RESUMEN
Emotional information is better remembered than neutral information. Extensive evidence indicates that the amygdala and its interactions with other cerebral regions play an important role in the memory-enhancing effect of emotional arousal. While the cerebellum has been found to be involved in fear conditioning, its role in emotional enhancement of episodic memory is less clear. To address this issue, we used a whole-brain functional MRI approach in 1,418 healthy participants. First, we identified clusters significantly activated during enhanced memory encoding of negative and positive emotional pictures. In addition to the well-known emotional memory-related cerebral regions, we identified a cluster in the cerebellum. We then used dynamic causal modeling and identified several cerebellar connections with increased connection strength corresponding to enhanced emotional memory, including one to a cluster covering the amygdala and hippocampus, and bidirectional connections with a cluster covering the anterior cingulate cortex. The present findings indicate that the cerebellum is an integral part of a network involved in emotional enhancement of episodic memory.
Asunto(s)
Nivel de Alerta , Emociones , Amígdala del Cerebelo , Mapeo Encefálico , Cerebelo , Humanos , Imagen por Resonancia Magnética , Recuerdo MentalRESUMEN
Previous studies have shown that females typically outperform males on episodic memory tasks. In this study, we investigated if (1) there are differences between males and females in their connectome characteristics, (2) if these connectivity patterns are associated with memory performance, and (3) if these brain connectome characteristics contribute to the differences in episodic memory performance between sexes. In a sample of 655 healthy young subjects (n = 391 females; n = 264 males), we derived brain network characteristics from diffusion-weighted imaging (DWI) data using models of crossing fibers within each voxel of the brain and probabilistic tractography (graph strength, shortest path length, global efficiency, and weighted transitivity). Group differences were analysed with linear models and mediation analyses were used to explore how connectivity patterns might relate to sex-dependent differences in memory performance. Our results show significant sex-dependent differences in weighted transitivity (d = 0.42), with males showing higher values. Further, we observed a negative association between weighted transitivity and memory performance (r = -0.12). Finally, these distinct connectome characteristics partially mediated the observed differences in memory performance (effect size of the indirect effect r = 0.02). Our findings indicate a higher interconnectedness in females compared to males. Additionally, we demonstrate that the sex-dependent differences in episodic memory performance can be partially explained by the differences in this connectome measure. These results further underscore the importance of sex-dependent differences in brain connectivity and their impact on cognitive function.
Asunto(s)
Conectoma , Memoria Episódica , Masculino , Femenino , Humanos , Encéfalo/diagnóstico por imagen , Recuerdo Mental , Cognición , Imagen de Difusión por Resonancia Magnética , Conectoma/métodos , Imagen por Resonancia Magnética/métodosRESUMEN
Episodic memory performance is the result of distinct mental processes, such as learning, memory maintenance, and emotional modulation of memory strength. Such processes can be effectively dissociated using computational models. Here we performed gene set enrichment analyses of model parameters estimated from the episodic memory performance of 1,765 healthy young adults. We report robust and replicated associations of the amine compound SLC (solute-carrier) transporters gene set with the learning rate, of the collagen formation and transmembrane receptor protein tyrosine kinase activity gene sets with the modulation of memory strength by negative emotional arousal, and of the L1 cell adhesion molecule (L1CAM) interactions gene set with the repetition-based memory improvement. Furthermore, in a large functional MRI sample of 795 subjects we found that the association between L1CAM interactions and memory maintenance revealed large clusters of differences in brain activity in frontal cortical areas. Our findings provide converging evidence that distinct genetic profiles underlie specific mental processes of human episodic memory. They also provide empirical support to previous theoretical and neurobiological studies linking specific neuromodulators to the learning rate and linking neural cell adhesion molecules to memory maintenance. Furthermore, our study suggests additional memory-related genetic pathways, which may contribute to a better understanding of the neurobiology of human memory.
