The ENIGMA Toolbox: multiscale neural contextualization of multisite neuroimaging datasets

Larivière, Sara; Paquola, Casey; Park, Bo‐yong; Royer, Jessica; Wang, Yezhou; Benkarim, Oualid; Wael, Reinder Vos de; Valk, Sofie L.; Thomopoulos, Sophia I.; Kirschner, Matthias; Lewis, Lindsay B.; Evans, Alan C.; Sisodiya, Sanjay M.; McDonald, Carrie R.; Thompson, Paul M.; Bernhardt, Boris C.

doi:10.1038/s41592-021-01186-4

Cited by 153 publications

(203 citation statements)

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“…See Supplementary Table S2 for information on sample demographics. For each condition, we retrieved a Cohen’s d map via the ENIGMA Toolbox (43) reflecting case-control differences in cortical thickness for 68 Desikan-Killiany parcels (44) ( Fig. 1A ).…”

Section: Resultsmentioning

confidence: 99%

Coordinated Cortical Thickness Alterations across Psychiatric Conditions: A Transdiagnostic ENIGMA Study

Hettwer

Larivière

Park

et al. 2022

Preprint

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Introduction: Mental disorders are increasingly conceptualized as overlapping spectra with underlying polygenicity, neurodevelopmental etiology, and clinical comorbidity. They share multi-level neurobiological alterations, including network-like brain structural alterations. However, whether alteration patterns covary across mental disorders in a biologically meaningful way is currently unknown. Methods: We accessed summary statistics on cortical thickness alterations from 12,024 patients with six mental disorders and 18,969 controls from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium. First, we studied cortical thickness co-alteration networks as a form of pathological structural covariance. We identified regions exhibiting high inter-regional covariance across disorders ("hubs"), and regions that strongly connect to these hubs facilitating network spreading of disease effects ("epicenters"). Next, we applied manifold learning to reveal organizational gradients guiding transdiagnostic patterns of illness effects. Last, we tested whether these gradients capture differential cortical susceptibility with respect to normative cortical thickness covariance, cytoarchitectonic, transcriptomic, and meta-analytical task-based profiles. Results: Co-alteration network hubs were linked to normative connectome hubs and anchored to prefrontal and temporal disease epicenters. The principal gradient derived from manifold learning captured maximally different embedding of prefrontal and temporal epicenters within co-alteration networks, followed a normative cortical thickness gradient, and established a transcriptomic link to cortico-cerebello-thalamic circuits. Moreover, gradients segregated functional networks involved in basic sensory, attentional/perceptual, and domain-general cognitive processes, and distinguished between regional cytoarchitectonic profiles. Conclusion: Together, our findings indicate that disease impact occurs in a synchronized fashion and along multiple levels of hierarchical cortical organization. Such axes can help to disentangle the different neurobiological pathways underlying mental illness.

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Section: Resultsmentioning

confidence: 99%

Coordinated Cortical Thickness Alterations across Psychiatric Conditions: A Transdiagnostic ENIGMA Study

Hettwer

Larivière

Park

et al. 2022

Preprint

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“…Recently, these studies were complemented by dimensional data decomposition approaches of cortical morphological data, for example a recent factor analysis Park et al | Cross-condition effects of major psychiatric conditions 11 [33] and principal component analyses [32]. We extended these prior studies by calculating mean effect size of the previously published condition-specific effects [32], as well as applying principal component analysis to the effect sizes and those sourced from the ENIGMA toolbox [61], confirming robust patterns. Specifically, the first shared dimension of cortical morphological alterations described a gradual axis running from sensory-motor regions at one end towards transmodal and most specifically paralimbic areas on the other end.…”

Section: Discussionmentioning

confidence: 60%

“…We then associated principal dimensions of morphological abnormalities with (i) in vivo myeloarchitecture and functional connectivity gradients obtained from the Human Connectome Project (HCP) [59], (ii) post mortem cytoarchitecture, by cross-referencing data to a ultra-high resolution 3D histological reconstruction of a human brain [60], and (iii) in vivo neurotransmitter topographies provided by PET/SPECT studies [52][53][54][55][56][57][58]. Approaches are openly available and replicable via the ENIGMA toolbox (https://enigma-toolbox.readthedocs.io) [61]. See Methods for more details.…”

Section: Study Overview and Participantsmentioning

confidence: 99%

“…S1B). We also directly ran principal component analysis on previously reported effect size maps (Cohen's d) concatenated across disorders, sourced from the ENIGMA toolbox [61] (Fig. S1C).…”

