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Transcranial direct current stimulation (tDCS) has been studied extensively for its potential to enhance human cognitive functions in healthy individuals and to treat cognitive impairment in various clinical populations. However, little is known about how tDCS modulates the neural networks supporting cognition and the complex interplay with mediating factors that may explain the frequently observed variability of stimulation effects within and between studies. Moreover, research in this field has been characterized by substantial methodological variability, frequent lack of rigorous experimental control and small sample sizes, thereby limiting the generalizability of findings and translational potential of tDCS. The present manuscript aims to delineate how these important issues can be addressed within a neuroimaging context, to reveal the neural underpinnings, predictors and mediators of tDCS-induced behavioral modulation. We will focus on functional magnetic resonance imaging (fMRI), because it allows the investigation of tDCS effects with excellent spatial precision and sufficient temporal resolution across the entire brain. Moreover, high resolution structural imaging data can be acquired for precise localization of stimulation effects, verification of electrode positions on the scalp and realistic current modeling based on individual head and brain anatomy. However, the general principles outlined in this review will also be applicable to other imaging modalities. Following an introduction to the overall state-of-the-art in this field, we will discuss in more detail the underlying causes of variability in previous tDCS studies. Moreover, we will elaborate on design considerations for tDCS-fMRI studies, optimization of tDCS and imaging protocols and how to assure high-level experimental control. Two additional sections address the pressing need for more systematic investigation of tDCS effects across the healthy human lifespan and implications for tDCS studies in age-associated disease, and potential benefits of establishing large-scale, multidisciplinary consortia for more coordinated tDCS research in the future. We hope that this review will contribute to more coordinated, methodologically sound, transparent and reproducible research in this field. Ultimately, our aim is to facilitate a better understanding of the underlying mechanisms by which tDCS modulates human cognitive functions and more effective and individually tailored translational and clinical applications of this technique in the future.
RESUMEN
Despite its significance for health and education, the neurocognitive mechanism of real-life self-control remains unclear. While recent studies focused on task-related brain activation patterns as predictors of self-control, the contribution and relevance of functional connectivity between large-scale brain networks mediating higher-order cognition is largely unknown. Using a saliency-based triple-network model of cognitive control, we tested the hypothesis that cross-network interactions among the salience network (SN), the central executive network (CEN), and the default mode network (DMN) are associated with real-life self-control. To this end, a large community sample (N = 294) underwent ecological momentary assessment of daily self-control as well as task-free fMRI to examine intrinsic inter-network organization and determine a SN-centered network interaction index (NII). Logistic multilevel regression analysis showed that higher NII scores were associated with increased real-life self-control. This suggests that the assumed role of the SN in initiating switching between the DMN and CEN is an important part of self-control.
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Mapeo Encefálico , Autocontrol , Encéfalo/diagnóstico por imagen , Cognición , Humanos , Imagen por Resonancia Magnética , Red Nerviosa , Vías Nerviosas/diagnóstico por imagenRESUMEN
Cognitive flexibility is essential to cope with changing task demands and often it is necessary to adapt to combined changes in a coordinated manner. The present fMRI study examined how the brain implements such multi-level adaptation processes. Specifically, on a "local," hierarchically lower level, switching between two tasks was required across trials while the rules of each task remained unchanged for blocks of trials. On a "global" level regarding blocks of twelve trials, the task rules could reverse or remain the same. The current task was cued at the start of each trial while the current task rules were instructed before the start of a new block. We found that partly overlapping and partly segregated neural networks play different roles when coping with the combination of global rule reversal and local task switching. The fronto-parietal control network (FPN) supported the encoding of reversed rules at the time of explicit rule instruction. The same regions subsequently supported local task switching processes during actual implementation trials, irrespective of rule reversal condition. By contrast, a cortico-striatal network (CSN) including supplementary motor area and putamen was increasingly engaged across implementation trials and more so for rule reversal than for nonreversal blocks, irrespective of task switching condition. Together, these findings suggest that the brain accomplishes the coordinated adaptation to multi-level demand changes by distributing processing resources either across time (FPN for reversed rule encoding and later for task switching) or across regions (CSN for reversed rule implementation and FPN for concurrent task switching).
