Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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Brain structure and function related to cognitive reserve variables in normal aging, mild cognitive impairment and Alzheimer's disease
(Elsevier B.V., 2009-07) Solé Padullés, Cristina; Bartrés Faz, David; Junqué i Plaja, Carme, 1955-; Vendrell i Gómez, Pere; Rami González, Lorena; Clemente, Immaculada; Bosch Capdevila, Beatriz; Villar, Amparo; Bargalló Alabart, Núria; Jurado, Ma. Ángeles (María Ángeles); Barrios Cerrejón, M. Teresa; Molinuevo, José Luis
Cognitive reserve (CR) is the brain's capacity to cope with cerebral damage to minimize clinical manifestations. The 'passive model' considers head or brain measures as anatomical substrates of CR, whereas the 'active model' emphasizes the use of brain networks effectively. Sixteen healthy subjects, 12 amnestic mild cognitive impairment (MCI) and 16 cases with mild Alzheimer's disease (AD) were included to investigate the relationships between proxies of CR and cerebral measures considered in the 'passive' and 'active' models. CR proxies were inferred premorbid IQ (WAIS Vocabulary test), 'education-occupation', a questionnaire of intellectual and social activities and a composite CR measure. MRI-derived whole-brain volumes and brain activity by functional MRI during a visual encoding task were obtained. Among healthy elders, higher CR was related to larger brains and reduced activity during cognitive processing, suggesting more effective use of cerebral networks. In contrast, higher CR was associated with reduced brain volumes in MCI and AD and increased brain function in the latter, indicating more advanced neuropathology but that active compensatory mechanisms are still at work in higher CR patients. The right superior temporal gyrus (BA 22) and the left superior parietal lobe (BA 7) showed greatest significant differences in direction of slope with CR and activation between controls and AD cases. Finally, a regression analysis revealed that fMRI patterns were more closely related to CR proxies than brain volumes. Overall, inverse relationships for healthy and pathological aging groups emerged between brain structure and function and CR variables.
Effects of androgenization on the white matter microstructure of female-to-male transsexuals. A diffusion tensor imaging study
(Elsevier Ltd., 2012-08-01) Rametti, Giuseppina; Carrillo, Beatriz; Gómez Gil, Esther; Junqué i Plaja, Carme, 1955-; Zubiaurre Elorza, Leire; Segovia, Santiago; Gómez Jiménez, Ángel; Karadi, Kazmer; Guillamon Fernández, Antonio
Diffusion tensor imaging (DTI) can sensitively detect white matter sex differences and the effects of pharmacological treatments. Before cross-sex hormone treatment, the white matter microstructure of several brain bundles in female-to-male transsexuals (FtMs) differs from those in females but not from that in males. The purpose of this study was to investigate whether cross-sex hormone treatment (androgenization) affects the brain white matter microstructure. Using a Siemens 3 T Trio Tim Magneton, DTI was performed twice, before and during cross-sex hormonal treatment with testosterone in 15 FtMs scanned. Fractional anisotropy (FA) was analyzed on white matter of the whole brain, and the latter was spatially analyzed using Tract-Based Spatial Statistics. Before each scan the subjects were assessed for serum testosterone, sex hormone binding globulin level (SHBG), and their free testosterone index. After at least seven months of cross-gender hormonal treatment, FA values increased in the right superior longitudinal fasciculus (SLF) and the right corticospinal tract (CST) in FtMs compared to their pre-treatment values. Hierarchical regression analyses showed that the increments in the FA values in the SLF and CST are predicted by the free testosterone index before hormonal treatment. All these observations suggest that testosterone treatment changes white matter microstructure in FtMs.
