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Frauke Nees

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13 papers

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YNICL Journal 2023 Journal Article

Uncontrolled eating and sensation-seeking partially explain the prediction of future binge drinking from adolescent brain structure

Roshan Prakash Rane
Milena Philomena Maria Musial
Anne Beck
Michael Rapp
Florian Schlagenhauf
Tobias Banaschewski
Arun L.W. Bokde
Marie-Laure Paillère Martinot

Binge drinking behavior in early adulthood can be predicted from brain structure during early adolescence with an accuracy of above 70%. We investigated whether this accurate prospective prediction of alcohol misuse behavior can be explained by psychometric variables such as personality traits or mental health comorbidities in a data-driven approach. We analyzed a subset of adolescents who did not have any prior binge drinking experience at age 14 (IMAGEN dataset, n = 555, 52.61% female). Participants underwent structural magnetic resonance imaging at age 14, binge drinking assessments at ages 14 and 22, and psychometric questionnaire assessments at ages 14 and 22. We derived structural brain features from T1-weighted magnetic resonance and diffusion tensor imaging. Using Machine Learning (ML), we predicted binge drinking (age 22) from brain structure (age 14) and used counterbalancing with oversampling to systematically control for 110 + variables from a wide range of social, personality, and other psychometric characteristics potentially associated with binge drinking. We evaluated if controlling for any variable resulted in a significant reduction in ML prediction accuracy. Sensation-seeking (-13.98 ± 1.68%), assessed via the Substance Use Risk Profile Scale at age 14, and uncontrolled eating (-13.98 ± 3.28%), assessed via the Three-Factor-Eating-Questionnaire at age 22, led to significant reductions in mean balanced prediction accuracy upon controlling for them. Thus, sensation-seeking and binge eating could partially explain the prediction of future binge drinking from adolescent brain structure. Our findings suggest that binge drinking and binge eating at age 22 share common neurobiological precursors discovered by the ML model. These neurobiological precursors seem to be associated with sensation-seeking at age 14. Our results facilitate early detection of increased risk for binge drinking and inform future clinical research in trans-diagnostic prevention approaches for adolescent alcohol misuse.

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YNIMG Journal 2021 Journal Article

Similarity and stability of face network across populations and throughout adolescence and adulthood

Zhijie Liao
Tobias Banaschewski
Arun L.W. Bokde
Sylvane Desrivières
Herta Flor
Antoine Grigis
Hugh Garavan
Penny Gowland

The ability to extract cues from faces is fundamental for social animals, including humans. An individual's profile of functional connectivity across a face network can be shaped by common organizing principles, stable individual traits, and time-varying mental states. In the present study, we used data obtained with functional magnetic resonance imaging in two cohorts, IMAGEN (N = 534) and ALSPAC (N = 465), to investigate - both at group and individual levels - the consistency of the regional profile of functional connectivity across populations (IMAGEN, ALSPAC) and time (Visits 1 to 3 in IMAGEN; age 14 to 22 years). At the group level, we found a robust canonical profile of connectivity both across populations and time. At the individual level, connectivity profiles deviated from the canonical profile, and the magnitude of this deviation related to the presence of psychopathology. These findings suggest that the brain processes faces in a highly stereotypical manner, and that the deviations from this normative pattern may be related to the risk of mental illness.

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YNIMG Journal 2020 Journal Article

Brain structure and habitat: Do the brains of our children tell us where they have been brought up?

Simone Kühn
Tobias Banaschewski
Arun L.W. Bokde
Christian Büchel
Erin Burke Quinlan
Sylvane Desrivières
Herta Flor
Antoine Grigis

Recently many lifestyle factors have been shown to be associated with brain structural alterations. At present we are facing increasing population shifts from rural to urban areas, which considerably change the living environments of human beings. To investigate the association between rural vs. urban upbringing and brain structure we selected 106 14-year old adolescents of whom half were exclusively raised in rural areas and the other half who exclusively lived in cities. Voxel-based morphometry revealed a group difference in left hippocampal formation (Rural > City), which was positively associated with cognitive performance in a spatial processing task. Moreover, significant group differences were observed in spatial processing (Rural > City). A mediation analysis revealed that hippocampal formation accounted for more than half of the association between upbringing and spatial processing. The results are compatible with studies reporting earlier and more intense opportunities for spatial exploration in children brought up in rural areas. The results are interesting in the light of urban planning where spaces enabling spatial exploration for children may deserve more attention.

