Theo G.M. van Erp

• University of California, Irvine

The past 10 years have seen an explosion of approaches that focus on the study of time-resolved change in functional connectivity (FC). FC characterization among networks at a whole-brain level is frequently termed functional network connectivity (FNC). Time-resolved or dynamic functional network connectivity (dFNC) focuses on the estimation of tra...

Most dynamic functional connectivity in fMRI data is focused on linear correlations, and to our knowledge, no study has studied whole brain explicitly nonlinear dynamic relationships within the data. While some approaches have attempted to study overall connectivity more generally using flexible models, we are particularly interested in whether the...

Numerous brain disorders demonstrate structural brain abnormalities, which are thought to arise from molecular perturbations or connectome miswiring. The unique and shared contributions of these molecular and connectomic vulnerabilities to brain disorders remain unknown, and has yet to be studied in a single multi-disorder framework. Using MRI morp...

Background: While functional connectivity is widely studied, there has been little work studying functional connectivity at different spatial scales. Likewise, the relationship of functional connectivity between spatial scales is unknown. Methods: We proposed an independent component analysis (ICA) - based approach to capture information at mult...

In this work, we focus on explicitly nonlinear relationships in functional networks. We introduce a technique using normalized mutual information (MI), that calculates the nonlinear correlation between different brain regions. We demonstrate our proposed approach using simulated data, then apply it to a dataset previously studied in (Damaraju et al...

Background: Brain imaging data collected from individuals are highly complex with unique variation; however, such variation is typically ignored in approaches that focus on group averages or even supervised prediction. State-of-the-art methods for analyzing dynamic functional network connectivity (dFNC) subdivide the entire time course into several...

Background: Previous work provided conversion equations for overall indices of positive and negative symptomatology between the two most widely used scales to assess symptom severity in schizophrenia, namely the Positive and Negative Syndrome Scale (PANSS) and the Scales for the Assessment of Positive/Negative Symptoms (SAPS/SANS). Our objective wa...

The 22q11.2 deletion (22q11DS) is a common chromosomal microdeletion and a potent risk factor for psychotic illness. Prior studies reported widespread cortical changes in 22q11DS, but were generally underpowered to characterize neuroanatomic abnormalities associated with psychosis in 22q11DS, and/or neuroanatomic effects of variability in deletion...

Background Negative symptoms can be seen to represent a continuum from subclinical manifestations in the general population to severe symptoms in schizophrenia. Neuroanatomical studies show evidence of fronto-striatal structural abnormalities linked to negative symptoms in patients with schizophrenia (Walton et al. 2018). However, it remains an ope...

A common limitation of neuroimaging studies is their small sample sizes. To overcome this hurdle, the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium combines neuroimaging data from many institutions worldwide. However, this introduces heterogeneity due to different scanning devices and sequences. ENIGMA projects commonly...

Background: Genomewide association studies have found significant genetic correlations among many neuropsychiatric disorders. In contrast, we know much less about the degree to which structural brain alterations are similar among disorders and, if so, the degree to which such similarities have a genetic etiology. Methods: From the Enhancing Neuroim...

Background Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample. Method To study the association between positive symptoms and aggression in s...

Negative symptoms are core contributors to vocational and social deficits in schizophrenia (SZ). Available antipsychotic medications typically fail to reduce these symptoms. The neurohormone oxytocin (OT) is a promising treatment for negative symptoms, given its role in complex social behaviors mediated by the amygdala. In sample 1, we used a doubl...

Background Neuroanatomical studies have provided some evidence for a neurobiological continuity between psychotic symptoms in patients with schizophrenia and subclinical psychotic-like experiences as identified via self-report questionnaires (or schizotypy) in otherwise healthy individuals. Despite a number of structural brain imaging studies publi...

Background: Autocorrelation (AC) in fMRI time-series is a well-known phenomenon, typically attributed to colored noise and therefore removed from the data. We hypothesize that AC reflects systematic and meaningful signal fluctuations that may be tied to neural activity and provide evidence to support this hypothesis. New method: Each fMRI time-s...