Asunto(s)
Biología Computacional , Memoria , Procesos Mentales , Adulto , Femenino , Voluntarios Sanos , Humanos , Imagen por Resonancia Magnética , Masculino , Adulto JovenRESUMEN
Extensive evidence indicates that women outperform men in episodic memory tasks. Furthermore, women are known to evaluate emotional stimuli as more arousing than men. Because emotional arousal typically increases episodic memory formation, the females' memory advantage might be more pronounced for emotionally arousing information than for neutral information. Here, we report behavioral data from 3398 subjects, who performed picture rating and memory tasks, and corresponding fMRI data from up to 696 subjects. We were interested in the interaction between sex and valence category on emotional appraisal, memory performances, and fMRI activity. The behavioral results showed that females evaluate in particular negative (p < 10(-16)) and positive (p = 2 × 10(-4)), but not neutral pictures, as emotionally more arousing (pinteraction < 10(-16)) than males. However, in the free recall females outperformed males not only in positive (p < 10(-16)) and negative (p < 5 × 10(-5)), but also in neutral picture recall (p < 3.4 × 10(-8)), with a particular advantage for positive pictures (pinteraction < 4.4 × 10(-10)). Importantly, females' memory advantage during free recall was absent in a recognition setting. We identified activation differences in fMRI, which corresponded to the females' stronger appraisal of especially negative pictures, but no activation differences that reflected the interaction effect in the free recall memory task. In conclusion, females' valence-category-specific memory advantage is only observed in a free recall, but not a recognition setting and does not depend on females' higher emotional appraisal.
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Nivel de Alerta/fisiología , Encéfalo/fisiología , Emociones/fisiología , Memoria/fisiología , Adolescente , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Recuerdo Mental/fisiología , Reconocimiento en Psicología/fisiología , Caracteres Sexuales , Adulto JovenRESUMEN
In the last decade there has been an exponential increase in knowledge about the genetic basis of complex human traits, including neuropsychiatric disorders. It is not clear, however, to what extent this knowledge can be used as a starting point for drug identification, one of the central hopes of the human genome project. The aim of the present study was to identify memory-modulating compounds through the use of human genetic information. We performed a multinational collaborative study, which included assessment of aversive memory--a trait central to posttraumatic stress disorder--and a gene-set analysis in healthy individuals. We identified 20 potential drug target genes in two genomewide-corrected gene sets: the neuroactive ligand-receptor interaction and the long-term depression gene set. In a subsequent double-blind, placebo-controlled study in healthy volunteers, we aimed at providing a proof of concept for the genome-guided identification of memory modulating compounds. Pharmacological intervention at the neuroactive ligand-receptor interaction gene set led to significant reduction of aversive memory. The findings demonstrate that genome information, along with appropriate data mining methodology, can be used as a starting point for the identification of memory-modulating compounds.
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Descubrimiento de Drogas/métodos , Genoma Humano/genética , Memoria/efectos de los fármacos , Trastornos por Estrés Postraumático/tratamiento farmacológico , Trastornos por Estrés Postraumático/genética , Sobrevivientes/psicología , Adulto , Estudios Cruzados , Minería de Datos/métodos , Difenhidramina/farmacología , Femenino , Fluorometría , Genotipo , Humanos , Entrevistas como Asunto , Modelos Logísticos , Masculino , Memoria/fisiología , Oligonucleótidos/genética , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido Simple/genética , Suiza , Adulto JovenRESUMEN
Positive and negative emotional events are better remembered than neutral events. Studies in animals suggest that this phenomenon depends on the influence of the amygdala upon the hippocampus. In humans, however, it is largely unknown how these two brain structures functionally interact and whether these interactions are similar between positive and negative information. Using dynamic causal modeling of fMRI data in 586 healthy subjects, we show that the strength of the connection from the amygdala to the hippocampus was rapidly and robustly increased during the encoding of both positive and negative pictures in relation to neutral pictures. We also observed an increase in connection strength from the hippocampus to the amygdala, albeit at a smaller scale. These findings indicate that, during encoding, emotionally arousing information leads to a robust increase in effective connectivity from the amygdala to the hippocampus, regardless of its valence.
