scholarly journals Mapping cortical brain asymmetry in 17,141 healthy individuals worldwide via the ENIGMA Consortium

2018 ◽  
Vol 115 (22) ◽  
pp. E5154-E5163 ◽  
Author(s):  
Xiang-Zhen Kong ◽  
Samuel R. Mathias ◽  
Tulio Guadalupe ◽  
David C. Glahn ◽  
Barbara Franke ◽  
...  

Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here, the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium presents the largest-ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and intracranial volume. Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets (n = 1,443 and 1,113, respectively), we found several asymmetries showing significant, replicable heritability. The structural asymmetries identified and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.

2017 ◽  
Author(s):  
Xiang-Zhen Kong ◽  
Samuel R. Mathias ◽  
Tulio Guadalupe ◽  
Christoph Abé ◽  
Ingrid Agartz ◽  
...  

AbstractHemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here the ENIGMA consortium presents the largest ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and brain size (indexed by intracranial volume). Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets (N = 1,443 and 1,113, respectively), we found several asymmetries showing modest but highly reliable heritability. The structural asymmetries identified, and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.Significance StatementLeft-right asymmetry is a key feature of the human brain's structure and function. It remains unclear which cortical regions are asymmetrical on average in the population, and how biological factors such as age, sex and genetic variation affect these asymmetries. Here we describe by far the largest ever study of cerebral cortical brain asymmetry, based on data from 17,141 participants. We found a global anterior-posterior 'torque' pattern in cortical thickness, together with various regional asymmetries at the population level, which have not been previously described, as well as effects of age, sex, and heritability estimates. From these data, we have created an on-line resource that will serve future studies of human brain anatomy in health and disease.


2016 ◽  
Vol 46 (10) ◽  
pp. 2083-2096 ◽  
Author(s):  
G. Roberts ◽  
R. Lenroot ◽  
A. Frankland ◽  
P. K. Yeung ◽  
N. Gale ◽  
...  

BackgroundFronto-limbic structural brain abnormalities have been reported in patients with bipolar disorder (BD), but findings in individuals at increased genetic risk of developing BD have been inconsistent. We conducted a study in adolescents and young adults (12–30 years) comparing measures of fronto-limbic cortical and subcortical brain structure between individuals at increased familial risk of BD (at risk; AR), subjects with BD and controls (CON). We separately examined cortical volume, thickness and surface area as these have distinct neurodevelopmental origins and thus may reflect differential effects of genetic risk.MethodWe compared fronto-limbic measures of grey and white matter volume, cortical thickness and surface area in 72 unaffected-risk individuals with at least one first-degree relative with bipolar disorder (AR), 38 BD subjects and 72 participants with no family history of mental illness (CON).ResultsThe AR group had significantly reduced cortical thickness in the left pars orbitalis of the inferior frontal gyrus (IFG) compared with the CON group, and significantly increased left parahippocampal gyral volume compared with those with BD.ConclusionsThe finding of reduced cortical thickness of the left pars orbitalis in AR subjects is consistent with other evidence supporting the IFG as a key region associated with genetic liability for BD. The greater volume of the left parahippocampal gyrus in those at high risk is in line with some prior reports of regional increases in grey matter volume in at-risk subjects. Assessing multiple complementary morphometric measures may assist in the better understanding of abnormal developmental processes in BD.


2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S195-S195
Author(s):  
Mathilde Antoniades ◽  
Igor Nenadic ◽  
Tilo Kircher ◽  
Alex Krug ◽  
Tina Meller ◽  
...  

