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Antecedentes y objetivo El ejercicio físico aumenta la capacidad funcional en personas mayores ayudando a evitar o retrasar situaciones de dependencia. En este estudio se evalúa el impacto de una intervención de ejercicio físico multicomponente basado en el programa Vivifrail realizado en un centro de atención primaria en dos años coincidente con la pandemia COVID. Sujetos y métodos Diseño descriptivo longitudinal con comparación antes-después sin grupo control. Personas mayores de 65 años con alteración de funcionalidad medida mediante test de ejecución, adscritos al centro de salud El Palo, Málaga. La intervención consiste en dos sesiones semanales grupales de ejercicio físico guiadas por monitor, según programa Vivifrail. Variables: índice de Barthel, velocidad de la marcha, categoría Vivifrail, calidad de vida (EuroQol 5-D [EQ-5D]) uso de ayudas para la marcha, número de caídas el año previo. Mediciones: basal, segunda (un año) y final (dos años). Análisis test de Kruskal-Wallis, nivel significación 0,05. Resultados Se incluyen evaluaciones de 20 pacientes. Entre primera y segunda valoración, objetivamos modificación significativa en uso de ayudas para la marcha (p 0,01) y categorías Vivifrail: de B inicial, 50% permanecen, 25% pasa a A, 16,7% C2 y 8,3% D (p 0,048). En análisis valoración basal-final, encontramos mejora estadísticamente significativa en calidad de vida medida por EQ-5D (aumento medio 24 puntos en medición de calidad de vida hoy, termómetro EQ-5D, con IC 95% (9,6-38,3), p 0,004) y de categoría Vivifrail (n=10) 60% permanecen categoría B y 40% pasan a D (autónomos) (p<0,0001). Se observa tendencia a mejoría en velocidad de la marcha, tiempo de paseo diario y número de caídas, sin alcanzar significación estadística. Conclusiones El ejercicio físico multicomponente mejora la calidad de vida percibida medida mediante EQ-5D y produce una tendencia a la mejora en capacidad funcional, estado de ánimo y número de caídas (AU)
Background and objective Physical exercise increases functional capacity in older adults, helping to prevent or delay dependence. This study evaluates the impact of a multicomponent physical exercise intervention based on the Vivifrail program, conducted in a primary care center over two years coinciding with the COVID pandemic. Subjects and methods Descriptive longitudinal design with before-after comparison without control group. Participants were older than 65 years old with functional impairment measured by execution test, enrolled in the El Palo Health Center, Málaga. The intervention consists of two weekly group sessions of physical exercise guided by a monitor, according to the Vivifrail program. Variables: Barthel Index, Gait Speed, Vivifrail Category, Quality of Life (EuroQol 5-D [EQ-5D]), use of walking aids, number of falls in the previous year. Measurements: baseline, second (one year) and final (two years). Analysis of the Kruskal-Wallis test, significance level 0.05. Results Twenty patients were evaluated. Between the first and second evaluation, we observed a significant modification in the use of walking aids (p 0.01) and Vivifrail categories: from an initial B category, 50% remained, 25% moved to A, 16.7% to C2 and 8.3% to D (p 0.048). In the analysis of the baseline-final evaluation, we found a statistically significant improvement in quality of life measured by EQ-5D (mean increase of 24 points in today's quality of life measurement, EQ-5D thermometer, with 95% CI (9.6-38.3), p 0.004) and Vivifrail category (n=10) with 60% remaining in category B and 40% moving to D (autonomous) (p<0.0001). There was a trend towards improvement in gait speed, daily walking time, and number of falls, but without reaching statistical significance. Conclusions Multicomponent physical exercise improves perceived quality of life measured by EQ-5D and leads to a trend towards improvement in functional capacity, mood, and number of falls (AU)
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Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Atenção Primária à Saúde , Exercício Físico/fisiologia , Qualidade de Vida , Acidentes por Quedas/prevenção & controle , Idoso Fragilizado , Desempenho Físico Funcional , Estatísticas não Paramétricas , Estudos LongitudinaisRESUMO
The crystal structure of the CH3NH3PbBr3 perovskite has been investigated under high-pressure conditions by synchrotron-based powder X-ray diffraction. We found that after the previously reported phase transitions in CH3NH3PbBr3 (Pm3Ì mâIm3Ì âPmn21), which occur below 2 GPa, there is a third transition to a crystalline phase at 4.6 GPa. This transition is reported here for the first time contradicting previous studies, which reported amorphization of CH3NH3PbBr3 between 2.3 and 4.6 GPa. Our X-ray diffraction measurements show that CH3NH3PbBr3 remains crystalline up to at least 7.6 GPa, the highest pressure covered by experiments. The new high-pressure phase is also described by the space group Pmn21; however, the transition involves abrupt changes in the unit-cell parameters and a 3% decrease of the unit-cell volume. Our conclusions are confirmed by optical-absorption experiments, by visual observations, and by the fact that pressure-induced changes up to 10 GPa are reversible. The optical studies also allow for the determination of the pressure dependence of the band-gap energy, which is discussed using the structural information obtained from X-ray diffraction.