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Amígdala del Cerebelo/fisiología , Nivel de Alerta/fisiología , Emociones/fisiología , Hipocampo/fisiología , Estimulación Luminosa/métodos , Adulto , Femenino , Humanos , Masculino , Vías Nerviosas/fisiología , Adulto JovenRESUMEN
Recent evidence suggests that altered expression and epigenetic modification of the glucocorticoid receptor gene (NR3C1) are related to the risk of post-traumatic stress disorder (PTSD). The underlying mechanisms, however, remain unknown. Because glucocorticoid receptor signaling is known to regulate emotional memory processes, particularly in men, epigenetic modifications of NR3C1 might affect the strength of traumatic memories. Here, we found that increased DNA methylation at the NGFI-A (nerve growth factor-induced protein A) binding site of the NR3C1 promoter was associated with less intrusive memory of the traumatic event and reduced PTSD risk in male, but not female survivors of the Rwandan genocide. NR3C1 methylation was not significantly related to hyperarousal or avoidance symptoms. We further investigated the relationship between NR3C1 methylation and memory functions in a neuroimaging study in healthy subjects. Increased NR3C1 methylation-which was associated with lower NR3C1 expression-was related to reduced picture recognition in male, but not female subjects. Furthermore, we found methylation-dependent differences in recognition memory-related brain activity in men. Together, these findings indicate that an epigenetic modification of the glucocorticoid receptor gene promoter is linked to interindividual and gender-specific differences in memory functions and PTSD risk.
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Epigénesis Genética/genética , Genocidio/psicología , Memoria , Receptores de Glucocorticoides/genética , Trastornos por Estrés Postraumático , Sobrevivientes/psicología , Adolescente , Adulto , Encéfalo/irrigación sanguínea , Encéfalo/patología , Metilación de ADN , Femenino , Estudios de Asociación Genética , Genotipo , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Pruebas Neuropsicológicas , Oxígeno/sangre , Regiones Promotoras Genéticas/genética , Escalas de Valoración Psiquiátrica , Riesgo , Rwanda , Trastornos por Estrés Postraumático/genética , Trastornos por Estrés Postraumático/patología , Trastornos por Estrés Postraumático/psicología , Suiza , Adulto JovenRESUMEN
Strong memory of a traumatic event is thought to contribute to the development and symptoms of posttraumatic stress disorder (PTSD). Therefore, a genetic predisposition to build strong memories could lead to increased risk for PTSD after a traumatic event. Here we show that genetic variability of the gene encoding PKCα (PRKCA) was associated with memory capacity--including aversive memory--in nontraumatized subjects of European descent. This finding was replicated in an independent sample of nontraumatized subjects, who additionally underwent functional magnetic resonance imaging (fMRI). fMRI analysis revealed PRKCA genotype-dependent brain activation differences during successful encoding of aversive information. Further, the identified genetic variant was also related to traumatic memory and to the risk for PTSD in heavily traumatized survivors of the Rwandan genocide. Our results indicate a role for PKCα in memory and suggest a genetic link between memory and the risk for PTSD.
