Translational Neuroscience Approach Research Articles

The Impact of Translational Neuroscience Approaches on the Treatment of Substance Use Disorders

The Impact of Translational Neuroscience Approaches on the Treatment of Substance Use Disorders

Impact of Early Life Stress on Neurobiological Vulnerability to Obsessive-Compulsive Disorder: Early Life Stress & Neurobiological OCD Risk

The impact of early life stress on neurobiological vulnerability to obsessive-compulsive disorder (OCD) is a major focus of psychiatric research. Individuals with OCD frequently report that psychosocial stress exacerbates their symptoms, with many attributing the onset of symptoms to stressful life events. However, the exact pathophysiological relationship between stress and OCD is not well understood. Stress has been shown in preclinical studies to have significant effects on cortico-striatal and limbic circuitry, including neuronal atrophy in the frontal cortices, dorsomedial striatum, and hippocampus, as well as neuronal hypertrophy in the dorsolateral striatum and amygdala. These neurobiological effects may contribute to an imbalance between goal-directed and habitual behaviour, which is associated with OCD symptoms. Furthermore, genetic and environmental factors, including early life stress, play an essential role in the advancement of OCD. Understanding gene-environment interactions and pathogenic mechanisms is critical to advancing precision medicine and improving treatment outcomes for OCD and related disorders. This review emphasises the need for additional research into how early life stress interacts with genetic factors to cause the behavioural, cellular, and molecular changes seen in OCD. Integrating global mental health and translational neuroscience approaches shows potential for enhancing our understanding and treatment of OCD and related disorders.

Understanding the heterogeneity of anxiety using a translational neuroscience approach.

Anxiety disorders affect millions of people worldwide and present a challenge in neuroscience research because of their substantial heterogeneity in clinical presentation. While a great deal of progress has been made in understanding the neurobiology of fear and anxiety, these insights have not led to effective treatments. Understanding the relationship between phenotypic heterogeneity and the underlying biology is a critical first step in solving this problem. We show translation, reverse translation, and computational modeling can contribute to a refined, cross-species understanding of fear and anxiety as well as anxiety disorders. More specifically, we outline how animal models can be leveraged to develop testable hypotheses in humans by using targeted, cross-species approaches and ethologically informed behavioral paradigms. We discuss reverse translational approaches that can guide and prioritize animal research in nontraditional research species. Finally, we advocate for the use of computational models to harmonize cross-species and cross-methodology research into anxiety. Together, this translational neuroscience approach will help to bridge the widening gap between how we currently conceptualize and diagnose anxiety disorders, as well as aid in the discovery of better treatments for these conditions.

Translational Neuroscience Approaches to Understanding Autism

While autism spectrum disorder affects nearly 2% of children in the United States, little is known with certainty concerning the etiologies and brain systems involved. This is due, in part, to the substantial heterogeneity in the presentation of the core symptoms of autism as well as the great number of co-occurring conditions that are common in autistic individuals. Understanding the neurobiology of autism is further hampered by the limited availability of postmortem brain tissue to determine the cellular and molecular alterations that take place in the autistic brain. Animal models therefore provide great translational value in helping to define the neural systems that constitute the social brain and mediate repetitive behaviors or interests. If they are based on genetic or environmental factors that contribute to autism, organisms from flies to nonhuman primates may serve as models of the neural structure or function of the autistic brain. Ultimately, successful models can also be employed to test the safety and effectiveness of potential therapeutics. This is an overview of the major animal species that are currently used as models of autism, including an appraisal of the advantages and limitations of each.

Rapid progress in neuroimaging technologies fuels central nervous system translational medicine.

Central nervous system (CNS) drug discovery suffers from high attrition rates; translational neuroscience approaches aiming to reduce these high rates include the use of brain imaging technologies. However, there is a need to better understand what methods are being used and for what diseases and purposes. Our analysis of the literature found that magnetic resonance imaging (MRI), positron emission tomography (PET), and single-photon emission computed tomography (SPECT) were the neuroimaging techniques used most often in clinical trials for the most prevalent CNS diseases: Alzheimer's disease (AD), Parkinson's disease (PD), depression, and schizophrenia. Moreover, the number of initiated clinical trials using MRI, PET, and SPECT increased over the period 1981-2021. Such insights indicate that the significant increase in the use of neuroimaging studies could decrease the attrition of novel drug candidates in late clinical development.