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Adaptación Psicológica/fisiología , Encéfalo/fisiología , Función Ejecutiva/fisiología , Aprendizaje Inverso/fisiología , Adulto , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiología , Plasticidad Neuronal/fisiología , Adulto JovenRESUMEN
The diagnosis of uterine smooth muscle tumors including leiomyosarcomas (LMS), smooth muscle tumors of uncertain malignant potential (STUMP), bizarre (atypical) leiomyoma (BLM), mitotically active leiomyoma (MAL) and leiomyoma (LM) depends on a combination of microscopic features, such as mitoses, cytologic atypia, and coagulative tumor cell necrosis. However, a small number of these tumors still pose difficult diagnostic challenges. The assessment of accurate mitotic figures (MF) is one of the major parameters in the proper classification of uterine smooth muscle tumors. This assessment can be hampered by the presence of increased number of apoptotic bodies or pyknotic nuclei, which frequently mimic mitoses. Phospho-histone H3 (PHH3) is a recently described immunomarker specific for cells undergoing mitoses. In our study, we collected 132 cases of uterine smooth muscle tumors, including 26 LMSs, 16 STUMPs, 30 BLMs, 30 MALs and 30 LMs. We used mitosis specific marker PHH3 to count mitotic indexes (MI) of uterine smooth muscle tumors and compared with the mitotic indexes of hematoxylin and eosin (H&E). There is a positive correlation with the number of mitotic figures in H&E-stained sections and PHH3-stained sections (r=0.944, P<0.05). The ratio of PHH3-MI to H&E-MI has no statistically significant difference in each group except for LMs (P>0.05). The counting value of PHH3 in LMSs have significantly higher than STUMPs, BLMs, MALs and LMs (P<0.001) and the counting value of PHH3 is 1.5±0.5 times of the number of mitotic indexes in H&E. To conclude, our results show that counting PHH3 is a useful index in the diagnosis of uterine smooth muscle tumors and it can provide a more accurate index instead of the time-honored mitotic figure counts at a certain ratio.
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Biomarcadores de Tumor/análisis , Histonas/análisis , Leiomioma/diagnóstico , Leiomiosarcoma/diagnóstico , Neoplasias Uterinas/diagnóstico , Adulto , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Índice Mitótico , Fosforilación , Estudios RetrospectivosRESUMEN
STUDY QUESTION: Does tumor necrosis factor-α (TNF-α) differentially regulate matrix metalloproteinase-2 (MMP-2) expression in leiomyomas compared with normal myometrium? SUMMARY ANSWER: TNF-α up-regulates MMP-2 expression and stimulates cell migration through the activation of extracellular signal-regulated kinase (ERK) signaling pathway in leiomyoma smooth muscle cells (SMCs), but not in normal myometrial SMCs. WHAT IS KNOWN ALREADY: Uterine leiomyoma, the benign smooth muscle cell tumor, is the single most common indication for hysterectomy. High expression of MMPs or TNF-α has been reported in uterine leiomyomas; however, the molecular mechanism underlying these observations remains unknown. STUDY DESIGN, SIZE, DURATION: Samples were obtained between 2009 and 2013 from 12 women of reproductive age at the proliferative phase of the menstrual cycle by hysterectomy. Leiomyomas and matched normal myometrium from each woman were analyzed in vitro. PARTICIPANTS/MATERIALS, SETTING, METHODS: Western blot, RT-qPCR and a wound-healing assay were used to investigate the effects of TNF-α on MMP-2 expression and intracellular signal transduction in cultured SMCs from leiomyomas and matched myometrium. MAIN RESULTS AND THE ROLE OF CHANCE: Western blot and RT-qPCR analyses using tissues from clinical patients showed that the levels of MMP-2 protein (P = 0.008) and mRNA (P = 0.009) were significantly higher in uterine leiomyomas compared with their matched myometrium. Treatment with TNF-α significantly up-regulated the protein (P = 0.039) and mRNA (P = 0.037) levels of MMP-2 in cultured leiomyoma SMCs but not in matched myometrial SMCs. The extracellular signal-regulated kinase (ERK) and nuclear factor-kappa B (NF-κB) pathways were activated by TNF-α in leiomyoma SMCs. Specific inhibitors of the ERK or NF-κB pathway (PD98059 or Bay11-7082) suppressed TNF-α-induced MMP-2 expression in leiomyoma SMCs. The wound-healing