Developmental Windows for Effects of Choline and Folate on Excitatory and Inhibitory Neurotransmission During Human Gestation.

Choline and folate are critical nutrients for fetal brain development, but the timing of their influence during gestation has not been previously characterized. At different periods during gestation, choline stimulation of α7-nicotinic receptors facilitates conversion of γ-aminobutyric acid (GABA) receptors from excitatory to inhibitory and recruitment of GluR1-R2 receptors for faster excitatory responses to glutamate. The outcome of the fetal development of inhibition and excitation was assessed in 159 newborns by P50 cerebral auditory-evoked responses. Paired stimuli, S1, S2, were presented 500 msec apart. Higher P50 amplitude in response to S1 (P50S1microV) assesses excitation, and lower P50S2microV assesses inhibition in this paired-stimulus paradigm. Development of inhibition was related solely to maternal choline plasma concentration and folate supplementation at 16 weeks' gestation. Development of excitation was related only to maternal choline at 28 weeks. Higher maternal choline concentrations later in gestation did not compensate for earlier lower concentrations. At 4 years of age, increased behavior problems on the Child Behavior Checklist 1½-5yrs were related to both newborn inhibition and excitation. Incomplete development of inhibition and excitation associated with lower choline and folate during relatively brief periods of gestation thus has enduring effects on child development.

Effects of Baduanjin practice on emotional, attention and cognitive function in acupuncturists: protocol for a clinical randomized controlled neuroimaging trial.

Background: In Chinese medicine, the mental focus and emotional stability of acupuncturists are key to optimal clinical outcomes. Many renowned acupuncturists utilize Traditional Chinese Qigong practices to enhance their concentration and emotional regulation abilities. Nevertheless, the existing literature lacks comprehensive evidence addressing this matter. Methods: This study will enroll 99 acupuncturists and randomly allocate them to one of three groups: Baduanjin, aerobic exercise, or a waiting-list control. The Baduanjin group will undertake 24 weeks of training, with three one-hour sessions weekly. The aerobic group will engage in brisk walking for the same duration and frequency. The control group will not receive any specific training. Assessments of emotion regulation, attention, cognitive functions, finger sensation, and athletic ability will be conducted at baseline (-1 week), mid-intervention (12 weeks), and post-intervention (24 weeks). Additionally, 20 participants from each group will undergo fMRI scans before and after the intervention to explore brain functional and structural changes relating to emotion, attention, cognition, motor skills, and sensory perception. Discussion: This study aims to contribute valuable insights into the effectiveness of Qigong practice, specifically Baduanjin, in enhancing emotional regulation, attention, and cognitive functions in acupuncturists and to investigate the neuroimaging mechanisms behind these effects. Ethics and dissemination: Approved by the Sichuan Regional Ethics Review Committee on Traditional Chinese Medicine (No. 2023KL - 118) and adhering to the Declaration of Helsinki. Results will be shared through policy briefs, workshops, peer-reviewed journals, and conferences.Clinical trial registrationwww.chictr.org.cn, ChiCTR2300076447.

Bright light therapy versus physical exercise to prevent co-occurring depression in adolescents and young adults with attention-deficit/hyperactivity disorder: a multicentre, three-arm, randomised controlled, pilot phase-IIa trial.

