摘要：The genetic architecture of brain structure and function is largelyunknown. To investigate this, we carried out genome-wide association studies of3,144 functional and structural brain imaging phenotypes from UK Biobank(discovery dataset 8,428 subjects). Here we show that many of these phenotypesare heritable. We identify 148 clusters of associations between singlenucleotide polymorphisms and imaging phenotypes that replicate at P < 0.05,when we would expect 21 to replicate by chance. Notable significant,interpretable associations include: iron transport and storage genes, relatedto magnetic susceptibility of subcortical brain tissue; extracellular matrixand epidermal growth factor genes, associated with white matter micro-structureand lesions; genes that regulate mid-line axon development, associated withorganization of the pontine crossing tract; and overall 17 genes involved indevelopment, pathway signalling and plasticity. Our results provide insightsinto the genetic architecture of the brain that are relevant to neurologicaland psychiatric disorders, brain development and ageing.
参考文献：Genome-wide association studies of brain imaging phenotypes in UKBiobank. Nature. 2018 Oct;562(7726):210-216.
Risk of stroke and brain atrophy in laterlife relate to levels of cardiovascular risk in early adulthood. However, it isunknown whether cerebrovascular changes are present in young adults.
To examine relationships between modifiablecardiovascular risk factors and cerebrovascular structure, function, and whitematter integrity in young adults.
DESIGN, SETTING, AND PARTICIPANTS:
A cross-sectional observational study of125 young adults (aged 18-40 years) without clinical evidence ofcerebrovascular disease. Data collection was completed between August 2014 andMay 2016 at the University of Oxford, United Kingdom. Final data collection wascompleted on May 31, 2016.
The number of modifiable cardiovascularrisk factors at recommended levels, based on the following criteria: body massindex (BMI) <25; highest tertile of cardiovascular fitness and/or physicalactivity; alcohol consumption <8 drinks/week; nonsmoker for >6 months;blood pressure on awake ambulatory monitoring <130/80 mm Hg; anonhypertensive diastolic response to exercise (peak diastolic blood pressure<90 mm Hg); total cholesterol <200 mg/dL; and fasting glucose<100mg/dL. Each risk factor at the recommended level was assigned a value of1, and participants were categorized from 0-8, according to the number of riskfactors at recommended levels, with higher numbers indicating healthier riskcategories.
MAIN OUTCOMES AND MEASURES:
Cerebral vessel density, caliber andtortuosity, brain white matter hyperintensity lesion count. In a subgroup(n = 52), brain blood arrival time and cerebral blood flow assessed by brainmagnetic resonance imaging (MRI).
A total of 125 participants, mean (SD) age25 (5) years, 49% women, with a mean (SD) score of 6.0 (1.4) modifiablecardiovascular risk factors at recommended levels, completed the cardiovascularrisk assessment and brain MRI protocol. Cardiovascular risk factors werecorrelated with cerebrovascular morphology and white matter hyperintensitycount in multivariable models. For each additional modifiable risk factorcategorized as healthy, vessel density was greater by 0.3 vessels/cm3 (95% CI,0.1-0.5; P = .003), vessel caliber was greater by 8 μm (95% CI, 3-13; P = .01),and white matter hyperintensity lesions were fewer by 1.6 lesions (95% CI, -3.0to -0.5; P = .006). Among the 52 participants with available data, cerebralblood flow varied with vessel density and was 2.5 mL/100 g/min higher for eachhealthier category of a modifiable risk factor (95% CI, 0.16-4.89; P = .03).
CONCLUSIONS AND RELEVANCE:
In this preliminary study involving youngadults without clinical evidence of cerebrovascular disease, a greater numberof modifiable cardiovascular risk factors at recommended levels was associatedwith higher cerebral vessel density and caliber, higher cerebral blood flow,and fewer white matter hyperintensities. Further research is needed to verifythese findings and determine their clinical importance.
Association of Cardiovascular Risk FactorsWith MRI Indices of Cerebrovascular Structure and Function and White MatterHyperintensities in Young Adults. JAMA. 2018 Aug 21;320(7):665-673.
摘要：Non-human primate neuroimaging is a rapidly growing area of researchthat promises to transform and scale translational and cross-speciescomparative neuroscience. Unfortunately, the technological and methodologicaladvances of the past two decades have outpaced the accrual of data, which is particularlychallenging given the relatively few centers that have the necessary facilitiesand capabilities. The PRIMatE Data Exchange (PRIME-DE) addresses this challengeby aggregating independently acquired non-human primate magnetic resonanceimaging (MRI) datasets and openly sharing them via the InternationalNeuroimaging Data-sharing Initiative (INDI). Here, we present the rationale,design, and procedures for the PRIME-DE consortium, as well as the initialrelease, consisting of 25 independent data collections aggregated across 22sites (total = 217 non-human primates). We also outline the unique pitfalls andchallenges that should be considered in the analysis of non-human primate MRIdatasets, including providing automated quality assessment of the contributeddatasets.
