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Fear extinction

Ronald M Rapee, Michael P Jones, Jennifer L Hudson, Gin S Malhi, Heidi J Lyneham, Sophie C Schneider
Use of the partial NMDA receptor agonist d-Cycloserine (DCS) to increase extinction to feared cues among anxious adults has shown mixed, although overall positive effects. Few studies have extended this effect to youth and none have addressed young people with broad-based anxiety such as separation anxiety, social anxiety, or generalised anxiety. In the current trial 51 children and adolescents with diagnosed anxiety disorders, aged 7-14 years received four sessions of graduated, experimenter-led, in vivo exposure to a hierarchy of feared cues relevant to their primary fear...
October 18, 2016: Behaviour Research and Therapy
Dongdong Chai, Hong Jiang, Qifang Li
OBJECTIVE: Previously, we found that the inhaled anesthetic isoflurane up-regulated the transcriptional factor hypoxia inducible factor (HIF)-1α protein levels during induction of neurodegeneration in the brain of neonatal rats. Here, we investigated the role of HIF-1α and the underlying signaling pathway in the neurodegenration induced by isoflurane in rodent developing brain. METHODS: Primary hippocampal neurons were exposed to isoflurane (0.4mM) for 12h. Neuron injury was analyzed by 3-(4,5-dimethyithiazol-2-yl)-2,5-diphenyl-tetra-zolium bromide (MTT) test and quantification of lactate dehydrogenaserelease...
October 18, 2016: Brain Research
Lars Marstaller, Hana Burianová, David C Reutens
Safety learning describes the ability to learn that certain cues predict the absence of a dangerous or threatening event. Although incidental observations of activity within the default mode network (DMN) during the processing of safety cues have been reported previously, there is as yet no evidence demonstrating that the DMN plays a functional rather than a corollary role in safety learning. Using functional magnetic resonance imaging and a Pavlovian fear conditioning and extinction paradigm, we investigated the neural correlates of danger and safety learning...
October 21, 2016: Human Brain Mapping
Kenneth M McCullough, Dennis Choi, Jidong Guo, Kelsey Zimmerman, Jordan Walton, Donald G Rainnie, Kerry J Ressler
Molecular characterization of neuron populations, particularly those controlling threat responses, is essential for understanding the cellular basis of behaviour and identifying pharmacological agents acting selectively on fear-controlling circuitry. Here we demonstrate a comprehensive workflow for identification of pharmacologically tractable markers of behaviourally characterized cell populations. Thy1-eNpHR-, Thy1-Cre- and Thy1-eYFP-labelled neurons of the BLA consistently act as fear inhibiting or 'Fear-Off' neurons during behaviour...
October 21, 2016: Nature Communications
Liat Helpman, Marie-France Marin, Santiago Papini, Xi Zhu, Gregory M Sullivan, Franklin Schneier, Mariana Neria, Erel Shvil, Maria Josefa Malaga Aragon, John C Markowitz, Martin A Lindquist, Tor Wager, Mohammad Milad, Yuval Neria
BACKGROUND: Neurobiological models of posttraumatic stress disorder (PTSD) implicate fear processing impairments in the maintenance of the disorder. Specific deficits in extinction recall, the retention of learned extinction, have been demonstrated. While deficient extinction recall, and the associated activation pattern of prefrontal and hippocampal regions, distinguishes individuals with PTSD from controls, research has not yet examined changes following treatment. We examined the behavioral and neural correlates of extinction recall before and after cognitive behavioral treatment of PTSD...
2016: NeuroImage: Clinical
Jasmin Remmes, Carina Bodden, S Helene Richter, Jörg Lesting, Norbert Sachser, Hans-Christian Pape, Thomas Seidenbecher
Behavioral profiles are strongly shaped by an individual's whole life experience. The accumulation of negative experiences over lifetime is thought to promote anxiety-like behavior in adulthood ("allostatic load hypothesis"). In contrast, the "mismatch hypothesis" of psychiatric disease suggests that high levels of anxiety-like behavior are the result of a discrepancy between early and late environment. The aim of the present study was to investigate how different life histories shape the expression of anxiety-like behavior and modulate fear memory...
2016: Frontiers in Behavioral Neuroscience
Amanda C Sharko, Jim R Fadel, Kris F Kaigler, Marlene A Wilson
Identifying the neurobiological mechanisms that underlie differential sensitivity to stress is critical for understanding the development and expression of stress-induced disorders, such as post-traumatic stress disorder (PTSD). Preclinical studies have suggested that rodents display different phenotypes associated with extinction of Pavlovian conditioned fear responses, with some rodent populations being resistant to extinction. An emerging literature also suggests a role for orexins in the consolidation processes associated with fear learning and extinction...
