Brain Volume Differences Research Articles

Compensatory Hippocampal Connectivity in Young Adults With Early-Stage Type 2 Diabetes.

Middle-aged to elderly patients with type 2 diabetes mellitus (T2DM) exhibit reduced functional connectivity and brain atrophy underlying cognitive decrements; however, little is known about brain abnormalities in young patients. To detect brain anatomical and functional changes in young patients with T2DM during the early disease stage. Case-control study. Tertiary referral hospital. Thirty-five young patients with T2DM (<40 years of age) with no detectable microangiopathy and 32 nondiabetic control subjects. None. Subjects underwent neuropsychological assessments and structural and resting-state functional MRI. Both voxel-based morphometry and resting-state functional connectivity analyses were performed. No significant differences in brain volume were observed between the patients with T2DM and the controls after controlling for age, sex, education, and body mass index. Compared with the controls, the patients showed greater connectivity of the left hippocampus with the left inferior frontal gyrus and the left inferior parietal lobule. Moreover, the enhanced functional connectivity of left hippocampus with the left inferior frontal gyrus significantly correlated with disease severity (urinary albumin-to-creatinine ratio) (r = 0.613, P < 0.001) and executive function (completion time of Stroop Color and Word Test) (r = -0.461, P = 0.005) after false discovery rate correction. Our findings suggest an adaptive compensation of brain function to counteract the insidious cognitive decrements during the early stage of T2DM. Additionally, the functional alterations occurring before changes in brain structure and peripheral microangiopathy might serve as early biomarkers related to cognitive decrements.

Novel findings from 2,838 Adult Brains on Sex Differences in Gray Matter Brain Volume

There is still disagreement among studies with respect to the magnitude, location, and direction of sex differences of local gray matter volume (GMV) in the human brain. Here, we applied a state-of-the-art technique examining GMV in a well-powered sample (n = 2,838) validating effects in two independent general-population cohorts, age range 21–90 years, measured using the same MRI scanner. More GMV in women than in men was prominent in medial and lateral prefrontal areas, the superior temporal sulcus, the posterior insula, and orbitofrontal cortex. In contrast, more GMV in men than in women was detected in subcortical temporal structures, such as the amygdala, hippocampus, temporal pole, fusiform gyrus, visual primary cortex, and motor areas (premotor cortex, putamen, anterior cerebellum). The findings in this large-scale study may clarify previous inconsistencies and contribute to the understanding of sex-specific differences in cognition and behavior.

Schizophrenia-associated genomic copy number variants and subcortical brain volumes in the UK Biobank

Schizophrenia is a highly heritable disorder for which anatomical brain alterations have been repeatedly reported in clinical samples. Unaffected at-risk groups have also been studied in an attempt to identify brain changes that do not reflect reverse causation or treatment effects. However, no robust associations have been observed between neuroanatomical phenotypes and known genetic risk factors for schizophrenia. We tested subcortical brain volume differences between 49 unaffected participants carrying at least one of the 12 copy number variants associated with schizophrenia in UK Biobank and 9063 individuals who did not carry any of the 93 copy number variants reported to be pathogenic. Our results show that CNV carriers have reduced volume in some of the subcortical structures previously shown to be reduced in schizophrenia. Moreover, these associations partially accounted for the association between pathogenic copy number variants and cognitive impairment, which is one of the features of schizophrenia.

Study the Longitudinal in vivo and Cross-Sectional ex vivo Brain Volume Difference for Disease Progression and Treatment Effect on Mouse Model of Tauopathy Using Automated MRI Structural Parcellation.