One of the features that distinguishes modern humans from our extinct relatives and ancestors is the globular shape of the braincase. As the endocranium closely mirrors the outer shape of the brain, these differences might reflect altered neural architecture. However, in the absence of fossil brain tissue the underlying neuroanatomical changes as w...

During collation of the Supplemental Information for this article, a formatting error occurred that affected the small values that were in scientific notation in the original text file. All data values reported in the paper and shown in the figures are correct, and this error in formatting the Supplemental Information for publication did not have a...

In a recent study, a neuroanatomical-based age prediction model observed neuromaturational deviance among clinical high-risk individuals who developed psychosis. Here we aimed to investigate whether incorporating “brain age gap” (discrepancy between neuroanatomical-based predicted age and chronological age) to the North American Prodromal Longitudi...

Schizophrenia is a complex disorder that affects perception, cognition, and emotion causing symptoms such as delusions, hallucinations, and suspiciousness. Schizophrenia is also associated with structural cortical abnormalities including lower gray matter (GM) concentration, GM volume, and cortical thickness relative to healthy control individuals....

We organized 10Kin1day, a pop-up scientific event with the goal to bring together neuroimaging groups from around the world to jointly analyze 10,000+ existing MRI connectivity datasets during a 3-day workshop. In this report, we describe the motivation and principles of 10Kin1day, together with a public release of 8,000+ MRI connectome maps of the...

Mounting evidence has shown disrupted brain network architecture across the psychosis spectrum. However, whether these changes relate to the development of psychosis is unclear. Here, we used graph theoretical analysis to investigate longitudinal changes in resting-state brain networks in samples of 72 subjects at clinical high risk (including 8 ca...

The analysis of time‐varying activity and connectivity patterns (i.e., the chronnectome) using resting‐state magnetic resonance imaging has become an important part of ongoing neuroscience discussions. The majority of previous work has focused on variations of temporal coupling among fixed spatial nodes or transition of the dominant activity/connec...

One of the features that distinguishes modern humans from our extinct relatives and ancestors is a globular shape of the braincase [1–4]. As the endocranium closely mirrors the outer shape of the brain, these differences might reflect altered neural architecture [4, 5]. However, in the absence of fossil brain tissue, the underlying neuroanatomical...

The brain is highly dynamic, reorganizing its activity at different interacting spatial and temporal scales including variation within and between brain networks. The chronnectome is a model of the brain in which nodal activity and connectivity patterns are changing in fundamental and recurring ways through time. Most previous work has assumed fixe...

Understanding the fundamental alterations in brain functioning that lead to psychotic disorders remains a major challenge in clinical neuroscience. In particular, it is unknown whether any state-independent biomarkers can potentially predict the onset of psychosis and distinguish patients from healthy controls, regardless of paradigm. Here, using m...

We present several deep learning models for assessing the morphometric fidelity of deep grey matter region models extracted from brain MRI. We test three different convolutional neural net architectures (VGGNet, ResNet and Inception) over 2D maps of geometric features. Further, we present a novel geometry feature augmentation technique based on par...

Memory deficits are a hallmark of psychotic disorders such as schizophrenia. However, whether the neural dysfunction underlying these deficits is present before the onset of illness and potentially predicts conversion to psychosis is unclear. In this study, we investigated brain functional alterations during memory processing in a sample of 155 ind...

Aim The hippocampus is considered a key region in schizophrenia pathophysiology, but the nature of hippocampal subregion abnormalities and how they contribute to disease expression remain to be fully determined. This study reviews findings from schizophrenia hippocampal subregion volumetric and physiological imaging studies published within the las...

We present several deep learning models for assessing the morphometric fidelity of deep grey matter region models extracted from brain MRI. We test three different convolutional neural net architectures (VGGNet, ResNet and Inception) over 2D maps of geometric features. Further, we present a novel geometry feature augmentation technique based on a p...

Schizophrenia is a complex, debilitating mental disorder characterized by wide-ranging symptoms including delusions, hallucinations (so-called positive symptoms), and impaired motor and speech/language production (so-called negative symptoms). Salience-monitoring theorists propose that abnormal functional communication between the salience network...

