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Individuals generally form their unique memories from shared experiences, yet the neural representational mechanisms underlying this subjectiveness of memory are poorly understood. The current study addressed this important question from the cross-subject neural representational perspective, leveraging a large functional magnetic resonance imaging dataset (n = 415) of a face-name associative memory task. We found that individuals' memory abilities were predicted by their synchronization to the group-averaged, canonical trial-by-trial activation level and, to a lesser degree, by their similarity to the group-averaged representational patterns during encoding. More importantly, the memory content shared between pairs of participants could be predicted by their shared local neural activation pattern, particularly in the angular gyrus and ventromedial prefrontal cortex, even after controlling for differences in memory abilities. These results uncover neural representational mechanisms for individualized memory and underscore the constructive nature of episodic memory.
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Memoria Episódica , Humanos , Corteza Prefrontal/diagnóstico por imagen , Lóbulo ParietalRESUMEN
Elucidating the neural mechanisms of general cognitive ability (GCA) is an important mission of cognitive neuroscience. Recent large-sample cohort studies measured GCA through multiple cognitive tasks and explored its neural basis, but they did not investigate how task number, factor models, and neural data type affect the estimation of GCA and its neural correlates. To address these issues, we tested 1,605 Chinese young adults with 19 cognitive tasks and Raven's Advanced Progressive Matrices (RAPM) and collected resting state and n-back task fMRI data from a subsample of 683 individuals. Results showed that GCA could be reliably estimated by multiple tasks. Increasing task number enhances both reliability and validity of GCA estimates and reliably strengthens their correlations with brain data. The Spearman model and hierarchical bifactor model yield similar GCA estimates. The bifactor model has better model fit and stronger correlation with RAPM but explains less variance and shows weaker correlations with brain data than does the Spearman model. Notably, the n-back task-based functional connectivity patterns outperform resting-state fMRI in predicting GCA. These results suggest that GCA derived from a multitude of cognitive tasks serves as a valid measure of general intelligence and that its neural correlates could be better characterized by task fMRI than resting-state fMRI data.
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Mapeo Encefálico , Encéfalo , Adulto Joven , Humanos , Reproducibilidad de los Resultados , Vías Nerviosas , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , CogniciónRESUMEN
Parietal alpha activity shows a specific pattern of phasic changes during working memory. It decreases during the encoding and recall phases but increases during the maintenance phase. This study tested whether online rTMS delivered to the parietal cortex during the maintenance phase of a working memory task would increase alpha activity and hence improve working memory. Then, 46 healthy volunteers were randomly assigned to two groups to receive 3-day parietal 10 Hz online rTMS (either real or sham, 3600 pulses in total) that were time-locked to the maintenance phase of a spatial span task (180 trials in total). Behavioral performance on another spatial span task and EEG signals during a change detection task were recorded on the day before the first rTMS (pretest) and the day after the last rTMS (posttest). We found that rTMS improved performance on both online and offline spatial span tasks. For the offline change detection task, rTMS enhanced alpha activity within the maintenance phase and improved interference control of working memory at both behavioral (K score) and neural (contralateral delay activity) levels. These results suggested that rTMS with alpha frequency time-locked to the maintenance phase is a promising way to boost working memory.
