Publications by authors named "Jesus Pujol"

149 Publications

Dysfunctional Brain Reward System in Child Obesity.

Cereb Cortex 2021 Apr 16. Epub 2021 Apr 16.

ISGlobal, 08003 Barcelona, Spain.

Eating habits leading to obesity may reflect nonhomeostatic behavior based on excessive immediate-reward seeking. However, it is currently unknown to what extent excess weight is associated with functional alterations in the brain's reward system in children. We tested the integrity of reward circuits using resting-state functional connectivity magnetic resonance imaging in a population of 230 children aged 8-12 years. The major components of the reward system were identified within the ventral striatum network defined on the basis of the nucleus accumbens connectivity pattern. The functional structure of the cerebral cortex was characterized using a combination of local functional connectivity measures. Higher body mass index was associated with weaker connectivity between the cortical and subcortical elements of the reward system, and enhanced the integration of the sensorimotor cortex to superior parietal areas relevant to body image formation. Obese children, unlike WHO-defined overweight condition, showed functional structure alterations in the orbitofrontal cortex and amygdala region similar to those previously observed in primary obsessive-compulsive disorder and Prader-Willi syndrome associated with obsessive eating behavior. Results further support the view that childhood obesity is not simply a deviant habit with restricted physical health consequences but is associated with reward system dysfunction characterizing behavioral control disorders.
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http://dx.doi.org/10.1093/cercor/bhab092DOI Listing
April 2021

Mapping the Synchronization Effect of Gamma-Aminobutyric Acid Inhibition on the Cerebral Cortex Using Magnetic Resonance Imaging.

Brain Connect 2021 Apr 1. Epub 2021 Apr 1.

MRI Research Unit, Department of Radiology, Hospital del Mar, Barcelona, Spain.

Functional magnetic resonance imaging (fMRI) of spontaneous brain activity permits the identification of functional networks on the basis of region synchrony. The functional coupling between the elements of a neural system increases during brain activation. However, neural synchronization may also be the effect of inhibitory gamma-aminobutyric acid (GABA) neurons in states of brain inhibition such as sleep or pharmacological sedation. We investigated the effects of an oral dose of alprazolam, a classical benzodiazepine known to enhance inhibitory neurotransmission, using recently developed measures of local functional connectivity. In a randomized, double-blind, placebo-controlled, crossover design, 32 non-treatment-seeking individuals with social anxiety underwent two identical resting-state fMRI sessions on separate days after receiving 0.75 mg of alprazolam and placebo. Functional connectivity maps of the cerebral cortex were generated by using multidistance functional connectivity measures defined within iso-distant local areas. Relative to placebo, increased intracortical functional connectivity was observed in the alprazolam condition in visual, auditory, and sensorimotor cortices, and in areas of sensory integration such as the posterior insula and orbitofrontal cortex (OFC). Alprazolam significantly reduced subjective arousal compared with placebo, and the change was associated with variations in multidistance functional connectivity measures in the OFC. In conclusion, we report evidence that alprazolam significantly modifies neural activity coupling at rest in the form of functional connectivity enhancement within the cerebral cortex. The effect of alprazolam was particularly evident in the cortical sensory system, which would further suggest a differentiated effect of GABA inhibition on sensory processing.
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http://dx.doi.org/10.1089/brain.2020.0844DOI Listing
April 2021

Altered Gesture Imitation and Brain Anatomy in Adult Prader-Willi Syndrome Patients.

J Int Neuropsychol Soc 2021 Mar 4:1-13. Epub 2021 Mar 4.

Specialized Service in Mental Health and Intellectual Disability Department, Institut Assistència Sanitària (IAS), Parc Hospitalari Martí i Julià, Girona, Spain.

Objective: To explore motor praxis in adults with Prader-Willi syndrome (PWS) in comparison with a control group of people with intellectual disability (ID) and to examine the relationship with brain structural measurements.

Method: Thirty adult participants with PWS and 132 with ID of nongenetic etiology (matched by age, sex, and ID level) were assessed using a comprehensive evaluation of the praxis function, which included pantomime of tool use, imitation of meaningful and meaningless gestures, motor sequencing, and constructional praxis.

Results: Results support specific praxis difficulties in PWS, with worse performance in the imitation of motor actions and better performance in constructional praxis than ID peers. Compared with both control groups, PWS showed increased gray matter volume in sensorimotor and subcortical regions. However, we found no obvious association between these alterations and praxis performance. Instead, praxis scores correlated with regional volume measures in distributed apparently normal brain areas.

Conclusions: Our findings are consistent in showing significant impairment in gesture imitation abilities in PWS and, otherwise, further indicate that the visuospatial praxis domain is relatively preserved. Praxis disability in PWS was not associated with a specific, focal alteration of brain anatomy. Altered imitation gestures could, therefore, be a consequence of widespread brain dysfunction. However, the specific contribution of key brain structures (e.g., areas containing mirror neurons) should be more finely tested in future research.
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http://dx.doi.org/10.1017/S1355617721000060DOI Listing
March 2021

A multicenter, observational study of pain and functional impairment in individuals with major depressive disorder in partial remission: the DESIRE study.

J Affect Disord 2021 02 12;281:657-660. Epub 2020 Nov 12.

Institute Mar of Medical Research, IMIM, Barcelona, Spain; Centro de Investigación en Red de Salud Mental, CIBERSAM, Madrid, Spain.

Background: The study explores the association between pain and functional impairment in patients with partially remitted MDD, considering both clinician and patient reported outcomes.

Methods: Multicenter, observational, and cross-sectional study, with 583 outpatients with partially remitted MDD. Measures of pain intensity (VAS), functional impairment (SOFAS), depressive symptomatology (HAM-D6), and remission from MDD and functional status from a patient-centered perspective (RDQ) were collected. VAS scores (cut-off: 30) were used to divide the sample in two groups: no pain (n = 274) and pain (n = 309). Descriptive data, correlation and regression analyses were obtained.

Results: Functional impairment (SOFAS) and pain (VAS) were negatively and significantly correlated in the total sample, and in the group with pain. Lower pain predicted higher functioning. The pain sub-sample was older, less educated, with higher medical comorbidities, higher HAM-D6 scores, and lower functionality (SOFAS). In the RDQ, the pain group showed significantly higher scores in the symptom-related subscales, and lower scores in the subscales related to positive mental health, functioning and wellbeing.

Limitations: Correlational and observational design. The criteria and instruments used to measure pain and to define a threshold might limit the generalizability of findings.

