Frederic Sampedro
@santpau.cat
Radiology, Hospital de Sant Pau Barcelona
Hospital de Sant Pau, Barcelona, Spain
10+ years of research in medical imaging. 80+ indexed papers, director of two PhD thesis.
EDUCATION
MD, computer scientist (honors), MSc in biomedical engineering, electrical engineering and technological-based business administration.
PhD (extraordinary award).
RESEARCH INTERESTS
Neuroimaging
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Saul Martinez‐Horta, Jesús Perez‐Perez, Rocío Perez‐Gonzalez, Frederic Sampedro, Andrea Horta‐Barba, Antonia Campolongo, Elisa Rivas‐Asensio, Arnau Puig‐Davi, Javier Pagonabarraga, and Jaime Kulisevsky
Wiley
AbstractObjectiveThe clinical phenotype of Huntington's disease (HD) can be very heterogeneous between patients, even when they share equivalent CAG repeat length, age, or disease burden. This heterogeneity is especially evident in terms of the cognitive profile and related brain changes. To shed light on the mechanisms participating in this heterogeneity, the present study delves into the association between Tau pathology and more severe cognitive phenotypes and brain damage in HD.MethodsWe used a comprehensive neuropsychological examination to characterize the cognitive phenotype of a sample of 30 participants with early‐to‐middle HD for which we also obtained 3 T structural magnetic resonance image (MRI) and cerebrospinal fluid (CSF). We quantified CSF levels of neurofilament light chain (NfL), total Tau (tTau), and phosphorylated Tau‐231 (pTau‐231). Thanks to the cognitive characterization carried out, we subsequently explored the relationship between different levels of biomarkers, the cognitive phenotype, and brain integrity.ResultsThe results confirmed that more severe forms of cognitive deterioration in HD extend beyond executive dysfunction and affect processes with clear posterior‐cortical dependence. This phenotype was in turn associated with higher CSF levels of tTau and pTau‐231 and to a more pronounced pattern of posterior‐cortical atrophy in specific brain regions closely linked to the cognitive processes affected by Tau.InterpretationOur findings reinforce the association between Tau pathology, cognition, and neurodegeneration in HD, emphasizing the need to explore the role of Tau in the cognitive heterogeneity of the disease.
Jon Rodríguez-Antigüedad, Saül Martínez-Horta, Andrea Horta-Barba, Arnau Puig-Davi, Antonia Campolongo, Frederic Sampedro, Helena Bejr-Kasem, Juan Marín-Lahoz, Javier Pagonabarraga, and Jaime Kulisevsky
Springer Science and Business Media LLC
Frederic Sampedro
Elsevier BV
Saul Martínez‐Horta, Jesús Perez‐Perez, Javier Oltra‐Cucarella, Frederic Sampedro, Andrea Horta‐Barba, Arnau Puig‐Davi, Javier Pagonabarraga, and Jaime Kulisevsky
Wiley
BACKGROUND
Cognitive impairment is a central feature of Huntington's disease (HD), but it is unclear to what extent more aggressive cognitive phenotypes exist in HD among individuals with the same genetic load and equivalence in other clinical and sociodemographic variables.
METHODS
We included Enroll-HD study participants in early and early-mid stages of HD at baseline and with three consecutive yearly follow-ups for whom several clinical and sociodemographic, as well as cognitive measures, were recorded. We excluded participants with low and large CAG (CAG < 39 & >55), juvenile or late-onset HD, and with dementia at baseline. We explored the existence of different groups according to the profile of cognitive progression using a two-step k-means cluster analysis model based on the combination of different cognitive outcomes.
RESULTS
We identified a slow cognitive progression group of 293 participants (S-CogHD) and an aggressive progression group (F-CogHD) of 235 for which there were no differences at the baseline visit in any of the measures explored, with the exception of a slightly higher motor score in the F-CogHD group. This group showed a more pronounced annual loss of functionality and a more marked motor and psychiatric deterioration.
CONCLUSIONS
The rate of progression of cognitive deterioration in HD is strongly variable even between patients sharing, among other variables, equivalent CAG repeat length, age and disease duration. We can recognize at least two phenotypes that differ in terms of rate of progression. Our findings open new avenues to study additional mechanisms contributing to HD heterogeneity.