Abstract Background Cortical neuroanatomical abnormalities have been reported along a continuum between individuals with chronic schizophrenia, first-episode psychosis, clinical high risk for psychosis, and healthy individuals self-reporting subclinical psychotic-like experiences (or schizotypy). Recently, the Schizophrenia Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) consortium provided meta-analytic evidence for robust cortical thickness abnormalities in schizophrenia, while also indicating that these abnormalities are influenced by illness severity and treatment with antipsychotic medications. In this context, schizotypy research allows the investigation of cortical neuroanatomy associated with the expression of subclinical psychotic-like symptoms without the potential influence of a psychotic illness, its severity, or the use of antipsychotics. This study presents the first large-scale imaging meta-analysis of cortical thickness in schizotypy using standardized methods from 23 datasets worldwide. Methods Cortical thickness and surface area were assessed in MRI scans of 2,695 healthy individuals (mean [range] age of 29.1 [17–55.8], 46.3% male) who had also completed validated self-report schizotypy questionnaires. Each site processed their local T1-weighted MRI scans using FreeSurfer and, following the protocol outlined in the ENIGMA Schizophrenia Working Group study, extracted cortical thickness for 70 Desikan-Killiany (DK) atlas regions (34 regions per hemisphere + left and right hemisphere mean thickness). At each site, partial correlation analyses were performed between regional cortical thickness by ROI and total schizotypy scores in R, predicting the left, right and mean cortical thickness, adjusting for sex, age and site. Random-effects meta-analyses of partial correlation effect sizes for each of the DK atlas regions were performed using R’s metafor package. False discovery rate (pFDR < .05) was used to control for multiple comparisons. Results We found significant positive associations between subclinical psychotic-like experiences and mean cortical thickness of the medial orbitofrontal cortex (r = .077; pFDR = .006) and the frontal pole (r = .073; pFDR = .006). When assessed separately by hemisphere, meta-analysis revealed a significant positive association between subclinical psychotic-like experiences and cortical thickness of the left medial orbitofrontal cortex (r = .066; pFDR = .044), and at trend-level with the right medial orbitofrontal cortex (r = .062; pFDR = .053) and the left frontal pole (r = .062; pFDR = .053). No significant associations were observed for surface area. Discussion Worldwide cooperative analyses of large-scale brain imaging data support a profile of cortical thickness abnormalities involving prefrontal cortical regions positively related to schizotypy in healthy individuals. These findings are not secondary to potential influences of disease chronicity or antipsychotic medication on the neuroanatomical correlates of psychotic-like experiences. The directionality of the observed meta-analytical effects in schizotypy is opposite to those previously reported in patients with schizophrenia (i.e., thinner cortex). The present findings of increased thickness may indicate early microstructural deficits (e.g. in myelination) that contribute to vulnerability for psychosis. Alternatively, these may reflect mechanisms of resilience associated with the expression of subclinical manifestations of psychotic symptoms in otherwise healthy individuals.


2021 ◽  
pp. 1-14
Author(s):  
Helena M. Blumen ◽  
Emily Schwartz ◽  
Gilles Allali ◽  
Olivier Beauchet ◽  
Michele Callisaya ◽  
...  

Background: The motoric cognitive risk (MCR) syndrome is a pre-clinical stage of dementia characterized by slow gait and cognitive complaint. Yet, the brain substrates of MCR are not well established. Objective: To examine cortical thickness, volume, and surface area associated with MCR in the MCR-Neuroimaging Consortium, which harmonizes image processing/analysis of multiple cohorts. Methods: Two-hundred MRIs (M age 72.62 years; 47.74%female; 33.17%MCR) from four different cohorts (50 each) were first processed with FreeSurfer 6.0, and then analyzed using multivariate and univariate general linear models with 1,000 bootstrapped samples (n-1; with resampling). All models adjusted for age, sex, education, white matter lesions, total intracranial volume, and study site. Results: Overall, cortical thickness was lower in individuals with MCR than in those without MCR. There was a trend in the same direction for cortical volume (p = 0.051). Regional cortical thickness was also lower among individuals with MCR than individuals without MCR in prefrontal, insular, temporal, and parietal regions. Conclusion: Cortical atrophy in MCR is pervasive, and include regions previously associated with human locomotion, but also social, cognitive, affective, and motor functions. Cortical atrophy in MCR is easier to detect in cortical thickness than volume and surface area because thickness is more affected by healthy and pathological aging.


2017 ◽  
Author(s):  
Stuart J. Ritchie ◽  
David Alexander Dickie ◽  
Simon R. Cox ◽  
Maria del C. Valdés Hernández ◽  
Alison Pattie ◽  
...  

