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The neural network mediating successful response inhibition mainly includes right hemisphere activation of the pre-supplementary motor area, inferior frontal gyrus (IFG), subthalamic nucleus (STN), and caudate nucleus. However, the causal role of these regions in the inhibitory network is undefined. Five patients with Parkinson's disease were assessed prior to and after therapeutic thermal ablation of the right STN in two separate functional magnetic resonance imaging (fMRI) sessions while performing a stop-signal task. Initiation times were faster but motor inhibition with the left hand (contralateral to the lesion) was significantly impaired as evident in prolonged stop-signal reaction times. Reduced inhibition after right subthalamotomy was associated (during successful inhibition) with the recruitment of basal ganglia regions outside the established inhibitory network. They included the putamen and caudate together with the anterior cingulate cortex and IFG of the left hemisphere. Subsequent network connectivity analysis (with the seed over the nonlesioned left STN) revealed a new inhibitory network after right subthalamotomies. Our results highlight the causal role of the right STN in the neural network for motor inhibition and the possible basal ganglia mechanisms for compensation upon losing a key node of the inhibition network.
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BACKGROUND: There is a lack of automated tools for the segmentation and quantification of neuromelanin (NM) and iron in the nigrosome-1 (N1). Existing tools evaluate the N1 sign, i.e., the presence or absence of the "swallow-tail" in iron-sensitive MRI, or globally analyze the MRI signal in an area containing the N1, without providing a volumetric delineation. PURPOSE: Present an automated method to segment the N1 and quantify differences in N1's NM and iron content between Parkinson's disease (PD) patients and healthy controls (HCs). Study whether N1 degeneration is clinically related to PD and could be used as a biomarker of the disease. STUDY TYPE: Prospective. SUBJECTS: Seventy-one PD (65.3 ± 10.3 years old, 34 female/37 male); 30 HC (62.7 ± 7.8 years old, 17 female/13 male). FIELD STRENGTH/SEQUENCE: 3 T Anatomical T1-weighted MPRAGE, NM-MRI T1-weighted gradient with magnetization transfer, susceptibility-weighted imaging (SWI). ASSESSMENT: N1 was automatically segmented in SWI images using a multi-image atlas, populated with healthy N1 structures manually annotated by a neurologist. Relative NM and iron content were quantified and their diagnostic performance assessed and compared with the substantia nigra pars compacta (SNc). The association between image parameters and clinically relevant variables was studied. STATISTICAL TESTS: Nonparametric tests were used (Mann-Whitney's U, chi-square, and Friedman tests) at P = 0.05. RESULTS: N1's relative NM content decreased and relative iron content increased in PD patients compared with HCs (NM-CRHC = 22.55 ± 1.49; NM-CRPD = 19.79 ± 1.92; NM-nVolHC = 2.69 × 10-5 ± 1.02 × 10-5 ; NM-nVolPD = 1.18 × 10-5 ± 0.96 × 10-5 ; Iron-CRHC = 10.51 ± 2.64; Iron-CRPD = 19.35 ± 7.88; Iron-nVolHC = 0.72 × 10-5 ± 0.81 × 10-5 ; Iron-nVolPD = 2.82 × 10-5 ± 2.04 × 10-5 ). Binary logistic regression analyses combining N1 and SNc image parameters yielded a top AUC = 0.955. Significant correlation was found between most N1 parameters and both disease duration (ρNM-CR = -0.31; ρiron-CR = 0.43; ρiron-nVol = 0.46) and the motor status (ρNM-nVol = -0.27; ρiron-CR = 0.33; ρiron-nVol = 0.28), suggesting NM reduction along with iron accumulation in N1 as the disease progresses. DATA CONCLUSION: This method provides a fully automatic N1 segmentation, and the analyses performed reveal that N1 relative NM and iron quantification improves diagnostic performance and suggest a relative NM reduction along with a relative iron accumulation in N1 as the disease progresses. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.