Crosstalk of Alzheimer's disease-phenotype, HPA axis, splenic oxidative stress and frailty in late-stages of dementia, with special concerns on the effects of social isolation: A translational neuroscience approach.

Coping with emotional stressors strongly impacts older people due to their age-related impaired neuroendocrine and immune systems. Elevated cortisol levels seem to be associated with an increased risk of cognitive decline and dementia. In Alzheimer’s disease (AD), alterations in the innate immune system result in crosstalk between immune mediators and neuronal and endocrine functions. Besides, neuropsychiatric symptoms such as depression, anxiety, or agitation are observed in most patients. Here, we studied the psychophysiological response to intrinsic (AD-phenotype) and extrinsic (anxiogenic tests) stress factors and their relation to liver, kidneys, heart, and spleen oxidative status in 18-months-old female gold-standard C57BL/6 mice and 3xTg-AD mice model for AD. The emotional, cognitive, and motor phenotypes were assessed under three different anxiogenic conditions. Survival, frailty index, and immunoendocrine status (corticosterone levels and oxidative stress of peripheral organs) were evaluated. Genotype differences in neuropsychiatric-like profiles and cognitive disfunction in 3xTg-AD females that survived beyond advanced stages of the disease persisted despite losing other behavioral and hypothalamic–pituitary–adrenal (HPA) physiological differences. A secondary analysis studied the impact of social isolation, naturally occurring in 3xTg-AD mice due to the death of cage mates. One month of isolation modified hyperactivity and neophobia patterns and disrupt the obsessive-compulsive disorder-like digging ethogram. Frailty index correlated with spleen organometrics in all groups, whereas two AD-specific salient functional correlations were identified: (1) Levels of corticosterone with worse performance in the T-maze, (2) and with a lower splenic GPx antioxidant enzymatic activity, which may suppose a potent risk of morbidity and mortality in AD.

Dissecting the Heterogeneity of Autism: Focus on Phelan-McDermid Syndrome

IntroductionAutism spectrum disorders (ASD) are a group of neurodevelopmental disorders that show delays and deficits in the development of multiple brain functions, which are characterized by social communication, poor language development, and restricted and stereotyped patterns of interests and behaviours. ASD affects about 1-2 % of the population and are considered to be highly genetic in nature. Structural variations of chromosomes have been identified in some ASD individuals, most common on chromosome 7q, 15q and 22q.Objectives1-To present a systematic literature review of the natural history of individuals with 22q13.3 deletion syndrome, Phelan-McDermid syndrome (PMS). PMS, increase awareness of different phenotypes 2- Correlation of clinical manifestations of PMS with hypothesized underlying biological mechanisms 3-Rational for novel treatments is inferred through translational neuroscience approaches.MethodsWe have conducted a systematic literature review of the natural history of individuals with PMS, including both cross-sectional and long-term longitudinal analyses and correlation with hypothesized underlying biological mechanisms, including roles in regulation synaptic development, function, and plasticity. This systematic review includes the basis for a promising common pathway for ASD pathogenesis and the clinical implications of novel therapeutic strategies inferred through translational neuroscience approaches.ResultsThis systematic review, therefore, outlines the: (1) Pathophysiological basis and clinical manifestations of PMS; (2) PMS pre-clinical models and applications to ASD; and (3) clinical implications of novel therapeutic strategies.ConclusionsA promising common pathway for ASD pathogenesis and rational for novel treatments is inferred through translational neuroscience approaches. Neurobiological basis for lithium treatment is indeed supported by experimental results and current clinical findings.DisclosureNo significant relationships.

Innovations in the Delivery of Exposure and Response Prevention for Obsessive-Compulsive Disorder.