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Memoria a Corto Plazo , Estimulación Magnética Transcraneal , Humanos , Estimulación Magnética Transcraneal/métodos , Memoria a Corto Plazo/fisiología , Lóbulo Parietal/diagnóstico por imagen , Lóbulo Parietal/fisiología , Recuerdo MentalRESUMEN
BACKGROUND: Episodic memory (EM) deteriorates as a result of normal aging as well as Alzheimer's disease. The neural underpinnings of such age-related memory impairments in older individuals are not well-understood. Although previous research has unveiled the association between gray matter volume (GMV) and EM in the elderly population, such findings exhibit variances across distinct age cohorts. Consequently, an investigation into the dynamic evolution of this relationship with advancing age is imperative. RESULT: The present study utilized a sliding window approach to examine how the correlation between EM and GMV varied with age in a cross-sectional sample of 926 Chinese older adults. We found that both verbal EM (VEM) and spatial EM (SEM) exhibited positive correlations with GMV in extensive areas primarily in the temporal and frontal lobes and that these correlations typically became stronger with older age. Moreover, there were variations in the strength of the correlation between EM and GMV with age, which differed based on sex and the specific type of EM. Specifically, the association between VEM and GMVs in the insula and parietal regions became stronger with age for females but not for males, whereas the association between SEM and GMVs in the parietal and occipital regions became stronger for males but not for females. At the brain system level, there is a significant age-related increase in the correlations between both types of EM and the GMV of both the anterior temporal (AT) system and the posterior medial (PM) system in male group. In females, both types of EM show stronger age-related correlations with the GMV of the AT system compared to males. CONCLUSIONS: Our study revealed a significant positive correlation between GMV in most regions associated with EM and age, particularly in the frontal and temporal lobes. This discovery offers new insights into the connection between brain structure and the diminishing episodic memory function among older individuals.
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Envejecimiento , Lóbulo Frontal , Sustancia Gris , Imagen por Resonancia Magnética , Memoria Episódica , Lóbulo Temporal , Humanos , Masculino , Femenino , Anciano , Sustancia Gris/diagnóstico por imagen , Lóbulo Frontal/diagnóstico por imagen , Envejecimiento/fisiología , Envejecimiento/patología , Lóbulo Temporal/diagnóstico por imagen , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Estudios Transversales , Anciano de 80 o más Años , Tamaño de los Órganos/fisiologíaRESUMEN
The leftward asymmetry of the visual field and posterior brain regions, a feature of the normal attention process, can be strengthened by brain stimulation, e.g. administering alpha frequency stimulation to the left posterior cortex. However, whether it can be strengthened by cognitive training, especially with nonlateralized tasks, is unknown. We used a dataset from a 2-month-long randomized controlled trial and compared the control group with 2 training groups trained with backward or forward memory span tasks. A lateralized change detection task with varied memory loads was administered as the pre-, mid-, and post-tests with simultaneous electroencephalographic recording. Intrasubject response variability (IRV) and the alpha modulation index (MI) were calculated. Analysis of IRV showed more enhanced leftward attentional bias in the backward group than in the other groups. Consistently, analysis of MI found that its enhancements in the left hemisphere (but not the right hemisphere) of the backward group were significantly higher than those of the other groups. Further analysis revealed that left MI changes predicted left IRV improvement. All of these results indicated that backward memory span training enhanced leftward attentional asymmetry at both the behavioral and neural levels.
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Sesgo Atencional , Memoria a Corto Plazo , Memoria a Corto Plazo/fisiología , Atención/fisiología , Encéfalo/fisiología , Campos VisualesRESUMEN
The ability to delay gratification is crucial for a successful and healthy life. An effective way for young children to learn this ability is to observe the action of adult models. However, the underlying neurocomputational mechanism remains unknown. Here, we tested the hypotheses that children employed either the simple imitation strategy or the goal-inference strategy when learning from adult models in a high-uncertainty context. Results of computational modeling indicated that children used the goal-inference strategy regardless of whether the adult model was their mother or a stranger. At the neural level, results showed that successful learning of delayed gratification was associated with enhanced interpersonal neural synchronization (INS) between children and the adult models in the dorsal lateral prefrontal cortex but was not associated with children's own single-brain activity. Moreover, the discounting of future reward's value obtained from computational modeling of the goal-inference strategy was positively correlated with the strength of INS. These findings from our exploratory study suggest that, even for 3-year-olds, the goal-inference strategy is used to learn delayed gratification from adult models, and the learning strategy is associated with neural interaction between the brains of children and adult models.