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Memoria/fisiología , Polimorfismo de Nucleótido Simple , Proteína Quinasa C-alfa/genética , Trastornos por Estrés Postraumático/genética , Trastornos por Estrés Postraumático/fisiopatología , Adolescente , Adulto , Anciano , Encéfalo/patología , Encéfalo/fisiopatología , Femenino , Genotipo , Homicidio/psicología , Humanos , Imagen por Resonancia Magnética , Masculino , Recuerdo Mental/fisiología , Persona de Mediana Edad , Estimulación Luminosa , Desempeño Psicomotor/fisiología , Factores de Riesgo , Rwanda/etnología , Trastornos por Estrés Postraumático/psicología , Sobrevivientes/psicología , Uganda , Adulto JovenRESUMEN
Animal studies have shown that pregnancy is associated with neural adaptations that promote maternal care. The hypothalamus represents a central structure of the mammalian maternal brain and hormonal priming of specific hypothalamic nuclei plays a key role in the induction and expression of maternal behavior. In humans, we have previously demonstrated that becoming a mother involves changes in grey matter anatomy, primarily in association areas of the cerebral cortex. In the current study, we investigated whether pregnancy renders anatomical changes in the hypothalamus. Using an advanced delineation technique, five hypothalamic substructures were defined in longitudinal MRI scans of 107 women extracted from two prospective pre-conception cohort studies, including 50 women who were scanned before and after pregnancy and 57 nulliparous control women scanned at a similar time interval. We showed that becoming a mother is associated with volume reductions in the anterior-superior, superior tuberal and posterior hypothalamus. In addition, these structural changes related to hormonal levels during pregnancy and specific aspects of self-reported maternal behavior in late pregnancy, including maternal-fetal attachment and nesting behavior. These findings show that pregnancy leads to changes in hypothalamic anatomy and suggest that these contribute to the development of maternal behavior in humans, supporting the conservation of key aspects of maternal brain circuitry and their role in maternal behavior across species.
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Encéfalo , Conducta Materna , Animales , Humanos , Embarazo , Femenino , Estudios Prospectivos , Madres , Hipotálamo Posterior , MamíferosRESUMEN
Perception of emotional valence and emotional memory performance vary across the menstrual cycle. However, the consequences of altered ovarian hormone levels due to the intake of hormonal contraceptives on these emotional and cognitive processes remain to be established. In the present study, which included 2169 healthy young females, we show that hormonal contraceptives (HC) users rated emotional pictures as more emotional than HC-non-users and outperformed non-users in terms of better memory recall of emotional pictures. The observed association between HC-status and memory performance was partially mediated by the perception of emotional picture valence, indicating that increased valence ratings of emotional pictures in HC-users led to their better emotional memory performance. These findings extend the knowledge about the relation of HC-intake with emotional valence perception and emotional memory performance. Further, the findings might stimulate further research investigating the interrelation of enhanced memory for emotional events and the increased risk for anxiety-related psychiatric disorders in women.
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Anticonceptivos Hormonales Orales/administración & dosificación , Emociones/fisiología , Hormonas Esteroides Gonadales/fisiología , Recuerdo Mental/fisiología , Percepción Visual/fisiología , Adolescente , Adulto , Nivel de Alerta/efectos de los fármacos , Emociones/efectos de los fármacos , Femenino , Humanos , Recuerdo Mental/efectos de los fármacos , Estimulación Luminosa , Percepción Visual/efectos de los fármacos , Adulto JovenRESUMEN
Working memory (WM) is an important cognitive domain for everyday life functioning and is often disturbed in neuropsychiatric disorders. Functional magnetic resonance imaging (fMRI) studies in humans show that distributed brain areas typically described as fronto-parietal regions are implicated in WM tasks. Based on data from a large sample of healthy young adults (N = 1369), we applied independent component analysis (ICA) to the WM-fMRI signal and identified two distinct networks that were relevant for differences in individual WM task performance. A parietally-centered network was particularly relevant for individual differences in task measures related to WM performance ("WM dependent") and a frontally-centered network was relevant for differences in attention-dependent task performance. Importantly, frontal areas that are typically considered as key regions for WM were either involved in both WM-dependent and attention-dependent performance, or in attention-dependent performance only. The networks identified here are provided as publicly available datasets. These networks can be applied in future studies to derive a low-dimensional representation of the overall WM brain activation.
