ERP Markers of Auditory Go/NoGo Processing

The Sequential Processing Schema is a data-driven model that uses event-related potential (ERP) components to chart the important psychophysiological processes activated when completing auditory equiprobable Go/NoGo tasks. This model is useful for measuring experimental effects on basic cognitive processes and provides a valuable framework to synthesise and test ERP component theories. Determining the cognitive and behavioural correlates of ERP components is critical for understanding their functional significance and utility in psychology. Additional research is also needed to refine the conceptualisation of the ERP components and cognitive processing requirements in equiprobable Go/NoGo tasks, which are commonly used in psychophysiological research. To do that, robust data-driven methods such as temporal Principal Components Analysis (PCA) are needed for effective ERP component quantification and analyses of the Go/NoGo ERP component ‘processing’ series. This doctoral thesis aimed to clarify ERP component functionality and refine our understanding of equiprobable Go/NoGo tasks by developing the Sequential Processing Schema and exploring how ERP/PCA components relate to cognitive and behavioural processing under different Go/NoGo task conditions. Study 1 compared the ERP component processing series associated with auditory equiprobable and oddball variants of the Go/NoGo task. The manipulation of probability and the relevant modulation of the ERP component series reflected a shift in particular cognitive demands or task requirements, which promoted the conceptual development of component functionality and the generalisability of the Schema. The results of Study 1 questioned the identity of a core ERP component (i.e., Processing Negativity) previously linked to auditory Go/NoGo processing; this was pursued in detail in Study 2, which aimed to clarify the ERP components associated with early information processing in auditory equiprobable and ‘frequent Go’ variants of the Go/NoGo task. Stimulus probability differences (this time the inverse of Study 1) were again used to elucidate component functionality and provide insight into the cognitive task demands. Study 3 and 4 explored ERP component functionality by examining Go stimulus- and response-locked ERP averaging effects, and the link between the equiprobable NoGo P3a and motor response inhibition. Studies 1–4 provided insight into the sequential processing requirements in auditory equiprobable Go/NoGo tasks, and the associated ERP/PCA components, promoting the development of common ERP components as indices of cognitive processes. These outcomes clarified the utility of the equiprobable Go/NoGo task, and highlight important similarities and differences between Go/NoGo and oddball processing, encouraging ERP theory development and integration between those common research paradigms. An update to the Schema was proposed to accommodate the ERP findings and reflect the refined interpretation of equiprobable Go/NoGo processing developed in this thesis, including a shift in the conceptualisation of the sensory processing and inhibitory requirements in the equiprobable task. This was considered to improve the conceptual framework of the Schema and its utility for charting the cognitive and behavioural processing in different task conditions. The outcomes also provide novel insight into how healthy young adults process information and encourage further studies of sequential processing to help delineate abnormalities in cognitive processing related to different psychopathologie

Neuronal correlates of cognitive control are altered in women with endometriosis and chronic pelvic pain

Endometriosis is a debilitating women's health condition and is the most common cause of chronic pelvic pain. Impaired cognitive control is common in chronic pain conditions, however, it has not yet been investigated in endometriosis. The aim of this study was to explore the neuronal correlates of cognitive control in women with endometriosis. Using a cross-sectional study design with data collected at a single time-point, event-related potentials were elicited during a cued continuous performance test from 20 women with endometriosis (mean age = 28.5 ± 5.2 years) and 20 age- and gender-matched controls (mean age = 28.5 ± 5.2 years). Event-related potential components were extracted and P3 component amplitudes were derived with temporal principal components analysis. Behavioral and ERP outcomes were compared between groups and subjective pain severity was correlated with ERP component amplitudes. No significant behavioral differences were seen in task performance between the groups (all p > 0.094). Target P3b (all p < 0.034) and SW (all p < 0.040), and non-target early P3a (eP3a; all p < 0.023) and late P3a (lP3a; all p < 0.035) amplitudes were smaller for the endometriosis compared to the healthy control group. Lower non-target eP3a (p < 0.001), lP3a (p = 0.013), and SW (p = 0.019) amplitudes were correlated with higher pain severity scores. Findings suggest that endometriosis-associated chronic pelvic pain is linked to alterations in stimulus-response processing and inhibitory control networks, but not impaired behavioral performance, due to compensatory neuroplastic changes in overlapping cognitive control and pain networks

