Application of non-invasive neuromodulation in children with neurodevelopmental disorders to improve their sleep quality and constipation.

BACKGROUND: Children with neurodevelopmental disorders have a very wide clinical variability. A common prevalent factor is problems with stool and sleep quality. Currently, there are multiple studies related to their evaluation, but not so much related to a specific intervention. The aim was to evaluate the effectiveness and safety of the application of non-invasive neuromodulation as a treatment in children with neurodevelopmental disorders to improve constipation and quality of sleep. METHODS: A total of 23 minors aged between 2 and 16 were included in this cross-sectional study. All participants were applied the microcurrent device for 60 min, 3 times per week for a total of 4 weeks. The technique was based on non-invasive neuromodulation using a surface-applied microcurrent electrostimulation device that administers an external, imperceptible, pulsed electrical stimulation. It is applied to the extremities, in a coordinated manner, using gloves and anklets connected with electrodes to a control console. Sleep latency and microarousals were evaluated through a sleep diary. To assess the evolution and type of defecation, the adapted and validated version in Spanish of the Bristol Stool Form Scale was used. RESULTS: No adverse events occurred during the study and no incidences were registered. Clinically relevant improvements were registered in defecation frequency and type as well as in sleep related parameters. An increase in the hours of sleep was registered, from 7,35 (0,83) to 9,09 (1,35), and sleep interruptions decreased from 3,83 (1,95) to 1,17 (1,11), (p < .001). CONCLUSION: Microcurrents can be used as an effective and safe treatment to improve quality of sleep and constipation in children with neurodevelopmental disorders. More studies are needed in order to obtain statistically significant results. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT05265702. FIRST REGISTRATION: 03/03/2022 PROTOCOL: https://clinicaltrials.gov/ct2/show/NCT05265702?term=baez+suarez&draw=2&rank=4.

Delivering paediatric precision medicine: Genomic and environmental considerations along the causal pathway of childhood neurodevelopmental disorders.

Precision medicine refers to treatments that are targeted to an individual's unique characteristics. Precision medicine for neurodevelopmental disorders (such as cerebral palsy, attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, Tourette syndrome, and autism spectrum disorder) in children has predominantly focused on advances in genomic sequencing technologies to increase our ability to identify single gene mutations, diagnose a multitude of rare neurodevelopmental disorders, and gain insights into pathogenesis. Although targeting specific gene variants with high penetrance will help some children with rare disease, this approach will not help most children with neurodevelopmental disorders. A 'pathway' driven approach targeting the cumulative influence of psychosocial, epigenetic, or cellular factors is likely to be more effective. To optimize the therapeutic potential of precision medicine, we present a biopsychosocial integrated framework to examine the 'gene-environment neuroscience interaction'. Such an approach would be supported through harnessing the power of big data, transdiagnostic assessment, impact and implementation evaluation, and a bench-to-bedside scientific discovery agenda with ongoing clinician and patient engagement. WHAT THIS PAPER ADDS: Precision medicine has predominantly focused on genetic risk factors. The impact of environmental risk factors, particularly inflammatory, metabolic, and psychosocial risks, is understudied. A holistic biopsychosocial model of neurodevelopmental disorder causal pathways is presented. The model will provide precision medicine across the full spectrum of neurodevelopmental disorders.

Using causal methods to map symptoms to brain circuits in neurodevelopment disorders: moving from identifying correlates to developing treatments.

A wide variety of model systems and experimental techniques can provide insight into the structure and function of the human brain in typical development and in neurodevelopmental disorders. Unfortunately, this work, whether based on manipulation of animal models or observational and correlational methods in humans, has a high attrition rate in translating scientific discovery into practicable treatments and therapies for neurodevelopmental disorders.With new computational and neuromodulatory approaches to interrogating brain networks, opportunities exist for "bedside-to bedside-translation" with a potentially shorter path to therapeutic options. Specifically, methods like lesion network mapping can identify brain networks involved in the generation of complex symptomatology, both from acute onset lesion-related symptoms and from focal developmental anomalies. Traditional neuroimaging can examine the generalizability of these findings to idiopathic populations, while non-invasive neuromodulation techniques such as transcranial magnetic stimulation provide the ability to do targeted activation or inhibition of these specific brain regions and networks. In parallel, real-time functional MRI neurofeedback also allow for endogenous neuromodulation of specific targets that may be out of reach for transcranial exogenous methods.Discovery of novel neuroanatomical circuits for transdiagnostic symptoms and neuroimaging-based endophenotypes may now be feasible for neurodevelopmental disorders using data from cohorts with focal brain anomalies. These novel circuits, after validation in large-scale highly characterized research cohorts and tested prospectively using noninvasive neuromodulation and neurofeedback techniques, may represent a new pathway for symptom-based targeted therapy.