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YNICL Journal 2020 Journal Article

Structural white and gray matter differences in a large sample of patients with Posttraumatic Stress Disorder and a healthy and trauma-exposed control group: Diffusion tensor imaging and region-based morphometry

Sebastian Siehl
Manon Wicking
Sebastian Pohlack
Tobias Winkelmann
Francesca Zidda
Frauke Steiger-White
John King
Neil Burgess

Differences in structural white and gray matter in survivors of traumatic experiences have been related to the development and maintenance of Posttraumatic Stress Disorder (PTSD). However, there are very few studies on diffusion tensor imaging and region based morphometry comparing patients with PTSD to two control groups, namely healthy individuals with or without trauma experience. It is also unknown if differences in white and gray matter are associated. In this cross-sectional study, we examined white- and gray matter differences between 44 patients with PTSD, 49 trauma control and 61 healthy control subjects. We compared the groups applying Tract-Based Spatial Statistics (TBSS) for a whole brain white matter analysis as well as region of interest analyses for white and gray matter. First, trauma control subjects in comparison to patients with PTSD and healthy control subjects showed significantly a) higher fractional anisotropy (FA) in the left corticospinal tract and inferior fronto-occipital fasciculus than patients with PTSD, b) higher FA in the left inferior fronto-occipital-, right inferior- and right superior longitudinal fasciculi, c) higher FA in the forceps minor and d) higher volume of the left and right anterior insulae. Second, we show significant correlations between the FA in the forceps minor and the gray matter volume in the left and right anterior insulae. Third, the mean FA value in the forceps minor correlated negatively with symptom severity of PTSD and depression as well as trait anxiety, whereas the gray matter volume in the left anterior insula correlated negatively with symptom severity in PTSD. Our findings underline the importance of brain structures critically involved in emotion regulation and salience mapping. While previous studies associated these processes primarily to functional and task-based differences in brain activity, we argue that morphometrical white and gray matter differences could serve as targets in neuroscientifically-informed prevention and treatment interventions for PTSD.

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YNIMG Journal 2020 Journal Article

The empirical replicability of task-based fMRI as a function of sample size

Han Bossier
Sanne P. Roels
Ruth Seurinck
Tobias Banaschewski
Gareth J. Barker
Arun L.W. Bokde
Erin Burke Quinlan
Sylvane Desrivières

Replicating results (i. e. obtaining consistent results using a new independent dataset) is an essential part of good science. As replicability has consequences for theories derived from empirical studies, it is of utmost importance to better understand the underlying mechanisms influencing it. A popular tool for non-invasive neuroimaging studies is functional magnetic resonance imaging (fMRI). While the effect of underpowered studies is well documented, the empirical assessment of the interplay between sample size and replicability of results for task-based fMRI studies remains limited. In this work, we extend existing work on this assessment in two ways. Firstly, we use a large database of 1400 subjects performing four types of tasks from the IMAGEN project to subsample a series of independent samples of increasing size. Secondly, replicability is evaluated using a multi-dimensional framework consisting of 3 different measures: (un)conditional test-retest reliability, coherence and stability. We demonstrate not only a positive effect of sample size, but also a trade-off between spatial resolution and replicability. When replicability is assessed voxelwise or when observing small areas of activation, a larger sample size than typically used in fMRI is required to replicate results. On the other hand, when focussing on clusters of voxels, we observe a higher replicability. In addition, we observe variability in the size of clusters of activation between experimental paradigms or contrasts of parameter estimates within these.

