Spelling principles matter: An ERP study investigating the processing of different types of pseudohomophones.

Spelling in any writing system is governed by fundamental principles. We examined the processing of two types of pseudohomophones constructed from words whose spellings are based on different principles - on the traditional principle of writing, requiring memorization of their spelling, and on the morphological principle, allowing the determination of their spelling from another word with the same morpheme (root) to examine the dependence of the occurrence of orthography-phonology conflict on spelling principles. Event-related potentials were recorded from 22 volunteers during silent reading. Pseudohomophones based on the morphological principle increased the N400 amplitude, emphasizing semantic and morphological processing importance. The P600 component showed significant effects for differentiating words and pseudohomophones based on the traditional principle, predominantly indicating the involvement of memory and reanalysis processes. Source reconstruction demonstrates that both pseudohomophones activate the left inferior frontal gyrus. However, pseudohomophones based on the traditional principle additionally activate the right and left postcentral gyrus, indicating the involvement of additional areas in the differentiation process. The earlier differences for stimuli based on the morphological principle indicate access to smaller units (morphemes), whereas stimuli based on the traditional principle require whole word processing. Our findings underscore the significant role of spelling principles in orthographic processing.

Electrophysiological signatures of spelling sensitivity development from primary school age to adulthood.

Recognizing spelling errors is important for correct writing and reading, and develops over an extended period. The neural bases of the development of orthographic sensitivity remain poorly understood. We investigated event-related potentials (ERPs) associated with spelling error recognition when performing the orthographic decision task with correctly spelled and misspelled words in children aged 8-10 years old, early adolescents aged 11-14 years old, and adults. Spelling processing in adults included an early stage associated with the initial recognition of conflict between orthography and phonology (reflected in the N400 time window) and a later stage (reflected in the P600 time window) related to re-checking the spelling. In children 8-10 years old, there were no differences in ERPs to correct and misspelled words; in addition, their behavioral scores were worse than those of early adolescents, implying that the ability to quickly recognize the correct spelling is just beginning to develop at this age. In early adolescents, spelling recognition was reflected only at the later stage, corresponding to the P600 component. At the behavioral level, they were worse than adults at recognizing misspelled words. Our data suggest that orthographic sensitivity can develop beyond 14 years.

EEG alpha reactivity on eyes opening discriminates patients with schizophrenia and schizoaffective disorder.

OBJECTIVE: Alpha activity in the electroencephalogram (EEG) is typically dominant during rest with closed eyes but suppressed by visual stimulation. Previous research has shown that alpha-blockade is less pronounced in schizophrenia patients compared to healthy individuals, but no studies have examined it in schizoaffective disorder. METHODS: A resting state EEG was used for the analysis of the alpha-reactivity between the eyes closed and the eyes opened conditions in overall (8 - 13 Hz), low (8 - 10 Hz) and high (10 - 13 Hz) alpha bands in three groups: schizophrenia patients (SC, n = 30), schizoaffective disorder (SA, n = 30), and healthy controls (HC, n = 36). All patients had their first psychotic episode and were receiving antipsychotic therapy. RESULTS: A significant decrease in alpha power was noted across all subjects from the eyes-closed to eyes-open condition, spanning all regions. Alpha reactivity over the posterior regions was lower in SC compared to HC within overall and high alpha. SA showed a trend towards reduced alpha reactivity compared to HC, especially evident over the left posterior region within the overall alpha. Alpha reactivity was more pronounced over the middle and right posterior regions of SA as compared to SC, particularly in the high alpha. Alpha reactivity in SC and SA patients was associated with various negative symptoms. CONCLUSIONS: Our findings imply distinct alterations in arousal mechanisms in SC and SA and their relation to negative symptomatology. Arousal is more preserved in SA. SIGNIFICANCE: This study is the first to compare the EEG features of arousal in SC and SA.

Top-down modulation of brain responses in spelling error recognition.

The task being undertaken can influence orthographic, phonological and semantic processes. In linguistic research, two tasks are most often used: a task requiring a decision in relation to the presented word and a passive reading task which does not require a decision regarding the presented word. The results of studies using these different tasks are not always consistent. This study aimed to explore brain responses associated with the process of recognition of spelling errors, as well as the influence of the task on this process. Event-related potentials (ERPs) were recorded in 40 adults during an orthographic decision task to determine correctly spelled words and words written with errors that did not change the phonology and during the passive reading. During spelling recognition, the early stages up to 100 ms after the stimulus were automatic and did not depend on the requirements of the task. The amplitude of the N1 component (90-160 ms) was greater in the orthographic decision task, but did not depend on the correct spelling of the word. Late word recognition after 350-500 ms was task dependent, but spelling effects were similar across the two tasks: misspelled words evoked an increase in the amplitude of the N400 component related to lexical and semantic processing regardless of the task. In addition, the orthographic decision task modulated spelling effects, this was reflected in an increase in the amplitude of the P2 component (180-260 ms) for correctly spelled words compared with misspelled words. Thus, our results show that spelling recognition involves general lexico-semantic processes independent of the task. Simultaneously, the orthographic decision task modulates the spelling-specific processes necessary to quickly detect conflicts between orthographic and phonological representations of words in memory.