Depression is common in attention-deficit/hyperactivity disorder (ADHD), but preventive behavioural interventions are lacking. This randomised controlled, pilot phase-IIa trial aimed to study a physical exercise intervention (EI) and bright light therapy (BLT)-both implemented and monitored in an individual, naturalistic setting via a mobile health (m-health) system-for feasibility of trial design and interventions, and to estimate their effects on depressive symptoms in young people with ADHD. Two hundred seven participants aged 14-45 years were randomised to 10-week add-on intervention of either BLT (10,000 lx; daily 30-min sessions) (n = 70), EI (aerobic and muscle-strengthening activities 3 days/ week) (n = 69), or treatment-as-usual (TAU) (n = 68), of whom 165 (80%) were retained (BLT: n = 54; EI: n = 52; TAU: n = 59). Intervention adherence (i.e. ≥ 80% completed sessions) was very low for both BLT (n = 13, 22%) and EI (n = 4, 7%). Usability of the m-health system to conduct interventions was limited as indicated by objective and subjective data. Safety was high and comparable between groups. Changes in depressive symptoms (assessed via observer-blind ratings, Inventory of Depressive Symptomatology) between baseline and end of intervention were small (BLT: -0.124 [95% CI: -2.219, 1.971], EI: -2.646 [95% CI: -4.777, -0.515], TAU: -1.428 [95% CI: -3.381, 0.526]) with no group differences [F(2,153) = 1.45, p = 0.2384]. These findings suggest that the m-health approach did not achieve feasibility of EI and BLT in young people with ADHD. Prior to designing efficacy studies, strategies how to achieve high intervention adherence should be specifically investigated in this patient group. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03371810, 13 December 2017.

Rising Trends of Childhood Attention-Deficit/Hyperactivity Disorder in a Large Integrated Healthcare Delivery System in Southern California, 2010-2021.

OBJECTIVE: To evaluate trends of attention-deficit/hyperactivity disorder (ADHD) diagnosis rates among children aged 5-17 years over the past decade (2010-2021) and to investigate whether there have been differences in temporal changes based on race and ethnicity, sex, or income. STUDY DESIGN: Childhood ADHD diagnosis was ascertained from electronic health records using International Classification of Diseases ninth revision (314.xx) and International Classification of Diseases tenth revision (F90.x) codes. Data were stratified by child's sex, race and ethnicity, and household income, and rates of ADHD were estimated before and after adjustment for potential confounders. RESULTS: The overall ADHD diagnosis rates increased from 3.5% in 2010 to 4.0% in 2021. ADHD diagnosis was most prevalent among White children (6.1%), then Black (4.6%), Other/multiple (3.7%), Hispanic (3.1%), and Asian/Pacific Islander (PI) (1.7%). ADHD was also highly prevalent among boys (73.3%) or family income≥$70,000 (50.0%). ADHD diagnosis increased among Black (4.2% to 5.1%), Hispanic (2.8% to 3.6%), and Asian/PI children (1.5% to 2.0%) but remained stable for White (6.2% to 6.1%) and Other/multiple race/ethnic children (3.7% to 3.7%). Increases in the prevalence among girls were also observed. CONCLUSION: The prevalence of ADHD in children has risen with the largest increases observed for Black, Hispanic, and Asian/PI children. Rates among less affluent families and girls have also been increasing, narrowing the gaps in diagnosis rates previously observed. These increases may reflect improvements in screening and provision of care among demographics where ADHD has been historically underdiagnosed.

Functional contribution of the intestinal microbiome in autism spectrum disorder, attention deficit hyperactivity disorder, and Rett syndrome: a systematic review of pediatric and adult studies.

Introduction: Critical phases of neurodevelopment and gut microbiota diversification occur in early life and both processes are impacted by genetic and environmental factors. Recent studies have shown the presence of gut microbiota alterations in neurodevelopmental disorders. Here we performed a systematic review of alterations of the intestinal microbiota composition and function in pediatric and adult patients affected by autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and Rett syndrome (RETT). Methods: We searched selected keywords in the online databases of PubMed, Cochrane, and OVID (January 1980 to December 2021) with secondary review of references of eligible articles. Two reviewers independently performed critical appraisals on the included articles using the Critical Appraisal Skills Program for each study design. Results: Our systematic review identified 18, 7, and 3 original articles describing intestinal microbiota profiles in ASD, ADHD, and RETT, respectively. Decreased Firmicutes and increased Bacteroidetes were observed in the gut microbiota of individuals affected by ASD and ADHD. Proinflammatory cytokines, short-chain fatty acids and neurotransmitter levels were altered in ASD and RETT. Constipation and visceral pain were related to changes in the gut microbiota in patients affected by ASD and RETT. Hyperactivity and impulsivity were negatively correlated with Faecalibacterium (phylum Firmicutes) and positively correlated with Bacteroides sp. (phylum Bacteroidetes) in ADHD subjects. Five studies explored microbiota-or diet-targeted interventions in ASD and ADHD. Probiotic treatments with Lactobacillus sp. and fecal microbiota transplantation from healthy donors reduced constipation and ameliorated ASD symptoms in affected children. Perinatal administration of Lactobacillus sp. prevented the onset of Asperger and ADHD symptoms in adolescence. Micronutrient supplementation improved disease symptomatology in ADHD without causing significant changes in microbiota communities' composition. Discussion: Several discrepancies were found among the included studies, primarily due to sample size, variations in dietary practices, and a high prevalence of functional gastrointestinal symptoms. Further studies employing longitudinal study designs, larger sample sizes and multi-omics technologies are warranted to identify the functional contribution of the intestinal microbiota in developmental trajectories of the human brain and neurobehavior. Systematic review registration: https://clinicaltrials.gov/, CRD42020158734.