Obsessive-Compulsive Disorder is an important cause of global health-related disability. In the last several decades, exposure and response prevention (EX/RP) has emerged as one of the most evidence-based treatments for adult and pediatric OCD. Recommended as a first-line treatment in practice guidelines for OCD, EX/RP, when expertly delivered, can be superior to serotonin reuptake inhibitor (SRI) medications alone and superior to adding antipsychotic medication to augment SRI treatment response. Despite a robust evidence base, EX/RP is not widely available. Moreover, although effective, only about half of patients who receive a standard course of EX/RP will achieve remission.This chapter will review innovations in delivering EX/RP, focusing on technology-based methods designed to increase access to EX/RP and translational neuroscience approaches to personalizing and optimizing EX/RP. Technology-based innovations to deliver EX/RP include video conferencing, internet-based treatment, and smartphone apps. Of these, internet-based, clinician-supported treatment has the most evidence base to date. Relevant to all technology-based innovations are the need for advances in the ethical, regulatory and financial aspects of understanding how access to EX/RP may be delivered to individuals of diverse socioeconomic backgrounds in accordance with professional standards and regulations and covered by healthcare.Advances in our understanding of the neural processes underlying learning and memory have led to new ways to combine EX/RP with medications, behavioral interventions, or neuromodulatory methods, with the goal of enhancing the functioning of brain circuits that subserve fear processing and cognitive control. Among the pharmacological approaches to enhancing EX/RP outcome, both ketamine and cannabinoids show promise in small open trials but are in need of further study. Studies to train cognitive control are at an early stage of development yet provide preliminary evidence that training neural processes may be a new path to personalize treatment. How best to combine EX/RP with different types of neuromodulation is being actively studied.Together these innovations in the delivery of EX/RP for OCD hold great promise for improving outcomes of care for individuals with OCD by increasing the availability and the individual treatment effects of this already effective treatment.

Impact of Social Isolation on the Behavioral, Functional Profiles, and Hippocampal Atrophy Asymmetry in Dementia in Times of Coronavirus Pandemic (COVID-19): A Translational Neuroscience Approach.

The impact of COVID-19 on the elderly is devastating, and nursing homes are struggling to provide the best care to the most fragile. The urgency and severity of the pandemic forces the use of segregation in restricted areas and confinement in individual rooms as desperate strategies to avoid the spread of disease and the worst-case scenario of becoming a deadly trap. The conceptualization of the post–COVID-19 era implies strong efforts to redesign all living conditions, care/rehabilitation interventions, and management of loneliness forced by social distance measures. Recently, a study of gender differences in COVID-19 found that men are more likely to suffer more severe effects of the disease and are over twice as likely to die. It is well-known that dementia is associated with increased mortality, and males have worse survival and deranged neuro-immuno-endocrine systems than females. The present study examines the impact of long-term isolation in male 3xTg-AD mice modeling advanced stages of Alzheimer's disease (AD) and as compared to age-matched counterparts with normal aging. We used a battery of ethological and unconditioned tests resembling several areas in nursing homes. The main findings refer to an exacerbated (two-fold increase) hyperactivity and emergence of bizarre behaviors in isolated 3xTg-AD mice, worrisome results since agitation is a challenge in the clinical management of dementia and an important cause of caregiver burden. This increase was consistently shown in gross (activity in most of the tests) and fine (thermoregulatory nesting) motor functions. Isolated animals also exhibited re-structured anxiety-like patterns and coping-with-stress strategies. Bodyweight and kidney weight loss were found in AD-phenotypes and increased by isolation. Spleen weight loss was isolation dependent. Hippocampal tau pathology was not modified, but asymmetric atrophy of the hippocampus, recently described in human patients with dementia and modeled here for the first time in an animal model of AD, was found to increase with isolation. Overall, the results show awareness of the impact of isolation in elderly patients with dementia, offering some guidance from translational neuroscience in these times of coronavirus and post–COVID-19 pandemic. They also highlight the relevance of personalized-based interventions tailored to the heterogeneous and complex clinical profile of the individuals with dementia and to consider the implications on caregiver burden.

470 - Improving homeostatic systems and healthy longevity by intergenerational relationships: Evidences from a translational neuroscience approach