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YNICL Journal 2019 Journal Article

Adolescent binge drinking disrupts normal trajectories of brain functional organization and personality maturation

Hongtao Ruan
Yunyi Zhou
Qiang Luo
Gabriel H. Robert
Sylvane Desrivières
Erin Burke Quinlan
ZhaoWen Liu
Tobias Banaschewski

Adolescent binge drinking has been associated with higher risks for the development of many health problems throughout the lifespan. Adolescents undergo multiple changes that involve the co-development processes of brain, personality and behavior; therefore, certain behavior, such as alcohol consumption, can have disruptive effects on both brain development and personality maturation. However, these effects remain unclear due to the scarcity of longitudinal studies. In the current study, we used multivariate approaches to explore discriminative features in brain functional architecture, personality traits, and genetic variants in 19-year-old individuals (n = 212). Taking advantage of a longitudinal design, we selected features that were more drastically altered in drinkers with an earlier onset of binge drinking. With the selected features, we trained a hierarchical model of support vector machines using a training sample (n = 139). Using an independent sample (n = 73), we tested the model and achieved a classification accuracy of 71.2%. We demonstrated longitudinally that after the onset of binge drinking the developmental trajectory of improvement in impulsivity slowed down. This study identified the disrupting effects of adolescent binge drinking on the developmental trajectories of both brain and personality.

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YNICL Journal 2019 Journal Article

Resting-state connectivity alterations during transient global amnesia

Francesca Zidda
Martin Griebe
Anne Ebert
Michaela Ruttorf
Christina Roßmanith
Achim Gass
Jamila Andoh
Frauke Nees

While the pathophysiology of transient global amnesia (TGA) is not understood, due to the specific nature of the clinical deficits, transient dysfunction in the medial temporal lobe, especially in the hippocampus, is assumed; however, concomitant disturbances in other brain regions and in executive function have been postulated. In this study, a cohort of 16 patients was prospectively recruited from the emergency department for resting-state functional MRI (fMRI) during the acute stage of TGA, as confirmed by a standardized neuropsychological assessment. Twenty age- and sex-matched controls, as well as twenty patients with a history of TGA, were recruited for comparison. Functional data were processed using independent component analysis (ICA), allowing the complete automatic (data-driven) identification of spontaneous network dynamics. We documented a severe disturbance in anterograde episodic long-term memory in all patients. Group-based ICA of resting-state data in acute TGA patients versus that of controls and patients with a past TGA episode demonstrated reduced FC mainly of structures belonging to the executive network (EN), but also the hippocampus, confirming its pathophysiological involvement in the disorder, as well as areas belonging to the salience network and other subcortical regions. No significant differences were found when comparing connectivity in patients with a history of TGA and controls. Our findings strengthen previous empirical and theoretical accounts of hippocampal and executive dysfunction in TGA. The disruption of frontal, parietal and insular control regions, together with disruption in the hippocampus, provides a new interpretation for the pathophysiology and neuropsychological profile of this neurological disorder on a large-scale network level.

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YNIMG Journal 2018 Journal Article

Default mode network connectivity of fear- and anxiety-related cue and context conditioning

Francesca Zidda
Jamila Andoh
Sebastian Pohlack
Tobias Winkelmann
Ramona Dinu-Biringer
Juliana Cavalli
Michaela Ruttorf
Frauke Nees

Classical fear conditioning is an important mechanism to adequately respond and adapt to environmental threats and has been related to the development of fear and anxiety. Both cue and context conditioning have been studied but little is known about their relation to relevant resting state networks. The default mode network (DMN) has been reported to be involved in affective learning and described as facilitating a state of readiness in responding to environmental changes. We examined resting state brain connectivity patterns of the default mode network (DMN) in 119 healthy volunteers. Specifically, we carried out correlation analyses between the DMN and skin conductance responses (SCRs) as well as arousal, valence and contingency ratings during learning. In addition, we examined the role of trait anxiety. Two different DMN patterns were identified in which stronger connectivity was linked to lower differential SCRs during fear and anxiety learning. One was related to cue conditioning and involved the amygdala and the medial prefrontal cortex, and one was associated with context conditioning and included the hippocampal formation and sensorimotor areas. These results were replicated in an independent sample. Functional connectivity of the DMN with these key regions at rest was also predictive of trait anxiety but this association could not be replicated in the second sample. We showed that DMN connectivity is differently associated with cued versus contextual learning mechanisms. Uncovering individual differences in baseline network connectivity of the DMN with these key regions might lead to a better understanding of fear and anxiety. Such findings could indeed help to identify vulnerability factors linked to network alterations at rest with dysregulation of learning processes involved in the pathophysiology of stress and anxiety disorders.

