Abnormal trial-to-trial variability in P300 time-varying directed eeg network of schizophrenia.

Cognitive disturbance in identifying, processing, and responding to salient or novel stimuli are typical attributes of schizophrenia (SCH), and P300 has been proven to serve as a reliable psychosis endophenotype. The instability of neural processing across trials, i.e., trial-to-trial variability (TTV), is getting increasing attention in uncovering how the SCH "noisy" brain organizes during cognition processes. Nevertheless, the TTV in the brain network remains unrevealed, notably how it varies in different task stages. In this study, resorting to the time-varying directed electroencephalogram (EEG) network, we investigated the time-resolved TTV of the functional organizations subserving the evoking of P300. Results revealed anomalous TTV in time-varying networks across the delta, theta, alpha, beta1, and beta2 bands of SCH. The TTV of cross-band time-varying network properties can efficiently recognize SCH (accuracy: 83.39%, sensitivity: 89.22%, and specificity: 74.55%) and evaluate the psychiatric symptoms (i.e., Hamilton's depression scale-24, r = 0.430, p = 0.022, RMSE = 4.891; Hamilton's anxiety scale-14, r = 0.377, p = 0.048, RMSE = 4.575). Our study brings new insights into probing the time-resolved functional organization of the brain, and TTV in time-varying networks may provide a powerful tool for mining the substrates accounting for SCH and diagnostic evaluation of SCH.

A systematic review of mobile brain/body imaging studies using the P300 event-related potentials to investigate cognition beyond the laboratory.

The P300 ERP component, related to the onset of task-relevant or infrequent stimuli, has been widely used in the Mobile Brain/Body Imaging (MoBI) literature. This systematic review evaluates the quality and breadth of P300 MoBI studies, revealing a maturing field with well-designed research yet grappling with standardization and global representation challenges. While affirming the reliability of measuring P300 ERP components in mobile settings, the review identifies significant hurdles in standardizing data cleaning and processing techniques, impacting comparability and reproducibility. Geographical disparities emerge, with studies predominantly in the Global North and a dearth of research from the Global South, emphasizing the need for broader inclusivity to counter the WEIRD bias in psychology. Collaborative projects and mobile EEG systems showcase the feasibility of reaching diverse populations, which is essential to advance precision psychiatry and to integrate varied data streams. Methodologically, a trend toward ecological validity is noted, shifting from lab-based to real-world settings with portable EEG system advancements. Future hardware developments are expected to balance signal quality and sensor intrusiveness, enriching data collection in everyday contexts. Innovative methodologies reflect a move toward more natural experimental settings, prompting critical questions about the applicability of traditional ERP markers, such as the P300 outside structured paradigms. The review concludes by highlighting the crucial role of integrating mobile technologies, physiological sensors, and machine learning to advance cognitive neuroscience. It advocates for an operational definition of ecological validity to bridge the gap between controlled experiments and the complexity of embodied cognitive experiences, enhancing both theoretical understanding and practical application in study design.

Approach bias in individuals with Internet gaming disorder: Evidence from an event-related potential-based approach-avoid task.

Individuals with Internet gaming disorder (IGD) often exhibit an approach bias towards gaming cues compared to non-gaming cues. Although previous studies suggested a positive correlation between approach bias and the severity of game use, the neuropsychological mechanisms that underpin the automatic action tendencies remain largely unexplored. The present study measured event-related potentials (ERPs) in 22 IGD and 23 healthy control (HC) participants who met the inclusion criteria, both groups conducted the Stimulus-Response Compatibility task (SRC), with their ERPs recorded during the task. Results revealed that the IGD group showed a significantly larger approach bias towards gaming cues (avoidance versus approach reaction time) compared to the HC group. The amplitude of P300 significantly increased, whereas N100 significantly decreased for game-approach compared to game-avoid for IGD compared to HC participants. The findings suggested that the enhanced integrated motivational value under compatible conditions as well as increased stimulus-response conflicts under incompatible conditions may contribute to the approach bias in IGD individuals. Further investigation on the intervention is prompted through longitudinal studies.