Interactions of cognitive reserve with regional brain anatomy and brain function during a working memory task in healthy elders
(Elsevier B.V., 2009-02) Bartrés Faz, David; Solé Padullés, Cristina; Junqué i Plaja, Carme, 1955-; Rami González, Lorena; Bosch Capdevila, Beatriz; Bargalló Alabart, Núria; Falcón Falcón, Carles Maria; Sánchez del Valle Díaz, Raquel; Molinuevo, José Luis
Cognitive reserve (CR) defines the capacity of the adult brain to cope with pathology in order to minimize symptomatology. Relevant lifetime social, cognitive and leisure activities represent measurable proxies of cognitive CR but its underlying structural and functional brain mechanisms remain poorly understood. We investigated the relationship between CR and regional gray matter volumes and brain activity (fMRI) during a working memory task in a sample of healthy elders. Participants with higher CR had larger gray matter volumes in frontal and parietal regions. Conversely, a negative correlation was observed between CR and fMRI signal in the right inferior frontal cortex, suggesting increased neural efficiency for higher CR individuals. This latter association however disappeared after adjusting for gray matter images in a voxel-based manner. Altogether, present results may reflect both general and specific anatomofunctional correlates of CR in the healthy elders. Thus, whereas heteromodal anterior and posterior gray matter regions correspond to passive (i.e. morphological) correlates of CR unrelated to functional brain activation during this particular cognitive task, the right inferior frontal area reveals interactions between active and passive components of CR related to the cognitive functions tested in the fMRI study.
Modulation of large-scale brain networks by transcranial direct current stimulation evidenced by resting-state functional MRI
(Elsevier, 2011-08-11) Peña-Gómez, Cleofé; Sala Llonch, Roser; Junqué i Plaja, Carme, 1955-; Clemente, Immaculada; Vidal Piñeiro, Dídac; Bargalló Alabart, Núria; Falcón Falcón, Carles Maria; Valls Solé, Josep; Pascual Leone, Álvaro, 1961-; Bartrés Faz, David
Background: Brain areas interact mutually to perform particular complex brain functions such as memory or language. Furthermore, under resting-state conditions several spatial patterns have been identified that resemble functional systems involved in cognitive functions. Among these, the default-mode network (DMN), which is consistently deactivated during task periods and is related to a variety of cognitive functions, has attracted most attention. In addition, in resting-state conditions some brain areas engaged in focused attention (such as the anticorrelated network, AN) show a strong negative correlation with DMN; as task demand increases, AN activity rises, and DMN activity falls. Objective: We combined transcranial direct current stimulation (tDCS) with functional magnetic resonance imaging (fMRI) to investigate these brain network dynamics. Methods: Ten healthy young volunteers underwent four blocks of resting-state fMRI (10-minutes), each of them immediately after 20 minutes of sham or active tDCS (2 mA), on two different days. On the first day the anodal electrode was placed over the left dorsolateral prefrontal cortex (DLPFC) (part of the AN) with the cathode over the contralateral supraorbital area, and on the second day, the electrode arrangement was reversed (anode right-DLPFC, cathode left-supraorbital). Results: After active stimulation, functional network connectivity revealed increased synchrony within the AN components and reduced synchrony in the DMN components. Conclusions: Our study reveals a reconfiguration of intrinsic brain activity networks after active tDCS. These effects may help to explain earlier reports of improvements in cognitive functions after anodal-tDCS, where increasing cortical excitability may have facilitated reconfiguration of functional brain networks to address upcoming cognitive demands.
Inferior frontal and insular cortical thinning is related to dysfunctional brain activation/deactivation during working memory task in schizophrenic patients
(Elsevier B.V., 2013-11-30) Pujol, Núria; Penadés Rubio, Rafael; Rametti, Giuseppina; Catalán Campos, Rosa; Vidal Piñeiro, Dídac; Palacios, Eva M.; Bargalló Alabart, Núria; Bernardo Arroyo, Miquel; Junqué i Plaja, Carme, 1955-
Although working memory is known to be impaired in schizophrenia the anatomical and functional relationships underlying this deficit remain to be elucidated. A combined imaging approach involving functional and structural magnetic resonance techniques was used, applying independent component analysis and surface-based morphometry to 14 patients with schizophrenia and 14 healthy controls. Neurocognitive functioning was assessed by a neuropsychological test battery that measured executive function. It was hypothesized that working memory dysfunctional connectivity in schizophrenia is related to underlying anatomical abnormalities. Patients with schizophrenia showed cortical thinning in the left inferior frontal gyrus and insula, which explained 57% of blood oxygenation level-dependent signal magnitude in functional magnetic resonance imaging in the central executive network (lateral prefrontal and parietal cortex) over-activation and default mode network (anterior and posterior cingulate) deactivation. No structure-function relationship emerged in the healthy control group. The study provides evidence to suggest that dysfunctional activation/deactivation patterns in schizophrenia may be explained in terms of underlying gray matter deficits.
Olfactory dysfunction after subarachnoid haemorrhage caused by ruptured aneurysms of the anterior communicating artery.