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YNIMG Journal 2018 Journal Article

Neural circuitry underlying sustained attention in healthy adolescents and in ADHD symptomatology

Laura O'Halloran
Zhipeng Cao
Kathy Ruddy
Lee Jollans
Matthew D. Albaugh
Andrea Aleni
Alexandra S. Potter
Nigel Vahey

Moment-to-moment reaction time variability on tasks of attention, often quantified by intra-individual response variability (IRV), provides a good indication of the degree to which an individual is vulnerable to lapses in sustained attention. Increased IRV is a hallmark of several disorders of attention, including Attention-Deficit/Hyperactivity Disorder (ADHD). Here, task-based fMRI was used to provide the first examination of how average brain activation and functional connectivity patterns in adolescents are related to individual differences in sustained attention as measured by IRV. We computed IRV in a large sample of adolescents (n = 758) across 'Go' trials of a Stop Signal Task (SST). A data-driven, multi-step analysis approach was used to identify networks associated with low IRV (i. e. , good sustained attention) and high IRV (i. e. , poorer sustained attention). Low IRV was associated with greater functional segregation (i. e. , stronger negative connectivity) amongst an array of brain networks, particularly between cerebellum and motor, cerebellum and prefrontal, and occipital and motor networks. In contrast, high IRV was associated with stronger positive connectivity within the motor network bilaterally and between motor and parietal, prefrontal, and limbic networks. Consistent with these observations, a separate sample of adolescents exhibiting elevated ADHD symptoms had increased fMRI activation and stronger positive connectivity within the same motor network denoting poorer sustained attention, compared to a matched asymptomatic control sample. With respect to the functional connectivity signature of low IRV, there were no statistically significant differences in networks denoting good sustained attention between the ADHD symptom group and asymptomatic control group. We propose that sustained attentional processes are facilitated by an array of neural networks working together, and provide an empirical account of how the functional role of the cerebellum extends to cognition in adolescents. This work highlights the involvement of motor cortex in the integrity of sustained attention, and suggests that atypically strong connectivity within motor networks characterizes poor attentional capacity in both typically developing and ADHD symptomatic adolescents.

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YNICL Journal 2018 Journal Article

Structural white matter changes in adults and children with posttraumatic stress disorder: A systematic review and meta-analysis

Sebastian Siehl
John A. King
Neil Burgess
Herta Flor
Frauke Nees

White matter plasticity occurs throughout life due to learning and can be a protective factor against as well as a vulnerability factor for the development of mental disorders. In this systematic review we summarize findings on structural white matter changes in children and adults with posttraumatic stress disorder (PTSD) and relate them to theoretical accounts of the pathophysiology of PTSD with a focus on the disturbed processing of contexts and associated problems in emotional and cognitive processing and PTSD symptomatology. We particularly examine studies reporting fractional anisotropy (FA) measured with diffusion tensor imaging (DTI). We further subdivided the studies in adult-onset PTSD with traumatic experience in adulthood, adult-onset PTSD with traumatic experience in childhood and children with PTSD. We included 30 studies comprising almost 1700 participants with 450 adults and 300 children suffering from PTSD. Our systematic review showed that for children with PTSD and adult-onset PTSD with childhood trauma, a decrease in FA in the corpus collosum, most prominently in the anterior and posterior midbody, the isthmus and splenium were reported. For adult-onset PTSD with traumatic experience in adulthood, changes in FA in the anterior and posterior part of the cingulum, the superior longitudinal fasciculus and frontal regions were found. Using GingerAle, we also performed a coordinate-based meta-analysis of 14 studies of adult-onset PTSD with traumatic experience in adulthood and did not find any significant clusters. Our results suggest that changes in white matter microstructure vary depending on traumatic experience and are associated with changes in brain circuits related to the processing of contexts. Finally, we present methodological considerations for future studies.