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BACKGROUND AND OBJECTIVE: Physical exercise increases functional capacity in older adults, helping to prevent or delay dependence. This study evaluates the impact of a multicomponent physical exercise intervention based on the Vivifrail program, conducted in a primary care center over two years coinciding with the COVID pandemic. SUBJECTS AND METHODS: Descriptive longitudinal design with before-after comparison without control group. Participants were older than 65 years old with functional impairment measured by execution test, enrolled in the El Palo Health Center, Málaga. The intervention consists of two weekly group sessions of physical exercise guided by a monitor, according to the Vivifrail program. VARIABLES: Barthel Index, Gait Speed, Vivifrail Category, Quality of Life (EuroQol 5-D [EQ-5D]), use of walking aids, number of falls in the previous year. MEASUREMENTS: baseline, second (one year) and final (two years). Analysis of the Kruskal-Wallis test, significance level 0.05. RESULTS: Twenty patients were evaluated. Between the first and second evaluation, we observed a significant modification in the use of walking aids (p 0.01) and Vivifrail categories: from an initial B category, 50% remained, 25% moved to A, 16.7% to C2 and 8.3% to D (p 0.048). In the analysis of the baseline-final evaluation, we found a statistically significant improvement in quality of life measured by EQ-5D (mean increase of 24 points in today's quality of life measurement, EQ-5D thermometer, with 95% CI (9.6-38.3), p 0.004) and Vivifrail category (n=10) with 60% remaining in category B and 40% moving to D (autonomous) (p<0.0001). There was a trend towards improvement in gait speed, daily walking time, and number of falls, but without reaching statistical significance. CONCLUSIONS: Multicomponent physical exercise improves perceived quality of life measured by EQ-5D and leads to a trend towards improvement in functional capacity, mood, and number of falls.
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Terapia por Exercício , Idoso Fragilizado , Humanos , Idoso , Qualidade de Vida , Pandemias , Exercício FísicoRESUMO
In line with the Research Domain Criteria (RDoC) , we set out to investigate the brain basis of psychopathology within a transdiagnostic, dimensional framework. We performed an integrative structural-functional linked independent component analysis to study the relationship between brain measures and a broad set of biobehavioral measures in a sample (n = 295) with both mentally healthy participants and patients with diverse non-psychotic psychiatric disorders (i.e. mood, anxiety, addiction, and neurodevelopmental disorders). To get a more complete understanding of the underlying brain mechanisms, we used gray and white matter measures for brain structure and both resting-state and stress scans for brain function. The results emphasize the importance of the executive control network (ECN) during the functional scans for the understanding of transdiagnostic symptom dimensions. The connectivity between the ECN and the frontoparietal network in the aftermath of stress was correlated with symptom dimensions across both the cognitive and negative valence domains, and also with various other health-related biological and behavioral measures. Finally, we identified a multimodal component that was specifically associated with the diagnosis of autism spectrum disorder (ASD). The involvement of the default mode network, precentral gyrus, and thalamus across the different modalities of this component may reflect the broad functional domains that may be affected in ASD, like theory of mind, motor problems, and sensitivity to sensory stimuli, respectively. Taken together, the findings from our extensive, exploratory analyses emphasize the importance of a dimensional and more integrative approach for getting a better understanding of the brain basis of psychopathology.