(American Association of Neurological Surgeons, 2009-04-10) Escartin Martin, Gemma; Junqué i Plaja, Carme, 1955-; Juncadella i Puig, Montserrat; Gabarrós, Andreu; Miquel, Maria Angels de; Rubio Borrego, Francisco Ramón
Object Olfactory dysfunction has an important impact on quality of life. In patients with subarachnoid hemorrhage (SAH), anosmia has mainly been reported after surgery for aneurysms of the anterior communicating artery (ACoA). The authors studied whether and how frequently patients with ACoA aneurysms present with smell identification deficits in 2 treatment groups (endovascular and surgical treatment). Methods A prospective study was conducted of patients with SAH caused by ruptured ACoAs and who had a Glasgow Outcome Scale score of 1 or 2, in comparison with a control group matched by age and sex. Olfactory function was assessed using the University of Pennsylvania Smell Identification Test (UPSIT). Results A total of 39 patients were enrolled. A marked olfactory impairment was observed in patients with ruptured ACoAs compared with the control group (p < 0.001). Seventeen patients with ruptured ACoAs (44%) compared with 1 patient in the control group (3%) showed a smell identification deficit according to performance on the UPSIT (p < 0.001). Both groups that underwent treatment presented with olfactory impairment. Ten (59%) of 17 patients who underwent aneurysmal clip placement versus 6 (28.5%) of 21 patients who underwent coil embolization scored below the 25th percentile on the UPSIT, and surgical patients also performed worse than endovascular patients (p = 0.048). The authors observed a worse performance on the olfactory test in patients subjected to endovascular coil embolization when cerebral vasospasm (p = 0.037) or frontal cerebral lesions (p = 0.009) were present. This difference was not observed in patients who underwent surgery. Conclusions Olfactory disorders after SAH caused by rupture of the ACoA are very frequent and were present in both treatment groups. Cerebral vasospasm and frontal lobe lesions are related to worse performance on an olfactory test in patients undergoing endovascular coil embolization.
Nuclear stiffness through lamin A/C overexpression differentially modulates chromosomal instability biomarkers
(Wiley, 2025-02-25) Bosch Calvet, Mireia; Pérez Venteo, Alejandro; Cebria Xart, Alex; Garcia Cajide, Marta; Mauvezin, Caroline
Background Information Mitosis is crucial for the faithful transmission of genetic material, and disruptions can result in chromosomal instability (CIN), a hallmark of cancer. CIN is a known driver of tumor heterogeneity and anti-cancer drug resistance, thus highlighting the need to assess CIN levels in cancer cells to design effective targeted therapy. While micronuclei are widely recognized as CIN markers, we have recently identified the toroidal nucleus, a novel ring-shaped nuclear phenotype arising as well from chromosome mis-segregation. Results Here, we examined whether increasing nuclear envelope stiffness through lamin A/C overexpression could affect the formation of toroidal nuclei and micronuclei. Interestingly, lamin A/C overexpression led to an increase in toroidal nuclei while reducing micronuclei prevalence. We demonstrated that chromatin compaction and nuclear stiffness drive the formation of toroidal nuclei. Furthermore, inhibition of autophagy and lysosomal function elevated the frequency of toroidal nuclei without affecting the number of micronuclei in the whole cell population. We demonstrated that this divergence between the two CIN biomarkers is independent of defects in lamin A processing. Conclusions and Significance These findings uncover a complex interplay between nuclear architecture and levels of CIN, advancing our understanding of the mechanisms supporting genomic stability and further contributing to cancer biology.
