Current Topics in Behavioral Neurosciences

Psychedelic drugs such as psilocybin and ketamine are returning to clinical research and intervention across several disorders including the treatment of depression. This chapter focusses on psychedelics that specifically target the 5-HT2A receptor such as psilocybin and DMT. These produce plasma-concentration related psychological effects such as hallucinations and out of body experiences, insightful and emotional breakthroughs as well as mystical-type experiences. When coupled with psychological support, effects can produce a rapid improvement in mood among people with depression that can last for months...

Opioid receptors are widely expressed in the brain, and the opioid system has a key role in modulating mood, reward processing and stress responsivity. There is mounting evidence that the endogenous opioid system may be dysregulated in depression and that drug treatments targeting mu, delta and kappa opioid receptors may show antidepressant potential. The mechanisms underlying the therapeutic effects of opioid system engagement are complex and likely multi-factorial. This chapter explores various pathways through which the modulation of the opioid system may influence depression...

The widespread adoption of selective serotonin reuptake inhibitors (SSRIs) as first-line pharmacological treatments in the management of clinical depression transformed the landscape of drug therapy for this condition. SSRIs are safer and better tolerated than the tricyclic antidepressants (TCAs) that they replaced. However, they have limitations that may have placed a ceiling on the expectations of first-line pharmacological treatment. Notable problems with SSRIs include induction of anxiety on treatment initiation, delayed onset of significant therapeutic effect, sexual dysfunction, sleep disturbance and overall modest efficacy...

Major Depressive Disorder (MDD) is a leading cause of disability worldwide. Conventional antidepressant treatment is characterised by a significant time to onset of therapeutic action (approximately 2 weeks) and fails to achieve a stable remission of symptoms in one-third of subjects with MDD. In the last 20 years the discovery of antidepressant effects of the N-methyl-d-aspartate (NMDA) receptor antagonist ketamine as a rapid acting (within hours) and sustained (up to 7 days) antidepressant has represented a major paradigm shift in the field...

The hypothalamic neuropeptide oxytocin (OT) is well known for its prosocial, anxiolytic, and ameliorating effects on various psychiatric conditions, including alcohol use disorder (AUD). In this chapter, we will first introduce the basic neurophysiology of the OT system and its interaction with other neuromodulatory and neurotransmitter systems in the brain. Next, we provide an overview over the current state of research examining the effects of acute and chronic alcohol exposure on the OT system as well as the effects of OT system manipulation on alcohol-related behaviors in rodents and humans...

As discussed in this chapter, there have been enormous advances in our understanding of how anxiety disorders develop, are maintained, and can be treated. Many of these advances have been the result of translational studies using fear conditioning and extinction models. Despite these successes, we recognize, as a field, that there are important limitations in the extent to which extinction can explain how anxiety disorders and behaviors remit. Clinically speaking, the outstanding challenge for treatment of anxiety disorders is to improve the current suboptimal success rates...

Neuroscience and neuroimaging research have now identified brain nodes that are involved in the acquisition, storage, and expression of conditioned fear and its extinction. These brain regions include the ventromedial prefrontal cortex (vmPFC), dorsal anterior cingulate cortex (dACC), amygdala, insular cortex, and hippocampus. Psychiatric neuroimaging research shows that functional dysregulation of these brain regions might contribute to the etiology and symptomatology of various psychopathologies, including anxiety disorders and post traumatic stress disorder (PTSD) (Barad et al...

A critical developmental task is learning what constitutes reliable threat and safety signals in the environment. In humans, atypical fear learning processes are implicated in many mental health conditions, particularly fear and anxiety disorders, pointing to the potential for laboratory measures of fear learning to facilitate early identification of at-risk individuals. This chapter reviews studies of fear learning and extinction learning that incorporate peripheral measures of psychophysiological response and include a developmental sample...

Increasingly, Virtual Reality technologies are finding a place in psychology and behavioral neuroscience labs. Immersing participants in virtual worlds enables researchers to investigate empirical questions in realistic or imaginary environments while measuring a wide range of behavioral responses, without sacrificing experimental control. In this chapter, we aim to provide a balanced appraisal of VR research methods. We describe how VR can help advance psychological science by opening pathways for addressing many pernicious challenges currently facing science (e...

Extinction is the process by which the memory of a learned conditioned association decreases over time and with introduction of new associations. It is a vital part of fear learning, and it is critical to recovery in multiple fear-related disorders, including Specific and Social Phobias, Panic Disorder, Obsessive Compulsive Disorder (OCD), and Posttraumatic Stress Disorder (PTSD). The process of extinction is also the underlying mechanism for recovery in gold-standard therapies for PTSD, including prolonged exposure, cognitive processing therapy, eye movement desensitization and procession, as well as other empirically-based paradigms...