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Neuromelanin (NM) loss in substantia nigra pars compacta (SNc) and locus coeruleus (LC) reflects neuronal death in Parkinson's disease (PD). Since genetically-determined PD shows varied clinical expressivity, we wanted to accurately quantify and locate brainstem NM and iron, to discover whether specific MRI patterns are linked to Leucine-rich repeat kinase 2 G2019S PD (LRRK2-PD) or idiopathic Parkinson's disease (iPD). A 3D automated MRI atlas-based segmentation pipeline (3D-ABSP) for NM/iron-sensitive MRI images topographically characterized the SNc, LC, and red nucleus (RN) neuronal loss and calculated NM/iron contrast ratio (CR) and normalized volume (nVol). Left-side NM nVol was larger in all groups. PD had lower NM CR and nVol in ventral-caudal SNc, whereas iron increased in lateral, medial-rostral, and caudal SNc. The SNc NM CR reduction was associated with psychiatric symptoms. LC CR and nVol discriminated better among subgroups: LRRK2-PD had similar LC NM CR and nVol as that of controls, and larger LC NM nVol and RN iron CR than iPD. PD showed higher iron SNc nVol than controls, especially among LRRK2-PD. ROC analyses showed an AUC > 0.92 for most pairwise subgroup comparisons, with SNc NM being the best discriminator between HC and PD. NM measures maintained their discriminator power considering the subgroup of PD patients with less than 5 years of disease duration. The SNc iron CR and nVol increase was associated with longer disease duration in PD patients. The 3D-ABSP sensitively identified NM and iron MRI patterns strongly correlated with phenotypic PD features.
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BACKGROUND: Assessing bleeding risk during the decision-making process of starting oral anticoagulation (OAC) therapy in atrial fibrillation (AF) patients is essential. Several bleeding risk scores have been proposed for vitamin K antagonist users but, few studies have focused on validation of these bleeding risk scores in patients taking direct oral anticoagulants (DOACs). The aim was to compare the predictive ability of HAS-BLED and ORBIT bleeding risk scores in AF patients taking rivaroxaban in the EMIR ('Estudio observacional para la identificación de los factores de riesgo asociados a eventos cardiovasculares mayores en pacientes con fibrilación auricular no valvular tratados con un anticoagulante oral directo [Rivaroxaban]) Study. METHODS AND RESULTS: EMIR Study was an observational, multicenter, post-authorization, and prospective study that involved AF patients under OAC with rivaroxaban at least 6 months before enrolment. We analysed baseline clinical characteristics and adverse events after 2.5 years of follow-up and validated the predictive ability of HAS-BLED and ORBIT scores for major bleeding (MB) events.We analysed 1433 patients with mean age of 74.2 ± 9.7 (44.5% female). Mean HAS-BLED score was 1.6 ± 1.0 and ORBIT score was 1.1 ± 1.2. The ORBIT score categorised a higher proportion of patients as 'low-risk' (87.1%) compared with 53.5% using the HAS-BLED score. There were 33 MB events (1.04%/year) and 87 patients died (2.73%/year). Both HAS-BLED and ORBIT had a good predictive ability for MB{Area under the curve (AUC) 0.770, [95% confidence interval (CI) 0.693-0.847; P <0.001] and AUC 0.765 (95% CI 0.672-0.858; P <0.001), respectively}. There was a non-significant difference for discriminative ability of the two tested scores (P = 0.930) and risk reclassification in terms of net reclassification improvement (NRI) -5.7 (95% CI -42.4-31.1; P = 0.762). HAS-BLED score showed the best calibration and ORBIT score showed the largest mismatch in calibration, particularly in higher predicted risk patients. CONCLUSION: In a prospective real-world AF population under rivaroxaban from EMIR registry, the HAS-BLED score had good predictive performance and calibration compared with ORBIT score for MB events. ORBIT score presented worse calibration than HAS-BLED in this DOAC treated population.
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Fibrilación Atrial , Humanos , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Masculino , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Rivaroxabán/efectos adversos , Estudios Prospectivos , Medición de Riesgo/métodos , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Sistema de Registros , Factores de RiesgoRESUMEN
The ability to appropriately perceive distances in activities of daily living, such as driving, is necessary when performing complex maneuvers. With aging, certain driving behaviors and cognitive functions change; however, it remains unknown if egocentric distance perception (EDP) performance is altered and whether its neural activity also changes as we grow older. To that end, 19 young and 17 older healthy adults drove in a driving simulator and performed an functional magnetic resonance imaging (fMRI) experiment where we presented adults with an EDP task. We discovered that (a) EDP task performance was similar between groups, with higher response times in older adults; (b) older adults showed higher prefrontal and parietal activation; and (c) higher functional connectivity within frontal and parietal-occipital-cerebellar networks; and (d) an association between EDP performance and hard braking behaviors in the driving simulator was found. In conclusion, EDP functioning remains largely intact with aging, possibly due to an extended and effective rearrangement in functional brain resources, and may play a role in braking behaviors while driving.
