Current topics in behavioral neurosciences最新文献

Alzheimer's disease is a highly complex and multifactorial neurodegenerative disorder, with age being the most significant risk factor. The incidence of Alzheimer's disease doubles every 5 years after the age of 65. Consequently, one of the major challenges in Alzheimer's disease research is understanding how the brain changes with age. Gaining insights into these changes could help identify individuals who are more prone to developing Alzheimer's disease as they age. Over the past 25 years, studies on brain aging have examined thousands of human brains to explore the neuronal basis of age-related cognitive decline. However, most of these studies have focused on adults over 60, often neglecting the critical menopause transition period. During menopause, women experience a substantial decline in ovarian sex hormone production, with a decrease of about 90% in estrogen levels. Estrogen is known for its neuroprotective effects, and its significant loss during menopause affects various biological systems, including the brain. Importantly, despite known differences in dementia risk between sexes, the impact of biological sex and sex hormones on brain aging and the development of Alzheimer's disease remains underexplored.

The functional complexity of brain circuits underlies the broad spectrum of behaviors, cognitive functions, and their associated disorders. Mitochondria, traditionally known for their role in cellular energy metabolism, are increasingly recognized as central to brain function and behavior. This review examines how mitochondria are pivotal in linking cellular energy processes with the functioning of neural circuits that govern fear and anxiety. Following an introductory section in which we summarize current knowledge about fear and anxiety neural circuits, we provide a brief summary of mitochondria fundamental roles (e.g., from energy production and calcium buffering to their involvement in reactive oxygen species (ROS) generation, mitochondrial dynamics, and signaling), particularly emphasizing their contribution to synaptic plasticity, neurodevelopment, and stress response mechanisms. The review's core focuses on the current state of knowledge regarding how mitochondrial function and dysfunction impact the neural substrates of fear and anxiety. Furthermore, we explore the implications of mitochondrial alterations in the context of posttraumatic stress disorder (PTSD) and anxiety disorders, underscoring the potential of mitochondrial pathways as new therapeutic targets. Integrating insights from genetic, biochemical, neurobiological, behavioral, and clinical studies, we propose a model in which mitochondrial function is critical for regulating the neural circuits that underpin fear and anxiety behaviors, highlighting how mitochondrial dysfunction can lead to their pathological manifestations. This integration emphasizes the potential for developing novel treatments targeting the biological roots of fear, anxiety, and related disorders. By merging mitochondrial biology with behavioral and circuit neuroscience, we enrich our neurobiological understanding of fear and anxiety, uncovering promising avenues for therapeutic intervention.

In this article, we briefly overview how the expression, measurement, and treatment of anxiety in autism may be different from the general population. We review the literature on links between sensory processing differences and anxiety, which show transdiagnostic patterns but are an especially prominent feature of anxiety in autism. Specifically, we focus on how the sense of interoception, i.e., how we perceive sensory information from within our bodies, contributes to anxiety in autism. We present new findings integrating multimodal interoceptive measures and total anxiety symptoms in a sample of n = 38 non-autistic and n = 43 autistic individuals, ages 8-55 years. Using principal components analysis, we found two components relating to interoceptive confusion (i.e., self-reported ability to localize and interpret interoceptive cues): one component that closely relates to anxiety symptoms and one component that is distinct from anxiety. Interoceptive perception (i.e., performance on a lab-based task) was uniformly related to interoceptive confusion when distinguished from anxiety but showed complex relations with total anxiety symptoms. Combined, these findings suggest meaningful subtypes of interoceptive difficulties and their interrelationship with anxiety. We present conclusions and future directions for consideration of individual differences, toward creating a personalized understanding of anxiety-interoception links.