Conclusions: Pain and functionality should be assessed and treated in patients with MDD in partial remission. Our results indicate that functionality should be assessed with a broader perspective, that also considers positive mental health features.
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http://dx.doi.org/10.1016/j.jad.2020.11.095DOI Listing
February 2021

Brain Functional Connectivity Correlates of Subclinical Obsessive-Compulsive Symptoms in Healthy Children.

J Am Acad Child Adolesc Psychiatry 2020 Sep 18. Epub 2020 Sep 18.

Hospital Universitari de Bellvitge, Institut d'Investigació Biomèdica de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; Instituto de Salud Carlos III-Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain; Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address:

Objective: Commonly observed subclinical obsessive-compulsive symptoms in healthy children may predispose to obsessive-compulsive disorder (OCD). Therefore, investigating the underlying neurobiology may be relevant to identify alterations in specific brain circuits potentially accounting for clinical heterogeneity in OCD without the confounding effects of clinical samples. We analyzed the brain correlates of different obsessive-compulsive symptoms in a large group of healthy children using functional connectivity measures.

Method: We evaluated 227 healthy children (52% girls; mean [SD] age 9.71 [0.86] years; range, 8-12.1 years). Participants underwent clinical assessment with the Obsessive-Compulsive Inventory-Child Version and a resting-state functional magnetic resonance imaging examination. Total and symptom-specific severity were correlated with voxelwise global functional connectivity degree values. Significant clusters were then used as seeds of interest in seed-to-voxel analyses. Modulating effects of age and sex were also assessed.

Results: Global functional connectivity of the left ventral putamen and medial dorsal thalamus correlated negatively with total obsessive-compulsive symptom severity. Seed-to-voxel analyses revealed specific negative correlations from these clusters with limbic, sensorimotor, and insular regions in association with obsessing, ordering, and doubt-checking symptoms, respectively. Hoarding symptoms were associated with negative correlations between the left medial dorsal thalamus and a widespread pattern of regions, with such associations modulated by sex and age.

Conclusion: Our findings concur with prevailing neurobiological models of OCD on the importance of cortico-striato-thalamo-cortical dysfunction to account for symptom severity. Notably, we showed that changes in cortico-striato-thalamo-cortical connectivity are present at subclinical stages, which may result in an increased vulnerability for OCD. Moreover, we mapped different symptom dimensions onto specific cortico-striato-thalamo-cortical circuit attributes.
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http://dx.doi.org/10.1016/j.jaac.2020.08.435DOI Listing
September 2020

Largest scale dissociation of brain activity at propofol-induced loss of consciousness.

Sleep 2021 01;44(1)

Department of Anesthesiology, Hospital del Mar-IMIM, Barcelona, Spain.

The brain is a functional unit made up of multilevel connected elements showing a pattern of synchronized activity that varies in different states. The wake-sleep cycle is a major variation of brain functional condition that is ultimately regulated by subcortical arousal- and sleep-promoting cell groups. We analyzed the evolution of functional MRI (fMRI) signal in the whole cortex and in a deep region including most sleep- and wake-regulating subcortical nuclei at loss of consciousness induced by the hypnotic agent propofol. Optimal data were obtained in 21 of the 30 healthy participants examined. A dynamic analysis of fMRI time courses on a time-scale of seconds was conducted to characterize consciousness transition, and functional connectivity maps were generated to detail the anatomy of structures showing different dynamics. Inside the magnet, loss of consciousness was marked by the participants ceasing to move their hands. We observed activity synchronization after loss of consciousness within both the cerebral cortex and subcortical structures. However, the evolution of fMRI signal was dissociated, showing a transient reduction of global cortico-subcortical coupling that was restored during the unconscious state. An exception to cortico-subcortical decoupling was a brain network related to self-awareness (i.e. the default mode network) that remained connected to subcortical brain structures. Propofol-induced unconsciousness is thus characterized by an initial, transitory dissociated synchronization at the largest scale of brain activity. Such cortico-subcortical decoupling and subsequent recoupling may allow the brain to detach from waking activity and reorganize into a functionally distinct state.
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http://dx.doi.org/10.1093/sleep/zsaa152DOI Listing
January 2021

Electric field causes volumetric changes in the human brain.

Elife 2019 10 23;8. Epub 2019 Oct 23.

Department of Psychiatry, University of New Mexico School of Medicine, Albuquerque, United States.

Recent longitudinal neuroimaging studies in patients with electroconvulsive therapy (ECT) suggest local effects of electric stimulation (lateralized) occur in tandem with global seizure activity (generalized). We used electric field (EF) modeling in 151 ECT treated patients with depression to determine the regional relationships between EF, unbiased longitudinal volume change, and antidepressant response across 85 brain regions. The majority of regional volumes increased significantly, and volumetric changes correlated with regional electric field (t = 3.77, df = 83, r = 0.38, p=0.0003). After controlling for nuisance variables (age, treatment number, and study site), we identified two regions (left amygdala and left hippocampus) with a strong relationship between EF and volume change (FDR corrected p<0.01). However, neither structural volume changes nor electric field was associated with antidepressant response. In summary, we showed that high electrical fields are strongly associated with robust volume changes in a dose-dependent fashion.
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http://dx.doi.org/10.7554/eLife.49115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874416PMC
October 2019

Brain activity during traditional textbook and audiovisual-3D learning.

Brain Behav 2019 10 30;9(10):e01427. Epub 2019 Sep 30.

MRI Research Unit, Department of Radiology, Hospital del Mar, Barcelona, Spain.

Introduction: Audiovisual educational tools have increasingly been used during the past years to complement and compete with traditional textbooks. However, little is known as to how the brain processes didactic information presented in different formats. We directly assessed brain activity during learning using both traditional textbook and audiovisual-3D material.

Methods: A homogeneous sample of 30 young adults with active study habits was assessed. Educational material on the subject of Cardiology was adapted to be presented during the acquisition of functional MRI.

Results: When tested after image acquisition, participants obtained similar examination scores for both formats. Evoked brain activity was robust during both traditional textbook and audiovisual-3D lessons, but a greater number of brain systems were implicated in the processing of audiovisual-3D information, consistent with its multisource sensory nature. However, learning was not associated with group mean brain activations, but was instead predicted by distinct functional MRI signal changes in the frontal lobes and showed distinct cognitive correlates. In the audiovisual-3D version, examination scores were positively correlated with late-evoked prefrontal cortex activity and working memory, and negatively correlated with language-related frontal areas and verbal memory. As for the traditional textbook version, the fewer results obtained suggested the opposite pattern, with examination scores negatively correlating with prefrontal cortex activity evoked during the lesson.