October 13, 2016: Physiology & Behavior
Mihee Song, Yong Sang Jo, Yeon-Kyung Lee, June-Seek Choi
The lateral habenula (LHb) is an epithalamic brain structure that provides strong projections to midbrain monoaminergic systems that are involved in motivation, emotion, and reinforcement learning. LHb neurons are known to convey information about aversive outcomes and negative prediction errors, suggesting a role in learning from aversive events. To test this idea, we examined the effects of electrolytic lesions of the LHb on signaled two-way active avoidance learning in which rats were trained to avoid an unconditioned stimulus (US) by taking a proactive shuttling response to an auditory conditioned stimulus (CS)...
October 9, 2016: Behavioural Brain Research
R Abend, I Jalon, G Gurevitch, R Sar-El, T Shechner, D S Pine, T Hendler, Y Bar-Haim
Research associates processes of fear conditioning and extinction with treatment of anxiety and stress-related disorders. Manipulation of these processes may therefore be beneficial for such treatment. The current study examines the effects of electrical brain stimulation on fear extinction processes in healthy humans in order to assess its potential relevance for treatment enhancement. Forty-five participants underwent a 3-day fear conditioning and extinction paradigm. Electrical stimulation targeting the medial prefrontal cortex was applied during the extinction-learning phase (Day 2)...
October 11, 2016: Translational Psychiatry
Vipan K Parihar, Barrett D Allen, Chongshan Caressi, Stephanie Kwok, Esther Chu, Katherine K Tran, Nicole N Chmielewski, Erich Giedzinski, Munjal M Acharya, Richard A Britten, Janet E Baulch, Charles L Limoli
The Mars mission will result in an inevitable exposure to cosmic radiation that has been shown to cause cognitive impairments in rodent models, and possibly in astronauts engaged in deep space travel. Of particular concern is the potential for cosmic radiation exposure to compromise critical decision making during normal operations or under emergency conditions in deep space. Rodents exposed to cosmic radiation exhibit persistent hippocampal and cortical based performance decrements using six independent behavioral tasks administered between separate cohorts 12 and 24 weeks after irradiation...
October 10, 2016: Scientific Reports
Kathryn D Baker, Amy C Reichelt
Anxiety disorders and obesity are both common in youth and young adults. Despite increasing evidence that over-consumption of palatable high-fat/high-sugar "junk" foods leads to adverse neurocognitive outcomes, little is known about the effects of palatable diets on emotional memories and fear regulation. In the present experiments we examined the effects of daily 2h consumption of a high-fat/high-sugar (HFHS) food across adolescence on fear inhibition and anxiety-like behaviour in young adult rats. Rats exposed to the HFHS diet exhibited impaired retention of fear extinction and increased anxiety-like behaviour in an emergence test compared to rats fed a standard diet...
October 5, 2016: Neurobiology of Learning and Memory
Claire Le Dorze, Pascale Gisquet-Verrier
Intrusive re-experiencing of a trauma is a core symptom in post-traumatic stress disorder (PTSD), and is often triggered by contextual cues associated with the event. It is not yet established if intrusive re-experiencing is the consequence of PTSD, or if it could contribute to the development of PTSD following a traumatic event. The present study (1) examined the impact of repeated brief re-exposures to trauma reminders on the strength of PTSD-like symptoms, as well as on their time-development and (2) investigated the reactivity over time to these cues in trauma resilient and vulnerable rats, defined on the basis of the PTSD-like symptoms they demonstrated...
October 4, 2016: Brain Research
Flurin Cathomas, Hannes Sigrist, Luca Schmid, Erich Seifritz, Martin Gassmann, Bernhard Bettler, Christopher R Pryce
Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain and is implicated in the pathophysiology of a number of neuropsychiatric disorders. The GABAB receptors are G-protein coupled receptors consisting of principle subunits and auxiliary potassium channel tetramerization domain (KCTD) subunits. The KCTD subunits 8, 12, 12b and 16 are cytosolic proteins that determine the kinetics of the GABAB receptor response. Previously, we demonstrated that Kctd12 null mutant mice (Kctd12(-/-)) exhibit increased auditory fear learning and that Kctd12(+/-) mice show altered circadian activity, as well as increased intrinsic excitability in hippocampal pyramidal neurons...