Most of the scientific research on alcohol consumption behavior in humans is laboratory-based, as reflected by the ratio of laboratory vs. real-life contributions to this handbook. Studies in daily life, although having a long history in addiction research (Shiffman et al., Ann Behav Med 16:203-209, 1994), are in the minority. This is surprising, given that patients with substance use disorders are suffering in daily life and not in the laboratory setting. In other words, drinking patterns and symptoms of alcohol use disorder evolve not in the lab but in daily life, where patients show difficulties in limiting their alcohol intake accompanied with all kinds of related problems. The ultimate goal of all interventions, independent of being tailored toward restricted drinking or abstinence, is again an altered behavior in real life. Translated to practice, patients' behavior in the lab may not translate to daily life, often showing minimal ecological validity. Therefore, we have to question to which degree lab-based research findings translate into daily life. Fortunately, the current digital revolution provided us with more and more tools, enabling us to monitor, analyze, and change behavior in human everyday life. Our chapter does not intend to give a comprehensive overview of the daily life research on alcohol consumption over the last few decades as others do (Morgenstern et al., Alcohol Res Curr Rev 36:109, 2014; Piasecki, Alcohol Clin Exp Res 43:564-577, 2019; Shiffman, Psychol Asses 21:486-497, 2009; Votaw and Witkiewitz, Clin Psychol Sci 9:535-562, 2021; Wray et al., Alcohol Res Curr Rev 36:19-27, 2014). Instead, we aim at the following: first, to highlight the key advantages of ecological momentary assessment to motivate scientists to add daily life research components to their laboratory research and, second, to provide some guidance on how to begin with daily life research.

Studies presented in this chapter show that: (1) in the brain, ethanol is metabolized by catalase to acetaldehyde, which condenses with dopamine forming salsolinol; (2) acetaldehyde-derived salsolinol increases the release of dopamine mediating, via opioid receptors, the reinforcing effects of ethanol during the acquisition of ethanol consumption, while (3) brain acetaldehyde does not influence the maintenance of chronic ethanol intake, it is suggested that a learned cue-induced hyperglutamatergic system takes precedence over the dopaminergic system. However, (4) following a prolonged ethanol deprivation, the generation of acetaldehyde in the brain again plays a role, contributing to the increase in ethanol intake observed during ethanol re-access, called the alcohol deprivation effect (ADE), a model of relapse behavior; (5) naltrexone inhibits the high ethanol intake seen in the ADE condition, suggesting that acetaldehyde-derived salsolinol via opioid receptors also contributes to the relapse-like drinking behavior. The reader is referred to glutamate-mediated mechanisms that trigger the cue-associated alcohol-seeking and that also contribute to triggering relapse.

Alcohol use disorder (AUD) can be defined by a compulsion to seek and take alcohol, the loss of control in limiting intake, and the emergence of a negative emotional state when access to alcohol is prevented. Alcohol use disorder impacts multiple motivational mechanisms and can be conceptualized as a disorder that includes a progression from impulsivity (positive reinforcement) to compulsivity (negative reinforcement). Compulsive drug seeking that is associated with AUD can be derived from multiple neuroadaptations, but the thesis argued herein is that a key component involves the construct of negative reinforcement. Negative reinforcement is defined as drug taking that alleviates a negative emotional state. The negative emotional state that drives such negative reinforcement is hypothesized to derive from the dysregulation of specific neurochemical elements that are involved in reward and stress within basal forebrain structures that involve the ventral striatum and extended amygdala, respectively. Specific neurochemical elements in these structures include decreases in reward neurotransmission (e.g., decreases in dopamine and opioid peptide function in the ventral striatum) and the recruitment of brain stress systems (e.g., corticotropin-releasing factor [CRF]) in the extended amygdala, which contributes to hyperkatifeia and greater alcohol intake that is associated with dependence. Glucocorticoids and mineralocorticoids may play a role in sensitizing the extended amygdala CRF system. Other components of brain stress systems in the extended amygdala that may contribute to the negative motivational state of withdrawal include norepinephrine in the bed nucleus of the stria terminalis, dynorphin in the nucleus accumbens, hypocretin and vasopressin in the central nucleus of the amygdala, and neuroimmune modulation. Decreases in the activity of neuropeptide Y, nociception, endocannabinoids, and oxytocin in the extended amygdala may also contribute to hyperkatifeia that is associated with alcohol withdrawal. Such dysregulation of emotional processing may also significantly contribute to pain that is associated with alcohol withdrawal and negative urgency (i.e., impulsivity that is associated with hyperkatifeia during hyperkatifeia). Thus, an overactive brain stress response system is hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into protracted abstinence, and to contribute to the compulsivity of AUD. The combination of the loss of reward function and recruitment of brain stress systems provides a powerful neurochemical basis for a negative emotional state that is responsible for the negative reinforcement that at least partially drives the compulsivity of AUD.