Section: Shared Dimensions Of Structural Alterations Across Psychiatric Conditionsmentioning

confidence: 99%

“…In the HCP, multimodal imaging data comprising T1-and T2-weighted as well as rs-fMRI were acquired on a Siemens Skyra 3T at Washington University. The cohort selection is identical to our prior work [61,122]. T1-weighted images were acquired using a magnetizationprepared rapid gradient echo (MPRAGE) sequence (repetition time (TR) = 2,400 ms; echo time (TE) = 2.14 ms; inversion time (TI) = 1,000 ms; flip angle = 8º; field of view (FOV) = 224 × 224 mm 2 ; voxel size = 0.7 mm isotropic; 256 slices).…”

Section: B) Hcp Datamentioning

confidence: 99%

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Multilevel neural gradients reflect transdiagnostic effects of major psychiatric conditions on cortical morphology

Park

Kebets

Larivière

et al. 2021

Preprint

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It is increasingly recognized that multiple psychiatric conditions are underpinned by shared neural pathways, affecting similar brain systems. Here, we assessed i) shared dimensions of alterations in cortical morphology across six major psychiatric conditions (autism spectrum disorder, attention deficit/hyperactivity disorder, major depression, obsessive-compulsive disorder, bipolar disorder, schizophrenia) and ii) carried out a multiscale neural contextualization, by cross-referencing shared anomalies against cortical myeloarchitecture and cytoarchitecture, as well as connectome and neurotransmitter organization. Pooling disease-related effects on MRI-based cortical thickness measures across six ENIGMA working groups, including a total of 28,546 participants (12,876 patients and 15,670 controls), we computed a shared disease dimension on cortical morphology using principal component analysis that described a sensory-fugal pattern with paralimbic regions showing the most consistent abnormalities across conditions. The shared disease dimension was closely related to cortical gradients of microstructure and intrinsic connectivity, as well as neurotransmitter systems, specifically serotonin and dopamine. Our findings embed the shared effects of major psychiatric conditions on brain structure in multiple scales of brain organization and may provide novel insights into neural mechanisms into transdiagnostic vulnerability.

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Association between structural brain MRI abnormalities and epilepsy in older adults

Gugger,

Walter,

Diaz‐Arrastia

et al. 2023

Ann Clin Transl Neurol

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ObjectiveTo determine the association between brain MRI abnormalities and incident epilepsy in older adults.MethodsMen and women (ages 45–64 years) from the Atherosclerosis Risk in Communities study were followed up from 1987 to 2018 with brain MRI performed between 2011 and 2013. We identified cases of incident late‐onset epilepsy (LOE) with onset of seizures occurring after the acquisition of brain MRI. We evaluated the relative pattern of cortical thickness, subcortical volume, and white matter integrity among participants with incident LOE after MRI in comparison with participants without seizures. We examined the association between MRI abnormalities and incident LOE using Cox proportional hazards regression. Models were adjusted for demographics, hypertension, diabetes, smoking, stroke, and dementia status.ResultsAmong 1251 participants with brain MRI data, 27 (2.2%) developed LOE after MRI over a median of 6.4 years (25–75 percentile 5.8–6.9) of follow‐up. Participants with incident LOE after MRI had higher levels of cortical thinning and white matter microstructural abnormalities before seizure onset compared to those without seizures. In longitudinal analyses, greater number of abnormalities was associated with incident LOE after controlling for demographic factors, risk factors for cardiovascular disease, stroke, and dementia (gray matter: hazard ratio [HR]: 2.3, 95% confidence interval [CI]: 1.0–4.9; white matter diffusivity: HR: 3.0, 95% CI: 1.2–7.3).InterpretationThis study demonstrates considerable gray and white matter pathology among individuals with LOE, which is present prior to the onset of seizures and provides important insights into the role of neurodegeneration, both of gray and white matter, and the risk of LOE.

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The ENIGMA Toolbox: multiscale neural contextualization of multisite neuroimaging datasets

Cited by 153 publications

References 9 publications

Coordinated Cortical Thickness Alterations across Psychiatric Conditions: A Transdiagnostic ENIGMA Study

Coordinated Cortical Thickness Alterations across Psychiatric Conditions: A Transdiagnostic ENIGMA Study

Multilevel neural gradients reflect transdiagnostic effects of major psychiatric conditions on cortical morphology

Association between structural brain MRI abnormalities and epilepsy in older adults

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