October 4, 2016: Behavioural Brain Research
Christine A Rabinak, Shoko Mori, Maryssa Lyons, Mohammed R Milad, K Luan Phan
BACKGROUND: Fear-based disorders, like social anxiety disorder (SAD) and posttraumatic stress disorder (PTSD), are characterized by an exaggerated fear response and avoidance to trigger cues, suggesting a transdiagnostic mechanism of psychopathology. Current theories suggest that abnormalities in conditioned fear is a primary contributor to the pathophysiology of these disorders. The primary goal of this study was to compare acquisition of conditioned stimulus (CS) and aversive unconditioned stimulus (US) contingencies during fear learning and extinction in individuals with SAD and PTSD...
September 23, 2016: Journal of Affective Disorders
Stella Li, Bronwyn M Graham
The first-line psychological treatment for anxiety disorders is exposure therapy, which can be modeled in the laboratory using fear extinction. In healthy women, estradiol levels predict return of fear following extinction, whereas low levels are associated with greater return of fear. Investigating whether estradiol is similarly associated with extinction in clinically anxious women may provide insight to mechanisms underlying symptom relapse following exposure therapy. In the present study, women with spider phobia and healthy women participated in a 2-day fear conditioning and extinction procedure during a period of high or low estradiol levels...
October 6, 2016: Behavioral Neuroscience
Marlene A Wilson, Jim R Fadel
Cholinergic activation regulates cognitive function, particularly long-term memory consolidation. This Review presents an overview of the anatomical, neurochemical, and pharmacological evidence supporting the cholinergic regulation of Pavlovian contextual and cue-conditioned fear learning and extinction. Basal forebrain cholinergic neurons provide inputs to neocortical regions and subcortical limbic structures such as the hippocampus and amygdala. Pharmacological manipulations of muscarinic and nicotinic receptors support the role of cholinergic processes in the amygdala, hippocampus, and prefrontal cortex in modulating the learning and extinction of contexts or cues associated with threat...
October 5, 2016: Journal of Neuroscience Research
Manon Wicking, Frauke Steiger, Frauke Nees, Slawomira J Diener, Oliver Grimm, Michaela Ruttorf, Lothar R Schad, Tobias Winkelmann, Gustav Wirtz, Herta Flor
BACKGROUND: Posttraumatic stress disorder (PTSD) might be maintained by deficient extinction memory. We used a cued fear conditioning design with extinction and a post-extinction phase to provoke the return of fear and examined the role of the interplay of amygdala, hippocampus and prefrontal regions. METHODS: We compared 18 PTSD patients with two healthy control groups: 18 trauma-exposed subjects without PTSD (nonPTSD) and 18 healthy controls (HC) without trauma experience...
September 26, 2016: Neurobiology of Learning and Memory
Susana S Correia, Anna G McGrath, Allison Lee, Ann M Graybiel, Ki A Goosens
In humans, activation of the ventral striatum, a region associated with reward processing, is associated with the extinction of fear, a goal in the treatment of fear-related disorders. This evidence suggests that extinction of aversive memories engages reward-related circuits, but a causal relationship between activity in a reward circuit and fear extinction has not been demonstrated. Here, we identify a basolateral amygdala (BLA)-ventral striatum (NAc) pathway that is activated by extinction training. Enhanced recruitment of this circuit during extinction learning, either by pairing reward with fear extinction training or by optogenetic stimulation of this circuit during fear extinction, reduces the return of fear that normally follows extinction training...
2016: ELife
Rie Ishikawa, Hotaka Fukushima, Paul W Frankland, Satoshi Kida
Forgetting of recent fear memory is promoted by treatment with memantine (MEM), which increases hippocampal neurogenesis. The approaches for treatment of post-traumatic stress disorder (PTSD) using rodent models have focused on the extinction and reconsolidation of recent, but not remote, memories. Here we show that, following prolonged re-exposure to the conditioning context, enhancers of hippocampal neurogenesis, including MEM, promote forgetting of remote contextual fear memory. However, these interventions are ineffective following shorter re-exposures...
2016: ELife
Alicia E Meuret, David Rosenfield, Lavanya Bhaskara, Richard Auchus, Israel Liberzon, Thomas Ritz, James L Abelson
OBJECTIVE: No simple way to augment fear extinction has been established. Cortisol has shown to enhance memory extinction and preliminary evidence suggest that extinction learning maybe more successful in the morning when cortisol is high. The aim was to determine whether exposure sessions conducted earlier in the day are associated with superior therapeutic gains in extinction-based psychotherapy. We also examined the role of cortisol levels as a mediator between time of day and therapeutic gains...
September 15, 2016: Psychoneuroendocrinology
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