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Recent imaging studies with the stop-signal task in healthy individuals indicate that the subthalamic nucleus, the pre-supplementary motor area and the inferior frontal gyrus are key components of the right hemisphere "inhibitory network". Limited information is available regarding neural substrates of inhibitory processing in patients with asymmetric Parkinson's disease. The aim of the current fMRI study was to identify the neural changes underlying deficient inhibitory processing on the stop-signal task in patients with predominantly left-sided Parkinson's disease. Fourteen patients and 23 healthy controls performed a stop-signal task with the left and right hands. Behaviorally, patients showed delayed response inhibition with either hand compared to controls. We found small imaging differences for the right hand, however for the more affected left hand when behavior was successfully inhibited we found reduced activation of the inferior frontal gyrus bilaterally and the insula. Using the stop-signal delay as regressor, contralateral underactivation in the right dorsolateral prefrontal cortex, inferior frontal and anterior putamen were found in patients. This finding indicates dysfunction of the right inhibitory network in left-sided Parkinson's disease. Functional connectivity analysis of the left subthalamic nucleus showed a significant increase of connectivity with bilateral insula. In contrast, the right subthalamic nucleus showed increased connectivity with visuomotor and sensorimotor regions of the cerebellum. We conclude that altered inhibitory control in left-sided Parkinson's disease is associated with reduced activation in regions dedicated to inhibition in healthy controls, which requires engagement of additional regions, not observed in controls, to successfully stop ongoing actions.
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Enfermedad de Parkinson , Núcleo Subtalámico , Humanos , Inhibición Psicológica , Imagen por Resonancia Magnética , Enfermedad de Parkinson/diagnóstico por imagen , Corteza Prefrontal , Núcleo Subtalámico/diagnóstico por imagenRESUMEN
BACKGROUND: Increasing clinical and scientific attention is given to the transition of neurological stages from child to adult. Data on brain plasticity during adolescence is interesting for providing adequate evidence-based medical attention to neurological conditions in this population. Acquired aphasia is well described in adults and children, but not in adolescence. OBJECTIVE: We describe a 5-year follow-up of language in three adolescent subjects with post-brain injury aphasia. METHODS: We analysed and scored formal aspects of language three times, language hemispheric dominance twice with dichotic listening test and functional magnetic resonance imaging (fMRI) brain activation patterns that supported expressive and comprehensive language during the recovery period. RESULTS: We found similarities to both paediatric and adult aphasia in these three adolescents. While the level of recovery resembled that of children with aphasia, a more efficient language rehabilitation occurred in those who remained with left hemispheric dominance in the chronic stage, as it is reported in adults. CONCLUSIONS: Our analysis and long-term follow-up provide data for a better understanding on how the injured brain matures during adolescence. More studies with larger samples will help to understand the function of the remaining networks and the recovery from injury in this particular age group.
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Afasia/fisiopatología , Encéfalo/fisiopatología , Lenguaje , Plasticidad Neuronal/fisiología , Recuperación de la Función/fisiología , Adolescente , Afasia/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Niño , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , MasculinoRESUMEN
The human brain undergoes structural and functional changes across the lifespan. The study of motor sequence learning in elderly subjects is of particularly interest since previous findings in young adults might not replicate during later stages of adulthood. The present functional magnetic resonance imaging (fMRI) study assessed the performance, brain activity and functional connectivity patterns associated with motor sequence learning in late middle adulthood. For this purpose, a total of 25 subjects were evaluated during early stages of learning [i.e., fast learning (FL)]. A subset of these subjects (n = 11) was evaluated after extensive practice of a motor sequence [i.e., slow learning (SL) phase]. As expected, late middle adults improved motor performance from FL to SL. Learning-related brain activity patterns replicated most of the findings reported previously in young subjects except for the lack of hippocampal activity during FL and the involvement of cerebellum during SL. Regarding functional connectivity, precuneus and sensorimotor lobule VI of the cerebellum showed a central role during improvement of novel motor performance. In the sample of subjects evaluated, connectivity between the posterior putamen and parietal and frontal regions was significantly decreased with aging during SL. This age-related connectivity pattern may reflect losses in network efficiency when approaching late adulthood. Altogether, these results may have important applications, for instance, in motor rehabilitation programs.