Midfrontal conflict theta and parietal P300 are linked to a latent factor of DSM externalising disorders.

Psychiatric illnesses form spectra rather than categories, with symptoms varying continuously across individuals, i.e., there is no clear break between health and disorder. Dimensional measures of behaviour and brain activity are promising targets for studying biological mechanisms that are common across disorders. Here, we assessed the extent to which neural measures of the sensitivity of the three biological systems in the reinforcement sensitivity theory (RST) could account for individual differences in a latent general factor estimated from symptom counts across externalising disorders (EXTs). RST explanatory power was pitted against reduced P300, a reliable indicator of externalising per previous research. We assessed 206 participants for DSM-5 EXTs (antisocial personality disorder, conduct disorder, attention-deficit/hyperactivity disorder, intermittent explosive disorder symptoms, alcohol use disorder, and cannabis use disorder). Of the final sample, 49% met diagnostic criteria for at least one of the EXTs. Electroencephalographic measures of the sensitivities of the behavioural activation system (BAS), the fight/flight/freeze system, and the behavioural inhibition system (BIS), as well as P300 were extracted from the gold bar-lemon and stop-signal tasks. As predicted, we found that low neural BIS sensitivity and low P300 were uniquely and negatively associated with our latent factor of externalising. Contrary to prediction, neural BAS/"dopamine" sensitivity was not associated with externalising. Our results provide empirical support for low BIS sensitivity and P300 as neural mechanisms common to disorders within the externalising spectrum; but, given the low N involved, future studies should seek to assess the replicability of our findings and, in particular, the differential involvement of the three RST systems.

Unsupervised Characterization of Prediction Error Markers in Unisensory and Multisensory Streams Reveal the Spatiotemporal Hierarchy of Cortical Information Processing.

Elicited upon violation of regularity in stimulus presentation, mismatch negativity (MMN) reflects the brain's ability to perform automatic comparisons between consecutive stimuli and provides an electrophysiological index of sensory error detection whereas P300 is associated with cognitive processes such as updating of the working memory. To date, there has been extensive research on the roles of MMN and P300 individually, because of their potential to be used as clinical markers of consciousness and attention, respectively. Here, we intend to explore with an unsupervised and rigorous source estimation approach, the underlying cortical generators of MMN and P300, in the context of prediction error propagation along the hierarchies of brain information processing in healthy human participants. The existing methods of characterizing the two ERPs involve only approximate estimations of their amplitudes and latencies based on specific sensors of interest. Our objective is twofold: first, we introduce a novel data-driven unsupervised approach to compute latencies and amplitude of ERP components accurately on an individual-subject basis and reconfirm earlier findings. Second, we demonstrate that in multisensory environments, MMN generators seem to reflect a significant overlap of "modality-specific" and "modality-independent" information processing while P300 generators mark a shift toward completely "modality-independent" processing. Advancing earlier understanding that multisensory contexts speed up early sensory processing, our study reveals that temporal facilitation extends to even the later components of prediction error processing, using EEG experiments. Such knowledge can be of value to clinical research for characterizing the key developmental stages of lifespan aging, schizophrenia, and depression.

Effects of parietal repetitive transcranial magnetic stimulation in prolonged disorders of consciousness: A pilot study.

Objective: Although the parietal cortex is related to consciousness, the dorsolateral prefrontal and primary motor cortices are the usual targets for repetitive transcranial magnetic stimulation (rTMS) for prolonged disorders of consciousness (pDoC). Herein, we applied parietal rTMS to patients with pDoC, to verify its neurobehavioral effects and explore a new potential rTMS target. Materials and methods: Twenty-six patients with pDoC were assigned to a rTMS or sham group. The rTMS group received 10 sessions of parietal rTMS; the sham group received 10 sessions of sham stimulation. The Coma Recovery Scale-Revised (CRS-R) and event-related potential (ERP) were collected before and after the 10 sessions or sham sessions. Results: After the 10 sessions, the rTMS group showed: a significant CRS-R score increase; ERP appearance of a P300 waveform and significantly increased Fz amplitudes; increased potentials on topographic mapping, especially in the left prefrontal cortex; and an increase in delta and theta band powers at Fz, Cz, and Pz. The sham group did not show such changes in CRS-R score or ERP results statistically. Conclusion: Parietal rTMS shows promise as a novel intervention in the recovery of consciousness in pDoC. It showed neurobehavioral enhancement of residual brain function and may promote frontal activity by enhancing frontal-parietal connections. The parietal cortex may thus be an alternative for rTMS therapy protocols.