The effects of neurofeedback training for children with cerebral palsy and co-occurring attention deficits: A pilot study.

BACKGROUND: Limited research exists regarding the effectiveness of electroencephalogram (EEG) neurofeedback training for children with cerebral palsy (CP) and co-occurring attention deficits (ADs), despite the increasing prevalence of these dual conditions. This study aimed to fill this gap by examining the impact of neurofeedback training on the attention levels of children with CP and AD. METHODS: Nineteen children with both CP and co-occurring ADs were randomly assigned to either a neurofeedback or control group. The neurofeedback group received 20 sessions of training, lasting approximately 1 h per day, twice a week. Theta/beta ratios of the quantitative electroencephalography (QEEG) recordings were measured pre-training and post-training in the resting state. The Continuous Performance Test (CPT), the Test of Visual Perceptual Skills-3rd Version (TVPS-3) and the Conners' Parent Rating Scale (CPRS) were measured at pre- and post-training. RESULTS: The neurofeedback group showed both decreased theta/beta ratios compared with control group (p = 0.04) at post-training and a within-group improvement during training (p = 0.02). Additionally, the neurofeedback group had a trend of decreased omission rates of the CPT (p = 0.08) and the visual sequential memory and the visual closure subscores in the TVPS-3, compared with the control group (p = 0.02 and p = 0.01, respectively). CONCLUSIONS: The results suggested that children with CP and co-occurring AD may benefit from neurofeedback training in their attention level. Further research is needed to explore long-term effects and expand its application in this population.

Are Sleep Aids Associated with the Severity of Attention Deficit Hyperactivity Disorder Symptoms in Adults Screened for Insomnia? A Cross-Sectional Study.

(1) Background: Attention Deficit Hyperactivity Disorder (ADHD)-like symptoms and insomnia are closely related. The present study examined whether the use of different sleep aids was related to severe ADHD-like symptoms in Jordanian adults screened for insomnia. (2) Methods: This cross-sectional study used predefined inclusion criteria. The severity of ADHD was assessed using the validated Arabic version of the Adult ADHD Self-Report Scale. (3) Results: Data were analyzed from 244 subjects who met the inclusion criteria for severe insomnia, of which 147 (65.3%) reported not using any sleep aid, 50 (22.3%) reported using homeopathy remedies as sleep aids, and 41 (18.3%) reported using over-the-counter antihistamines as sleep aids. Regression analysis revealed that the use of such sleep aids-namely, "homeopathy herbal remedies" and "over-the-counter antihistamines"-was not associated (p > 0.05) with ADHD-like symptoms. However, "age above 31 years old" was significantly associated (B = -3.95, t = -2.32, p = 0.002) with lower ADHD severity, while the "diagnosis with chronic diseases" was significantly associated (B = 4.15, t = 1.99, p = 0.04) with higher ADHD severity. (4) Conclusions: Sleep aids are not associated with ADHD-like symptoms in adults. More research is required to uncover the risk factors for adult ADHD, especially insomnia.

