搜索结果：Current topics in behavioral neurosciences

Numerous studies carried out in the last 30-40 years have strongly demonstrated that the endocannabinoid system exerts important modulatory functions in the central nervous system (CNS). These neuromodulatory functions encompass the whole life of animals, with specific activities during neurodevelopment (prenatal, postnatal and adolescent periods), adulthood and possibly senescence too. However, this is the life stage less investigated in relation with the endocannabinoid system to date. In the aged brain, the activity of this system appears to be altered, which contributes to subtle impairments that typically occur during ageing in learning and memory, motor behaviour, social behaviour and other neurobiological functions. Some of the changes in endocannabinoid activity may represent a process to attenuate ageing-related impairment in the brain function, which is consistent with its role as a pro-homeostatic system. An important observation is that these alterations become extreme when normal brain ageing acquires pathological characteristics, as happens in chronic neurodegenerative disorders. This includes the cannabinoid type-1 (CB1) receptor downregulation or impairment in its signalling and the increase in endocannabinoid-inactivating enzymes, both hypothesised to contribute to pathogenic events. By contrast, elevated levels of endocannabinoids due to a reduced Fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL) expression and the upregulation of cannabinoid type-2 (CB2) receptors may in turn serve as endogenous pro-homeostatic adaptations against brain impairment. This review synthesises information on: (i) subtle alterations in the endocannabinoid system in the senescent brain in the absence of pathology, with the purpose of demonstrating that these alterations are representative of the extreme changes experienced by this system in the brain pathological ageing; and (ii) the development of neuroprotective therapies based on the pharmacological management of specific endocannabinoid targets to combat neurodegenerative pathologies. Together, research in this area comes at a critical time as global lifespan is increasing, incidence of age-related neurodegenerative disorders is expanding, and the unmet need for efficacious neuroprotective treatments is a public health necessity.

Cannabinoids are increasingly being used to manage pain resulting from a variety of conditions. Both preclinical animal models and human studies have played a crucial role in advancing our knowledge of cannabinoids, their involvement in pain mechanisms, and their potential utility as novel analgesics. This chapter first reviews basic pain neurobiology and the most common experimental pain paradigms, which provide a basis for our discussion of preclinical, human laboratory, and clinical research characterizing the effectiveness of cannabinoids for managing pain. While a substantial body of literature exists describing these effects, findings are complex and largely mixed, dependent on the cannabinoid administered, route of administration, and pain modality/syndrome tested. Herein, we highlight the need for more rigorous, placebo-controlled research defining the therapeutic efficacy of cannabinoids. The chapter concludes by emphasizing the need for further investigation of other cannabis constituents (e.g., minor cannabinoids and terpenes), potential interactions between cannabinoids and other analgesic medications, as well as other emerging issues in the intersection between cannabinoids and pain management.

At the start of the twenty-first century, Arthur D. (Bud) Craig brought back to the fore the Island of Reil (insular cortex or insula). He did so by following, step by step, with rigor and tenacity, the afferent sensory pathway that informs the forebrain about the ongoing physiological status of the organs and tissues of the body. Along with his demonstration of the existence of a primate-specific ascending interoceptive pathway and his subsequent re-interpretation of Sherrington's concept of interoception, Bud Craig's seminal experiments and profound interpretations led him to make the groundbreaking proposals that the dorsal posterior insular cortex provides an ideal substrate for James's concept of emotional embodiment, that the insular cortex contextualizes interoception across a posterior-to-mid-to-anterior integration with multimodal activities, and that the anterior insular cortex has a crucial role in the evolutionary emergence of the awareness of subjective feelings in humans, for the purpose of optimizing metabolic energy usage. Bud Craig's unique work paves the path for further elucidation of the role of the insula and other brain regions in subjective feelings. His discoveries and proposals rest on implacable attention to neuroanatomical and neurophysiological details and a serendipitous quest for the fundamental evolutionary Logic of Life. This chapter provides a detailed description of the ascending interoceptive pathway and the functional and comparative neuroanatomy of the insular cortex in primates. Building on Bud Craig's work, our recent findings suggest that the primary interoceptive cortex serves as a representation of the spino-solitary-parabrachial neuraxis, merging with posterior-to-mid-anterior and dorsal-to-ventral processing streams that form a latticework integration pattern. At the ventral anterior tip of this integration, the von Economo neuron area closes the corticofugal interoceptive-autonomic loop of the sensory-motor homeostatic system through projections to all brainstem nuclei integrating interoceptive afferences.

