Maarten Mennes

Radboud University | RU · Donders Institute for Brain, Cognition, and Behaviour

Atypical functional connectivity (FC) in autism is a common finding, but the results of individual studies are often inconsistent and sometimes contradictory. Classical reliance on case-control comparisons of group means that ignore the inter-individual heterogeneity autism may be a key drive of this inconsistency. Here, we used normative modelling...

Importance In the neurotypical brain, regions develop in coordinated patterns, providing a fundamental scaffold for brain function and behavior. Whether altered patterns contribute to clinical profiles in neurodevelopmental conditions, including autism, remains unclear. Objectives To examine if, in autism, brain regions develop differently in rela...

Background The connectome, constituting a unique fingerprint of a person’s brain, may be influenced by its prenatal environment, potentially affecting later-life resilience and mental health. Methods We conducted a prospective resting-state functional Magnetic Resonance Imaging study in 28-year-old offspring (N = 49) of mothers whose anxiety was m...

Background Attenuated social attention is a key marker of autism spectrum disorder (ASD). Recent neuroimaging findings also emphasize an altered processing of sensory salience in ASD. The locus coeruleus–norepinephrine system (LC-NE) has been established as a modulator of this sensory salience processing (SSP). We tested the hypothesis that altered...

Background: Autism spectrum disorder (autism) is a complex neurodevelopmental condition with pronounced behavioral, cognitive, and neural heterogeneities across individuals. Here, our goal was to characterize heterogeneity in autism by identifying patterns of neural diversity as reflected in BOLD fMRI in the way individuals with autism engage with...

Clinical neuroimaging data availability has grown substantially in the last decade, providing the potential for studying heterogeneity in clinical cohorts on a previously unprecedented scale. Normative modeling is an emerging statistical tool for dissecting heterogeneity in complex brain disorders. However, its application remains technically chall...

Background Neuroimaging studies on functional connectivity (FC) in autism have been hampered by small sample sizes and inconsistent findings with regard to whether connectivity is increased or decreased in autistic individuals, whether these alterations affect focal systems or reflect a brain-wide pattern, and whether these are age- and/or sex-depe...

Objective: The male preponderance in prevalence of autism is among the most pronounced sex ratios across neurodevelopmental conditions. The authors sought to elucidate the relationship between autism and typical sex-differential neuroanatomy, cognition, and related gene expression. Methods: Using a novel deep learning framework trained to predic...

Background: Understanding the development of the neuronal circuitry underlying autism spectrum disorder (ASD) is critical to shed light into its etiology and for the development of treatment options. Resting state EEG provides a window into spontaneous local and long-range neuronal synchronization and has been investigated in many ASD studies, but...

Objectives The male preponderance in autism spectrum conditions (ASC) prevalence is among the most pronounced sex ratios across different neurodevelopmental conditions. Here, we aimed to elucidate the relationship between autism and typical sex-differential neuroanatomy, cognition, and related gene expression. Methods Using a novel deep learning f...

Neuroimaging studies on functional connectivity (FC) in autism have been hampered by small sample sizes and inconsistent findings with regard to whether connectivity is increased or decreased in individuals with autism, whether these alterations affect focal systems or reflect a brain-wide dysfunction, and whether these are age- and/or sex-dependen...

Background The neurocognitive mechanisms underlying autism spectrum disorder (ASD) remain unclear. Progress has been largely hampered by small sample sizes, variable age ranges and resulting inconsistent findings. There is a pressing need for large definitive studies to delineate the nature and extent of key case/control differences to direct resea...

A bstract Clinical neuroimaging data availability has grown substantially in the last decade, providing the potential for studying heterogeneity in clinical cohorts on a previously unprecedented scale. Normative modeling is an emerging statistical tool for dissecting heterogeneity in complex brain disorders. However, its application remains technic...

Attention-deficit/hyperactivity disorder (ADHD) is associated with altered functioning in multiple cognitive domains and neural networks. This paper offers an overarching biological perspective across these. We applied a novel strategy that extracts functional connectivity modulations in the brain across one ( P single ), two ( P mix ) or three ( P...

