Electrodermal and central measures of the tonic orienting reflex (OR).

Sokolov described both phasic and tonic aspects of the Orienting Reflex (OR), but subsequent research and theory development has focussed primarily on the phasic OR at the expense of the tonic OR. The present study used prestimulus skin conductance level (SCL) during a dishabituation paradigm to model the tonic OR, examining its amplitude patterning over repeated standard stimulus presentations and a change stimulus. We expected sensitisation (increased amplitude) following the initial and change trials, and habituation (decrement) over the intervening trials. Prestimulus EEG alpha level was explored as a potential central measure of the tonic OR (as an inverse correlate), examining its pattern over stimulus repetition and change in relation to the SCL model. We presented a habituation series of innocuous auditory stimuli to two groups (each N = 20) at different ISIs (Long 13-15 s and Short 5-7 s) and recorded electrodermal and EEG data during two counterbalanced conditions; Indifferent: no task requirements; Significant: silent counting. Across groups and conditions, prestimulus SCLs and alpha amplitudes generally showed the expected trials patterns, confirming our main hypotheses. Findings have important implications for including the assessment of Sokolov's tonic OR in modelling central and autonomic nervous system interactions of fundamental attention and learning processes.

Real-World Experience in the Use of Immunosuppression for the Management of Inflammatory Eye Disease.

PURPOSE: Patients with sight-threatening inflammatory eye disease (IED) are maintained on systemic immunosuppression whilst in long-term clinical remission. There are no clear guidelines on the duration of remission before implementing treatment withdrawal. We present a real-world analysis on the use of immunosuppression in IED in long-term remission and consider strategies for withdrawal. METHODS: Adult IED patients on systemic immunosuppression were categorised into four disease groups: Corneal Transplant Survival Strategies (CTSS), Ocular Surface Disease (OSD), Non-infectious Uveitis (NIU) and Scleritis. Patients with Behçet's disease were excluded. Data on systemic immunosuppressants and biologics used; duration of treatment; reasons for drug discontinuation; disease activity/remission status; duration of clinical remission with an emphasis on patients who had been in remission for a minimum of 24 months were captured. RESULTS: Out of a total of 303 IED patients, 128 were on systemic immunosuppression with a clinical remission of their ocular disease for ≥24 months. The median duration of remission was 4-5 years with the longest duration of remission 22 years, and some patients on immunosuppression for up to 23 years. Sixty patients stopped at least one immunosuppressive agent without prior discussion with a health-care practitioner. CONCLUSION: Progressive conditions, such as cicatrising conjunctivitis may require lifelong immunosuppression, but patients with NIU and Scleritis and those on CTSS, immunosuppression withdrawal should be considered if they remain in remission for 2 years. Any patient stopping a medication should be contacted immediately for counselling. These data will better inform patients, encourage adherence and aide formal guideline development.

Replacement of Dietary Fish Protein with Bacterial Protein Results in Decreased Adiposity Coupled with Liver Gene Expression Changes in Female Danio rerio.

Background: Effective use of Danio rerio as a preclinical model requires standardization of macronutrient sources to achieve scientific reproducibility across studies and labs. Objective: Our objective was to evaluate a bacterial-based single-cell protein (SCP) for the production of open-source standardized diets with defined health characteristics for the zebrafish research community. Methods: We completed a 16-wk feeding trial using juvenile D. rerio 31 d postfertilization (10 tanks per diet and 14 D. rerio per tank) with formulated diets containing either a typical fish protein ingredient [standard reference (SR) diet] or a novel bacterial SCP source [bacterial protein (BP) diet]. At the end of the feeding trial, growth metrics, body composition, reproductive success, and bulk transcriptomics of the liver (RNAseq on female D. rerio with confirmatory rtPCR) were performed for each diet treatment. Results: D. rerio fed the BP diet had body weight gains equivalent to the D. rerio fed fish protein, and females had significantly lower total carcass lipid, indicating reduced adiposity. Reproductive success was similar between treatments, suggesting normal physiological function. Genes differentially expressed in female D. rerio fed the BP diet compared with females fed the SR diet were overrepresented in the gene ontologies of metabolism, biosynthesis of cholesterol precursors and products, and protein unfolding responses. Conclusion: Protein source substantially affected body growth metrics and composition as well as gene expression. These data support the development of an open-source diet utilizing an ingredient that correlates with improved health profiles and reduced variability in notable outcomes.