A phase II trial of lenalidomide, dexamethasone and cyclophosphamide for newly diagnosed patients with systemic immunoglobulin light chain amyloidosis
(2015-09-01) Cibeira López, Maria Teresa; Oriol, Albert; Lahuerta, Juan José ; Mateos, M. Victoria; De La Rubia, Javier ; Hernández, Miguel T. ; Granell, Miquel ; Fernández de Larrea Rodríguez, Carlos José ; San Miguel, Jesús F. ; Bladé Creixenti, Joan
Immunomodulatory drugs have been shown to be of benefit in relapsed/refractory immunoglobulin light-chain (AL) amyloidosis. We designed a prospective, multicentre phase II trial of lenalidomide, dexamethasone and cyclophosphamide for newly diagnosed patients with AL amyloidosis not eligible for autologous stem-cell transplantation. Twenty-eight patients were included in the study. Cardiac involvement was present in 23 patients; 14 of them had cardiac stage III. The overall haematological response rate was 46%, including complete and very good partial responses in 25% and 18% of patients respectively. Haematological response was mainly associated with absence of cardiac stage III and lower tumour burden. Organ response was observed in 46% of patients. After a median follow-up of 24 months, median progression-free and overall survival have not been reached, both being significantly longer in responders (P < 0·001 and P = 0·001 respectively). Seventeen patients have discontinued treatment, mostly due to amyloid-related death, disease progression or lack of response. Only 14% of the patients discontinued treatment due to therapy-related adverse events. Our results support the efficacy of this regimen, with high quality responses and prolonged survival, as well as its tolerability, in patients with AL amyloidosis not eligible for stem cell transplant and without advanced cardiac involvement (clinicaltrials.gov identifier: NCT01194791).
Polo-like kinase 1 inhibitors in refractory colorectal cancer: deciphering the myth of synthetic lethality
(AME Publishing Company, 2024-08-25) Rojas, Mariam; Gonzalez, Laura; Cascante i Serratosa, Marta; Maurel Santasusana, Joan
Metastatic colorectal cancer (mCRC) remains a highly lethal disease because resistance to chemotherapy and targeted agents—including anti-VEGF and anti-EGFR therapies—emerges rapidly and universally. In RAS‑mutant mCRC, second-line treatment with FOLFIRI plus bevacizumab achieves modest clinical benefit, underscoring the need to understand mechanisms of resistance and develop rational combination strategies. Recent evidence implicates oxidative phosphorylation (OXPHOS), antioxidant programs such as the pentose phosphate pathway (PPP), and polo-like kinase 1 (PLK1)–dependent cell‑cycle regulation as key determinants of therapeutic refractoriness. In a recent phase Ib study, onvansertib, a PLK1 inhibitor, combined with FOLFIRI and bevacizumab produced a notable 44% response rate and a median progression-free survival of 12.6 months in RAS‑mutant tumors, suggesting a subset of patients may derive meaningful benefit. Integrating these clinical findings with current metabolic and genomic insights, we highlight how OXPHOS‑driven tumors activate antioxidant networks, sustain chromosome instability, and remodel nutrient usage—features that may blunt synthetic lethality and foster resistance to DNA‑damaging agents, PARP inhibitors, and PLK1 inhibition. We also discuss how altered DNA‑repair reliance (HR, NHEJ, and MMEJ), lactate‑supported mitochondrial metabolism, ENPP1‑mediated immunosuppression, and MYC activation converge to shape chemoresistance and impaired immune responses in microsatellite‑stable colorectal cancer. A more precise therapeutic approach may require selecting patients with combined OXPHOS and PPP activation and leveraging rational combinations involving PLK1, PARP, or ENPP1 inhibitors together with immune checkpoint blockade. Such strategies could enhance the efficacy of ongoing clinical trials and refine future treatment paradigms for heavily pretreated colorectal cancer.
Competing signaling pathways controls electrotaxis
(Elsevier, 2025-05-16) Kulkarni, Shardool; Tebar Ramon, Francesc; Rentero Alfonso, Carles; Zhao, Min; Sáez, Pablo
Understanding how cells follow exogenous cues is a key question for biology, medicine, and bioengineering. Growing evidence shows that electric fields represent a precise and programmable method to control cell migration. Most data suggest that the polarization of membrane proteins and the following downstream signaling are central to electrotaxis. Unfortunately, how these multiple mechanisms coordinate with the motile machinery of the cell is still poorly understood. Here, we develop a mechanistic model that explains electrotaxis across different cell types. Using the zebrafish proteome, we identify membrane proteins directly related to migration signaling pathways that polarize anodally and cathodally. Further, we show that the simultaneous and asymmetric distribution of these membrane receptors establish multiple cooperative and competing stimuli for directing the anodal and cathodal migration of the cell. Using electric fields, we enhance, cancel, or switch directed cell migration, with clear implications in promoting tissue regeneration or arresting tumor progression.