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Transtorno do Espectro Autista , Transtornos Mentais , Humanos , Encéfalo/diagnóstico por imagem , Psicopatologia , Transtornos de Ansiedade , Imageamento por Ressonância Magnética/métodosRESUMO
Disturbed sleep is a key symptom in major depressive disorder (MDD). REM sleep alterations are well described in the current literature, but little is known about non-REM sleep alterations. Additionally, sleep disturbances relate to a variety of cognitive symptoms in MDD, but which features of non-REM sleep EEG contribute to this, remains unknown. We comprehensively analyzed non-REM sleep EEG features in two central channels in three independently collected datasets (N = 284 recordings of 216 participants). This exploratory and descriptive study included MDD patients with a broad age range, varying duration and severity of depression, unmedicated or medicated, age- and gender-matched to healthy controls. We explored changes in sleep architecture including sleep stages and cycles, spectral power, sleep spindles, slow waves (SW), and SW-spindle coupling. Next, we analyzed the association of these sleep features with acute measures of depression severity and overnight consolidation of procedural memory. Overall, no major systematic alterations in non-REM sleep architecture were found in patients compared to controls. For the microstructure of non-REM sleep, we observed a higher spindle amplitude in unmedicated patients compared to controls, and after the start of antidepressant medication longer SWs with lower amplitude and a more dispersed SW-spindle coupling. In addition, long-term, but not short-term medication seemed to lower spindle density. Overnight procedural memory consolidation was impaired in medicated patients and associated with lower sleep spindle density. Our results suggest that alterations of non-REM sleep EEG in MDD might be more subtle than previously reported. We discuss these findings in the context of antidepressant medication intake and age.
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Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/complicações , Polissonografia , Fases do Sono , Sono , EletroencefalografiaRESUMO
Neutral events preceding emotional experiences can be better remembered, likely by assigning them as significant to guide possible use in future. Yet, the neurobiological mechanisms of how emotional learning enhances memory for past mundane events remain unclear. By two behavioral studies and one functional magnetic resonance imaging study with an adapted sensory preconditioning paradigm, we show rapid neural reactivation and connectivity changes underlying emotion-charged retroactive memory enhancement. Behaviorally, emotional learning retroactively enhanced initial memory for neutral associations across the three studies. Neurally, emotional learning potentiated trial-specific reactivation of overlapping neural traces in the hippocampus and stimulus-relevant neocortex. It further induced rapid hippocampal-neocortical functional reorganization supporting such retroactive memory benefit, as characterized by enhanced hippocampal-neocortical coupling modulated by the amygdala during emotional learning, and a shift of hippocampal connectivity from stimulus-relevant neocortex to distributed transmodal prefrontal-parietal areas at post-learning rests. Together, emotional learning retroactively promotes memory integration for past neutral events through stimulating trial-specific reactivation of overlapping representations and reorganization of associated memories into an integrated network to foster its priority for future use.
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Rememoração Mental , Neocórtex , Rememoração Mental/fisiologia , Emoções/fisiologia , Aprendizagem , Hipocampo/fisiologia , Neocórtex/fisiologia , Imageamento por Ressonância MagnéticaRESUMO
The high-pressure crystal structure evolution of CH3NH3PbBr3 (MAPbBr3) perovskite has been investigated by single-crystal X-ray diffraction and synchrotron-based powder X-ray diffraction. Single-crystal X-ray diffraction reveals that the crystal structure of MAPbBr3 undergoes two phase transitions following the space-group sequence: Pm3Ì m â Im3Ì â Pmn21, unveiling the occurrence of a nonpolar/polar transition (Im3Ì â Pmn21). The transitions take place at around 0.8 and 1.8 GPa, respectively. This result contradicts the previously reported phase transition sequence: Pm3Ì m â Im3Ì âPnma. In this work, the crystal structures of each of the three phases are determined from single-crystal X-ray diffraction analysis, which is later supported by Rietveld refinement of powder X-ray diffraction patterns. The pressure dependence of the crystal lattice parameters and unit-cell volumes are determined from the two aforementioned techniques, as well as the bulk moduli for each phase. The bandgap behavior of MAPbBr3 has been studied up to around 4 GPa, by means of single-crystal optical absorption experiments. The evolution of the bandgap has been well explained using the pressure dependence of the Pb-Br bond distance and Pb-Br-Pb angles as determined from single-crystal X-ray diffraction experiments.