Hippotherapy in neurodevelopmental disorders: a narrative review focusing on cognitive and behavioral outcomes.

Hippotherapy (HT) is a rehabilitative tool inducing psychological and motor improvements using human-horse interaction. HT provides sensory stimulation to the rider through the rhythmic and repetitive movements of the horse, facilitating communication between patients and healthcare professionals, favoring the establishment of a therapeutic alliance. The purpose of this review is to evaluate the effects of HT treatment on cognitive-behavioral processes in neurodevelopmental disorders. We screened studies published between 2002 and 2020 on PubMed, Scopus, Cochrane, and Web of Sciences databases. The search combined the following terms: "hippotherapy"; "horseback riding"; "equine-assisted therapy"; "developmental disorder"; "autism spectrum disorder"; "dyspraxia"; "infantile cerebral palsy"; and "attention-deficit/hyperactivity disorder". This review shows that HT can be a valuable tool for the treatment of developmental disorders. The psychological, cognitive and relational areas could benefit from the animal-child interaction to promote child autonomy, self-esteem, self-efficacy and openness to others. Physical, motor and psychosocial benefits were found in adolescents with anxiety and/or depression disorders, in autism spectrum disorders, dyspraxia, as well as in infantile cerebral palsy and attention deficit hyperactivity disorder. HT could be considered an alternative therapeutic tool thanks to the relationship between patient-horse-instructor and to the sensory-motor and cognitive stimulation that enforce learning processes.

CRISPR/dCas9 as a Therapeutic Approach for Neurodevelopmental Disorders: Innovations and Limitations Compared to Traditional Strategies.

Brain development is a complex process that requires a series of precise and coordinated events to take place. When alterations in some of those events occur, neurodevelopmental disorders (NDDs) may appear, with their characteristic symptoms, including cognitive, social motor deficits, and epilepsy. While pharmacologic treatments have been the only therapeutic options for many years, more recently the research is turning to the direct removal of the underlying genetic cause of each specific NDD. This is possible thanks to the increased knowledge of genetic basis of those diseases and the enormous advances in genome-editing tools. Together with clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-based strategies, there is a great development also of nuclease defective Cas9 (dCas9) tools that, with an extreme flexibility, allow the recruitment of specific protein functions to the desired genomic sites. In this work, we review dCas9-based tools and discuss all the published applications in the setting of therapeutic approaches for NDDs at the preclinical level. In particular, dCas9-based therapeutic strategies for Dravet syndrome, transcallosal dysconnectivity caused by mutations in C11orf46 gene, and Fragile X syndrome are presented and discussed. A direct comparison with other possible therapeutic strategies, such as classic gene replacement or CRISPR/Cas9-based strategies, is provided. We also highlight not only those aspects that constitute a clear advantage compared to previous strategies but also the main technical hurdles related to their applications that need to be overcome.

The Importance of Marine Omega-3s for Brain Development and the Prevention and Treatment of Behavior, Mood, and Other Brain Disorders.

Most of the global population is deficient in long-chain marine omega-3s. In particular, docosahexaenoic acid (DHA), a long-chain omega-3 fatty acid, is important for brain and eye development. Additionally, DHA plays a significant role in mental health throughout early childhood and even into adulthood. In the brain, DHA is important for cellular membrane fluidity, function and neurotransmitter release. Evidence indicates that a low intake of marine omega-3s increases the risk for numerous mental health issues, including Attention Deficit Hyperactivity Disorder (ADHD), autism, bipolar disorder, depression and suicidal ideation. Studies giving supplemental marine omega-3s have shown promise for improving numerous mental health conditions. This paper will review the evidence surrounding marine omega-3s and mental health conditions.

Caring for children with neurodevelopmental disability: Experiences from caretakers and health workers in rural eastern Uganda.

