Mindfulness meditation alters neural oscillations independently of arousal.

Neuroscience has identified that mindfulness meditation induces a state of relaxed alertness, characterised by changes in theta and alpha oscillations and reduced sympathetic arousal, although the underlying mechanisms remain unclear. This study aims to address this gap by examining changes in neural oscillations and arousal during mindfulness meditation using both traditional and data-driven methods. Fifty-two healthy young adults underwent electroencephalography (EEG) and skin conductance level (SCL) recordings during resting baseline and mindfulness meditation conditions, both conducted with eyes closed. The EEG data revealed a significant decrease in traditional alpha (8-13 Hz) amplitude during mindfulness meditation compared to rest. However, no significant differences were observed between conditions in traditional delta, theta, beta, or gamma amplitudes. Frequency Principal Components Analysis (fPCA) was employed as a data-driven approach, identifying six components consistent across conditions. A complex delta-theta-alpha component significantly increased during mindfulness meditation. In contrast, low alpha (~9.5 Hz) and low alpha-beta (~11 Hz) components decreased significantly during mindfulness meditation. No significant differences were observed between conditions in the delta, high alpha, and high alpha-beta components. Additionally, there were no significant differences in SCL between conditions, nor were there correlations between traditional alpha or fPCA components and SCL. These findings support the conceptualisation of mindfulness meditation as a state of relaxed alertness, characterised by changes in neural oscillations likely associated with attention and awareness. However, the observed changes do not appear to be driven by arousal.

Global alpha power fluctuations in a self-caught mind-wandering paradigm are independent of arousal.

Mind-wandering is characterised as the emergence of thought and emotions which shift attention away from a primary task. It is thought to consume up to 50 % of our waking lives and has several negative implications. Breath-counting is one task that has been utilised in conjunction with electroencephalography (EEG) to examine the brain states associated with mind-wandering. Research has consistently found reductions in alpha oscillations during periods of mind-wandering relative to breath-focus. It is possible that such fluctuations reflect an arousal mechanism warranting further investigation. Thirty-seven participants completed a 15 min breath-counting task, with simultaneous recording of EEG and skin conductance level (SCL). During this task participants were required to self-identify periods of mind-wandering via button-press. Event-related spectral perturbation (ERSP) analysis was used to quantify changes in global alpha power (8-13 Hz) relative to the button press. The -8 to -4 s period prior to button-press was assessed as mind-wandering, and the 4 to 8 s period following the button-press as breath-focus. Relative to breath-focus, mind-wandering was associated with a significant decrease in global alpha power and significant increase in SCL, consistent with perceptual decoupling theory. However, changes in global alpha power and SCL did not correlate. These results suggest arousal is not the primary mechanism underlying alpha changes observed during breath-counting, thus additional processes should be considered.

Resuscitation on the field of play: a best-practice guideline from Resuscitation Council UK.

Sudden cardiac arrest (SCA) is the leading cause of sudden death in athletes during high-level, organised sport. Patient-related and event-related factors provide an opportunity for rapid intervention and the potential for high survival rates. The aim of this consensus was to develop a best-practice guideline for dedicated field-of-play medical teams responding to SCA during an organised sporting event. A task-and-finish group from Resuscitation Council UK identified a stakeholder group of relevant experts and cardiac arrest survivors in March and April 2022. Together, they developed a best-practice guideline using the best available evidence. A public consultation period further refined the guideline before it was finalised in December 2023. Any sudden collapse, without rapid recovery during sporting activity, should be considered an SCA until proven otherwise. Field-of-play medical teams should be empowered to access the collapsed athlete as soon as possible and perform initial essential interventions in situ. This includes a suggested minimum of three cycles of cardiopulmonary resuscitation and defibrillation in persistent shockable rhythms while other aspects of advanced life support are initiated. There should be careful organisation and practice of the medical response, including plans to transport athletes to dedicated facilities for definitive medical care. This best-practice guideline complements, rather than supersedes, existing resuscitation guidelines. It provides a clear approach to how to best treat an athlete with SCA and how to organise the medical response so treatments are delivered effectively and optimise outcomes.

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.

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.

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.

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.

Resting state EEG power research in Attention-Deficit/Hyperactivity Disorder: A review update.