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YNIMG Journal 2015 Journal Article

Robust regression for large-scale neuroimaging studies

Virgile Fritsch
Benoit Da Mota
Eva Loth
Gaël Varoquaux
Tobias Banaschewski
Gareth J. Barker
Arun L.W. Bokde
Rüdiger Brühl

Multi-subject datasets used in neuroimaging group studies have a complex structure, as they exhibit non-stationary statistical properties across regions and display various artifacts. While studies with small sample sizes can rarely be shown to deviate from standard hypotheses (such as the normality of the residuals) due to the poor sensitivity of normality tests with low degrees of freedom, large-scale studies (e. g. >100 subjects) exhibit more obvious deviations from these hypotheses and call for more refined models for statistical inference. Here, we demonstrate the benefits of robust regression as a tool for analyzing large neuroimaging cohorts. First, we use an analytic test based on robust parameter estimates; based on simulations, this procedure is shown to provide an accurate statistical control without resorting to permutations. Second, we show that robust regression yields more detections than standard algorithms using as an example an imaging genetics study with 392 subjects. Third, we show that robust regression can avoid false positives in a large-scale analysis of brain–behavior relationships with over 1500 subjects. Finally we embed robust regression in the Randomized Parcellation Based Inference (RPBI) method and demonstrate that this combination further improves the sensitivity of tests carried out across the whole brain. Altogether, our results show that robust procedures provide important advantages in large-scale neuroimaging group studies.

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YNIMG Journal 2014 Journal Article

Randomized parcellation based inference

Benoit Da Mota
Virgile Fritsch
Gaël Varoquaux
Tobias Banaschewski
Gareth J. Barker
Arun L.W. Bokde
Uli Bromberg
Patricia Conrod

Neuroimaging group analyses are used to relate inter-subject signal differences observed in brain imaging with behavioral or genetic variables and to assess risks factors of brain diseases. The lack of stability and of sensitivity of current voxel-based analysis schemes may however lead to non-reproducible results. We introduce a new approach to overcome the limitations of standard methods, in which active voxels are detected according to a consensus on several random parcellations of the brain images, while a permutation test controls the false positive risk. Both on synthetic and real data, this approach shows higher sensitivity, better accuracy and higher reproducibility than state-of-the-art methods. In a neuroimaging–genetic application, we find that it succeeds in detecting a significant association between a genetic variant next to the COMT gene and the BOLD signal in the left thalamus for a functional Magnetic Resonance Imaging contrast associated with incorrect responses of the subjects from a Stop Signal Task protocol.

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YNIMG Journal 2012 Journal Article

Manual dexterity correlating with right lobule VI volume in right-handed 14-year-olds

Simone Kühn
Alexander Romanowski
Christina Schilling
Tobias Banaschewski
Alexis Barbot
Gareth J. Barker
Rüdiger Brühl
Christian Büchel

Background Dexterity is a fundamental skill in our everyday life. Particularly, the fine-tuning of reaching for objects is of high relevance and crucially coordinated by the cerebellum. Although neuronal cerebellar structures mediate dexterity, classical whole brain voxel-based morphometry (VBM) has not identified structural correlates of dexterity in the cerebellum. Methods Clusters of gray matter (GM) volume associated with the Purdue Pegboard Dexterity Test, a test of fine motor skills and complex upper limb movements, were identified in a cerebellum-optimized VBM analysis using the Spatially Unbiased Infratentorial (SUIT) toolbox in 65 healthy, right-handed 14-year-olds. For comparison, classical whole brain VBM was performed. Results The cerebellum-optimized VBM indicated a significant positive correlation between manual dexterity and GM volume in the right cerebellum Lobule VI, corrected for multiple comparisons and non-stationary smoothness. The classical whole brain VBM revealed positive associations (uncorrected) between dexterity performance and GM volume in the left SMA (BA 6), right fusiform gyrus (BA 20) and left cuneus (BA 18), but not cerebellar structures. Conclusions The results indicate that cerebellar GM volumes in the right Lobule VI predict manual dexterity in healthy untrained humans when cerebellum-optimized VBM is employed. Although conventional VBM identified brain motor network areas it failed to detect cerebellar structures. Thus, previous studies might have underestimated the importance of cerebellum in manual dexterity.

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