Conclusions: Overall, the results indicate that a similar level of knowledge may be achieved via different cognitive strategies. In our experiment, audiovisual learning appeared to benefit from prefrontal executive resources (as opposed to memorizing verbal information) more than traditional textbook learning.
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http://dx.doi.org/10.1002/brb3.1427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790317PMC
October 2019

Effects of prenatal exposure to particulate matter air pollution on corpus callosum and behavioral problems in children.

Environ Res 2019 11 7;178:108734. Epub 2019 Sep 7.

ISGLOBAL, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; Pompeu Fabra University, Barcelona, Catalonia, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Institut Hospital del Mar d'Investigacions Mèdiques-Parc de Salut Mar, Barcelona, Catalonia, Spain.

Objective: Air pollution (AP) may affect neurodevelopment, but studies about the effects of AP on the growing human brain are still scarce. We aimed to investigate the effects of prenatal exposure to AP on lateral ventricles (LV) and corpus callosum (CC) volumes in children and to determine whether the induced brain changes are associated with behavioral problems.

Methods: Among the children recruited through a set of representative schools of the city of Barcelona, (Spain) in the Brain Development and Air Pollution Ultrafine Particles in School Children (BREATHE) study, 186 typically developing participants aged 8-12 years underwent brain MRI on the same 1.5 T MR unit over a 1.5-year period (October 2012-April 2014). Brain volumes were derived from structural MRI scans using automated tissue segmentation. Behavioral problems were assessed using the Strengths and Difficulties Questionnaire (SDQ) and the criteria of the Attention Deficit Hyperactivity Disorder DSM-IV list. Prenatal fine particle (PM) levels were retrospectively estimated at the mothers' residential addresses during pregnancy with land use regression (LUR) models. To determine whether brain structures might be affected by prenatal PM exposure, linear regression models were run and adjusted for age, sex, intracranial volume (ICV), maternal education, home socioeconomic vulnerability index, birthweight and mothers' smoking status during pregnancy. To test for associations between brain changes and behavioral outcomes, negative binomial regressions were performed and adjusted for age, sex, ICV.

Results: Prenatal PM levels ranged from 11.8 to 39.5 μg/m during the third trimester of pregnancy. An interquartile range increase in PM level (7 μg/m) was significantly linked to a decrease in the body CC volume (mm) (β = -53.7, 95%CI [-92.0, -15.5] corresponding to a 5% decrease of the mean body CC volume) independently of ICV, age, sex, maternal education, socioeconomic vulnerability index at home, birthweight and mothers' smoking status during the third trimester of pregnancy. A 50 mm decrease in the body CC was associated with a significant higher hyperactivity subscore (Rate Ratio (RR) = 1.09, 95%CI [1.01, 1.17) independently of age, sex and ICV. The statistical significance of these results did not survive to False Discovery Rate correction for multiple comparisons.

Conclusions: Prenatal exposure to PM may be associated with CC volume decrease in children. The consequences might be an increase in behavioral problems.
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http://dx.doi.org/10.1016/j.envres.2019.108734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892268PMC
November 2019

Compulsions in Prader-Willi syndrome: occurrence and severity as a function of genetic subtype.

Actas Esp Psiquiatr 2019 May 1;47(3):79-87. Epub 2019 May 1.

Specialized Service in Mental Health and Intellectual Disability (SESM-DI), and Girona Biomedical Research Institute (IdibGi), Parc Hospitalari Martí i Julià, Institut d´Assistència Sanitària, Salt (Girona), Spain Department of Psychology, Philipps-Universität Marburg, Marburg, Germany.

Introduction: Compulsions are among the most typical behaviors in Prader-Willi syndrome (PWS). The most frequent causes of PWS are deletion of the genes located in the segment 15q11-q13 of the paternal allele and maternal uniparental disomy of cromosome 15. The aim of the present work was to study compulsive behavior in a sample of adults with PWS and analyze potential differences as a function of the genetic cause/subtype.

Material And Methods: In the 27 study participants, existence of type I deletion (n=7), type II deletion (n=13), and maternal disomy (n=7) was determined by means of genetic tests. The Yale-Brown Obsessive Compulsive Scale, the Compulsive Behavior Checklist, and the Repetitive Behavior Questionnaire were used to assess occurrence and severity of compulsions.

Results: Most of the participants showed compulsive behavior, the most frequent compulsions were those of inappropriate grooming (skin picking) and order (hoarding). The occurrence of compulsions was less frequent in the maternal disomy group than in the deletion groups. Severe compulsions were more frequent in those participants with type II deletion than in the other groups.

Conclusions: Differences in occurrence and severity of compulsions exist as a function of PWS genetic subtype. Our results support the idea that individuals with maternal disomy are less affected by compulsive behavior. More research on the severity of compulsions as a function of deletion type should be done, as the studies conducted so far have shown contradictory results.
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May 2019

[Prevalence and characteristics of chronic obstructive pulmonary disease in non-smokers].

Aten Primaria 2019 11 20;51(9):589-590. Epub 2019 Jun 20.

Institut de Recerca Biomèdica (IRB) de Lleida, Lleida, España; Agència de Salut Pública de Catalunya, Departament de Salut, Lleida, España; Facultat de Medicina, Universitat de Lleida, Lleida, España.

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http://dx.doi.org/10.1016/j.aprim.2019.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945132PMC
November 2019

Testing the effects of gentle vibrotactile stimulation on symptom relief in fibromyalgia.

Arthritis Res Ther 2019 06 14;21(1):148. Epub 2019 Jun 14.

MRI Research Unit, Department of Radiology, Hospital del Mar, Passeig Marítim 25-29, 08003, Barcelona, Spain.

Background: Sensory disturbances in fibromyalgia extend beyond nociception. It has been proposed that imbalance in the mutual competition between painful input and non-painful sensory activity may, to a significant extent, account for the augmented subjective perception of pain. In this context, non-nociceptive somatosensory stimulation could arguably attenuate fibromyalgia symptoms by restoring the sensory balance. We specifically tested the effect of vibrotactile stimulation on symptom relief in fibromyalgia patients with a randomized, double-blind, sham-controlled, crossover clinical trial.

Methods: Seventy-seven female patients were randomized and data from 63 valid cases were analyzed. Active intervention involved extensive body stimulation with gentle mechanical vibrations administered during 3 h at night for 3 weeks, and the placebo effect was controlled using identical instruments to simulate an alternative treatment option. The primary outcome measure combined pain, fatigue, and complaints of poor cognition.