Effects of the cardiac cycle on auditory processing: A preregistered study on mismatch negativity.

The systolic and diastolic phases of the cardiac cycle are known to affect perception and cognition differently. Higher order processing tends to be facilitated at systole, whereas sensory processing of external stimuli tends to be impaired at systole compared to diastole. The current study aims to examine whether the cardiac cycle affects auditory deviance detection, as reflected in the mismatch negativity (MMN) of the event-related brain potential (ERP). We recorded the intensity deviance response to deviant tones (70 dB) presented among standard tones (60 or 80 dB, depending on blocks) and calculated the MMN by subtracting standard ERP waveforms from deviant ERP waveforms. We also assessed intensity-dependent N1 and P2 amplitude changes by subtracting ERPs elicited by soft standard tones (60 dB) from ERPs elicited by loud standard tones (80 dB). These subtraction methods were used to eliminate phase-locked cardiac-related electric artifacts that overlap auditory ERPs. The endogenous MMN was expected to be larger at systole, reflecting the facilitation of memory-based auditory deviance detection, whereas the exogenous N1 and P2 would be smaller at systole, reflecting impaired exteroceptive sensory processing. However, after the elimination of cardiac-related artifacts, there were no significant differences between systole and diastole in any ERP components. The intensity-dependent N1 and P2 amplitude changes were not obvious in either cardiac phase, probably because of the short interstimulus intervals. The lack of a cardiac phase effect on MMN amplitude suggests that preattentive auditory processing may not be affected by bodily signals from the heart.

Effects of interstimulus interval and significance on electrodermal and central measures of the phasic orienting reflex (OR) in a dishabituation task.

Although the P300 event-related potential (ERP) is the most likely central measure of Sokolov's Orienting Reflex (OR), there are few systematic comparisons with the skin conductance response (SCR), the "gold standard" electrodermal OR measure. We examine habituation, stimulus significance, and inter-stimulus interval (ISI) effects in SCRs and components of the P300 from single-trial ERPs in an auditory dishabituation paradigm. Single trial ERP components were separated by temporal principal components analysis, and five components of the P300 were examined as potential phasic OR measures: P3a, P3b, Novelty P3, and two Slow Waves (SW1, SW2). Across the factors of ISI and significance, SCRs showed decrement over trials, recovery at a deviant, and dishabituation at the subsequent standard. This general pattern was not present in any of the components of the P300. SCRs were also larger to significant stimuli and at the long ISI; effects differed between P300 components. The electrodermal SCR showed the complete profile over trials expected of the phasic OR, and was enhanced by stimulus significance, confirming it as the model measure of Sokolov's phasic OR. Components of the P300 failed to match this profile, but instead appear to reflect different aspects of the stimulus processing involved in OR elicitation.

Replacement of Dietary Fish Protein With Bacterial Single Cell Protein Results in Decreased Adiposity Coupled With Liver Expression Changes in Female Danio Rerio.