Brain volume measurements extracted from structural MRI data sets are a widely accepted neuroimaging biomarker to study mouse models of neurodegeneration. Whether to acquire and analyze data in vivo or ex vivo is a crucial decision during the phase of experimental designs, as well as data analysis. In this work, we extracted the brain structures for both longitudinal in vivo and single-time-point ex vivo MRI acquired from the same animals using accurate automatic multi-atlas structural parcellation, and compared the corresponding statistical and classification analysis. We found that most gray matter structures volumes decrease from in vivo to ex vivo, while most white matter structures volume increase. The level of structural volume change also varies between different genetic strains and treatment. In addition, we showed superior statistical and classification power of ex vivo data compared to the in vivo data, even after resampled to the same level of resolution. We further demonstrated that the classification power of the in vivo data can be improved by incorporating longitudinal information, which is not possible for ex vivo data. In conclusion, this paper demonstrates the tissue-specific changes, as well as the difference in statistical and classification power, between the volumetric analysis based on the in vivo and ex vivo structural MRI data. Our results emphasize the importance of longitudinal analysis for in vivo data analysis.

Cognitive Dysfunction in Type 1 Diabetes Mellitus.

We have summarized key studies assessing the epidemiology, mechanisms, and consequences of cognitive dysfunction (CD) in type 1 diabetes. In a number of studies, the severity of CD in type 1 diabetes was affected by the age of onset and duration, and the presence of proliferative retinopathy and autonomic neuropathy. Diabetes-related CD has been observed, not only in adults, but also in children and adolescents. Most neuroimaging studies of patients with type 1 diabetes did not show any differences in whole brain volumes; however, they did reveal selective deficits in gray matter volume or density within the frontal, posterior, and temporal cortex and subcortical gray matter. Studies of middle-age adults with long-standing type 1 diabetes using diffusion tensor imaging have demonstrated partial lesions in the white matter and decreased fractional anisotropy in posterior brain regions. The mechanisms underlying diabetes-related CD are very complex and include factors related to diabetes per se and to diabetes-related cardiovascular disease and microvascular dysfunction, including chronic hyperglycemia, hypoglycemia, macro- and microvascular disease, and increased inflammatory cytokine expression. These mechanisms might contribute to the development and progression of both vascular dementia and Alzheimer disease. Higher rates of CD and faster progression in type 1 diabetes can be explained by both the direct effects of altered glucose metabolism on the brain and diabetes-related cardiovascular disease. Because the presence and progression of CD significantly worsens the quality of life of patients with diabetes, further multidisciplinary studies incorporating the recent progress in both neuroimaging and type 1 diabetes management are warranted to investigate this problem.

Common Polygenic Variations for Psychiatric Disorders and Cognition in Relation to Brain Morphology in the General Pediatric Population.

This study examined the relation between polygenic scores (PGSs) for 5 major psychiatric disorders and 2 cognitive traits with brain magnetic resonance imaging morphologic measurements in a large population-based sample of children. In addition, this study tested for differences in brain morphology-mediated associations between PGSs for psychiatric disorders and PGSs for related behavioral phenotypes. Participants included 1,139 children from the Generation R Study assessed at 10 years of age with genotype and neuroimaging data available. PGSs were calculated for schizophrenia, bipolar disorder, major depression disorder, attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, intelligence, and educational attainment using results from the most recent genome-wide association studies. Image processing was performed using FreeSurfer to extract cortical and subcortical brain volumes. Greater genetic susceptibility for ADHD was associated with smaller caudate volume (strongest prior= 0.01: β=-0.07, p= .006). In boys, mediation analysis estimates showed that 11% of the association between the PGS for ADHD and the PGS attention problems was mediated by differences in caudate volume (n= 535), whereas mediation was not significant in girls or the entire sample. PGSs for educational attainment and intelligence showed positive associations with total brain volume (strongest prior= 0.5: β= 0.14, p= 7.12× 10-8; and β= 0.12, p= 6.87× 10-7, respectively). The present findings indicate that the neurobiological manifestation of polygenic susceptibility for ADHD, educational attainment, and intelligence involve early morphologic differences in caudate and total brain volumes in childhood. Furthermore, the genetic risk for ADHD might influence attention problems through the caudate nucleus in boys.

Absolute brain size predicts dog breed differences in executive function.