AbstractFully characterizing age differences in the brain is a key task for combatting ageing-related cognitive decline. Using propensity score matching on two independent, narrow-age cohorts, we used data on childhood cognitive ability, socioeconomic background, and intracranial volume to match participants at mean age 92 years (n = 42) to very similar participants at mean age 73 (n = 126). Examining a variety of global and regional structural neuroimaging variables, there were large differences in grey and white matter volumes, cortical surface area, cortical thickness, and white matter hyperintensity volume and spatial extent. In a mediation analysis, the total volume of white matter hyperintensities and total cortical surface area jointly mediated 24.9% of the relation between age and general cognitive ability (tissue volumes and cortical thickness were not significant mediators in this analysis). These findings provide an unusual and valuable perspective on neurostructural ageing, in which brains from the eighth and tenth decades of life differ widely despite the same cognitive, socio-economic, and brain-volumetric starting points.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Teija Kujala ◽  
Aleksi J. Sihvonen ◽  
Anja Thiede ◽  
Peter Palo-oja ◽  
Paula Virtala ◽  
...  

AbstractDevelopmental dyslexia (DD) is the most prevalent neurodevelopmental disorder with a substantial negative influence on the individual’s academic achievement and career. Research on its neuroanatomical origins has continued for half a century, yielding, however, inconsistent results, lowered total brain volume being the most consistent finding. We set out to evaluate the grey matter (GM) volume and cortical abnormalities in adult dyslexic individuals, employing a combination of whole-brain voxel- and surface-based morphometry following current recommendations on analysis approaches, coupled with rigorous neuropsychological testing. Whilst controlling for age, sex, total intracranial volume, and performance IQ, we found both decreased GM volume and cortical thickness in the left insula in participants with DD. Moreover, they had decreased GM volume in left superior temporal gyrus, putamen, globus pallidus, and parahippocampal gyrus. Higher GM volumes and cortical thickness in these areas correlated with better reading and phonological skills, deficits of which are pivotal to DD. Crucially, total brain volume did not influence our results, since it did not differ between the groups. Our findings demonstrating abnormalities in brain areas in individuals with DD, which previously were associated with phonological processing, are compatible with the leading hypotheses on the neurocognitive origins of DD.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Qi Zhou ◽  
Mohammed Goryawala ◽  
Mercedes Cabrerizo ◽  
Warren Barker ◽  
Ranjan Duara ◽  
...  

This study establishes a new approach for combining neuroimaging and neuropsychological measures for an optimal decisional space to classify subjects with Alzheimer’s disease (AD). This approach relies on a multivariate feature selection method with different MRI normalization techniques. Subcortical volume, cortical thickness, and surface area measures are obtained using MRIs from 189 participants (129 normal controls and 60 AD patients). Statistically significant variables were selected for each combination model to construct a multidimensional space for classification. Different normalization approaches were explored to gauge the effect on classification performance using a support vector machine classifier. Results indicate that the Mini-mental state examination (MMSE) measure is most discriminative among single-measure models, while subcortical volume combined with MMSE is the most effective multivariate model for AD classification. The study demonstrates that subcortical volumes need not be normalized, whereas cortical thickness should be normalized either by intracranial volume or mean thickness, and surface area is a weak indicator of AD with and without normalization. On the significant brain regions, a nearly perfect symmetry is observed for subcortical volumes and cortical thickness, and a significant reduction in thickness is particularly seen in the temporal lobe, which is associated with brain deficits characterizing AD.


2021 ◽  
Author(s):  
Teija Kujala ◽  
Aleksi Sihvonen ◽  
Anja Thiede ◽  
Peter Palo-Oja ◽  
Paula Virtala ◽  
...  

Abstract Developmental dyslexia (DD) is the most prevalent neurodevelopmental disorder with a substantial negative influence on the individual’s academic achievement and career. Research on its neuroanatomical origins has continued for half a century, yielding, however, inconsistent results, lowered total brain volume being the most consistent finding. We set out to evaluate the grey matter (GM) volume and cortical abnormalities in adult dyslexic individuals, employing a combination of whole-brain voxel- and surface-based morphometry following current recommendations on analysis approaches, coupled with rigorous neuropsychological testing. Whilst controlling for age, sex, total intracranial volume, and performance IQ, we found both decreased GM volume and cortical thickness in the left insula in participants with DD. Moreover, they had decreased GM volume in left superior temporal gyrus, putamen, globus pallidus, and parahippocampal gyrus. Higher GM volumes and cortical thickness in these areas correlated with better reading and phonological skills, deficits of which are pivotal to DD. Crucially, total brain volume did not influence our results, since it did not differ between the groups. Our findings demonstrating abnormalities in brain areas in individuals with DD, which previously were associated with phonological processing, are compatible with the leading hypotheses on the neurocognitive origins of DD.