Background: Effective use of Danio rerio as a preclinical model requires standardization of macronutrient sources to achieve scientific reproducibility across studies and labs. Our objective was to evaluate single cell protein (SCP) for production of open-source standardized diets with defined heath characteristics for the zebrafish research community. We completed a 16-week feeding trial using juvenile D. rerio 31 days post-fertilization (dpf) (10 tanks per diet, 14 D. rerio per tank) with formulated diets containing either a typical fish protein ingredient or a novel bacterial SCP source. At the end of the feeding trial, growth metrics, body composition, reproductive success, and bulk transcriptomics of the liver (RNAseq on female D. rerio only with confirmatory rtPCR) were performed for each diet treatment. Results: D. rerio fed the SCP containing diet had body weight gains equivalent to the D. rerio fed fish protein, and females had significantly lower total carcass lipid, indicating reduced adiposity. Reproductive success was similar between treatments. Genes differentially expressed in female D. rerio provided the bacterial SCP compared to females given fish protein were overrepresented in the gene ontologies of metabolism, biosynthesis of cholesterol precursors and products, and protein unfolding responses. Conclusion: These data support the development of an open-source diet utilizing an ingredient that correlates with improved health profiles and reduced variability in notable outcomes.

Clinical Outcomes of Observed and Treated Acute Posterior Multifocal Placoid Pigment Epitheliopathy and Relentless Placoid Chorioretinitis.

PURPOSE: To assess the efficacy of treatment on acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and relentless placoid chorioretinopathy (RPC). METHODS: Cases were identified from three UK uveitis centers. Retrospective analysis of visual acuity recovery; OCT structural outcomes; and retinal lesion quantification in observed and treated cases of APMPPE/RPC. RESULTS: There were nine APMPPE and three RPC cases. Out of 12 patients, six were female. Median age: 26.5 years (range, 20-57 years). Four cases (six eyes) were observed, and eight cases (15 eyes) received corticosteroids ± immunosuppression. 4/4 observed and 6/10 treated foveal involving eyes regained 0.00 LogMAR vision. Observed lesions achieved more favorable anatomical outcomes. New lesions post-presentation developed in 1/6 (16%) observed eye versus 10/15 (66%) treated eyes. In three cases, a delayed, rebound lesion occurrence was observed post-high-dose corticosteroids. CONCLUSIONS: While subject to potential treatment bias, in this small case series, natural history alone appears non-inferior to corticosteroid treatment.

Frontocentral delta-beta amplitude coupling in endometriosis-related chronic pelvic pain.

OBJECTIVE: Endometriosis is associated with neuroplastic changes in cognitive control and pain processing networks. This was the first study to assess eyes-closed resting electroencephalogram (EEG) oscillatory amplitudes in women with endometriosis compared to healthy controls, and explore the relationship with chronic pelvic pain. METHODS: Women with endometriosis-related chronic pelvic pain and individually age-matched pain-free controls (N = 20 per group) documented pelvic pain for 28 days before having continuous EEG recorded during a 2 min eyes closed resting state. Natural frequency components were extracted for each group using frequency principal components analysis. Corresponding components were assessed for group differences and correlated with pain scores. RESULTS: Relative to controls, the endometriosis group had greater component amplitudes in delta (0.5 Hz) and beta (∼28 Hz), and reduced alpha (∼10 Hz). Delta and beta amplitudes were positively associated with pain severity, but only beta maintained this association after delta-beta amplitude coupling was controlled. CONCLUSIONS: Enhanced resting delta and beta amplitudes were seen in women with endometriosis experiencing chronic pelvic pain. This delta-beta coupling varied with pelvic pain severity, perhaps reflecting altered cholinergic tone and/or stress reactivity. SIGNIFICANCE: Endometriosis-related changes in central pain processing demonstrate a distinct neuronal oscillatory signature detectable at rest.

The Effects of Concentrative Meditation on the Electroencephalogram in Novice Meditators.

