Pavlovian Research Articles

Activation, but not inactivation, of the medial or lateral orbitofrontal cortex impaired context-specific fear encoding

In laboratories, classical fear conditioning and extinction procedures are commonly used to study the behavioral and neural mechanisms underlying fear regulation. Contextual fear conditioning involves the association of an aversive event with the environment where it occurs, which engages the hippocampus and its interactions with the amygdala. The orbitofrontal cortex (OFC), divided into the lateral OFC (lOFC) and medial OFC (mOFC) subregions, plays a crucial role in integrating contextual information from the hippocampus and modulating behavioral responses based on the anticipated outcomes of the context. Because of the extensive anatomical connections of the OFC with the fear circuit, including the hippocampus, the amygdala, and the medial prefrontal cortex, and the reasoning that proper retrieval of fear-related memory is context-dependent, we raised the question to investigate the ability of the animals to discriminate between contexts when they were trained under differential OFC activation levels during the encoding of contextual fear memory. In this study, we conducted a contextual fear conditioning procedure in rats using footshock as an unconditioned stimulus (US), followed by the test of their fear levels in contexts same (dangerous) or different (safe) from the conditioning context. We used a pharmacological approach to modulate the activation levels of the lOFC or the mOFC during conditioning to examine their roles on context-specific fear encoding. Our findings showed that the animals could accurately distinguish between the two contexts in control and OFC hypoactivation groups, but failed to do so if they were trained under OFC hyperactivation. Therefore, OFC hyperactivity disturbed the encoding of contextual information during fear acquisition.

Behavioral and neural correlates of diverse conditioned fear responses in male and female rats

Pavlovian fear conditioning is a widely used tool that models associative learning in rodents. For decades the field has used predominantly male rodents and focused on a sole conditioned fear response: freezing. However, recent work from our lab and others has identified darting as a female-biased conditioned response, characterized by an escape-like movement across a fear conditioning chamber. It is also accompanied by a behavioral phenotype: Darters reliably show decreased freezing compared to Non-darters and males and reach higher velocities in response to the foot shock (“shock response”). However, the relationship between shock response and conditioned darting is not known. This study investigated if this link is due to differences in general processing of aversive stimuli between Darters, Non-darters and males. Across a variety of modalities, including corticosterone measures, the acoustic startle test, and sensitivity to thermal pain, Darters were found not to be more reactive or sensitive to aversive stimuli, and, in some cases, they appear less reactive to Non-darters and males. Analyses of cFos activity in regions involved in pain and fear processing following fear conditioning identified discrete patterns of expression among Darters, Non-darters, and males exposed to low and high intensity foot shocks. The results from these studies further our understanding of the differences between Darters, Non-darters and males and highlight the importance of studying individual differences in fear conditioning as indicators of fear state.

Effects of Standard Tai Chi on Exercise Capacity and Mental Health in Exercise-Deprived Overweight/Obese Adults and Assessment of Participant Adherence.

To explore the effects of Tai Chi on body mass index (BMI), exercise capacity, and mental health of overweight/obese adults, and investigate factors influencing adherence to enhance adherence of Tai Chi as a sustainable exercise method. A randomized, controlled, exploratory clinical trial was conducted paired with a qualitative study of adherence management. A total of 20 overweight/obese participants were randomly assigned to a standard Tai Chi group (experimental) and a simplified Tai Chi group (control) for an 8-week intervention, 10 patients in each group, with a 12-month follow-up. BMI was calculated and exercise capacity including an isokinetic muscle strength and balance ability test were evaluated. Mental health was assessed using the General Well-Being Schedule (GWB), Pittsburgh Sleep Quality Index (PSQI), and Coping Self Efficacy Scale (CSES) at baseline, 4th week, and 8th week, respectively. The qualitative research included open-interviews with Tai Chi practitioners and semi-structured interviews with subjects. The intervention was conducted in Haidian Park, Beijing, China from October 6, 2022, to January 1, 2023, without dropouts. After an 8-week intervention, the participants in the experimental group exhibited a significant decrease in BMI (P<0.05). Both groups demonstrated significant improvements in exercise capacity (P<0.05). The experimental group exhibited a significant enhancement in the GWB, PSQI and CSES (P<0.05). Only GWB had significant difference in the control group (P<0.05). The experimental group surpassed the control group in GWB and CSES (P<0.05). The adherence rate was 87.5% in the experimental group and 57.9% in the control group after 8 weeks intervention. Analysis on adherence identified 15 themes, the top 3 themes mentioned were as follows: mind-body effects, online and on-site guidance, training schedule (for subjects); mind-body effects, difficulties in practicing, and understanding of Tai Chi (for practitioners). Both interventions were effective in improving exercise capacity. Tai Chi, integrating both physical and mental conditioning, reduced weight, improved exercise capacity and mental happiness, and increased adherence, providing a sustainable exercise program (ChiCTR2200063599).

High-Energy Ball Milling Enables an Ultra-Fast Wittig Olefination Under Ambient and Solvent-free Conditions.

30 Seconds to success!-The Wittig reaction, a fundamental and extensively utilized reaction in organic chemistry, enables the efficient conversion of carbonyl compounds to olefins using phosphonium salts. Traditionally, meticulous reaction setup, including the pre-formation of a reactive ylide species via deprotonation of a phosphonium salt, is crucial for achieving high-yielding reactions under classical solution-based conditions. In this report, we present an unprecedented protocol for an ultra-fast mechanically induced Wittig reaction under solvent-free and ambient conditions, often eliminating the need for tedious ylide pre-formation under strict air and moisture exclusion. A range of aldehydes and ketones were reacted with diverse phosphonium salts under high-energy ball milling conditions, frequently giving access to the respective olefins in only 30 seconds.