参考文献：An Open Resource for Non-human Primate Imaging. Neuron. 2018 Oct10;100(1):61-74.
四. 《Nature neuroscience》：基因表达和全脑功能连接整合分析揭示小鼠海马的层级功能网络。
Understanding the organization of thehippocampus is fundamental to understanding brain function related to learning,memory, emotions, and diseases such as Alzheimer's disease. Physiologicalstudies in humans and rodents have suggested that there is both structural andfunctional heterogeneity along the longitudinal axis of the hippocampus. However,the recent discovery of discrete gene expression domains in the mousehippocampus has provided the opportunity to re-evaluate hippocampalconnectivity. To integrate mouse hippocampal gene expression and connectivity,we mapped the distribution of distinct gene expression patterns in mousehippocampus and subiculum to create the Hippocampus Gene Expression Atlas(HGEA). Notably, previously unknown subiculum gene expression patterns revealeda hidden laminar organization. Guided by the HGEA, we constructed the mostdetailed hippocampal connectome available using Mouse Connectome Project (http://www.mouseconnectome.org ) tract tracing data. Our results define thehippocampus' multiscale network organization and elucidate each subnetwork'sunique brain-wide connectivity patterns.
参考文献：Integration of gene expression and brain-wide connectivity revealsthe multiscale organization of mouse hippocampal networks. Nat Neurosci. 2018Nov;21(11):1628-1643.
摘要：Brain size variation over primate evolution and human development isassociated with shifts in the proportions of different brain regions.Individual brain size can vary almost twofold among typically developinghumans, but the consequences of this for brain organization remain poorlyunderstood. Using in vivo neuroimaging data from more than 3000 individuals, wefind that larger human brains show greater areal expansion in distributedfrontoparietal cortical networks and related subcortical regions than inlimbic, sensory, and motor systems. This areal redistribution recapitulates corticalremodeling across evolution, manifests by early childhood in humans, and islinked to multiple markers of heightened metabolic cost and neuronalconnectivity. Thus, human brain shape is systematically coupled to naturallyoccurring variations in brain size through a scaling map that integratesspatiotemporally diverse aspects of neurobiology.
参考文献：Normative brain size variation and brain shape diversity in humans. Science.2018 Jun 15;360(6394):1222-1227.
Patterns of spontaneous brain activity,typically measured in humans at rest with fMRI, are used routinely to assessthe brain's functional organization. The mechanisms that generate andcoordinate the underlying neural fluctuations are largely unknown. Here weinvestigate the hypothesis that the nucleus basalis of Meynert (NBM), theprincipal source of widespread cholinergic and GABAergic projections to thecortex, contributes critically to such activity. We reversibly inactivated twodistinct sites of the NBM in macaques while measuring fMRI activity across thebrain. We found that inactivation led to strong, regionalized suppression ofshared or "global" signal components of cortical fluctuationsipsilateral to the injection. At the same time, the commonly studied resting-statenetworks retained their spatial structure under this suppression. The resultsindicate that the NBM contributes selectively to the global component offunctional connectivity but plays little if any role in the specificcorrelations that define resting-state networks.
参考文献：The Basal Forebrain Regulates Global Resting-State fMRIFluctuations. Neuron. 2018 Feb 21;97(4):940-952.
七. 《Nature neuroscience》：fMRI研究揭示感知决策变化的神经机制。
摘要：Changing one's mind on the basis of new evidence is a hallmark ofcognitive flexibility. To revise our confidence in a previous decision, weshould use new evidence to update beliefs about choice accuracy. How thisprocess unfolds in the human brain, however, remains unknown. Here wemanipulated whether additional sensory evidence supports or negates a previousmotion direction discrimination judgment while recording markers of neuralactivity in the human brain using fMRI. A signature of post-decision evidence(change in log-odds correct) was selectively observed in the activity ofposterior medial frontal cortex. In contrast, distinct activity profiles inanterior prefrontal cortex mediated the impact of post-decision evidence onsubjective confidence, independently of changes in decision value. Together ourfindings reveal candidate neural mediators of post-decisional changes of mindin the human brain and indicate possible targets for ameliorating deficits incognitive flexibility.
参考文献：Neural mediators of changes of mind about perceptual decisions. NatNeurosci. 2018 Apr;21(4):617-624.