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Encéfalo/fisiología , Memoria a Corto Plazo , Adolescente , Adulto , Mapeo Encefálico/métodos , Interpretación Estadística de Datos , Femenino , Lóbulo Frontal/fisiología , Humanos , Imagen por Resonancia Magnética , Masculino , Vías Nerviosas/fisiología , Lóbulo Parietal/fisiología , Adulto JovenRESUMEN
INTRODUCTION: Memory functions are highly variable between healthy humans. The neural correlates of this variability remain largely unknown. METHODS: Here, we investigated how differences in free recall performance are associated with DTI-based properties of the brain's structural connectome and with grey matter volumes in 664 healthy young individuals tested in the same MR scanner. RESULTS: Global structural connectivity, but not overall or regional grey matter volumes, positively correlated with recall performance. Moreover, a set of 22 inter-regional connections, including some with no previously reported relation to human memory, such as the connection between the temporal pole and the nucleus accumbens, explained 7.8% of phenotypic variance. CONCLUSIONS: In conclusion, this large-scale study indicates that individual memory performance is associated with the level of structural brain connectivity.
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Encéfalo/diagnóstico por imagen , Conectoma , Sustancia Gris/diagnóstico por imagen , Recuerdo Mental/fisiología , Adulto , Imagen de Difusión Tensora , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
DNA methylation represents an important link between structural genetic variation and complex phenotypes. The study of genome-wide CpG methylation and its relation to traits relevant to psychiatry has become increasingly important. Here, we analyzed quality metrics of 394,043 CpG sites in two samples of 568 and 319 mentally healthy young adults. For 25% of all CpGs we observed medium to large common epigenetic variation. These CpGs were overrepresented in open sea and shore regions, as well as in intergenic regions. They also showed a strong enrichment of significant hits in association analyses. Furthermore, a significant proportion of common DNA methylation is at least partially genetically driven and thus may be observed similarly across tissues. These findings could be of particular relevance for studies of complex neuropsychiatric traits, which often rely on proxy tissues.
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Islas de CpG/genética , Epigénesis Genética/genética , Salud Mental , Adulto , Metilación de ADN/genética , Epigenómica/métodos , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Estudio de Asociación del Genoma Completo , Voluntarios Sanos , Humanos , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Polimorfismo de Nucleótido Simple/genética , Adulto JovenRESUMEN
The dorsolateral prefrontal cortex (DLPFC) plays a key role in working memory. Evidence indicates that transcranial magnetic stimulation (TMS) over the DLPFC can interfere with working memory performance. Here we investigated for how long continuous theta-burst stimulation (cTBS) over the DLPFC decreases working memory performance and whether the effect of cTBS on performance depends on working memory load. Forty healthy young subjects received either cTBS over the left DLPFC or sham stimulation before performing a 2-, and 3-back working memory letter task. An additional 0-back condition served as a non-memory-related control, measuring general attention. cTBS over the left DLPFC significantly impaired 2-back working memory performance for about 15 min, whereas 3-back and 0-back performances were not significantly affected. Our results indicate that the effect of left DLPFC cTBS on working memory performance lasts for roughly 15 min and depends on working memory load.
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Memoria a Corto Plazo , Corteza Prefrontal/fisiología , Ritmo Teta , Adolescente , Adulto , Femenino , Humanos , Masculino , Estimulación Magnética TranscranealRESUMEN
IMPORTANCE: Human episodic memory performance is linked to the function of specific brain regions, including the hippocampus; declines as a result of increasing age; and is markedly disturbed in Alzheimer disease (AD), an age-associated neurodegenerative disorder that primarily affects the hippocampus. Exploring the molecular underpinnings of human episodic memory is key to the understanding of hippocampus-dependent cognitive physiology and pathophysiology. OBJECTIVE: To determine whether biologically defined groups of genes are enriched in episodic memory performance across age, memory encoding-related brain activity, and AD. DESIGN, SETTING, AND PARTICIPANTS: In this multicenter collaborative study, which began in August 2008 and is ongoing, gene set enrichment analysis was done by using primary and meta-analysis data from 57â¯968 participants. The Swiss cohorts consisted of 3043 healthy young adults assessed for episodic memory performance. In