Neda Jahanshad

University of California, Los Angeles | UCLA · Department of Neurology

National and international biobanking efforts led to the collection of large and inclusive imaging genetics datasets that enable examination of the contribution of genetic and environmental factors to human brains in illness and health. High‐resolution neuroimaging (~104–6 voxels) and genetic (106–8 single nucleotide polymorphic [SNP] variants) dat...

Background Impaired cardiac function is associated with cognitive impairment and brain imaging features of aging. Cardiac arrhythmias, including atrial fibrillation, are implicated in clinical and subclinical brain injuries. Even in the absence of a clinical diagnosis, subclinical or prodromal substrates of arrhythmias, including an abnormally long...

Alterations in subcortical brain regions are linked to motor and non-motor symptoms in Parkinson’s disease (PD). However, associations between clinical expression and regional morphological abnormalities of the basal ganglia, thalamus, amygdala and hippocampus are not well established. We analyzed 3D T1-weighted brain MRI and clinical data from 252...

White matter alterations are increasingly implicated in neurological diseases and their progression. International-scale studies use diffusion-weighted magnetic resonance imaging (DW-MRI) to qualitatively identify changes in white matter microstructure and connectivity. Yet, quantitative analysis of DW-MRI data is hindered by inconsistencies stemmi...

White matter alterations are increasingly implicated in neurological diseases and their progression. International-scale studies use diffusion-weighted magnetic resonance imaging (DW-MRI) to qualitatively identify changes in white matter microstructure and connectivity. Yet, quantitative analysis of DW-MRI data is hindered by inconsistencies stemmi...

Although specific risk factors for brain alterations in bipolar disorders (BD) are currently unknown, obesity impacts the brain and is highly prevalent in BD. Gray matter correlates of obesity in BD have been well documented, but we know much less about brain white matter abnormalities in people who have both obesity and BD. We obtained body mass i...

Meditation is a family of ancient and contemporary contemplative mind-body practices that can modulate psychological processes, awareness, and mental states. Over the last 40 years, clinical science has manualised meditation practices and designed various meditation interventions (MIs), that have shown therapeutic efficacy for disorders including d...

Advances in deep learning hold promise for predicting clinical factors from human brain images. In this study, we applied a spherical harmonics-based convolutional neural network approach (SPHARM-Net) to MRI-derived brain shape metrics to predict age, sex, and Alzheimer’s disease (AD) diagnosis. MRI-derived brain features included vertex-wise corti...

Background: Stroke leads to complex chronic structural and functional brain changes that specifically affect motor outcomes. The brain-predicted age difference (brain-PAD) has emerged as a sensitive biomarker. Our previous study showed higher global brain-PAD associated with poorer motor function post-stroke. However, the relationship between local...

Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. Here we performed genome-wide association studies meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and the ventral diencephalon)...

The magnetic resonance imaging (MRI) Core has been operating since Alzheimer's Disease Neuroimaging Initiative's (ADNI) inception, providing 20 years of data including reliable, multi‐platform standardized protocols, carefully curated image data, and quantitative measures provided by expert investigators. The overarching purposes of the MRI Core in...

White matter alterations are increasingly implicated in neurological diseases and their progression. International-scale studies use diffusion-weighted magnetic resonance imaging (DW-MRI) to qualitatively identify changes in white matter microstructure and connectivity. Yet, quantitative analysis of DW-MRI data is hindered by inconsistencies stemmi...

Brain Age Gap Estimation (BrainAGE) is an estimate of the gap between a person's chronological age (CA) and a measure of their brain's 'biological age' (BA). This metric is often used as a marker of accelerated aging, albeit with some caveats. Age prediction models trained on brain structural and functional MRI have been employed to derive BrainAGE...

Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. We performed GWAS meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and, for the first time, the ventral diencephalon) in 74,898...

The progression of Parkinson’s disease (PD) is associated with microstructural alterations in neural pathways, contributing to both motor and cognitive decline. However, conflicting findings have emerged due to the use of heterogeneous methods in small studies. Here we performed a large diffusion MRI study in PD, integrating data from 17 cohorts wo...