This article reviews the eyes-open and eyes-closed resting electroencephalogram (EEG) literature for Attention-Deficit/Hyperactivity Disorder (AD/HD) from 2002 to 2019. This time has seen substantial increase in interest in resting state EEG, with investigations moving from a comparison of an AD/HD sample to a control group, to research investigating a wide range of theoretical and clinical aspects of the disorder. This has included investigations of subgroups based on their EEG profile, sex differences in the EEG, increasing interest in the EEG of adults, and the effects of comorbid disorders on the EEG of people with AD/HD. Research has further investigated the hyper- and hypo- arousal models of AD/HD, as well as the developmental deviation model. From a clinical perspective, a growing body of literature is emerging trying to ascertain if the EEG can be used as a diagnostic test, particularly the theta/beta ratio. While these advances have been made, there is widespread use of both the eyes-open and eyes-closed resting paradigms as being interchangeable, despite the two paradigms differ on a number of important factors. There is also lack of independent replication within the literature, which is needed to consolidate many of the findings that have been published.

Preferred EEG brain states at stimulus onset in normal ageing: Explorations in a fixed interstimulus interval Go/NoGo task.

Some 40 years ago, Erol Basar began an interesting line of brain dynamics research on the phase of oscillatory EEG activity. Stimuli presented at a fixed interstimulus interval (ISI) were reported to produce a "preferred phase angle" at stimulus onset in the ongoing EEG oscillations, so that cortical negativity occurred more often than expected. Our previous work has confirmed this phenomenon in young adults, and linked it to enhancements in stimulus-elicited ERP components and behaviour. The present study sought evidence for this phenomenon in older adults. Twenty healthy independent-living participants (5 males) aged 59.8 to 74.8 years (M = 68.2) completed a fixed ISI equiprobable auditory oddball task. EEG phases in four traditional bands were computed separately for each artefact-free Go and NoGo trial. These were used to group accepted trials according to the phase quartile at stimulus onset in each band, forming 16 mean ERPs for each participant at each phase quartile/band combination, separately for Go and NoGo. The 32 mean ERPs were decomposed by separate Principal Component Analyses, and the N1 and P3 components were examined as a function of EEG phase at stimulus onset in each band. Differential preferential occurrence of phase states was found in all bands, generally confirming prior results in young adults despite important age differences in both EEG spectra and ERP morphology. Substantial effects on N1 and P3 components, as well as prestimulus CNVs, are discussed. The stability of this phenomenon across age indicates its important role in perception and cognition.

Correction to: Development and Utility of an ELISA Method for Sensitive and Specific Detection of IgE Antidrug Antibodies.

During the production process, the author order of Zhandong Don Zhong and Lynn L. Jiang were inadvertently placed. Lynn L. Jiang is the first author of this manuscript; Zhandong Don Zhong is the last author.

Development and Utility of an ELISA Method for Sensitive and Specific Detection of IgE Antidrug Antibodies.

Biologics can potentially induce unwanted immune responses, leading to formation of antidrug antibodies (ADA) of various affinity, isotypes, and subclasses. Among them, antigen and drug-specific immunoglobulin E (IgE) antibodies have been reported to have potential correlation with hypersensitivity and anaphylaxis in particular. Recent regulatory guidance on immunogenicity testing has recommended the measurement of antigen-specific IgE antibodies for biologics with a reported high risk of anaphylaxis using assays with sensitivities in the high pg/mL to low ng/mL range. Nevertheless, IgE ADA remains challenging to detect due to their being the least abundant isotype in blood serum samples and the potential for interference in the bioanalytical methods due to high levels of endogenous immunoglobulin G (IgG) and immunoglobulin M (IgM) ADA, not to mention the nonspecific total serum IgE antibodies. Another challenge in developing IgE ADA assays is the need to create a surrogate drug-specific IgE antibody positive control to monitor the performance of the assay for the intended use. In this case study, utilizing a human IgE antidrug antibody positive control and a human IgE receptor as capture, an enzyme-linked immunosorbent assay (ELISA) method was developed for the measurement of IgE ADA, meeting the regulatory expectations, with excellent assay sensitivity, selectivity, specificity, and tolerance towards potential interference in serum samples. This assay format could be readily adapted and implemented to assess drug-specific IgE antibodies in the event of drug-related anaphylaxis in clinical and in nonclinical development programs.