The focus of this chapter is an overview of integrating virtual reality (VR) technology within the context of exposure therapy for anxiety disorders, a gold standard treatment, with a focus on how VR can help facilitate extinction learning processes integral to these interventions. The chapter will include an overview of advantages of incorporating VR within exposure therapy, and benefits specifically within an inhibitory learning approach for extinction training. A review of the empirical literature on the effectiveness of VR exposure therapy for specific phobia and PTSD will be provided, as well as practical overview of how to effectively incorporate VR within exposure therapy...

Fear memories can be updated behaviorally by delivering extinction trials during the reconsolidation window, which results in a persistent attenuation of fear memories (Monfils et al., Science 324:951-955, 2009). This safe and non-invasive paradigm, termed retrieval-extinction (or post-retrieval extinction), has also been found to be successful at preventing the return of fear in healthy fear conditioned humans (Schiller et al., Nature 463:49-53, 2010), and in the time since its discovery, there has been an explosion of research on the use of retrieval-extinction in fear memories in humans and other animals, some of which have found a long-term reduction in conditioned responding, and some who have not...

Impairments in fear extinction processes have been implicated in the genesis and maintenance of debilitating psychopathologies, including Posttraumatic stress disorder (PTSD). PTSD, classified as a trauma- and stressor-related disorder, is characterized by four symptom clusters: intrusive recollections of trauma, avoidance of trauma-related stimuli, alterations in cognition and mood, and hyperarousal. One of the key pathological feature associated with the persistence of these symptoms is impaired fear extinction, as delineated in multiple studies employing Pavlovian fear-conditioning paradigms...

Translational neuroscience for anxiety has had limited success despite great progress in understanding the neurobiology of Pavlovian fear conditioning and extinction. This chapter explores the idea that conditioning paradigms have had a modest impact on translation because studies in animals and humans are misaligned in important ways. For instance, animal conditioning studies typically use imminent threats to assess short-duration fear states with single behavioral measures (e.g., freezing), whereas human studies typically assess weaker or more prolonged anxiety states with physiological (e...

Alterations in extinction learning relate to the development and maintenance of anxiety disorders across the lifespan. While exposure therapy, based on principles of extinction, can be highly effective for treating anxiety, many patients do not show sufficient improvement following treatment. In particular, evidence suggests that exposure therapy does not work sufficiently for up to 40% of children who receive this evidence-based treatment.Importantly, fear learning and extinction, as well as the neural circuitry supporting these processes, undergo dynamic changes across development...

Exposure therapy is the gold-standard treatment approach for pathological anxiety. This therapeutic approach builds on principles of extinction training from traditional fear conditioning and extinction protocols. In this chapter, we discuss principles of exposure therapy in the clinic and the laboratory experimental results that guide our decisions in the therapy. We discuss emotional processing theory and inhibitory learning principles, with a focus on expectation violation. We conclude with future research directions needed to improve exposure therapy outcomes among patients with anxiety-related disorders...

Fear extinction memories are strongly modulated by sex and hormonal status, but the exact mechanisms are still being discovered. In humans, there are some basal and task-related features in which male and female individuals differ in fear conditioning paradigms. However, analyses considering the effects of sex hormones demonstrate a role for estradiol in fear extinction memory consolidation. Translational studies are taking advantage of the convergent findings between species to understand the brain structures implicated...

The study of fear extinction has been driven largely by Pavlovian fear conditioning methods across the translational spectrum. The primary methods used to study these processes in humans have been recordings of skin conductance (historically termed galvanic skin response) and fear-potentiation of the acoustic startle reflex. As outlined in the following chapter, the combined corpus of this work has demonstrated the value of psychophysiology in better understanding the underlying neurobiology of extinction learning in healthy humans as well as those with psychopathologies...

This chapter reviews the literature on the impact of stress and exercise on fear extinction. Given that key brain regions of the fear circuitry (e.g., hippocampus, amygdala and frontal cortex) can be modulated by stress hormones, it is important to investigate how stress influences this process. Laboratory-based studies performed in healthy adults have yielded mixed results, which are most likely attributable to various methodological factors. Among these factors, inter-individual differences modulating the stress response and timing of stressor administration with respect to the task may contribute to this heterogeneity...

Fear extinction is a topic of central importance in translational neuroscience. It integrates knowledge from various disciplines, including clinical psychology, experimental psychology, psychiatry, cellular and systems neuroscience, and pharmacology. The experimental phenomenon of extinction was first discovered by Ivan P. Pavlov more than 100 years ago and still forms the basis for investigating the psychological and physiological mechanisms that drive extinction of fear. Here, I present old and new ways to think about fear conditioning and extinction from a psychologist's point of view...