Results: Vibrotactile stimulation was significantly superior to sham in alleviating fibromyalgia symptoms globally. However, univariate analyses showed that the effect was not universal. Benefits were perceived on unpleasant somatic sensations such as generalized pain and fatigue, but not on poor cognition, anxiety, and depression. Vibrotactile stimulation was notably well tolerated and sleep quality significantly improved despite the fact that vibrations were administered at night.

Conclusions: Results thus provide new evidence that non-nociceptive somatosensory stimulation may favorably act upon altered somatosensory balance in fibromyalgia. From a clinical perspective, both the degree of improvement and the easy application of our proposal would seem to support a potential role for vibrotactile stimulation in the symptomatic treatment of fibromyalgia.

Trial Registration: ClinicalTrials.gov registration number NCT03227952 . Registered 24 July, 2017.
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http://dx.doi.org/10.1186/s13075-019-1932-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6570892PMC
June 2019

Effectiveness of antitussives, anticholinergics or honey versus usual care in adults with uncomplicated acute bronchitis: a study protocol of an open randomised clinical trial in primary care.

BMJ Open 2019 05 16;9(5):e028159. Epub 2019 May 16.

Primary Healthcare Centre Barcelona-2B (via Roma), Barcelona, Catalonia.

Introduction: Despite the frequent use of therapies in acute bronchitis, the evidence of their benefit is lacking, since only a few clinical trials have been published, with low sample sizes, poor methodological quality and mainly in children. The objective of this study is to compare the effectiveness of three symptomatic therapies (dextromethorphan, ipratropium or honey) associated with usual care and the usual care in adults with acute bronchitis.

Methods And Analysis: This will be a multicentre, pragmatic, parallel group, open randomised trial. Patients aged 18 or over with uncomplicated acute bronchitis, with cough for less than 3 weeks as the main symptom, scoring ≥4 in either daytime or nocturnal cough on a 7-point Likert scale, will be randomised to one of the following four groups: usual care, dextromethorphan 30 mg three times a day, ipratropium bromide inhaler 20 µg two puffs three times a day or honey 30 mg (a spoonful) three times a day, all taken for up to 14 days. The exclusion criteria will be pneumonia, criteria for hospital admission, pregnancy or lactation, concomitant pulmonary disease, associated significant comorbidity, allergy, intolerance or contraindication to any of the study drugs or admitted to a long-term residence.

Sample: 668 patients. The primary outcome will be the number of days with moderate-to-severe cough. All patients will be given a paper-based symptom diary to be self-administered. A second visit will be scheduled at day 2 or 3 for assessing evolution, with two more visits at days 15 and 29 for clinical assessment, evaluation of adverse effects, re-attendance and complications. Patients still with symptoms at day 29 will be called 6 weeks after the baseline visit.

Ethics And Dissemination: The study has been approved by the Ethical Board of IDIAP Jordi Gol (reference number: AC18/002). The findings of this trial will be disseminated through research conferences and peer-review journals.

Trial Registration Number: NCT03738917; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2018-028159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530348PMC
May 2019

Differential patterns of brain activation between hoarding disorder and obsessive-compulsive disorder during executive performance.

Psychol Med 2020 03 25;50(4):666-673. Epub 2019 Mar 25.

Department of Psychiatry, Bellvitge University Hospital, Bellvitge Biomedical Research Institute - IDIBELL, Barcelona, Spain.

Background: Preliminary evidence suggests that hoarding disorder (HD) and obsessive-compulsive disorder (OCD) may show distinct patterns of brain activation during executive performance, although results have been inconclusive regarding the specific neural correlates of their differential executive dysfunction. In the current study, we aim to evaluate differences in brain activation between patients with HD, OCD and healthy controls (HCs) during response inhibition, response switching and error processing.

Methods: We assessed 17 patients with HD, 18 patients with OCD and 19 HCs. Executive processing was assessed inside a magnetic resonance scanner by means of two variants of a cognitive control protocol (i.e. stop- and switch-signal tasks), which allowed for the assessment of the aforementioned executive domains.

Results: OCD patients performed similar to the HCs, differing only in the number of successful go trials in the switch-signal task. However, they showed an anomalous hyperactivation of the right rostral anterior cingulate cortex during error processing in the switch-signal task. Conversely, HD patients performed worse than OCD and HC participants in both tasks, showing an impulsive-like pattern of response (i.e. shorter reaction time and more commission errors). They also exhibited hyperactivation of the right lateral orbitofrontal cortex during successful response switching and abnormal deactivation of frontal regions during error processing in both tasks.

Conclusions: Our results support that patients with HD and OCD present dissimilar cognitive profiles, supported by distinct neural mechanisms. Specifically, while alterations in HD resemble an impulsive pattern of response, patients with OCD present increased error processing during response conflict protocols.
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http://dx.doi.org/10.1017/S0033291719000515DOI Listing
March 2020

Association of chronic inflammation and perceived stress with abnormal functional connectivity in brain areas involved with interoception in hepatitis C patients.

Brain Behav Immun 2019 08 11;80:204-218. Epub 2019 Mar 11.

Department of Psychiatry and Psychology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigacion Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain; Department of Medicine, Faculty of Medicine, and Institute of Neuroscience, University of Barcelona (UB), Barcelona, Spain. Electronic address:

Background: Sickness behavioral changes elicited by inflammation may become prolonged and dysfunctional in patients with chronic disease, such as chronic hepatitis C (CHC). Neuroimaging studies show that the basal ganglia and insula are sensitive to systemic inflammation.

Aim: To elucidate the clinical and neurobiological aspects of prolonged illnesses in patients with CHC.

Methods: Thirty-five CHC patients not treated with interferon-α or other antiviral therapy, and 30 control subjects matched for age and sex, were evaluated for perceived stress (perceived stress scale; PSS), depression (PHQ-9), fatigue and irritability through a visual analog scale (VAS), as well as serum levels of interleukin-6 (IL-6), prostaglandin E (PGE) and oxidative stress markers. Functional MRI was performed, measuring resting-state functional connectivity using a region-of-interest (seed)-based approach focusing on the bilateral insula, subgenual anterior cingulate cortex and bilateral putamen. Between-group differences in functional connectivity patterns were assessed with two-sample t-tests, while the associations between symptoms, inflammatory markers and functional connectivity patterns were analyzed with multiple regression analyses.