Adiponectin Stimulates Apolipoprotein A-1 Gene Expression in HepG2 Cells via AMPK, PPARα, and LXRs Signaling Mechanisms.

Adiponectin is an adipose tissue hormone, participating in energy metabolism and involved in atherogenesis. Previously, it was found that adiponectin increases expression of the APOA1 (apolipoprotein A-1) gene in hepatocytes, but the mechanisms of this effect remained unexplored. Our aim was to investigate the role of adiponectin receptors AdipoR1/R2, AMP-activated protein kinase (AMPK), nuclear peroxisome proliferator-activated receptor alpha (PPARα) and liver X receptors (LXRs) in mediating the action of adiponectin on hepatic APOA1 expression in human hepatoma HepG2 cells. The level of APOA1 expression was determined by RT-qPCR and ELISA. We showed that the siRNA-mediated knockdown of genes coding for AdipoR1, AdipoR2, AMPK, PPARα, and LXRα and ß prevented adiponectin-induced APOA1 expression in HepG2 cells and demonstrated that interaction of PPARα and LXRs with the APOA1 gene hepatic enhancer is important for the adiponectin-dependent APOA1 transcription. The results of this study point out to the involvement of both types of adiponectin receptors, AMPK, PPARα, and LXRs in the adiponectin-dependent upregulation of the APOA1 expression.

Frequency Effects on Spelling Error Recognition: An ERP Study.

Spelling errors are ubiquitous in all writing systems. Most studies exploring spelling errors focused on the phonological plausibility of errors. However, unlike typical pseudohomophones, spelling errors occur in naturally produced written language. We investigated the time course of recognition of the most frequent orthographic errors in Russian (error in an unstressed vowel in the root) and the effect of word frequency on this process. During event-related potentials (ERP) recording, 26 native Russian speakers silently read high-frequency correctly spelled words, low-frequency correctly spelled words, high-frequency words with errors, and low-frequency words with errors. The amplitude of P200 was more positive for correctly spelled words than for misspelled words and did not depend on the frequency of the words. In addition, in the 350-500-ms time window, we found a more negative response for misspelled words than for correctly spelled words in parietal-temporal-occipital regions regardless of word frequency. Considering our results in the context of a dual-route model, we concluded that recognizing misspelled high-frequency and low-frequency words involves common orthographic and phonological processes associated with P200 and N400 components such as whole word orthography processing and activation of phonological representations correspondingly. However, at the 500-700 ms stage (associated with lexical-semantic access in our study), error recognition depends on the word frequency. One possible explanation for these differences could be that at the 500-700 ms stage recognition of high-frequency misspelled and correctly spelled words shifts from phonological to orthographic processes, while low-frequency misspelled words are accompanied by more prolonged phonological activation. We believe these processes may be associated with different ERP components P300 and N400, reflecting a temporal overlap between categorization processes based on orthographic properties for high-frequency words and phonological processes for low-frequency words. Therefore, our results complement existing reading models and demonstrate that the neuronal underpinnings of spelling error recognition during reading may depend on word frequency.

Differentiation of human macrophages with anaphylatoxin C3a impairs alternative M2 polarization and decreases lipopolysaccharide-induced cytokine secretion.

Anaphylatoxin C3a is a small signaling polypeptide that is generated during complement activation. C3a is involved in the regulation of various innate and adaptive immune system processes; however, the role of C3a in macrophage differentiation and polarization is poorly elucidated. Here we showed that C3a impairs alternative M2 polarization of human macrophages and suppressed CD206, IL1Ra and CCL22 expression. C3a leads to a decrease of nuclear receptor PPARγ expression via the ERK1/2 signaling pathway, resulting in repressed PPARγ-dependent activation of CD36, FABP4 and LXRα genes and blunted response to an LXR ligand TO901317. Using small interfering RNA and agonist/antagonist approaches we showed that C3a decreases CD206, IL1Ra and CCL22 transcription at least partly in a PPARγ-dependent manner in M2 macrophages. Moreover, C3a impairs efferocytosis by M2 macrophages and inhibits their migratory activity. By contrast, macrophages treated with C3a during differentiation show blunted response to lipopolysaccharide stimulation owing to downregulation of TLR4 and lipid raft content. At the same time, differentiation of macrophages with C3a does not change M1 polarization in interferon gamma (IFNγ) and IFNγ + lipopolysaccharide-treated macrophages. These data provide a novel role of complement system and C3a in the regulation of M2 macrophage polarizations and suggest crosstalk between C3a, TLR4, PPARγ and LXR signaling pathways.