We present several deep learning models for assessing the morphometric fidelity of deep grey matter region models extracted from brain MRI. We test three different convolutional neural net architectures (VGGNet, ResNet and Inception) over 2D maps of geometric features. Further, we present a novel geometry feature augmentation technique based on a p...

The analysis of time-varying activity and connectivity patterns (i.e., the chronnectome) using resting-state magnetic resonance imaging has become an important part of ongoing neuroscience discussions. The majority of previous work has focused on variations of temporal coupling among fixed spatial nodes or transition of the dominant activity/connec...

Cognitive impairment is a feature of many psychiatric diseases, including schizophrenia. Here we aim to identify multimodal biomarkers for quantifying and predicting cognitive performance in individuals with schizophrenia and healthy controls. A supervised learning strategy is used to guide three-way multimodal magnetic resonance imaging (MRI) fusi...

Importance Altered neurodevelopmental trajectories are thought to reflect heterogeneity in the pathophysiologic characteristics of schizophrenia, but whether neural indicators of these trajectories are associated with future psychosis is unclear. Objective To investigate distinct neuroanatomical markers that can differentiate aberrant neurodevelop...

Many studies have shown that schizophrenia patients have aberrant functional network connectivity (FNC) among brain regions, suggesting schizophrenia manifests with significantly diminished (in majority of the cases) connectivity. Schizophrenia is also associated with a lack of hemispheric lateralization. Hoptman et al. (2012) reported lower inter-...

This study assessed genetic contributions to six cognitive domains, identified by the MATRICS Cognitive Consensus Battery as relevant for schizophrenia, cognition-enhancing, clinical trials. Psychiatric Genomics Consortium Schizophrenia polygenic risk scores showed significant negative correlations with each cognitive domain. Genome-wide associatio...

Aims: To provide quantitative conversions between commonly used scales for the assessment of negative symptoms in schizophrenia. Method: Linear regression analyses generated conversion equations between symptom scores from the Scale for the Assessment of Negative Symptoms (SANS), the Schedule for the Deficit Syndrome (SDS), the Positive and Nega...

The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizop...

Background: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics throu...

Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brai...

Background Both early (pre- and perinatal) and late (adolescent) neurodevelopmental disturbances are hypothesized to contribute to the pathophysiology of schizophrenia. Disturbances originating earlier in life (e.g., resulting from the interplay of genetic factors and obstetric complications) would be expected to affect brain integrity from birth o...

Background Memory deficits are a hallmark of psychotic disorders such as schizophrenia. However, whether neural dysfunction underlying these deficits is present prior to onset of illness and potentially predicts conversion to psychosis are unclear. This study aimed to investigate: 1) baseline brain functional alterations during memory processing in...

While graph theoretical modeling has dramatically advanced our understanding of complex brain systems, the feasibility of aggregating connectomic data in large imaging consortia remains unclear. Here, using a battery of cognitive, emotional and resting fMRI paradigms, we investigated the generalizability of functional connectomic measures across si...

Hallucinations characterize schizophrenia, with approximately 59% of patients reporting auditory hallucinations and 27% reporting visual hallucinations. Prior neuroimaging studies suggest that hallucinations are linked to disrupted communication across distributed (sensory, salience-monitoring and subcortical) networks. Yet, our understanding of th...

Genetic factors are known to influence both risk for schizophrenia (SZ) and variation in brain structure. A pressing question is whether the genetic underpinnings of brain phenotype and the disorder overlap. Using multivariate analytic methods and focusing on 1,402 common single-nucleotide polymorphisms (SNPs) mapped from the Psychiatric Genomics C...

Background Schizophrenia (SZ) is a severe neuropsychiatric disorder associated with disrupted connectivity within the thalamic-cortico-cerebellar network. Resting-state functional connectivity studies have reported thalamic hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic hyperconnectivity with sensory cortical regions...