Comparative Pharmacokinetics Research of 13 Bioactive Components of Jieyu Pills in Control and Attention Deficit Hyperactivity Disorder Model Rats Based on UPLC-Orbitrap Fusion MS.

Jieyu Pills (JYPs), a Chinese medicine consisting of 10 herbal elements, have displayed promising clinical effectiveness and low by-effects in the treatment of depression. Prior investigations mostly focused on elucidating the mechanism and therapeutic efficacy of JYPs. In our earlier study, we provided an analysis of the chemical composition, serum pharmacochemistry, and concentrations of the main bioactive chemicals found in JYPs. However, our precise understanding of the pharmacokinetics and metabolism remained vague. This study involved a comprehensive and meticulous examination of the pharmacokinetics of 13 bioactive compounds in JYPs. Using UPLC-Orbitrap Fusion MS, we analyzed the metabolic characteristics and established the pharmacokinetic parameters in both control rats and model rats with attention deficit hyperactivity disorder (ADHD) following oral administration of the drug. Before analysis, plasma samples that were collected at different time intervals after the administration underwent methanol pre-treatment with Puerarin used as the internal standard (IS) solution. Subsequently, the sample was chromatographed on a C18 column employing gradient elution. The mobile phase consisted of methanol solution containing 0.1% formic acid in water. The electrospray ionization source (ESI) was utilized for ionization, whereas the scanning mode employed was selected ion monitoring (SIM). The UPLC-Orbitrap Fusion MS method was subjected to a comprehensive validation process to assess its performance. The method demonstrated excellent linearity (r ≥ 0.9944), precise measurements (RSD < 8.78%), accurate results (RE: -7.88% to 8.98%), and appropriate extraction recoveries (87.83-102.23%). Additionally, the method exhibited minimal matrix effects (87.58-101.08%) and satisfactory stability (RSD: 1.52-12.42%). These results demonstrated adherence to the criteria for evaluating and determining biological material. The 13 bioactive compounds exhibited unique pharmacokinetic patterns in vivo. In control rats, all bioactive compounds except Ferulic acid exhibited linear pharmacokinetics within the dose ranges. In the ADHD model, the absorption rate and amount of most of the components were both observed to have increased. Essentially, this work is an important reference for examining the metabolism of JYPs and providing guidelines for clinical therapy.

Four weeks of meditation training improves sustained attention in community-dwelling older adults: a proof-of-concept randomized controlled trial.

Introduction: With our rapidly expanding population of older adults, identifying effective intervention strategies to improve cognitive functioning is an increasing priority. This study sought to examine whether 4 weeks of thrice-weekly meditation training can improve attention in older adults, as well as whether such benefits may extend to other domains of cognition as well as mobility. Methods: Forty-three participants (mean age 68 years) were randomized into either the focused attention meditation group or the music listening control group (Clinicaltrials.gov ID NCT03417635). Participants completed three 20-minute guided group sessions per week for four consecutive weeks. Our primary outcome measure was behavioural performance on the Sustained Attention to Response Task (SART). Secondary and tertiary outcome measures included event-related potentials (ERPs) during the SART task, measures of executive functioning, and measures of mobility. Results: We found that meditation training significantly improved attention, as demonstrated by improved SART accuracy and changes in N2 ERP amplitude and latency. Discussion: These findings suggest that meditation may lead to changes in attention and underlying cognitive processing in older adults, although a full-scale definitive trial is needed. Future research on the long-term benefits with real world applications is warranted.

Observation of human-animal interaction for research (OHAIRE) behavior coding in a randomized control trial of children with attention-deficit hyperactivity disorder (ADHD) and a canine-assisted intervention.