Large-scale phylogenetic studies of animal cognition have revealed robust links between absolute brain volume and species differences in executive function. However, past comparative samples have been composed largely of primates, which are characterized by evolutionarilyderived neural scaling rules. Therefore, it is currently unknown whether positive associations between brain volume and executive function reflect a broad-scale evolutionary phenomenon, or alternatively, a unique consequence of primate brain evolution. Domestic dogs provide a powerful opportunity for investigating this question due to their close genetic relatedness, but vast intraspecific variation. Using citizen science data on more than 7000 purebred dogs from 74 breeds, and controlling for genetic relatedness between breeds, we identify strong relationships between estimated absolute brain weight and breed differences in cognition. Specifically, larger-brained breeds performed significantly better on measures of short-term memory and self-control. However, the relationships between estimated brain weight and other cognitive measures varied widely, supporting domain-specific accounts of cognitive evolution. Our results suggest that evolutionary increases in brain size are positively associated with taxonomic differences in executive function, even in the absence of primate-like neuroanatomy. These findings also suggest that variation between dog breeds may present a powerful model for investigating correlated changes in neuroanatomy and cognition among closely related taxa.

Conditional False Discovery Rate Analysis Of Genome-Wide Association Studies Uncovers Genetic LOCI Shared Between Schizophrenia And Volumes Of Hippocampus, Putamen And Intracranial Volume

Schizophrenia (SCZ) is a severe mental disorder associated with differences in subcortical brain volumes and intracranial volume (ICV). However, the molecular mechanisms underlying these brain abnormalities are poorly understood. Subcortical brain structures regulate a variety of higher-order functions including emotion, movement, cognition, and reward-seeking behavior. Moreover, the majority of dopamine D2-receptors targeted by antipsychotic drugs are located in the basal ganglia, and treatment with antipsychotics may alter the volumes of the basal ganglia and the hippocampus. Hence, elucidating whether SCZ and brain structure volumes share causative factors may provide important insights into SCZ pathogenesis and its relationship to brain structure formation. Both SCZ and brain structure volumes have high heritability estimates (60-80% and 70–90%, respectively), and brain volume alterations are also present in unaffected relatives of patients with SCZ, suggesting that genetic risk underlying SCZ may also influence brain structure volumes. Despite this, a recent study reported no evidence of shared genetic influences between subcortical brain volumes and SCZ after using a battery of (frequentist) statistical tools to analyze genome-wide association study (GWAS) data of these phenotypes (Franke et al, 2016).Here, we used an alternative approach to address the question of genetic overlap, by applying the conditional false discovery rate (cFDR) approach. This statistical framework increases power for discovery by leveraging overlapping signal across GWAS. Importantly, cFDR analysis allows for identifying overlapping loci regardless of their direction of allelic effects. Applying the cFDR methodology, we have previously demonstrated shared genetic variants between SCZ, Alzheimer’s disease, immune-related diseases and related phenotypes, and substantially increased the number of identified risk loci. Here, we analyzed summary data (p-values and z-scores) from GWAS on seven subcortical brain volumes and ICV (n=11,840) from the ENIGMA Consortium (Enhancing NeuroImaging Genetics through Meta-Analysis) and GWAS on SCZ (n=82,315) from PGC (Psychiatric Genomics Consortium). To validate our approach and assess the replicability of the identified variants, we studied them in larger GWAS samples on ICV and hippocampal volume (n≥26,577).We observed polygenic overlap between SCZ and volumes of hippocampus, putamen, and ICV. Based on conjunctional cFDR<0.05, we identified two loci shared between SCZ and ICV implicating genes FOXO3 (rs10457180) and ITIH4 (rs4687658), two loci shared between SCZ and hippocampal volume implicating SLC4A10 (rs4664442) and SPATS2L (rs1653290), and two loci shared between SCZ and volume of putamen implicating DCC (rs4632195) and DLG2 (rs11233632). Three of the six identified loci are novel for SCZ. The loci shared between SCZ and hippocampal volume or ICV had not reached significance in the primary GWAS on brain phenotypes. Proving our point of increased power, two loci did reach genome-wide significance with ICV (rs10457180) and hippocampal volume (rs4664442) in the larger GWAS. In conclusion, the findings indicate that SCZ and volumes of hippocampus, putamen and ICV share genetic influences. The results provide new insights into the common genetic architecture underlying SCZ and brain structure formation, suggesting novel molecular genetic mechanisms.