Accumulating evidence points to the association of epilepsy, particularly, temporal lobe epilepsy (TLE), with psychiatric disorders, such as schizophrenia. Among these illnesses, the hippocampus is considered the regional focal point of the brain, playing an important role in cognition, psychosis, and seizure activity and potentially suggesting com...

As very large studies of complex neuroimaging phenotypes become more common, human quality assessment of MRI-derived data remains one of the last major bottlenecks. Few attempts have so far been made to address this issue with machine learning. In this work, we optimize predictive models of quality for meshes representing deep brain structure shape...

Clinical and cognitive symptoms domain-based subtyping in schizophrenia (Sz) has been critiqued due to the lack of neurobiological correlates and heterogeneity in symptom scores. We, therefore, present a novel data-driven framework using biclustered independent component analysis to detect subtypes from the reliable and stable gray matter concentra...

Individuals with schizophrenia (SZ) consistently show deficits in spatial working memory (WM) and associated atypical patterns of neural activity within key WM regions, including the dorsolateral prefrontal cortex (dlPFC) and parietal cortices. However, little research has focused on adolescent psychosis (AP) and potential age-associated disruption...

As very large studies of complex neuroimaging phenotypes become more common, human quality assessment of MRI-derived data remains one of the last major bottlenecks. Few attempts have so far been made to address this issue with machine learning. In this work, we optimize predictive models of quality for meshes representing deep brain structure shape...

By exploiting cross-information among multiple imaging data, multimodal fusion has often been used to better understand brain diseases. However, most current fusion approaches are blind, without adopting any prior information. There is increasing interest to uncover the neurocognitive mapping of specific clinical measurements on enriched brain imag...

Background: Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial o...

Despite over 400 peer-reviewed structural MRI publications documenting neuroanatomic abnormalities in bipolar disorder and schizophrenia, the confounding effects of head motion and the regional specificity of these defects are unclear. Using a large cohort of individuals scanned on the same research dedicated MRI with broadly similar protocols, we...

The aetiology of suicidal behaviour is complex, and knowledge about its neurobiological mechanisms is limited. Neuroimaging methods provide a noninvasive approach to explore the neural correlates of suicide vulnerability in vivo. The ENIGMA-MDD Working Group is an international collaboration evaluating neuroimaging and clinical data from thousands...

Objective: Based on the role of the superior temporal gyrus (STG) in auditory processing, language comprehension and self-monitoring, this study aimed to investigate the relationship between STG cortical thickness and positive symptom severity in schizophrenia. Method: This prospective meta-analysis includes data from 1987 individuals with schiz...

Background: Genetics is known to influence both schizophrenia risk and brain structure. Thereby a question emerges as to whether the genetic underpinnings of these two traits overlap. Methods: We focused on 1402 common single nucleotide polymorphisms (SNPs) which were mapped from the psychiatric genomics consortium (PGC) 108 regions and showed rela...

Background: Individuals with schizophrenia (Sz) show abnormal functional connectivity between resting state networks (RSNs), yet the relation between disrupted connectivity and symptoms remains unclear. Using a combination of resting-state fMRI analyses – independent component analysis (ICA) and analysis of the mean amplitudes of low-frequency fluc...

Background: In a recent prospective longitudinal neuroimaging study, clinical high-risk (CHR) individuals who later developed full-blown psychosis showed an accelerated rate of gray matter thinning in superior and medial prefrontal cortex (PFC) and expansion of the ventricular system after applying a stringent correction for multiple comparisons. A...

Background: Neuroimaging studies have shown structural alterations in several brain regions in children and adults with attention deficit hyperactivity disorder (ADHD). Through the formation of the international ENIGMA ADHD Working Group, we aimed to address weaknesses of previous imaging studies and meta-analyses, namely inadequate sample size an...

In a recent prospective longitudinal neuroimaging study, clinical high-risk (CHR) individuals who later developed full-blown psychosis showed an accelerated rate of gray matter thinning in superior and medial prefrontal cortex (PFC) and expansion of the ventricular system after applying a stringent correction for multiple comparisons. Although cort...

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide...