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Post-traumatic stress disorder (PTSD) is a debilitating neuropsychiatric condition closely linked to neuroinflammation, with a higher prevalence in women. Cannabidiol (CBD), a non-psychoactive cannabinoid, has shown promise as a potential treatment for PTSD. In this study, we used a PTSD model in which female rats were subjected to a severe foot shock followed by contextual situational reminders (SRs). Testing was conducted one month after exposure. The rats received daily CBD injections for three weeks during the SRs, from days 7 to 28. Two days after the final SR, the rats underwent five extinction trials, followed by the forced swim test (FST). After a five-day rest period, the rats were sacrificed, and brain tissues from the medial prefrontal cortex (mPFC) and ventral subiculum (vSUB) were analyzed for inflammatory markers. Chronic CBD treatment reversed impairments in fear extinction caused by shock and SR. It also reduced learned helplessness in the FST and decreased the upregulation of mPFC-il1β induced by shock and SRs. Additionally, exposure to shock and SRs downregulated mPFC-il6 while upregulating vSUB-il6. CBD treatment further downregulated il6 expression in the vSUB compared to the vehicle groups. Our findings show that CBD effectively inhibited the development of PTSD-like behaviors and suppressed neuroinflammation in the mPFC. [ABSTRACT FROM AUTHOR]

MDMA-assisted psychotherapy has shown potential as an effective treatment for post-traumatic stress disorder (PTSD). Preclinical studies involving rodents have demonstrated that MDMA can facilitate the extinction of fear memories. It has been noted that MDMA impacts oxytocin neurons and pro-inflammatory cytokines. Thus, the aim of this study was to explore the role of oxytocinergic signaling and neuroinflammatory markers in the therapeutic effects of MDMA. To achieve this, male rats were subjected to a model of PTSD involving exposure to shock and situational reminders. MDMA was microinjected into the medial prefrontal cortex (mPFC) before extinction training, followed by behavioral tests assessing activity levels, anxiety, and social function. Our findings indicate that MDMA treatment facilitated fear extinction and mitigated the shock-induced increase in freezing, as well as deficits in social behavior. Shock exposure led to altered expression of the gene coding for OXT-R and neuroinflammation in the mPFC and basolateral amygdala (BLA), which were restored by MDMA treatment. Importantly, the OXT-R antagonist L-368,899 prevented MDMA's therapeutic effects on extinction and freezing behavior. In conclusion, MDMA's therapeutic effects in the PTSD model are associated with alterations in OXT-R expression and neuroinflammation, and MDMA's effects on extinction and anxiety may be mediated by oxytocinergic signaling. [ABSTRACT FROM AUTHOR]

Fear-related disorders, including post-traumatic stress disorder (PTSD), and anxiety disorders are pervasive psychiatric conditions marked by persistent fear, stemming from its dysregulated acquisition and extinction. The primary treatment for these disorders, exposure therapy (ET), relies heavily on fear extinction (FE) principles. Adolescence, a vulnerable period for developing psychiatric disorders, is characterized by neurobiological changes in the fear circuitry, leading to impaired FE and increased susceptibility to relapse following ET. Ketamine, known for relieving anxiety and reducing PTSD symptoms, influences fear-related learning processes and synaptic plasticity across the fear circuitry. Our study aimed to investigate the effects of ketamine (10 mg/kg) on FE in adolescent male C57 BL/6 mice at the behavioral and molecular levels. We analyzed the protein and gene expression of synaptic plasticity markers in the hippocampus (HPC) and prefrontal cortex (PFC) and sought to identify neural correlates associated with ketamine's effects on adolescent extinction learning. Ketamine ameliorated FE in the adolescent males, likely affecting the consolidation and/or recall of extinction memory. Ketamine also increased the Akt and mTOR activity and the GluA1 and GluN2A levels in the HPC and upregulated BDNF exon IV mRNA expression in the HPC and PFC of the fear-extinguished mice. Furthermore, ketamine increased the c-Fos expression in specific brain regions, including the ventral HPC (vHPC) and the left infralimbic ventromedial PFC (IL vmPFC). Providing a comprehensive exploration of ketamine's mechanisms in adolescent FE, our study suggests that ketamine's effects on FE in adolescent males are associated with the activation of hippocampal Akt-mTOR-GluA1 signaling, with the vHPC and the left IL vmPFC as the proposed neural correlates. [ABSTRACT FROM AUTHOR]

Posttraumatic stress disorder (PTSD) is a widespread fear-related psychiatric affection associated with fear extinction impairments and important avoidance behaviors. Trauma-related exposure therapy is the current first-hand treatment for PTSD, yet it needs to be improved to shorten the time necessary to reach remission and increase responsiveness. Additional studies to decipher the neurobiological bases of extinction and effects on PTSD-like symptoms could therefore be of use. However, a PTSD-like animal model exhibiting pronounced PTSD-related phenotypes even after an extinction training directly linked to the fearful event is necessary. Thus, using a contextual fear conditioning model of PTSD, we increased the severity of stress during conditioning to search for effects on extinction acquisition and on pre- and post-extinction behaviors. During conditioning, mice received either two or four electrical shocks while a control group was constituted of mice only exposed to the context. Stressed mice exhibited important fear generalization, high fear reaction to the context and selective avoidance of a contextual reminder even after the extinction protocol. Increasing the number of footshocks did not induce major changes on these behaviors. [ABSTRACT FROM AUTHOR]

Fear extinction is a phenomenon that involves a gradual reduction in conditioned fear responses through repeated exposure to fear-inducing cues. Functional brain connectivity assessments, such as functional magnetic resonance imaging (fMRI), provide valuable insights into how brain regions communicate during these processes. Stress, a ubiquitous aspect of life, influences fear learning and extinction by changing the activity of the amygdala, prefrontal cortex, and hippocampus, leading to enhanced fear responses and/or impaired extinction. Glucocorticoid receptors (GRs) are key to the stress response and show a dual function in fear regulation: while they enhance the consolidation of fear memories, they also facilitate extinction. Accordingly, GR dysregulation is associated with anxiety and mood disorders. Recent advancements in cognitive neuroscience underscore the need for a comprehensive understanding that integrates perspectives from the molecular, cellular, and systems levels. In particular, neuropharmacology provides valuable insights into neurotransmitter and receptor systems, aiding the investigation of mechanisms underlying fear regulation and potential therapeutic targets. A notable player in this context is cortisol, a key stress hormone, which significantly influences both fear memory reconsolidation and extinction processes. Gaining a thorough understanding of these intricate interactions has implications in terms of addressing psychiatric disorders related to stress. This review sheds light on the complex interactions between cognitive processes, emotions, and their neural bases. In this endeavor, our aim is to reshape the comprehension of fear, stress, and their implications for emotional well-being, ultimately aiding in the development of therapeutic interventions. [ABSTRACT FROM AUTHOR]

Balanced fear supports human rational decision-making and useful behavioral responses. In contrast, overwhelming, persistent, and unbalanced fear can paralyze the individual and result in heightened anxiety, lack of cognitive flexibility, fear-based public compliance and serious mental health issues. Psychobiotics research has established that a healthy microbiome is required for balanced fear and mental health protection via control of fear extinction. The recent COVID-19 pandemic featured daily, persistent, fear-of-a-single-contagion conditioning on a global scale paired with various behavioral mandates (e.g., lockdowns of the healthy, required wearing of face masks in many locations including schools, isolation from environmental microbes and each other through the closure of beaches and parks, and restrictions on social gatherings including access to family members in hospitals and senior-assisted facilities). Such mandates degraded the human microbiome and isolated us from each other and useful environmental microbes. It also ignored the historic role of secondary bacterial pathogens in pandemic deaths. This narrative review examines how the institutional promotion of fear-of-a-single-contagion, lack of balanced risk communication, and appalling disregard of our fundamental nature (as majority-microbial human superorganisms) resulted in problems rather than solutions. This review illustrates that government-public health-media promotion of pervasive fear and microbiome-degrading behaviors: (1) increased public compliance, (2) reduced cognitive flexibility, and (3) increased risk of mental health conditions. However, a portion of the general public chose a healthier path through their increased consumption of microbiome- and immune-supportive supplements and fermented foods during and after the COVID-19 pandemic. For a healthier future, public health must follow the lead of this population to ensure that human freedom, rather than paralyzing fear, dominates our future. [ABSTRACT FROM AUTHOR]

Fear extinction is the basis of exposure therapies for posttraumatic stress disorder (PTSD), but half of patients do not improve. Predicting fear extinction in individuals with PTSD may inform personalized exposure therapy development. The participants were 125 trauma-exposed adults (96 female) with a range of PTSD symptoms. Electromyography, electrocardiogram, and skin conductance were recorded at baseline, during dark-enhanced startle, and during fear conditioning and extinction. Using a cross-validated, hold-out sample prediction approach, three penalized regressions and conventional ordinary least squares were trained to predict fear-potentiated startle during extinction using 50 predictor variables (5 clinical, 24 self-reported, and 21 physiological). The predictors, selected by penalized regression algorithms, were included in multivariable regression analyses, while univariate regressions assessed individual predictors. All the penalized regressions outperformed OLS in prediction accuracy and generalizability, as indexed by the lower mean squared error in the training and holdout subsamples. During early extinction, the consistent predictors across all the modeling approaches included dark-enhanced startle, the depersonalization and derealization subscale of the dissociative experiences scale, and the PTSD hyperarousal symptom score. These findings offer novel insights into the modeling approaches and patient characteristics that may reliably predict fear extinction in PTSD. Penalized regression shows promise for identifying symptom-related variables to enhance the predictive modeling accuracy in clinical research. [ABSTRACT FROM AUTHOR]

Acid sphingomyelinase (ASM) regulates a variety of physiological processes and plays an important role in emotional behavior. The role of ASM in fear-related behavior has not been investigated so far. Using transgenic mice overexpressing ASM (ASMtg) and ASM deficient mice, we studied whether ASM regulates fear learning and expression of cued and contextual fear in a classical fear conditioning paradigm, a model used to investigate specific attributes of post-traumatic stress disorder (PTSD). We show that ASM does not affect fear learning as both ASMtg and ASM deficient mice display unaltered fear conditioning when compared to wild-type littermates. However, ASM regulates the expression of contextual fear in a sex-specific manner. While ASM overexpression enhances the expression of contextual fear in both male and female mice, ASM deficiency reduces the expression of contextual fear specifically in male mice. The expression of cued fear, however, is not regulated by ASM as ASMtg and ASM deficient mice display similar tone-elicited freezing levels. This study shows that ASM modulates the expression of contextual fear but not of cued fear in a sex-specific manner and adds a novel piece of information regarding the involvement of ASM in hippocampal-dependent aversive memory. [ABSTRACT FROM AUTHOR]

Fear conditioning evokes a physiologic release of glucocorticoids that assists learning. As a cochaperone in the glucocorticoid receptor complex, FKBP51 modulates stress-induced glucocorticoid signaling and may influence conditioned fear responses. This study combines molecular and behavioral approaches to examine whether locally reducing FKBP51 expression in the ventral hippocampus is sufficient to affect fear-related behaviors. We hypothesized that reducing FKBP51 expression in the VH would increase glucocorticoid signaling to alter auditory fear conditioning. Adult male rats were injected with an adeno-associated virus (AAV) vector expressing short hairpin - RNAs (shRNA) targeting FKBP5 into the ventral hippocampus to reduce FKBP5 levels or a control AAV. Infusion of FKBP5-shRNA into the ventral hippocampus decreased auditory fear acquisition and recall. Although animals injected with FKBP5-shRNA showed less freezing during extinction recall, the difference was due to a reduced fear recall rather than improved extinction. Reducing ventral hippocampus FKBP51 did not affect exploratory behavior in either the open field test or the elevated zero maze test but did increase passive behavior in the forced swim test, suggesting that the reduction in auditory fear recall was not due to more active responses to acute stress. Furthermore, lower ventral hippocampus FKBP51 levels did not alter corticosterone release in response to restraint stress, suggesting that the reduced fear recall was not due to lower corticosterone release. Our findings suggest FKBP51 in the ventral hippocampus plays a selective role in modulating fear-learning processes and passive behavioral responses to acute stress rather than hypothalamic-pituitary-adrenal axis reactivity or exploratory responses.

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition for which pharmacological therapy is not always solvable. Various treatments have been suggested and deep brain stimulation (DBS) is currently under investigation for patients affected by PTSD. We review the neurocircuitry and up-to-date clinical concepts which are behind the use of DBS in posttraumatic stress disorder (PTSD). The role of DBS in treatment-refractory PTSD patients has been investigated relying on both preclinical and clinical studies. DBS for PTSD is in its preliminary phases and likely to provide hope for patients with medical refractory PTSD following the results of randomized controlled studies. [ABSTRACT FROM AUTHOR]

Inter-individual and sex differences in pain responses are recognized but their mechanisms are not well understood. This study was intended to provide the behavioral framework for analyses of pain mechanisms using fear extinction learning as a predictor of phenotypic and sex differences in sensory (mechanical withdrawal thresholds) and emotional-affective aspects (open field tests for anxiety-like behaviors and audible and ultrasonic components of vocalizations) of acute and chronic pain. In acute arthritis and chronic neuropathic pain models, greater increases in vocalizations were found in females than males and in females with poor fear extinction abilities than females with strong fear extinction, particularly in the neuropathic pain model. Female rats showed higher anxiety-like behavior than males under baseline conditions but no inter-individual or sex differences were seen in the pain models. No inter-individual and sex differences in mechanosensitivity were observed. The data suggest that vocalizations are uniquely suited to detect inter-individual and sex differences in pain models, particularly in chronic neuropathic pain, whereas no such differences were found for mechanosensitivity, and baseline differences in anxiety-like behaviors disappeared in the pain models. [ABSTRACT FROM AUTHOR]

Several psychiatric conditions such as phobias, generalized anxiety, and post-traumatic stress disorder (PTSD) are characterized by pathological fear and anxiety. The main therapeutic approach used in the management of these disorders is exposure-based therapy, which is conceptually based upon fear extinction with the formation of a new safe memory association, allowing the reduction in behavioral conditioned fear responses. Nevertheless, this approach is only partially resolutive, since many patients have difficulty following the demanding and long process, and relapses are frequently observed over time. One strategy to improve the efficacy of the cognitive therapy is the combination with pharmacological agents. Therefore, the identification of compounds able to strengthen the formation and persistence of the inhibitory associations is a key goal. Recently, growing interest has been aroused by the neuropeptide oxytocin (OXT), which has been shown to have anxiolytic effects. Furthermore, OXT receptors and binding sites have been found in the critical brain structures involved in fear extinction. In this review, the recent literature addressing the complex effects of OXT on fear extinction at preclinical and clinical levels is discussed. These studies suggest that the OXT roles in fear behavior are due to its local effects in several brain regions, most notably, distinct amygdaloid regions. [ABSTRACT FROM AUTHOR]

Fear extinction requires coordinated neural activity within the amygdala and medial prefrontal cortex (mPFC). Any behavior has a transcriptomic signature that is modified by environmental experiences, and specific genes are involved in functional plasticity and synaptic wiring during fear extinction. Here, we investigated the effects of optogenetic manipulations of prelimbic (PrL) pyramidal neurons and amygdala gene expression to analyze the specific transcriptional pathways associated to adaptive and maladaptive fear extinction. To this aim, transgenic mice were (or not) fear-conditioned and during the extinction phase they received optogenetic (or sham) stimulations over photo-activable PrL pyramidal neurons. At the end of behavioral testing, electrophysiological (neural cellular excitability and Excitatory Post-Synaptic Currents) and morphological (spinogenesis) correlates were evaluated in the PrL pyramidal neurons. Furthermore, transcriptomic cell-specific RNA-analyses (differential gene expression profiling and functional enrichment analyses) were performed in amygdala pyramidal neurons. Our results show that the optogenetic activation of PrL pyramidal neurons in fear-conditioned mice induces fear extinction deficits, reflected in an increase of cellular excitability, excitatory neurotransmission, and spinogenesis of PrL pyramidal neurons, and associated to strong modifications of the transcriptome of amygdala pyramidal neurons. Understanding the electrophysiological, morphological, and transcriptomic architecture of fear extinction may facilitate the comprehension of fear-related disorders. [ABSTRACT FROM AUTHOR]

In many social anxiety disorder (SAD) patients, the efficacy of antidepressant therapy is unsatisfactory. Here, we investigated whether mice deficient for the lysosomal glycoprotein acid sphingomyelinase (ASM−/−) represent an appropriate tool to study antidepressant-resistant social fear. We also investigated whether neuropeptide Y (NPY) reduces this antidepressant-resistant social fear in ASM−/− mice, given that NPY reduced social fear in a mouse model of SAD, namely social fear conditioning (SFC). We show that neither chronic paroxetine nor chronic amitriptyline administration via drinking water were successful in reducing SFC-induced social fear in ASM−/− mice, while the same treatment reduced social fear in ASM+/− mice and completely reversed social fear in ASM+/+ mice. This indicates that the antidepressants paroxetine and amitriptyline reduce social fear via the ASM-ceramide system and that ASM−/− mice represent an appropriate tool to study antidepressant-resistant social fear. The intracerebroventricular administration of NPY, on the other hand, reduced social fear in ASM−/− mice, suggesting that NPY might represent an alternative pharmacotherapy for antidepressant-resistant social fear. These results suggest that medication strategies aimed at increasing brain NPY concentrations might improve symptoms of social fear in SAD patients who fail to respond to antidepressant treatments. [ABSTRACT FROM AUTHOR]

Background: Fear, stress, and anxiety-like behaviors originate from traumatic events in life. Stress response is managed by endocannabinoids in the body by limiting the uncontrolled retrieval of aversive memories. Pharmacotherapy-modulating endocannabinoids, especially anandamide, presents a promising tool for treating anxiety disorders. Here, we investigated the effect of kaempferol, a flavonoid, in the extinction of fear related memories and associated anxiety-like behavior. Methods: The ability of kaempferol to inhibit fatty-acid amide hydrolase (FAAH, the enzyme that catabolizes anandamide) was assessed in vitro using an enzyme-linked immunosorbent assay (ELISA) kit. For animal studies (in vivo), the extinction learning was evaluated using contextual fear conditioning (CFC, a behavioral paradigm based on ability to learn and remember aversive stimuli). Furthermore, an elevated plus-maze (EPM) model was used for measuring anxiety-like behavior, while serum corticosterone served as a biochemical indicator of anxiety. Lastly, the interaction of kaempferol with FAAH enzyme was also assessed in silico (computational study). Results: Our data showed that kaempferol inhibited the FAAH enzyme with an IC50 value of 1 µM. In CFC, it reduced freezing behavior in rats. EPM data demonstrated anxiolytic activity as exhibited by enhanced number of entries and time spent in the open arm. No change in blood corticosterone levels was noted. Our computational study showed that Kaempferol interacted with the catalytic amino acids (SER241, PHE192, PHE381, and THR377) of FAAH enzyme Conclusion: Our study demonstrate that kaempferol facilitated the extinction of aversive memories along with a reduction of anxiety. The effect is mediated through the augmentation of endocannabinoids via the inhibition of FAAH enzyme. [ABSTRACT FROM AUTHOR]

Existing memories, when retrieved under certain circumstances, can undergo modification through the protein synthesis-dependent process of reconsolidation. Disruption of this process can lead to the weakening of a memory trace, an approach which is being examined as a potential treatment for disorders characterized by pathological memories, such as Post-Traumatic Stress Disorder. The success of this approach relies upon the ability to robustly attenuate reconsolidation; however, the available literature brings into question the reliability of the various drugs used to achieve such a blockade. The identification of a drug or intervention that can reliably disrupt reconsolidation without requiring intracranial access for administration would be extremely useful. Electroconvulsive shock (ECS) delivered after memory retrieval has been demonstrated in some studies to disrupt memory reconsolidation; however, there exists a paucity of literature characterizing its effects on Pavlovian fear memory. Considering this, we chose to examine ECS as an inexpensive and facile means to impair reconsolidation in rats. Here we show that electroconvulsive seizure induction, when administered after memory retrieval, (immediately, after 30 min, or after 1 h), does not impair the reconsolidation of cued or contextual Pavlovian fear memories. On the contrary, ECS administration immediately after extinction training may modestly impair the consolidation of fear extinction memory. [ABSTRACT FROM AUTHOR]

Recent research indicates that there is mixed success in using exposure therapies on patients with post-traumatic stress disorder (PTSD). Our study argues that there are two major reasons for this: The first is that there are nonassociative aspects of PTSD, such as hyperactive amygdala activity, that cannot be attenuated using the exposure therapy; The second is that exposure therapy is conceptualized from the theoretical framework of Pavlovian fear extinction, which we know is heavily context dependent. Thus, reducing fear response in a therapist's office does not guarantee reduced response in other situations. This study also discusses work relating to the role of the hippocampus in context encoding, and how these findings can be beneficial for improving exposure therapies. [ABSTRACT FROM AUTHOR]

Neuroimaging studies in the area of mindfulness research have provided preliminary support for the idea of fear extinction as a plausible underlying mechanism through which mindfulness exerts its positive benefits. Whilst brain regions identified in the fear extinction network are typically found at a subcortical level, studies have also demonstrated the feasibility of cortical measures of the brain, such as electroencephalogram (EEG), in implying subcortical activations of the fear extinction network. Such EEG studies have also found evidence of a relationship between brain reactivity to unpleasant stimuli (i.e., fear extinction) and severity of posttraumatic stress symptoms (PTSS). Therefore, the present paper seeks to briefly review the parallel findings between the neurophysiological literature of mindfulness and fear extinction (particularly that yielded by EEG measures), and discusses the implications of this for fear-based psychopathologies, such as trauma, and finally presents suggestions for future studies. This paper also discusses the clinical value in integrating EEG in psychological treatment for trauma, as it holds the unique potential to detect neuromarkers, which may enable earlier diagnoses, and can also provide neurofeedback over the course of treatment. [ABSTRACT FROM AUTHOR]

Adolescence is a developmental phase characterized by emotional turmoil and coincides with the emergence of affective disorders. Inherited serotonin transporter (5-HTT) downregulation in humans increases sensitivity to these disorders. To reveal whether and how 5-HTT gene variance affects fear-driven behavior in adolescence, we tested wildtype and serotonin transporter knockout (5-HTT−/−) rats of preadolescent, adolescent, and adult age for cued fear extinction and extinction recall. To analyze neural circuit function, we quantified inhibitory synaptic contacts and, through RT-PCR, the expression of c-Fos, brain-derived neurotrophic factor (BDNF), and NDMA receptor subunits, in the medial prefrontal cortex (mPFC) and amygdala. Remarkably, the impaired recall of conditioned fear that characterizes preadolescent and adult 5-HTT−/− rats was transiently normalized during adolescence. This did not relate to altered inhibitory neurotransmission, since mPFC inhibitory immunoreactivity was reduced in 5-HTT−/− rats across all ages and unaffected in the amygdala. Rather, since mPFC (but not amygdala) c-Fos expression and NMDA receptor subunit 1 expression were reduced in 5-HTT−/− rats during adolescence, and since PFC c-Fos correlated negatively with fear extinction recall, the temporary normalization of fear extinction during adolescence could relate to altered plasticity in the developing mPFC. [ABSTRACT FROM AUTHOR]

Anxiety disorders that develop in adolescence represent a significant burden and are particularly challenging to treat, due in no small part to the high occurrence of relapse in this age group following exposure therapy. This pattern of persistent fear is preserved across species; relative to those younger and older, adolescents consistently show poorer extinction, a key process underpinning exposure therapy. This suggests that the neural processes underlying fear extinction are temporarily but profoundly compromised during adolescence. The formation, retrieval, and modification of fear- and extinction-associated memories are regulated by a forebrain network consisting of the prefrontal cortex (PFC), the amygdala, and the hippocampus. These regions undergo robust maturational changes in early life, with unique alterations in structure and function occurring throughout adolescence. In this review, we focus primarily on two of these regions—the PFC and the amygdala—and discuss how changes in plasticity, synaptic transmission, inhibition/excitation, and connectivity (including modulation by hippocampal afferents to the PFC) may contribute to transient deficits in extinction retention. We end with a brief consideration of how exposure to stress during this adolescent window of vulnerability can permanently disrupt neurodevelopment, leading to lasting impairments in pathways of emotional regulation. [ABSTRACT FROM AUTHOR]

Post-traumatic stress disorder (PTSD) is an often debilitating disease with a lifetime prevalence rate between 5–8%. In war veterans, these numbers are even higher, reaching approximately 10% to 25%. Although most patients benefit from the use of medications and psychotherapy, approximately 20% to 30% do not have an adequate response to conventional treatments. Neuromodulation strategies have been investigated for various psychiatric disorders with promising results, and may represent an important treatment option for individuals with difficult-to-treat forms of PTSD. We review the relevant neurocircuitry and preclinical stimulation studies in models of fear and anxiety, as well as clinical data on the use of transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and deep brain stimulation (DBS) for the treatment of PTSD. [ABSTRACT FROM AUTHOR]

The extinction of conditioned-fear represents a hallmark of current exposure therapies as it has been found to be impaired in people suffering from post-traumatic stress disorder (PTSD) and anxiety. A large body of knowledge focusing on psychophysiological animal and human studies suggests the involvement of key brain structures that interact via neural oscillations during the acquisition and extinction of fear. Consequently, neural oscillatory correlates of such mechanisms appear relevant regarding the development of novel therapeutic approaches to counterbalance abnormal activity in fear-related brain circuits, which, in turn, could alleviate fear and anxiety symptoms. Here, we provide an account of state-of-the-art neural oscillatory correlates for the conditioning and extinction of fear, and also deal with recent translational efforts aimed at fear extinction by neural oscillatory modulation. [ABSTRACT FROM AUTHOR]