Following investigations into the benefits of meditation on psychological health and well-being, research is now seeking to understand the mechanisms underlying these outcomes. This study aimed to identify natural alpha and theta frequency components during eyes-closed resting and concentrative meditation states and examined their differences within and between two testing sessions. Novice meditators had their EEG recorded during eyes-closed resting and concentrative meditation conditions, before and after engaging in a brief daily concentrative meditation practice for approximately one-month. Separate frequency Principal Components Analyses (f-PCA) yielded four spectral components of interest, congruent between both conditions and sessions: Delta-Theta-Alpha, Low Alpha, High Alpha, and Alpha-Beta. While all four components showed some increase in the meditation condition at the second session, only Low Alpha (∼9.5-10.0 Hz) showed similar increases while resting. These findings support the use of f-PCA as a novel method of data analysis in the investigation of psychophysiological states in meditation.

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's 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's 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.

Child sex differences in the auditory equiprobable Go/NoGo task.

Our previous studies of the equiprobable auditory Go/NoGo task have been used to substantiate a perceptual/cognitive Processing Schema in young and older adults, and in children. The processes in the Schema are linked to PCA components derived separately from Go and NoGo ERPs. Here we investigated sex differences in the child Schema. Two groups of fourteen children (aged 8 to 13 years) were individually matched on age and presented with four stimulus blocks of the equiprobable Go/NoGo task, each containing 75 NoGo and 75 Go tones in random order. Separate NoGo and Go ERPs were obtained from each child and submitted to temporal Principal Components Analyses (PCAs). Each ERP was analysed in two epochs (-100-400 ms and 300-800 ms) to improve the cases:variables ratio. Four pairs of temporal PCAs, each with unrestricted VARIMAX rotation, separately quantified the NoGo and Go ERPs of each epoch in each group. After these pairs were combined in temporal order, four sets of similar components were extracted. Many identified components were differentially enhanced to either NoGo or Go, as in previous work with children. The Female group had NoGo component latencies that were systematically some 3.5% greater than in Males, but there were no sex differences in Go latencies. Females also displayed fewer NoGo commission and Go omission errors, and faster Go RT than Males. Females had larger NoGo N2b, and larger Go components from N2b through to the late positivity. These results, including their ERP component/behaviour correlations, can be integrated as a task-specific behavioural and ERP processing enhancement in girls that suggests their developmental advantage over boys in this age range.

Stimulus intensity effects and sequential processing in the passive auditory ERP.

Auditory stimulus intensity of innocuous tones is generally thought to have a direct effect on the amplitude of ERP components, but these effects have rarely been explored across a wide component range, or in multiple paradigms. Here we investigate component sensitivity to stimulus intensity differences in two studies. Study 1 (N = 36) employed a between-participants paradigm in which repeated trains of standard stimuli were presented as 50 or 80 dB SPL 1000 Hz tones. Study 2 (N = 18) used a within-participant presentation of alternating 60 and 80 dB SPL 1000 Hz tones. Electrode caps with 19 channels (referred to linked ears) generated ERPs covering the first 600 ms of each participant's EEG responses; these were submitted to separate temporal PCAs in each study. A similar series of components was obtained in each study: P1, N1a, N1b, N1c, P2, P3a, P3b, nP3, SW1, and SW2; an N2 was found in Study 2 only. Loud tones in Study 1 produced greater amplitudes in all components except SW1. In Study 2, Loud cf. Soft tones produced smaller P1 and nP3, larger N1 components, P2, and P3a, with no effect on N2, P3b, SW1 or SW2. These results indicate similar sequential processes underlying sensory processing in one- and two-stimulus paradigms, with the later stimulus intensity effects varying with paradigm.

Age-related changes in the EEG in an eyes-open condition: II. Subtypes of AD/HD.

