Neurobiological Domains Research Articles

499. Identification of a Composite Latent Dimension of Reward and Impulsivity Across Clinical, Behavioral and Neurobiological Domains Among Youth

499. Identification of a Composite Latent Dimension of Reward and Impulsivity Across Clinical, Behavioral and Neurobiological Domains Among Youth

After the trans brain: a critique of the neurobiological accounts of embodied trans* identities

This paper critically analyses three main neurobiological hypotheses on trans* identities: the neurobiological theory about the origin of gender dysphoria, the neurodevelopmental cortical hypothesis, and the alternative hypothesis of self-referential thinking and body perception. In this study I focus then the attention on three elements: the issue of (de)pathologisation, the idea of the trans brain, and the aetiology of trans* identities. While the neurobiological theory about the origin of gender dysphoria and the neurodevelopmental cortical hypothesis claim the existence of the trans brain, each offering its own neurobiological depiction, the hypothesis of self-referential thinking and body perception doesn’t postulate a distinctive neurobiological trait for all trans* people. I problematize both portrayals of the trans brain departing from the findings and conceptualizations of the paradigm shifting brain mosaicism. Unlike the hypothesis of self-referential thinking and body perception that keeps the question of causation open, both the neurobiological theory about the origin of gender dysphoria and the neurodevelopmental cortical hypothesis situate the origin of trans* identities in the neurobiological domain. I challenge the biological deterministic framework in which this aetiology is inscribed from a dynamic processual entanglement perspective. Finally, concerning the issue of (de)pathologisation of trans* identities, an evolution can be seen in each of the hypothesis and among them, from the least to the most depathologising. However, I question their complete departure from a pathologising framework.

Identification of a Composite Latent Dimension of Reward and Impulsivity Across Clinical, Behavioral, and Neurobiological Domains Among Youth

BackgroundIndividual differences in reward processing are central to heightened risk-taking behaviors during adolescence, but there is inconsistent evidence for the relationship between risk-taking phenotypes and the neural substrates of these behaviors. MethodsHere, we identify latent features of reward in an attempt to provide a unifying framework linking together aspects of the brain and behavior during early adolescence using a multivariate pattern learning approach. Data (N = 8295; n male = 4190; n female = 4105) were acquired as part of the Adolescent Brain Cognitive Development (ABCD) Study and included neuroimaging (regional neural activity responses during reward anticipation) and behavioral (e.g., impulsivity measures, delay discounting) variables. ResultsWe revealed a single latent dimension of reward driven by shared covariation between striatal, thalamic, and anterior cingulate responses during reward anticipation, negative urgency, and delay discounting behaviors. Expression of these latent features differed among adolescents with attention-deficit/hyperactivity disorder and disruptive behavior disorder, compared with those without, and higher expression of these latent features was negatively associated with multiple dimensions of executive function and cognition. ConclusionsThese results suggest that cross-domain patterns of anticipatory reward processing linked to negative features of impulsivity exist in both the brain and in behavior during early adolescence and that these are representative of 2 commonly diagnosed reward-related psychiatric disorders, attention-deficit/hyperactivity disorder and disruptive behavior disorder. Furthermore, they provide an explicit baseline from which multivariate developmental trajectories of reward processes may be tracked in later waves of the ABCD Study and other developmental cohorts.

Research Review: The neuroscience of emerging adulthood - reward, ambiguity, and social support as building blocks of mental health.

The interval between adolescence and adulthood, 'emerging adulthood' (EA), lays the foundation for lifelong health and well-being. To date, there exist little empirical data - particularly in the neurobiological domain - to establish markers of risk and resilience during the transition to adulthood. This gap in the literature is concerning given the numerous forms of psychiatric illness that emerge or worsen during this period. In this review, we focus on two strands of research with distinct importance for EA: reward sensitivity, and tolerance of ambiguity. We begin by placing these domains in a framework that considers the unique developmental goals of EA and then synthesize emerging neurobiological research on how these domains develop during EA. We then consider their role in common mental health problems that occur during this interval as well as how social support may moderate outcomes. Finally, we offer recommendations for advancing research to understand developmental process and outcomes in EA. Few longitudinal studies specifically address emerging adult development and the milestones that characterize this interval. Data on neurobiological development are similarly sparse. Understanding neurobiological development during this window and its links to key adjustment outcomes is crucial for optimizing outcomes.