Microstructural differences in visual white matter tracts in people with aniridia.

Aniridia is a panocular disorder characterized chiefly by iris hypoplasia. Most cases result from mutations of the PAX6 gene, which is important in both eye and brain development. In addition to ocular alterations, differences in global brain volume and functional connectivity have been reported in humans with aniridia. Understanding neural alterations in aniridia may require examination of possible differences in white matter structure, as few studies have assessed white matter in this population. The current study utilized diffusion-weighted imaging to assess white matter structure in 11 people with aniridia and 11 healthy comparison participants, matched for sex and age. A map of the local connectome was calculated to compare quantitative anisotropy (QA), an index of white matter tract density, in all white matter voxels, revealing subcomponents of white matter tracts with differing QA between people with aniridia and healthy comparisons. The analysis indicated that QA was lower for people with aniridia in portions of bilateral optic tract [t(20)=-4.23, P=0.001, d=-1.80], bilateral optic radiation [t(20)=-4.06, P=0.001, d=-1.73], forceps major [t(20)=-3.65, P=0.002, d=-1.55], bilateral superior longitudinal fasciculus [left: t(20)=-3.15, P=0.005, d=-1.34; right, t(20)=-4.28, P<0.001, d=-1.83], and right posterior corona radiata [t(20)=-3.19, P=0.006, d=-1.36]. These differences demonstrate that white matter structure is altered in people with aniridia in both visual tracts and associated posterior visual pathways.

Thalamic and ventricular volumes predict motor response to deep brain stimulation for Parkinson's disease

BackgroundBrain atrophy frequently occurs with Parkinson's disease (PD) and relates to increased motor symptoms of PD. The predictive value of neuroimaging-based measures of global and regional brain volume on motor outcomes in deep brain stimulation (DBS) remains unclear but potentially could improve patient selection and targeting. ObjectivesTo determine the predictive value of preoperative volumetric MRI measures of cortical and subcortical brain volume on motor outcomes of subthalamic nucleus (STN) DBS in PD. MethodsPreoperative T1 3D MP-RAGE structural brain MRI images were analyzed for each participant to determine subcortical, ventricular, and cortical volume and thickness. Change in Unified Parkinson's Disease Rating Scale (UPDRS) scores for subsection 3, representing motor outcomes, was computed preoperatively and postoperatively following DBS programming in 86 participants. A multiple linear regression analysis was performed to investigate the relationship between volumetric data and the effect of DBS on UPDRS 3 scores. ResultsLarger ventricular and smaller thalamic volumes predicted significantly less improvement of UPDRS 3 scores after STN DBS. ConclusionsOur findings demonstrate in PD that regional brain volumes, in particular thalamic and ventricular volumes, predict motor outcomes after DBS. Differences in regional brain volumes may alter electrode targeting, reflect a specific disease trait such as postoperative progression of subclinical dementia, or directly interfere with the action of DBS.

Does Family History of Alcohol Use Disorder Relate to Differences in Regional Brain Volumes? A Descriptive Review with New Data.

