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Nuria Bargallo

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9 papers

1 author row

YNICL Journal 2023 Journal Article

Different whole-brain functional connectivity correlates of reactive-proactive aggression and callous-unemotional traits in children and adolescents with disruptive behaviors

Julia E. Werhahn
Lukasz Smigielski
Seda Sacu
Susanna Mohl
David Willinger
Jilly Naaijen
Leandra M. Mulder
Jeffrey C. Glennon

BACKGROUND: Disruptive behavior in children and adolescents can manifest as reactive aggression and proactive aggression and is modulated by callous-unemotional traits and other comorbidities. Neural correlates of these aggression dimensions or subtypes and comorbid symptoms remain largely unknown. This multi-center study investigated the relationship between resting state functional connectivity (rsFC) and aggression subtypes considering comorbidities. METHODS: The large sample of children and adolescents aged 8-18 years (n = 207; mean age = 13.30±2.60 years, 150 males) included 118 cases with disruptive behavior (80 with Oppositional Defiant Disorder and/or Conduct Disorder) and 89 controls. Attention-deficit/hyperactivity disorder (ADHD) and anxiety symptom scores were analyzed as covariates when assessing group differences and dimensional aggression effects on hypothesis-free global and local voxel-to-voxel whole-brain rsFC based on functional magnetic resonance imaging at 3 Tesla. RESULTS: Compared to controls, the cases demonstrated altered rsFC in frontal areas, when anxiety but not ADHD symptoms were controlled for. For cases, reactive and proactive aggression scores were related to global and local rsFC in the central gyrus and precuneus, regions linked to aggression-related impairments. Callous-unemotional trait severity was correlated with ICC in the inferior and middle temporal regions implicated in empathy, emotion, and reward processing. Most observed aggression subtype-specific patterns could only be identified when ADHD and anxiety were controlled for. CONCLUSIONS: This study clarifies that hypothesis-free brain connectivity measures can disentangle distinct though overlapping dimensions of aggression in youths. Moreover, our results highlight the importance of considering comorbid symptoms to detect aggression-related rsFC alterations in youths.

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YNICL Journal 2021 Journal Article

Disease-related cortical thinning in presymptomatic granulin mutation carriers

Sergi Borrego-Écija
Roser Sala-Llonch
John van Swieten
Barbara Borroni
Fermín Moreno
Mario Masellis
Carmela Tartaglia
Caroline Graff

Mutations in the granulin gene (GRN) cause familial frontotemporal dementia. Understanding the structural brain changes in presymptomatic GRN carriers would enforce the use of neuroimaging biomarkers for early diagnosis and monitoring. We studied 100 presymptomatic GRN mutation carriers and 94 noncarriers from the Genetic Frontotemporal dementia initiative (GENFI), with MRI structural images. We analyzed 3T MRI structural images using the FreeSurfer pipeline to calculate the whole brain cortical thickness (CTh) for each subject. We also perform a vertex-wise general linear model to assess differences between groups in the relationship between CTh and diverse covariables as gender, age, the estimated years to onset and education. We also explored differences according to TMEM106B genotype, a possible disease modifier. Whole brain CTh did not differ between carriers and noncarriers. Both groups showed age-related cortical thinning. The group-by-age interaction analysis showed that this age-related cortical thinning was significantly greater in GRN carriers in the left superior frontal cortex. TMEM106B did not significantly influence the age-related cortical thinning. Our results validate and expand previous findings suggesting an increased CTh loss associated with age and estimated proximity to symptoms onset in GRN carriers, even before the disease onset.

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YNICL Journal 2020 Journal Article

Specific cortical and subcortical alterations for reactive and proactive aggression in children and adolescents with disruptive behavior

Jilly Naaijen
Leandra M Mulder
Shahrzad Ilbegi
Sanne de Bruijn
Renee Kleine-Deters
Andrea Dietrich
Pieter J Hoekstra
Jan-Bernard C Marsman