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Repetitive negative thinking (RNT) captures an important transdiagnostic factor that predisposes to a maladaptive stress response and contributes to diverse psychiatric disorders. Although RNT can best be seen as a continuous symptom dimension that cuts across boundaries from health to various psychiatric disorders, the neural mechanisms underlying RNT have almost exclusively been studied in health and stress-related disorders, such as depression and anxiety disorders. We set out to study RNT from a large-scale brain network perspective in a diverse population consisting of healthy subjects and patients with a broader range of psychiatric disorders. We studied 46 healthy subjects along with 153 patients with a stress-related and/or neurodevelopmental disorder. We focused on three networks, that are associated with RNT and diverse psychiatric disorders: the salience network, default mode network (DMN) and frontoparietal network (FPN). We investigated the relationship of RNT with both network connectivity strength at rest and with the stress-induced changes in connectivity. Across our whole sample, the level of RNT was positively associated with the connectivity strength of the left FPN at rest, but negatively associated with stress-induced changes in DMN connectivity. These findings may reflect an upregulation of the FPN in an attempt to divert attention away from RNT, while the DMN result may reflect a less flexible adaptation to stress, related to RNT. Additionally, we discuss how our findings fit into the non-invasive neurostimulation literature. Taken together, our results provide initial insight in the neural mechanisms of RNT across the spectrum from health to diverse psychiatric disorders.
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[This corrects the article DOI: 10.1371/journal.pone.0260952.].
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Alterations in long-range functional connectivity between distinct brain regions are thought to contribute to the encoding of memory. However, little is known about how the activation of an existing network of neocortical and hippocampal regions might support the assimilation of relevant new information into the preexisting knowledge structure or 'schema'. Using functional mapping for expression of plasticity-related immediate early gene products, we sought to identify the long-range functional network of paired-associate memory, and the encoding and assimilation of relevant new paired-associates. Correlational and clustering analyses for expression of immediate early gene products revealed that midline neocortical-hippocampal connectivity is strongly associated with successful memory encoding of new paired-associates against the backdrop of the schema, compared to both (1) unsuccessful memory encoding of new paired-associates that are not relevant to the schema, and (2) the mere retrieval of the previously learned schema. These findings suggest that the certain midline neocortical and hippocampal networks support the assimilation of newly encoded associative memories into a relevant schema.
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Encéfalo , Hipocampo , Encéfalo/fisiologia , Córtex Cerebral , Hipocampo/fisiologia , Aprendizagem , Imageamento por Ressonância MagnéticaRESUMO
Measures taken to reduce the rate of contagion during the first months of the COVID-19 pandemic in Spain led to the interruption of nursing interventions for many patients with serious mental illness (SMI), while others stayed in touch with their nurses telematically. However, published research into the impact of mental telehealth and the outcome of the changes that took place in the pandemic is very limited. Aim: The aim of this study was to analyze the changes in nursing interventions received by severe mental illness (SMI) patients and to test whether telemental health (TH) has been effective in reducing relapses during the COVID-19 pandemic. Materials and methods: Information was gathered retrospectively from about 270 patients under treatment at 15 mental health day hospitals (MHDHs) in Spain during the year 2020. Results: Face-to-face nursing interventions were found to have decreased and TH interventions were found to have increased in the first few months of the pandemic. In the following months, TH interventions-especially those conducted by video call-helped reduce the number of relapses. Conclusions: TH helps provide news forms of effective telematic nursing interventions that reduce the number of relapses and admissions in patients with serious mental health disorders.
