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.

Feed Intake as an Estimation of Attractability in Pacific White Shrimp Litopenaeus vannamei.

A simple bioassay that quantifies feed intake as an estimation of relative attractability of feeds containing different ingredients in the Pacific white shrimp Litopenaeus vannamei is described. Fish meal (FM), fish protein hydrolysate (FPH), squid meal (SqM) and casein (CN) were assessed at the same dietary level for their relative influence on feed intake rates of Litopenaeus vannamei. A bland diet containing 92% whole wheat grain meal, 6% diatomaceous earth and 2% alginate with a known low attractability was used as the standard control or base diet. Ingredients were added to the bland base control diet at a level of 3% as fed. Shrimp were stocked into 80 L glass tanks (n= 20 per tank) in a recirculating aquaculture system. Tanks were randomly assigned to one of five diet treatments (3tanks/treatment). Experiments measuring the attractability of each feed were conducted twice daily at 0900 hours and 1330 hours over a five day period. For each experiment, 40 feed pellets (ca. 1 g) corresponding to the assigned treatment were provided to each tank. To calculate the rate of feed intake, pellets remaining in each tank were counted at six minute intervals for a seventy-two minute period. Differences in rate of feed intake among diets were evaluated using Cox Regression Analysis. This attractability assay required only small amounts of ingredients and incorporated ingredients into a bland feed, which significantly reduces the influence from other ingredients or compound in the pellets. All of the test protein ingredients, especially SqM, in the feeds significantly increased the feed consumption rate. The diet containing SqM was consumed at a significantly higher rate than those containing casein and FM but not FPH. FPH and CN containing diets were not significantly different but consumed at a higher rate than the diet containing FM. Results of these trials indicate that the presence of certain ingredients can increase feed intake, thereby increasing nutrient availability of the diets. This reported method to determine consumption of diets containing certain ingredients can be considered as a valid method to estimate attractability.

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.

Interrogating the Relationship Between Schizotypy, the Catechol-O-Methyltransferase (COMT) Val158Met Polymorphism, and Neuronal Oscillatory Activity.

The COMT Val158Met polymorphism affects the availability of synaptic dopamine in the prefrontal cortex and has been widely studied as a genetic risk factor for psychosis. Schizotypy is associated with an increased risk of psychosis, with some studies implicating similar neurobiological mechanisms to schizophrenia. The present study sought to interrogate the link between the COMT Val158Met polymorphism and schizotypy using electroencephalogram (EEG) to identify neurophysiological mechanisms underpinning psychosis risk. Neurotypical (N = 91) adults were genotyped for the COMT Val158Met polymorphism, completed the Schizotypal Personality Questionnaire (SPQ), and had eyes open resting-state EEG recorded for 4 min. SPQ suspiciousness subscale scores were higher for individuals homozygous for Val/Val and Met/Met versus Val/Met genotypes. Delta, theta, alpha-2, beta-1, and beta-2 amplitudes were lower for Val/Val than Met/Met individuals. Lower theta amplitudes were correlated with higher total SPQ scores (P = 0.050), and multiple regression revealed that higher delta, and lower theta and beta-2 amplitudes (but not COMT genotype) best predicted total SPQ scores (P = 0.014). This study demonstrates the importance of COMT genotype in determining trait suspiciousness and EEG oscillatory activity. It also highlights relationships between dopaminergic alterations, EEG and schizotypy that are dissimilar to those observed in schizophrenia.

Time Effects on Resting EEG in Children With/Without AD/HD.

In this study we extend on behavioural evidence to examine the effect of time on EEG measures related to arousal and emotion/motivation in children with/without AD/HD. Thirty children with AD/HD and 30 age- and sex-matched controls participated. EEG was recorded during an eyes-closed resting condition and divided into three 2.5 min blocks after pre-processing. Time effects for absolute and relative alpha activity were found in healthy controls; these effects did not interact with AD/HD status. Interactions between time and AD/HD status were found for absolute theta, relative theta, and theta/beta ratio (TBR), with these EEG indices increasing over time in children with AD/HD. Moreover, IQ played a role in the interaction between time and AD/HD status. These results are consistent with predictions from both the optimal stimulation model and the delay aversion model, and suggest important methodological considerations for future EEG research in children with/without AD/HD.

The EEG Theta/Beta Ratio: A marker of Arousal or Cognitive Processing Capacity?