Andrea Horta‐Barba, Saul Martinez‐Horta, Frederic Sampedro, Jesús Pérez‐Pérez, Javier Pagonabarraga, and Jaime Kulisevsky
Wiley
Individuals with pre-manifest and early symptomatic Huntington's disease (HD) have shown deficits in solving arithmetic word-problems. However, the neural correlates of these deficits in HD are poorly understood. We explored the structural (gray-matter volume; GMV) and metabolic (18F-FDG PET; SUVr) brain correlates of arithmetic performance using the recently developed HD-word problem arithmetic task (HD-WPA) in seventeen preHD and sixteen HD individuals. Symptomatic participants showed significantly lower scores in the HD-WPA than preHD participants. Lower performance in the HD-WPA was associated with reduced GMV in subcortical, medial frontal, and several posterior-cortical clusters in HD participants. No significant GMV loss was found in preHD participants. 18F-FDG data revealed a widespread pattern of hypometabolism in association with lower arithmetic performance in all participants. In preHD participants, this pattern was restricted to the ventrolateral and orbital prefrontal cortex, the insula, and the precentral gyrus. In HD participants, the pattern extended to several parietal-temporal regions. Word-problem solving arithmetic deficits in HD is subserved by a pattern of asynchronous metabolic and structural compromise across the cerebral cortex as a function of disease stage. In preHD individuals, arithmetic deficits were associated with prefrontal alterations, whereas in symptomatic HD patients, more severe arithmetic deficits are associated with the compromise of several frontal-subcortical and temporo-parietal regions. Our results support the hypothesis that cognitive deficits in HD are not exclusively dominated by frontal-striatal dysfunctions but also involve fronto-temporal and parieto-occipital damage.
Frederic Sampedro, Arnau Puig-Davi, Saul Martinez-Horta, Javier Pagonabarraga, Andrea Horta-Barba, Ignacio Aracil-Bolaños, and Jaime Kulisevsky
Elsevier BV
Pilar M. Ferraro, Nicola Spotorno, Eoin Finegan, Frederic Sampedro, and Francesca Caso
Frontiers Media SA
COPYRIGHT © 2022 Ferraro, Spotorno, Finegan, Sampedro and Caso. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: Genotype–phenotype correlations in neurodegenerative diseases: From clinical features to neuroimaging signatures
Juan Marín‐Lahoz, Saül Martinez‐Horta, Javier Pagonabarraga, Andrea Horta‐Barba, Ignacio Aracil‐Bolaños, Helena Bejr‐kasem, Frederic Sampedro, Antonia Campolongo, and Jaime Kulisevsky
Wiley
This study was undertaken to evaluate whether the feedback‐related negativity (FRN)—a neurophysiological marker of incentive processing—can be used to predict the development of impulse control disorders (ICDs) in Parkinson disease (PD).
Frederic Sampedro, Saul Martínez‐Horta, Andrea Horta‐Barba, Michel J. Grothe, Miguel A. Labrador‐Espinosa, Silvia Jesús, Astrid Adarmes‐Gomez, Fatima Carrillo, Arnau Puig‐Davi, Florinda Roldan‐Lora,et al.
Wiley
Reduced facial expression of emotions is a very frequent symptom of Parkinson's disease (PD) and has been considered part of the motor features of the disease. However, the neural correlates of hypomimia and the relationship between hypomimia and other non‐motor symptoms of PD are poorly understood.
Javier Pagonabarraga, Rocío Pérez-González, Helena Bejr-kasem, Juan Marín-Lahoz, Andrea Horta-Barba, Saul Martinez-Horta, Ignacio Aracil-Bolaños, Frederic Sampedro, Antonia Campolongo, Elisa Rivas,et al.
Elsevier BV
Frederic Sampedro, Saul Martínez-Horta, Jesus Pérez-Pérez, Rocío Pérez-González, Andrea Horta-Barba, Antonia Campolongo, Cristina Izquierdo, Ignacio Aracil-Bolaños, Elisa Rivas, Arnau Puig-Davi,et al.
Springer Science and Business Media LLC
Marina Sizova, Valle Camacho, Frederic Sampedro, Aida Sabaté-Llobera, Safae Abouzian, Patricia Stefaneli, Joan Duch, Alejandro Fernández-León, Diego Alfonso López-Mora, Montserrat Estorch,et al.