The aging process is associated with a deterioration of the physiological systems, especially the homeostatic (nervous, immune and endocrine) systems with the consequent increase in morbidity and mortality. With the aging population, increasing number of studies focus on lifestyle interventions to slow down these aging derangements. Here, animal models can be useful to assess their long-term effects and potential value taking into advantage their shorter life span. In a previous work, old animals beneficed of 2 months of continuous cohabitation with adult, with improvements on behaviour, immune function and redox state as well as a higher longevity. However, their adult counterparts showed impairments in these parameters. In the present study, this social strategy was modified with the aim to improve the homeostatic systems in both the old and the adult animals.) Animals of the experimental group with “two old ICR-CD1 female mice cohabiting 15 minutes each day for 2 months with five adult mic” were studied and compared to adult and old controls. After this time, mice were submitted to a behavioural battery of tests to analyse their sensorimotor abilities, anxiety-like behaviours, and exploratory capacities. Peritoneal leukocytes were collected and several immune functions, oxidative and inflammatory stress parameters as well as catecholamine concentrations were assessed. When the adult mice reached old age the same parameters were again analysed. The life span of each animal was also recorded. Several mice of each group were sacrificed to obtain plasma and the hormone oxytocin was evaluated. The results show that old mice presented an improvement of behavioural capacities, immune functions and lower oxidative and inflammatory stress after the two months of social interaction with adult animals, and consequently they exhibited an extended life span. Adult mice, in general, did not show any changes after social interaction, but when they achieved old age an improvement of all the parameters studied and of longevity was observed in comparison with those mice that never had a social interaction with old animals. In conclusion, a short social interaction between old and adult individuals can be an excellent strategy for improving in both the health state and longevity.

417 - Olfactory signatures in models of aging and Alzheimer’s disease and the effect of social isolation: A translational neuroscience approach in times of coronavirus pandemic (COVID-19)

Sensory systems ensure the ability to perceive and recognize the world. Therefore, the temporal course and the severity of their involution through the aging process can be critical. In the elderly, sensory impairments significantly increase their risk of biological, psychological and social impoverishment. Olfactory loss, known to happen in bacterial and viral infections and considered an early biomarker in Alzheimer’s and Parkinson’s diseases neurodegenerative processes, has been reported also as an early indicator of current infection by SARS-CoV-2. At the translational level, in the present work, we have studied olfactory ethograms in normal and advanced AD-related pathological aging using wildtype and the 3xTg-AD mice, a genetic model of Alzheimer’s disease that presents AD-cognitive dysfunction but also a conspicuous BPSD-like phenotype. An olfactory paradigm, involving the equivalent to one day food deprivation, was used to investigate in middle-aged males and females with normal and AD-pathological aging the ethological patterns shown in the olfactory inspection of a new cage with beddings and the posterior detection, finding and consumption of food pellets hidden in this new anxiogenic environment. Males with normal and pathological aging were equally delayed in their first contact with food pellets, while in female sex this latency was dependent on the genotype (longer in 3xTg-AD mice, shorter in those with normal aging). Once the animals had inspected the arena, the latencies to smell, find and eat the food pellets were found progressively increased in males with normal aging, but consecutively developed in 3xTg-AD mice. In contrast, both groups of females exhibited longer delays as compared to males, and the temporal pattern of their ethogram to smell-find-eat the food was faster. In 3xTg-AD males, social isolation (naturally occurring due to death of counterparts) emphasized these olfactory patterns, which were independent of the punctual loss of weight of this paradigm. The results show that this paradigm provides distinct contextual, sex and genotype olfactory ethogram signatures useful to investigate olfactory function in normal and AD-pathological aging. Also, that isolation has an impact enhancing the changes in the olfactory signature here described, for the first time, in the 3xTg-AD mice model of Alzheimer’s disease.

419 - Brain atrophy asymmetry in dementia is worsened by social isolation: A translational neuroscience approach in times of coronavirus pandemic (COVID-19)

The coronavirus pandemic (COVID-19) that has ravaged the entire world presents the most dramatic scenarios in the most vulnerable populations, with exacerbated focus on the elderly people, especially the most frail needing home-care or living in nursing homes. The urgency and severity of the outbreaks forces the use of segregation in restricted areas and confinement in individual rooms as desperate strategies to avoid the spreading of disease and the worse scenario of becoming a deadly trap. Residents are becoming socially isolated, lacking the social and environmental enrichment that are key rehabilitation factors against their progressive physical and/or mental deterioration. Recently, a study on gender perspective in COVID -19 found that men have more severe disease and are over twice as likely to die. It is well known that dementia is associated with increased mortality and males show worse survival than females. On the other hand, the asymmetric neurodegeneration of subcortical structures in Alzheimer’s disease (AD) has been recently demonstrated and proposed as a powerful imaging biomarker. In the present work, we studied the impact of long-term isolation in old male 3xTg-AD mice modeling advanced-stages of AD and as compared to age-matched counterparts with normal aging. A battery of behavioral tests resembling several areas in nursery homes was used. Atrophy of left and right hippocampus, cortex and cerebellum was measured. Our results are the first evidences of brain atrophy asymmetry being demonstrated in an animal model of AD, thus modeling that found in human patients. The main findings aware of a consistent impact of isolation increasing the hippocampal and cortical atrophy asymmetries. Isolated animals showed a prominent hyperactive pattern in both gross and fine-motor functions, re-structured negative valence system with the emergence of bizarre behaviors and flight copying-with-stress strategies. Overall, these results from translational neuroscience aware of the impact of isolation enhancing the neurodegenerative asymmetry and BPSD-like behaviors. They also highlight the relevance of personalized-based interventions tailored to the heterogeneous and complex clinical profile of the individuals with dementia, and to pay special attention to BPSD behaviors that may worse their caregivers’ burden in these times of coronavirus and post-COVID-19 pandemic scenario.