assay revealed that TNF-α promoted the migration of cultured leiomyoma SMCs (P = 0.036); however, PD98059 compromised the cell migration triggered by TNF-α. LIMITATIONS, REASONS FOR CAUTION: This study is descriptive and although we observed clear differential regulation of MMP-2 by TNF-α at mRNA and protein levels in leiomyoma, future studies are needed to identify why the difference in TNF-α response exists between human leiomyoma tissue and normal myometrium. Including some of the experiments such as transfection studies for TNF-α and MMP-2 promoter mapping could have added more insight as to why this difference exists. In addition, further studies in vivo are needed to verify the results obtained from primary cultured SMCs. WIDER IMPLICATIONS OF THE FINDINGS: Considering the positive effect of TNF-α on leiomyoma SMC migration, strategies targeting TNF-α, in parallel with the production of more speciï¬c inhibitors of MMPs, may provide alternative therapeutic approaches for the treatment of leiomyoma. STUDY FUNDING/COMPETING INTERESTS: This work was partially supported by grants from the Program for New Century Excellent Talents in University (NCET-12-0282), National Natural Science Foundation of China (81371620) and Tianjin Natural Science Foundation (12JCZDJC24900). The authors have no conflicts of interest to declare.
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Leiomioma/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Miometrio/metabolismo , Factor de Necrosis Tumoral alfa/fisiología , Adulto , Movimiento Celular , Células Cultivadas , Femenino , Fase Folicular/metabolismo , Humanos , Sistema de Señalización de MAP Quinasas , Persona de Mediana Edad , Miocitos del Músculo Liso/metabolismo , FN-kappa B/metabolismo , Transducción de Señal , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Unclassified mixed germ cell-sex cord-stromal tumor composed of germ cells and sex cord derivatives is a rare neoplasm. Approximately 10% of such tumors have malignant germ cell components. We report the case of a 28 year-old female with a right adnexal mass measuring 8 cm in greatest dimension, containing areas with both germ cell and sex cord components. The germ cell portion contained multiple growth patterns with a malignant appearance, while the sex cord element consisted mainly of annular tubules. Within the malignant germ cell elements was a dysgerminoma that accounted for approximately 75% of the tumor volume. Other malignant germ cell elements included yolk sac tumor, embryonal carcinoma, and choriocarcinoma, which comprised about 15% of the tumor volume. The annular tubule structures comprised about 10% of the total tumor volume. To our knowledge, this is the first case reported in the literature of an unclassified mixed germ cell-sex cord-stromal tumor associated with embryonal carcinoma components. The patient had a 46XX karyotype, regular menstrual periods, and no evidence of gross abnormalities in the contralateral ovary. The patient remained clinically well and disease-free 2 years after surgery. In addition to a thorough case description, the literature concerning this entity is reviewed and discussed.
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Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias Ováricas/patología , Tumores de los Cordones Sexuales y Estroma de las Gónadas/patología , Adulto , Biomarcadores de Tumor/análisis , Femenino , Humanos , InmunohistoquímicaRESUMEN
The association of low-grade endometrioid carcinoma with undifferentiated carcinoma (UC) was first reported in endometrium carcinoma, termed with dedifferentiated carcinoma (DC). However, the coexistence of low-grade endometrioid carcinoma (LGEC) or serous carcinoma (LGSC) with UC has received minimal attention in ovary, and the behavior of this kind of neoplasm remains at further discussion. In this study, we reported a case of low-grade ovarian endometrioid carcinoma associated with UC and reviewed another four cases previously reported. We found a histological continuity between the LGEC and UC components in H&E section, which suggested a dedifferentiation from LGEC to UC components. In summary, this kind of pathological type has aggressive behavior and these patients have very poor prognosis regardless of the amount of undifferentiated carcinoma.