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Descuento por Demora , Adulto , Femenino , Humanos , Niño , Preescolar , Recompensa , Corteza Prefrontal , Aprendizaje , MotivaciónRESUMEN
Numerous studies have demonstrated the role of making choices as an internal motivator to improve performance, and recent studies in the domain of memory have focused on adults. To chart the developmental trend of the choice effect on memory, we conducted a series of seven experiments involving children, adolescents, and young adults. Participants (N = 512) aged 5 to 26 years performed a choice encoding task that manipulated the opportunities to choose and then took a memory test. Using different types of experimental materials and corroborated by a mini meta-analysis, we found that the choice effect on memory was significant in childhood and early adolescence but not significant in late adolescence and early adulthood. The developmental changes were statistically significant, particularly evident during the transition from early to late adolescence. These findings suggest that the internal value of choice decreases across development and contributes to our understanding of developmental differences in the role of choice in memory.
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Desarrollo Infantil , Conducta de Elección , Humanos , Adolescente , Conducta de Elección/fisiología , Femenino , Masculino , Niño , Adulto Joven , Adulto , Preescolar , Desarrollo Infantil/fisiología , Memoria , Factores de EdadRESUMEN
BACKGROUND: Mental health in the elderly has multiple determinants, and studies indicate household and family composition, economic status, and family support are key factors. However, these are difficult to modify, and better lifestyle for the elderly can be a possible intervention. The current study examined the mediating role of lifestyle in the association between these three types of the household and family composition (living alone, living with a spouse, and living with children) and mental health in older adults. METHODS: We studied 5,407 participants (58.7% female, age 45 + years) from the Beijing Aging Brain Rejuvenation Initiative Project. All participants underwent a battery of examinations to measure degree loneliness, depression, and global cognitive function. We also surveyed personal lifestyles. We used a mediation analysis to determine the relative contribution of each lifestyle factor on mental health outcomes. RESULTS: Older adults living alone rarely participated in mental and social activities and often had irregular diets; those adults living with children spent most of their time caring for grandchildren and had irregular eating and sleeping schedules; those living with a spouse often engaged in a variety of leisure activities and had the best life habits. Mediation analyses showed that dietary and sleeping irregularity partially mediated the negative effects of living alone on mental health, and were moderated by age and gender. CONCLUSIONS: Living with a spouse was associated with benefits for the mental health of middle-aged and older adults (especially older and female individuals), through modifying better lifestyles than those of individuals with the other two types of the household and family composition.
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Composición Familiar , Estilo de Vida , Salud Mental , Humanos , Femenino , Masculino , Anciano , Persona de Mediana Edad , Salud Mental/estadística & datos numéricos , Anciano de 80 o más Años , Beijing , Soledad/psicología , Depresión/epidemiología , Depresión/psicologíaRESUMEN
Previous studies have investigated factors related to the degree of cross-language overlap in brain activations in bilinguals/multilinguals. However, it is still unclear whether and how the depth of semantic processing (a critical task-related factor) affects the neural pattern similarity between native and second languages. To address this question, 26 Chinese-English bilinguals were scanned with fMRI while performing a word naming task (i.e., a task with shallow semantic processing) and a semantic judgment task (i.e., a task with deep semantic processing) in both native and second languages. Based on three sets of representational similarity analysis (whole brain, ROI-based, and within-language vs. cross-language semantic representation), we found that select regions in the reading brain network showed higher cross-language pattern similarity and higher cross-language semantic representations during deep semantic processing than during shallow semantic processing. These results suggest that compared to shallow semantic processing, deep semantic processing may lead to greater language-independent processing (i.e., cross-language semantic representation) and cross-language pattern similarity, and provide direct quantitative neuroimaging evidence for cognitive models of bilingual lexical memory.