PSAEEGNet: pyramid squeeze attention mechanism-based CNN for single-trial EEG classification in RSVP task.

Introduction: Accurate classification of single-trial electroencephalogram (EEG) is crucial for EEG-based target image recognition in rapid serial visual presentation (RSVP) tasks. P300 is an important component of a single-trial EEG for RSVP tasks. However, single-trial EEG are usually characterized by low signal-to-noise ratio and limited sample sizes. Methods: Given these challenges, it is necessary to optimize existing convolutional neural networks (CNNs) to improve the performance of P300 classification. The proposed CNN model called PSAEEGNet, integrates standard convolutional layers, pyramid squeeze attention (PSA) modules, and deep convolutional layers. This approach arises the extraction of temporal and spatial features of the P300 to a finer granularity level. Results: Compared with several existing single-trial EEG classification methods for RSVP tasks, the proposed model shows significantly improved performance. The mean true positive rate for PSAEEGNet is 0.7949, and the mean area under the receiver operating characteristic curve (AUC) is 0.9341 (p < 0.05). Discussion: These results suggest that the proposed model effectively extracts features from both temporal and spatial dimensions of P300, leading to a more accurate classification of single-trial EEG during RSVP tasks. Therefore, this model has the potential to significantly enhance the performance of target recognition systems based on EEG, contributing to the advancement and practical implementation of target recognition in this field.

A human papillomavirus 16 E2-TopBP1 dependent SIRT1-p300 acetylation switch regulates mitotic viral and human protein levels and activates the DNA damage response.

An interaction between human papillomavirus 16 (HPV16) E2 and the cellular proteins TopBP1 and BRD4 is required for E2 plasmid segregation function. The E2-TopBP1 interaction promotes increased mitotic E2 protein levels in U2OS and N/Tert-1 cells, as well as in human foreskin keratinocytes immortalized by HPV16 (HFK + HPV16). SIRT1 deacetylation reduces E2 protein stability and here we demonstrate that increased E2 acetylation occurs during mitosis in a TopBP1 interacting-dependent manner, promoting E2 mitotic stabilization. p300 mediates E2 acetylation and acetylation is increased due to E2 switching off SIRT1 function during mitosis in a TopBP1 interacting-dependent manner, confirmed by increased p53 stability and acetylation on lysine 382, a known target for SIRT1 deacetylation. SIRT1 can complex with E2 in growing cells but is unable to do so during mitosis due to the E2-TopBP1 interaction; SIRT1 is also unable to complex with p53 in mitotic E2 wild-type cells but can complex with p53 outside of mitosis. E2 lysines 111 and 112 are highly conserved residues across all E2 proteins and we demonstrate that K111 hyper-acetylation occurs during mitosis, promoting E2 interaction with Topoisomerase 1 (Top1). We demonstrate that K112 ubiquitination promotes E2 proteasomal degradation during mitosis. E2-TopBP1 interaction promotes mitotic acetylation of CHK2, promoting phosphorylation and activation of the DNA damage response (DDR). The results present a new model in which the E2-TopBP1 complex inactivates SIRT1 during mitosis, and activates the DDR. This is a novel mechanism of HPV16 activation of the DDR, a requirement for the viral life cycle. IMPORTANCE: Human papillomaviruses (HPVs) are causative agents in around 5% of all human cancers. While there are prophylactic vaccines that will significantly alleviate HPV disease burden on future generations, there are currently no anti-viral strategies available for the treatment of HPV cancers. To generate such reagents, we must understand more about the HPV life cycle, and in particular about viral-host interactions. Here, we describe a novel mitotic complex generated by the HPV16 E2 protein interacting with the host protein TopBP1 that controls the function of the deacetylase SIRT1. The E2-TopBP1 interaction disrupts SIRT1 function during mitosis in order to enhance acetylation and stability of viral and host proteins. We also demonstrate that the E2-TopBP1 interaction activates the DDR. This novel complex is essential for the HPV16 life cycle and represents a novel anti-viral therapeutic target.