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Carcinoma Endometrioide/patología , Carcinoma/patología , Neoplasias Complejas y Mixtas/patología , Neoplasias Ováricas/patología , Biomarcadores de Tumor/análisis , Femenino , Humanos , Persona de Mediana EdadRESUMEN
To investigate the role of posterior brain regions related to task-relevant stimulus processing in task preparation, we used a cued task-switching paradigm in which a pre-cue informed participants about the upcoming task on a trial: face discrimination or number comparison. Employing an event-related fMRI design, we examined for changes of activity in face- and number-related posterior brain regions (right fusiform face area (FFA) and right intraparietal sulcus (IPSnum), respectively), and explored the functional connectivity of these areas with other brain regions, during the (preparation) interval between cue onset and onset of the (to-be-responded) target stimulus. The results revealed task-relevant posterior brain regions to be modulated during this period: activation in task-relevant stimulus-specific regions was selectively enhanced and their functional connectivity to task-relevant anterior brain regions strengthened (right FFA - face task, right IPSnum - number task) while participants prepared for the cued task. Additionally, activity in task-relevant posterior brain regions was influenced by residual activation from the preceding trial in the right FFA and the right IPSnum, respectively. These findings indicate that, during task preparation, the activation pattern in currently task-relevant posterior brain regions is shaped by residual activation as well as preparatory modulation prior to the onset of the critical stimulus, even without participants being instructed to imagine the stimulus.
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Encéfalo/fisiología , Función Ejecutiva/fisiología , Desempeño Psicomotor/fisiología , Adulto , Mapeo Encefálico , Señales (Psicología) , Discriminación en Psicología/fisiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Estimulación Luminosa , Tiempo de Reacción , Percepción Visual/fisiología , Adulto JovenRESUMEN
Malignant germ cell tumors of the ovary are very rare and account for about 2-5% of all ovarian tumors of germ origin. Most patients are adolescent and young women, approximately two-thirds of them are under 20 years of age, occasionally in postmenopausal women. But clear cell carcinoma usually occurs in older patients (median age: 57-year old), and closely related with endometriosis. Here we report a case of a 55-year old woman with right ovarian mass that discovered by B ultrasonic. Her serum levels of human chorionic gonadotropin (hCG) and α-fetoprotein (AFP) were elevated. Pathological examination revealed the tumor to be a mixed germ cell tumor (yolk sac tumor, embryonal carcinoma and mature teratoma) with clear cell carcinoma in a background of endometriosis. Immunohistochemical staining showed SALL4 and PLAP were positive in germ cell tumor area, hCG, CD30 and OCT4 were positive in epithelial-like cells and giant synctiotrophoblastic cells, AFP, AAT, CD117 and Glyp3 were positive in yolk sac component, EMA and CK7 were positive in clear cell carcinoma, CD10 was positive in endometrial cells of endometriotic area. She was treated with surgery followed by seven courses of chemotherapy. She is well and serum levels of hCG and AFP have been decreased to normal levels.
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Carcinoma Embrionario/patología , Tumor del Seno Endodérmico/patología , Neoplasias Complejas y Mixtas/patología , Neoplasias Ováricas/patología , Posmenopausia , Teratoma/patología , Biomarcadores de Tumor/sangre , Biopsia , Carcinoma Embrionario/sangre , Carcinoma Embrionario/química , Carcinoma Embrionario/diagnóstico por imagen , Carcinoma Embrionario/terapia , Gonadotropina Coriónica/sangre , Tumor del Seno Endodérmico/sangre , Tumor del Seno Endodérmico/química , Tumor del Seno Endodérmico/diagnóstico por imagen , Tumor del Seno Endodérmico/terapia , Endometriosis/patología , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Neoplasias Complejas y Mixtas/sangre , Neoplasias Complejas y Mixtas/química , Neoplasias Complejas y Mixtas/diagnóstico por imagen , Neoplasias Complejas y Mixtas/terapia , Neoplasias Ováricas/sangre , Neoplasias Ováricas/química , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias Ováricas/terapia , Teratoma/sangre , Teratoma/química , Teratoma/diagnóstico por imagen , Teratoma/terapia , Resultado del Tratamiento , Ultrasonografía , alfa-Fetoproteínas/metabolismoRESUMEN
OBJECTIVE: To investigate the expression of DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6 and PMS2) in endometrial adenocarcinoma (EC) of patients under 50 years and to explore the relationship between MMR expression and clinicopathological features including body mass index (BMI), histological grade and pathological stage of EC. METHODS: MMR gene expression was investigated by immunohistochemical S-P method in endometrial adenocarcinomas of patients under age of 50. The control groups included complexity atypical hyperplasia endometrium (CAHE), simple hyperplasia endometrium (SHE), normal endometrium (NE) of patients under age of 50 and EC of patients older than 65 years. RESULTS: Twenty seven of 40 EC (67.5%) lost at least one MMR protein expression. Loss of at least one MMR protein expression was seen in 5/15 cases of CAHE, 1/13 SHE and 1/11 NE, respectively (P < 0.01). The rates of loss of expression of MLH1, MSH2, MSH and PMS2 proteins in EC were 52.5%, 12.5%, 35.0%, and 30.0%, respectively. The difference between MLH1 and MSH6 expression among the four groups were significant (P < 0.05), but the expression of MSH2 showed no significant difference among the groups (P = 0.295). The expression of MMR protein had no relationship with histological grade and pathological stage, although loss of MSH6 was more frequently seen in patients of higher BMI. CONCLUSIONS: Abnormal expression of MMR proteins is correlated with the development of EC from complex atypical hyperplasia. With the exception of the correlation of MSH6 expression with higher BMI, the expression of MMR proteins in EC has no significant relationship with histological grade and pathological stage.