a subgroup (n = 1119) of one of these cohorts, functional magnetic resonance imaging was used to identify gene set-dependent differences in brain activity related to episodic memory. The German Study on Aging, Cognition, and Dementia in Primary Care Patients cohort consisted of 763 elderly participants without dementia who were assessed for episodic memory performance. The International Genomics of Alzheimer's Project case-control sample consisted of 54â¯162 participants (17â¯008 patients with sporadic AD and 37â¯154 control participants). Analyses were conducted between January 2014 and June 2015. Gene set enrichment analysis in all samples was done using genome-wide single-nucleotide polymorphism data. MAIN OUTCOMES AND MEASURES: Episodic memory performance in the Swiss cohort and German Study on Aging, Cognition, and Dementia in Primary Care Patients cohort was quantified by picture and verbal delayed free recall tasks. In the functional magnetic resonance imaging experiment, activation of the hippocampus during encoding of pictures served as the phenotype of interest. In the International Genomics of Alzheimer's Project sample, diagnosis of sporadic AD served as the phenotype of interest. RESULTS: In the discovery sample, we detected significant enrichment for genes constituting the calcium signaling pathway, especially those related to the elevation of cytosolic calcium (P = 2 × 10-4). This enrichment was replicated in 2 additional samples of healthy young individuals (P = .02 and .04, respectively) and a sample of healthy elderly participants (P = .004). Hippocampal activation (P = 4 × 10-4) and the risk for sporadic AD (P = .01) were also significantly enriched for genes related to the elevation of cytosolic calcium. CONCLUSIONS AND RELEVANCE: By detecting consistent significant enrichment in independent cohorts of young and elderly participants, this study identified that calcium signaling plays a central role in hippocampus-dependent human memory processes in cognitive health and disease, contributing to the understanding and potential treatment of hippocampus-dependent cognitive pathology.
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Enfermedad de Alzheimer/genética , Señalización del Calcio/genética , Hipocampo/fisiopatología , Memoria Episódica , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/fisiopatología , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Neuroimagen Funcional , Humanos , Imagen por Resonancia Magnética , Masculino , Memoria/fisiología , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
Cognitive functions, such as working memory, depend on neuronal excitability in a distributed network of cortical regions. It is not known, however, if interindividual differences in cortical excitability are related to differences in working memory performance. In the present transcranial magnetic stimulation study, which included 188 healthy young subjects, we show that participants with lower resting motor threshold, which is related to higher corticospinal excitability, had increased 2-back working memory performance. The findings may help to better understand the link between cortical excitability and cognitive functions and may also have important clinical implications with regard to conditions of altered cortical excitability.
RESUMEN
Memory performance is the result of many distinct mental processes, such as memory encoding, forgetting, and modulation of memory strength by emotional arousal. These processes, which are subserved by partly distinct molecular profiles, are not always amenable to direct observation. Therefore, computational models can be used to make inferences about specific mental processes and to study their genetic underpinnings. Here we combined a computational model-based analysis of memory-related processes with high density genetic information derived from a genome-wide study in healthy young adults. After identifying the best-fitting model for a verbal memory task and estimating the best-fitting individual cognitive parameters, we found a common variant in the gene encoding the brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2) that was related to the model parameter reflecting modulation of verbal memory strength by negative valence. We also observed an association between the same genetic variant and a similar emotional modulation phenotype in a different population performing a picture memory task. Furthermore, using functional neuroimaging we found robust genotype-dependent differences in activity of the parahippocampal cortex that were specifically related to successful memory encoding of negative versus neutral information. Finally, we analyzed cortical gene expression data of 193 deceased subjects and detected significant BAIAP2 genotype-dependent differences in BAIAP2 mRNA levels. Our findings suggest that model-based dissociation of specific cognitive parameters can improve the understanding of genetic underpinnings of human learning and memory.