Classic psychedelics such as psilocybin, lysergic acid diethylamide (LSD), and 5-methoxy-dimethyltryptamine (5-MeO-DMT) have shown promising effects in the treatment of certain mental health conditions. Enthusiastic claims about their therapeutic potential have led to overly optimistic reactions in the media and the public, subsequently resulting in increased use outside of clinical contexts and a heightened rate of psychedelic-related complications. As psychedelics exhibit low toxicity and hardly any habit-forming potential, the typical risks and harms of these substances are often overlooked by mental health professionals and under-assessed in psychedelic research. Similar to the medical history of other psychoactive substances introduced as medicines such as opioids, cocaine, and benzodiazepines, awareness for psychedelic-related complications has emerged with delay. Psychedelics are characterized by a wide range of acute effects on the human psyche and by a particular temporal dynamic in which these effects unfold, including acute, subacute, and long-term effects. Knowledge of how psychedelic effects unfold is not only essential for their use in therapy but also for the understanding and management of risks and complications.Here we provide an overview of complications that may be associated with the use of classic psychedelics, drawing on historical and current classification approaches and using the typical temporal dynamics of drug effects as a guiding thread. We will also discuss to what extent psychedelic-related disorders can be causally and specifically attributed to psychedelic use. Finally, considerations regarding the placement of psychedelic-related disorders within nosological-diagnostic classification systems will be discussed. The increasing interest in using psychedelics within the framework of psychotherapy and the rise of non-medical use underscore the need for a more nuanced classification of psychedelic-related risks and harms. The suggested classification can be used as a comprehensive starting point for the assessment of psychedelic-related complications, contributing to maximizing benefits and minimizing risks of these substances in research, therapy, and beyond.

The elucidation of the functional neuroanatomy of human fear, or threat, extinction has started in the 2000s by a series of enthusiastically greeted functional magnetic resonance imaging (fMRI) studies that were able to translate findings from rodent research about an involvement of the ventromedial prefrontal cortex (vmPFC) and the hippocampus in fear extinction into human models. Enthusiasm has been painfully dampened by a meta-analysis of human fMRI studies by Fullana and colleagues in 2018 who showed that activation in these areas is inconsistent, sending shock waves through the extinction research community. The present review guides readers from the field (as well as non-specialist readers desiring safe knowledge about human extinction mechanisms) during a series of exposures with corrective information. New information about extinction-related brain activation not considered by Fullana et al. will also be presented. After completion of this exposure-based fear reduction program, readers will trust that the reward learning system, the cerebellum, the vmPFC, the hippocampus, and a wider brain network are involved in human fear extinction, along with the neurotransmitters dopamine and noradrenaline. Specific elements of our exposure program include exploitation of the temporal dynamics of extinction, of the spatial heterogeneity of extinction-related brain activation, of functional connectivity methods, and of large sample sizes. Implications of insights from studies in healthy humans for the understanding and treatment of anxiety-related disorders are discussed.