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Multilingüismo , Semántica , Humanos , Encéfalo/diagnóstico por imagen , Lenguaje , Imagen por Resonancia MagnéticaRESUMEN
Metal-C core-shell nanoparticles have been recently demonstrated to be promising candidates for microwave absorption applications. However, the underlying absorption mechanism, such as the contributions of the metal cores and C shells on their absorption performance, remains far from clear due to the complicated interfaces and synergetic effects between metal cores and C shells, as well as the significant challenges in the preparation of samples with well-defined comparability. In this study, Cu-C core-shell nanoparticles and their derivatives, i.e., bare Cu and hollow C nanoparticles, were synthesized for a comparative study on their microwave absorption properties. Electric energy loss models of the three samples were established, and based on these models, the comparative study suggested that the polarization loss could be significantly improved by C shells, and Cu cores had negligible influences on the conduction loss of Cu-C core-shell nanoparticles. The interface between C shells and Cu cores tuned the conduction loss and polarization loss to establish improved impedance matching and achieve optimal microwave absorption performances. A wide effective bandwidth of 5.4 GHz and a low reflection loss of -42.6 dB were achieved for Cu-C core-shell nanoparticles. This work provides new insights into how metal nanocores and C nanoshells affect the microwave absorption of core-shell nanostructures from experimental and theoretical points of view, which has reference values for the construction of highly efficient metal-C-based absorbers.
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The role of the visuospatial network in mathematical processing has been established, but the role of the semantic neural network in mathematical processing is still poorly understood. The current study used high-definition transcranial direct current stimulation (HD-tDCS) to examine whether the semantic network supports mathematical processing. Using a single-blind, randomized, sham-controlled experimental design, 48 participants were randomly assigned to receive either anodal or sham HD-tDCS on the left middle temporal gyrus (LMTG), a core region of the semantic network. A number series completion task was used to measure mathematical reasoning and an arithmetical computation task was used as a control condition. Both tasks were administered before and after the 20 min HD-tDCS. The results showed that anodal HD-tDCS on the LMTG enhanced performance on the number series completion task, but not on the arithmetical computation task. Trial-level analysis further showed greater improvement at the more difficult problems of the number series completion task. These results demonstrate that the semantic network plays an important role in mathematical processing.
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Estimulación Transcraneal de Corriente Directa , Humanos , Estimulación Transcraneal de Corriente Directa/métodos , Método Simple Ciego , Lóbulo Temporal , SemánticaRESUMEN
The hippocampus plays an important role in representing spatial locations and sequences and in transforming representations. How these representational structures and operations support memory for the temporal order of random items is still poorly understood. We addressed this question by leveraging the method of loci, a powerful mnemonic strategy for temporal order memory that particularly recruits hippocampus-dependent computations of spatial locations and associations. Applying representational similarity analysis to functional magnetic resonance imaging activation patterns revealed that hippocampal subfields contained representations of multiple features of sequence structure, including spatial locations, location distance, and sequence boundaries, as well as episodic-like temporal context. Critically, the hippocampal CA1 exhibited spatial transformation of representational patterns, showing lower pattern similarity for items in same locations than closely matched different locations during retrieval, whereas the CA23DG exhibited sequential transformation of representational patterns, showing lower pattern similarity for items in near locations than in far locations during encoding. These transformations enabled the encoding of multiple items in the same location and disambiguation of adjacent items. Our results suggest that the hippocampus can flexibly reconfigure multiplexed event structure representations to support accurate temporal order memory.