Natural alpha frequency components in resting EEG and their relation to arousal.

OBJECTIVE: Global EEG alpha activity is negatively correlated with skin conductance level (SCL), supporting alpha as an inverse marker of arousal. Frequency Principal Components Analysis (f-PCA) of resting EEG amplitude spectra has demonstrated natural components in the alpha band of healthy persons. This is a preliminary exploration of whether such components differ with arousal, possibly underpinning the anomalous ADHD hypoarousal link to reduced alpha. METHOD: Twenty-seven right-handed undergraduate students participated in three 2 minute blocks of resting eyes-open/closed EEG and SCL: EO1, EC, EO2. For each condition, mean EEG spectra were submitted to separate f-PCAs. RESULTS: The inverse alpha/SCL relationship was confirmed for band amplitudes. EO had two alpha components; both correlated negatively with SCL. EC alpha contained four components, but only one had a substantial negative correlation with SCL; two had no relationship, suggesting natural alpha components with different non-arousal functionality in EC. CONCLUSION: Some alpha components in both EC and EO reflect arousal, with other non-arousal components in EC. Our f-PCA approach offers insight into previously-noted alpha anomalies in disorders such as ADHD. SIGNIFICANCE: This proof of concept demonstration in typical participants may provide the basis for a new research effort in clinical disorders involving atypical arousal patterns.

The Theta/Beta Ratio as an Index of Cognitive Processing in Adults With the Combined Type of Attention Deficit Hyperactivity Disorder.

An elevated theta/beta ratio in the EEG has long been observed among individuals with Attention Deficit Hyperactivity Disorder (ADHD). The theta/beta ratio was previously hypothesised to be an index of arousal, but a number of studies failed to find any association between the ratio and indices of arousal, instead proposing that the theta/beta ratio may actually be indicative of cognitive processing. This hypothesis was tested by Clarke et al using a sample of healthy adults, with results indicating that the theta/beta ratio correlated with a marker of cognitive processing (P300 latency in an auditory oddball task), while P300 amplitude correlated with an arousal marker (alpha power). The aim of this study was to test whether similar results could be found in a sample of 41 adults with the combined type of ADHD. EEGs were recorded during an eyes-closed resting condition and an auditory oddball task. Results demonstrated that the theta/beta ratio correlated significantly with P300 latency. Absolute alpha power did not correlate significantly with P300 amplitude or P300 latency. These results support the hypotheses that the theta/beta ratio is a marker of cognitive processing capacity in both the general population and in participants with ADHD, and that the alpha/arousal linkage is anomalous in ADHD.

Biphenyl Acid Derivatives as APJ Receptor Agonists.

The APJ receptor and its endogenous peptidic ligand apelin have been implicated as important modulators of cardiovascular function, and APJ receptor agonists may be beneficial in the treatment of heart failure. In this article, we describe the discovery of a series of biphenyl acid derivatives as potent APJ receptor agonists. Following the identification of initial high-throughput screen lead 2, successive optimization led to the discovery of lead compound 15a. Compound 15a demonstrated comparable in vitro potency to apelin-13, the endogenous peptidic ligand for the APJ receptor. In vivo, compound 15a demonstrated a dose-dependent improvement in the cardiac output in male Sprague Dawley rats with no significant changes in either mean arterial blood pressure or heart rate, consistent with the hemodynamic profile of apelin-13 in an acute pressure volume loop model.

EEG development in Attention Deficit Hyperactivity Disorder: From child to adult.

OBJECTIVE: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common psychiatric disorders found in children. While an extensive literature has documented the EEG in this clinical population, few studies have investigated EEG throughout the lifespan in ADHD. This study aimed to investigate EEG maturational changes, in subjects with ADHD combined type, that spanned from childhood into adulthood. METHOD: Twenty five male adults with ADHD were assessed between the ages of 8-12 years and again as adults. At both ages, an EEG was recorded during an eyes-closed resting period, and power estimates were calculated for relative delta, theta, alpha and beta. RESULTS: At the childhood assessment, the ADHD subjects had elevated posterior delta. Relative theta was elevated, with diminished alpha activity across all sites. Significant maturational changes were observed, with reductions in the delta and theta bands, and increases in the alpha and beta bands across all electrodes. In adulthood, relative to controls, diminished frontal delta and elevated global theta activity were apparent. CONCLUSIONS: Substantial developmental changes occurred in the EEG of these subjects. These results identify important issues when using EEG as part of the diagnosis for ADHD. SIGNIFICANCE: This study is the first to explore EEG changes from childhood to adulthood over an 11 year period in the same subjects with ADHD.