BACKGROUND: Long term outcomes of children with neurodevelopmental disability are influenced by the condition itself, available health services and caretakers' coping ability to nurture the children which may be related to their beliefs and experiences. Most children with neurodevelopmental disabilities live in resource constrained settings. To inform design of contextually appropriate interventions, this study explored health workers' and caretakers' experiences in caring for infants with neurodevelopmental disability in rural eastern Uganda. METHODS: A qualitative case study was carried out in December 2017 and involved in-depth interviews with 14 caretakers of infants with severe neurodevelopmental disability, and five health workers in Iganga/Mayuge Demographic Surveillance Site in eastern Uganda. The interviews with caretakers were conducted in Lusoga, the local language, and in English for the health workers, using a pre-determined open-ended interview guide. Data were analyzed using latent content analysis. RESULTS: Caretakers described the experience of caring for children with neurodevelopmental disability as impoverishing and 'imprisoning' due to high care costs, inability to return to income generating activities and nursing challenges. The latter resulted from failure in body control and several aspects of nutrition and maintaining vital functions, coupled with limited support from the community and the health system. Many caretakers expressed beliefs in supernatural causes of neurodevelopmental disability though they reported about complications during and shortly after the birth of the affected child. Care-seeking was often challenging and impeded by costs and the feeling of lack of improvement. The health care system was also found to be incapable of adequately addressing the needs of such children due to lack of commodities, and human resource limitations. CONCLUSION: The caretakers expressed a feeling of emotional stress due to being left alone with a high nursing burden. Improvement in the health services including a holistic approach to care, improved community awareness and parental support could contribute to nursing of children with NDD.

An Integrative Review of Non-Pharmacological Therapeutic Interventions in Children with Mental Health Problems.

We provide an integrative review of non-pharmacological interventions for children with mental health problems. A total of 262 studies were found in three databases, of which 12 met the inclusion criteria, indicating a shortage of research on the subject. The most frequently used type of intervention was cognitive-behavioural therapy-based interventions, and attention deficit hyperactivity disorder was the most frequent problem. Non-pharmacological interventions help to improve the symptoms of childhood mental health problems, so there is a need to carry out further research on this issue in Brazil and the rest of Latin America.

Psychological treatment strategies for challenging behaviours in neurodevelopmental disorders: what lies beyond a purely behavioural approach?

PURPOSE OF REVIEW: Challenging behaviour shown by individuals with neurodevelopmental disorders (NDDs) has a major negative impact. There is robust evidence for the efficacy of treatments based on applied behaviour analysis. However, such approaches are limited in important ways - providing only part of the whole solution. We reviewed the literature to provide an overview of recent progress in psychological treatments for challenging behaviour and how these advance the field beyond a purely behavioural approach. RECENT FINDING: We identified 1029 articles via a systematic search and screened for those implementing a psychological intervention with individuals with NDD (or caregivers) and measuring the potential impact on challenging behaviour. Of the 69 included studies published since 2018, more than 50% implemented a purely behavioural intervention. Other studies could generally be categorized as implementing parent training, meditation, skill training or technology-assisted interventions. SUMMARY: Greater consideration of the interplay between behavioural and nonbehavioural intervention components; systematic approaches to personalization when going beyond the behavioural model; mental health and broad social communication needs; and models that include cognitive and emotional pathways to challenging behaviour; is needed to advance the field. Furthermore, technology should not be overlooked as an important potential facilitator of intervention efforts.

Effect of prebiotic and probiotic supplementation on neurodevelopment in preterm very low birth weight infants: findings from a meta-analysis.

BACKGROUND: Preterm very low birth weight (VLBW) infants are at risk of gut dysbiosis and neurodevelopmental deficits. Prebiotics and probiotics may modulate gut microbiota and influence brain functions. This review synthesizes literature on effect of prebiotic and/or probiotic supplementation in preterm VLBW on their neurodevelopmental outcomes. METHODS: Search was done using PubMed and CENTRAL. Randomized controlled trials (RCTs) in preterm infants (<37 weeks gestation) and/or infants with birth weight <1500 g that evaluated the effect of prebiotic and/or probiotic supplementation on neurodevelopmental outcomes were included. Weighted mean difference in cognitive and motor scores; pooled relative risks for cognitive and motor impairment, cerebral palsy, hearing, and visual impairment were estimated. Quality of evidence was assessed using the GRADE criteria. RESULTS: Out of 275 articles identified, seven were included for review. All, except one, were done in preterms <33 weeks of gestation. Age of assessment of outcomes was ≥18-22 months of corrected age in five studies. Interventions did not decrease or increase the risk of cognitive and motor impairment, cerebral palsy, visual, and hearing impairment. Quality of evidence was "low" to "very low." CONCLUSIONS: Limited evidence from RCTs does not demonstrate a difference in neurodevelopmental outcomes between prebiotic/probiotic treated and untreated control groups.