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INTRODUCTION: Essential tremor (ET) is one of the most common movement disorders. Despite its high prevalence and heritability, its genetic etiology remains elusive with only a few susceptibility genes identified and poorly replicated. Our aim was to find novel candidate genes involved in ET predisposition through whole exome sequencing. METHODS: We studied eight multigenerational families (N = 40 individuals) with an autosomal-dominant inheritance using a comprehensive strategy combining whole exome sequencing followed by case-control association testing of prioritized variants in a separate cohort comprising 521 ET cases and 596 controls. We further performed gene-based burden analyses in an additional dataset comprising 789 ET patients and 770 healthy individuals to investigate whether there was an enrichment of rare deleterious variants within our candidate genes. RESULTS: Fifteen variants co-segregated with disease status in at least one of the families, among which rs749875462 in CCDC183, rs535864157 in MMP10 and rs114285050 in GPR151 showed a nominal association with ET. However, we found no significant enrichment of rare variants within these genes in cases compared with controls. Interestingly, MMP10 protein is involved in the inflammatory response to neuronal damage and has been previously associated with other neurological disorders. CONCLUSIONS: We prioritized a set of promising genes, especially MMP10, for further genetic and functional studies in ET. Our study suggests that rare deleterious coding variants that markedly increase susceptibility to ET are likely to be found in many genes. Future studies are needed to replicate and further infer biological mechanisms and potential disease causality for our identified genes.
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Temblor Esencial/genética , Predisposición Genética a la Enfermedad , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Metaloproteinasa 10 de la Matriz/genética , Persona de Mediana Edad , Linaje , Secuenciación del Exoma , Adulto JovenRESUMEN
The morphological changes that occur in the central nervous system of patients with severe acute intermittent porphyria (AIP) have not yet been clearly established. The aim of this work was to analyze brain involvement in patients with severe AIP without epileptic seizures or clinical posterior reversible encephalopathy syndrome, as well as in a mouse model receiving or not liver-directed gene therapy aimed at correcting the metabolic disorder. We conducted neuroradiologic studies in 8 severely affected patients (6 women) and 16 gender- and age-matched controls. Seven patients showed significant enlargement of the cerebral ventricles and decreased brain perfusion was observed during the acute attack in two patients in whom perfusion imaging data were acquired. AIP mice exhibited reduced cerebral blood flow and developed chronic dilatation of the cerebral ventricles even in the presence of slightly increased porphyrin precursors. While repeated phenobarbital-induced attacks exacerbated ventricular dilation in AIP mice, correction of the metabolic defect using liver-directed gene therapy restored brain perfusion and afforded protection against ventricular enlargement. Histological studies revealed no signs of neuronal loss but a denser neurofilament pattern in the periventricular areas, suggesting compression probably caused by imbalance in cerebrospinal fluid dynamics. In conclusion, severely affected AIP patients exhibit cerebral ventricular enlargement. Liver-directed gene therapy protected against the morphological consequences of the disease seen in the brain of AIP mice. The observational study was registered at Clinicaltrial.gov as NCT02076763.
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Encéfalo/patología , Ventrículos Cerebrales/patología , Modelos Animales de Enfermedad , Hidroximetilbilano Sintasa/genética , Porfiria Intermitente Aguda/fisiopatología , Adulto , Animales , Encéfalo/metabolismo , Estudios de Casos y Controles , Ventrículos Cerebrales/metabolismo , Ensayos Clínicos Fase I como Asunto , Femenino , Terapia Genética , Humanos , Masculino , Ratones , Persona de Mediana Edad , Porfiria Intermitente Aguda/genética , Porfiria Intermitente Aguda/metabolismo , Estudios ProspectivosRESUMEN
Visuomotor impairments characterize numerous neurological disorders and neurogenetic syndromes, such as autism spectrum disorder (ASD) and Dravet, Fragile X, Prader-Willi, Turner, and Williams syndromes. Despite recent advances in systems neuroscience, the biological basis underlying visuomotor functional impairments associated with these clinical conditions is poorly understood. In this study, we used neuroimaging connectomic approaches to map the visuomotor integration (VMI) system in the human brain and investigated the topology approximation of the VMI network to the Allen Human Brain Atlas, a whole-brain transcriptome-wide atlas of cortical genetic expression. We found the genetic expression of four genes-TBR1, SCN1A, MAGEL2, and CACNB4-to be prominently associated with visuomotor integrators in the human cortex. TBR1 gene transcripts, an ASD gene whose expression is related to neural development of the cortex and the hippocampus, showed a central spatial allocation within the VMI system. Our findings delineate gene expression traits underlying the VMI system in the human cortex, where specific genes, such as TBR1, are likely to play a central role in its neuronal organization, as well as on specific phenotypes of neurogenetic syndromes.