Classic psychedelics such as LSD, psilocybin, and DMT from unregulated markets pose considerable risks through unknown adulterants and potencies. In this chapter, we explore the importance of drug checking in minimizing harm among users of classic psychedelics and examine the opportunities and challenges associated with intervention settings, analytical techniques, and risk communication strategies. Gas chromatography (GC) and liquid chromatography (LC) coupled with mass spectrometry (MS) provide the most reliable and comprehensive analysis results for classic psychedelics. However, they are relatively costly, stationary, and require legal permission to obtain reference standards. Combined presumptive tests, such as thin-layer chromatography (TLC) and reagent testing, offer a time-efficient and cost-effective approach to initial substance screening. For certain compounds, Fourier-transform infrared spectroscopy (FTIR) serves as a valuable complementary technique, although potent psychedelics, such as LSD and NBOMe on blotter paper or in diluted solution, and complex botanical matrices challenge its detection limit, requiring the use of multiple analytical methods to confirm results. Such combination can effectively prevent acute risks, while confirmatory instrumental analysis remains essential for ongoing monitoring and public health efforts. Alongside robust testing procedures, drug checking's consultative component is crucial for clarifying analytical constraints, promoting safer use practices, and offering referrals to health services. By identifying mislabeled samples and ensuring tailored risk communication, drug checking not only protects individual users but also informs the public and health professionals regarding dangerous or novel substances. This chapter situates drug checking as a key public health measure that reduces acute harm from misrepresented psychedelic substances while supporting monitoring efforts.

In the last two decades, the endocannabinoid system has emerged as a crucial modulator of motivation and emotional processing. Due to its widespread neuroanatomical distribution and characteristic retrograde signaling nature, cannabinoid type I receptors and their endogenous ligands finely orchestrate somatic and axon terminal activity of dopamine neurons. Owing to these unique features, this signaling system is a promising pharmacological target to ameliorate dopamine-mediated drug-seeking behaviors while circumventing the adverse side effects of, for instance, dopaminergic antagonists. Despite considerable preclinical efforts, an agreement on the efficacy of endocannabinoid-targeting compounds for treating drug substance use disorders in humans has not been reached. In the following chapter, we will summarize preclinical and clinical evidence addressing the therapeutic potential of cannabinoids and endocannabinoid-targeting compounds in substance use disorders. To bridge the gap between animal and clinical research, we capitalize on studies evaluating the impact of endocannabinoid-targeting compounds in relevant settings, such as the management of drug relapse. Finally, we discuss the therapeutic potential of novel cannabinoid compounds that hold promise for treating substance use disorders.

This chapter is dedicated to the intellectual legacy of A.D. Bud Craig and advancing the understanding of interoception. The chapter is organized into three critical domains of interoceptive research: Bodily Self, Emotion, and Subjective Time. Beginning with foundational neuroanatomical research on temperature and pain processing, the volume progresses to explore how interoceptive signals integrate to form our bodily self-representation and emotional experiences. This leads to discussion of the interoceptive self and its foundation role in emotional experience. Finally, this culminates in how interoception shapes our perception of time, including experiences in altered states of consciousness. This exploration into interoception points to promising future research focused on computational modeling of interoceptive processing, personalized treatment approaches based on interoceptive principles, and clinical applications for psychiatric, neurological, and pain conditions. In this chapter, we aim to outline the goals of this collection and the remaining gaps in the continuance of Bud Craig's seminal career.

The subacute period following the use of classic psychedelics is often marked by an "afterglow" - a state characterized by elevated mood; enhanced psychological well-being; increased emotional openness toward self, others, and nature; and sometimes a heightened sense of clarity and existential meaning. From a neurobiological perspective, subacute psychedelic states have been associated with changes in brain network connectivity, amygdala reactivity, and neuroplasticity.However, individual responses to psychedelics vary considerably, and not all users experience positive aftereffects. Some struggle to make sense of their psychedelic experiences or to integrate them into daily life. Others report psychological instability, including mood swings, anxiety, panic attacks, sleep disturbances, depressive symptoms, feelings of alienation, depersonalization, derealization, persisting perceptual changes, flashbacks, prolonged psychosis, mania, or suicidal ideation.Many of these issues can be mitigated through interventions commonly referred to as "psychedelic integration," often practiced individually or provided by peers within the psychedelic community or through other forms of social support. In cases of severe or persistent symptoms, however, professional mental health care may be required. Key components in managing subacute complications include establishing safety, mobilizing internal and external resources, supporting the psychological processing of the experience, addressing maladaptive interpretations, monitoring symptom progression, and, when indicated, pharmacotherapy. Persistent complications may furthermore warrant established disorder-specific treatment to prevent further chronification.This chapter outlines and discusses strategies for managing clinically significant subacute complications, with the aim of advancing a nuanced harm-reduction framework relevant to research, clinical, and non-clinical contexts.

