cell current and decreased ß3 subunit protein on the cell surface due to impaired intracellular ß3 subunit processing. We thus provide the first evidence of an association between a specific GABA(A) receptor defect and autism, direct evidence that this defect causes synaptic dysfunction that is autism relevant and the first maternal risk effect in the 15q11-q13 autism duplication region that is linked to a coding variant.

Event-related brain potentials: comparison between children and adults.

Event-related brain potentials in response to tachistoscopically presented stimuli were recorded from adults and children. Rare, nontarget stimuli (both novel and easily recognized) elicited different brain potentials in children and adults, while equally rare, target stimuli elicited similar potentials in children and adults.

Attentional activation of the cerebellum independent of motor involvement.

The cerebellum traditionally has been viewed as a neural device dedicated to motor control. Although recent evidence shows that it is involved in nonmotor operations as well, an important question is whether this involvement is independent of motor control and motor guidance. Functional magnetic resonance imaging was used to demonstrate that attention and motor performance independently activate distinct cerebellar regions. These findings support a broader concept of cerebellar function, in which the cerebellum is involved in diverse cognitive and noncognitive neurobehavioral systems, including the attention and motor systems, in order to anticipate imminent information acquisition, analysis, or action.

Electrophysiological signs of split-second decision-making.

When young adults detected auditory stimuli at split-second intervals, different components of the event-related brain potentials showed markedly different speeds of recovery. The P3 component (latency 300 to 350 milliseconds) was fully recovered at intervals of less than 1.0 second, while the N1--P2 components (latencies 100 to 180 milliseconds) were markedly attenuated with stimulus repetition even at longer interstimulus intervals. Thus, the N1--P2 recovers much more slowly than a subject's ability to evaluate signals, whereas the P3 appears to be generated at the same high rates as the decision processes with which it is associated.

The influence of magnetic order on the magnetoresistance anisotropy of Fe1 + δ-x Cu x Te.

We performed resistance measurements on [Formula: see text]Cu x Te with [Formula: see text] in the presence of in-plane applied magnetic fields, revealing a resistance anisotropy that can be induced at a temperature far below the structural and magnetic zero-field transition temperatures. The observed resistance anisotropy strongly depends on the field orientation with respect to the crystallographic axes, as well as on the field-cooling history. Our results imply a correlation between the observed features and the low-temperature magnetic order. Hysteresis in the angle-dependence indicates a strong pinning of the magnetic order within a temperature range that varies with the Cu content. The resistance anisotropy vanishes at different temperatures depending on whether an external magnetic field or a remnant field is present: the closing temperature is higher in the presence of an external field. For [Formula: see text] the resistance anisotropy closes above the structural transition, at the same temperature at which the zero-field short-range magnetic order disappears and the sample becomes paramagnetic. Thus we suggest that under an external magnetic field the resistance anisotropy mirrors the magnetic order parameter. We discuss similarities to nematic order observed in other iron pnictide materials.

Brainstem, cerebellar and limbic neuroanatomical abnormalities in autism.

Recent autopsy and/or quantitative magnetic resonance imaging studies of autistic patients have identified agenesis of the superior olive, dysgenesis of the facial nucleus, reduced numbers of Purkinje neurons, hypoplasia of the brainstem and posterior cerebellum, and increased neuron-packing density of the medial, cortical and central nuclei of the amygdala and the medial septum. As neurogenesis occurs for these different neuron types during approximately the fifth week of gestation, the possibility is raised that this may be a 'window of vulnerability' for autism; the likely etiologic heterogeneity of autism suggests that other windows of vulnerability are also possible.

The effects of post-growth annealing on the structural and magnetic properties of BaFe2As2.