Abstract Background Marked sex differences in autism prevalence accentuate the need to understand the role of biological sex-related factors in autism. Efforts to unravel sex differences in the brain organization of autism have, however, been challenged by the limited availability of female data. Methods We addressed this gap by using a large sampl...

Clinical neuroimaging has recently witnessed explosive growth in data availability which brings studying heterogeneity in clinical cohorts to the spotlight. Normative modeling is an emerging statistical tool for achieving this objective. However, its application remains technically challenging due to difficulties in properly dealing with nuisance v...

Background Marked sex differences in autism prevalence accentuate the need to understand the role of biological sex-related factors in autism. Efforts to unravel sex differences in the brain organization of autism have, however, been challenged by the limited availability of female data. Methods We addressed this gap by using the largest sample of...

Evidence is building for an association between the level of anxiety experienced by a mother during pregnancy and offspring cognition and structural and functional brain correlates. The current study uses fMRI to examine the association between prenatal exposure to maternal anxiety and brain activity associated with endogenous versus exogenous cogn...

Clinical neuroimaging has recently witnessed explosive growth in data availability which brings studying heterogeneity in clinical cohorts to the spotlight. Normative modeling is an emerging statistical tool for achieving this objective. However, its application remains technically challenging due to difficulties in properly dealing with nuisance v...

Obsessive-compulsive disorder (OCD) is increasingly considered to be a neurodevelopmental disorder. However, despite insights in neural substrates of OCD in adults, less is known about mechanisms underlying compulsivity during brain development in children and adolescents. Therefore, we developed an adolescent rat model of compulsive checking behav...

Background: Multiple cognitive theories have been proposed to explain the cognitive impairments observed in Attention-deficit/Hyperactivity Disorder (ADHD). Functional imaging studies building on these theories reveal a heterogeneous pattern of neuronal dysfunction and fail to provide an overarching perspective on the pathophysiology of ADHD. Going...

Functional connectivity between brain regions is modulated by cognitive states or experimental conditions. Such connectivity variations can be appreciated in covariance or correlation matrices obtained from fMRI data. A multivariate methodology that can capture fMRI connectivity maps in light of different experimental conditions would be of primary...

Objectives: Neuroimaging studies have independently demonstrated brain anatomical and functional impairments in participants with ADHD. The aim of the current study was to explore the relationship between structural and functional brain alterations in ADHD through an integrated analysis of multimodal neuroimaging data. Methods: We performed a mu...

Objective: Neuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonreplications are frequent. The authors sought to identify cortical characteristics related to ADHD using large-scale studies. Methods: Cortical thickness and surface area (b...

Background: Psychiatric disorders are highly heterogeneous, defined based on symptoms with little connection to potential underlying biological mechanisms. A possible approach to dissect biological heterogeneity is to look for biologically meaningful subtypes. A recent study Drysdale et al. (2017) showed promising results along this line by simult...

BACKGROUND Resting-state functional magnetic resonance imaging-based studies on functional connectivity in autism spectrum disorder (ASD) have generated inconsistent results. Interpretation of findings is further hampered by small samples and a focus on a limited number of networks, with networks underlying sensory processing being largely underexa...

Background: Resting-state functional magnetic resonance imaging-based studies on functional connectivity in autism spectrum disorder (ASD) have generated inconsistent results. Interpretation of findings is further hampered by small samples and a focus on a limited number of networks, with networks underlying sensory processing being largely undere...

In the review article by Adamson, Letourneau and Lebel (J Affect Disord 2018, 241, 117–126) the article of Mennes, Van den Bergh, Lagae & Stiers (Clin Neurophysiolol 2009, 120, 116–1122) was rated as "weak, due to lack of information provided regarding the sample population of mothers". However, Mennes et al. (2009) had referred to previous article...

Background: Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental disorder, putatively induced by dissociable dysfunctional biobehavioral pathways. Here, we present a proof-of-concept study to parse ADHD-related heterogeneity in its underlying neurobiology by investigating functional connectivity across multiple bra...

Prenatal stress and the developing brain: Risks for neurodevelopmental disorders — ERRATUM - Bea R. H. Van den Bergh, Robert Dahnke, Maarten Mennes

Importance Young mouse plasma restores memory in aged mice, but, to our knowledge, the effects are unknown in patients with Alzheimer disease (AD). Objective To assess the safety, tolerability, and feasibility of infusions of young fresh frozen plasma (yFFP) from donors age 18 to 30 years in patients with AD. Design, Setting, and Participants The...