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Mapeo Encefálico , Memoria Episódica , Mapeo Encefálico/métodos , Hipocampo/diagnóstico por imagen , Hipocampo/fisiología , Imagen por Resonancia Magnética/métodosRESUMEN
Previous studies on dual-brain social interaction have shown different patterns of interpersonal neural synchronization (INS) between conflictual and supportive interactions, but the role of emotion in the dual-brain mechanisms of such interactions is not well understood. Furthermore, little is known about how the dual-brain mechanisms are affected by relationship type (e.g., romantic relationship vs. friendship) and interaction mode (e.g., verbal vs. nonverbal). To elaborate on these issues, this study used functional near-infrared spectroscopy to collect hemodynamic signals from romantic couples and cross-sex friends while they were discussing conflictual, neutral, or supportive topics. For the couples but not the friends, INS between the sensorimotor cortex of both participants was greater when discussing the conflictual topic than when discussing the supportive topic. INS was positively correlated with the arousal level but not the valence level of communication contents. INS was also positively correlated with interpersonal physiological synchronization based on galvanic skin response, a physiological measure of arousal. Furthermore, the differences in INS between the conflictual and supportive topics were closely associated with verbal rather than nonverbal behaviors. Together, these findings suggest that it is the arousal level induced by verbal interactions during interpersonal conflicts that increases romantic couples' INS.
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Conflicto Psicológico , Relaciones Interpersonales , Encéfalo , Comunicación , Emociones , HumanosRESUMEN
OBJECTIVE: Acculturative stress, often experienced by members of minority groups, is related to problematic eating behaviors. What remains poorly understood is the function of perceived social support in this link. This study evaluated the moderating role of perceived support from family, the significant other, and friends in the association between acculturative stress and problematic eating behaviors, including emotional eating, uncontrolled eating, and cognitive restraint eating. METHOD: An online cross-sectional study was conducted with 497 Asian and Latinx college students using standardized questionnaires. Three hierarchical multivariable models were analyzed, with each eating behavior included as the outcome variable. Demographic variables (Step 1), general perceived stress (Step 2), and predictor variables (i.e., acculturative stress, perceived support; Step 3) were added using Method Enter. Interaction terms were entered using Method Stepwise (Step 4) to test for moderation effects. RESULTS: As perceived family support increased, the magnitude of the link between acculturative stress and higher uncontrolled eating increased (p = .002). When perceived significant other support was higher, the magnitude of the relationship between acculturative stress and higher emotional eating increased (p = .02). Higher perceived friend support was directly related to reduced uncontrolled eating (p = .002). DISCUSSION: This study highlights the heterogeneous effects of various sources of perceived support on the link between acculturative stress and problematic eating behaviors. Findings imply that problematic eating prevention and intervention programs might benefit from considering not only the acculturative stress experienced by racial/ethnic minority young adults but also the sources of support perceived. PUBLIC SIGNIFICANCE: Perceived support from family and the significant other increased the magnitude of the link between higher acculturative stress and increased problematic eating behaviors, whereas support from friends showed a direct relationship with reduced uncontrolled eating. The results highlight the nuanced functions of various sources of perceived social support and contribute to a deeper understanding of potential moderators in the relationship between acculturative stress and problematic eating behaviors among racial/ethnic minorities.
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Aculturación , Etnicidad , Conducta Alimentaria , Humanos , Adulto Joven , Estudios Transversales , Etnicidad/psicología , Amigos , Hispánicos o Latinos/psicología , Grupos Minoritarios/psicología , Estrés Psicológico/psicología , Asiático/psicologíaRESUMEN
Many cross-sectional studies have shown that number line estimation is associated with other mathematical skills, but there has been limited longitudinal research. To systematically examine such associations longitudinally at the earliest stage of mathematical learning, the current study tested 40 Chinese preschoolers (mean age = 4.97 years, SD = 0.18) and followed them up 8 months later. For both waves of data collection, children were administered six tasks: number line estimation, dot counting, comparison of two dot arrays, comparison of triple dot arrays, symbolic number comparison, and simple addition. Results of two-wave cross-lagged panel analysis showed that (a) dot counting and non-symbolic numerical comparison at Time 1 had significant longitudinal associations with number line estimation at Time 2, (b) number line estimation had bidirectional associations with symbolic number comparison, and (c) number line estimation at Time 1 had a marginally significant longitudinal association with simple addition at Time 2. These results extend the small but accumulating literature on the longitudinal relations between number line estimation and other mathematical skills and specify the important role of number line estimation in the early development of mathematical skills.