The Bucharest Early Intervention Project: Adolescent mental health and adaptation following early deprivation.

Over the last 20 years, we have learned much about the extent to which early-life deprivation affects the mental health of children and adolescents. This body of evidence comes predominantly from studies of children raised in institutional care. The Bucharest Early Intervention Project (BEIP) is the only randomized controlled trial designed to evaluate whether the transition to family-based foster care early in development can ameliorate the long-term impact of institutional deprivation on psychopathology during vulnerable developmental windows such as adolescence. In this review, we detail the extent to which early deprivation affects mental health during this period, the capacity of family-based care to facilitate recovery from early deprivation, and the mechanisms underpinning these effects spanning social-emotional, cognitive, stress, and neurobiological domains. We end by discussing the implications and directions for the BEIP and other studies of youth raised in institutions.

Binge eating disorder.

Binge eating disorder (BED) is characterized by regular binge eating episodes during which individuals ingest comparably large amounts of food and experience loss of control over their eating behaviour. The worldwide prevalence of BED for the years 2018-2020 is estimated to be 0.6-1.8% in adult women and 0.3-0.7% in adult men. BED is commonly associated with obesity and with somatic and mental health comorbidities. People with BED experience considerable burden and impairments in quality of life, and, at the same time, BED often goes undetected and untreated. The aetiology of BED is complex, including genetic and environmental factors as well as neuroendocrinological and neurobiological contributions. Neurobiological findings highlight impairments in reward processing, inhibitory control and emotion regulation in people with BED, and these neurobiological domains are targets for emerging treatment approaches. Psychotherapy is the first-line treatment for BED. Recognition and research on BED has increased since its inclusion into DSM-5; however, continuing efforts are needed to understand underlying mechanisms of BED and to improve prevention and treatment outcomes for this disorder. These efforts should also include screening, identification and implementation of evidence-based interventions in routine clinical practice settings such as primary care and mental health outpatient clinics.

A data-driven framework for mapping domains of human neurobiology.

Functional neuroimaging has been a mainstay of human neuroscience for the past 25 years. Interpretation of fMRI data has often occurred within knowledge frameworks crafted by experts, which have the potential to amplify biases that limit the replicability of findings. Here, we employ a computational approach to derive a data-driven framework for neurobiological domains that synthesizes the texts and data of nearly 20,000 human neuroimaging articles. Across multiple levels of domain specificity, the structure-function links within domains better replicate in held-out articles than those mapped from dominant frameworks in neuroscience and psychiatry. We further show that the data-driven framework partitions the literature into modular subfields, for which domains serve as generalizable prototypes of structure-function patterns in single articles. The approach to computational ontology we present here is the most comprehensive characterization of human brain circuits quantifiable with fMRI and may be extended to synthesize other scientific literatures.

Neuro-Behavioral Correlates of Executive Dysfunctions in Dyslexia Over Development From Childhood to Adulthood.

Dyslexia is a neurobiological learning disability in the reading domain that has symptoms in early childhood and persists throughout life. Individuals with dyslexia experience difficulties in academia and cognitive and emotional challenges that can affect wellbeing. Early intervention is critical to minimize the long-term difficulties of these individuals. However, the behavioral and neural correlates which predict dyslexia are challenging to depict before reading is acquired. One of the precursors for language and reading acquisition is executive functions (EF). The present review aims to highlight the current atypicality found in individuals with dyslexia in the domain of EF using behavioral measures, brain mapping, functional connectivity, and diffusion tensor imaging along development. Individuals with dyslexia show EF abnormalities in both behavioral and neurobiological domains, starting in early childhood that persist into adulthood. EF impairment precedes reading disability, therefore adding an EF assessment to the neuropsychological testing is recommended for early intervention. EF training should also be considered for the most comprehensive outcomes.