Extracorporeal photopheresis for refractory BK virus-associated nephropathy in kidney transplantation
(ERA Oxford University Press, 2025-12-01) Escudero-Saiz, Victor J.; Xipell Font, Marc; Gonzalez Rojas, Ángela; Rodriguez Espinoza, Diana María; Cacho, Judit; Arana Aliaga, Carolt; Piñeiro, Gastón Julio ; Ventura Abreu Aguiarà, Pedro; Rovira Juárez, Jordi ; Larque, Ana B.; Charry, Paola; Cid Vidal, Joan; Oppenheimer, Federico; Bodro, Marta; Lozano Molero, Miguel; Diekmann, Fritz
Background BK virus-associated nephropathy (BKVAN) remains an important risk factor for kidney graft loss. The current strategy to treat the BKVAN consists in reducing immunosuppressants. However, this strategy increases the risk of graft rejection, especially in highly sensitized patients or those with previous rejection episodes. Extracorporeal photopheresis (ECP) has been used for the treatment of T cell-mediated disorders, such as solid organ rejection in cardiac, lung and hepatic transplantation, due to its immunotolerogenic effect. In addition, some data suggest that ECP might also have an immunogenic effect, generating an immune response against infections. Methods Herein we present a single-center case series of 13 patients with refractory histological-diagnosed BKVAN, where ECP was used after the failure of standard therapy. The cohort had a median age of 51 years (interquartile range 42-59), with 46% considered low immunological risk (cPRA 0%) and 54% high risk (cPRA >50%). ECP was initiated a median of 21.3 weeks (5.9-49.1) after BKVAN diagnosis, with patients receiving a median of 11 sessions (10-20). Results After starting ECP, serum BK viral load significantly decreased by 55.3%, 95.9%, 99.7% and 99.9% at 3, 6, 12 and 18 months after ECP, respectively, while kidney function slowly decreased but at a lower rate than the historical group not treated with ECP, and no adverse events were observed. Despite the reduction in immunosuppression, only one patient experienced graft rejection during follow-up, with no major impact on graft function. These findings indicate that ECP may provide potential therapeutic benefits for BKVAN and could warrant further investigation in the context of kidney transplantation.
Hippocampal abnormalities and age in chronic schizophrenia: morphometric study across the adult lifespan
(The Royal College of Psychiatrists, 2014-09-11) Pujol, Núria; Penadés Rubio, Rafael; Junqué i Plaja, Carme, 1955-; Dinov, Ivo; Fu, Cynthia H. Y.; Catalán Campos, Rosa; Ibarretxe Bilbao, Naroa ; Bargalló Alabart, Núria; Bernardo Arroyo, Miquel; Toga, Arthur; Howard, Robert J.; Costafreda, Sergi G.
Background: Hippocampal abnormalities have been demonstrated in schizophrenia. It is unclear whether these abnormalities worsen with age, and whether they affect cognition and function. Aims: To determine whether hippocampal abnormalities in chronic schizophrenia are associated with age, cognition and socio-occupational function. Method: Using 3 T magnetic resonance imaging we scanned 100 persons aged 19-82 years: 51 were out-patients with stable schizophrenia at least 2 years after diagnosis and 49 were healthy volunteers matched for age and gender. Automated analysis was used to determine hippocampal volume and shape. Results: There were differential effects of age in the schizophrenia and control samples on total hippocampal volume (group × age interaction: F(1,95) = 6.57, P = 0.012), with steeper age-related reduction in the schizophrenia group. Three-dimensional shape analysis located the age-related deformations predominantly in the mid-body of the hippocampus. In the schizophrenia group similar patterns of morphometric abnormalities were correlated with impaired cognition and poorer socio-occupational function. Conclusions: Hippocampal abnormalities are associated with age in people with chronic schizophrenia, with a steeper decline than in healthy individuals. These abnormalities are associated with cognitive and functional deficits, suggesting that hippocampal morphometry may be a biomarker for cognitive decline in older patients with schizophrenia.