Development of an animal-assisted activity program on a pediatric behavioral health unit.

Animal-assisted activities (AAA), a form of animal-assisted interaction, have the potential to improve positive coping for youth with significant psychiatric symptoms admitted to acute behavioral health units. However, little is known regarding the appropriateness of an AAA program in short-term mental health hospital settings. The goal of this investigation is to describe and report on the feasibility and acceptability of embedding a canine-AAA program within the therapeutic programming of a pediatric behavioral health unit. Both patient participants and unit staff completed quantitative and qualitative measures. Outcomes yielded preliminary data suggesting AAA was feasible and acceptable to patients and unit staff. Initial efficacy outcomes demonstrated decreases in subjective distress. Qualitative data provided areas for further refinement of the AAA program.

Infants born preterm, stress, and neurodevelopment in the neonatal intensive care unit: might music have an impact?

AIM: The neonatal intensive care unit (NICU) provides life-saving medical care for an increasing number of newborn infants each year. NICU care, while lifesaving, does have attendant consequences which can include repeated activation of the stress response and reduced maternal interaction, with possible negative long-term impacts on brain development. Here we present a neuroscientific framework for considering the impact of music on neurodevelopment in the NICU of infants born preterm and evaluate current literature on the use of music with this population to determine what is most reliably known of the physiological effects of music interventions. METHOD: Using online academic databases we collected relevant, experimental studies aimed at determining effects of music listening in infants in the NICU. These articles were evaluated for methodological rigor, ranking the 10 most experimentally stringent as a representative sample. RESULTS: The selected literature seems to indicate that effects are present on the cardio-pulmonary system and behavior of neonates, although the relative effect size remains unclear. INTERPRETATION: These findings indicate a need for more standardized longitudinal studies aimed at determining not only whether NICU music exposure has beneficial effects on the cardio-pulmonary system, but also on the hypothalamic-pituitary-adrenal axis, brain structures, and cognitive behavioral status of these children as well. WHAT THIS PAPER ADDS: Provides a neuroscience framework for considering how music might attenuate stress in neonatal intensive care unit (NICU) infants. Considers how repeated stress may cause negative neurodevelopmental impacts in infants born preterm. Posits epigenetics can serve as a mechanistic pathway for music moderating the stress response.

Emerging Clinical Benefits of New-Generation Fat Emulsions in Preterm Neonates.

Soybean oil-based intravenous fat emulsions (IVFEs) have been the predominant parenteral nutrition IVFE used in the United States for neonates over the past 45 years. Even though this emulsion has proven useful in supplying infants with energy for growth and essential fatty acids, there have been concerns over its composition in the development of several morbidities, ranging from sepsis to liver disease, bronchopulmonary dysplasia, and impaired neurodevelopment and growth. The exact mechanisms that drive these morbidities in preterm infants are multifactorial, but potential contributors include high ω-6 (n-6) fatty acid composition, low docosahexaenoic acid and antioxidant supplementation, and the presence of potentially harmful nonnutritive components (eg, phytosterols). To address these issues, new-generation IVFEs with various types and amounts of fat have been developed containing greater amounts of the medium-chain fatty acids, long-chain polyunsaturated fatty acid, docosahexaenoic acid, lower concentrations of ω-6 polyunsaturated fatty acids, supplemental vitamin E, and low or negligible amounts of phytosterols. This review examines the clinical outcomes associated with different morbidities of parenteral nutrition in neonates who have received either soybean oil-based or new-generation IVFEs and addresses whether the proposed benefits of new-generation IVFEs have improved outcomes in the neonatal population.

Elevated kynurenine pathway metabolism during neurodevelopment: Implications for brain and behavior.