Higher Binding Affinity and in vitro Potency of Reslizumab for Interleukin-5 Compared With Mepolizumab.

Reslizumab and mepolizumab are recently approved monoclonal antibodies for the treatment of severe (uncontrolled) eosinophilic asthma. Both are effective in neutralizing the function of interleukin-5 (IL-5). This study is the first to compare the binding affinity and in vitro potency of both antibodies in head-to-head assays. Two assays assessed binding affinity (using the equilibrium dissociation constant [KD]) of each drug for human IL-5. In the Biacore surface plasmon resonance assay, the association constant (kon) values for human IL-5 for reslizumab and mepolizumab were 3.93 × 106 and 1.83 × 105, respectively. The dissociation constant (koff) values were 4.29 × 10⁻4 and 2.14 × 10⁻4, respectively. Calculated KD values for human IL-5 for reslizumab and mepolizumab were 109 and 1,170 pM, respectively, representing an approximately 11-fold stronger binding affinity with reslizumab. In the Kinetic Exclusion Assay, the kon values for human IL-5 for reslizumab and mepolizumab were 3.17 × 106 and 1.32 × 105, respectively. The koff values were 1.36 × 10⁻5 and 1.48 × 10⁻5, respectively. Measured KD values for human IL-5 for reslizumab and mepolizumab were 4.3 and 112 pM, respectively, representing an approximately 26-fold stronger binding affinity for reslizumab. A human-IL-5-dependent cell proliferation assay was developed to assess in vitro potency, based on a human cell line selected for enhanced surface expression of IL-5 receptor-alpha and consistent proliferation response to IL-5. The concentration at which 50% inhibition occurred (IC50) was determined for both antibodies. Reslizumab and mepolizumab inhibited IL-5-dependent cell proliferation, with IC50 values of approximately 91.1 and 286.5 pM, respectively, representing on average 3.1-fold higher potency with reslizumab. In conclusion, comparative assays show that reslizumab has higher affinity binding for and in vitro potency against human IL-5 compared with mepolizumab. However, these results do not take into consideration the different methods of administration of reslizumab and mepolizumab.

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.

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.

Beneficial Effects of Human Anti-Interleukin-15 Antibody in Gluten-Sensitive Rhesus Macaques with Celiac Disease.

Overexpression of interleukin-15 (IL-15) is linked with immunopathology of several autoimmune disorders including celiac disease. Here, we utilized an anti-human IL-15 antibody 04H04 (anti-IL-15) to reverse immunopathogenesis of celiac disease. Anti-IL-15 was administered to six gluten-sensitive rhesus macaques with celiac disease characteristics including gluten-sensitive enteropathy (GSE), and the following celiac-related metrics were evaluated: morphology (villous height/crypt depth ratio) of small intestine, counts of intestinal intraepithelial lymphocytes, IFN-γ-producing CD8+ and CD4+ T cells, plasma levels of anti-gliadin and anti-intestinal tissue transglutaminase IgG antibodies, as well as peripheral effector memory (CD3+CD28-CD95+) T cells. Anti-IL-15 treatment reversed the clinically relevant disease endpoints, intraepithelial lymphocyte counts, and villous height/crypt depth ratios within jejunal biopsies to normal levels (P < 0.001). Additionally, intestinal CD8+ and CD4+ T cell IFN-γ production was reduced (P < 0.05). Extra-intestinally, anti-IL-15 treatment reduced peripheral NK cell counts (P < 0.001), but otherwise, non-NK peripheral lymphocytes including effector memory T cells and serum blood chemistry were unaffected. Overall, providing the beneficial disease-modulatory and immunomodulatory effects observed, anti-IL-15 treatment might be considered as a novel therapy to normalize intestinal lymphocyte function in celiac disease patients with GSE.