Research into the brain basis of psychopathology is challenging due to the heterogeneity of psychiatric disorders, extensive comorbidities, underdiagnosis or overdiagnosis, multifaceted interactions with genetics and life experiences, and the highly multivariate nature of neural correlates. Therefore, increasingly larger datasets that measure more...

Alzheimer's disease (AD) is characterized by cognitive decline and memory loss due to the abnormal accumulation of amyloid-beta (Abeta) plaques and tau tangles in the brain; its onset and progression also depend on genetic factors such as the apolipoprotein E (APOE) genotype. Understanding how these factors affect the brain's neural pathways is imp...

Chronic motor impairments are a leading cause of disability after stroke. Previous studies have associated motor outcomes with the degree of damage to predefined structures in the motor system, such as the corticospinal tract. However, such theory-based approaches may not take full advantage of the information contained in clinical imaging data. Th...

Importance The lack of an in vivo measure for α-synuclein (α-syn) pathology until recently has limited thorough characterization of its brain atrophy pattern, especially during early disease stages. Objective To assess the association of state-of-the-art cerebrospinal fluid (CSF) seed amplification assays (SAA) α-syn positivity (SAA α-syn+) with m...

The corpus callosum (CC) is the largest set of white matter fibers connecting the two hemispheres of the brain. In humans, it is essential for coordinating sensorimotor responses, performing associative/executive functions, and representing information in multiple dimensions. Understanding which genetic variants underpin corpus callosum morphometry...

Only a small number of studies have assessed structural differences between the two hemispheres during childhood and adolescence. However, the existing findings lack consistency or are restricted to a particular brain region, a specific brain feature, or a relatively narrow age range. Here, we investigated associations between brain asymmetry and a...

Machine learning can be used to define subtypes of psychiatric conditions based on shared biological foundations of mental disorders. Here we analyzed cross-sectional brain images from 4,222 individuals with schizophrenia and 7038 healthy subjects pooled across 41 international cohorts from the ENIGMA, non-ENIGMA cohorts and public datasets. Using...

Objective: Specific phobia is a common anxiety disorder, but the literature on associated brain structure alterations exhibits substantial gaps. The ENIGMA Anxiety Working Group examined brain structure differences between individuals with specific phobias and healthy control subjects as well as between the animal and blood-injection-injury (BII) s...

Objective: Specific phobia is a common anxiety disorder, but the literature on associated brain structure alterations exhibits substantial gaps. The ENIGMA Anxiety Working Group examined brain structure differences between individuals with specific phobias and healthy control subjects as well as between the animal and blood-injection-injury (BII)...

Neuroimaging consortia can enhance reliability and generalizability of findings by pooling data across studies to achieve larger sample sizes. To adjust for site and MRI protocol effects, imaging datasets are often harmonized based on healthy controls. When data from a control group were not collected, statistical harmonization options are limited...

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread...

Introduction: Diffusion MRI is sensitive to the microstructural properties of brain tissues and shows great promise in detecting the effects of degenerative diseases. However, many approaches analyze single measures averaged over regions of interest, without considering the underlying fiber geometry. Methods: Here, we propose a novel Macrostructure...

Meditation is a family of ancient and contemporary contemplative mind-body practices that can modulate psychological processes, awareness, and mental states. Over the last 40 years, clinical science has manualised meditation practices and designed various meditation interventions (MIs), that have shown therapeutic efficacy for disorders including d...

We launched the ENIGMA-Neuroendocrinology working group with the aim to address knowledge gaps about the role of sex hormones in the brain, which lead to prevalent sex- and gender-based health disparities in biomedical research. We approach this by adopting a lifespan perspective to explore the interplay of hormonal dynamics and mental health in th...

We introduce a novel framework for the classification of functional data supported on nonlinear, and possibly random, manifold domains. The motivating application is the identification of subjects with Alzheimer’s disease from their cortical surface geometry and associated cortical thickness map. The proposed model is based upon a reformulation of...