Attention-Deficit/Hyperactivity Disorder (AD/HD) is the most common psychiatric disorder of childhood and has been extensively researched using EEG technology. Within this literature, one of the most widely examined measures has been the theta/beta ratio. The theta/beta ratio was initially hypothesised to represent the arousal mechanism. However, subsequent research has shown this to be inaccurate and it was hypothesised that the ratio represents cognitive processing capacity. To examine that hypothesis, this study aimed to test the relationship between the P300 and the theta/beta ratio. The P300, absolute alpha and the theta/beta ratio were measured at Fz, Cz and Pz, and correlated in a group of 47 normal adults. A significant positive correlation was found between P300 latency and the theta/beta ratio. No relationship was found between P300 amplitude and the theta/beta ratio. P300 amplitude, but not latency, significantly correlated with alpha power. These results support the hypothesis that the theta/beta ratio is a marker of cognitive processing capacity.

Anti-tumour necrosis factor biological therapies for the treatment of uveitic macular oedema (UMO) for non-infectious uveitis.

BACKGROUND: Non-infectious uveitis describes a heterogenous group of ocular disorders characterised by intraocular inflammation in the absence of infection. Uveitis is a leading cause of visual loss, most commonly due to uveitic macular oedema (UMO). Treatment is aimed at reducing disease activity by suppression of the intraocular inflammatory response. In the case of macular oedema, the aim is to restore macular architecture as quickly as possible, in order to prevent irreversible photoreceptor damage in this area. Acute exacerbations are typically managed with corticosteroids, which may be administered topically, locally or systemically. Whilst these are often rapidly effective in achieving disease control, long-term use is associated with significant local and systemic side effects, and 'steroid sparing agents' are typically used to achieve prolonged control in severe or recalcitrant disease. Anti-tumour necrosis factor (TNF) drugs block a critical cytokine in the inflammatory signalling process, and have emerged as effective steroid-sparing immunomodulatory agents in a wide range of non-ocular conditions. There is mechanistic data to suggest that they may provide a more targeted approach to disease control in UMO than other agents, but to date, these agents have predominantly been used 'off label' as the majority are not licensed for ocular use. This review aims to summarise the available literature reporting the use of anti-TNF therapy in UMO, thus developing the evidence-base on which to make future treatment decisions and develop clinical guidelines in this area. OBJECTIVES: To assess the efficacy of anti-TNF therapy in treatment of UMO. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 2), which contains the Cochrane Eyes and Vision Trials Register; Ovid MEDLINE; Ovid Embase; LILACS; Web of Science Conference Proceedings Citation Index- Science (CPCI-S); System for Information on Grey Literature in Europe (OpenGrey); the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. The date of the search was 29 March 2018. SELECTION CRITERIA: We planned to include all relevant randomised controlled trials assessing the use of anti-TNF agents in treatment of UMO. No limits were applied to participant age, gender or ethnicity. The primary comparisons of this review were: anti-TNF versus no treatment or placebo; anti-TNF versus another pharmacological agent; comparison of different anti-TNF drugs; comparison of different doses and routes of administration of the same anti-TNF drug. The primary outcome measure that we assessed for this review was best-corrected visual acuity (BCVA) in the treated eye. Secondary outcome measures were anatomical macular change, clinical estimation of vitreous haze and health-related quality of life. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts retrieved through the database searches. We retrieved full-text reports of studies categorised as 'unsure' or 'include' after we had reviewed the abstracts. Two review authors independently reviewed each full-text report for eligibility. We resolved discrepancies through discussion. MAIN RESULTS: We identified no completed or ongoing trial that was eligible for this Cochrane Review. AUTHORS' CONCLUSIONS: Our review did not identify any evidence from randomised controlled trials for or against the role of anti-TNF agents in the management of UMO. Although there are a number of high-quality randomised controlled trials that demonstrate the efficacy of anti-TNF agents in preventing recurrence of inflammation in uveitis, the reported study outcomes do not include changes in UMO. As a result, there were insufficient data to conclude whether there was a significant treatment effect specifically for UMO. Future trials should be designed to include quantitative measures of UMO as primary study outcomes, for example by reporting the presence or absence of UMO, or by measuring central macular thickness for study participants. Furthermore, whilst UMO is an important complication of uveitis, we acknowledge that uveitis is associated with many significant structural and functional complications. It is not possible to determine treatment efficacy based on a single outcome measure. We recommend that future reviews of therapeutic interventions in uveitis should use composite measures of treatment response comprising a range of potential complications of disease.