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Emociones/fisiología , Memoria/fisiología , Proteínas del Tejido Nervioso/genética , Adolescente , Adulto , Mapeo Encefálico , Femenino , Expresión Génica , Estudio de Asociación del Genoma Completo , Genotipo , Voluntarios Sanos , Humanos , Imagen por Resonancia Magnética , Masculino , Modelos Neurológicos , Proteínas del Tejido Nervioso/metabolismo , Giro Parahipocampal/fisiología , Polimorfismo de Nucleótido Simple , ARN Mensajero/genética , Análisis y Desempeño de Tareas , Adulto JovenRESUMEN
Working memory, the capacity of actively maintaining task-relevant information during a cognitive task, is a heritable trait. Working memory deficits are characteristic for many psychiatric disorders. We performed genome-wide gene set enrichment analyses in multiple independent data sets of young and aged cognitively healthy subjects (n = 2,824) and in a large schizophrenia case-control sample (n = 32,143). The voltage-gated cation channel activity gene set, consisting of genes related to neuronal excitability, was robustly linked to performance in working memory-related tasks across ages and to schizophrenia. Functional brain imaging in 707 healthy participants linked this gene set also to working memory-related activity in the parietal cortex and the cerebellum. Gene set analyses may help to dissect the molecular underpinnings of cognitive dimensions, brain activity, and psychopathology.
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Canales de Calcio/genética , Canales de Calcio/fisiología , Estudio de Asociación del Genoma Completo/métodos , Imagen por Resonancia Magnética/métodos , Memoria a Corto Plazo/fisiología , Esquizofrenia/fisiopatología , Adulto , Anciano , Algoritmos , Encéfalo/fisiología , Estudios de Casos y Controles , Cerebelo/fisiología , Cognición/fisiología , Femenino , Voluntarios Sanos , Humanos , Masculino , Lóbulo Parietal/fisiología , Corteza Prefrontal/fisiología , Esquizofrenia/genética , Adulto JovenRESUMEN
Testosterone is a steroid hormone thought to influence both emotional and cognitive functions. It is unknown, however, if testosterone also affects the interaction between these two domains, such as the emotional arousal-induced enhancement of memory. Healthy subjects (N=234) encoded pictures taken from the International Affective Picture System (IAPS) during functional magnetic resonance imaging (fMRI) and underwent a free recall test 10 min after memory encoding. We show that higher endogenous testosterone levels at encoding were associated with higher arousal ratings of neutral pictures in men. fMRI analysis revealed that higher testosterone levels were related to increased brain activation in the amygdala during encoding of neutral pictures. Moreover, endogenous testosterone levels were positively correlated with the number of freely recalled neutral pictures. No such relations were found in women. These findings point to a male-specific role for testosterone in enhancing memory by increasing the biological salience of incoming information.
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Amígdala del Cerebelo/fisiología , Memoria/fisiología , Testosterona/metabolismo , Adolescente , Adulto , Nivel de Alerta/fisiología , Femenino , Neuroimagen Funcional , Humanos , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , Saliva/química , Testosterona/análisisRESUMEN
Carmustine is used in the treatment of glioblastomas as locally applied chemotherapy in the form of biodegradable wafers, which are lined on the walls of the resection cavity at the end of the resection, to increase local concentrations and decrease systemic toxicity. A total of 44 patients with glioblastoma with gross macroscopic tumor removal were included. MRIs were performed at various times postoperatively (within 24 hours, 1 week, 1 month, 2 months, 3 months, 6 months, 9 months, and 1 year). MR protocols included a T2-, diffusion-weighted, and T1-weighted sequences with and without intravenous administration of gadolinium. On T1, the wafers change from their initial hypointense to an isointense appearance after a period during which they appear to be hypointense, with a hyperintense rim most prominent less than 1 month postoperatively. On T2 they change from a hypointense to an isointense appearance. Restricted diffusivity reshaping the silhouette of the wafer's surface at the rim of the resection cavity can be found as early as day 1 postoperatively; however, 1 month after implantation, they all show areas of restricted diffusion, which may remain up to 1 year. Contrast enhancement at the rim of the resection cavity can already be found at day 1 postoperatively, with a peak shortly after 1 month after surgery. These changes can easily be mistaken for an abscess and hamper the early differentiation between residual tumor tissue and normal postoperative changes. However, early changes in either appearance do not predict overall survival or the progression free interval.