418 - Digging signatures modeling anxiety and OCD disorders in very old age and end-of-life Alzheimer’s disease and the effect of social isolation: A translational neuroscience approach in times of coronavirus pandemic (COVID-19)

The severity of the current scenarios in this pandemic will leave important psychological traces. In fact, the first clinical reports available already refer to increased incidence of depression and anxiety disorders such as obsessive-compulsive disorder (OCD) and post-traumatic stress disorder. At the translational level, modelling of such neuropsychiatric alterations in animal models relays in neuroethological perspectives since response to fearful situations and traumatic events, critical for survival and adaptation to the environment, are strongly preserved in phylogeny. In the wild, mice dig as a ‘defensive behavior’ which is considered to reflect the anxiety state of animals. In the laboratory, mice dig vigorously in deep bedding to bury food pellets or small objects they may find. Thus this behavior, initially used to screen anxiolytic activity was later proposed to better model meaningless repetitive and perseverative behaviors characteristic of OCD or autism spectrum disorders. In the present work, we have studied the digging ethograms in normal and advanced AD-related pathological aging using wildtype and the 3xTg-AD mice, a genetic model of Alzheimer’s disease that presents AD-cognitive dysfunction but also a conspicuous BPSD-like phenotype. We also studied the effects of isolation in this respect, using very old (18 month-old) 3xTg-AD mice that survived to their cage mates, as mortality rates in this animal model are high after 13 months of age. Two digging paradigms, involving different anxiogenic and contextual situations were used to investigate the digging patterns in these very old males with normal and AD-pathological aging, as well as the effects of isolation. The temporal course and intensity of this behavior was found increased in those 3xTg-AD mice that had lost their ‘room partner’ and lived isolated. However, when they were tested under neophobia conditions, incidence of this behavior was smaller and the pattern of digging was disrupted. The results show that this combined paradigm unveils distinct features of digging signatures that can be useful to provide an animal model for these perseverative behaviors and their interplay with anxiety states, which represent an important part of BPSD or can now emerge as a result of the enhancement of obsessive-convulsive behaviors by social-isolation.

Obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a highly prevalent and chronic condition that is associated with substantial global disability. OCD is the key example of the 'obsessive-compulsive and related disorders', a group of conditions which are now classified together in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and the International Classification of Diseases, 11th Revision, and which are often underdiagnosed and undertreated. In addition, OCD is an important example of a neuropsychiatric disorder in which rigorous research on phenomenology, psychobiology, pharmacotherapy and psychotherapy has contributed to better recognition, assessment and outcomes. Although OCD is a relatively homogenous disorder with similar symptom dimensions globally, individualized assessment of symptoms, the degree of insight, and the extent of comorbidity is needed. Several neurobiological mechanisms underlying OCD have been identified, including specific brain circuits that underpin OCD. In addition, laboratory models have demonstrated how cellular and molecular dysfunction underpins repetitive stereotyped behaviours, and the genetic architecture of OCD is increasingly understood. Effective treatments for OCD include serotonin reuptake inhibitors and cognitive-behavioural therapy, and neurosurgery for those with intractable symptoms. Integration of global mental health and translational neuroscience approaches could further advance knowledge on OCD and improve clinical outcomes.

Exercise Intervention in PTSD: A Narrative Review and Rationale for Implementation.