We investigate the effects of post-growth annealing on the structural and magnetic properties of BaFe2As2. Magnetic susceptibility measurements, which exhibit a signal corresponding to the magnetic phase transition, and high-resolution x-ray diffraction measurements, which directly probe the structural order parameter, show that annealing causes the ordering temperatures of both the phase transitions to increase, sharpen and converge. In the as grown sample, our measurements show two distinct transitions corresponding to structural and magnetic ordering, which are separated in temperature by approximately 1 K. After 46 days (d) of annealing at 700 °C, the two become concurrent in temperature. These measurements demonstrate that the structural phase transition is second-order like when the magnetic and structural phase transitions are separated in temperature, and first-order like when the two phase transition temperatures coincide. This observation indicates that annealing causes the system to cross a hitherto undiscovered tricritical point. In addition, x-ray diffraction measurements show that the c-axis lattice parameter increases with annealing up to 30 d, but remains constant for longer annealing times. Comparisons of BaFe2As2 to SrFe2As2 are made when possible.

Increased distractibility in schizophrenic patients. Electrophysiologic and behavioral evidence.

The inability of schizophrenics to filter irrelevant information has often been implicated in the psychopathology of schizophrenia. Despite numerous attempts at characterizing the behavior of schizophrenics in the presence of distractors, evidence of increased distractibility has been equivocal due to the difficulty of assessing simultaneously the behavioral and neurophysiological effects of distracting stimuli. We report the results of an experiment in which event-related potential and performance measures were used to assess distractibility during reaction time tasks under different distracting conditions. The results supported the view of an increased distractibility in schizophrenic patients. Event-related potential data suggested that in schizophrenic patients, a reduced amount of processing resources is allocated to process external stimuli and attention is abnormally apportioned to task-irrelevant vs task-relevant stimuli.

Evidence for a cerebellar role in reduced exploration and stereotyped behavior in autism.

BACKGROUND: Although limited environmental exploration in autism is an obvious behavioral feature and may be a manifestation of "restricted interests" as described in DSM-IV criteria, there have been no behavioral or neurobiological studies of this important aspect of the disorder. Given consistent reports of cerebellar abnormality in autism, combined with animal research showing a relationship between exploration and the cerebellum, this study aimed to test the possible link between cerebellar abnormality and exploration in autism. METHODS: The relationship between visuospatial exploration, stereotyped motor movements, and magnetic resonance imaging measures of the cerebellar vermis, whole brain volume, and frontal lobes in 14 autistic and 14 normal children was investigated. Children were exposed to a large room with several exploration containers and instructed to play. Exploration behavior was videotaped and scored for percentage of time engaged in exploration, number of containers explored, as well as stereotyped movements. RESULTS: Children with autism spent significantly less time in active exploration and explored fewer containers overall than normal children. Measures of decreased exploration were significantly correlated with the magnitude of cerebellar hypoplasia of vermal lobules VI-VII in the autistic children, but no relationship to vermis size was found with normal control children. Further, measures of rates of stereotyped behavior were significantly negatively correlated with area measures of cerebellar vermis lobules VI-VII and positively correlated with frontal lobe volume in the autism sample. CONCLUSIONS: Reduced environmental exploration and repetitive behavior may have particularly important developmental consequences for children with autism because it may lead them to miss learning opportunities that fall outside their scope of interest. Our findings represent the first documented link between the restricted range of interests and stereotyped behaviors pathognomonic of autism and particular neuroanatomic sites.

Atypical patterns of cerebral motor activation in autism: a functional magnetic resonance study.

BACKGROUND: Early neurodevelopmental pathogenesis in autism potentially affects emerging functional maps, but little imaging evidence is available. METHODS: We studied eight male autistic and eight matched normal subjects, using functional magnetic resonance imaging during visually paced finger movement, compared to a control condition (visual stimulation in the absence of motor response). RESULTS: Groupwise analyses showed activation in contralateral perirolandic cortex, basal ganglia, and thalamus, bilateral supplementary motor area, and ipsilateral cerebellum for both groups. However, activations were less pronounced in the autism group. Direct group comparisons demonstrated greater activation in perirolandic and supplementary motor areas in the control group and greater activation (or reduced deactivation) in posterior and prefrontal cortices in the autism group. Intraindividual analyses further showed that strongest activations were consistently located along the contralateral central sulcus in control subjects but occurred in locations differing from individual to individual in the autism group. CONCLUSIONS: Our findings, though based on a rather small sample, suggest abnormal individual variability of functional maps and less distinct regional activation/deactivation patterns in autism. The observations may relate to known motor impairments in autism and are compatible with the general hypothesis of disturbances of functional differentiation in the autistic cerebrum.