Adolescent brain and nicotine

Adolescence is a period of transition between childhood and adulthood that involves major changes in development in the physical, psychological, social and neurobiological domains. During this phase of life, multiple physical and emotional events occur throughout the body, markedly in the central nervous system, regulated by neurohormones, which are fundamental for human development, responsible for changes in thoughts, attitudes and behaviors that culminate in complete maturity for a laborious and reproductive life. Due to the lability of the neurological tissue in this period, external aggressions by means of chemical substances can cause serious and lasting effects. Nicotine is one of the substances considered legal and that more easily the adolescent comes into contact early, and can cause many harm to current and future health. This article presents some characteristics of the development of the adolescent's nervous system and the deleterious actions that can be caused by nicotine in its various forms of social presentation.
 Keywords: Adolescence – nicotine – smoking – nicotine addiction

Long-lasting Behavioral and Neuroanatomical Effects of Postnatal Valproic Acid Treatment

Valproic acid (VPA) administered to mice during the early postnatal period causes social, cognitive, and motor deficits similar to those observed in humans with autism spectrum disorder (ASD). However, previous studies on the effects of early exposure to VPA have largely focused on behavioral deficits occurring before or during the juvenile period of life. Given that ASD is a life-long condition, the present study ought to extend our understanding of the behavioral profile following early postnatal VPA into adulthood. Male mice treated with VPA on postnatal day 14 (P14) displayed increased aggression, decreased avoidance of the open arms in the elevated plus maze, and impaired reversal learning in the Y maze. This may indicate a disinhibited or impulsive phenotype in male, but not female, mice treated with VPA during the second week of postnatal life. Decreased dendritic spine density and dendritic spine morphological abnormalities in the mPFC of VPA-treated mice may be indicative of PFC hypofunction, consistent with the observed behavioral differences. Since these types of long-lasting deficits are not exclusively found in ASD, early life exposure to VPA may reflect dysfunction of a neurobiological domain common to several developmental disorders, including ASD, ADHD, and conduct disorder.

Grant Report on the Effects of Childhood Maltreatment on Neurocircuitry in Adolescent Depression.

This report describes the protocol for an ongoing project funded by the National Institutes of Health (R01MH108155) that is focused on effects of childhood maltreatment (MALTX) on neurocircuitry changes associated with adolescent major depressive disorder (MDD). Extant clinical and neuroimaging literature on MDD is reviewed, which has relied on heterogeneous samples that do not parse out the unique contribution of MALTX on neurobiological changes in MDD. Employing a 2 × 2 study design (controls with no MALTX or MDD, MALTX only, MDD only, and MDD + MALTX), and based on a cohesive theoretical model that incorporates behavioral, cognitive and neurobiological domains, we describe the multi-modal neuroimaging techniques used to test whether structural and functional alterations in the fronto-limbic and fronto-striatal circuits associated with adolescent MDD are moderated by MALTX. We hypothesize that MDD + MALTX youth will show alterations in the fronto-limbic circuit, with reduced connectivity between the amygdala (AMG) and the prefrontal cortex (PFC), as the AMG is sensitive to stress/threat during development. Participants with MDD will exhibit increased functional connectivity between the AMG and PFC due to self-referential negative emotions. Lastly, MDD + MALTX will only show changes in motivational/anticipatory aspects of the fronto-striatal circuit, and MDD will exhibit changes in motivational and consummatory/outcome aspects of reward-processing. Our goal is to identify distinct neural substrates associated with MDD due to MALTX compared to other causes, as these markers could be used to more effectively predict treatment outcome, index treatment response, and facilitate alternative treatments for adolescents who do not respond well to traditional approaches.

The BDNF Val66Met Polymorphism Promotes Changes in the Neuronal Integrity and Alters the Time Perception.

Studies at the molecular level aim to integrate genetic and neurobiological data to provide an increasingly detailed understanding of phenotypes related to the synchronization ability and brain oscillations in time perception. Genetic variation as a modifying factor at cellular and neurochemical levels permeates several neurofunctional aspects in time-lapse duration concentrating from milliseconds to hours. Thus, the review presents the BDNF Val66Met polymorphism association in a dynamic frame of brain neurotrophic factor expression in the adaptation, integrity, and neuronal synchronism processes in the ability to estimate multisensory stimuli at different time intervals. Our study aims to understand the molecular aspects involved in a neurobiological domain pertinent to the time judgment, tracing a genetic profile of association with psychometric functions and behavioral performances related to timing stimuli.