Differences in regional brain volumes as a function of family history (FH) of alcohol use disorder (AUD) have been reported, and it has been suggested that these differences might index genetic risk for AUD. However, results have been inconsistent. The aims of the current study were (i) to provide an updated descriptive review of the existing literature and (ii) to examine the association of FH with indices of subcortical volumes and cortical thickness in a sample of youth recruited based on FH status. To address aim 1, a literature search located 15 published studies comprising 1,735 participants. Studies were characterized according to population, analytic methods, regions of interest, and primary findings. To address the second aim, we examined volumetric and cortical thickness in a sample of 69 youth (mean age=19.71years, SD=0.79) recruited based on FH status and matched on drinking variables. Associations of sex and alcohol use with volumetric outcomes were also examined. Our descriptive review revealed an inconsistent pattern of results with respect to the presence, direction, and regional specificity of volumetric differences across FH groups. The most consistent finding, significantly smaller amygdala volumes in FH+ participants, was not replicated in all studies. In the current sample of youth, measures of subcortical volumes and cortical thickness did not significantly differ as a function of FH, sex, or their interaction. Evidence for FH group differences in regional brain volumes is inconsistent, and the current study failed to detect any group differences. Further research is needed to confirm the reproducibility of FH group differences and implications for AUD risk.

Smaller medial temporal lobe volumes in individuals with subjective cognitive decline and biomarker evidence of Alzheimer's disease—Data from three memory clinic studies

IntroductionPrevious studies showed associations of brain volume differences and biomarker evidence for Alzheimer's disease (AD) in subjective cognitive decline (SCD). The consistency of this finding across SCD studies has not been investigated. MethodsWe studied gray matter volume differences between SCD subjects with and without cerebrospinal fluid biomarker evidence for AD across three European memory clinic samples (German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia study, Amsterdam, Barcelona). Analysis of covariance models with samples and cerebrospinal fluid biomarkers as between-subject factors were calculated. ResultsA significant main effect for AD biomarker (Aβ42− > Aβ42+) in the left medial temporal lobe (MTL) was found, with the absence of main effects for sample or interaction effects between AD biomarker and sample. This indicates consistent lower left MTL volume across three samples in SCD subjects with abnormal Aβ42 levels. DiscussionOur results support the model that in the presence of AD pathology, SCD corresponds to the late preclinical stage (stage 2 of AD) with smaller MTL volumes.

A15943 Cerebral atrophy in patients with type 2 diabetes and left ventricular hypertrophy

Objectives: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of dementia. Left ventricular hypertrophy (LVH) is prevalent in T2DM and an independent predictor of cognitive impairment. In this preliminary analysis, we compared brain atrophy between healthy participants and T2DM, and those with T2DM according to the presence or not of LVH. Methods: Non-demented healthy participants without diabetes (n = 37, controls) participating in the Cognition And Neocortical Volume After Stroke study were compared to 39 patients with T2DM. A 3T MRI was undertaken and FreeSurfer v6.0 was used to perform volumetric segmentation of the MR images. Differences in total brain volume (TBV), mean cortical thickness and subcortical volumes were compared. T2DM patients also had an echocardiographic assessment of LVH and 24-hour blood pressure monitoring. Results: Compared to controls, T2DM patients were younger (mean ± SD) 63 ± 7 vs. 68 ± 6 years (p = 0.003), with more obesity (BMI 31 ± 6 vs. 26 ± 4, p < 0.0001) and hypertension (73 vs. 43%, p = 0.013). T2DM patients had significantly more atrophy of the amygdala (p = 0.016), nucleus accumbens (p = 0.001) and brainstem (p = 0.010). Differences remained significant after adjustment for age, education level, total intracranial volume (TIV), BMI and hypertension. T2DM patients with LVH (36%) had more atrophy in the amygdala (p = 0.020) and reduced TBV (p = 0.006) compared to T2DM patients without LVH. Differences in TBV were independent of sex, TIV and education level (p = 0.005). Conclusion: T2DM contributes to accelerated structural brain aging, manifesting as cerebral atrophy. The co-presence of LVH in T2DM may represent a risk factor for subsequent cognitive impairment and dementia.

