Prediction is pervasive in human cognition and plays a central role in language comprehension. At an electrophysiological level, this cognitive function contributes substantially in determining the amplitude of the N400. In fact, the amplitude of the N400 to words within a sentence has been shown to depend on how predictable those words are: The more predictable a word, the smaller the N400 elicited. However, predictive processing can be based on different sources of information that allow anticipation of upcoming constituents and integration in context. In this study, we investigated the ERPs elicited during the comprehension of idioms, that is, prefabricated multiword strings stored in semantic memory. When a reader recognizes a string of words as an idiom before the idiom ends, she or he can develop expectations concerning the incoming idiomatic constituents. We hypothesized that the expectations driven by the activation of an idiom might differ from those driven by discourse-based constraints. To this aim, we compared the ERP waveforms elicited by idioms and two literal control conditions. The results showed that, in both cases, the literal conditions exhibited a more negative potential than the idiomatic condition. Our analyses suggest that before idiom recognition the effect is due to modulation of the N400 amplitude, whereas after idiom recognition a P300 for the idiomatic sentence has a fundamental role in the composition of the effect. These results suggest that two distinct predictive mechanisms are at work during language comprehension, based respectively on probabilistic information and on categorical template matching.

Background: Brain activity has been investigated by several methods with different principles, notably optical ones. Each method may offer information on distinct physiological or pathological aspects of brain function. The ideal instrument to measure brain activity should include complementary techniques and integrate the resultant information. As a "low cost" approach towards this objective, we combined the well-grounded electroencephalography technique with the newer near infrared spectroscopy methods to investigate human visual function.

Most types of cancer cells are characterized by aberrant methylation of promoter genes. In this study, we described a rapid, reproducible, and relatively inexpensive approach allowing the detection of multiple human methylated promoter genes from many tissue samples, without the need of bisulfite conversion. The Methylation Ligation-dependent Macroarray (MLM), an array-based analysis, was designed in order to measure methylation levels of 58 genes previously described as putative biomarkers of cancer. The performance of the design was proven by screening the methylation profile of DNA from esophageal cell lines, as well as microdissected formalin-fixed and paraffin-embedded (FFPE) tissues from esophageal adenocarcinoma (EAC). Using the MLM approach, we identified 32 (55%) hypermethylated promoters in EAC, and not or rarely methylated in normal tissues. Among them, 21promoters were found aberrantly methylated in more than half of tumors. Moreover, seven of them (ADAMTS18, APC, DKK2, FOXL2, GPX3, TIMP3 and WIF1) were found aberrantly methylated in all or almost all the tumor samples, suggesting an important role for these genes in EAC. In addition, dysregulation of the Wnt pathway with hypermethylation of several Wnt antagonist genes was frequently observed. MLM revealed a homogeneous pattern of methylation for a majority of tumors which were associated with an advanced stage at presentation and a poor prognosis. Interestingly, the few tumors presenting less methylation changes had a lower pathological stage. In conclusion, this study demonstrated the feasibility and accuracy of MLM for DNA methylation profiling of FFPE tissue samples.

Aberrant methylation of multiple promoter CpG islands could be related to the biology of ovarian tumors and its determination could help to improve treatment strategies. DNA methylation profiling was performed using the Methylation Ligation-dependent Macroarray (MLM), an array-based analysis. Promoter regions of 41 genes were analyzed in 102 ovarian tumors and 17 normal ovarian samples. An average of 29% of hypermethylated promoter genes was observed in normal ovarian tissues. This percentage increased slightly in serous, endometrioid, and mucinous carcinomas (32%, 34%, and 45%, respectively), but decreased in germ cell tumors (20%). Ovarian tumors had methylation profiles that were more heterogeneous than other epithelial cancers. Unsupervised hierarchical clustering identified four groups that are very close to the histological subtypes of ovarian tumors. Aberrant methylation of three genes (BRCA1, MGMT, and MLH1), playing important roles in the different DNA repair mechanisms, were dependent on the tumor subtype and represent powerful biomarkers for precision therapy. Furthermore, a promising relationship between hypermethylation of MGMT, OSMR, ESR1, and FOXL2 and overall survival was observed. Our study of DNA methylation profiling indicates that the different histotypes of ovarian cancer should be treated as separate diseases both clinically and in research for the development of targeted therapies.

Cloze-probability levels are inversely correlated with N400 amplitude, indicating an easier integration for expected words in semantic-pragmatic contexts. Here we exploited the prespecified standard order of complex prepositions and measured the ERPs time-locked to the last preposition in sentences in which complex prepositions were presented in their standard form or with the last preposition changed. The expected preposition elicited an N280 followed by an N400-700, two ERP components previously associated to the processing of closed-class words. The unexpected preposition elicited only an N280, and the N400-700 was reduced. These results reflect the specificity of the contextual constraints linked to the complex preposition word sequence.