Maladaptive aggression, as present in conduct disorder (CD) and, to a lesser extent, oppositional defiant disorder (ODD), has been associated with structural alterations in various brain regions, such as ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), amygdala, insula and ventral striatum. Although aggression can be subdivided into reactive and proactive subtypes, no neuroimaging studies have yet investigated if any structural brain alterations are associated with either of the subtypes specifically. Here we investigated associations between aggression subtypes, CU traits and ADHD symptoms in predefined regions of interest. T1-weighted magnetic resonance images were acquired from 158 children and adolescents with disruptive behavior (ODD/CD) and 96 controls in a multi-center study (aged 8-18). Aggression subtypes were assessed by questionnaires filled in by participants and their parents. Cortical volume and subcortical volumes and shape were determined using Freesurfer and the FMRIB integrated registration and segmentation tool. Associations between volumes and continuous measures of aggression were established using multilevel linear mixed effects models. Proactive aggression was negatively associated with amygdala volume (b = -10.7, p = 0.02), while reactive aggression was negatively associated with insula volume (b = -21.7, p = 0.01). No associations were found with CU traits or ADHD symptomatology. Classical group comparison showed that children and adolescents with disruptive behavior had smaller volumes than controls in (bilateral) vmPFC (p = 0.003) with modest effect size and a reduced shape in the anterior part of the left ventral striatum (p = 0.005). Our study showed negative associations between reactive aggression and volumes in a region involved in threat responsivity and between proactive aggression and a region linked to empathy. This provides evidence for aggression subtype-specific alterations in brain structure which may provide useful insights for clinical practice.

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YNICL Journal 2019 Journal Article

White matter hyperintensities in progranulin-associated frontotemporal dementia: A longitudinal GENFI study

Carole H. Sudre
Martina Bocchetta
Carolin Heller
Rhian Convery
Mollie Neason
Katrina M. Moore
David M. Cash
Ione O.C. Woollacott

Frontotemporal dementia (FTD) is a heterogeneous group of neurodegenerative disorders with both sporadic and genetic forms. Mutations in the progranulin gene (GRN) are a common cause of genetic FTD, causing either a behavioural presentation or, less commonly, language impairment. Presence on T2-weighted images of white matter hyperintensities (WMH) has been previously shown to be more commonly associated with GRN mutations rather than other forms of FTD. The aim of the current study was to investigate the longitudinal change in WMH and the associations of WMH burden with grey matter (GM) loss, markers of neurodegeneration and cognitive function in GRN mutation carriers. 336 participants in the Genetic FTD Initiative (GENFI) study were included in the analysis: 101 presymptomatic and 32 symptomatic GRN mutation carriers, as well as 203 mutation-negative controls. 39 presymptomatic and 12 symptomatic carriers, and 73 controls also had longitudinal data available. Participants underwent MR imaging acquisition including isotropic 1 mm T1-weighted and T2-weighted sequences. WMH were automatically segmented and locally subdivided to enable a more detailed representation of the pathology distribution. Log-transformed WMH volumes were investigated in terms of their global and regional associations with imaging measures (grey matter volumes), biomarker concentrations (plasma neurofilament light chain, NfL, and glial fibrillary acidic protein, GFAP), genetic status (TMEM106B risk genotype) and cognition (tests of executive function). Analyses revealed that WMH load was higher in both symptomatic and presymptomatic groups compared with controls and this load increased over time. In particular, lesions were seen periventricularly in frontal and occipital lobes, progressing to medial layers over time. However, there was variability in the WMH load across GRN mutation carriers - in the symptomatic group 25.0% had none/mild load, 37.5% had medium and 37.5% had a severe load - a difference not fully explained by disease duration. GM atrophy was strongly associated with WMH load both globally and in separate lobes, and increased WMH burden in the frontal, periventricular and medial regions was associated with worse executive function. Furthermore, plasma NfL and to a lesser extent GFAP concentrations were seen to be associated with increased lesion burden. Lastly, the presence of the homozygous TMEM106B rs1990622 TT risk genotypic status was associated with an increased accrual of WMH per year. In summary, WMH occur in GRN mutation carriers and accumulate over time, but are variable in their severity. They are associated with increased GM atrophy and executive dysfunction. Furthermore, their presence is associated with markers of WM damage (NfL) and astrocytosis (GFAP), whilst their accrual is modified by TMEM106B genetic status. WMH load may represent a target marker for trials of disease modifying therapies in individual patients but the variability across the GRN population would prevent use of such markers as a global outcome measure across all participants in a trial.