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Auditory stimulus- and response-locked ERP components and behavior

To clarify the functional significance of Go event-related potential (ERP) components, this study aimed to explore stimulus- and response-locked ERP averaging effects on the series of ERP components elicited during an auditory Go/NoGo task. Go stimulus- and response-locked ERP data from 126 healthy young adults (Mage = 20.3, SD = 2.8 years, 83 female) were decomposed using temporal principal components analysis (PCA). The extracted components were then identified as stimulus- specific, response-specific, or common to both stimulus- and response-locked data. MANOVAs were then used to test for stimulus- versus response-locked averaging effects on common component amplitudes to determine their primary functional significance (i.e., stimulus- or response-related). Go stimulus- and response-related component amplitudes were then entered into stepwise linear regressions predicting the reaction time (RT), RT variability, and omission errors. Nine ERP components were extracted from the stimulus- and response-locked data, including N1-1, processing negativity (PN), P2, response-related N2 (RN2), motor potential (MP), P3b, P420, and two slow wave components; SW1 and SW2. N1-1, PN, and P2 were stimulus-specific, whereas, RN2, MP, and P420 were response-specific; P3b, SW1, and SW2 were common to both data sets. P3b, SW1, and SW2 were significantly larger in the response-locked data, indicating that they were primarily response-related. RT, RT variability, and omission errors were predicted by various stimulus- and response-related components, providing further insight into ERP markers of auditory information processing and cognitive control. Further, the results of this study indicate the utility of quantifying some common components (i.e., Go P3b, SW1, and SW2) using the response-locked ERP

Sequential processing in the classic oddball task : ERP components, probability, and behavior

This study compared the ERP components and behavior associated with the auditory equiprobable and classic oddball tasks, to relate the cognitive processing stages in those paradigms and continue the development of the sequential processing schema. Target and nontarget ERP data were acquired from 66 healthy young adults (M age = 20.1, SD = 2.4 years, 14 male) who completed both equiprobable (target p = 0.5) and oddball tasks (target p = 0.3). Separate temporal PCAs were used to decompose the ERP data in each task and condition, and the similarity of the components identified in each condition was examined between tasks. Probability effects on component amplitudes and behavior were also analyzed to identify task differences in cognitive demands. A highly similar series of components was identified in each task, closely matching the schema: targets elicited N1‐3, N1‐1, PN, N2c, P3b, SW1, SW2; whereas nontargets elicited N1‐3, N1‐1, PN, N2b, P3a, SW1, SW2. N1‐1 and PN amplitudes increased as stimulus probability decreased, irrespective of the condition. N2b, P3b, SW1, and SW2 amplitudes also varied between tasks, illustrating task‐specific demands on those processing stages. These findings complemented the behavioral outcomes, which demonstrated greater accuracy and control in the classic oddball task. Overall, this study demonstrated comparable processing in the auditory equiprobable and classic oddball tasks, extending the generalizability of the schema and enabling further integration of the ERP theory associated with these tasks. This study also clarifies stimulus probability effects on the schema, providing important insight into the functionality of common ERP components

Auditory equiprobable NoGo P3: A single-trial latency-adjusted ERP analysis

The NoGo P3 event-related potential (ERP) component is often related to response inhibition, although its function in equiprobable Go/NoGo tasks is debated. Previous findings concerning the auditory equiprobable NoGo P3 (or P3a) could be distorted by averaging latency-variable ERP components. This study aimed to control NoGo P3 latency jitter to investigate the component\u27s relationship with inhibitory demands and its neuronal sources across trials. P3 latency jitter was controlled using a novel procedure to enable single-trial P3 quantification across 126 healthy young adults (Mage = 20.3, SD = 2.8 years) using principal components analysis. NoGo inhibitory demands and performance were measured using the Lateralised Readiness Potential and error rates, respectively. The stimulus-locked P3 (SL-P3) was also analysed to assess the ‘blurring effect’ (i.e., smearing) associated with averaging latency-variable ERP trial data. A Spearman\u27s rank correlation across 4700 NoGo trials demonstrated that the relationship between latency-adjusted P3 (LA-P3) and inhibitory demands was inconsequential. The cortical sources associated with LA-P3, using eLORETA, were in the premotor and prefrontal cortices, cingulate, and precuneus. SL-P3 was smaller than LA-P3, and that difference was positively related to P3 latency jitter; its source solution was also limited to lower activation in the prefrontal cortex. SL-P3 was not related to inhibitory demands or performance. This study indicates that NoGo P3 should not index response inhibition in auditory equiprobable tasks. Instead, the findings support a neuroinhibition account relating NoGo P3 to attention. Blurring effects were also shown to impact a standard ERP measure and its source solution, encouraging ERP latency-adjustment in future research