Introduction: Diagnosed in about 10% of children in the United States, attention-deficit hyperactivity disorder (ADHD) is characterized by symptoms including inattention, hyperactivity, and impulsivity. Traditional interventions, such as pharmacological and psychological interventions, are often used in conjunction with integrative health options, such as animal-assisted interventions. The objective of this manuscript is to report behavior coding findings from a randomized control trial of children with ADHD. Methods: As part of a larger randomized control trial focused on the efficacy of combining a canine-assisted intervention (live therapy dog or control stuffed dog) with cognitive behavioral therapy for children with ADHD, the current manuscript focuses on video-captured behavior observations (n = 35 children, approximately 322 minutes of data). Data were extracted and coded using the Observation of Human-Animal Interaction Research (OHAIRE) Coding System. Behavior codes are reported as summary scores for the following domains: animal social interaction and human social interaction (further separated into human-adult social interaction and human-peer social interaction). Repeated measures mixed models analyses were performed using SAS PROC GLIMMIX to evaluate group differences and change across the study period. Results: There were no significant differences in how much children interacted with the live therapy dogs versus control stuffed dogs. With respect to human-to-human social interactions, children showed greater increases over time in human-directed social interactions in the presence of live therapy dogs compared to stuffed dogs (p = .020). Over the course of the 12-week intervention, children increased in interactions with both adults (p = .006) and their peers (p = .014); however, there were more increases over time in adult-directed social interactions in the live animal condition compared to the control stuffed animal condition (p < 0.0001). Discussion & conclusions: Findings suggest changes in social interaction when participating in this canine-assisted intervention, specifically greater increases in human-to-human social interactions over time when a live therapy dog is present compared to a control stuffed dog. Children appear to engage relatively equally with both live and stuffed dogs; however, the impact of animals on human socialization differs based on if a live animal is present. Future studies should consider incorporating behavior coding analysis into studies of canine-assisted interventions to identify how human-animal interactions may be moderators or mechanisms for psychosocial outcomes.

Detecting mental and physical disorders using multi-task learning equipped with knowledge graph attention network.

Mental and physical disorders (MPD) are inextricably linked in many medical cases; psychosomatic diseases can be induced by mental concerns and psychological discomfort can ensue from physiological diseases. However, existing medical informatics studies focus on identifying mental or physical disorders from a unilateral perspective. Consequently, no existing domain knowledge base, corpus, or detection modeling approach considers mental as well as physical aspects concurrently. This paper proposes a joint modeling approach to detect MPD. First, we crawl through online medical consultation records of patients from websites and build an MPD knowledge ontology by extracting the core conceptual features of the text. Based on the ontology, an MPD knowledge graph containing 12,673 nodes and 82,195 relations is obtained using term matching with a domain thesaurus of each concept. Subsequently, an MPD corpus with fine-grained severities (None, Mild, Moderate, Severe, Dangerous) and 8909 records is constructed by formulating MPD classification criteria and a data annotation process under the guidance of domain experts. Taking the knowledge graph and corpus as the dataset, we design a multi-task learning model to detect the MPD severity, in which a knowledge graph attention network (KGAT) is embedded to better extract knowledge features. Experiments are performed to demonstrate the effectiveness of our model. Furthermore, we employ ontology-based and centrality-based methods to discover additional potential inferred knowledge, which can be captured by KGAT so as to improve the prediction performance and interpretability of our model. Our dataset has been made publicly available, so it can be further used as a medical informatics reference in the fields of psychosomatic medicine, psychiatrics, physical co-morbidity, and so on.

Corrigendum: Phytotherapy for attention deficit hyperactivity disorder (ADHD): a systematic review and meta-analysis.

[This corrects the article DOI: 10.3389/fphar.2022.827411.].

GraphormerDTI: A graph transformer-based approach for drug-target interaction prediction.