Posttraumatic stress disorder (PTSD) is a prominent mental health problem in veteran and community populations. There is accumulating evidence to suggest that aerobic exercise may serve as an effective treatment option for individuals with PTSD. The purpose of this review is to summarize the existing literature exploring aerobic exercise and PTSD and briefly discuss potential mechanisms of PTSD symptom reduction. A search of electronic databases and reference sections of relevant articles published through October 1, 2018 revealed 19 relevant studies that examined aerobic exercise and PTSD symptomatology. A narrative review of extant studies provides encouraging evidence that aerobic exercise interventions alone or as an adjunct to standard treatment may positively impact PTSD symptoms. Potential mechanisms by which aerobic exercise could exert a positive impact in PTSD include exposure and desensitization to internal arousal cues, enhanced cognitive function, exercise-induced neuroplasticity, normalization of hypothalamic pituitary axis (HPA) function, and reductions in inflammatory markers. Randomized clinical trials and translational neuroscience approaches are required to clarify the efficacy of exercise intervention for PTSD and elucidate potential mechanisms of exercise-induced PTSD symptom reduction.

The value of clinical and translational neuroscience approaches to psychiatric illness.

Borsboom et al. confuse biological approaches with extreme biological reductionism and common-cause models of psychopathology. In muddling these concepts, they mistakenly throw the baby out with the bathwater. Here, we highlight recent work underscoring the unique value of clinical and translational neuroscience approaches for understanding the nature and origins of psychopathology and for developing improved intervention strategies.

Behavioral activation, effort-based choice, and elasticity of demand for motivational stimuli: Basic and translational neuroscience approaches.

Behavioral activation, effort-based choice, and elasticity of demand for motivational stimuli: Basic and translational neuroscience approaches.

A translational neuroscience approach to body image disturbance and its remediation in anorexia nervosa.

Deviant perception of the body is a fundamental component of anorexia nervosa. Here we offer a potential mechanistic explanation that involves perturbations within the visual system and the brain circuits that modulate perceptual organization. Based on the model proposed, we also suggest a mechanistic strategy for altering neuronal activity in the visual system to normalize perception of the body, and set out a strategy for empirically testing its clinical application.

Use of a Piglet Model for the Study of Anesthetic-induced Developmental Neurotoxicity (AIDN): A Translational Neuroscience Approach

Anesthesia cannot be avoided in many cases when surgery is required, particularly in children. Recent investigations in animals have raised concerns that anesthesia exposure may lead to neuronal apoptosis, known as anesthesia-induced developmental neurotoxicity (AIDN). Furthermore, some clinical studies in children have suggested that anesthesia exposure may lead to neurodevelopmental deficits later in life. Nonetheless, an ideal animal model for preclinical study has yet to be developed. The neonatal piglet represents a valuable model for preclinical study, as they share a striking number of developmental similarities with humans. The anatomy and physiology of piglets allow for implementation of rigorous human perioperative conditions in both survival and non-survival procedures. Femoral artery catheterization allows for close monitoring, thus enabling prompt correction of any deviation of the piglet's vital signs and chemistries. In addition, there are multiple developmental similarities between piglets and human neonates. The techniques required to use piglets for experimentation will require experience to master. A pediatric anesthesiologist is a critical member of the investigative team. We describe, in a general sense, the appropriate use of a piglet model for neurodevelopmental study.

Use of a Piglet Model for the Study of Anesthetic-induced Developmental Neurotoxicity (AIDN): A Translational Neuroscience Approach.

Anesthesia cannot be avoided in many cases when surgery is required, particularly in children. Recent investigations in animals have raised concerns that anesthesia exposure may lead to neuronal apoptosis, known as anesthesia-induced developmental neurotoxicity (AIDN). Furthermore, some clinical studies in children have suggested that anesthesia exposure may lead to neurodevelopmental deficits later in life. Nonetheless, an ideal animal model for preclinical study has yet to be developed. The neonatal piglet represents a valuable model for preclinical study, as they share a striking number of developmental similarities with humans.The anatomy and physiology of piglets allow for implementation of rigorous human perioperative conditions in both survival and non-survival procedures. Femoral artery catheterization allows for close monitoring, thus enabling prompt correction of any deviation of the piglet's vital signs and chemistries. In addition, there are multiple developmental similarities between piglets and human neonates. The techniques required to use piglets for experimentation will require experience to master. A pediatric anesthesiologist is a critical member of the investigative team. We describe, in a general sense, the appropriate use of a piglet model for neurodevelopmental study.