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Cognición , Pueblos del Este de Asia , Humanos , Preescolar , Estudios Transversales , Aprendizaje , MatemáticaRESUMEN
Both external motivational incentives (e.g., monetary reward) and internal motivational incentives (e.g., self-determined choice) have been found to promote memory, but much less is known about how these two types of incentives interact with each other to affect memory. The current study (N = 108) examined how performance-dependent monetary rewards affected the role of self-determined choice in memory performance, also known as the choice effect. Using a modified and better controlled version of the choice paradigm and manipulating levels of reward, we demonstrated an interactive effect between monetary reward and self-determined choice on 1-day delayed memory performance. Specifically, the choice effect on memory decreased when we introduced the performance-dependent external rewards. These results are discussed in terms of understanding how external and internal motivators interact to impact learning and memory.
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Aprendizaje , Memoria , Pruebas Psicológicas , Humanos , Recompensa , Motivación , Autonomía Personal , Masculino , Femenino , AdultoRESUMEN
AIM: Patients with Turner syndrome have a high rate of developmental dyscalculia, but the underlying neurocognitive mechanisms are not well-understood. Some studies have implicated visuospatial impairments in patients with Turner syndrome, but others have focused on poor procedural skills in patients with Turner syndrome. This study used brain imaging data to test these two alternative views. METHODS: This study recruited 44 girls with Turner syndrome (mean age, 12.91 years; SD, 2.02), with 13 (29.5%) of them meeting the criterion for developmental dyscalculia, and 14 normally developing girls (mean age, 14.26 years; SD, 2.18) as a comparison group. All participants were given basic mathematical ability tests and an intelligence test and were scanned using magnetic resonance imaging. We compared patients with Turner syndrome who had dyscalculia, patients with Turner syndrome who did not have dyscalculia, and the normal controls in terms of brain structures and resting-state functional activity. RESULTS: Compared with normal controls, both groups of patients with Turner syndrome (with or without dyscalculia) showed similarly altered functional connectivity in the occipitoparietal dorsal stream. Importantly, compared with patients with Turner syndrome without dyscalculia and normal controls, patients with Turner syndrome with dyscalculia showed decreased functional connectivity between the prefrontal and the lateral occipital cortex. CONCLUSION: We concluded that both groups of patients with Turner syndrome shared visual deficits, and patients with Turner syndrome with dyscalculia had a deficit in frontal cortex-based higher cognitive processing. It is not their visuospatial deficits but rather their deficits in higher cognitive processing that are responsible for the development of dyscalculia in patients with Turner syndrome.
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Discalculia , Síndrome de Turner , Femenino , Humanos , Niño , Adolescente , Síndrome de Turner/complicaciones , Síndrome de Turner/diagnóstico por imagen , Discalculia/diagnóstico por imagen , Discalculia/etiología , Encéfalo , Cognición , Corteza Prefrontal/diagnóstico por imagen , Imagen por Resonancia MagnéticaRESUMEN
Restudying word lists (e.g., dream, awake, and bed) strengthens true memory of the studied words and reduces false memory for unstudied but semantically related lures (e.g., sleep). Yet, the neural mechanisms involved in this repetition effect on false memory remain unclear. Possible mechanisms involve item-specific and semantic neural representations at encoding, and the memory strength between encoding and retrieval. This study first replicated the behavioral results (Exp. 1) and then investigated various neural mechanisms by using slow event-related functional magnetic resonance imaging (fMRI) and representational similarity analysis (Exp. 2). Behavioral results confirmed that restudy improved true memory and reduced false memory. The fMRI results showed that restudy induced item-specific neural representations at encoding in the left occipital pole, but reduced neural overlap between semantic representations at encoding in the left temporal pole. Individual differences in these two encoding neural mechanisms were correlated with the behavioral measure of false memory, with greater restudy-induced representational changes at encoding (item-specific neural representations and reduced neural overlap between semantic representations) being associated with lower false memory. Moreover, restudy enhanced the memory strength between encoding and retrieval in the visuoparietal cortex but reduced it in the frontal cortex. These findings suggest that dynamic changes in neural representations underlie the repetition effect on false memory, supporting a dual-coding neural framework.