The application of Artificial Intelligence (AI) to screen drug molecules with potential therapeutic effects has revolutionized the drug discovery process, with significantly lower economic cost and time consumption than the traditional drug discovery pipeline. With the great power of AI, it is possible to rapidly search the vast chemical space for potential drug-target interactions (DTIs) between candidate drug molecules and disease protein targets. However, only a small proportion of molecules have labelled DTIs, consequently limiting the performance of AI-based drug screening. To solve this problem, a machine learning-based approach with great ability to generalize DTI prediction across molecules is desirable. Many existing machine learning approaches for DTI identification failed to exploit the full information with respect to the topological structures of candidate molecules. To develop a better approach for DTI prediction, we propose GraphormerDTI, which employs the powerful Graph Transformer neural network to model molecular structures. GraphormerDTI embeds molecular graphs into vector-format representations through iterative Transformer-based message passing, which encodes molecules' structural characteristics by node centrality encoding, node spatial encoding and edge encoding. With a strong structural inductive bias, the proposed GraphormerDTI approach can effectively infer informative representations for out-of-sample molecules and as such, it is capable of predicting DTIs across molecules with an exceptional performance. GraphormerDTI integrates the Graph Transformer neural network with a 1-dimensional Convolutional Neural Network (1D-CNN) to extract the drugs' and target proteins' representations and leverages an attention mechanism to model the interactions between them. To examine GraphormerDTI's performance for DTI prediction, we conduct experiments on three benchmark datasets, where GraphormerDTI achieves a superior performance than five state-of-the-art baselines for out-of-molecule DTI prediction, including GNN-CPI, GNN-PT, DeepEmbedding-DTI, MolTrans and HyperAttentionDTI, and is on a par with the best baseline for transductive DTI prediction. The source codes and datasets are publicly accessible at https://github.com/mengmeng34/GraphormerDTI.

Carbon reduction attention and financial market stress: A network spillover analysis based on quantile VAR modeling.

As climate change intensifies, attention to the issue of carbon emission reduction has gradually increased. This research constructs a complete set of indicators of carbon reduction attention and financial market stress and applies the quantile VAR method to calculate the volatility spillover between carbon reduction attention and financial market stress. We conclude with the following. Firstly, a relatively close volatility spillover association exists between carbon reduction attention and financial market stress. In the research system, carbon reduction attention mainly assumes the role of information receiver. Additionally, when examining the spillover status in different quantiles, the total spillover level shows an irregular "bowl" structure, while the net spillover level of each variable has different shapes. Secondly, the dynamic spillover level in the extreme quantile condition maintains a connectivity range of 60-80%, significantly higher than that of the median condition. Finally, this study finds two sets of significant complementary spillovers within the system, namely, "carbon reduction attention - crude oil market stress" and "stock market stress - real estate market stress", which provide investors with an opportunity to explore the potential of the carbon reduction attention and real estate market stress in the future.

Paying attention to attention: a program evaluation of faculty-delivered mindfulness-based attention training to optimize wellness and professionalism in medical students.

BACKGROUND: As physician distress rises, medical schools must provide programs to counter such distress at the earliest stages of training. Mindfulness training (MT) is one intervention that can alleviate stress during medical school. However, framing MT around wellness alone misses the opportunity to connect core cognitive and psychological capacities strengthened by MT to professional goals and skill acquisition inherent to successful medical training. Here, we highlight how the attentional components of MT align with students' goals of becoming attending physicians while promoting academic, psychological, and interpersonal flourishing. MT courses that focus on strengthening attentional capacities can intuitively link academic and professional development with wellness, appealing to a wide array of students. METHODS: We iteratively recontextualized an existing short-form mindfulness training program for high-stress pre-professionals, known as Mindfulness Based Attention Training (MBAT), to the medical school context (MBAT-Rx). MBAT-Rx was offered by physician trainers to first-year medical students at Warren Alpert Medical School of Brown University as a tool for improving study habits and focus in addition to the development of both self-care and patient care strategies. MBAT-Rx consists of weekly, two-hour sessions over four weeks, with 10-15 min of daily mindfulness practice between sessions. At the end of the four weeks, students submitted voluntary program evaluation responses detailing their experience of the program. RESULTS: Optional program evaluation responses (n = 67) highlight that students found the program to be useful for their academic success and ability to pay attention, their interpersonal relationships, and their psychological health. By framing MT as an opportunity to boost core attentional capacities and connecting this to professional and academic goals in addition to wellness, MBAT-Rx appealed to a wide variety of students. CONCLUSIONS: Our ongoing work suggests that framing MT as both a professional development and wellness promotion tool, taught by physicians themselves, and structured around students' time demands, may be a successful model for medical schools looking to increase the impact of their mindfulness offerings. Such programs are needed to equip medical students to navigate the demands of a challenging healthcare training landscape.

