Association between cortical hyperexcitability and visual disturbances – evidence from behaviour and electroencephalogram

This thesis presents four studies that sought to examine the presence and role of cortical hyperexcitability underlying aberrant / anomalous perceptions in neurotypical and self-reported migraine groups. The current thesis developed new screening tools for assessing and conceptualising cortical hyperexcitability leading to essential advancements in our understanding of its presence and its role in different forms of anomalous experience. In chapter II, the latent structure of a proxy measure was uncovered and constructed to reflect cortical hyperexcitability, namely Cortical Hyperexcitability Index – II (CHi-II), by conducting an exploratory factor analysis on the behavioural data that indicates the frequency and intensity of the 300 non-clinical participants’ everyday life anomalous visual experiences. In chapter III, a revised pattern glare test was employed to investigate a direct linkage between everyday life visual stress symptoms and pattern glare. The quantitative analyses were implemented by exploring the statistical relationships between the scores of the extracted factors on CHi-II and pattern glare scores and on a set of migraine patients and healthy controls. In chapter IV, where the gratings typically used in a pattern glare test were revised as visual stimuli with a VEP paradigm. The association between cortical hyperexcitability and pattern glare was examined by electrophysiological measurement. Here the early (0 – 200 ms) and late VEP (300 –700 ms) components are compared between the groups of self-reported migraineurs and neurotypical participants. Finally, aiming to isolate the effect of cortical hyperexcitability from migraine, the above VEP study on a clinically normal sample was replicated in chapter V. In order to observe how cortical hyperexcitability may influence the VEPs, non-clinical subjects were split into hyperexcitable and non-hyperexcitable based on their pattern glare scores. The early and late VEP components are, again, compared between these two groups

Evidence for Distinct Clusters of Diverse Anomalous Experiences and Their Selective Association with Signs of Elevated Cortical Hyperexcitability

Visual cortical hyperexcitability (VCH) is an underlying factor for aberrant visual experience. Utilizing an exploratory factor analysis (n=300), study 1 developed a revised proxy screening measure for VCH - the Cortical Hyperexcitability index – II(CHi-II). The result revealed a stable 3-factor solution. Study 2 tested both a migraine group and a control group on the CHi-II with a behavioural task that is known to reflect VCH. The migraine group produced significantly elevated scores two factors of CHi-II. Among the non-migraine group, subjects with high VCH also produced significantly elevated scores on CHi-II compared to those with low VCH. These findings support the utility of CHi-II as an indirect proxy measure for signs of VCH and reveal new categorical distinctions for the nature of the anomalous perceptions. These perceptions may well reflect diverse neurocognitive underpinnings leading to advancements in our understanding of aberrations in conscious experience

Differences in early and late pattern-onset visual-evoked potentials between self-reported migraineurs and controls

Striped patterns have been shown to induce strong visual illusions and discomforts to migraineurs in previous literature. Previous research has suggested that these unusual visual symptoms to be linked with the hyperactivity on the visual cortex of migraine sufferers. The present study searched for evidence supporting this hypothesis by comparing the visual evoked potentials (VEPs) elicited by striped patterns of specific spatial frequencies (0.5, 3, and 13 cycles-per-degree) between a group of 29 migraineurs (17 with aura/12 without) and 31 non-migraineurs. In addition, VEPs to the same stripped patterns were compared between non-migraineurs who were classified as hyperexcitable versus non-hyperexcitable using a previously established behavioural pattern glare task. We found that the migraineurs had a significantly increased N2 amplitude for stimuli with 13 cpd gratings but an attenuated late negativity (LN: 400 - 500 ms after the stimuli onset) for all the spatial frequencies. Interestingly, non-migraineurs who scored as hyperexcitable appeared to have similar response patterns to the migraineurs, albeit in an attenuated form. We propose that the enhanced N2 could reflect disruption of the balance between parvocellular and magnocellular pathway, which is in support of the cortical hyperexcitation hypothesis in migraineurs. In addition, the attenuation of the late negativity could reflect a top-down feedback mechanism to suppress visual processing of an aversive stimulus

Attenuated alpha oscillation and hyperresponsiveness reveals impaired perceptual learning in migraineurs.