Results: CHC patients had higher PSS, PHQ-9 and VAS scores for fatigue and irritability, as well as increased IL-6 levels, PGE concentrations and antioxidant system activation compared to controls. PSS scores positively correlated with functional connectivity between the right anterior insula and right putamen, whereas PHQ-9 scores correlated with functional connectivity between most of the seeds and the right anterior insula. PGE (positively) and IL-6 (negatively) correlated with functional connectivity between the right anterior insula and right caudate nucleus and between the right ventral putamen and right putamen/globus pallidus. PGE and PSS scores accounted for 46% of the variance in functional connectivity between the anterior insula and putamen.

Conclusions: CHC patients exhibited increased perceived stress and depressive symptoms, which were associated with changes in inflammatory marker levels and in functional connectivity between the insula and putamen, areas involved in interoceptive integration, emotional awareness, and orientation of motivational state.
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http://dx.doi.org/10.1016/j.bbi.2019.03.008DOI Listing
August 2019

An examination of orbitofrontal sulcogyral morphology in obsessive-compulsive disorder.

Psychiatry Res Neuroimaging 2019 04 22;286:18-23. Epub 2019 Feb 22.

Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & Melbourne Health, Melbourne, Australia. Electronic address:

Obsessive-compulsive disorder (OCD) has been consistently associated with structural and functional alteration of the orbitofrontal cortex (OFC) and its subcortical connections. In exploring these alterations, a neurodevelopmental basis to OCD has been suggested. While some studies have examined outcomes of early cortical maturation processes, such as global cortical thickness and gyrification, no work has specifically examined the OFC. Within the OFC, three types of sulcogyral patterns have been identified as a result of variance in cortical folding. The distribution of these patterns has been found to differ in patients of various neuropsychiatric disorders relative to the general population, however no study has yet investigated this distribution in individuals with OCD. Eighty OCD patients and 78 healthy controls were evaluated using magnetic resonance imaging, with identification of the sulcogyral pattern based on the method of Chiavaras and Petrides (2000). While gross changes in OFC sulcogyral patterning did not distinguish OCD patients from healthy controls, expression of both the Type II and Type III patterns was significantly associated with increased OCD illness severity. This finding indicates that early neurodevelopmental factors may influence illness severity.
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http://dx.doi.org/10.1016/j.pscychresns.2019.02.004DOI Listing
April 2019

Neurodevelopmental correlates of the emerging adult self.

Dev Cogn Neurosci 2019 04 16;36:100626. Epub 2019 Feb 16.

Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Parkville, Australia.

The self-concept - the set of beliefs that a person has about themselves - shows significant development from adolescence to early adulthood, in parallel with brain development over the same period. We sought to investigate how age-related changes in self-appraisal processes corresponded with brain network segregation and integration in healthy adolescents and young adults. We scanned 88 participants (46 female), aged from 15 to 25 years, as they performed a self-appraisal task. We first examined their patterns of activation to self-appraisal, and replicated prior reports of reduced dorsomedial prefrontal cortex activation with older age, with similar reductions in precuneus, right anterior insula/operculum, and a region extending from thalamus to striatum. We used independent component analysis to identify distinct anterior and posterior components of the default mode network (DMN), which were associated with the self-appraisal and rest-fixation parts of the task, respectively. Increasing age was associated with reduced functional connectivity between the two components. Finally, analyses of task-evoked interactions between pairs of nodes within the DMN identified a subnetwork that demonstrated reduced connectivity with increasing age. Decreased network integration within the DMN appears to be an important higher-order maturational process supporting the emerging adult self.
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http://dx.doi.org/10.1016/j.dcn.2019.100626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969193PMC
April 2019

Brain Structure and Function in School-Aged Children With Sluggish Cognitive Tempo Symptoms.

J Am Acad Child Adolesc Psychiatry 2019 02 26;58(2):256-266. Epub 2018 Nov 26.

Institut de Salut Global de Barcelona (ISGlobal), Barcelona, Spain; Hospital del Mar Research Institute, Barcelona, and the Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.

Objective: Sluggish cognitive tempo (SCT) is a cluster of symptoms associated with poor function in various domains of major life activities that may comprise a novel attention disorder distinct from attention-deficit/hyperactivity disorder (ADHD). Nevertheless, very little is known about the neural substrate of SCT in children. The present study aimed to examine associations between SCT symptoms and brain structure and function in school-aged children.

Method: We performed a cross-sectional MRI study in 178 children 8 to 12 years old from primary schools in Barcelona, Spain. Data were collected between January 2012 and March 2013. Parents completed the Sluggish Cognitive Tempo-Child Behavior Checklist (SCT-CBCL). Participants underwent magnetic resonance imaging to assess regional brain volume, white matter integrity using diffusion tensor imaging, and functional connectivity in major neural networks.

Results: SCT symptoms were associated with altered anatomy of the frontal lobe in the form of increased regional volume. The anomalously large cortical regions were less mature in terms of functional connectivity. Importantly, all the anatomical and functional anomalies identified remained significant after adjusting the analyses for ADHD symptom scores.

Conclusion: Our results suggest that SCT symptoms are associated with distinct features of brain structure and function that differ from the classical neural substrates described in ADHD.
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http://dx.doi.org/10.1016/j.jaac.2018.09.441DOI Listing
February 2019

Mapping Alterations of the Functional Structure of the Cerebral Cortex in Obsessive-Compulsive Disorder.

Cereb Cortex 2019 12;29(11):4753-4762

Centro Investigación Biomédica en Red de Salud Mental, CIBERSAM, Barcelona, Spain.

We mapped alterations of the functional structure of the cerebral cortex using a novel imaging approach in a sample of 160 obsessive-compulsive disorder (OCD) patients. Whole-brain functional connectivity maps were generated using multidistance measures of intracortical neural activity coupling defined within isodistant local areas. OCD patients demonstrated neural activity desynchronization within the orbitofrontal cortex and in primary somatosensory, auditory, visual, gustatory, and olfactory areas. Symptom severity was significantly associated with the degree of functional structure alteration in OCD-relevant brain regions. By means of a novel imaging perspective, we once again identified brain alterations in the orbitofrontal cortex, involving areas purportedly implicated in the pathophysiology of OCD. However, our results also indicated that weaker intracortical activity coupling is also present in each primary sensory area. On the basis of previous neurophysiological studies, such cortical activity desynchronization may best be interpreted as reflecting deficient inhibitory neuron activity and altered sensory filtering.
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http://dx.doi.org/10.1093/cercor/bhz008DOI Listing
December 2019

Lack of response to disgusting food in the hypothalamus and related structures in Prader Willi syndrome.

Neuroimage Clin 2019 4;21:101662. Epub 2019 Jan 4.

Endocrinology and Nutrition Department, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí I3PT- UAB, 08208 Sabadell, Spain.