VGLL2 and TEAD1 fusion proteins drive YAP/TAZ-independent transcription and tumorigenesis by engaging p300.

Studies on Hippo pathway regulation of tumorigenesis largely center on YAP and TAZ, the transcriptional co-regulators of TEAD. Here, we present an oncogenic mechanism involving VGLL and TEAD fusions that is Hippo pathway-related but YAP/TAZ-independent. We characterize two recurrent fusions, VGLL2-NCOA2 and TEAD1-NCOA2, recently identified in spindle cell rhabdomyosarcoma. We demonstrate that, in contrast to VGLL2 and TEAD1, the fusion proteins are strong activators of TEAD-dependent transcription, and their function does not require YAP/TAZ. Furthermore, we identify that VGLL2 and TEAD1 fusions engage specific epigenetic regulation by recruiting histone acetyltransferase p300 to control TEAD-mediated transcriptional and epigenetic landscapes. We showed that small molecule p300 inhibition can suppress fusion proteins-induced oncogenic transformation both in vitro and in vivo. Overall, our study reveals a molecular basis for VGLL involvement in cancer and provides a framework for targeting tumors carrying VGLL, TEAD, or NCOA translocations.

AR coactivators, CBP/p300, are critical mediators of DNA repair in prostate cancer.

Castration resistant prostate cancer (CRPC) remains an incurable disease stage with ineffective treatments options. Here, the androgen receptor (AR) coactivators CBP/p300, which are histone acetyltransferases, were identified as critical mediators of DNA damage repair (DDR) to potentially enhance therapeutic targeting of CRPC. Key findings demonstrate that CBP/p300 expression increases with disease progression and selects for poor prognosis in metastatic disease. CBP/p300 bromodomain inhibition enhances response to standard of care therapeutics. Functional studies, CBP/p300 cistrome mapping, and transcriptome in CRPC revealed that CBP/p300 regulates DDR. Further mechanistic investigation showed that CBP/p300 attenuation via therapeutic targeting and genomic knockdown decreases homologous recombination (HR) factors in vitro, in vivo, and in human prostate cancer (PCa) tumors ex vivo. Similarly, CBP/p300 expression in human prostate tissue correlates with HR factors. Lastly, targeting CBP/p300 impacts HR-mediate repair and patient outcome. Collectively, these studies identify CBP/p300 as drivers of PCa tumorigenesis and lay the groundwork to optimize therapeutic strategies for advanced PCa via CBP/p300 inhibition, potentially in combination with AR-directed and DDR therapies.

The use of happy faces as visual stimuli improves the performance of the hybrid SSVEP+P300 brain computer interface.

BACKGROUND: This study illustrates a hybrid brain-computer interface (BCI) in which steady-state visual evoked potentials (SSVEP) and event-related potentials (P300) are evoked simultaneously. The goal of this study was to improve the performance of the current hybrid SSVEP+P300 BCI systems by incorporating a happy face into visual stimuli. NEW METHOD: In this study, happy and sad faces were added to a visual stimulus to induce stronger cortical signals in a hybrid SSVEP+P300 BCI. Additionally, we developed a paradigm in which SSVEP responses were triggered by non-face stimuli, whereas P300 responses were triggered by face stimuli. We tested four paradigms: happy face paradigm (HF), sad face paradigm (SF), happy face and flicker paradigm (HFF), and sad face and flicker paradigm (SFF). RESULTS AND CONCLUSIONS: The results demonstrated that the HFF paradigm elicited more robust cortical responses, which resulted in enhanced system accuracy and information transfer rate (ITR). The HFF paradigm has a system communication rate of 25.9 bits per second and an average accuracy of 96.1%. Compared with other paradigms, the HFF paradigm is the best choice for BCI applications because it has the highest ITR and maximum level of comfort.