Background: Anomalous phantom visual perceptions coupled to an aversion and discomfort to some visual patterns (especially grating in mid-range spatial frequency) have been associated with the hyperresponsiveness in migraine patients. Previous literature has found fluctuations of alpha oscillation (8-14 Hz) over the visual cortex to be associated with the gating of the visual stream. In the current study, we examined whether alpha activity was differentially modulated in migraineurs in anticipation of an upcoming stimulus as well as post-stimulus periods. Methods: We used EEG to examine the brain activity in a group of 28 migraineurs (17 with aura/11 without) and 29 non-migraineurs and compared their alpha power in the pre/post-stimulus period relative to the onset of stripped gratings. Results: Overall, we found that migraineurs had significantly less alpha power prior to the onset of the stimulus relative to controls. Moreover, migraineurs had significantly greater post-stimulus alpha suppression (i.e event-related desynchronization) induced by the grating in 3 cycles per degree at the 2nd half of the experiment. Conclusions: These findings taken together provide strong support for the presence of the hyperresponsiveness of the visual cortex of migraine sufferers. We speculate that it could be the consequence of impaired perceptual learning driven by the dysfunction of GABAergic inhibitory mechanism

Genome-Wide Association Study of Hepatocellular Carcinoma in Southern Chinese Patients with Chronic Hepatitis B Virus Infection

One of the most relevant risk factors for hepatocellular carcinoma (HCC) development is chronic hepatitis B virus (HBV) infection, but only a fraction of chronic HBV carriers develop HCC, indicating that complex interactions among viral, environmental and genetic factors lead to HCC in HBV-infected patients. So far, host genetic factors have incompletely been characterized. Therefore, we performed a genome-wide association (GWA) study in a Southern Chinese cohort consisting of 95 HBV-infected HCC patients (cases) and 97 HBV-infected patients without HCC (controls) using the Illumina Human610-Quad BeadChips. The top single nucleotide polymorphisms (SNPs) were then validated in an independent cohort of 500 cases and 728 controls. 4 SNPs (rs12682266, rs7821974, rs2275959, rs1573266) at chromosome 8p12 showed consistent association in both the GWA and replication phases (ORcombined = 1.31–1.39; pcombined = 2.71×10−5–5.19×10−4; PARcombined = 26–31%). We found a 2.3-kb expressed sequence tag (EST) in the region using in-silico data mining and verified the existence of the full-length EST experimentally. The expression level of the EST was significantly reduced in human HCC tumors in comparison to the corresponding non-tumorous liver tissues (P<0.001). Results from sequence analysis and in-vitro protein translation study suggest that the transcript might function as a long non-coding RNA. In summary, our study suggests that variations at chromosome 8p12 may promote HCC in patients with HBV. Further functional studies of this region may help understand HBV-associated hepatocarcinogenesis

PHIL and Squid Embolization of Cerebral Arteriovenous Malformation: A Retrospective Case Series of 23 Patients

Precipitating hydrophobic injectable liquid (PHIL; MicroVention, Aliso Viejo, CA, USA) and Squid (Balt, Irvine, CA, USA) are 2 newer liquid embolic agents used in endovascular embolization of cerebral arteriovenous malformation (AVM). This study aims to investigate and compare the effectiveness and safety profile of the 2 newer liquid embolic agents in the embolization of cerebral AVM. This is a retrospective study on all patients diagnosed with cerebral AVM undergoing endovascular embolization with liquid embolic agents PHIL and Squid admitted to the Division of Neurosurgery, Department of Surgery in Prince of Wales Hospital from January 2014 to June 2021. Twenty-three patients with cerebral AVM were treated with 34 sessions of endovascular embolization with either PHIL or Squid (17 sessions each) liquid embolic agents with a male to female ratio of 2.3:1 (male 16; female 7) and mean age of 44.6 (range, 12 to 67). The mean total nidus obliteration rate per session was 57% (range, 5% to 100%). Twenty-one patients (91.3%) received further embolization, stereotactic radiosurgery, or surgical excision after initial endovascular embolization. There were 2 morbidities (1 neurological and 1 non-neurological, 6%) and no mortalities (0%). All patients had static or improvement in modified Rankin Scale at 3 to 6 months at discharge. PHIL and Squid are effective and safe liquid embolic agents for endovascular embolization of cerebral AVM, achieving satisfactory nidal obliteration rates and patient functional outcomes