On Mourning and Recovery: Integrating Stages of Grief and Change Toward a Neuroscience-Based Model of Attachment Adaptation in Addiction Treatment.

Interpersonal attachment and drug addiction share many attributes across their behavioral and neurobiological domains. Understanding the overlapping brain circuitry of attachment formation and addiction illuminates a deeper understanding of the pathogenesis of trauma-related mental illnesses and comorbid substance use disorders, and the extent to which ending an addiction is complicated by being a sort of mourning process. Attention to the process of addiction recovery-as a form of grieving-in which Kubler-Ross's stages of grief and Prochaska's stages of change are ultimately describing complementary viewpoints on a general process of neural network and attachment remodeling, could lead to more effective and integrative psychotherapy and medication strategies.

Neurobiological Correlates of Psychological Treatments for Insomnia

Abstract. Sleep disorders and sleep disturbances are considered nowadays a major public health problem. Within sleep problems, insomnia is the most common health complaint. The maintenance of insomnia symptoms may lead to a clinical disorder – Insomnia Disorder (ID). A significant amount of literature has shown the efficacy and effectiveness of psychological treatments for ID. Often, the evaluation of therapeutic processes and outcomes focuses on subjective measures such as sleep diaries. In this work, we review the few published studies that evaluate modifications in neurobiological domain related to evidence-based psychological interventions, namely cognitive-behavioral therapy for insomnia (CBT-I). The search was carried out consulting Scopus, PubMed, and ISI Web of Knowledge databases. Only 12 studies were found. From the reviewed papers it was observed that the results are diverse, perhaps due to significant differences pertaining to the methodologies used. However, one interesting finding emerged: daytime experiments on insomnia comprising mainly cognitive tasks denoted hypofunction in ID patients, whereas nighttime experiments mainly associated with affective/emotional tasks denoted hyperarousal. We suggest that the study of the neural changes prompted by CBT-I is a major topic in the domain of psychotherapy and sleep medicine. Despite the scarce studies on neurobiological mechanisms of CBT-I, the results achieved until now are promising and should be taken into account in the future. Nonetheless, more research on this topic is needed.

Revisiting visual dysfunctions in schizophrenia from the retina to the cortical cells: A manifestation of defective neurodevelopment

This review highlights morphological and functional anomalies found along the entire visual pathway in schizophrenia, from the retina to the cortex. Based on the evidence of widespread anatomical and functional visual abnormalities, we posited that a neurodevelopmental anomaly occurring early in life was likely to explain those. Incidentally, support to the neurodevelopmental theory of schizophrenia is strongly emerging from many neurobiological domains. In vertebrates, the first visual structures migrate toward the orbit position at the end of the fourth week of gestation. A neurodevelopmental defect around that time on these embryonic structures could account for the visual anomalies in schizophrenia. Retinol activity might be involved in the process. Future research in schizophrenia should focus on early visual testing, on trials combining multiple visual anomaly assessments and a closer look to retinol activity during the pregnancy.

Towards a computational(ist) neurobiology of language: correlational, integrated and explanatory neurolinguistics

We outline what an integrated approach to language research that connects experimental, theoretical and neurobiological (NB) domains of inquiry would look like and ask to what extent unification is possible across the domains. At the centre of the programme is the idea that computational/representational (CR) theories of language must be used to investigate its NB foundations. We consider different ways in which CR and NB might be connected. These are (1) a correlational way, in which NB computation is correlated with the CR theory; (2) an integrated way, in which NB data provide crucial evidence for choosing among CR theories; and (3) an explanatory way, in which properties of NB explain why a CR theory is the way it is. We examine various questions concerning the prospects for explanatory connections in particular, including to what extent it makes sense to say that NB could be specialised for particular computations.