Extra-axial cerebrospinal fluid in high-risk and normal-risk children with autism aged 2–4 years: a case-control study

We previously showed, in two separate cohorts, that high-risk infants who were later diagnosed with autism spectrum disorder had abnormally high extra-axial cerebrospinal fluid (CSF) volume from age 6-24 months. The presence of increased extra-axial CSF volume preceded the onset of behavioural symptoms of autism and was predictive of a later diagnosis of autism spectrum disorder. In this study, we aimed to establish whether increased extra-axial CSF volume is found in a large, independent sample of children diagnosed with autism spectrum disorder, whether extra-axial CSF remains abnormally increased beyond infancy, and whether it is present in both normal-risk and high-risk children with autism. In this case-control MRI study, children with autism spectrum disorder or with typical development aged 2-4 years were recruited from the community to the UC Davis MIND Institute Autism Phenome Project, based in Sacramento, CA, USA. The autism spectrum disorder group comprised children with autism spectrum disorder who were either normal risk (ie, from simplex families) or high risk (ie, from multiplex families). Measurements of extra-axial CSF volume, brain volume, head circumference, sleep problems, and familial risk status were derived from MRI and behavioural assessments. We applied a previously validated machine learning algorithm based on extra-axial CSF volume, brain volume, age, and sex to the current dataset. Between July 20, 2007, and Dec 13, 2012, 159 children with autism spectrum disorder (132 male, 27 female) and 77 with typical development (49 male, 28 female) underwent MRI scans. The autism spectrum disorder group had an average of 15·1% more extra-axial CSF than controls after accounting for differences in brain volume, weight, age, and sex (least-squares mean 116·74 cm3 [SE 3·33] in autism group vs 101·40 cm3 [3·93] in typical development group; p=0·007; Cohen's d = 0·39). Subgroups of normal-risk (n=132) and high-risk (n=27) children with autism spectrum disorder had nearly identical extra-axial CSF volumes (p=0·78), and both subgroups had significantly greater volumes than controls. Both extra-axial CSF volume (p=0·004) and brain volume (p<0·0001) uniquely contributed to enlarged head circumference in the autism spectrum disorder group (p=0·04). Increased extra-axial CSF volume was associated with greater sleep disturbances (p=0·03) and lower non-verbal ability (p=0·04). The machine learning algorithm correctly predicted autism spectrum disorder diagnosis with a positive predictive value of 83% (95% CI 76·2-88·3). Increased extra-axial CSF volume is a reliable brain anomaly that has now been found in three independent cohorts, comprising both high-risk and normal-risk children with autism spectrum disorder. Increased extra-axial CSF volume is detectable using conventional structural MRI scans from infancy through to age 3 years. These results suggest that increased extra-axial CSF volume could be an early stratification biomarker of a biologically based subtype of autism that might share a common underlying pathophysiology. US National Institutes of Health.

Reward-related brain structures are smaller in patients with schizophrenia and comorbid metabolic syndrome.

Metabolic syndrome (MS) is highly prevalent in schizophrenia and often a consequence of unhealthy behaviour. Reward-related brain areas might be associated with MS, since they play a major role in regulating health behaviour. This study examined the relationship between MS and brain volumes related to the reward system in schizophrenia. We included patients with schizophrenia, with MS (MS+; n=23), patients with schizophrenia, without MS (MS-; n=48), and healthy controls (n=54). Global brain volumes and volumes of (sub)cortical areas, part of the reward circuit, were compared between patients and controls. In case of a significant brain volume difference between patients and controls, the impact of MS in schizophrenia was examined. Patients had smaller total brain (TB; P=0.001), GM (P=0.010), larger ventricles (P=0.026), and smaller reward circuit volume (P<0.001) than controls. MS+ had smaller TB (P=0.017), GM (P=0.008), larger ventricles (P=0.015), and smaller reward circuit volume (P=0.002) than MS-. MS+ had smaller orbitofrontal cortex (OFC; P=0.002) and insula volumes (P=0.005) and smaller OFC (P=0.008) and insula cortical surface area (P=0.025) compared to MS-. In schizophrenia, structural brain volume reductions in areas of the reward circuitry appear to be related to comorbid MS.