Objective: To investigate, based on a putative abnormal neural processing of disgusting signals in Prader Willi syndrome (PWS) patients, the brain response to visual representations of disgusting food in PWS using functional MRI (fMRI).

Methods: Twenty-one genetically-confirmed PWS patients, 30 age- and sex-matched and 28 BMI-matched control subjects viewed a movie depicting disgusting food-related scenes interspersed with scenes of appetizing food while fMRI was acquired. Brain activation maps were compared between groups and correlated with disgust and hunger ratings.

Results: At the cortical level, the response to disgusting food representations in PWS patients was qualitatively similar to that of control subjects, albeit less extensive, and engaged brain regions typically related to visually-evoked disgust, such as the anterior insula/frontal operculum, the lateral frontal cortex and visual areas. By contrast, activation was almost absent in limbic structures directly concerned with the regulation of instinctive behavior robustly activated in control subjects, such as the hypothalamus, amygdala/hippocampus and periaqueductal gray.

Conclusions: Our study provides novel insights into the neural substrates of appetite control in a genetically-mediated cause of obesity. The presence of significant cortical changes further indicates that PWS patients consciously process disgusting stimuli, but the virtual absence of response in deep, limbic structures suggests that disgusting signals do not adequately reach the primary brain system for the appetite control.
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http://dx.doi.org/10.1016/j.nicl.2019.101662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412080PMC
January 2020

Brain Volumetric Correlates of Right Unilateral Versus Bitemporal Electroconvulsive Therapy for Treatment-Resistant Depression.

J Neuropsychiatry Clin Neurosci 2019 21;31(2):152-158. Epub 2018 Nov 21.

From the Department of Psychiatry, Bellvitge University Hospital-IDIBELL, L'Hospitalet de Llobregat, Barcelona (MC, IM-Z, RH-R, OC-R, JMM, MU, CS-M); the Department of Clinical Sciences, School of Medicine, University of Barcelona (MC, IM-Z, RH-R, JMM, MU); CIBERSAM, Carlos III Health Institute, Madrid (MC, NC, JP, EV, RH-R, OC-R, JMM, MU, CS-M); the Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston (MC, EL, NM, MH, JAC); the Mental Health Department, Parc Taulí Sabadell, Universitat Autònoma de Barcelona (NC); the Radiology Department, MRI Research Unit, Hospital del Mar, Barcelona (JP); Sant Joan de Déu Barcelona-Children's Hospital, Barcelona (EV); and the Department of Psychobiology and Methodology in Health Sciences, Universitat Autònoma de Barcelona (CS-M).

Objective: The selection of a bitemporal (BT) or right unilateral (RUL) electrode placement affects the efficacy and side effects of ECT. Previous studies have not entirely described the neurobiological underpinnings of such differential effects. Recent neuroimaging research on gray matter volumes is contributing to our understanding of the mechanism of action of ECT and could clarify the differential mechanisms of BT and RUL ECT.

Methods: To assess the whole-brain gray matter volumetric changes observed after treating patients with treatment-resistant depression with BT or RUL ECT, the authors used MRI to assess 24 study subjects with treatment-resistant depression (bifrontotemporal ECT, N=12; RUL ECT, N=12) at two time points (before the first ECT session and after ECT completion).

Results: Study subjects receiving BT ECT showed gray matter volume increases in the bilateral limbic system, but subjects treated with RUL ECT showed gray matter volume increases limited to the right hemisphere. The authors observed significant differences between the two groups in midtemporal and subcortical limbic structures in the left hemisphere.

Conclusions: These findings highlight that ECT-induced gray matter volume increases may be specifically observed in the stimulated hemispheres. The authors suggest that electrode placement may relevantly contribute to the development of personalized ECT protocols.
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http://dx.doi.org/10.1176/appi.neuropsych.18080177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857738PMC
December 2019

[Prevalence and characteristics of chronic obstructive pulmonary disease in non-smokers].

Aten Primaria 2019 12 16;51(10):602-609. Epub 2018 Nov 16.

Institut de Recerca Biomèdica (IRB) de Lleida, Lleida, España; Agència de Salut Pública de Catalunya, Departament de Salut, Lleida, España; Facultat de Medicina, Universitat de Lleida, Lleida, España.

Objective: The objective of the study was to know the profile of patients diagnosed with chronic obstructive pulmonary disease (COPD) and who have never been smokers.

Design: A transversal study.

Location: Primary Care Centre of Pla d'Urgell (Primary care setting in Lleida, Spain).

Participants: 512 patients older than 40 years with COPD from Primary Care Centre of Pla d'Urgell with a compatible spirometry [forced expiratory volume in one second (FEV)/forced vital capacity (FVC) ratio <0.7) to the beginning of the study.

Main Measurements: The dependent variable was de COPD in non-smokers and the independents were variables collected from the information on the respiratory clinical history, the risk factors of the patients and on quality of life. We designed a predictor model of COPD in non-smokers compared to smokers.

Results: 33.2% of COPD patients had never been smokers, 59.4% of whom were women. The average FEV for non-smokers was 70.5 (SD=17.1), higher than 62.6 (SD=18.5) for smokers/former smokers (p<0.001). The coverage of pneumococcal vaccination 23V was better in non-smokers (75.3%), p<0.001. COPD in non-smokers (compared to smokers/former smokers) were: mostly women (OR=16.46), older (OR=1.1), with better FEV (OR=1.1), better perception of quality, EuroQoL-5D (OR=0.8), with lower prevalence of diabetes (OR=0.5), lower level of studies (OR=0.2), and with fewer previous hospitalizations (OR=0.3).

Conclusions: The study evidences a high proportion of non-smokers in COPD patients. Our study aims that older women with less severity would be associated with an increased risk of COPD in non-smokers. It seems to indicate that COPD in non-smokers would appear at later ages and would be milder than smoking-related COPD.
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http://dx.doi.org/10.1016/j.aprim.2017.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930941PMC
December 2019

The contribution of brain imaging to the understanding of psychopathy.

Psychol Med 2019 01 12;49(1):20-31. Epub 2018 Sep 12.

Department of Mental Health, Corporació Sanitaria Parc Taulí, Sabadell, and Department of Psychiatry,Autonomous University of Barcelona,Barcelona,Spain.