Radiomics in urolithiasis: Systematic review of current applications, limitations, and future directions

Radiomics is increasingly applied to the diagnosis, management, and outcome prediction of various urological conditions. Urolithiasis is a common benign condition with a high incidence and recurrence rate. The purpose of this scoping review is to evaluate the current evidence of the application of radiomics in urolithiasis, especially its utility in diagnostics and therapeutics. An electronic literature search on radiomics in the setting of urolithiasis was conducted on PubMed, EMBASE, and Scopus from inception to 21 March 2022. A total of 7 studies were included. Radiomics has been successfully applied in the field of urolithiasis to differentiate phleboliths from calculi and classify stone types and composition pre-operatively. More importantly, it has also been utilized to predict outcomes and complications after endourological procedures. Although radiomics in urolithiasis is still in its infancy, it has the potential for large-scale implementation. Its greatest potential lies in the correlation with conventional established diagnostic and therapeutic factors

A population-based cohort study of 394,401 children followed for 10 years exhibits sustained effectiveness of scoliosis screening

© 2015 Elsevier Inc. All rights reserved. Background context: The value of scoliosis screening has been recently shown in a multicenter randomized controlled trial. However, the long-term sustainability of the clinical effectiveness of scoliosis screening as a routine health service remains unknown. Purpose: The aim of this study was to assess the sustainability of the clinical effectiveness of school scoliosis screening. Study design/setting: A large population-based cohort study with a 10-year follow-up was conducted. Patient sample: A total of 394,401 students who were in the fifth grade during the five academic years from 1995/1996 to 1999/2000 formed five consecutive annual cohorts. The students were eligible for the Hong Kong scoliosis screening program, with their screening history and medical records until their nineteenth birthdays being assessed. Outcome measures: The outcome measures considered in the study were development of adolescent idiopathic scoliosis by the 19 years of age and the Cobb angle. Methods: The clinical effectiveness of scoliosis screening was assessed by referral rate for radiographic diagnosis, sensitivity, specificity, and predictive values. Results: A total of 306,144 students (78%) participated in scoliosis screening, which used a two-tier system. The prevalence of curves of 20 or greater was 1.8% (95% confidence interval [CI], 1.7-1.8%), whereas the referral rate for radiography, the sensitivity, and the positive predictive value (PPV) for curves of 20 or greater were 4.1% (95% CI, 4.0-4.2%), 91% (95% CI, 90-92%), and 40% (95% CI, 39-41%), respectively. Across the five consecutive annual cohorts, the prevalence and sensitivity for curves of 20 or greater increased by 0.23% (95% CI, 0.21-0.25%; p<.001) and 0.76% (95% CI, 0.43-1.04%; p<.001) per year, respectively; however, the PPV was reduced by 1.71% (95% CI, 1.09-2.33%; p<.001) per year. Conclusions: This report describes the first large population-based study with a long-term follow-up indicating that a scoliosis screening program can have sustained clinical effectiveness in identifying patients with adolescent idiopathic scoliosis needing clinical observation. As the prevalence of adolescent idiopathic scoliosis increases, scoliosis screening should be continued as a routine health service in schools or by general practitioners if there is no scoliosis screening policy.postprin

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data