Current topics in behavioral neurosciences最新文献

Over a decade after the first edition of "Behavioral Neurobiology of Alcohol Addiction," this chapter revisits the field at a critical juncture, marked by both persistent challenges and emerging opportunities. We reflect on the translational gap that has stalled the development of new treatments for alcohol use disorder (AUD), despite decades of promising preclinical findings. Particular attention is given to the replicability crisis in animal research, publication biases, and the limited predictive validity of existing models. At the same time, we highlight advances that offer renewed hope, including molecular and circuit-level technologies, AI-driven data analysis, real-world assessments, and new pharmacological candidates, such as GLP-1 agonists and psychedelics. These breakthroughs are considered alongside the increasing recognition of inflammation, pain, and neuroimmune factors as integral to AUD. However, we caution against exaggerated claims and urge the field to avoid oversimplified models, especially those that conflate habits and compulsions. Finally, we argue that neurobiological progress must be complemented by public health strategies aimed at reducing stigma and improving access to care. By fostering empirical rigor, embracing complexity, and maintaining critical self-reflection, addiction science can better align its innovations with real-world clinical and societal needs.

Research in the field of preclinical alcohol research, but also science in general, has a problem: Many published scientific results cannot be repeated. As a result, findings from preclinical research often do not translate well to humans, causing increasing disappointment and calls for restructuring of preclinical research, that is, better reproducibility of preclinical research. However, the replication crisis is an inherent problem in biomedical research. Replication failures are not only due to small experimental variations but are often the result of poor methodology. In response to the replication crisis, numerous guidelines and recommendations have been proposed to promote transparency, rigor, and reproducibility in scientific research. What is missing today is a framework that integrates all the confusing information that results from all these guidelines and recommendations. Here we present STRINGENCY, an integrative approach to good practice guidelines for preclinical alcohol research, which can also apply to behavioral research in general and which aims to improve preclinical research to better prepare it for translation and minimize the "valley of death" in translational research. STRINGENCY includes systematic review and, when possible, meta-analysis prior to study design, sample size calculation, preregistration, multisite experiments, scientific data management (FAIR), reporting of data using ARRIVE, generalization of research data, and transparent publications that allow reporting of null results. We invite the scientific community to adopt STRINGENCY to improve the reliability and impact of preclinical alcohol research.

Several studies have been done to investigate the role of hearing loss (HL) in cognitive decline. A co-existence of these two conditions has been identified. Recently, thanks to the use of functional MRI and EEG it has been shown that untreated HL can expose patients with cognitive decline to a higher risk of developing Alzheimer Disease (AD). This chapter will discuss the difference between central and peripheral HL, the link between HL and cognition and the relationship between HL and AD. At the end of the chapter the available technologies to treat HL will be discussed as well as their impact on memory and cognition.

A decline in hippocampal function has long been associated with the progression of cognitive impairments in patients with Alzheimer's disease (AD). The disruption of hippocampal synaptic plasticity [primarily the reduction of long-term potentiation LTP] by excess production of soluble beta-amyloid (Aβ) has long been accepted as the mechanism by which AD pathology impairs memory, at least during the early stages of AD pathogenesis. However, the premise that hippocampal LTP underpins the formation of associative, long-term memories has been challenged. Here, we consider evidence that this canonical view of LTP needs to be refined. Similarly, the view that the hippocampus simply supports memory ignores the wealth of data showing that the hippocampus is functionally heterogeneous along its septo-temporal axis. The ventral (but not the dorsal) hippocampus plays a major role in modulating emotional reactions to conflict. Here, we suggest that hippocampal LTP is not involved in forming long-term associative memories, but instead contributes to the disambiguation of overlapping memories in situations of conflict and associative interference. This conceptualisation of hippocampal synaptic plasticity may help explain how early-stage AD pathology may impact both memory and anxiety.

Behavioral and psychological symptoms of dementia (BPSD), such as agitation, apathy, and psychosis, are highly prevalent and have a significant impact on patients and their care partners. The neurobiology of BPSD involves a complex interplay of structural brain changes and alterations in the neurotransmitter system. Various genetic and plasma biomarkers have also been studied. Research in BPSD has been limited by heterogeneity in the diagnostic criteria and assessment tools. As such, there have been ongoing efforts to develop a gold-standard assessment tool and diagnostic criteria. Current practice guidelines recommend nonpharmacological therapies as first-line treatments. Pharmacological options are often used when there is an insufficient response to nonpharmacological strategies, but there can be serious adverse effects with existing pharmacological agents. This has resulted in growing efforts to develop novel therapeutics with more favorable tolerability profiles, with some showing promising results. Other biological therapies, such as neurostimulation, have also demonstrated positive results. As our understanding of BPSD evolves, ongoing research efforts in treatment of BPSD are warranted in order to enhance the quality of life for patients and their care partners.