Psychopathy is a personality type characterized by both callous emotional dysfunction and deviant behavior that affects society in the form of actions that harm others. Historically, researchers have been concerned with seeking data and arguments to support a neurobiological foundation of psychopathy. In the past few years, increasing research has begun to reveal brain alterations putatively underlying the enigmatic psychopathic personality. In this review, we describe the brain anatomical and functional features that characterize psychopathy from a synthesis of available neuroimaging research and discuss how such brain anomalies may account for psychopathic behavior. The results are consistent in showing anatomical alterations involving primarily a ventral system connecting the anterior temporal lobe to anterior and ventral frontal areas, and a dorsal system connecting the medial frontal lobe to the posterior cingulate cortex/precuneus complex and, in turn, to medial structures of the temporal lobe. Functional imaging data indicate that relevant emotional flow breakdown may occur in both these brain systems and suggest specific mechanisms via which emotion is anomalously integrated into cognition in psychopathic individuals during moral challenge. Directions for future research are delineated emphasizing, for instance, the relevance of further establishing the contribution of early life stress to a learned blockage of emotional self-exposure, and the potential role of androgenic hormones in the development of cortical anomalies.
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http://dx.doi.org/10.1017/S0033291718002507DOI Listing
January 2019

Sparse multiple factor analysis to integrate genetic data, neuroimaging features, and attention-deficit/hyperactivity disorder domains.

Int J Methods Psychiatr Res 2018 09 14;27(3):e1738. Epub 2018 Aug 14.

ISGlobal, Barcelona Institute for Global Health, Barcelona, Spain.

Objectives: We proposed the application of a multivariate cross-sectional framework based on a combination of a variable selection method and a multiple factor analysis (MFA) in order to identify complex meaningful biological signals related to attention-deficit/hyperactivity disorder (ADHD) symptoms and hyperactivity/inattention domains.

Methods: The study included 135 children from the general population with genomic and neuroimaging data. ADHD symptoms were assessed using a questionnaire based on ADHD-DSM-IV criteria. In all analyses, the raw sum scores of the hyperactivity and inattention domains and total ADHD were used. The analytical framework comprised two steps. First, zero-inflated negative binomial linear model via penalized maximum likelihood (LASSO-ZINB) was performed. Second, the most predictive features obtained with LASSO-ZINB were used as input for the MFA.

Results: We observed significant relationships between ADHD symptoms and hyperactivity and inattention domains with white matter, gray matter regions, and cerebellum, as well as with loci within chromosome 1.

Conclusions: Multivariate methods can be used to advance the neurobiological characterization of complex diseases, improving the statistical power with respect to univariate methods, allowing the identification of meaningful biological signals in Imaging Genetic studies.
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http://dx.doi.org/10.1002/mpr.1738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6877273PMC
September 2018

Traffic-Related Air Pollution, ε4 Status, and Neurodevelopmental Outcomes among School Children Enrolled in the BREATHE Project (Catalonia, Spain).

Environ Health Perspect 2018 08 2;126(8):087001. Epub 2018 Aug 2.

ISGlobal, Barcelona Institute for Global Health, Barcelona, Spain

Background: Traffic-related air pollution is emerging as a risk factor for Alzheimer's disease (AD) and impaired brain development. Individual differences in vulnerability to air pollution may involve the ε4 allele of () gene, the primary genetic risk factor for AD.

Objective: We analyzed whether the association between traffic air pollution and neurodevelopmental outcomes is modified by ε4 status in children.

Methods: Data on parent-reported behavior problems (total difficulties scores, Strengths and Difficulties Questionnaire), teacher-reported attention-deficit hyperactivity disorder (ADHD) symptom scores, cognitive performance trajectories (computerized tests of inattentiveness and working memory repeated 2-4 times during January 2012-March 2013), and genotypes were obtained for 1,667 children age 7-11 y attending 39 schools in or near Barcelona. Basal ganglia volume (putamen, caudate, and globus pallidum) was measured in 163 of the children by MRI (October 2012-April 2014.) Average annual outdoor polycyclic aromatic hydrocarbons (PAHs), elemental carbon (EC), and nitrogen dioxide (NO) concentrations were estimated based on measurements at each school (two 1-wk campaigns conducted 6 months apart in 2012).

Results: ε4 allele carriers had significantly higher behavior problem scores than noncarriers, and adverse associations with PAHs and NO were stronger or limited to ε4 carriers for behavior problem scores (-interaction 0.03 and 0.04), caudate volume (-interaction 0.04 and 0.03), and inattentiveness trajectories (-interaction 0.15 and 0.08, respectively). Patterns of associations with the same outcomes were similar for EC.

Conclusion: PAHs, EC, and NO were associated with higher behavior problem scores, smaller reductions in inattentiveness over time, and smaller caudate volume in ε4 allele carriers in our study population, and corresponding associations were weak or absent among ε4 noncarriers. These findings support a potential role of in biological mechanisms that may contribute to associations between air pollution and neurobehavioral outcomes in children. https://doi.org/10.1289/EHP2246.
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http://dx.doi.org/10.1289/EHP2246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108838PMC
August 2018

The Effects of Air Pollution on the Brain: a Review of Studies Interfacing Environmental Epidemiology and Neuroimaging.

Curr Environ Health Rep 2018 09;5(3):351-364

Pompeu Fabra University, Barcelona, Catalonia, Spain.

Purpose Of Review: An emerging body of evidence has raised concern regarding the potentially harmful effects of inhaled pollutants on the central nervous system during the last decade. In the general population, traffic-related air pollution (TRAP) exposure has been associated with adverse effects on cognitive, behavior, and psychomotor development in children, and with cognitive decline and higher risk of dementia in the elderly. Recently, studies have interfaced environmental epidemiology with magnetic resonance imaging to investigate in vivo the effects of TRAP on the human brain. The aim of this systematic review was to describe and synthesize the findings from these studies. The bibliographic search was carried out in PubMed with ad hoc keywords.

Recent Findings: The selected studies revealed that cerebral white matter, cortical gray matter, and basal ganglia might be the targets of TRAP. The detected brain damages could be involved in cognition changes. The effect of TRAP on cognition appears to be biologically plausible. Interfacing environmental epidemiology and neuroimaging is an emerging field with room for improvement. Future studies, together with inputs from experimental findings, should provide more relevant and detailed knowledge about the nature of the relationship between TRAP exposure and cognitive, behavior, and psychomotor disorders observed in the general population.
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http://dx.doi.org/10.1007/s40572-018-0209-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132565PMC
September 2018

Strategies for integrated analysis in imaging genetics studies.

Neurosci Biobehav Rev 2018 10 23;93:57-70. Epub 2018 Jun 23.