Proposer's moral identity modulates fairness processing in the ultimatum game: Evidence from behavior and brain potentials.

Economic decision-making is pivotal to both human private interests and the national economy. People pursue fairness in economic decision-making, but a proposer's moral identity can influence fairness processing. Previous ERP studies have revealed that moral identity has an effect on fairness considerations in the Ultimatum Game (UG), but the findings are inconsistent. To address the issue, we revised the moral-related sentences and used the ERP technique to measure the corresponding neural mechanism. We have observed that the fairness effect in UG can be mirrored in both MFN and P300 changes, whereas the moral identity effect on fairness in UG can be reflected by MFN but not P300 changes. These findings indicate that the moral identity of the proposer can modulate fairness processing in UG. The current study opens new avenues for clarifying the temporal course of the relationship between the proposer's moral identity and fairness in economic decision-making, which is beneficial for understanding the influencing mechanism of fairness processing and fair allocations in complex social contexts.

Pharmacological inhibition of p300 ameliorates steatosis, inflammation, and fibrosis in mice with non-alcoholic steatohepatitis.

The histone acetyltransferase p300 plays a pivotal role in regulating gene expression and cellular phenotype through epigenetic mechanisms. It significantly influences lipid metabolism, which is a key factor in the pathogenesis of non-alcoholic steatohepatitis (NASH), by modulating the transcription of genes involved in lipid synthesis and accumulation. This study aimed to investigate the protective potential of inhibiting p300 in NASH. Male C57BL/6J mice were subjected to a methionine- and choline-deficient (MCD) diet for 4 weeks to induce NASH, and during this period, the p300 inhibitor C646 (10 mg/kg) was administered three times a week. C646 treatment reduced the elevation of p300 expression and histone H3 acetylation, leading to a decrease in liver injury markers in the serum and an improvement in the histological abnormalities observed in MCD diet-fed mice. C646 also reduced lipid accumulation by modulating de novo lipogenesis and suppressed inflammation, including cytokine overproduction and macrophage infiltration. Furthermore, C646 mitigated liver fibrosis and myofibroblast accumulation. This protective effect was achieved through the inhibition of apoptosis by reducing p53 and Bax expression and the suppression of ferroptosis by decreasing lipid peroxidation while enhancing antioxidant defenses. Additionally, C646 alleviated endoplasmic reticulum stress, as evidenced by the downregulation of unfolded protein response signaling molecules. These results highlight the potential of p300 as a therapeutic target for NASH.

Neural mechanisms of Chinese character recognition, updating, and maintenance in the N-back task.

Using the N-back task, we investigated how memory load influences the neural activity of the Chinese character cognitive subprocess (recognition, updating, and maintenance) in Mainland Chinese speakers. Twenty-seven participants completed the Chinese character N-back paradigm while having their event-related potentials recorded. The study employed time and frequency domain analyses of EEG data. Results showed that accuracy decreased and response times increased with larger N values. For ERPs, N2pc and P300 amplitudes decreased and SW amplitude increased with larger N values. For time frequency analyses, the desynchronization of alpha oscillations decreased after stimulus onset, but the synchronization of alpha oscillations increased during the maintenance phase. The results suggest that greater memory load is related to a decrease in cognitive resources during updating and an increase in cognitive resources during information maintenance. The results of a behavioral-ERP data structural equation model analysis showed that the ERP indicators in the maintenance phase predicted behavioral performance.

Apigenin suppresses epithelial-mesenchymal transition in high glucose-induced retinal pigment epithelial cell by inhibiting CBP/p300-mediated histone acetylation.