Drug discovery in ophthalmology: past success, present challenges, and future opportunities.

BACKGROUND: Drug discovery has undergone major transformations in the last century, progressing from the recognition and refinement of natural products with therapeutic benefit, to the systematic screening of molecular libraries on whole organisms or cell lines and more recently to a more target-based approach driven by greater knowledge of the physiological and pathological pathways involved. Despite this evolution increasing challenges within the drug discovery industry are causing escalating rates of failure of development pipelines. DISCUSSION: We review the challenges facing the drug discovery industry, and discuss what attempts are being made to increase the productivity of drug development, including a refocusing on the study of the basic biology of the disease, and an embracing of the concept of 'translational research'. We consider what ophthalmic drug discovery can learn from the sector in general and discuss strategies to overcome the present limitations. This includes advances in the understanding of the pathogenesis of disease; improvements in animal models of human disease; improvements in ophthalmic drug delivery and attempts at patient stratification within clinical trials. As we look to the future, we argue that investment in ophthalmic drug development must continue to cover the whole translational spectrum (from 'bench to bedside and back again') with recognition that both biological discovery and clinical understanding will drive drug discovery, providing safe and effective therapies for ocular disease.

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.

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.

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.

Preferred pre-stimulus EEG states affect cognitive event-related potentials.

Current views of the genesis of the event-related potential (ERP) emphasize the contribution of ongoing oscillations - the ongoing electroencephalogram (EEG) is recognized as much more than "background noise" to be removed by response averaging to find the ERP. Early work from Basar's group noted that repetitive stimuli led to selective phase re-ordering of activity in the delta and alpha bands, such that enhanced brain negativity occurred at the time of the regular stimulus. Other work related negativity in alpha activity at stimulus onset to improved reaction times and ERP enhancements. These findings led us to begin a program of brain dynamics studies exploring pre-stimulus EEG phase states, their preferential occurrence in paradigms with regularly presented stimuli, and their relation to ERP outcomes. In particular, with very narrow EEG bands, we have repeatedly found that certain phase states preferentially occur at stimulus onset, implying ongoing phase re-ordering driven by stimulus occurrence. Effects are weakened with slightly varying inter-stimulus intervals, but still occur reliably. Further, these preferential phase states are functionally effective in relation to the ERP correlates of efficient stimulus processing. Preferential phase occurrence and their effects were originally reported in auditory oddball tasks, using narrow EEG bands derived by digital filtering. A recent study is presented illustrating generalization of the phenomenon in the auditory Go/NoGo task, using narrow bands derived by FFT techniques. Our current work is extending this research in normal children (to provide a comparative context for research in children with AD/HD), and well-functioning elderly (to provide a context for future work in relation to Alzheimer's disease).

Resting state brain oscillations and symptom profiles in attention deficit/hyperactivity disorder.

Our perspective on resting-state electroencephalogram (EEG) is that it provides a window into the substrate of cognitive and perceptual processing, reflecting the dynamic potential of the brain's current functional state. In an extended research program into the electrophysiology of attention deficit/hyperactivity disorder (AD/HD), we have examined resting-state EEG power and coherence, and event-related potentials (ERPs), in children, adolescents, and adults with the disorder. We sought initially to identify consistent AD/HD anomalies in these measures, relative to normal control subjects, and then to understand how these differences related to existing models of AD/HD. An emergent strand in this program has been to clarify the EEG correlates of "arousal" and to understand the role of arousal dysfunction as a core anomaly in AD/HD. To date, findings in this strand serve to rule out a commonly held dictum in the AD/HD field: that elevated theta/beta ratio is an indicator of hypo-arousal. In turn, this requires further work to elucidate the ratio's functional significance in the disorder. Our brain dynamics studies relating prestimulus EEG amplitude and phase states to ERP outcomes are expected to help in this regard, but we are still at a relatively early stage, currently examining these relationships in control children, in order to better understand normal aspects of brain dynamics before turning to children with AD/HD. This range of studies provides a framework for our recent work relating resting-state EEG anomalies, in individuals with AD/HD, to their symptom profile. This has had promising results, indicating links between increased inattention scores and reduced resting EEG gamma power. With resting-state EEG coherence, reduced left lateralized coherences across several bands have correlated negatively with inattention scores, while reduced frontal interhemispheric coherence has been correlated negatively with hyperactivity/impulsivity scores. Such linkages appear to provide encouraging leads for future EEG research in AD/HD.

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.

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.

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.

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.

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.

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.