Barcelona Research Institute for Global Health (ISGlobal), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. Electronic address:

Imaging Genetics (IG) integrates neuroimaging and genomic data from the same individual, deepening our knowledge of the biological mechanisms behind neurodevelopmental domains and neurological disorders. Although the literature on IG has exponentially grown over the past years, the majority of studies have mainly analyzed associations between candidate brain regions and individual genetic variants. However, this strategy is not designed to deal with the complexity of neurobiological mechanisms underlying behavioral and neurodevelopmental domains. Moreover, larger sample sizes and increased multidimensionality of this type of data represents a challenge for standardizing modeling procedures in IG research. This review provides a systematic update of the methods and strategies currently used in IG studies, and serves as an analytical framework for researchers working in this field. To complement the functionalities of the Neuroconductor framework, we also describe existing R packages that implement these methodologies. In addition, we present an overview of how these methodological approaches are applied in integrating neuroimaging and genetic data.
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http://dx.doi.org/10.1016/j.neubiorev.2018.06.013DOI Listing
October 2018

Characteristics and prognosis of patients admitted to a hospital emergency department for traumatic brain injury and with anticoagulant or antiplatelet treatment.

Neurocirugia (Astur) 2018 Sep - Oct;29(5):233-239. Epub 2018 Jun 10.

Servei d'Atenció Primària, Regió Sanitària de Lleida, Lleida, España; Institut Universitari d'Investigació d'Atenció Primaria, IDIAP, Lleida, España; Facultat de Medicina, Universitat de Lleida, Lleida, España.

Background And Objective: To determine mortality and complications of patients with traumatic brain injury (TBI) with antiplatelet or anticoagulant treatment in a hospital emergency department.

Materials And Methods: Study of hospital cohorts of the 243 patients who attended with pure TBI to the emergency service of the Arnau de Vilanova University Hospital in Lleida between June 1, 2015 and June 1, 2016. Sociodemographic, clinical and other variables related to clinical management were collected. Presence of complications and in-hospital mortality were registered at 24hours, at 48hours and one week after TBI.

Results: Overall, 50.2% of patients were men, with median age of 80.8years, and without CT-scan findings at admission in 62.3% of cases. A total of 14 patients died (5.8%). Overall mortality was associated with comorbidity, with knowledge loss and with fluctuation of the Glasgow comma scale in the acute process. Patients treated with anticoagulants (39.5%) or antiplatelet agents (33.3%) were older, with higher degree of dependency and more comorbidity, but did not present more complications. Without reaching statistical significance, higher mortality was observed during the first week in anticoagulated patients (7.3% vs 4.8%, P=.585) or with antiplatelet treatment (8.6% vs 4.3%, P=.241) with respect to those not treated.

Conclusions: No worse results have been observed in number of complications in patients with TBI treated with anticoagulant or antiplatelet treatment, so clinical management seems appropriate. The higher mortality could be explained by the greater complexity of these patients. It would be necessary to carry out more studies, preferably prospective with follow-up after discharge, in order to establish causal mechanisms between clinical management and mortality or associated complications to TBI.
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http://dx.doi.org/10.1016/j.neucir.2018.05.001DOI Listing
October 2019

A longitudinal study of brain anatomy changes preceding dementia in Down syndrome.

Neuroimage Clin 2018 28;18:160-166. Epub 2018 Jan 28.

Specialized Service in Mental Health and Intellectual Disability, Institut Assistència Sanitària (IAS), Parc Hospitalari Martí i Julià, 17190 Girona, Spain.

Background: We longitudinally assessed Down syndrome individuals at the age of risk of developing dementia to measure changes in brain anatomy and their relationship to cognitive impairment progression.

Methods: Forty-two Down syndrome individuals were initially included, of whom 27 (mean age 46.8 years) were evaluable on the basis of completing the 2-year follow-up and success in obtaining good quality MRI exams. Voxel-based morphometry was used to estimate regional brain volumes at baseline and follow-up on 3D anatomical images. Longitudinal volume changes for the group and their relationship with change in general cognitive status and specific cognitive domains were mapped.

Results: As a group, significant volume reduction was identified in the substantia innominata region of the basal forebrain, hippocampus, lateral temporal cortex and left arcuate fasciculus. Volume reduction in the substantia innominata and hippocampus was more prominent in individuals whose clinical status changed from cognitively stable to mild cognitive impairment or dementia during the follow-up. Relevantly, longitudinal memory score change was specifically associated with volume change in the hippocampus, prospective memory with prefrontal lobe and verbal comprehension with language-related brain areas.

Conclusions: Results are notably concordant with the well-established anatomical changes signaling the progression to dementia in Alzheimer's disease, despite the dense baseline pathology that developmentally accumulates in Down syndrome. This commonality supports the potential value of Down syndrome as a genetic model of Alzheimer's neurodegeneration and may serve to further support the view that Down syndrome patients are best candidates to benefit from treatment research in Alzheimer's disease.
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http://dx.doi.org/10.1016/j.nicl.2018.01.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5984600PMC
January 2019

The right occipital lobe and poor insight in first-episode psychosis.

PLoS One 2018 1;13(6):e0197715. Epub 2018 Jun 1.

CIBERSAM, Centro Investigación Biomédica en Red de Salud Mental, Santander, Spain.

Lack of insight is a core feature of non-affective psychosis and has been associated with poorer outcomes. Brain abnormalities underlying lack of insight have been suggested, mostly in the frontal lobe, although previous research showed mixed results. We used a voxel-based morphometry (VBM) analysis in 108 first-episode non-affective psychosis patients to investigate the pattern of brain structural abnormalities related to lack of insight. In addition, 77 healthy volunteers were compared with the patients classified as having poor and good insight. The shortened version of the Scale to Assess Unawareness of Mental Disorder was used to evaluate insight. Patients with poor insight (n = 68) compared with patients with good insight (n = 40) showed a single significant cluster (kc = 5834; PcFWE = 0.001) of reduced grey matter volume (GMV) in the right occipital lobe extending to its lateral and medial surfaces, the cuneus, and the middle temporal gyrus. In addition, GMV at this cluster showed a negative correlation with the score of the SUMD (r = -0.305; p = 0.001). When comparing patients with poor insight with healthy subjects overall reductions of GMV were found, mainly in frontal and occipital lobes. Hence, poor insight in non-affective psychosis seems to be associated with specific brain abnormalities in the right occipital and temporal cortical regions. Dysfunction in any combination of these areas may contribute to lack of insight in non-affective psychosis. Specifically, the 'right' hemisphere dysfunction underlying impaired insight in our sample is consistent with previously reported similarities between lack of insight in psychosis and anosognosia in neurological disorders.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0197715PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983855PMC
December 2018