Epithelial mesenchymal transition (EMT) is a critical process implicated in the pathogenesis of retinal fibrosis and the exacerbation of diabetic retinopathy (DR) within retinal pigment epithelium (RPE) cells. Apigenin (AP), a potential dietary supplement for managing diabetes and its associated complications, has demonstrated inhibitory effects on EMT in various diseases. However, the specific impact and underlying mechanisms of AP on EMT in RPE cells remain poorly understood. In this study, we have successfully validated the inhibitory effects of AP on high glucose-induced EMT in ARPE-19 cells and diabetic db/db mice. Notably, our findings have identified CBP/p300 as a potential therapeutic target for EMT in RPE cells and have further substantiated that AP effectively downregulates the expression of EMT-related genes by attenuating the activity of CBP/p300, consequently reducing histone acetylation alterations within the promoter region of these genes. Taken together, our results provide novel evidence supporting the inhibitory effect of AP on EMT in RPE cells, and highlight the potential of specifically targeting CBP/p300 as a strategy for inhibiting retinal fibrosis in the context of DR.

The priming effect of emotional words on body expressions: Two ERP studies.

The impact of emotional words on the recognition of body expression and the underlying neurodynamic mechanisms remain poorly understood. This study used a classic supraliminal priming paradigm and event related potential (ERP) to investigate the effect of emotion-label words (Experiment 1) and emotional verbs (Experiment 2) on the recognition of body expressions. The behavioral results revealed that individuals exhibited a higher accuracy in recognizing happy expressions when presented with a happy-label word condition, in contrast to neutral expressions. Furthermore, it was observed that the accuracy of recognizing happy body expressions was reduced when preceded by angry verb priming, compared to happy and neutral priming conditions. Conversely, the accuracy of recognizing angry body expressions was higher in response to angry verb priming than happy and neutral priming. The ERP results showed that, in the recognition of happy body expressions, the P300 amplitude elicited by angry-label words was more positive, while a congruent verb-expression condition elicited more positive P300 amplitude than an incongruent condition in the left hemisphere and midline. However, in the recognition of angry body expressions, the N400 amplitude elicited by a congruent verb-expression condition was smaller than that elicited by an incongruent condition. These results suggest that both abstract emotion-label words and specific emotional verbs influence the recognition of body expressions. In addition, integrating happy semantic context and body expression might occur at the P300 stage, whereas integrating angry semantic context and body expression might occur at the N400 stage. These findings present novel evidence regarding the criticality of emotional context in the recognition of emotions.

Design, synthesis and biological evaluation of new RNF126-based p300/CBP degraders.

Histone acetyltransferase CREB-binding protein (CBP) and its homologous protein p300 are key transcriptional activators that can activate oncogene transcription, which present promising targets for cancer therapy. Here, we designed and synthesized a series of p300/CBP targeted low molecular weight PROTACs by assembling the covalent ligand of RNF126 E3 ubiquitin ligase and the bromodomain ligand of the p300/CBP. The optimal molecule A8 could effectively degrade p300 and CBP through the ubiquitin-proteasome system in time- and concentration-dependent manners, with half-maximal degradation (DC50) concentrations of 208.35/454.35 nM and 82.24/79.45 nM for p300/CBP in MV4-11 and Molm13 cell lines after 72 h of treatment. And the degradation of p300/CBP by A8 is dependent on the ubiquitin-proteasome pathway and its simultaneous interactions with the target proteins and RNF126. A8 exhibits good antiproliferative activity in a series of p300/CBP-dependent cancer cells. It could transcriptionally inhibit the expression of c-Myc, induce cell cycle arrest in the G0/G1 phase and apoptosis in MV4-11 cells. This study thus provided us a new chemotype for the development of drug-like PROTACs targeting p300/CBP, which is expected to be applied in cancer therapy.

Comparing the 'When' and the 'Where' of Electrocortical Activity in Patients with Tourette Syndrome, Body-Focused Repetitive Behaviors, and Obsessive Compulsive Disorder.