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Canales de Calcio/genética , Corteza Motora/fisiopatología , Canal de Sodio Activado por Voltaje NAV1.1/genética , Trastornos del Neurodesarrollo/patología , Proteínas/genética , Proteínas de Dominio T Box/genética , Corteza Visual/fisiopatología , Adulto , Anciano , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/patología , Mapeo Encefálico , Estudios de Cohortes , Epilepsias Mioclónicas/genética , Epilepsias Mioclónicas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos del Neurodesarrollo/genética , Síndrome de Prader-Willi/genética , Síndrome de Prader-Willi/patología , Desempeño Psicomotor , Percepción VisualRESUMEN
When humans make decisions, objective rewards are mainly discounted by delay, risk and effort. Whereas recent research has demonstrated that several brain areas process costs and code subjective value in effort-based decision making, it remains obscure how neural activity patterns change when effort costs are reduced due to the acquisition of healthy habits, such as moving from sedentary to active lifestyles. Here, a sample of sedentary volunteers was behaviorally assessed and fMRI-scanned before and after completing a 3-month fitness plan. The impact of effort cost on decisions, measured as the constant defining a hyperbolic decaying function, was reduced after the plan. A logistic mixed model demonstrated that the explanatory power of effort decreased with time. At a neural level, there was a marginally significant disruption of effort-cost related functional activity in the anterior cingulate after the plan. Functional connectivity between the amygdala and anterior cingulate cortex was strengthened after habit acquisition. In turn, this interaction was stronger in those participants with lower effort discounting. Thus, we show for the first time changes in value-based decision making after moving from a sedentary to an active lifestyle, which points to the relevance of the amygdala-cingulate interplay when the impact of effort on decisions fades away.
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Amígdala del Cerebelo/fisiología , Toma de Decisiones/fisiología , Ejercicio Físico/psicología , Giro del Cíngulo/fisiología , Adolescente , Adulto , Mapeo Encefálico , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Vías Nerviosas/fisiología , Esfuerzo Físico , Conducta Sedentaria , Adulto JovenRESUMEN
BACKGROUND: Patients with acute coronary syndrome (ACS) and previous cardiovascular disease (CVD) (stroke, peripheral arterial disease [PAD] or coronary artery disease [CAD]) are at high risk of serious events and mortality. Current clinical guidelines recommend new antiplatelet drugs (NADs) for high cardiovascular risk patients with ACS; however, these drugs are underused in different scenarios. METHODS: This study included 1717 ACS patients from 3 tertiary hospitals. Of them, 641 (37.33%) suffered from previous CVD: 149 patients with stroke, 154 patients with PAD and 541 patients with CAD. Bleeding, mortality and major adverse cardiac events (MACE) at 1 year of follow-up after hospital discharge were analyzed. RESULTS: NADs administration during hospital stay and at discharge was less frequent in patients with previous CVDs (P<0.001, for both). Cox analysis in this cohort of patients showed that clopidogrel prescription at discharge was independently associated with MACEs (HR: 1.59 [95% CI: 1.03-2.45]; P=0.036) and with death (HR: 1.99 [95% CI: 1.00-3.98]; P=0.049) in multivariate analysis. More specifically, when ticagrelor prescription at discharge was compared with clopidogrel, a significant death reduction was found in both, the univariate and the multivariate Cox analysis (HR: 4.54 [95% CI: 2.26-9.13]; P<0.001 and HR: 2.61 [95% CI: 1.16-5.90]; P=0.021, respectively). CONCLUSIONS: New antiplatelet drugs, especially ticagrelor, showed lower rates of mortality in patients with CVD without differences for bleeding. Despite the recommendations of current clinical guidelines for high risk patients with ACS, the use of NADs is very low in "real-life" patients with previous CVD.