Improving the SIENA performance using BEaST brain extraction

We present an improved image analysis pipeline to detect the percent brain volume change (PBVC) using SIENA (Structural Image Evaluation, using Normalization, of Atrophy) in populations with Alzheimer’s dementia. Our proposed approach uses the improved brain extraction mask from BEaST (Brain Extraction based on nonlocal Segmentation Technique) instead of the conventional BET (Brain Extraction Tool) for SIENA. We compared four varying options of BET as well as BEaST and applied these five methods to analyze scan-rescan MRIs in ADNI from 332 subjects, longitudinal ADNI MRIs from the same 332 subjects, their repeat scans over time, and OASIS longitudinal MRIs from 123 subjects. The results showed that BEaST brain masks were consistent in scan-rescan reproducibility. The cross-sectional scan-rescan error in the absolute percent brain volume difference measured by SIENA was smallest (p≤0.0187) with the proposed BEaST-SIENA. We evaluated the statistical power in terms of effect size, and the best performance was achieved with BEaST-SIENA (1.2789 for ADNI and 1.095 for OASIS). The absolute difference in PBVC between scan-dataset (volume change from baseline to year-1) and rescan-dataset (volume change from baseline repeat scan to year-1 repeat scan) was also the smallest with BEaST-SIENA compared to the BET-based SIENA and had the highest correlation when compared to the BET-based SIENA variants. In conclusion, our study shows that BEaST was robust in terms of reproducibility and consistency and that SIENA’s reproducibility and statistical power are improved in multiple datasets when used in combination with BEaST.

The Canadian Dementia Imaging Protocol: Harmonizing National Cohorts.

Harmonized protocols to collect imaging data must be devised, employed, and maintained in multicentric studies to reduce interscanner variability in subsequent analyses. To present a standardized protocol for multicentric research on dementia linked to neurodegeneration in aging, harmonized on all three major vendor platforms. The protocol includes a common procedure for qualification, quality control, and quality assurance and feasibility in large-scale studies. Prospective. The study involved a geometric phantom, a single individual volunteer, and 143 cognitively healthy, mild cognitively impaired, and Alzheimer's disease participants in a large-scale, multicentric study. MRI was perform with 3T scanners (GE, Philips, Siemens) and included 3D T1 w, PD/T2 w, , T2 w-FLAIR, diffusion, and BOLD resting state acquisitions. Measures included signal- and contrast-to-noise ratios (SNR and CNR, respectively), total brain volumes, and total scan time. SNR, CNR, and scan time were compared between scanner vendors using analysis of variance (ANOVA) and Tukey tests, while brain volumes were tested using linear mixed models. Geometric phantom T1 w SNR was significantly (P < 0.001) higher in Philips (mean: 71.4) than Siemens (29.5), while no significant difference was observed between vendors for T2 w (32.0 and 37.2, respectively, P = 0.243). Single individual volunteer T1 w CNR was higher in subcortical regions for Siemens (P < 0.001), while Philips had higher cortical CNR (P = 0.044). No significant difference in brain volumes was observed between vendors (P = 0.310/0.582/0.055). The average scan time was 41.0 minutes (SD: 2.8) and was not significantly different between sites (P = 0.071) and cognitive groups (P = 0.853). The harmonized Canadian Dementia Imaging Protocol suits the needs of studies that need to ensure quality MRI data acquisition for the measurement of brain changes across adulthood, due to aging, neurodegeneration, and other etiologies. A detailed description, exam cards, and operators' manual are freely available at the following site: www.cdip-pcid.ca. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:456-465.

Changes in neonatal regional brain volume associated with preterm birth and perinatal factors

BackgroundPreterm birth is associated with altered brain development, with younger gestational age (GA) at birth often associated with greater brain volume reduction. Such volume alterations at term equivalent age (TEA) have been found with differing magnitude across different brain regions, although this has mostly been investigated with regards to whole tissue volumes and large-scale subdivisions. In addition to degree of prematurity, many other perinatal factors have been found to influence brain structure and development in infants born preterm. We aimed to clarify the relationships between degree of prematurity and regional brain volumes at TEA, and between perinatal factors and regional brain volumes at TEA, in finer spatial detail. Methods285 preterm and term-born infants (GA at birth 24.6–42.1 weeks; 145 female; 59 born at term) were scanned at TEA. Data on perinatal factors were obtained by chart review, including sex, multiple birth, birthweight standard deviation (SD) score, postnatal growth and social risk. The Melbourne Children's Regional Infant Brain (M-CRIB) atlas was registered to the current sample, then 100 brain regions were labelled for volumetric analyses. Linear regressions with generalised estimating equations and likelihood ratio tests were performed to investigate whether GA at birth or perinatal factors were associated with regional volumes at TEA. ResultsYounger GA at birth was associated with smaller volumes at TEA in some regions including bilateral cerebral white matter, middle temporal gyri, amygdalae, pallidum and brainstem. In other regions, younger GA at birth was associated with larger volumes, including in primary visual, motor and somatosensory cortices. Positive associations between perinatal factors and regional volumes at TEA were found in many brain regions for birthweight SD score, and male sex, independent of GA at birth. These associations were seen on both univariable analyses, and multivariable analyses controlling for other perinatal factors. Social risk and multiple birth were generally not associated with regional brain volumes, and postnatal growth was associated with volume in many regions only after adjusting for other perinatal factors. ConclusionsThese results elucidate regional brain volume differences associated with preterm birth and perinatal factors at a more detailed parcellated level than previously reported, and contribute to understanding of the complex array of correlates of preterm birth.

Exploration of the Effect of Race on Cortical Current Flow Due to Transcranial Direct Current Stimulation: Comparison across Caucasian, Chinese, and Indian Standard Brains.

It is well known that genetic and environmental factors amongst others make different ethnic populations dissimilar reflected by the difference in overall skull and brain volume, shape, and size. We sought to investigate in this study the effects of race related morphological changes by comparing across standard Caucasian, Chinese and Indian templates on brain current flow due to transcranial Direct Current Stimulation. Findings indicate up to 1.4 fold variation in induced electrical field magnitude in both target and non-target regions across the electrode montage and average heads considered. The observed variation is similar to the variation observed in adults of Caucasian race indicating that variation observed due to race are not significantly more than within race variation.

Structural Magnetic Resonance Imaging Correlates of Aggression in Psychosis: A Systematic Review and Effect Size Analysis.

Background: Aggression in psychoses is of high clinical importance, and volumetric MRI techniques have been used to explore its structural brain correlates.Methods: We conducted a systematic review searching EMBASE, ScienceDirect, and PsycINFO through September 2017 using thesauri representing aggression, psychosis, and brain imaging. We calculated effect sizes for each study and mean Hedge's g for whole brain (WB) volume. Methodological quality was established using the PRISMA checklist (PROSPERO: CRD42014014461).Results: Our sample consisted of 12 studies with 470 patients and 155 healthy controls (HC). After subtracting subjects due to cohort overlaps, 314 patients and 96 HC remained. Qualitative analyses showed lower volumes of WB, prefrontal regions, temporal lobe, hippocampus, thalamus and cerebellum, and higher volumes of lateral ventricles, amygdala, and putamen in violent vs. non-violent people with schizophrenia. In quantitative analyses, violent persons with schizophrenia exhibited a significantly lower WB volume than HC (p = 0.004), and also lower than non-violent persons with schizophrenia (p = 0.007).Conclusions: We reviewed evidence for differences in brain volume correlates of aggression in persons with schizophrenia. Our results point toward a reduced whole brain volume in violent as opposed to non-violent persons with schizophrenia. However, considerable sample overlap in the literature, lack of reporting of potential confounding variables, and missing research on affective psychoses limit our explanatory power. To permit stronger conclusions, further studies evaluating structural correlates of aggression in psychotic disorders are needed.