When an individual engages in a task, the associated evoked activities build upon already ongoing activity, shaped by an underlying functional connectivity baseline (Fox et al., 2009; Smith et al., 2009; Tavor et al., 2016). Building on the idea that rest represents the brain's full functional repertoire, we here incorporate the idea that task-indu...

The prenatal period is increasingly considered as a crucial target for the primary prevention of neurodevelopmental and psychiatric disorders. Understanding their pathophysiological mechanisms remains a great challenge. Our review reveals new insights from prenatal brain development research, involving (epi)genetic research, neuroscience, recent im...

It is being hypothesised that the developing adolescent brain is increasingly enlisting long-range connectivity, allowing improved communication between spatially distant brain regions. The developmental trajectories of such maturational changes remain elusive. Here, we aim to study how the brain engages in multiple tasks (working memory, reward pr...

When an individual engages in a task, the associated evoked activities build upon already ongoing activity, itself shaped by an underlying functional connectivity baseline (Fox et al., 2009; Smith et al., 2009; Tavor et al., 2016). To facilitate understanding the building blocks of cognition we incorporate the idea that task-induced functional conn...

We recently reported that the serotonin transporter polymorphism 5-HTTLPR moderates the relation between stress exposure and attention-deficit/hyperactivity disorder (ADHD) severity. This gene-environment interaction (GxE) has been previously tied to the processing of emotional stimuli, which is increasingly recognized to be a key factor in ADHD-re...

Background Autism spectrum disorders (ASD) are characterized by substantial clinical, etiological and neurobiological heterogeneity. Despite this heterogeneity, previous imaging studies have highlighted the role of specific cortical and subcortical structures in ASD and have forwarded the notion of an ASD specific neuroanatomy in which abnormalitie...

Functional neuroimaging studies have led to understanding the brain as a collection of spatially segregated functional networks. It is thought that each of these networks is in turn composed of a set of distinct sub-regions that together support each network's function. Considering the sub-regions to be an essential part of the brain's functional a...

Smoking rates are particularly high during adolescence and young adulthood, when the brain is still undergoing significant developmental changes. Cross-sectional studies have revealed altered brain structure in smokers, such as thinner frontal cortical areas. Attention-deficit/hyperactivity disorder (ADHD) increases the risk of becoming nicotine-de...

Objective: Few studies have investigated verbal working memory-related functional connectivity patterns in participants with attention-deficit/hyperactivity disorder (ADHD). Thus, we aimed to compare working memory-related functional connectivity patterns in healthy children and those with ADHD, and study effects of methylphenidate (MPH). Method:...

We introduce an approach to index task- induced changes in fMRI connectivity that: 1) gives full multivariate characterisation 2) provides optimal discriminative linear filters in terms of variance.

We examined whether adolescents’ neural responses to social exclusion and inclusion are influenced by their own popularity and acceptance and by the popularity of their excluders and includers. Accepted adolescents are highly prosocial. In contrast, popular adolescents, who are central and influential, show prosocial as well as antisocial behaviors...

Introduction: Reward processing is a key aspect of cognitive control processes, putatively instantiated by mesolimbic and mesocortical brain circuits. Deficient signaling within these circuits has been associated with psychopathology. We applied a network discovery approach to assess specific functional networks associated with reward processing i...

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...

Brainhack events offer a novel workshop format with participant-generated content that caters to the rapidly growing open neuroscience community. Including components from hackathons and unconferences, as well as parallel educational sessions, Brainhack fosters novel collaborations around the interests of its attendees. Here we provide an overview...

Evidence is building for an association between the level of anxiety experienced by a mother during pregnancy and the cognitive development of her offspring. The current study uses fMRI to examine whether there is an association between prenatal exposure to maternal anxiety and brain activity in 20 year old adolescents. In line with previous result...

Supplementary material

Background Many patients with attention-deficit/hyperactivity disorder (ADHD) display aberrant reward-related behavior. Task-based fMRI studies have related atypical reward processing in ADHD to altered BOLD activity in regions underlying reward processing such as ventral striatum and orbitofrontal cortex. However, it remains unclear whether the ob...