Altered hierarchical auditory predictive processing after lesions to the orbitofrontal cortex.

Orbitofrontal cortex (OFC) is classically linked to inhibitory control, emotion regulation, and reward processing. Recent perspectives propose that the OFC also generates predictions about perceptual events, actions, and their outcomes. We tested the role of the OFC in detecting violations of prediction at two levels of abstraction (i.e., hierarchical predictive processing) by studying the event-related potentials (ERPs) of patients with focal OFC lesions (n = 12) and healthy controls (n = 14) while they detected deviant sequences of tones in a local-global paradigm. The structural regularities of the tones were controlled at two hierarchical levels by rules defined at a local (i.e., between tones within sequences) and at a global (i.e., between sequences) level. In OFC patients, ERPs elicited by standard tones were unaffected at both local and global levels compared to controls. However, patients showed an attenuated mismatch negativity (MMN) and P3a to local prediction violation, as well as a diminished MMN followed by a delayed P3a to the combined local and global level prediction violation. The subsequent P3b component to conditions involving violations of prediction at the level of global rules was preserved in the OFC group. Comparable effects were absent in patients with lesions restricted to the lateral PFC, which lends a degree of anatomical specificity to the altered predictive processing resulting from OFC lesion. Overall, the altered magnitudes and time courses of MMN/P3a responses after lesions to the OFC indicate that the neural correlates of detection of auditory regularity violation are impacted at two hierarchical levels of rule abstraction.

Non-pharmacological treatment of Attention Deficit Disorder with or without Hyperactivity (ADHD). Overview and report of the first international symposium on the non-pharmacological management of ADHD.

Attention Deficit Disorder with or without Hyperactivity (ADHD is a neurodevelopmental disorder which affects the day-to-day functioning of children and adults with this condition. Pharmacological treatment can reduce the symptoms associated with ADHD, but it has some limitations. The objective of this symposium is to determine the effects of non-pharmacological approaches on ADHD symptoms. Results indicate that the following intervention are promising approaches: cognitive behavioral therapy (CBT), mindfulness-based interventions (MBI), yoga, cognitive and metacognitive intervention, neurofeedback and parental training programs. Current research advocates multimodal approaches in conjunction with school or work accommodations integrating innovative technologies.

Mindfulness meditation styles differently modulate source-level MEG microstate dynamics and complexity.

Background: The investigation of mindfulness meditation practice, classically divided into focused attention meditation (FAM), and open monitoring meditation (OMM) styles, has seen a long tradition of theoretical, affective, neurophysiological and clinical studies. In particular, the high temporal resolution of magnetoencephalography (MEG) or electroencephalography (EEG) has been exploited to fill the gap between the personal experience of meditation practice and its neural correlates. Mounting evidence, in fact, shows that human brain activity is highly dynamic, transiting between different brain states (microstates). In this study, we aimed at exploring MEG microstates at source-level during FAM, OMM and in the resting state, as well as the complexity and criticality of dynamic transitions between microstates. Methods: Ten right-handed Theravada Buddhist monks with a meditative expertise of minimum 2,265 h participated in the experiment. MEG data were acquired during a randomized block design task (6 min FAM, 6 min OMM, with each meditative block preceded and followed by 3 min resting state). Source reconstruction was performed using eLORETA on individual cortical space, and then parcellated according to the Human Connect Project atlas. Microstate analysis was then applied to parcel level signals in order to derive microstate topographies and indices. In addition, from microstate sequences, the Hurst exponent and the Lempel-Ziv complexity (LZC) were computed. Results: Our results show that the coverage and occurrence of specific microstates are modulated either by being in a meditative state or by performing a specific meditation style. Hurst exponent values in both meditation conditions are reduced with respect to the value observed during rest, LZC shows significant differences between OMM, FAM, and REST, with a progressive increase from REST to FAM to OMM. Discussion: Importantly, we report changes in brain criticality indices during meditation and between meditation styles, in line with a state-like effect of meditation on cognitive performance. In line with previous reports, we suggest that the change in cognitive state experienced in meditation is paralleled by a shift with respect to critical points in brain dynamics.