Anxiety disorders in children lead to substantial impairment in functioning and development. Even the most effective gold standard treatments for childhood anxiety have 50% remission rates, suggesting a critical need to improve current treatments. Optimising exposure, the key component of anxiety treatments, represents a promising way to do so. This chapter explains how to optimise exposure outcomes for childhood anxiety through inhibitory learning theory. This chapter describes the background of inhibitory learning, including its different components and the empirical evidence supporting it. We then discuss how to improve the formation of inhibitory associations through enhancing expectancy violation, the proposed mechanism underlying inhibitory learning. Strategies to enhance inhibitory learning for child anxiety treatment are provided. These include strategies to enhance the formation of inhibitory associations, such as psychoeducation, eliminating safety signals, deepened extinction, occasional reinforced extinction, and affect-based strategies. Additionally, strategies to enhance retrieval include variability, multiple contexts, and retrieval cues. Suggestions are made on how to adapt these strategies to child populations. Further, a clinical guide for using inhibitory learning strategies in child anxiety treatment is included as an appendix. This details how clinicians can utilise these strategies to enhance current treatments, including examples of case studies and scripts.

This chapter will review the basic pharmacology of the canonical cannabinoid receptors. The endocannabinoid system is a complex signalling network involved in a wide range of physiological processes, including pain modulation, appetite regulation, and synaptic plasticity. The canonical cannabinoid receptors, CB1 and CB2, are central in orchestrating this system. CB1 is highly enriched in the central nervous system (CNS), where it plays a crucial role in modulating neurotransmitter release and synaptic plasticity. In contrast, CB2 is predominantly expressed in peripheral tissues and immune cells, participating in anti-inflammatory processes. Here, we focus on cannabinoid receptor distribution, intracellular signalling, and receptor regulation. We describe the intracellular signalling pathways activated by CB1, including the modulation of ion channels, second messengers, and protein kinases. Overall, this chapter provides an overview of the canonical cannabinoid receptors and their role in the regulation of neuronal signalling and plasticity, highlighting the molecular and cellular mechanisms underlying their effects in the CNS.

Since cannabis and nicotine are two of most commonly used substances and are often used together, this paper will review the effects of cannabis (specifically THC, or tetrahydrocannabinol) and nicotine on selective attention, sustained attention, visuospatial attention, attentional bias, and attentional disorders. This review includes preclinical and clinical findings throughout all periods of development and adulthood. Selective attention is directly impacted by cannabis use, while reaction time is dependent on the timing of the last cannabis exposure. Among individuals who use cannabis, there is an attentional bias that reduces anxiety and increases focus on cannabis-related cues. Preclinical studies show that cannabis induces attention deficits that persist even after an abstinence period. Preclinical and clinical studies of prenatal cannabis exposure (PCE) provide evidence that offspring will have an increased risk for drug-seeking behavior, attention deficits, and impulsivity, which may lead to attentional disorders such as attention deficit hyperactivity disorder (ADHD) and schizophrenia. Nicotine has a dose-dependent effect on attention in adults, though preclinical studies have shown mixed results, possibly due to differences in experimental design. Prenatal nicotine exposure (PNE) impairs attentional networks by increasing one's risk for ADHD, oppositional defiant disorder, and conduct disorder. Additionally, maternal secondhand smoke exposure is linked to ADHD/conduct disorder risk in offspring. Preclinical studies on prenatal nicotine exposure suggest that there may be sex differences in which males are affected more so than females with PNE. Summary: Overall, cannabis/THC impairs attention, and nicotine enhances attention; however, both substances impair attention when individuals are exposed prenatally.