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.

Eating disorders (EDs) are characterized by abnormal responses to food and weight-related stimuli and are associated with significant distress, impairment, and poor outcomes. Because many of the cardinal symptoms of EDs involve disturbances in perception of one's body or abnormal affective or cognitive reactions to food intake and how that affects one's size, there has been longstanding interest in characterizing alterations in sensory perception among differing ED diagnostic groups. Within the current review, we aimed to critically assess the existing research on exteroceptive and interoceptive perception and how sensory perception may influence ED behavior. Overall, existing research is most consistent regarding alterations in taste, visual, tactile, and gastric-specific interoceptive processing in EDs, with emerging work indicating elevated respiratory and cardiovascular sensitivity. However, this work is far from conclusive, with most studies unable to speak to the precise etiology of observed perceptual differences in these domains and disentangle these effects from affective and cognitive processes observed within EDs. Further, existing knowledge regarding perceptual disturbances in EDs is limited by heterogeneity in methodology, lack of multimodal assessment protocols, and inconsistent attention to different ED diagnoses. We propose several new avenues for improving neurobiology-informed research on sensory processing to generate actionable knowledge that can inform the development of innovative interventions for these serious disorders.

Pediatric anxiety disorders and post-traumatic stress disorder (PTSD) are associated with elevated threat sensitivity and impaired emotion regulation, accompanied by dysfunction in the neural circuits involved in these processes. Despite established treatments like cognitive behavioral therapy (CBT) and selective serotonin reuptake inhibitors, many children do not achieve remission, underscoring the importance of understanding the neurobiological underpinnings of these disorders. This review synthesizes current research on the neural predictors of treatment response and the neurofunctional changes associated with treatment in pediatric anxiety and PTSD during threat and reward processing. Several key findings emerged. First, enhanced threat/safety discrimination in the amygdala predicted better outcomes of pediatric anxiety and PTSD treatments. Second, differences in pretreatment activation within the lateral prefrontal and dorsal anterior cingulate cortices predicted treatment response, likely reflecting baseline executive control differences. Third, post-CBT decreases in activation in default mode, visuo-attentional, and sensorimotor areas may support treatment-related increases in task engagement. Finally, functional connectivity between the amygdala and other limbic, prefrontal, and default mode network nodes predicts treatment response in anxiety and PTSD, highlighting its potential as a biomarker for therapeutic efficacy. Understanding these neurofunctional markers could lead to more targeted interventions, optimizing treatment planning and potentially leading to the development of "pretreatment" strategies to enhance the efficacy of existing treatments. This review highlights the necessity for future research to establish more direct links between neuroimaging findings and clinical outcomes to facilitate the translation of these findings into clinical practice.

Alcohol impacts neural circuitry throughout the brain and has wide-ranging effects on the biophysical properties of neurons in these circuits. Articulating how these wide-ranging effects might eventually result in altered computational properties has the potential to provide a tractable working model of how alcohol alters neural encoding. This chapter reviews what is currently known about how acute alcohol influences neural activity in cortical, hippocampal, and dopaminergic circuits as these have been the primary focus of understanding how alcohol alters neural computation. While other neural systems have been the focus of exhaustive work on this topic, these brain regions are the ones where in vivo neural recordings are available, thus optimally suited to make the link between changes in neural activity and behavior. Rodent models have been key in developing an understanding of how alcohol impacts the function of these circuits, and this chapter therefore focuses on work from mice and rats. While progress has been made, it is critical to understand the challenges and caveats associated with experimental procedures, especially when performed in vivo, which are designed to answer this question and if/how to translate these data to humans. The hypothesis is discussed that alcohol impairs the ability of neural circuits to acquire states of neural activity that are transiently elevated and characterized by increased complexity. It is hypothesized that these changes are distinct from the traditional view of alcohol being a depressant of neural activity in the forebrain.