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STUDY OBJECTIVES: The learning brain establishes schemas (knowledge structures) that benefit subsequent learning. We investigated how sleep and having a schema might benefit initial learning followed by rearranged and expanded memoranda. We concurrently examined the contributions of sleep spindles and slow-wave sleep to learning outcomes. METHODS: Fifty-three adolescents were randomly assigned to an 8 h Nap schedule (6.5 h nocturnal sleep with a 90-minute daytime nap) or an 8 h No-Nap, nocturnal-only sleep schedule. The study spanned 14 nights, simulating successive school weeks. We utilized a transitive inference task involving hierarchically ordered faces. Initial learning to set up the schema was followed by rearrangement of the hierarchy (accommodation) and hierarchy expansion (assimilation). The expanded sequence was restudied. Recall of hierarchical knowledge was tested after initial learning and at multiple points for all subsequent phases. As a control, both groups underwent a No-schema condition where the hierarchy was introduced and modified without opportunity to set up a schema. Electroencephalography accompanied the multiple sleep opportunities. RESULTS: There were main effects of Nap schedule and Schema condition evidenced by superior recall of initial learning, reordered and expanded memoranda. Improved recall was consistently associated with higher fast spindle density but not slow-wave measures. This was true for both nocturnal sleep and daytime naps. CONCLUSION: A sleep schedule incorporating regular nap opportunities compared to one that only had nocturnal sleep benefited building of robust and flexible schemas, facilitating recall of the subsequently rearranged and expanded structured knowledge. These benefits appear to be strongly associated with fast spindles. CLINICAL TRIAL REGISTRATION: NCT04044885 (https://clinicaltrials.gov/ct2/show/NCT04044885).
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Sono de Ondas Lentas , Sono , Adolescente , Eletroencefalografia , Humanos , Aprendizagem , Rememoração MentalRESUMO
Abundant evidence shows that early-life stress (ELS) predisposes for the development of stress-related psychopathology when exposed to stressors later in life, but the underlying mechanisms remain unclear. To study predisposing effects of mild ELS on stress sensitivity, we examined in a healthy human population the impact of a history of ELS on acute stress-related changes in corticolimbic circuits involved in emotional processing (i.e., amygdala, hippocampus and ventromedial prefrontal cortex [vmPFC]). Healthy young male participants (n = 120) underwent resting-state functional magnetic resonance imaging (fMRI) in two separate sessions (stress induction vs. control). The Childhood Trauma Questionnaire (CTQ) was administered to index self-reported ELS, and stress induction was verified using salivary cortisol, blood pressure, heart rate and subjective affect. Our findings show that self-reported ELS was negatively associated with baseline cortisol, but not with the acute stress-induced cortisol response. Critically, individuals with more self-reported ELS exhibited an exaggerated reduction of functional connectivity in corticolimbic circuits under acute stress. A mediation analysis showed that the association between ELS and stress-induced changes in amygdala-hippocampal connectivity became stronger when controlling for basal cortisol. Our findings show, in a healthy sample, that the effects of mild ELS on functioning of corticolimbic circuits only become apparent when exposed to an acute stressor and may be buffered by adaptations in hypothalamic-pituitary-adrenal axis function. Overall, our findings might reveal a potential mechanism whereby even mild ELS might confer vulnerability to exposure to stressors later in adulthood.
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Experiências Adversas da Infância , Adulto , Humanos , Hidrocortisona , Sistema Hipotálamo-Hipofisário , Imageamento por Ressonância Magnética , Masculino , Sistema Hipófise-Suprarrenal , Estresse PsicológicoRESUMO
How do we encode our continuous life experiences for later retrieval? Theories of event segmentation and integration suggest that the hippocampus binds separately represented events into an ordered narrative. Using a functional Magnetic Resonance Imaging (fMRI) movie watching-recall dataset, we quantified two types of neural similarities (i.e., "activation pattern" similarity and within-region voxel-based "connectivity pattern" similarity) between separate events during movie watching and related them to subsequent retrieval of events as well as retrieval of sequential order. We demonstrated that compared with forgotten events, successfully remembered events were associated with distinct "activation patterns" in the hippocampus and medial prefrontal cortex. In contrast, similar "connectivity pattern" between events were associated with memory formation and were also relevant for retaining events in the correct order. We applied the same approaches to an independent movie watching fMRI dataset as validation and highlighted again the role of hippocampal activation pattern and connectivity pattern in memory formation. We propose that distinct activation patterns represent neural segmentation of events, while similar connectivity patterns encode context information and, therefore, integrate events into a narrative. Our results provide novel evidence for the role of hippocampal-medial prefrontal event segmentation and integration in episodic memory formation of real-life experience.