Frontal cortical thinning and subcortical volume reductions in early adulthood obesity
(Elsevier B.V., 2013-11-30) Marqués Iturria, Idoia; Pueyo Benito, Roser; Garolera i Freixa, Maite; Segura i Fàbregas, Bàrbara; Junqué i Plaja, Carme, 1955-; García-García, Isabel; Sender-Palacios, Maria José; Vernet-Vernet, Maria; Narberhaus, Ana; Ariza González, Mar; Jurado, Ma. Ángeles (María Ángeles)
Obesity depends on homeostatic and hedonic food intake behavior, mediated by brain plasticity changes in cortical and subcortical structures. The aim of this study was to investigate cortical thickness and subcortical volumes of regions related to food intake behavior in a healthy young adult sample with obesity. Thirty-seven volunteers, 19 with obesity (age=33.7±5.7 (20-39) years body-mass index (BMI)=36.08±5.92 (30.10-49.69)kg/m(2)) and 18 controls (age=32.3±5.9 (21-40) years; BMI=22.54±1.94 (19.53-24.97)kg/m(2)) participated in the study. Patients with neuropsychiatric or biomedical disorders were excluded. We used FreeSurfer software to analyze structural magnetic resonance images (MRI) and obtain global brain measures, cortical thickness and subcortical volume estimations. Finally, correlation analyses were performed for brain structure data and obesity measures. There were no between-group differences in age, gender, intelligence or education. Results showed cortical thickness reductions in obesity in the left superior frontal and right medial orbitofrontal cortex. In addition, the obesity group had lower ventral diencephalon and brainstem volumes than controls, while there were no differences in any other subcortical structure. There were no statistically significant correlations between brain structure and obesity measures. Overall, our work provides evidence of the structural brain characteristics associated with metabolically normal obesity. We found reductions in cortical thickness, ventral diencephalon and brainstem volumes in areas that have been implicated in food intake behavior.
Cortical thinning is associated with disease stages and dementia in Parkinson's Disease
(British Medical Journal, 2013-03-05) Zarei, Mohammad; Ibarretxe Bilbao, Naroa; Compta, Yaroslau; Hough, Morgan; Junqué i Plaja, Carme, 1955-; Bargalló Alabart, Núria; Tolosa, Eduardo; Martí Domènech, Ma. Josep
Objective: To investigate the pattern of cortical thinning in Parkinson's disease (PD) across different disease stages and to elucidate to what extent cortical thinning is related to cognitive impairment. Design: Ninety-six subjects including 39 controls and 57 PD patients participated in this study. PD subjects were divided into three groups (early, n=24; moderate, n=18; with dementia, n=15). High field structural brain MRI images were acquired in a 3T scanner and analyses of cortical thickness and surface were carried out. Vertex-wise group comparisons were performed and cortical thickness was correlated with motor and cognitive measures. Results: We found a positive correlation between Mini-Mental State Examination scores and cortical thickness in the anterior temporal, dorsolateral prefrontal, posterior cingulate, temporal fusiform and occipitotemporal cortex. Unified Parkinson's Disease Rating Scale-III (motor subsection) scores showed a robust negative correlation with caudate volumes. We found that disease stage in PD was associated with thinning of the medial frontal (premotor and supplementary motor cortex), posterior cingulate, precuneus, lateral occipital, temporal and dorsolateral prefrontal cortex. Discriminant analysis and a receiver operating characteristics approach showed that mean cortical thickness and hippocampus volume have 80% accuracy in identifying PD patients with dementia. PD stage and PD dementia can be characterised by a specific pattern of cortical thinning. Conclusions: We conclude that measuring cortical thickness can be useful in assessing disease stage and cognitive impairment in patients with PD. In addition, cortical thickness may be useful in identifying dementia in PD.
High cognitive reserve in bipolar disorders as a moderator of neurocognitive impairment
(Elsevier B.V., 2017-01-15) Grande i Fullana, Iria; Sánchez-Moreno, José; Solé Cabezuelo, Brisa; Jiménez Martínez, Ester; Torrent Font, Carla; Bonnín Roig, Caterina del Mar; Varo, Cristina; Tabarés-Seisdedos, Rafael; Balanzá-Martínez, Vicent; Valls, Elia; Morilla, Ivette; Carvalho, André F.; Ayuso-Mateos ,J.L.; Vieta i Pascual, Eduard, 1963-; Martínez-Arán, Anabel, 1971-
Background: Cognitive reserve (CR) reflects the capacity of the brain to endure neuropathology, minimize clinical manifestations and successfully complete cognitive tasks. The present study aims to determine whether high CR may constitute a moderator of cognitive functioning in bipolar disorder (BD). Methods: 102 patients with BD and 32 healthy controls were enrolled. All patients met DSM-IV criteria for I or II BD and were euthymic (YMRS≤6 and HDRS≤8) during a 6-month period. All participants were tested with a comprehensive neuropsychological battery, and a Cerebral Reserve Score (CRS) was estimated. Subjects with a CRS below the group median were classified as having low CR, whereas participants with a CRS above the median value were considered to have high CR. Results: Participants with BD with high CR displayed a better performance in measures of attention (digits forward: F=4.554, p=0.039); phonemic and semantic verbal fluency (FAS: F=9.328, p=0.004; and Animal Naming: F=8.532, p=0.006); and verbal memory (short cued recall of California Verbal Learning Test: F=4.236, p=0.046), after multivariable adjustment for potential confounders, including number of admissions and prior psychotic symptoms. Limitations: The cross-sectional design of the study does not allow the establishment of causal inferences. Additionally, the small size of the sample may have limited some results. Conclusions: High cognitive reserve may therefore be a valuable construct to explore for predicting neurocognitive performance in patients with BD regarding premorbid status.