Maternal choline supplementation lessens the behavioral dysfunction produced by developmental manganese exposure in a rodent model of ADHD.

Studies in children have reported associations between elevated manganese (Mn) exposure and ADHD-related symptoms of inattention, impulsivity/hyperactivity, and psychomotor impairment. Maternal choline supplementation (MCS) during pregnancy/lactation may hold promise as a protective strategy because it has been shown to lessen cognitive dysfunction caused by numerous early insults. Our objectives were to determine whether (1) developmental Mn exposure alters behavioral reactivity/emotion regulation, in addition to impairing learning, attention, impulse control, and sensorimotor function, and (2) MCS protects against these Mn-induced impairments. Pregnant Long-Evans rats were given standard diet, or a diet supplemented with additional choline throughout gestation and lactation (GD 3 - PND 21). Male offspring were exposed orally to 0 or 50 mg Mn/kg/day over PND 1-21. In adulthood, animals were tested in a series of learning, attention, impulse control, and sensorimotor tasks. Mn exposure caused lasting dysfunction in attention, reactivity to errors and reward omission, learning, and sensorimotor function, recapitulating the constellation of symptoms seen in ADHD children. MCS lessened Mn-induced attentional dysfunction and partially normalized reactivity to committing an error or not receiving an expected reward but provided no protection against Mn-induced learning or sensorimotor dysfunction. In the absence of Mn exposure, MCS produces lasting offspring benefits in learning, attention, and reactivity to errors. To conclude, developmental Mn exposure produces a constellation of deficits consistent with ADHD symptomology, and MCS offered some protection against the adverse Mn effects, adding to the evidence that maternal choline supplementation is neuroprotective for offspring and improves offspring cognitive functioning.

Processing Speed and Attentional Shift/Mental Flexibility in Patients with Stroke: A Comprehensive Review on the Trail Making Test in Stroke Studies.

The Trail Making Test (TMT) is one of the most commonly administered tests in clinical and research neuropsychological settings. The two parts of the test (part A (TMT-A) and part B (TMT-B)) enable the evaluation of visuoperceptual tracking and processing speed (TMT-A), as well as divided attention, set-shifting and cognitive flexibility (TMT-B). The main cognitive processes that are assessed using TMT, i.e., processing speed, divided attention, and cognitive flexibility, are often affected in patients with stroke. Considering the wide use of TMT in research and clinical settings since its introduction in neuropsychological practice, the purpose of our review was to provide a comprehensive overview of the use of TMT in stroke patients. We present the most representative studies assessing processing speed and attentional shift/mental flexibility in stroke settings using TMT and applying scoring methods relying on conventional TMT scores (e.g., time-to-complete part A and part B), as well as derived measures (e.g., TMT-(B-A) difference score, TMT-(B/A) ratio score, errors in part A and part B). We summarize the cognitive processes commonly associated with TMT performance in stroke patients (e.g., executive functions), lesion characteristics and neuroanatomical underpinning of TMT performance post-stroke, the association between TMT performance and patients' instrumental activities of daily living, motor difficulties, speech difficulties, and mood statue, as well as their driving ability. We also highlight how TMT can serve as an objective marker of post-stroke cognitive recovery following the implementation of interventions. Our comprehensive review underscores that the TMT stands as an invaluable asset in the stroke assessment toolkit, contributing nuanced insights into diverse cognitive, functional, and emotional dimensions. As research progresses, continued exploration of the TMT potential across these domains is encouraged, fostering a deeper comprehension of post-stroke dynamics and enhancing patient-centered care across hospitals, rehabilitation centers, research institutions, and community health settings. Its integration into both research and clinical practice reaffirms TMT status as an indispensable instrument in stroke-related evaluations, enabling holistic insights that extend beyond traditional neurological assessments.