摘要：Macroscopic cortical networks are important for cognitive function,but it remains challenging to construct anatomically plausible individualstructural connectomes from human neuroimaging. We introduce a new techniquefor cortical network mapping based on inter-regional similarity of multiplemorphometric parameters measured using multimodal MRI. In three cohorts (twohuman, one macaque), we find that the resulting morphometric similaritynetworks (MSNs) have a complex topological organization comprising modules andhigh-degree hubs. Human MSN modules recapitulate known cortical cytoarchitectonicdivisions, and greater inter-regional morphometric similarity was associatedwith stronger inter-regional co-expression of genes enriched for neuronalterms. Comparing macaque MSNs with tract-tracing data confirmed thatmorphometric similarity was related to axonal connectivity. Finally, variationin the degree of human MSN nodes accounted for about 40% of between-subjectvariability in IQ. Morphometric similarity mapping provides a novel, robust,and biologically plausible approach to understanding how human corticalnetworks underpin individual differences in psychological functions.
参考文献：Morphometric Similarity Networks Detect Microscale CorticalOrganization and Predict Inter-Individual Cognitive Variation. Neuron. 2018 Jan3;97(1):231-247.e7.
Patients with schizophrenia (SCZ)experience chronic cognitive deficits. Histone deacetylases (HDACs) are enzymesthat regulate cognitive circuitry; however, the role of HDACs in cognitivedisorders, including SCZ, remains unknown in humans. We previously determinedthat HDAC2 mRNA levels were lower in dorsolateral prefrontal cortex (DLPFC)tissue from donors with SCZ compared with controls. Here we investigated therelationship between in vivo HDAC expression and cognitive impairment inpatients with SCZ and matched healthy controls using [11C]Martinostat positronemission tomography (PET).
In a case-control study, relative[11C]Martinostat uptake was compared between 14 patients with SCZ orschizoaffective disorder (SCZ/SAD) and 17 controls using hypothesis-drivenregion-of-interest analysis and unbiased whole brain voxel-wise approaches.Clinical measures, including the MATRICS consensus cognitive battery, wereadministered.
Relative HDAC expression was lower in theDLPFC of patients with SCZ/SAD compared with controls, and HDAC expressionpositively correlated with cognitive performance scores across groups. Patientswith SCZ/SAD also showed lower relative HDAC expression in the dorsomedialprefrontal cortex and orbitofrontal gyrus, and higher relative HDAC expressionin the cerebral white matter, pons, and cerebellum compared with controls.
These findings provide in vivo evidence ofHDAC dysregulation in patients with SCZ and suggest that altered HDACexpression may impact cognitive function in humans.
National Institute of Mental Health (NIMH),Brain and Behavior Foundation, Massachusetts General Hospital (MGH), AthinoulaA. Martinos Center for Biomedical Imaging, National Institute of BiomedicalImaging and Bioengineering (NIBIB), NIH Shared Instrumentation Grant Program.
参考文献：PET neuroimaging reveals histone deacetylase dysregulation inschizophrenia. J Clin Invest. 2018 Dec 10. pii: 123743.
摘要：People's ability to think creatively is a primary means oftechnological and cultural progress, yet the neural architecture of the highlycreative brain remains largely undefined. Here, we employed a recentlydeveloped method in functional brain imaging analysis-connectome-basedpredictive modeling-to identify a brain network associated with high-creativeability, using functional magnetic resonance imaging (fMRI) data acquired from163 participants engaged in a classic divergent thinking task. At thebehavioral level, we found a strong correlation between creative thinkingability and self-reported creative behavior and accomplishment in the arts andsciences (r = 0.54). At the neural level, we found a pattern of functionalbrain connectivity related to high-creative thinking ability consisting offrontal and parietal regions within default, salience, and executive brainsystems. In a leave-one-out cross-validation analysis, we show that this neuralmodel can reliably predict the creative quality of ideas generated by novelparticipants within the sample. Furthermore, in a series of external validationanalyses using data from two independent task fMRI samples and a largetask-free resting-state fMRI sample, we demonstrate robust prediction ofindividual creative thinking ability from the same pattern of brainconnectivity. The findings thus reveal a whole-brain network associated withhigh-creative ability comprised of cortical hubs within default, salience, andexecutive systems-intrinsic functional networks that tend to work inopposition-suggesting that highly creative people are characterized by theability to simultaneously engage these large-scale brain networks.
参考文献：Robust prediction of individual creative ability from brainfunctional connectivity. Proc Natl Acad Sci U S A. 2018 Jan30;115(5):1087-1092.
27、神经科学临床和基础Learning & Memory亚群；