Functional network centrality in obesity: a resting-state and task fMRI study
(Elsevier B.V., 2015-06-19) García-García, Isabel; Jurado, Ma. Ángeles (María Ángeles); Garolera i Freixa, Maite; Marqués Iturria, Idoia; Horstmann, Annette; Segura i Fàbregas, Bàrbara; Pueyo Benito, Roser; Sender-Palacios, Maria José; Vernet-Vernet, Maria; Villringer, Arno; Junqué i Plaja, Carme, 1955-; Margulies, Daniel S.; Neumann, Jane
Obesity is associated with structural and functional alterations in brain areas that are often functionally distinct and anatomically distant. This suggests that obesity is associated with differences in functional connectivity of regions distributed across the brain. However, studies addressing whole brain functional connectivity in obesity remain scarce. Here, we compared voxel-wise degree centrality and eigenvector centrality between participants with obesity (n=20) and normal-weight controls (n=21). We analyzed resting state and task-related fMRI data acquired from the same individuals. Relative to normal-weight controls, participants with obesity exhibited reduced degree centrality in the right middle frontal gyrus in the resting-state condition. During the task fMRI condition, obese participants exhibited less degree centrality in the left middle frontal gyrus and the lateral occipital cortex along with reduced eigenvector centrality in the lateral occipital cortex and occipital pole. Our results highlight the central role of the middle frontal gyrus in the pathophysiology of obesity, a structure involved in several brain circuits signaling attention, executive functions and motor functions. Additionally, our analysis suggests the existence of task-dependent reduced centrality in occipital areas; regions with a role in perceptual processes and that are profoundly modulated by attention.
Psychoeducation in bipolar disorder with a SIMPLe smartphone application: Feasibility, acceptability and satisfaction
(Elsevier B.V., 2016-08-01) Hidalgo Mazzei, Diego; Mateu, Ainoa; Reinares, María; Murru, Andrea; del Mar Bonnín Roig, Caterina; Varo, Cristina; Valentí Ribas, Marc; Undurraga, Juan; Strejilevich, Sergio; Sánchez Moreno, José; Vieta i Pascual, Eduard, 1963-; Colom, Francesc
Background: During the last fifteen years, the possibility of delivering psychoeducation programs through Internet-based platforms have been explored. Studies evaluating those programs have shown good to acceptable retention rates. In this context, we developed a smartphone application (SIMPLe) collecting information about mood symptoms and offering personalized psychoeducation messages. The main aims of this study were to evaluate the feasibility, acceptability and satisfaction of the smartphone application. Methods: The study was conducted from March to August 2015. Participation in the study was proposed to a consecutive sample of adult patients attending an outpatient mental health clinic. Sociodemographic data, clinical and functional assessments alongside smartphone ownership and uses were collected at baseline and at 3 months' follow-up. A 5 item Likert-scale satisfaction questionnaire was also employed. Results: 51 participants were initially enrolled in the study, 36 (74%) remained actively using the application after 3 months. The whole sample interacted with the application a mean of 77 days (SD=26.2). During these days they completed 88% of the daily tests. Over 86% of the participants agreed that the experience using the application was satisfactory. Limitations: The diversity of smartphones operating systems led to a moderate, although representative, sample number. Additionally, the subjective data reporting, narrow time frame of use and stability of the patients could have affected the results. Conclusions: The results confirm that this particular intervention is feasible and represent a satisfactory and acceptable instrument for the self-management of bipolar disorder as an add-on to the usual treatment but future clinical trials must still probe its efficacy.