Recent functional neuroimaging studies have shown that the brain can be divided into several spatially separate, functionally distinct networks. The investigation of these networks has become an active field of research to understand the brain as a set of interacting subunits. Key to this understanding is the manner in which these network break dow...

Supplementary material

Callous-unemotional (CU) traits, i.e., unconcernedness and lack of prosocial feelings, may manifest in Conduct Disorder (CD), but also in Oppositional Defiant Disorder (ODD) and Attention Deficit Hyperactivity Disorder (ADHD). These disorders have been associated with aberrant reward processing, while the influence of CU traits is unclear. Using fu...

Objective: Attention-deficit/hyperactivity disorder (ADHD) is characterized by cognitive deficits (e.g., interference control) and altered reward processing. Cognitive control is influenced by incentive motivation and according to current theoretical models, ADHD is associated with abnormal interactions between incentive motivation and cognitive c...

Background: Cortico-striatal network dysfunction in attention-deficit/hyperactivity disorder (ADHD) is generally investigated by comparing functional connectivity of the main striatal sub-regions (i.e., putamen, caudate, and nucleus accumbens) between an ADHD and a control group. However, dimensional analyses based on continuous symptom measures m...

Heterogeneity is a key feature of all psychiatric disorders and manifests on many levels including symptoms, disease course and biological underpinnings. These form a substantial barrier to understanding disease mechanisms and developing effective, personalised treatments. In response, many studies have aimed to stratify psychiatric disorders, aimi...

Supplementary material.

Background: Magnetic resonance imaging (MRI) is able to provide detailed insights into the structural organization of the brain, e.g., by means of mapping brain anatomy and white matter microstructure. Understanding interrelations between MRI modalities, rather than mapping modalities in isolation, will contribute to unraveling the complex neural m...

'Big Data' and 'Population Imaging' are becoming integral parts of inspiring research aimed at delineating the biological underpinnings of psychiatric disorders. The scientific strategies currently associated with big data and population imaging are typically embedded in so-called discovery science, thereby pointing to the hypothesis-generating rat...

Background: Task-based and resting-state functional Magnetic Resonance Imaging (fMRI) studies report attention-deficit/hyperactivity disorder (ADHD)-related alterations in brain regions implicated in cortico-striatal networks. We assessed whether ADHD is associated with changes in the brain's global cortico-striatal functional architecture, or whe...

Amygdala dysfunction is hypothesized to underlie the social deficits observed in autism spectrum disorders (ASD). However, the neurobiological basis of this hypothesis is underspecified because it is unknown whether ASD relates to abnormalities of the amygdaloid input or output nuclei. Here, we investigated the functional connectivity of the amygda...

Attention-deficit/hyperactivity disorder (ADHD) is a common childhood psychiatric disorder that often persists into adulthood. While several studies have identified altered functional connectivity in brain networks during rest in children with ADHD, few studies have been performed on adults with ADHD. Existing studies have generally investigated sm...

Background: Data on structural brain alterations in patients with attention-deficit/hyperactivity disorder (ADHD) have been inconsistent. Both ADHD and brain volumes have a strong genetic loading, but whether brain alterations in patients with ADHD are familial has been underexplored. We aimed to detect structural brain alterations in adolescents...

The long-lasting effects of fetal exposure to early life influences (ELI) such as maternal anxiety, stress, and micronutrient deficiencies as well as mediating and moderating factors are quite well established in animal studies, but remain unclear in humans. Here, we report about effects on cognition, behavior, and emotion in offspring aged 5-20 ye...

Background: One neurodevelopmental theory hypothesizes remission of attention-deficit/hyperactivity disorder (ADHD) to result from improved prefrontal top-down control, while ADHD, independent of the current diagnosis, is characterized by stable non-cortical deficits (Halperin & Schulz, 2006). We tested this theory using resting state functional M...

Individuals with autism spectrum disorder (ASD) exhibit severe difficulties in social interaction, motor coordination, behavioral flexibility, and atypical sensory processing, with considerable interindividual variability. This heterogeneous set of symptoms recently led to investigating the presence of abnormalities in the interaction across large-...