Brain, language, and handedness: a family affair

The left planum temporale is a marker of left hemisphere language specialization. We investigated the effect of individual handedness and familial sinistrality on left planum temporale surface area and found the size is reduced in proportion with the number of left-handed immediate family members and is lowest when one's mother is left-handed. This reduction is independent of an individual's handedness or sex and has no counterpart in the right hemisphere

Fish Intake and MRI Burden of Cerebrovascular Disease in Older Adults

BACKGROUND AND OBJECTIVE: Fish intake may prevent cerebrovascular disease (CVD), yet the mechanisms are unclear, especially regarding its impact on subclinical damage. Assuming that fish may have pleiotropic effect on cerebrovascular health, we investigated the association of fish intake with global CVD burden based on brain MRI markers. METHODS: This cross-sectional analysis included participants from the Three-City Dijon population-based cohort (aged >/=65 years) without dementia, stroke, or history of hospitalized cardiovascular disease, who underwent brain MRI with automated assessment of white matter hyperintensities, visual detection of covert infarcts, and grading of dilated perivascular spaces. Fish intake was assessed through a frequency questionnaire and the primary outcome measure was defined as the first component of a factor analysis of mixed data applied to MRI markers. The association of fish intake with the CVD burden indicator was studied using linear regressions. RESULTS: In total, 1,623 participants (mean age, 72.3 years; 63% women) were included. The first component of factor analysis (32.4% of explained variance) was associated with higher levels of all three MRI markers. Higher fish intake was associated with lower CVD burden. In a model adjusted for total intracranial volume, compared to participants consuming fish /=4 times per week had a beta = -0.19 (95% CI, -0.37; -0.01) and beta = -0.30 (-0.57; -0.03) lower indicator of CVD burden, respectively (P trend /=75 years. For comparison, in the younger age group, consuming fish 2-3 times a week was roughly equivalent (in opposite direction) to the effect of hypertension. DISCUSSION: In this large population-based study, higher frequency of fish intake was associated with lower CVD burden, especially among participants younger than 75 years, suggesting a beneficial effect on brain vascular health before manifestation of overt brain disease. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in individuals without stroke or dementia, higher fish intake is associated with lower subclinical CVD at MRI

Cortical Terminations of the Inferior Fronto-Occipital and Uncinate Fasciculi: Anatomical Stem-Based Virtual Dissection

International audienceWe combined the neuroanatomists' approach of defining a fascicle as all fibers passing through its compact stem with diffusion-weighted tractography to investigate the cortical terminations of two association tracts, the inferior fronto-occipital fasciculus (IFOF) and the uncinate fasciculus (UF), which have recently been implicated in the ventral language circuitry. The aim was to provide a detailed and quantitative description of their terminations in 60 healthy subjects and to do so to apply an anatomical stem-based virtual dissection, mimicking classical post-mortem dissection, to extract with minimal a priori the IFOF and UF from tractography datasets. In both tracts, we consistently observed more extensive termination territories than their conventional definitions, within the middle and superior frontal, superior parietal and angular gyri for the IFOF and the middle frontal gyrus and superior, middle and inferior temporal gyri beyond the temporal pole for the UF. We revealed new insights regarding the internal organization of these tracts by investigating for the first time the frequency, distribution and hemispheric asymmetry of their terminations. Interestingly, we observed a dissociation between the lateral right-lateralized and medial left-lateralized fronto-occipital branches of the IFOF. In the UF, we observed a rightward lateralization of the orbito-frontal and temporal branches. We revealed a more detailed map of the terminations of these fiber pathways that will enable greater specificity for correlating with diseased populations and other behavioral measures. The limitations of the diffusion tensor model in this study are also discussed. We conclude that anatomical stem-based virtual dissection with diffusion tractography is a fruitful method for studying the structural anatomy of the human white matter pathways

Dementia and Stroke Risk Associated with Brain Artery Luminal Diameters

Background: It is unclear whether brain artery diameters measured on conventional T2-weighted brain MRI images relate to dementia and stroke outcomes across distinct populations. We aimed this study to evaluate the association of T2-weighted brain artery luminal diameters with dementia and stroke in three distinct population‑based studies. Methods: Three longitudinal population-based studies with 8420 adults \u3e40 years old (Northern Manhattan Study [NOMAS] from the United States, and the Rotterdam Study [RS], from the Netherlands, and Three-City, from France) with brain MRI scans obtained between 1999 and 2015. The median follow-up time for clinical events ranged between 7 and 12.5 years. We tested our hypothesis in each cohort separately due to local data‑sharing regulations. The exposure variable was brain carotid and basilar artery luminal diameters measured on MRI axial T2‑weighted scans. Multivariable hazard ratios (HRs) and their 95% confidence intervals (CI) expressed the risk of dementia and stroke (primary outcomes) associated with the lowest (\u3c5th) and highest (\u3e95th) percentiles of the rank‑normalized brain artery diameters compared to a reference group defined as the diameters distributed between the 5th and 95th percentiles. Secondary outcomes included total and vascular mortality, and fatal and nonfatal cardiovascular and coronary end points. Results: Among the three cohorts (mean age ranged from 65 to 73 y, ≥57% women), 335 participants developed dementia and 331 strokes. Compared with the reference group, participants with arterial diameters \u3e95th percentile had a higher risk of dementia (HR range 1.15-4.50) and any stroke (HR range 1.29-2.03). For secondary outcomes, participants with arterial diameters \u3e95th percentile had a consistent higher risk of coronary outcomes, vascular mortality and a composite of any vascular events. The results were less supportive of a higher risk of events among participants with arterial diameters \u3c5th percentile except for vascular mortality. Conclusions: Individuals with dilated brain arteries are at higher risk of dementia and vascular events. Our findings were consistency across distinct populations in spite of using a non-enhanced, conventional T2-weighted MRI sequence. Understanding the underlying physiopathology of the reported associations, particularly with dementia and stroke, might reveal novel vascular contributions to dementi

Hum Brain Mapp

Given the anatomical and functional similarities between the retina and the brain, the retina could be a "window" for viewing brain structures. We investigated the association between retinal nerve fiber layers (peripapillary retinal nerve fiber layer, ppRNFL; macular ganglion cell-inner plexiform layer, GC-IPL; and macular ganglion cell complex, GCC), and brain magnetic resonance imaging (MRI) parameters in young health adults. We included 857 students (mean age: 23.3 years, 71.3% women) from the i-Share study. We used multivariate linear models to study the cross-sectional association of each retinal nerve layer thickness assessed by spectral-domain optical coherence tomography (SD-OCT) with structural (volumes and cortical thickness), and microstructural brain markers, assessed on MRI globally and regionally. Microstructural MRI parameters included diffusion tensor imaging (DTI) and Neurite Orientation Dispersion and Density Imaging (NODDI). On global brain analysis, thicker ppRNFL, GC-IPL and GCC were all significantly associated with patterns of diffusion metrics consistent with higher WM microstructural integrity. In regional analyses, after multiple testing corrections, our results suggested significant associations of some retinal nerve layers with brain regional gray matter occipital volumes and with diffusion MRI parameters in a region involved in the visual pathway and in regions containing associative tracts. No associations were found with global volumes or with global or regional cortical thicknesses. Results of this study suggest that some retinal nerve layers may reflect brain structures. Further studies are needed to confirm these results in young subjects

Brain artery diameters and risk of dementia and stroke

INTRODUCTION: We tested the association of brain artery diameters with dementia and stroke risk in three distinct population-based studies using conventional T2-weighted brain magnetic resonance imaging (MRI) images.METHODS: We included 8420 adults &gt; 40 years old from three longitudinal population-based studies with brain MRI scans. We estimated and meta-analyzed the hazard ratios (HRs) of the brain and carotids and basilar diameters associated with dementia and stroke. RESULT: Overall and carotid artery diameters &gt; 95th percentile increased the risk for dementia by 1.74 (95% confidence interval [CI], 1.13–2.68) and 1.48 (95% CI, 1.12–1.96) fold, respectively. For stroke, meta-analyses yielded HRs of 1.59 (95% CI, 1.04–2.42) for overall arteries and 2.11 (95% CI, 1.45–3.08) for basilar artery diameters &gt; 95th percentile. DISCUSSION: Individuals with dilated brain arteries are at higher risk for dementia and stroke, across distinct populations. Our findings underline the potential value of T2-weighted brain MRI-based brain diameter assessment in estimating the risk of dementia and stroke.</p