A processing schema for children in the auditory equiprobable Go/NoGo task : ERP components and behaviour

A sequential processing model for adults in the auditory equiprobable Go/NoGo task has been developed in recent years. This used temporal principal components analysis (PCA) to decompose Go/NoGo event related potential (ERP) data into components that mark stages of perceptual and cognitive processing. The model has been found useful in frameworking several studies in young and older adults, and in children. Recently, it has been demonstrated that the common PCA approach of decomposing Go and NoGo ERP data together results in misallocation of variance between the conditions, distorting the timing, topography, and amplitudes of the resultant components in each condition. The present study thus reanalyses data from a child study, conducting separate PCAs on the data from each condition. Multiple regression was then used to seek links with behavioural measures from the task. In addition to confirming the previous NoGo N2b/inhibitory processing link, novel NoGo Negative Slow Wave/error evaluation and Go N1-1/RT variability links were obtained. Based on these outcomes, the recommended separate application of PCAs to Go and NoGo data was confirmed. The present data were used to develop a child-specific sequential processing schema for this paradigm, suggesting earlier separation of the Go and NoGo processing chains, and the need to include an additional inhibition and evaluation stage. The child schema should be useful in future studies involving this and other two-choice reaction tasks

EEG phase states at stimulus onset in a variable-ISI Go/NoGo task : effects on ERP components

Previous EEG-ERP dynamics studies found non-random “preferred” EEG phases at stimulus onset in a fixed interstimulus interval (ISI) equiprobable auditory Go/NoGo paradigm, with substantial effects on ERP components. Here we changed to a variable ISI task to prevent/reduce preferential phase occurrence. Discrete Fourier transforms decomposed prestimulus EEG at Cz for each trial to calculate the phase of different frequencies at stimulus onset; we combined these into the delta, theta, alpha, and beta bands, and then sorted trials into phase quartiles for each. ERPs from the raw EEG, assessed using temporal Principal Components Analyses, were examined as a function of phase at stimulus onset. Preferential phase occurrence was reduced as predicted, but random phase substantially impacted component amplitudes. For example, negativity in delta enhanced Go and NoGo P3b; and in theta reduced NoGo but not Go P3b. Overall, EEG phases at stimulus onset support differential cognitive processing in this two-choice task

ERP Go/NoGo condition effects are better detected with separate PCAs

We explored the separation of Go and NoGo effects in the ERP components elicited in an equiprobable Go/NoGo task, using different forms of temporal Principal Components Analysis (PCA). Following exploratory simulation studies assessing the PCA impact of latency jitter and between-condition latency differences in the P3 latency range, an empirical study compared results of a Combined PCA carried out using both Go and NoGo ERPs together as input, with those from two Separate PCAs carried out on the Go and NoGo ERPs separately. The simulation studies indicated that Separate PCAs provide adequate component recovery in the presence of P3 latency jitter, and that Combined PCAs provide good separation of components only when systematic condition-related latency differences are sufficiently large (here ~ 110 ms). In the empirical data, broadly-similar components were obtained from the Combined and Separate PCAs, supporting previous findings from Combined PCA investigations, and the consequent interpretations of the sequential processing involved. However, the Separate PCAs generated latency differences for components in the Go and NoGo processing chains that better matched the late Go/NoGo ERP peaks, and produced better-defined and larger components that fitted the stages in a hypothetical processing schema developed for this paradigm. Overall, the Separate PCAs yielded a better partitioning of the ERP variance associated with the Go and NoGo conditions, and should be considered as the first choice in future investigations if systematic component or subcomponent latency differences are present or suspected