Regulation of Apolipoprotein A-I Gene Expression in Human Macrophages by Oxidized Low-Density Lipoprotein.

Apolipoprotein A-I (ApoA-I) is a key component of reverse cholesterol transport in humans. In the previous studies, we demonstrated expression of the apoA-I gene in human monocytes and macrophages; however, little is known on the regulation of the apoA-I expression in macrophages during the uptake of modified low-density lipoprotein (LDL), which is one of the key processes in the early stages of atherogenesis leading to formation of foam cells. Here, we demonstrate a complex nature of the apoA-I regulation in human macrophages during the uptake of oxidized LDL (oxLDL). Incubation of macrophages with oxLDL induced expression of the apoA-I gene within the first 24 hours, but suppressed it after 48 h. Both effects depended on the interaction of oxLDL with the TLR4 receptor, rather than on the oxLDL uptake by the macrophages. The oxLDL-mediated downregulation of the apoA-I gene depended on the ERK1/2 and JNK cascades, as well as on the NF-κB cascade.

EEG activity for semantic task in paranoid schizophrenia.

We identified a potential neurophysiological marker for processing of verbal cues in paranoid schizophrenia: high desynchronization in the beta-2 band in the right parietal area for meaningless cues, and no synchronization differences in the beta-2 and gamma bands in the left prefrontal area pointing to deficient categorization of the stimuli.

Mu rhythm separation from the mix with alpha rhythm: Principal component analyses and factor topography.

BACKGROUND: EEG mu rhythm suppression is assessed in experiments on the execution, observation and imagination of movements. It is utilised for studying of actions, language, empathy in healthy individuals and preservation of sensorimotor system functions in patients with schizophrenia and autism spectrum disorders. While EEG alpha and mu rhythms are recorded in the same frequency range (8-13 Hz), their specification becomes a serious issue. THE NEW METHOD: is based on the spatial and functional characteristics of the mu wave, which are: (1) the mu rhythm is located over the sensorimotor cortex; (2) it desynchronises during movement processing and does not respond on the eyes opening. In EEG recordings, we analysed the mu rhythm under conditions with eyes opened and eyes closed (baseline), and during a motor imagery task with eyes closed. EEG recordings were processed by principal component analysis (PCA). RESULTS: The analysis of EEG data with the proposed approach revealed the maximum spectral power of mu rhythm localised in the sensorimotor areas. During motor imagery, mu rhythm was suppressed more in frontal and central sites than in occipital sites, whereas alpha rhythm was suppressed more in parietal and occipital sites. Mu rhythm desynchronization in sensorimotor sites during motor imagery was greater than alpha rhythm desynchronization. The proposed method enabled EEG mu rhythm separation from its mix with alpha rhythm. CONCLUSIONS: EEG mu rhythm separation with the proposed method satisfies its classical definition.

Tumor necrosis factor α stimulates endogenous apolipoprotein A-I expression and secretion by human monocytes and macrophages: role of MAP-kinases, NF-κB, and nuclear receptors PPARα and LXRs.

Apolipoprotein A-I (ApoA-I) is the main structural and functional protein component of high-density lipoprotein. ApoA-I has been shown to regulate lipid metabolism and inflammation in macrophages. Recently, we found the moderate expression of endogenous apoA-I in human monocytes and macrophages and showed that pro-inflammatory cytokine tumor necrosis factor α (TNFα) increases apoA-I mRNA and stimulates ApoA-I protein secretion by human monocytes and macrophages. Here, we present data about molecular mechanisms responsible for the TNFα-mediated activation of apoA-I gene in human monocytes and macrophages. This activation depends on JNK and MEK1/2 signaling pathways in human monocytes, whereas inhibition of NFκB, JNK, or p38 blocks an increase of apoA-I gene expression in the macrophages treated with TNFα. Nuclear receptor PPARα is a ligand-dependent regulator of apoA-I gene, whereas LXRs stimulate apoA-I mRNA transcription and ApoA-I protein synthesis and secretion by macrophages. Treatment of human macrophages with PPARα or LXR synthetic ligands as well as knock-down of LXRα, and LXRß by siRNAs interfered with the TNFα-mediated activation of apoA-I gene in human monocytes and macrophages. At the same time, TNFα differently regulated the levels of PPARα, LXRα, and LXRß binding to the apoA-I gene promoter in THP-1 cells. Obtained results suggest a novel tissue-specific mechanism of the TNFα-mediated regulation of apoA-I gene in monocytes and macrophages and show that endogenous ApoA-I might be positively regulated in macrophage during inflammation.