A.D. (Bud) Craig was best known to us colloquially as Bud Craig; his groundbreaking work has advanced our understanding of the neuroanatomical basis of the bodily self, emotion, and subjective time. His research elucidated the intricate pathways of interoception - the brain's processing of internal body signals - and highlighted the insula's pivotal role in integrating these signals. Craig's pioneering insights demonstrated that bodily sensations, such as pain and temperature, are deeply intertwined with emotional experiences and homeostatic needs. By mapping the thalamocortical pathways and emphasizing the insula's function in predicting future bodily states, he provided a comprehensive framework that connects physiological states to emotional and temporal experiences. This fundamental work has profoundly influenced a new generation of scientists and inspired the current volume. In this book, we have invited researchers influenced by Craig's theories to explore the neural correlates of emotion, pain, interoception, and time. In this chapter, we present how the editors of this book were directly influenced by Craig's findings and lay the groundwork for the large collective contribution of the authors of the subsequent chapters that continue to explore this ever-evolving scientific landscape.

Interoception, the process of detecting, perceiving, and interpreting signals from within the body, is essential for physiological regulation and adaptive behavior. A growing body of research underscores important potential links between interoceptive dysfunction and psychiatric disorders. Parallel advancements in the field of computational psychiatry have led to the development of biologically plausible models of information processing in the brain. This review surveys the current state of traditional and computational research approaches to study interoceptive processes in psychiatry. We also provide a foundational description of predominant computational approaches and theoretical models of interoception. Finally, we discuss the potential molecular foundations of interoceptive computation and consider future directions for incorporating computational models to enhance clinical insights and inform personalized treatments. We conclude that combining interoception and computational modeling approaches holds considerable promise in moving the field forward, both in addressing unresolved mechanistic questions and identifying novel potential therapeutic targets.

Psychotic symptoms are uncommon and non-specific adverse effects of classic (serotonergic) psychedelics such as lysergic acid diethylamide (LSD), psilocybin, and mescaline. They can emerge during the acute phase of psychedelic drug effects, persist into the subacute ("afterglow") period, or, in rare cases, develop into long-term psychotic illness. Across all three scenarios, the symptoms can be deeply distressing due to their rapid changes, unpredictability, and significant adverse behavioral consequences.Psychedelics have a long history of use as research models for schizophrenia because of the phenomenological overlaps between their acute effects and the core symptoms of psychosis. This "model psychosis" paradigm, however, has been widely criticized: although certain acute symptoms may appear similar, the etiology and psychodynamic background of primary psychosis only partially apply to psychedelic-related psychosis. Moreover, it remains unclear whether psychotic symptoms following the use of classic psychedelics differ meaningfully from those associated with other substances, such as dopaminergic stimulants or cannabis.A transient porosity of ego boundaries is a core feature of acute psychedelic states, ranging from heightened feelings of connectedness with oneself and others to complete ego dissolution. These experiences are often perceived as positive and may be followed by a subacute phase characterized by sustained increases in openness to new experiences. In some cases, however, ego dissolution may become fear-inducing and progress from challenging but manageable experiences to paranoid psychotic reactions that require therapeutic guidance and intervention.In this chapter, we examine phenomenological similarities and differences between psychedelic-induced psychosis and primary psychosis. Consistent with current international diagnostic classification systems, we conclude that, with increasing temporal distance from the initial psychedelic "index" experience that predated the symptoms, persisting psychedelic-induced psychotic symptoms become indistinguishable from primary psychosis. Finally, we present a psychodynamic therapeutic approach for schizophrenia-spectrum psychosis that may, to some extent, be adapted to psychotic symptoms observed across all three phases of psychedelic drug effects.