Author(s):  
Sophia Frangou ◽  
Amirhossein Modabbernia ◽  
Gaelle E Doucet ◽  
Efstathios Papachristou ◽  
Steven CR Williams ◽  
...  

AbstractDelineating age-related cortical trajectories in healthy individuals is critical given the association of cortical thickness with cognition and behaviour. Previous research has shown that deriving robust estimates of age-related brain morphometric changes requires large-scale studies. In response, we conducted a large-scale analysis of cortical thickness in 17,075 individuals aged 3-90 years by pooling data through the Lifespan Working group of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium. We used fractional polynomial (FP) regression to characterize age-related trajectories in cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma (LMS) method. Inter-individual variability was estimated using meta-analysis and one-way analysis of variance. Overall, cortical thickness peaked in childhood and had a steep decrease during the first 2-3 decades of life; thereafter, it showed a gradual monotonic decrease which was steeper in men than in women particularly in middle-life. Notable exceptions to this general pattern were entorhinal, temporopolar and anterior cingulate cortices. Inter-individual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results reconcile uncertainties about age-related trajectories of cortical thickness; the centile values provide estimates of normative variance in cortical thickness, and may assist in detecting abnormal deviations in cortical thickness, and associated behavioural, cognitive and clinical outcomes.


2021 ◽  
Author(s):  
Maria Jalbrzikowski ◽  
Rebecca A. Hayes ◽  
Stephen J. Wood ◽  
Dorte Nordholm ◽  
Juan H. Zhou ◽  
...  

AbstractImportanceThe ENIGMA clinical high risk for psychosis (CHR) initiative, the largest pooled CHR-neuroimaging sample to date, aims to discover robust neurobiological markers of psychosis risk in a sample with known heterogeneous outcomes.ObjectiveWe investigated baseline structural neuroimaging differences between CHR subjects and healthy controls (HC), and between CHR participants who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-). We assessed associations with age by group and conversion status, and similarities between the patterns of effect size maps for psychosis conversion and those found in other large-scale psychosis studies.Design, Setting, and ParticipantsBaseline T1-weighted MRI data were pooled from 31 international sites participating in the ENIGMA CHR Working Group. MRI scans were processed using harmonized protocols and analyzed within a mega- and meta-analysis framework from January-October 2020.Main Outcome(s) and Measure(s)Measures of regional cortical thickness (CT), surface area (SA), and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR, HC) and conversion status (CHR-PS+, CHR-PS-, HC).ResultsThe final dataset consisted of 3,169 participants (CHR=1,792, HC=1,377, age range: 9.5 to 39.8 years, 45% female). Using longitudinal clinical information, we identified CHR-PS+ (N=253) and CHR-PS-(N=1,234). CHR exhibited widespread thinner cortex compared to HC (average d=-0.125, range: −0.09 to −0.17), but not SA or subcortical volume. Thinner cortex in the fusiform, superior temporal, and paracentral regions was associated with psychosis conversion (average d=-0.22). Age showed a stronger negative association with left fusiform and left paracentral CT in HC, compared to CHR-PS+. Regional CT psychosis conversion effect sizes resembled patterns of CT alterations observed in other ENIGMA studies of psychosis.Conclusions and RelevanceWe provide evidence for widespread subtle CT reductions in CHR. The pattern of regions displaying greater CT alterations in CHR-PS+ were similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread CT disruptions coupled with abnormal age associations in CHR may point to disruptions in postnatal brain developmental processes.Key PointsQuestionHow do baseline brain morphometric features relate to later psychosis conversion in individuals at clinical high risk (CHR)?FindingsIn the largest coordinated international analysis to date, reduced baseline cortical thickness, but not cortical surface area or subcortical volume, was more pronounced in CHR, in a manner highly consistent with thinner cortex in established psychosis. Regions that displayed greater cortical thinning in future psychosis converters additionally displayed abnormal associations with age.MeaningCHR status and later transition to psychosis is robustly associated with reduced cortical thickness. Abnormal age associations and specificity to cortical thickness may point to aberrant postnatal brain development in CHR, including pruning and myelination.


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