Impaired cardiac function is associated with cognitive impairment and brain imaging features of aging. Cardiac arrhythmias, including atrial fibrillation, are implicated in clinical and subclinical brain injuries. Even in the absence of a clinical diagnosis, subclinical or prodromal substrates of arrhythmias, including an abnormally long or short P...

Since 2009, the ENIGMA Consortium has brought together neuroimaging researchers from over 45 countries to perform some of the largest international studies of over 30 major brain disorders. The ENIGMA working groups tackle the growing challenge of data harmonization and standardization in analytic workflows, and address the need for well-powered, m...

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 q...

Age-related white matter (WM) microstructure maturation and decline occur throughout the human lifespan with a unique trajectory in the brain, complementing the process of gray matter development and degeneration. Normative modeling can establish lifespan reference curves for typical WM microstructural aging patterns by pooling data from many indep...

The Adolescent Brain and Cognitive Development (ABCD) project is the largest longitudinal study of brain development that tracts 11,820 subjects from 21 sites using standardized protocols for multi-site data collection and analysis. Adolescence is a critical period of brain development associated with white matter myelination and requires reliable...

White matter pathways, typically studied with diffusion tensor imaging (DTI), have been implicated in the neurobiology of obsessive-compulsive disorder (OCD). However, due to limited sample sizes and the predominance of single-site studies, the generalizability of OCD classification based on diffusion white matter estimates remains unclear. Here, w...

This study introduces the Deep Normative Tractometry (DNT) framework, that encodes the joint distribution of both macrostructural and microstructural profiles of the brain white matter tracts through a variational autoencoder (VAE). By training on data from healthy controls, DNT learns the normative distribution of tract data, and can delineate alo...

Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitat...

Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Con...

Introduction Regional gray matter (GM) alterations have been reported in early-onset psychosis (EOP, onset before age 18), but previous studies have yielded conflicting results, likely due to small sample sizes and the different brain regions examined. In this study, we conducted a whole brain voxel-based morphometry (VBM) analysis in a large sampl...

Neuroanatomical findings on youth anxiety disorders are notoriously difficult to replicate, small in effect size and have limited clinical relevance. These concerns have prompted a paradigm shift toward highly powered (that is, big data) individual-level inferences, which are data driven, transdiagnostic and neurobiologically informed. Here we buil...

Neuroanatomical findings on youth anxiety disorders are notoriously difficult to replicate, small in effect size and have limited clinical relevance. These concerns have prompted a paradigm shift toward highly powered (that is, big data) individual-level inferences, which are data driven, transdiagnostic and neurobiologically informed. Here we buil...

Background Microstructural abnormalities likely precede macrostructural changes in the Alzheimer’s disease (AD) cascade. Diffusion MRI (dMRI) is sensitive to microstructural properties of brain tissue but few studies have evaluated dMRI measures in cortical gray matter where many early AD histopathological changes occur. Event‐based modeling (EBM)...

Background People from the Middle East and North Africa (MENA) are highly underrepresented in health studies, yet, they are forecasted to contribute the most to increasing projections of dementia over the next 30 years (Nichols, 2022). Cerebral microhemorrhages, or microbleeds (CMBs) in the aging brain have been linked to small vessel disease and n...

Background Large‐scale multi‐study analyses are required to ensure reproducibility, reliability and generalizability in mapping neurodegeneration and risk for ADRD. However, the heterogeneity in data collection paradigms can complicate and confound data pooling; data harmonization is essential. Longitudinal studies add to the complexity of harmoniz...

Background There is a “diversity” crisis in brain research, as most brain research is conducted in Caucasian populations. This lack of ethnic diversity means that we do not know if predictors of health (and disease) generalize to other ethnic groups. We have recently launched the India ENIGMA Initiative for Global Aging & Mental Health ‐ a globally...