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Memória Episódica , Mapeamento Encefálico/métodos , Hipocampo/diagnóstico por imagem , Hipocampo/fisiologia , Imageamento por Ressonância Magnética , Rememoração Mental/fisiologiaRESUMO
The endeavor to understand the human brain has seen more progress in the last few decades than in the previous two millennia. Still, our understanding of how the human brain relates to behavior in the real world and how this link is modulated by biological, social, and environmental factors is limited. To address this, we designed the Healthy Brain Study (HBS), an interdisciplinary, longitudinal, cohort study based on multidimensional, dynamic assessments in both the laboratory and the real world. Here, we describe the rationale and design of the currently ongoing HBS. The HBS is examining a population-based sample of 1,000 healthy participants (age 30-39) who are thoroughly studied across an entire year. Data are collected through cognitive, affective, behavioral, and physiological testing, neuroimaging, bio-sampling, questionnaires, ecological momentary assessment, and real-world assessments using wearable devices. These data will become an accessible resource for the scientific community enabling the next step in understanding the human brain and how it dynamically and individually operates in its bio-social context. An access procedure to the collected data and bio-samples is in place and published on https://www.healthybrainstudy.nl/en/data-and-methods/access. Trail registration: https://www.trialregister.nl/trial/7955.
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Encéfalo/fisiologia , Meio Social , Adulto , Afeto/fisiologia , Comportamento , Encéfalo/diagnóstico por imagem , COVID-19/diagnóstico , Cognição/fisiologia , Feminino , Humanos , Masculino , Neuroimagem , Sensação/fisiologia , Inquéritos e QuestionáriosRESUMO
Flexible behavior requires switching between different task conditions. It is known that such task switching is associated with costs in terms of slowed RT, reduced accuracy, or both. The neural correlates of task switching have usually been studied by requiring participants to switch between distinct task conditions that recruit different brain networks. Here, we investigated the transition of neural states underlying switching between two opposite memory-related processes (i.e., memory retrieval and memory suppression) in a memory task. We investigated 26 healthy participants who performed a think/no-think task while being in the fMRI scanner. Behaviorally, we show that it was more difficult for participants to suppress unwanted memories when a no-think was preceded by a think trial instead of another no-think trial. Neurally, we demonstrate that think-no-think switches were associated with an increase in control-related and a decrease in memory-related brain activity. Neural representations of task condition, assessed by decoding accuracy, were lower immediately after task switching compared with the nonswitch transitions, suggesting a switch-induced delay in the neural transition toward the required task condition. This suggestion is corroborated by an association between condition-specific representational strength and condition-specific performance in switch trials. Taken together, we provided neural evidence from the time-resolved decoding approach to support the notion that carryover of the previous task set activation is associated with the switching cost, leading to less successful memory suppression.
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Encéfalo , Memória , Encéfalo/diagnóstico por imagem , Voluntários Saudáveis , Humanos , Imageamento por Ressonância MagnéticaRESUMO
Children's learning capabilities change while growing up. One framework that describes the cognitive and neural development of children's growing learning abilities is the two-component model. It distinguishes processes that integrate separate features into a coherent memory representation (associative component) and executive abilities, such as elaboration, evaluation, and monitoring, that support memory processing (strategic component). In an fMRI study using an object-location association paradigm, we investigated how the two components influence memory performance across development. We tested children (10-12 years, n = 31), late adolescents (18 years, n = 29), and adults (25+ years, n = 30). For studying the associative component, we also probed how the utilisation of prior knowledge (schemas) facilitates memory across age groups. Children had overall lower retrieval performance, while adolescents and adults did not differ from each other. All groups benefitted from schemas, but this effect did not differ between groups. Performance differences between groups were associated with deactivation of the dorsal medial prefrontal cortex (dmPFC), which in turn was linked to executive functioning. These patterns were stronger in adolescents and adults and seemed absent in children. Thus, the children's executive system, the strategic component, is not as mature and thus cannot facilitate memory performance in the same way as in adolescents/adults. In contrast, we did not find age-related differences in the associative component; with activity in the angular gyrus predicting memory performance systematically across groups. Overall, our results suggest that differences of executive rather than associative abilities explain memory differences between children, adolescents, and adults.