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Adenocarcinoma/metabolismo , Reparación de la Incompatibilidad de ADN , Enzimas Reparadoras del ADN/metabolismo , Proteínas de Unión al ADN/metabolismo , Neoplasias Endometriales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenosina Trifosfatasas/metabolismo , Adulto , Índice de Masa Corporal , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto , Homólogo 1 de la Proteína MutL , Proteína 2 Homóloga a MutS/metabolismo , Clasificación del Tumor , Estadificación de Neoplasias , Proteínas Nucleares/metabolismoRESUMEN
To isolate the neural correlates for task rule activation from those related to general task preparation, the effect of a cue explicitly specifying the S-R correspondences (rule-cue) was contrasted with the effects of a cue specifying only the task to performed (task-cue). While the task-cue provides merely information about the type of task, the rule-cue is explicit about both the task type and the task rule (i.e., the set of S-R correspondences). The rule-cue was expected to activate the task rule more efficiently in the preparation period (prior to target presentation); by contrast, in the task-cue condition, part of the task rule activation was expected to be postponed into the task execution period (following the presentation of the target). In an event-related fMRI experiment, we found the right anterior and middle parts of the middle frontal and superior frontal gyri, the right inferior frontal junction, the pre-SMA, as well as the right superior and inferior parietal lobes to show larger activation elicited by the rule-cue than by the task-cue prior to target presentation. Conversely, the results revealed larger activations in these regions in the task-cue than in the rule-cue condition during the task execution period. In summary, this study identified some of the neural correlates of task rule activation and showed that these are a subset of the general task preparation network.
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Atención/fisiología , Señales (Psicología) , Toma de Decisiones/fisiología , Potenciales Evocados/fisiología , Imagen por Resonancia Magnética/métodos , Análisis y Desempeño de Tareas , Adulto , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
OBJECTIVE: To understand antibody responses to and RNA sequences of Hantavirus in patients with hemorrhagic fever renal syndrome (HFRS) in Yantai areas and to demonstrate the type of the prevalent viruses caused HFRS. METHODS: Serum specimens collected at acute and convalescent stages from 90 patients with HFRS and IgM and IgG antibodies against Hantavirus were detected with ELISA, and cross plaque reduction neutralizing tests were performed to detect neutralizing antibody. Viral RNA was extracted from the patients? sera by using Trizol method and nested PCR was utilized to amplify the specific segments of the viral cDNA and the products of the PCR were TA cloned and then the nucleotide sequences were determined. RESULTS: The IgM antibody was positive in 82.2% (88/107) of the patients while the IgG antibody was positive in 85.7% (66/77) of the patients. Both the serologic and sequence analyses demonstrated that the epidemic of HFRS in Yantai areas was caused by mixed types of Hantavirus. The prevalent strains of Hantavirus had higher homology with the strains isolated in Korea than with those isolated previously in China. CONCLUSIONS: The serologic and sequencing analyses indicated that the epidemic of HFRS in Yantai areas was caused by mixed types of Hantavirus dominated by type SEO.