The journey from RDC/DSM diagnoses toward RDoC dimensions

The journey from RDC/DSM diagnoses toward RDoC dimensions

Genetics, Cognition, and Neurobiology of Schizotypal Personality: A Review of the Overlap with Schizophrenia

Schizotypy refers to a set of temporally stable traits that are observed in the general population and that resemble the signs and symptoms of schizophrenia. Here, we review evidence from studies on genetics, cognition, perception, motor and oculomotor control, brain structure, brain function, and psychopharmacology in schizotypy. We specifically focused on identifying areas of overlap between schizotypy and schizophrenia. Evidence was corroborated that significant overlap exists between the two, covering the behavioral brain structural and functional as well molecular levels. In particular, several studies showed that individuals with high levels of schizotypal traits exhibit alterations in neurocognitive task performance and underlying brain function similar to the deficits seen in patients with schizophrenia. Studies of brain structure have shown both volume reductions and increase in schizotypy, pointing to schizophrenia-like deficits as well as possible protective or compensatory mechanisms. Experimental pharmacological studies have shown that high levels of schizotypy are associated with (i) enhanced dopaminergic response in striatum following administration of amphetamine and (ii) improvement of cognitive performance following administration of antipsychotic compounds. Together, this body of work suggests that schizotypy shows overlap with schizophrenia across multiple behavioral and neurobiological domains, suggesting that the study of schizotypal traits may be useful in improving our understanding of the etiology of schizophrenia.

Optimizing the phenotyping of rodent ASD models: enrichment analysis of mouse and human neurobiological phenotypes associated with high-risk autism genes identifies morphological, electrophysiological, neurological, and behavioral features

BackgroundThere is interest in defining mouse neurobiological phenotypes useful for studying autism spectrum disorders (ASD) in both forward and reverse genetic approaches. A recurrent focus has been on high-order behavioral analyses, including learning and memory paradigms and social paradigms. However, well-studied mouse models, including for example Fmr1 knockout mice, do not show dramatic deficits in such high-order phenotypes, raising a question as to what constitutes useful phenotypes in ASD models.MethodsTo address this, we made use of a list of 112 disease genes etiologically involved in ASD to survey, on a large scale and with unbiased methods as well as expert review, phenotypes associated with a targeted disruption of these genes in mice, using the Mammalian Phenotype Ontology database. In addition, we compared the results with similar analyses for human phenotypes.FindingsWe observed four classes of neurobiological phenotypes associated with disruption of a large proportion of ASD genes, including: (1) Changes in brain and neuronal morphology; (2) electrophysiological changes; (3) neurological changes; and (4) higher-order behavioral changes. Alterations in brain and neuronal morphology represent quantitative measures that can be more widely adopted in models of ASD to understand cellular and network changes. Interestingly, the electrophysiological changes differed across different genes, indicating that excitation/inhibition imbalance hypotheses for ASD would either have to be so non-specific as to be not falsifiable, or, if specific, would not be supported by the data. Finally, it was significant that in analyses of both mouse and human databases, many of the behavioral alterations were neurological changes, encompassing sensory alterations, motor abnormalities, and seizures, as opposed to higher-order behavioral changes in learning and memory and social behavior paradigms.ConclusionsThe results indicated that mutations in ASD genes result in defined groups of changes in mouse models and support a broad neurobiological approach to phenotyping rodent models for ASD, with a focus on biochemistry and molecular biology, brain and neuronal morphology, and electrophysiology, as well as both neurological and additional behavioral analyses. Analysis of human phenotypes associated with these genes reinforced these conclusions, supporting face validity for these approaches to phenotyping of ASD models. Such phenotyping is consistent with the successes in Fmr1 knockout mice, in which morphological changes recapitulated human findings and electrophysiological deficits resulted in molecular insights that have since led to clinical trials. We propose both broad domains and, based on expert review of more than 50 publications in each of the four neurobiological domains, specific tests to be applied to rodent models of ASD.

Neuropsychiatric Complications of Efavirenz Therapy: Suggestions for a New Research Paradigm

Neuropsychiatric Complications of Efavirenz Therapy: Suggestions for a New Research Paradigm