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Aprendizagem por Associação/fisiologia , Mapeamento Encefálico , Função Executiva/fisiologia , Desenvolvimento Humano/fisiologia , Memória/fisiologia , Córtex Pré-Frontal/fisiologia , Adolescente , Adulto , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Córtex Pré-Frontal/diagnóstico por imagem , Adulto JovemRESUMO
Upon awakening from nighttime sleep, the stress hormone cortisol in humans exhibits a robust rise within thirty to forty-five minutes. This cortisol awakening response (CAR), a crucial point of reference within the healthy cortisol circadian rhythm, has been linked to various psychological, psychiatric and health-related conditions. The CAR is thought to prepare the brain for anticipated challenges of the upcoming day to maintain one's homeostasis and promote adaptive responses. Using brain imaging with a prospective design and pharmacological manipulation, we investigate the neurobiological mechanisms underlying this preparation function of the CAR across two studies. In Study 1, a robust CAR is predictive of less hippocampal and prefrontal activity, though enhanced functional coupling between those regions during a demanding task hours later in the afternoon. Reduced prefrontal activity is in turn linked to better working memory performance, implicating that the CAR proactively promotes brain preparedness based on improved neurocognitive efficiency. In Study 2, pharmacologically suppressed CAR using Dexamethasone mirrors this proactive effect, which further causes a selective reduction of prefrontal top-down functional modulation over hippocampal activity. These findings establish a causal link between the CAR and its proactive role in optimizing functional brain networks involved in neuroendocrine control, executive function and memory.
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Hipocampo , Vigília , Encéfalo , Humanos , Hidrocortisona , Estudos Prospectivos , SalivaRESUMO
A key aspect of conceptual knowledge is that it can be flexibly applied at different levels of abstraction, implying a hierarchical organization. It is yet unclear how this hierarchical structure is acquired and represented in the brain. Here we investigate the computations underlying the acquisition and representation of the hierarchical structure of conceptual knowledge in the hippocampal-prefrontal system of 32 human participants (22 females). We assessed the hierarchical nature of learning during a novel tree-like categorization task via computational model comparisons. The winning model allowed to extract and quantify estimates for accumulation and updating of hierarchical compared with single-feature-based concepts from behavior. We find that mPFC tracks accumulation of hierarchical conceptual knowledge over time, and mPFC and hippocampus both support trial-to-trial updating. As a function of those learning parameters, mPFC and hippocampus further show connectivity changes to rostro-lateral PFC, which ultimately represented the hierarchical structure of the concept in the final stages of learning. Our results suggest that mPFC and hippocampus support the integration of accumulated evidence and instantaneous updates into hierarchical concept representations in rostro-lateral PFC.SIGNIFICANCE STATEMENT A hallmark of human cognition is the flexible use of conceptual knowledge at different levels of abstraction, ranging from a coarse category level to a fine-grained subcategory level. While previous work probed the representational geometry of long-term category knowledge, it is unclear how this hierarchical structure inherent to conceptual knowledge is acquired and represented. By combining a novel hierarchical concept learning task with computational modeling of categorization behavior and concurrent fMRI, we differentiate the roles of key concept learning regions in hippocampus and PFC in learning computations and the representation of a hierarchical category structure.
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Formação de Conceito/fisiologia , Hipocampo/diagnóstico por imagem , Aprendizagem/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem , Adulto , Mapeamento Encefálico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Resolução de Problemas/fisiologia , Adulto JovemRESUMO
People often experience high level of distress during invasive interventions, which may exceed their coping abilities. This may be in particular evident when confronted with the suspicion of cancer. Taking the example of prostate biopsy sampling, we aimed at investigating the impact of an MRI guided prostate biopsy on the acute stress response and its mechanistic basis. We recruited 20 men with a clinical suspicion of prostate cancer. Immediately before an MRI guided biopsy procedure, we conducted fMRI in the same scanner to assess resting-state brain connectivity. Physiological and hormonal stress measures were taken during the procedure and associated with questionnaires, hair cortisol levels and brain measures to elucidate mechanistic factors for elevated stress. As expected, patients reported a stress-related change in affect. Decreased positive affect was associated with higher hair but not saliva cortisol concentration. Stronger use of maladaptive emotion regulation techniques, elevated depression scores and higher within-salience-network connectivity was associated with stronger increase in negative affect and/or decrease of positive affect during the procedure. While being limited in its generalization due to age, sample size and gender, our proof of concept study demonstrates the utility of real-life stressors and large-scale brain network measures in stress regulation research with potential impact in clinical practice.