Brain artery diameters and risk of dementia and stroke

INTRODUCTION: We tested the association of brain artery diameters with dementia and stroke risk in three distinct population-based studies using conventional T2-weighted brain magnetic resonance imaging (MRI) images.METHODS: We included 8420 adults &gt; 40 years old from three longitudinal population-based studies with brain MRI scans. We estimated and meta-analyzed the hazard ratios (HRs) of the brain and carotids and basilar diameters associated with dementia and stroke. RESULT: Overall and carotid artery diameters &gt; 95th percentile increased the risk for dementia by 1.74 (95% confidence interval [CI], 1.13–2.68) and 1.48 (95% CI, 1.12–1.96) fold, respectively. For stroke, meta-analyses yielded HRs of 1.59 (95% CI, 1.04–2.42) for overall arteries and 2.11 (95% CI, 1.45–3.08) for basilar artery diameters &gt; 95th percentile. DISCUSSION: Individuals with dilated brain arteries are at higher risk for dementia and stroke, across distinct populations. Our findings underline the potential value of T2-weighted brain MRI-based brain diameter assessment in estimating the risk of dementia and stroke.</p

Normative Modelling of Brain Morphometry Across the Lifespan With CentileBrain: Algorithm Benchmarking and Model Optimisation

The value of normative models in research and clinical practice relies on their robustness and a systematic comparison of different modelling algorithms and parameters; however, this has not been done to date. We aimed to identify the optimal approach for normative modelling of brain morphometric data through systematic empirical benchmarking, by quantifying the accuracy of different algorithms and identifying parameters that optimised model performance. We developed this framework with regional morphometric data from 37 407 healthy individuals (53% female and 47% male; aged 3-90 years) from 87 datasets from Europe, Australia, the USA, South Africa, and east Asia following a comparative evaluation of eight algorithms and multiple covariate combinations pertaining to image acquisition and quality, parcellation software versions, global neuroimaging measures, and longitudinal stability. The multivariate fractional polynomial regression (MFPR) emerged as the preferred algorithm, optimised with non-linear polynomials for age and linear effects of global measures as covariates. The MFPR models showed excellent accuracy across the lifespan and within distinct age-bins and longitudinal stability over a 2-year period. The performance of all MFPR models plateaued at sample sizes exceeding 3000 study participants. This model can inform about the biological and behavioural implications of deviations from typical age-related neuroanatomical changes and support future study designs. The model and scripts described here are freely available through CentileBrain

Association of a schizophrenia-risk nonsynonymous variant with putamen volume in adolescents

Importance Deviation from normal adolescent brain development precedes manifestations of many major psychiatric symptoms. Such altered developmental trajectories in adolescents may be linked to genetic risk for psychopathology. Objective To identify genetic variants associated with adolescent brain structure and explore psychopathologic relevance of such associations. Design, Setting, and Participants Voxelwise genome-wide association study in a cohort of healthy adolescents aged 14 years and validation of the findings using 4 independent samples across the life span with allele-specific expression analysis of top hits. Group comparison of the identified gene-brain association among patients with schizophrenia, unaffected siblings, and healthy control individuals. This was a population-based, multicenter study combined with a clinical sample that included participants from the IMAGEN cohort, Saguenay Youth Study, Three-City Study, and Lieber Institute for Brain Development sample cohorts and UK biobank who were assessed for both brain imaging and genetic sequencing. Clinical samples included patients with schizophrenia and unaffected siblings of patients from the Lieber Institute for Brain Development study. Data were analyzed between October 2015 and April 2018. Main Outcomes and Measures Gray matter volume was assessed by neuroimaging and genetic variants were genotyped by Illumina BeadChip. Results The discovery sample included 1721 adolescents (873 girls [50.7%]), with a mean (SD) age of 14.44 (0.41) years. The replication samples consisted of 8690 healthy adults (4497 women [51.8%]) from 4 independent studies across the life span. A nonsynonymous genetic variant (minor T allele of rs13107325 in SLC39A8, a gene implicated in schizophrenia) was associated with greater gray matter volume of the putamen (variance explained of 4.21% in the left hemisphere; 8.66; 95% CI, 6.59-10.81; P = 5.35 × 10−18; and 4.44% in the right hemisphere; t = 8.90; 95% CI, 6.75-11.19; P = 6.80 × 10−19) and also with a lower gene expression of SLC39A8 specifically in the putamen (t127 = −3.87; P = 1.70 × 10−4). The identified association was validated in samples across the life span but was significantly weakened in both patients with schizophrenia (z = −3.05; P = .002; n = 157) and unaffected siblings (z = −2.08; P = .04; n = 149). Conclusions and Relevance Our results show that a missense mutation in gene SLC39A8 is associated with larger gray matter volume in the putamen and that this association is significantly weakened in schizophrenia. These results may suggest a role for aberrant ion transport in the etiology of psychosis and provide a target for preemptive developmental interventions aimed at restoring the functional effect of this mutation