Ovid Technologies (Wolters Kluwer Health)
Although there is evidence that chemotherapy can have side effects on metabolism and brain function, there are few studies on the occurrence of these side effects with immunotherapy. The present study was conducted to assess whether brain metabolic changes occur in patients with malignant melanoma under immunotherapy. Thirty-nine patients after surgical intervention and with a diagnosis of malignant melanoma were retrospectively included and were divided into two groups: one group under the first-line therapy with anti-programmed cell death-1 ± anti-cytotoxic T lymphocyte antigen-4 monoclonal antibodies and the other group without any treatment after surgery, which served as a control. Basal and follow-up whole body and brain 2-[18F]fluoro-2-deoxy-D-glucose (18F]FDG) PET/computed tomography (CT) studies were performed. Changes in brain glucose metabolism after treatment initiation of the immunotherapy group were compared with the findings in the control group. In addition, longitudinal regression analysis to investigate whether the time under immunotherapy influenced the changes of brain metabolism was performed. None of the patients presented cognitive impairment or other neurological alterations between basal and follow-up brain [18F]FDG PET/CT examinations. The statistical analysis revealed a significant relative SUV (SUVr)-loss in the left frontal region in patients of the immunotherapy group compared with the control group, with radjusted = −0.62 and P = 0.008. Severity of SUVr-loss was correlated with duration of treatment. Patients with disseminated malignant melanoma receiving immunotherapy may present a decrease of brain metabolism in the left frontal region, which is related with time-under-treatment, without any clinical evidence of neurological disorder.
Helena Bejr-kasem, Saül Martínez-Horta, Javier Pagonabarraga, Juan Marín-Lahoz, Andrea Horta-Barba, Frederic Sampedro, Ignacio Aracil-Bolaños, Jesús Pérez-Pérez, Antonia Campolongo, Cristina Izquierdo,et al.
Elsevier BV
Frederic Sampedro, Saul Martínez-Horta, and Jaime Kulisevsky
Elsevier BV
Andrea Horta-Barba, Saül Martínez-Horta, Jesus Pérez-Pérez, Frederic Sampedro, Arnau Puig-Davi, Javier Pagonabarraga, and Jaime Kulisevsky
Springer Science and Business Media LLC
Abstract Background Patients with Huntington’s disease (HD) exhibit a variable predominance of cognitive, behavioral and motor symptoms. A specific instrument focusing on the impact of cognitive impairment in HD over functional capacity is lacking. Objective To address the need for a brief and specifically developed HD questionnaire able to capture functional aspects suspected to be sensitive to cognitive impairment. Methods We developed and validated the “Huntington’s Disease-Cognitive Functional Rating Scale” (HD-CFRS) in 78 symptomatic carriers of the Huntington’s disease mutation. We also administered the HD-CFRS to a knowledgeable informant to measure the level of agreement. To explore the association between HD-CFRS scores and participants’ cognitive status, we administered objective measures of cognition. Participants were classified as cognitively preserved (HD-NC), as having mild cognitive impairment (HD-MCI), or as having dementia (HD-Dem). Results The HD-CFRS showed concurrent validity and internal consistency in the three groups. HD carriers and informants in the HD-NC group obtained similar HD-CFRS scores. However, in patients with mild cognitive impairment and dementia, informers reported greater functional impairment than HD participants. The HD-CFRS total score showed strong correlations with measures assessing cognition. Conclusions These findings support the utility of the HD-CFRS as a brief and reliable instrument to measure functional defects associated with cognitive impairment in HD. We believe this questionnaire could be a useful tool both for clinical practice and research.
Ignacio Aracil-Bolaños, Frederic Sampedro, Juan Marín-Lahoz, Andrea Horta-Barba, Saül Martínez-Horta, José María Gónzalez-de-Echávarri, Jesús Pérez-Pérez, Helena Bejr-Kasem, Berta Pascual-Sedano, Mariángeles Botí,et al.
Springer Science and Business Media LLC
Frederic Sampedro, Saul Martínez-Horta, Andrea Horta-Barba, Michel J. Grothe, Miguel A. Labrador-Espinosa, Silvia Jesús, Astrid Adarmes-Gómez, Fátima Carrillo, Arnau Puig-Davi, Florinda Roldán Lora,et al.
Elsevier BV
Ignacio Aracil‐Bolaños, Saül Martínez‐Horta, Jose M. González‐de‐Echávarri, Frederic Sampedro, Jesús Pérez‐Pérez, Andrea Horta‐Barba, Antonia Campolongo, Cristina Izquierdo, Beatriz Gómez‐Ansón, Javier Pagonabarraga,et al.
Wiley
Huntington's disease is a neurodegenerative disorder characterized by clinical alterations in the motor, behavioral, and cognitive domains. However, the structure and disruptions to large‐scale brain cognitive networks have not yet been established.