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YNIMG Journal 2013 Journal Article

Normalization of similarity-based individual brain networks from gray matter MRI and its association with neurodevelopment in infants with intrauterine growth restriction

Dafnis Batalle
Emma Muñoz-Moreno
Francesc Figueras
Nuria Bargallo
Elisenda Eixarch
Eduard Gratacos

Obtaining individual biomarkers for the prediction of altered neurological outcome is a challenge of modern medicine and neuroscience. Connectomics based on magnetic resonance imaging (MRI) stands as a good candidate to exhaustively extract information from MRI by integrating the information obtained in a few network features that can be used as individual biomarkers of neurological outcome. However, this approach typically requires the use of diffusion and/or functional MRI to extract individual brain networks, which require high acquisition times and present an extreme sensitivity to motion artifacts, critical problems when scanning fetuses and infants. Extraction of individual networks based on morphological similarity from gray matter is a new approach that benefits from the power of graph theory analysis to describe gray matter morphology as a large-scale morphological network from a typical clinical anatomic acquisition such as T1-weighted MRI. In the present paper we propose a methodology to normalize these large-scale morphological networks to a brain network with standardized size based on a parcellation scheme. The proposed methodology was applied to reconstruct individual brain networks of 63 one-year-old infants, 41 infants with intrauterine growth restriction (IUGR) and 22 controls, showing altered network features in the IUGR group, and their association with neurodevelopmental outcome at two years of age by means of ordinal regression analysis of the network features obtained with Bayley Scale for Infant and Toddler Development, third edition. Although it must be more widely assessed, this methodology stands as a good candidate for the development of biomarkers for altered neurodevelopment in the pediatric population.

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YNIMG Journal 2012 Journal Article

Altered small-world topology of structural brain networks in infants with intrauterine growth restriction and its association with later neurodevelopmental outcome

Dafnis Batalle
Elisenda Eixarch
Francesc Figueras
Emma Muñoz-Moreno
Nuria Bargallo
Miriam Illa
Ruthy Acosta-Rojas
Ivan Amat-Roldan

Intrauterine growth restriction (IUGR) due to placental insufficiency affects 5–10% of all pregnancies and it is associated with a wide range of short- and long-term neurodevelopmental disorders. Prediction of neurodevelopmental outcomes in IUGR is among the clinical challenges of modern fetal medicine and pediatrics. In recent years several studies have used magnetic resonance imaging (MRI) to demonstrate differences in brain structure in IUGR subjects, but the ability to use MRI for individual predictive purposes in IUGR is limited. Recent research suggests that MRI in vivo access to brain connectivity might have the potential to help understanding cognitive and neurodevelopment processes. Specifically, MRI based connectomics is an emerging approach to extract information from MRI data that exhaustively maps inter-regional connectivity within the brain to build a graph model of its neural circuitry known as brain network. In the present study we used diffusion MRI based connectomics to obtain structural brain networks of a prospective cohort of one year old infants (32 controls and 24 IUGR) and analyze the existence of quantifiable brain reorganization of white matter circuitry in IUGR group by means of global and regional graph theory features of brain networks. Based on global and regional analyses of the brain network topology we demonstrated brain reorganization in IUGR infants at one year of age. Specifically, IUGR infants presented decreased global and local weighted efficiency, and a pattern of altered regional graph theory features. By means of binomial logistic regression, we also demonstrated that connectivity measures were associated with abnormal performance in later neurodevelopmental outcome as measured by Bayley Scale for Infant and Toddler Development, Third edition (BSID-III) at two years of age. These findings show the potential of diffusion MRI based connectomics and graph theory based network characteristics for estimating differences in the architecture of neural circuitry and developing imaging biomarkers of poor neurodevelopment outcome in infants with prenatal diseases.