Reduced size of corpus callosum in autism.

OBJECTIVE: To determine via magnetic resonance imaging if the posterior corpus callosum is reduced in the midline cross-sectional area in autistic patients, consistent with previous reports of parietal lobe abnormalities. DESIGN: Case-control study. SETTING: Tertiary care facility. PATIENTS AND OTHER PARTICIPANTS: Fifty-one autistic patients (45 males and six females; age range, 3 to 42 years), including both mentally retarded and nonretarded patients who met several diagnostic criteria for autism were prospectively selected. Fifty-one age-and sex-matched volunteer normal control subjects were also included. INTERVENTION: None. MAIN OUTCOME MEASURES: Computer-aided measurement of cross-sectional area, areas of five subregions, and thickness profile. RESULTS: Overall size reduction, concentrated in posterior subregions. CONCLUSIONS: Evidence is found of a reduced size of the corpus callosum in autistic patients. This reduction is localized to posterior regions, where parietal lobe fibers are known to project. This finding further supports the idea that parietal lobe involvement may be a consistent feature in autism.

Absence of magnetic resonance imaging evidence of pontine abnormality in infantile autism.

In vivo studies involving magnetic resonance imaging and studies of neuropathologic specimens have shown that autism is most consistently associated with developmental hypoplasia of the neocerebellum. We investigated whether the cerebellar hypoplasia was accompanied by gross structural abnormalities in the major input (cerebrocerebellar) and output (cerebrorubral) pathways to the cerebellum by measuring the area of the ventral pons (including the pontine nuclei and the transverse fibers) and the midbrain on midsagittal magnetic resonance images in 34 autistic and 44 subjects. The area of the entire pons and several regions of interest within the midbrain (including the superior and inferior colliculi) were also determined with midsagittal magnetic resonance images. We found no significant difference between measurements of the pons and midbrain in autistic and control subjects. Our data show no evidence of gross anatomic abnormalities in the input and output pathways to the cerebellum in autism, a finding that is consistent with previous studies of neuropathologic specimens; rather, the reduced size of the neocerebellum in autism appears to be the result of maldevelopment within the cerebellum itself.

Abnormal neuroanatomy in a nonretarded person with autism. Unusual findings with magnetic resonance imaging.

Recent studies of infantile autism using computed tomographic scanning emphasized the importance of studying cases of classic autism (Kanner's syndrome) without complicating conditions such as mental retardation. Computed tomographic scan studies of such patients reported no evidence of anatomical abnormalities of cerebral hemispheres or of subcortical structures, which are defined by landmarks such as the lateral ventricles and lentiform nuclei. Examination of the cerebellum was not mentioned. The most recent postmortem neuropathologic study reported significant cerebellar abnormality, but the study was of a severely retarded autistic individual. Using magnetic resonance imaging, we have found in vivo evidence of a significant and unusual cerebellar malformation in a person with the classic form of autism uncomplicated by mental retardation (current nonverbal IQ = 112), epilepsy, history of drug use, postnatal trauma, or disease. The finding showed hypoplasia of the declive, folium, and tuber in posterior vermis, but not of the anterior vermis, and hypoplasia of only the medial aspect of each cerebellar hemisphere. The right posterior cerebral hemisphere also showed pathologic findings.

Reduced cerebellar hemisphere size and its relationship to vermal hypoplasia in autism.

Cerebellar hemisphere size was calculated in 10 autistic and 8 normal control subjects by summing the cross-sectional areas of cerebellar hemisphere tissue measured on paramidline sagittal magnetic resonance images. The areas of two cerebellar vermal regions (lobules I through V and lobules VI through VII) were also measured using the midsagittal image. Our cumulative slice area measure of cerebellar hemisphere size was significantly smaller in the autistic subjects than in the control group. The cumulative slice area correlated positively with the area of vermal lobules VI through VII only in the autistic subjects. Our results indicated that the decreased size of the cerebellar hemispheres and vermal lobules VI through VII was associated with autism.