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Mapeo Encefálico , Recuerdo Mental , Humanos , Imagen por Resonancia Magnética , Memoria , SemánticaRESUMEN
The crucial role of the parietal cortex in working memory (WM) storage has been identified by fMRI studies. However, it remains unknown whether repeated parietal intermittent theta-burst stimulation (iTBS) can improve WM. In this within-subject randomized controlled study, under the guidance of fMRI-identified parietal activation in the left hemisphere, 22 healthy adults received real and sham iTBS sessions (five consecutive days, 600 pulses per day for each session) with an interval of 9 months between the two sessions. Electroencephalography signals of each subject before and after both iTBS sessions were collected during a change detection task. Changes in contralateral delay activity (CDA) and K-score were then calculated to reflect neural and behavioral WM improvement. Repeated-measures ANOVA suggested that real iTBS increased CDA more than the sham one (p = .011 for iTBS effect). Further analysis showed that this effect was more significant in the left hemisphere than in the right hemisphere (p = .029 for the hemisphere-by-iTBS interaction effect). Pearson correlation analyses showed significant correlations for two conditions between CDA changes in the left hemisphere and K score changes (ps <.05). In terms of the behavioral results, significant K score changes after real iTBS were observed for two conditions, but a repeated-measures ANOVA showed a nonsignificant main effect of iTBS (p = .826). These results indicate that the current iTBS protocol is a promising way to improve WM capability based on the neural indicator (CDA) but further optimization is needed to produce a behavioral effect.
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Electroencefalografía/métodos , Memoria a Corto Plazo/fisiología , Lóbulo Parietal/fisiología , Desempeño Psicomotor/fisiología , Estimulación Magnética Transcraneal , Adulto , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Adulto JovenRESUMEN
Recent studies show that intracellular accumulation of cholesterol leads to acquired resistance to gefitinib in non-small cell lung cancer (NSCLC) cells. In this study we investigated how to regulate the cholesterol levels in gefitinib-resistant NSCLC cells. We showed that intracellular cholesterol levels in gefitinib-resistant cell lines (PC-9/GR, H1975, H1650, and A549) were significantly higher than that in gefitinib-sensitive cell line (PC-9). Treatment with gefitinib (5 µM) significantly increased intracellular cholesterol levels in PC-9/GR, H1975, and H1650 cells. Gefitinib treatment downregulated the expression of PPARα, LXRα, and ABCA1, leading to dysregulation of cholesterol efflux pathway. We found that a lipid-lowering drug fenofibrate (20, 40 µM) dose-dependently increased the expression of PPARα, LXRα, and ABCA1, decreased the intracellular cholesterol levels, and enhanced the antiproliferative effects of gefitinib in PC-9/GR, H1975, and H1650 cells. We revealed that fenofibrate increased the gefitinib-induced apoptosis via regulating the key proteins involved in the intrinsic apoptosis pathway. In PC-9/GR, H1975 and H1650 cells, fenofibrate dose-dependently increased the expression of AMPK, FoxO1, and decreased the expression of AKT, which were remarkably weakened by knockdown of PPARα. In PC-9/GR cell xenograft mice, combined administration of gefitinib (25 mg · kg-1 · d-1) and fenofibrate (100 mg · kg-1 · d-1) caused remarkable inhibition on tumor growth as compared to treatment with either drug alone. All the results suggest that fenofibrate relieves acquired resistance to gefitinib in NSCLC by promoting apoptosis via regulating PPARα/AMPK/AKT/FoxO1 pathway. We propose that combination of gefitinib and fenofibrate is a potential strategy for overcoming the gefitinib resistance in NSCLC.