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Síndrome Coronario Agudo/tratamiento farmacológico , Enfermedad Coronaria/complicaciones , Enfermedad Arterial Periférica/complicaciones , Inhibidores de Agregación Plaquetaria/uso terapéutico , Accidente Cerebrovascular/complicaciones , Síndrome Coronario Agudo/etiología , Síndrome Coronario Agudo/mortalidad , Cuidados Posteriores , Clopidogrel/efectos adversos , Clopidogrel/uso terapéutico , Comorbilidad , Utilización de Medicamentos/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Humanos , Estimación de Kaplan-Meier , Masculino , Síndrome Metabólico/epidemiología , Inhibidores de Agregación Plaquetaria/efectos adversos , Clorhidrato de Prasugrel/uso terapéutico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Fumar/epidemiología , España , Centros de Atención Terciaria/estadística & datos numéricos , Ticagrelor/efectos adversos , Ticagrelor/uso terapéuticoRESUMEN
Poverty-related food insecurity can be viewed as a form of economic and nutritional uncertainty that can lead, in some situations, to a desire for more filling and satisfying food. Given the current obesogenic food environment and the nature of the food supply, those food choices could engage a combination of sensory, neurophysiological, and genetic factors as potential determinants of obesity.
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Motivación , Obesidad , Abastecimiento de Alimentos , Humanos , Pobreza , IncertidumbreRESUMEN
According to the theory of value-based decision making, subjects tend to choose the most valuable among a set of options. However, agents may not be consistent when facing the same decision several times. In this paper, Shannon's entropy (H) is employed as a measure of behavioral inconsistency: it is a central measure of information theory that, applied to decision making, allows the estimation of behavioral preferences among a set of options. We scanned (functional magnetic resonance imaging, fMRI) 24 young (18-25 year) subjects (14 female) while performing a decision-making task, where monetary rewards were devalued by physical effort (minutes running in the treadmill) and risk. Twenty different pairs of options were presented nine times each, and H was calculated for each pair and subject. Behavioral analyses showed that subjective value (SV) significantly explained agents' preferences only in pairs with a low inconsistent response. Averaged response time positively correlated with H, confirming entropy as an indicator of choice difficulty. Group analyses on fMRI data revealed a cluster in the paracingulate cortex as the neural correlate of H. Besides, BOLD signal in the posterior cingulate correlated with the SV of the pair only in consistent decisions, confirming that SV loses its explanatory power on highly inconsistent decisions. Finally, the anterior and central cingulate were especially recruited when predicting a secured effortless reward, compared with a secured reward that involved a maximum effort. Our study shows that different regions of the cingulate cortex are involved in choice inconsistency, SV and processing effort costs.
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Encéfalo/diagnóstico por imagen , Conducta de Elección/fisiología , Esfuerzo Físico/fisiología , Adolescente , Adulto , Mapeo Encefálico , Toma de Decisiones/fisiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Tiempo de Reacción/fisiología , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVE: Dual antiplatelet therapy is one of the main treatments in acute coronary syndrome (ACS). Switching antiplatelet agents may be necessary in some patients to improve efficacy or safety. The objective of this study was to determine the prevalence, predictors, and implications of clinical switching in patients during hospital admission and 1-year follow-up at discharge. METHODS: Observational, prospective, multicenter registry study in patients discharged following an admission for ACS and followed up for 1 year. We analyzed ischemic and bleeding events as well as treatment changes. RESULTS: We recruited 1717 patients; in-hospital switching occurred in 425 (24.8%): 15.1% to clopidogrel and 84.9% to newer antiplatelet drugs (prasugrel or ticagrelor). Those switched to newer antiplatelets were younger, with lower scores on the GRACE and CRUSADE scales, admitted more frequently for ST-elevation myocardial infarction and underwent more invasive management and percutaneous revascularization. The clinical cardiologist was responsible for most in-hospital switching to newer antiplatelets (79.6%). The loading dose of the second antiplatelet did not affect incidence of bleeding events. Post-discharge switching was infrequent (2%) and depended mainly on clinical indications; only 30% was related to a new ACS. CONCLUSIONS: In a contemporary registry with ACS, in-hospital switching of antiplatelet drugs was frequent. Those switched to newer antiplatelets were younger and admitted more frequently for ST-elevation myocardial infarction. Post-discharge switching was infrequent.