Background/Objectives: Tourette Syndrome (TS), Obsessive Compulsive Disorder (OCD), and Body-Focused Repetitive Behaviors (BFRB) are three disorders that share many similarities in terms of phenomenology, neuroanatomy, and functionality. However, despite the literature pointing toward a plausible spectrum of these disorders, only a few studies have compared them. Studying the neurocognitive processes using Event-Related Potentials (ERPs) offers the advantage of assessing brain activity with excellent temporal resolution. The ERP components can then reflect specific processes known to be potentially affected by these disorders. Our first goal is to characterize 'when' in the processing stream group differences are the most prominent. The second goal is to identify 'where' in the brain the group discrepancies could be. Methods: Participants with TS (n = 24), OCD (n = 18), and BFRB (n = 16) were matched to a control group (n = 59) and were recorded with 58 EEG electrodes during a visual counting oddball task. Three ERP components were extracted (i.e., P200, N200, and P300), and generating sources were modelized with Standardized Low-Resolution Electromagnetic Tomography. Results: We showed no group differences for the P200 and N200 when controlling for anxiety and depressive symptoms, suggesting that the early cognitive processes reflected by these components are relatively intact in these populations. Our results also showed a decrease in the later anterior P300 oddball effect for the TS and OCD groups, whereas an intact oddball effect was observed for the BFRB group. Source localization analyses with sLORETA revealed activations in the lingual and middle occipital gyrus for the OCD group, distinguishing it from the other two clinical groups and the controls. Conclusions: It seems that both TS and OCD groups share deficits in anterior P300 activation but reflect distinct brain-generating source activations.

Cognitive functions in idiopathic intracranial hypertension.

OBJECTIVE: Cognitive problems in idiopathic intracranial hypertension (IIH) is generally overlooked in the presence of disabling headache and threat to visual function. The aim of this study was to search for cognitive deficits in patients with IIH using neuropsychologic tests in addition to P300 potential recordings to assess cognition related brain activity. METHODS: Fifty IIH patients were examined using Montreal Cognitive Assessment Test, Stroop Test and Visual Aural Digit Span Test to measure different domains of cognition at the time of diagnosis. P300 potentials were recorded by using an oddball paradigm. Hospital Anxiety and Depression Scale was used to determine anxiety and depression. Quality of life (QoL) was assessed by SF-36. The results were compared with fifty healthy controls with matching age, gender and body mass index. RESULTS: Neuropsychologic tests revealed wide cognitive impairment including attention, working memory, executive function, naming, language, delayed recall and orientation in IIH patients. In addition, quality of life was affected in the sub-parameters of general health perceptions, emotional role functioning, vitality, mental health and bodily pain. P300 potential latencies were long and the amplitudes were reduced indicating deficits in attention and working memory. Anxiety scores were high, and health-related QoL was low mainly involving vitality, emotional and mental health. Cognitive dysfunction was not correlated with the levels of anxiety and the correlation with headache severity was mild. CONCLUSION: A multidomain cognitive decline mainly involving attention and working memory was recorded in IIH patients. It was not correlated with anxiety and only a mild correlation with headache severity was present which may indicate a casual relationship between raised intracranial pressure and cognitive deficits. Screening is important as neuropsychological rehabilitation might be relevant in these patients.

Amino Terminal Acetylation of HOXB13 Regulates the DNA Damage Response in Prostate Cancer.

Advanced localized prostate cancers (PC) recur despite chemotherapy, radiotherapy and/or androgen deprivation therapy. We recently reported HOXB13 lysine (K)13 acetylation as a gain-of-function modification that regulates interaction with the SWI/SNF chromatin remodeling complex and is critical for anti-androgen resistance. However, whether acetylated HOXB13 promotes PC cell survival following treatment with genotoxic agents is not known. Herein, we show that K13-acetylated HOXB13 is induced rapidly in PC cells in response to DNA damage induced by irradiation (IR). It colocalizes with the histone variant γH2AX at sites of double strand breaks (DSBs). Treatment of PCs with the Androgen Receptor (AR) antagonist Enzalutamide (ENZ) did not suppress DNA-damage-induced HOXB13 acetylation. In contrast, HOXB13 depletion or loss of acetylation overcame resistance of PC cells to ENZ and synergized with IR. HOXB13K13A mutants show diminished replication fork progression, impaired G2/M arrest with significant cell death following DNA damage. Mechanistically, we found that amino terminus regulates HOXB13 nuclear puncta formation that is essential for proper DNA damage response. Therefore, targeting HOXB13 acetylation with CBP/p300 inhibitors in combination with DNA damaging therapy may be an effective strategy to overcome anti-androgen resistance of PCs.