Frederic Sampedro, Estela Camara, and Jaime Kulisevsky
Frontiers Media SA
Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, 2 Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain, Centro de Investigación en Red-Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain, Cognition and Brain Plasticity Unit, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain, Cognition, Development and Educational Psychology, University of Barcelona, Barcelona, Spain
Frederic Sampedro, Saul Martínez-Horta, Juan Marín-Lahoz, Javier Pagonabarraga, and Jaime Kulisevsky
IOS Press
Background: Apathy represents a core neuropsychiatric symptom in Parkinson’s disease (PD). As there is currently no established effective treatment for apathy in PD, further investigating the biological origin of this symptom is needed to design novel therapeutic strategies. Among the multiple neurotransmitter alterations that have been associated with apathy, the involvement of extra-striatal dopaminergic degeneration remains to be fully explored. Objective: To investigate whether apathy in PD reflects increased dopaminergic degeneration extending beyond striatal regions. Methods: In the de novo PD cohort of the Parkinson’s Progression Markers Initiative (PPMI), we performed whole-brain I123-Ioflupane Single Photon Emission Computed Tomography (DAT-SPECT) analyses to characterize cross-sectional and longitudinal differences in DAT uptake associated with the presence of apathy. We also assessed the relationship between apathy and cognition in this sample, as apathy has been suggested to herald cognitive decline. Results: Apathetic PD patients (N = 70) had similar sociodemographic, clinical, and biomarker profiles compared to the non-apathetic group (N = 333) at baseline. However, apathy was associated with an increased risk of developing cognitive impairment after a four-year follow-up period (p = 0.006). Compared to non-apathetic patients, apathetic patients showed a widespread reduction of extra-striatal DAT uptake at baseline as well as an increased longitudinal loss of DAT uptake (corrected p < 0.05). Conclusions: Isolated apathy in PD is associated with extra-striatal dopaminergic degeneration. As this abnormal dopamine depletion was in turn related to cognitive performance, this might explain, at least partially, the increased risk of apathetic PD patients to develop cognitive impairment or dementia.
Genís Ona, Frederic Sampedro, Sergio Romero, Marta Valle, Valle Camacho, Carolina Migliorelli, Miguel Ángel Mañanas, Rosa Maria Antonijoan, Montserrat Puntes, Jimena Coimbra,et al.
Oxford University Press (OUP)
Abstract Background The mechanisms through which kappa opioid receptor (KOR) agonists induce psychotomimetic effects are largely unknown, although the modulation of this receptor has attracted attention for its clinical use. In this work, we characterize the neuropharmacological effects of salvinorin-A, a highly selective KOR agonist. Methods Changes in multimodal electroencephalography, single-photon emission computed tomography, and subjective effects following the acute administration of salvinorin-A are reported. The study included 2 sub-studies that employed a double-blind, crossover, randomized, placebo-controlled design. Results The electroencephalography measures showed a marked increase in delta and gamma waves and a decrease in alpha waves while subjects were under the effect of salvinorin-A. Regarding single-photon emission computed tomography measures, significant decreases in regional cerebral blood flow were detected in multiple regions of the frontal, temporal, parietal, and occipital cortices. Significant regional cerebral blood flow increases were observed in some regions of the medial temporal lobe, including the amygdala, the hippocampal gyrus, and the cerebellum. The pattern of subjective effects induced by salvinorin-A was similar to those observed in relation to other psychotomimetic drugs but with an evidently dissociative nature. No dysphoric effects were reported. Conclusion The salvinorin-A–mediated KOR agonism induced dramatic psychotomimetic effects along with a generalized decrease in cerebral blood flow and electric activity within the cerebral cortex.
Frederic Sampedro, Ignacio Aracil-Bolaños, Cristina Carmona i Farrés, Joaquim Soler, Carlos Schmidt, Matilde Elices, Edith Pomarol-Clotet, Raymond Salvador, Daniel Vega, and Juan C. Pascual
Ovid Technologies (Wolters Kluwer Health)
Supplemental digital content is available in the text. ABSTRACT Objective Previous imaging studies in patients with borderline personality disorder (BPD) have detected functional brain dysfunctions. Mindfulness training may improve the symptoms of BPD, although the neural mechanisms involved remain poorly understood. This study had several key aims: a) to investigate the role of right anterior insula (rAI) functional connectivity in modulating baseline emotional status in BPD, b) to compare differences in connectivity changes after mindfulness training versus interpersonal effectiveness intervention, and c) to explore the correlation between longitudinal changes in imaging data and clinical indicators. Methods Thirty-eight patients with BPD underwent resting-state functional magnetic resonance imaging. Participants completed self-report clinical scales and participated in a dialectical-behavioral therapy (mindfulness versus interpersonal effectiveness modules). Changes in clinical and imaging variables were evaluated longitudinally after completion of the first 10-week sessions of psychotherapeutic intervention. Results At baseline, the rAI was strongly connected with the other salience network nodes and anticorrelated with most core nodes of the default mode network (p < .05, corrected). The functional connectivity of the rAI correlated with emotional dysregulation and deficits in mindfulness capacities (p < .05, corrected). After completion of psychotherapeutic intervention, both groups (mindfulness and interpersonal effectiveness) showed divergent posttherapy functional connectivity changes, which were in turn associated with the clinical response. Conclusions The functional connectivity of the rAI seems to play an important role in emotion dysregulation and deficits in mindfulness capacities in individuals with BPD. Psychotherapy seems to modulate this functional connectivity, leading to beneficial changes in clinical variables.