Substance use disorders (SUDs) represent complex public health challenges characterized by a blend of genetic, cognitive, environmental, and psychosocial factors. This chapter explores the critical role of interoceptive processing - the internal sensing of physiological states - in the neurobiology and treatment of SUDs. Interoceptive dysfunctions are highlighted as central to the craving, emotional regulation, and decision-making processes that underpin addictive behaviors. The importance of the insula in sustaining drug use, particularly nicotine, underscores a broader involvement of interoceptive pathways in SUDs. Altered interoceptive processing is evident across various SUDs, where individuals demonstrate both a heightened sensitivity to drug-related cues and a diminished ability to process aversive stimuli, suggesting substantial neurobiological underpinnings that complicate treatment outcomes. Moreover, we delve into the theoretical and computational approach to understanding interoceptive processing in SUDs. This perspective utilizes a predictive coding framework, positing that the brain continuously generates and updates predictions about internal states based on sensory inputs. In SUDs, disruptions in this predictive mechanism can lead to inaccuracies in interoceptive perception, contributing significantly to the compulsive nature of drug-seeking behaviors and the challenges associated with treatment. We explore how computational models, such as Bayesian inference, provide insights into the interplay between expected and received interoceptive signals, highlighting the role of hyper-precise prior beliefs in the persistence of craving and impulsivity. This theoretical approach not only deepens our understanding of the neural and cognitive bases of addiction but also suggests novel intervention strategies. By recalibrating interoceptive predictions through targeted therapies, such as neuromodulation and mindfulness training, we can potentially restore the interoceptive accuracy, thereby offering new avenues for effective treatment of SUDs.

With his elegant studies, Bud Craig determined the structural neural basis for interoception and critically expanded our conceptual understanding of it. Importantly, he placed pain in the framework of interoception and redefined pain as a homeostatic emotion. Craig understood emotions and pain as experiences based on inferential brain processes within the theoretical model of prediction processing. This chapter aims to give a brief overview of relevant research. Mind-body therapies, such as meditation, mindfulness, yoga, Tai Chi, and others, are included as first-line non-pharmacological approaches in clinical guidelines for the management of chronic pain. Craig's groundbreaking work provided the background for our contemporary understanding of mind-body therapies and for the key role that interoceptive processes play in these therapies as they apply to a wide range of clinical conditions, including pain. This chapter reviews the tremendous influence that Craig's work had on the current state of research on mind-body therapies for managing chronic pain and how it led to new directions for cutting-edge clinical and neuroscientific research.

Currently available therapeutic modalities for alcohol use disorder (AUD) produce limited effect sizes or long-term compliance. Recent methods that were developed to modulate brain activity represent potential novel treatment options. Various methods of brain stimulation, when applied repeatedly, can induce long-term neurobiological, behavioral, and cognitive modifications. Recent studies in alcoholic subjects indicate the potential of brain stimulation methods to reduce alcohol craving, consumption, and relapse. Specifically, deep brain stimulation (DBS) of the nucleus accumbens or non-surgical stimulation of the dorsolateral prefrontal cortex (PFC) or medial PFC and anterior cingulate cortex using transcranial magnetic stimulation (TMS) has shown clinical benefit. However, further preclinical and clinical research is needed to establish understanding of mechanisms and the treatment protocols of brain stimulation for AUD. While efforts to design comparable apparatus in rodents continue, preclinical studies can be used to examine targets for DBS protocols, or to administer temporal patterns of pulsus similar to those used for TMS, to more superficial targets through implanted electrodes. The clinical field will benefit from studies with larger sample sizes, higher numbers of stimulation sessions, maintenance sessions, and long follow-up periods. The effect of symptoms provocation before and during stimulation should be further studied. Larger studies may have the power to explore predictive factors for the clinical outcome and thereby to optimize patient selection and eventually even develop personalization of the stimulation parameters.

Brain-imaging studies show that the development and maintenance of alcohol use disorder (AUD) is determined by a complex interaction of different neurotransmitter systems and multiple psychological factors. In this context, the dopaminergic reinforcement system appears to be of fundamental importance. We focus on the excitatory and depressant effects of acute versus chronic alcohol intake and its impact on dopaminergic neurotransmission. Furthermore, we describe alterations in dopaminergic neurotransmission as associated with symptoms of alcohol dependence. We specifically focus on neuroadaptations to chronic alcohol consumption and their effect on central processing of alcohol-associated and reward-related stimuli. Altered reward processing, complex conditioning processes, impaired reinforcement learning, and increased salience attribution to alcohol-associated stimuli enable alcohol cues to drive alcohol seeking and consumption. Finally, we will discuss how the neurobiological and neurochemical mechanisms of alcohol-associated alterations in reward processing and learning can interact with stress, cognition, and emotion processing.

The use of antipsychotic drugs in children has greatly expanded over the past 30 years. This increase occurred despite a lack of research addressing how these drugs affect brain development. This review summarizes and synthesizes preclinical studies that have ascertained the short- and long-term consequences of prenatal and early postnatal antipsychotic drug administration. Antipsychotic drugs are well-known for their ability to block D₂-type dopamine receptors and this action features in two main themes that emerge from the literature. First, prenatal antipsychotic drug exposure generally leads to a long-term hypodopaminergic state while early postnatal antipsychotic drug exposure produces a hyperdopaminergic one. Second, the effects of postnatal antipsychotic drug exposure appear roughly similar regardless of age, but drug administration any time prior to puberty (pre or early postnatal) leaves a lasting imprint on neural and behavioral function that persists long after treatment cessation. The enduring brain and behavioral changes seen after early-life antipsychotic administration in animal models provide support for initiatives aimed at reducing the number of children treated with antipsychotics and limiting the dose and length of treatment for those that need them.