This study investigated age-related changes in the EEG of subtypes of Attention-Deficit/Hyperactivity Disorder (AD/HD) compared with neurotypical controls, using an eyes-open resting condition. Two hundred and twenty five children between the ages of 5 and 16 years participated in this study. Groups consisted of AD/HD of the combined (AD/HDcom) and inattentive (AD/HDin) types, which were compared with controls for each of three age ranges: Young (5-8 years), Middle (9-12 years), and Old (13-16 years). The EEG was recorded and analyzed using AMLAB hardware and software, and Fourier transformed to provide estimates for total power, and absolute and relative power in the delta, theta, alpha and beta bands. Compared to controls, the AD/HD groups had globally increased relative theta. Regional differences were found for absolute and relative alpha and beta. Compared to AD/HDcom, AD/HDin had globally reduced total power, absolute and relative theta, and absolute alpha. Regional differences only were found for absolute and relative delta, absolute beta, and relative alpha. No simple interactions were found for diagnostic factors with age. These results indicate that maturational effects can be observed between subtypes of AD/HD and controls in the eyes-open condition with similarities to those reported in eyes-closed conditions, although substantial differences are apparent in the maturation of fast wave activity, primarily alpha. These results provide evidence of maturational differences between subtypes of AD/HD in eyes-open conditions, and provide additional support for the suggestion that subtypes of AD/HD differ in severity rather than the nature of underlying neurological impairment.

Creating a Health Utility Value for Birdshot Chorioretinopathy.

PURPOSE: To create a health utility value for birdshot chorioretinopathy (BCR) using Time Trade-Off (TTO) and Standard Gamble (SG) utilities. METHOD: Adult BCR patients completed TTO, SG, EQ-5D-5L, and NEI VFQ-25 questionnaires and underwent a detailed history and clinical examination. RESULTS: A total of 28 BCR patients (9 M, 19 F; mean age 62 years, range 47-83) were included. There were 22 patients with a logMAR vision of 0.3 or better in both eyes. Mean TTO was 0.90 ± SD 0.18 (range 0.33-1.0) and mean SG was 0.94 ± SD 0.14 (range 0.5-1.0). TTO correlated with EQ-5D-5L index value (p = .024) and NEI VFQ-25 composite score (p = .015). CONCLUSIONS: Of 28 patients with BCR, 11 would trade remaining life (mean 5.4 years), and 6 would take a risk of immediate death (mean 28% risk), in return for perfect vision in both eyes for the rest of their life.

Development of children's performance and ERP components in the equiprobable Go/NoGo task.

Since the equiprobable Go/NoGo task lacks the dominant Go imperative of the usual Go/NoGo (with more Go than NoGo stimuli), it is generally regarded as involving little inhibition. However, children have relative difficulty with this task, and have a large frontal NoGo N2. We previously found that this 'child N2' does play an inhibitory role, with larger frontal N2b associated with fewer commission errors. Here we investigated age-related developmental differences in the N2b and other components in the equiprobable Go/NoGo task. Two groups of eighteen Younger children (aged 8.0 to 10.3 years) and eighteen Older children (aged 10.4 to 12.8 years), matched on sex, were presented with three stimulus blocks each containing 100 Go and 100 NoGo tone stimuli in random order. Four temporal PCAs, each with unrestricted VARIMAX rotation, separately quantified the Go and NoGo ERPs of each group, and similar components were extracted from each set. Most identified components were differentially enhanced to either Go or NoGo, as in adults, supporting a previously-proposed differential sequential processing schema. The Older group had Go component latencies that were systematically reduced by some 7.4% from the Younger group, and they displayed faster RT and fewer omission and commission errors. Between subjects in the Older group, larger frontocentral NoGo N2b was associated with fewer commission errors. Hence the NoGo N2b in this paradigm can be interpreted as an individual marker of inhibition in older, but not young, children.

Age-related changes in the EEG in an eyes-open condition: I. Normal development.