The kynurenine pathway (KP) of tryptophan degradation contains several neuroactive metabolites that may influence brain function in health and disease. Mounting focus has been dedicated to investigating the role of these metabolites during neurodevelopment and elucidating their involvement in the pathophysiology of psychiatric disorders with a developmental component, such as schizophrenia. In this review, we describe the changes in KP metabolism in the brain from gestation until adulthood and illustrate how environmental and genetic factors affect the KP during development. With a particular focus on kynurenic acid, the antagonist of α7 nicotinic acetylcholine (α7nACh) and N-methyl-d-aspartate (NMDA) receptors, both implicated in modulating brain development, we review animal models designed to ascertain the role of perinatal KP elevation on long-lasting biochemical, neuropathological, and behavioral deficits later in life. We present new data demonstrating that combining perinatal choline-supplementation, to potentially increase activation of α7nACh receptors during development, with embryonic kynurenine manipulation is effective in attenuating cognitive impairments in adult rat offspring. With these findings in mind, we conclude the review by discussing the advancement of therapeutic interventions that would target not only symptoms, but potentially the root cause of central nervous system diseases that manifest from a perinatal KP insult. This article is part of the Special Issue entitled 'The Kynurenine Pathway in Health and Disease'.

New Horizons in Pediatric Psychopharmacology.

Preclinical Research Recent advances in pediatric psychopharmacology have been rather uneven. Increased use of psychotropic drugs among the pediatric population has raised concerns regarding their inappropriate use and safety. While clinical trials have been conducted on various pediatric psychopharmacological drugs, there has been an insignificant amount of importance to innovation in holistic treatment. A rational approach toward elucidating the various challenges would be contingent on the convergence of the development of novel efficacious psychotropic drugs with concrete conceptual frameworks and guidelines fostering enhanced outcomes. A research infrastructure concerning the relevance of the clinician's perspective, combining drugs with alternative therapies, the need for pediatric specific formulations and relevance of these in developing countries provides a basis on which innovative treatment/development can be constructed. The current commentary highlights these comprehensive and targeted treatment guidelines as aspects necessary for building the future of the field. Drug Dev Res 77 : 474-478, 2016. © 2016 Wiley Periodicals, Inc.

Integrating care for neurodevelopmental disorders by unpacking control: A grounded theory study.

BACKGROUND: To establish integrated healthcare pathways for patients with neurodevelopmental disorders (ND) such as autism spectrum disorder and attention-deficit hyperactivity disorder is challenging. This study sets out to investigate the main concerns for healthcare professionals when integrating ND care pathways and how they resolve these concerns. METHODS: Using classic grounded theory (Glaser), we analysed efforts to improve and integrate an ND care pathway for children and youth in a Swedish region over a period of 6 years. Data from 42 individual interviews with a range of ND professionals, nine group interviews with healthcare teams, participant observation, a 2-day dialogue conference, focus group meetings, regional media coverage, and reports from other Swedish regional ND projects were analysed. RESULTS: The main concern for participants was to deal with overwhelming ND complexity by unpacking control, which is control over strategies to define patients' status and needs. Unpacking control is key to the professionals' strivings to expand constructive life space for patients, to squeeze health care to reach available care goals, to promote professional ideologies, and to uphold workplace integrity. Control-seeking behaviour in relation to ND unpacking is ubiquitous and complicates integration of ND care pathways. CONCLUSIONS: The Unpacking control theory expands central aspects of professions theory and may help to improve ND care development.

Integrating neurocritical care approaches into neonatology: should all infants be treated equitably?

To improve the neurologic outcomes for infants with brain injury, neonatal providers are increasingly implementing neurocritical care approaches into clinical practice. Term infants with brain injury have been principal beneficiaries of neurologically-integrated care models to date, as evidenced by the widespread adoption of therapeutic hypothermia protocols for hypoxic-ischemic encephalopathy. Innovative therapeutic and diagnostic support for very low birth weight infants with brain injury has lagged behind. Given that concern for significant future neurodevelopmental impairment can lead to decisions to withdraw life supportive care at any gestational age, providing families with accurate prognostic information is essential for all infants. Current variable application of multidisciplinary neurocritical care approaches to infants at different gestational ages may be ethically problematic and reflect distinct perceptions of brain injury for infants born extremely premature.