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YNIMG Journal 2011 Journal Article

Dysfunctions of cerebral networks precede recognition memory deficits in early Parkinson's disease

Naroa Ibarretxe-Bilbao
Mojtaba Zarei
Carme Junque
Maria Jose Marti
Barbara Segura
Pere Vendrell
Francesc Valldeoriola
Nuria Bargallo

We aimed to investigate changes in the verbal recognition memory network in patients with early Parkinson's disease (PD) without overt recognition memory alteration. Verbal recognition memory was assessed in 24 PD patients in early stages of the disease and a control group of 24 healthy subjects during fMRI data acquisition. Participants were presented with a list of 35 words before imaging, and later during fMRI scanning they were required to recognize these previously presented words. Both model-based (FEAT) and model-free (MELODIC) analyses of the fMRI data were carried out with FSL software. Memory was also assessed by means of Rey's Auditory Verbal Learning Test (RAVLT). PD patients showed no difference in the fMRI recognition memory task and recognition memory assessed by the RAVLT compared to healthy controls. Model-based analysis did not show significant differences between groups. On the other hand, model-free analysis identified components that fitted the task-model and were common to all the participants, as well as components that differed between PD and healthy controls. PD patients showed decreased task-related activations in areas involved in the recognition memory network and decreased task-related deactivations in the default mode network in comparison with controls. In conclusion, model-free fMRI analysis detected alterations in functional cerebral networks involved in a verbal memory task in PD patients without evident recognition memory deficit.

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YNIMG Journal 2009 Journal Article

Identifying the structures involved in seizure generation using sequential analysis of ictal-fMRI data

Antonio Donaire
Nuria Bargallo
Carlos Falcón
Iratxe Maestro
Mar Carreno
Javier Setoain
Jordi Rumià
Santiago Fernández

The aim of this study was to investigate if sequential analysis of BOLD signal changes induced by seizures is useful for preoperative identification of the site of seizure onset in patients with pharmaco-resistant focal epilepsy. Method We analyzed BOLD raw data from 5 patients with focal medically refractory epilepsy who experienced partial seizures during fMRI as part of a preoperative evaluation. To sequence the changes in BOLD signal seizure-induced, each seizure epoch was divided into groups of five consecutive images (ten-second blocks). t-maps were calculated continuously from 120 s before the onset of clinical/EEG seizure onwards by comparing two consecutive groups of five images. Time lag between each comparison was 2 s. Relative changes in BOLD signal between two consecutive groups of five images along the seizure epoch were determined. Results were compared with those of subtraction ictal SPECT coregistered with MRI (SISCOM) and intracranial EEG (2 patients). Results A typical seizure was registered in each patient. After sequential analysis, a well-localized and statistically significant (t: 7–14) area of signal increase was consistently found at seizure initiation in each patient. This area invariably preceded the onset of clinical/electrical seizure by several seconds (6–52 s); was concordant with SISCOM results in all but one patient; and overlapped with the ictal onset zone determined by intracranial EEG in those 2 patients who underwent invasive-EEG recordings. Complete resection of this initial area of signal increase resulted in seizure remission. Three out of four patients who underwent epilepsy surgery remained seizure-free. Conclusion Sequential analysis of ictal-fMRI data may be useful to precisely and non-invasively delineate the ictal onset zone within the brain; and provide insights into the cerebral substrates involved in the generation and propagation of seizures.

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YNIMG Journal 2008 Journal Article

A longitudinal fMRI study of working memory in severe TBI patients with diffuse axonal injury

Rocio Sanchez-Carrion
Davinia Fernandez-Espejo
Carme Junque
Carles Falcon
Nuria Bargallo
Teresa Roig
Montserrat Bernabeu
José M. Tormos

Traumatic brain injury (TBI) patients have working memory deficits and altered patterns of brain activation during this function. The evolution of the impairment has not been examined to date. This study investigated longitudinal changes in brain activation during a working memory task. Twelve patients with severe and diffuse TBI and ten healthy matched controls were fMRI scanned twice at a 6-month interval during an n-back task (0-, 2- and 3-back). All the TBI patients selected presented signs of diffuse axonal injury on CT but had no evidence of focal lesions on MRI clinical examination. Significant changes in brain activation over time were observed in patients, but not in controls. During the first examination, though both groups engaged bilateral fronto-parietal regions known to be involved in working memory, activation of the right superior frontal gyrus was low in the TBI group. However, the difference between TBI and controls had decreased significantly after 6 months. A factor analysis confirmed the greater increase in activation in the right superior frontal cortex in the TBI group than in healthy controls, leading to normalization of the brain activation pattern. In conclusion, this longitudinal study provides evidence of a progressive normalization of the working memory activation pattern after diffuse axonal injury in severe TBI, coinciding with an improvement in performance on this function.

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