This study investigated age related changes in the EEG of normal children in an eyes-open condition, in order to provide developmental norms for the study of children and adolescents with Attention-Deficit/Hyperactivity Disorder (AD/HD) - see our companion paper (Mason et al., submitted). EEG was recorded at 17 sites from 75 children (63 boys and 12 girls, in the approximately 5:1 ratio common in AD/HD) between the ages of 5 and 16 years. They comprised three groups, each of 25 children (21 boys and 4 girls), divided into Young (5-8 years), Middle (9-12 years), and Old (13-16 years). The EEG was recorded during an eyes-open resting condition and Fourier transformed to provide estimates for total power, and absolute and relative power in the delta, theta, alpha and beta bands. Total power and absolute delta, theta, alpha, and beta decreased with increasing age, as did relative delta, while relative alpha increased with increasing age. Changes occurred faster in the posterior regions for total power, absolute theta and alpha, relative theta, and in frontal regions for absolute and relative beta. Some lateral developmental effects differed with band. These results indicate that maturation effects observed in the eyes-open EEG show some similarities to those reported in eyes-closed conditions, although substantial differences are apparent in the maturation of fast wave activity, particularly alpha. The data provide simple age-norms for eyes-open investigations of EEG differences in young clinical groups, particularly AD/HD. They encourage further investigations of the activational effects of this simple eyes-closed/eyes-open manipulation, which may aid understanding of the energetics of behaviour.

The effects of dietary saturated fat source on weight gain and adiposity are influenced by both sex and total dietary lipid intake in zebrafish.

The effects of saturated fat intake on obesity and cardiovascular health remain inconclusive, likely due in part to their varied nature and interactions with other nutrients. Investigating the synergistic effects of different saturated fat sources with other dietary lipid components will help establish more accurate nutritional guidelines for dietary fat intake. Over the past two decades, zebrafish (Danio rerio) have been established as an attractive model system to address questions regarding contributions of dietary lipid intake to diet-induced obesity in humans. The goal of the present study was to assess interactions of three different saturated fat sources (milk fat, palm oil, and coconut oil) with sex and total dietary lipid intake on weight gain and body composition in adult zebrafish. Larvae were raised on live feeds until 28 days post fertilization, and then fed a formulated maintenance diet until three months of age. An eight-week feeding trial was then initiated, in which zebrafish were fed nine experimental low- and high-fat diets varying in saturated fatty acid and long-chain polyunsaturated fatty acid content, in addition to a low-fat and high-fat control diet. At termination of the feeding trial, each treatment was evaluated according to body mass, moisture content, and adiposity. Sex and diet significantly interacted in their effects on body mass (P = 0.026), moisture content (P = 0.044), and adiposity (P = 0.035). The influence of saturated fat source on body mass was observed to be dependent on intake of total dietary lipid. In females, all three saturated fat sources had similar effects on adiposity. From these observations, we hypothesize that impacts of saturated fat intake on energy allocation and obesity-related phenotypes are influenced by both sex and intake of other dietary lipid components. Our results suggest that current nutritional guidelines for saturated fat intake may need to be re-evaluated and take sex-specific recommendations into consideration.

DSM-5 Adult Attention-Deficit/Hyperactivity Disorder: Sex Differences in EEG Activity.

This study examined sex differences in the EEG of adults diagnosed with Attention-Deficit/Hyperactivity Disorder (AD/HD) according to DSM-5 criteria. Sixteen females and 16 males with AD/HD, and age- and sex-matched control groups, had an eyes-closed resting EEG recorded from 19 electrode sites. EEGs were Fast Fourier transformed and estimates for total power, absolute and relative power in the delta, theta, alpha, beta and gamma bands, and the theta/beta ratio, were analysed across nine cortical regions. Males with AD/HD, compared with male controls, had globally reduced absolute beta, globally elevated relative theta, and a larger theta/beta ratio. In contrast, no global effects emerged between females with and without AD/HD. Significant group interactions indicated that globally elevated relative theta and elevated frontal-midline theta/beta ratio noted in males with AD/HD differed significantly from results in females. There are statistically significant EEG differences in relative theta and the theta/beta ratio between males and females with and without AD/HD. These results indicate that AD/HD affects the EEG activity of males and females differently. This study helps confirm the need for further independent examination of AD/HD within female populations.