Treatment of neurocognitive symptoms in unipolar depression: A systematic review and future perspectives
(Elsevier B.V., 2017-10-15) Salagre Muñoz, Estela; Solé Cabezuelo, Brisa; Tomioka, Yoko; Fernandes, Brisa; Hidalgo Mazzei, Diego; Garriga, Marina; Jiménez Martínez, Ester; Sánchez Moreno, José; Vieta i Pascual, Eduard, 1963-; Grande i Fullana, Iria
Background: Cognitive symptoms in Major Depressive Disorder (MDD) are persistent and commonly entail neurocognitive impairment and a decline in quality of life. This systematic review gathers the current scientific evidence on therapeutic strategies for neuropsychological impairment in MDD. Method: A systematic search on PubMed, PsycINFO and Clinicaltrials.gov was carried out on December 2016 according to PRISMA using Boolean terms to identify interventions for the treatment of cognitive dysfunction in MDD. Only English-written articles providing original data and focusing in adults with MDD were included with no time restrictions. Results: A total of 95 studies reporting data on 40 pharmacological and non-pharmacological interventions were included. Interventions were grouped into the following categories: 1) Pharmacological Therapies (antidepressants, stimulants, compounds acting on NMDA receptors, compounds acting on the cholinergic system, compounds showing anti-inflammatory or antioxidant properties, other mechanisms of action), 2) Physical Therapies and 3) Psychological Therapies, 4) Exercise. There are some promising compounds showing a positive impact on cognitive symptoms including vortioxetine, lisdexamfetamine or erythropoietin. Limitations: The studies included showed significant methodological differences in heterogeneous samples. The lack of a standardized neuropsychological battery makes comparisons between studies difficult. Conclusion: Current evidence is not sufficient to widely recommend the use of procognitive treatments in MDD although promising results are coming to light.
Sharing brain imaging data in the Open Science era: how and why?
(Elsevier, 2024-07) Giehl, Kathrin; Mutsaerts, Henk-Jan; Aarts, Kristien; Barkhof, Frederik; Caspers. Svenja; Chetelat, Gaël; Colin, Marie-Elisabeth; Düzel, Emrah; Frisoni, Giovanni B.; Ikram, M. Arfan; Jovicich, Jorge; Morbelli, Silvia; Oertel, Wolfgang; Paret, Christian; Perani, Daniela; Ritter, Petra; Segura i Fàbregas, Bàrbara; Wisse, Laura E.M.; De Witte, Elke; Cappa, Stefano F.; van Eimeren, Thilo
The sharing of human neuroimaging data has great potential to accelerate the development of imaging biomarkers in neurological and psychiatric disorders; however, major obstacles remain in terms of how and why to share data in the Open Science context. In this Health Policy by the European Cluster for Imaging Biomarkers, we outline the current main opportunities and challenges based on the results of an online survey disseminated among senior scientists in the field. Although the scientific community fully recognises the importance of data sharing, technical, legal, and motivational aspects often prevent active adoption. Therefore, we provide practical advice on how to overcome the technical barriers. We also call for a harmonised application of the General Data Protection Regulation across EU countries. Finally, we suggest the development of a system that makes data count by recognising the generation and sharing of data as a highly valuable contribution to the community
PVR (CD155) epigenetic status mediates immunotherapy response in multiple myeloma
(Springer Nature, 2024-09-24) Salsench, Sergi V.; Ferrer, Gerardo; Garcia Ortiz, Almudena; Esteller, Manel, 1968-; Valeri, Antonio; Rojas, Elizabeta A.; Barrena, Naroa; Gutiérrez, Norma C.; Prosper, Felipe; Agirre, Xabier; Fernández de Larrea Rodríguez, Carlos José ; Martínez-Verbo, Laura; Veselinova, Yoana; Llinàs Arias, Pere; García-Prieto, Carlos A.; Noguera Castells, Aleix; López Pato, Miguel; Bueno Costa, Alberto; Campillo Marcos, Ignacio; Villanueva, Lorea; Oliver Caldés, Aina; Cardús, Oriol; Martínez López, Joaquín
he immune system is tightly regulated but plastic in humans. It has several lines of control, and its imbalance has severe consequences for our health. Epigenetics encompasses heritable biochemical changes of the chromatin that do not affect the DNA sequence.

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