Antenatal mood disturbances are experienced by as many as 20% of pregnant mothers and are commonly treated with serotonin reuptake inhibitor (SRI) antidepressants. Both maternal depression and SRIs during pregnancy are associated with low birth weight and infant neurobehavioral disturbances, as well as longer-term impacts on child neurodevelopment, behavior, and mental health. As maternal depression and its pharmacotherapy are inherently interrelated prenatal exposures, distinguishing how these early life factors uniquely impact child development remains methodologically challenging. Over the past several years, however, advanced neuroimaging has been successfully used to identify neural correlates of prenatal depression and SRI antidepressant exposure on the developing brain, extending from the early newborn period through adolescence. In this review, we examine the use of magnetic resonance imaging and electroencephalography to study child brain structure or function, with a specific focus on prenatal antidepressants as the primary exposure in relation to either typical development or exposure to maternal depressed mood alone. We include both cross-sectional and longitudinal neuroimaging studies, as well as those that link early brain findings with cognitive or behavioral outcome in childhood. We also discuss factors that may shape neurodevelopmental risk (e.g., maternal mental illness severity, sex differences, genetic variability) and present suggestions for future research that will advance our understanding of child brain development in the context of maternal mood disturbances during pregnancy.

This chapter explores the insula's role in shaping body image through interoception - the neural process of sensing, interpreting, and integrating internal bodily signals to facilitate a coherent sense of self. Drawing on A.D. (Bud) Craig's hierarchical model, which emphasizes the insula's integration of sensory input into higher-order self-representations, we examine how disruptions in interoceptive processing may contribute to body image disturbance. This framework is applied to mental health conditions such as anorexia nervosa, body dysmorphic disorder, as well as physical health conditions including phantom limb pain and cancer, highlighting evidence for impaired interoceptive signaling and altered insular cortex function. We propose a mechanistic model describing how such disruptions can affect both sensory processing and the subjective experience of the body, leading to distorted body perception. We conclude with a discussion of future research directions and the potential for interoception-based therapeutic interventions targeting body image disturbance.

A.D. (Bud) Craig (1951-2023) redefined the concept of interoception and provided a novel, revolutionary understanding of the neural basis for human awareness. In unsurpassed anatomical-physiological studies in monkeys, Craig showed that the insular cortex is the primary sensory cortex for interoception, or the image of the "material me" that provides a homeostatic representation of the physiological condition of the body. He showed that the insula contains a postero-anteriorly organized somatotopic map of the interoceptive sensations, and that it encodes both the localization and the intensity discrimination of interoceptive sensations. In seminal work in humans, he demonstrated that the interoceptive feelings are re-represented, and multimodally integrated, in anterior portions of the insula in sequence of increasingly homeostatically efficient representations that integrate all salient neural activity. He further showed that subjective awareness is associated with activation of the anterior insular cortex and suggested that this brain region also is critical for fluid intelligence and the perception of time. His work has led to a paradigm shift in our understanding of interoception and how interoceptive sensations underlie consciousness, a topic that long has been considered elusive, or even beyond our comprehension.

Stress is a ubiquitous facet of life. Ranging in form (e.g., psychosocial, physical, nutritional, economic) and longevity (e.g., acute, chronic), stressors affect the biology of those directly in their line of attack. As is becoming increasingly appreciated, the pernicious effects of stress echo across generations (Dias et al. 2015; Yehuda and Lehrner 2018; Jawaid et al. 2021; Dion et al. 2022; Zhou and Ryan 2023; Dias 2024). With a focus on learning and memory, this chapter addresses how stressors derail learning and memory in the generation directly exposed to them andin future generations. To do so, with a specific emphasis on associative fear conditioning in humans and rodents, we touch upon the relevance of extinction training in the aftermath of such conditioning and the recall of such extinction training as windows into normative and disrupted learning. Next, we briefly discuss underlying neuroanatomical substrates mediating these processes. We then draw attention to influences of postnatal, in utero, and pre-conceptional stress on learning and memory across generations. Finally, we briefly outline biological factors that underlie how learning and memory is derailed by these stressors.