Background Cerebral microbleeds (CMBs) are associated with neurodegenerative diseases (Charidimou, 2011) and have been identified as an adverse amyloid‐related imaging abnormality event (ARIA‐H) related to amyloid clearing medications (Sperling, 2011). Identifying risk factors for CMBs can help refine inclusion criteria for clinical trials and miti...

Background Microstructural abnormalities likely precede macrostructural changes in the Alzheimer’s disease (AD) cascade. Diffusion MRI (dMRI) is sensitive to microstructural properties of brain tissue but few studies have evaluated dMRI measures in cortical gray matter where many early AD histopathological changes occur. Event‐based modeling (EBM)...

Diffusion MRI (dMRI) can be used to probe microstructural properties of brain tissue and holds great promise as a means to non-invasively map Alzheimer’s disease (AD) pathology. Few studies have evaluated multi-shell dMRI models such as neurite orientation dispersion and density imaging (NODDI) and mean apparent propagator (MAP)-MRI in cortical gra...

Posttraumatic stress disorder (PTSD) is associated with lower cortical thickness (CT) in prefrontal, cingulate, and insular cortices in diverse trauma-affected samples. However, some studies have failed to detect differences between PTSD patients and healthy controls or reported that PTSD is associated with greater CT. Using data-driven dimensional...

Objectives Dramatic brain morphological changes occur throughout the third trimester of gestation. In this study, we investigated whether the predicted brain age (PBA) derived from graph convolutional network (GCN) that accounts for cortical morphometrics in third trimester is associated with postnatal abnormalities and neurodevelopmental outcome....

Background Increasing evidence points to a pathophysiological role for the cerebellum in Parkinson's disease (PD). However, regional cerebellar changes associated with motor and non‐motor functioning remain to be elucidated. Objective To quantify cross‐sectional regional cerebellar lobule volumes using three dimensional T1‐weighted anatomical brai...

Positron emission tomography (PET) can detect brain amyloid-β (Aβ) deposits, a diagnostic hallmark of Alzheimer’s disease and a target for disease modifying treatment. However, PET-Aβ is expensive, not widely available, and, unlike magnetic resonance imaging (MRI), exposes the patient to ionizing radiation. Here we propose a novel 3D multimodal gen...

In older adults, changes in brain structure can be used to identify and predict the risk of neurodegenerative disorders and dementias. Traditional ‘brainAge’ methods seek to identify differences between chronological age and biological brain age predicted from MRI that can indicate deviations from normative aging trajectories. These methods provide...

Machine learning can be used to define subtypes of psychiatric conditions based on shared clinical and biological foundations, presenting a crucial step toward establishing biologically based subtypes of mental disorders. With the goal of identifying subtypes of disease progression in schizophrenia, here we analyzed cross-sectional brain structural...

Importance The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in individuals at psychosis risk may be nested within the range observed in healthy individuals. Objective To quantify deviations from the normative ran...

Modifiable lifestyle factors, including diet, can impact brain structure and influence dementia risk, but the extent to which diet may impact brain health for an individual is not clear. Clinical trials allow for the modification of a single variable at a time, but these may not generalize to populations due to uncaptured confounding effects. Large...

Background Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generaliz...

An extensive library of symptom inventories has been developed over time to measure clinical symptoms, but this variety has led to several long standing issues. Most notably, results drawn from different settings and studies are not comparable, which limits reproducibility. Here, we present an artificial intelligence (AI) approach using semantic te...

Converging evidence suggests that schizophrenia (SZ) with primary, enduring negative symptoms (i.e., Deficit SZ (DSZ)) represents a distinct entity within the SZ spectrum while the neurobiological underpinnings remain undetermined. In the largest dataset of DSZ and Non-Deficit (NDSZ), we conducted a meta-analysis of data from 1560 individuals (168...

According to the operational diagnostic criteria, psychiatric disorders such as schizophrenia (SZ), bipolar disorder (BD), major depressive disorder (MDD), and autism spectrum disorder (ASD) are classified based on symptoms. While its cluster of symptoms defines each of these psychiatric disorders, there is also an overlap in symptoms between the d...