Frederic Sampedro and Jaime Kulisevsky
Wiley
Diffusion tensor imaging (DTI) allows the quantification of water diffusivity within the cerebral cortex. Alterations in cortical mean diffusivity (MD) have been suggested to reflect microstructural damage. Interestingly, microstructural changes can be detected in the absence of macrostructural alterations such as cortical thinning or gray matter volume loss. However, volume‐based neuroimaging techniques for the study of cortical MD have shown some limitations in terms of intersubject registration, partial volume correction, and smoothing artifacts. In this review, we summarize how a surface‐based approach for the assessment of intracortical MD has not only overcome these technical limitations, but also provided important contributions to the fields of neurology and psychiatry. Since its proposal in 2018, the use of this neuroimaging technique has revealed cortical microstructural alterations in a wide range of clinical contexts, including Alzheimer's disease, Parkinson's disease, schizophrenia, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, and primary progressive aphasia. In most cases, the detection of early intracortical MD alterations preceded the identification of macrostructural changes. Importantly, microstructural damage significantly correlated with cognitive performance and biomarker measures, suggesting a potential role for its use in clinical trials as a sensitive imaging marker of neurodegeneration. Given that DTI is a widely available imaging modality, these encouraging results motivate further research using this novel neuroimaging metric in other clinical contexts. Overall, this technique has shed light into the key role of early cortical degeneration in many diseases where cortical involvement was previously thought to have limited clinical and biological significance.
Frederic Sampedro, Saul Martinez‐Horta, Jesús Pérez‐Pérez, Rocio Perez‐Gonzalez, Andrea Horta‐Barba, Antonia Campolongo, Ignacio Aracil‐Bolaños, Beatriz Gomez‐Anson, and Jaume Kulisevsky
Wiley
Female Huntington’s disease (HD) patients have consistently shown a faster clinical worsening than male, but the underlying mechanisms responsible for this observation remain unknown. Here, we describe how sex modifies the impact of neurodegeneration on brain atrophy and clinical severity in HD. Cerebrospinal fluid neurofilament light chain (NfL) levels were used as a biological measure of neurodegeneration, and brain atrophy was assessed by structural magnetic resonance imaging. We found that larger NfL values in women reflect higher brain atrophy and clinical severity than in men (p < 0.05 for an interaction model). This differential vulnerability could have important implications in clinical trials.
Ignacio Aracil‐Bolaños, Frederic Sampedro, Jesus Pujol, Carles Soriano‐Mas, José María Gónzalez‐de‐Echávarri, Jaime Kulisevsky, and Javier Pagonabarraga
Wiley
Dopamine‐replacing therapies are an effective treatment for the motor aspects of Parkinson's disease. However, its precise effect over the cognitive resting‐state networks is not clear; whether dopaminergic treatment normalizes their functional connectivity‐as in other networks‐ and the links with cognitive decline are presently unknown. We recruited 35 nondemented PD patients and 16 age‐matched controls. Clinical and neuropsychological assessments were performed at baseline, and conversion to dementia was assessed in a 10 year follow‐up. Structural and functional brain imaging were acquired in both the ON and practical OFF conditions. We assessed functional connectivity in both medication states compared to healthy controls, connectivity differences within participants related to the ON/OFF condition, and baseline connectivity of PD participants that converted to dementia compared to those who did not convert. PD participants showed and increased frontoparietal connectivity compared to controls: a pattern of higher connectivity between salience (SN) and default‐mode (DMN) networks both in the ON and OFF states. Within PD patients, this higher SN‐DMN connectivity characterized the participants in the ON state, while within‐DMN connectivity prevailed in the OFF state. Interestingly, participants who converted to dementia also showed higher SN‐DMN connectivity in their baseline ON scans compared to nonconverters. To conclude, PD patients showed higher frontoparietal connectivity in cognitive networks compared to healthy controls, irrespective of medication status, but dopaminergic treatment specifically promoted SN‐DM hyperconnectivity.