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Síndrome Coronario Agudo/tratamiento farmacológico , Clopidogrel/administración & dosificación , Clorhidrato de Prasugrel/administración & dosificación , Ticagrelor/administración & dosificación , Administración Oral , Anciano , Anciano de 80 o más Años , Femenino , Hemorragia/epidemiología , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/administración & dosificación , Prevalencia , Pronóstico , Estudios Prospectivos , Antagonistas del Receptor Purinérgico P2Y/administración & dosificación , Sistema de Registros , Infarto del Miocardio con Elevación del ST/tratamiento farmacológicoRESUMEN
We present a dynamic atlas composed of neuromelanin-enhanced magnetic resonance brain images of 40 healthy subjects. The performance of this atlas is evaluated on the fully automated segmentation of two paired neuromelanin-rich brainstem healthy structures: the substantia nigra pars compacta and the locus coeruleus. We show that our dynamic atlas requires in average 60% less images and, therefore, 60% less computation time than a static multi-image atlas while achieving a similar segmentation performance. Then, we show that by applying our dynamic atlas, composed of healthy subjects, to the segmentation and neuromelanin quantification of a set of brain images of 39 Parkinson disease patients, we are able to find significant quantitative differences in the level of neuromelanin between healthy subjects and Parkinson disease patients, thus opening the door to the use of these structures as image biomarkers in future computer aided diagnosis systems for the diagnosis of Parkinson disease.
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Atlas como Asunto , Tronco Encefálico/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Enfermedad de Parkinson/diagnóstico por imagen , Biomarcadores , Estudios de Casos y Controles , Humanos , Melaninas/análisis , Reproducibilidad de los Resultados , Reino UnidoRESUMEN
The aim of this study is to compare the properties of free-walking at a natural pace between mild Parkinson's disease (PD) patients during the ON-clinical status and two control groups. In-shoe pressure-sensitive insoles were used to quantify the temporal and force characteristics of a 5-min free-walking in 11 PD patients, in 16 young healthy controls, and in 12 age-matched healthy controls. Inferential statistics analyses were performed on the kinematic and kinetic parameters to compare groups' performances, whereas feature selection analyses and automatic classification were used to identify the signature of parkinsonian gait and to assess the performance of group classification, respectively. Compared to healthy subjects, the PD patients' gait pattern presented significant differences in kinematic parameters associated with bilateral coordination but not in kinetics. Specifically, patients showed an increased variability in double support time, greater gait asymmetry and phase deviation, and also poorer phase coordination. Feature selection analyses based on the ReliefF algorithm on the differential parameters in PD patients revealed an effect of the clinical status, especially true in double support time variability and gait asymmetry. Automatic classification of PD patients, young and senior subjects confirmed that kinematic predictors produced a slightly better classification performance than kinetic predictors. Overall, classification accuracy of groups with a linear discriminant model which included the whole set of features (i.e., demographics and parameters extracted from the sensors) was 64.1%.
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Marcha/fisiología , Enfermedad de Parkinson/fisiopatología , Zapatos , Caminata/fisiología , Adulto , Algoritmos , Fenómenos Biomecánicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico , PresiónRESUMEN
Numerous daily tasks, including car driving, require fine visuospatial tuning. One such visuospatial ability, speed discrimination, declines with aging but its neural underpinnings remain unknown. In this study, we use fMRI to explore the effect of aging during a high speed discrimination task and its neural underpinnings, along with a complete neuropsychological assessment and a simulated driving evaluation in order to examine how they interact with each other through a multivariate regression approach. Beyond confirming that high speed discrimination performance is diminished in the elderly, we found that this deficit might be partly due to a lack of modulation in the activity and connectivity of the default mode network (DMN) in this age group, as well as an over-recruitment of frontoparietal and cerebellar regions, possibly as a compensatory mechanism. In addition, younger adults tended to drive at faster speeds, a behavior that was associated to adequate DMN dynamics and executive functioning, an effect that seems to be lost in the elderly. In summary, these results reveal how age-related declines in fine visuospatial abilities, such as high speed discrimination, were distinctly mediated by DMN functioning, a mechanism also associated to speeding behavior in a driving simulator.