Coupling of Fluid and Particle-in-Cell Simulations of Ambipolar Plasma Thrusters

Ambipolar plasma thrusters are an appealing technology due to multiple system-related advantages, including propellant flexibility and the absence of electrodes or neutralizer. Understanding the plasma generation and acceleration mechanisms is key to improving the performance and capabilities of these thrusters. However, the source and plume regions inside are often simulated separately, and no self-consistent strategy exists which can couple these different simulations together. This paper introduces the MUlti-regime Plasma Equilibrium Transport Solver (MUPETS), a self-consistent coupled model integrating a fluid solver for the plasma dynamics in the source, which are collision-driven, with a kinetic Particle-In-Cell (PIC) code for the plasma dynamics in the magnetic nozzle, which involve expansion across a diverging magnetic field. The methodology begins by solving the plasma source with the classical Bohm condition at the thruster’s throat. The resulting plasma profiles (density, temperature, speed) are input into the PIC code for the magnetic nozzle. The PIC code calculates the plasma plume expansion and determines the electric field at the thruster’s throat. This electric field is then used as a boundary condition in the fluid code, where it replaces the Bohm assumption, and the fluid simulation is repeated. This iterative process continues until convergence. In comparing the MUPETS results with those for an experimental thruster, the plasma densities at the thruster’s throat differed by less than 2–5% between the fluid and PIC regions. The thrust predictions agreed with the experimental trend, and were kept well within the measurement’s uncertainty band. These results validate the effectiveness of the coupling strategy for enhancing plasma thruster simulation accuracy.

Effects of separate and combined estradiol and progesterone administration on fear extinction in healthy pre-menopausal women

Altered fear conditioning and extinction learning are discussed as key etiological features in anxiety disorders. Women have an increased risk for anxiety disorders and fear conditioning has been shown to be influenced by the menstrual cycle phase and circulating gonadal hormones. The objective of our study was to investigate the effects of separate and combined estradiol and progesterone administration on fear extinction in healthy women. We conducted a placebo-controlled, randomized study in healthy women, who completed a fear conditioning paradigm on three consecutive days: fear acquisition training on day 1, fear extinction training on day 2, and return of fear test on day 3. Skin conductance responses (SCRs) served as main outcome variable. Two hours before testing on day 2, participants received pills containing either placebo, estradiol (2 mg), progesterone (400 mg) or the combination of both. We examined 116 women (mean age 25.7 ± 6.0 years), who showed significantly stronger conditioned SCRs to the CS+ than CS- during fear acquisition training indicating successful fear learning. At the beginning of the fear extinction training, estradiol administration reduced the differentiation between the conditioned stimuli. In the return of fear test, the estradiol groups showed heightened SCR responses to the previously extinguished stimulus, i.e., impaired extinction recall. Administration of progesterone did not have any significant influence on SCRs. There were also no effects on fear potentiated startle response. In our interpretation, exogenous estradiol administration affected the extinction of the conditioned fear response which led subsequently to a stronger return of fear. From a clinical perspective our findings suggest that estradiol levels may have an influence on the success of exposure therapy and could be taken into consideration when planning exposure sessions.

Avoidance of hot air blast in Rattus norvegicus.

The hegemonic use of electric shock as an aversive stimulus limits what is known about the generality of avoidance behavior and related phenomena. The purpose of this study was to investigate the effects of using the hot air blast (HAB) instead of electric shock as an aversive stimulus in avoidance conditioning. Four male Wistar rats were exposed to a discrete-trial procedure. In the first phase, the emission of a lever-press response during a trial was positively reinforced. In the second phase, the same contingency was employed, but an escapable HAB was presented at the end of a trial when no response was emitted. In the third phase, positive reinforcement was suspended and a discrete-trial avoidance procedure was employed. In the fourth phase, HAB presentation was completely suspended. As a result, all subjects learned the avoidance response and showed a marked reduction in its frequency during HAB suspension. These results offer evidence indicating that avoidance behavior is controlled by the HAB, thereby advancing the understanding of the generality of this stimulus as being aversive.

Cannabinoid hyperemesis syndrome: genetic susceptibility to toxic exposure

Cannabinoid hyperemesis syndrome presents as a complex of symptoms and signs encompassing nausea, vomiting, abdominal pain, and hot water bathing behavior, most typically in a heavy cannabis user. Its presentation is frequently associated with hypothalamic-pituitary-adrenal axis activation with stress and weight loss. Recent investigation has identified five statistically significant mutations in patients distinct from those of frequent cannabis users who lack the symptoms, affecting the TRPV1 receptor, two dopamine genes, the cytochrome P450 2C9 enzyme that metabolizes tetrahydrocannabinol, and the adenosine triphosphate-binding cassette transporter. The syndrome is associated with escalating intake of high potency cannabis, or alternatively, other agonists of the cannabinoid-1 receptor including synthetic cannabinoids. Some patients develop environmental triggers in scents or foods that suggest classical conditioned responses. Various alternative “causes” are addressed and refuted in the text, including exposure to pesticides, neem oil or azadirachtin. Nosological confusion of cannabinoid hyperemesis syndrome has arisen with cyclic vomiting syndrome, whose presentation and pathophysiology are clearly distinct. The possible utilization of non-intoxicating antiemetic cannabis components in cannabis for treatment of cannabinoid hyperemesis syndrome is addressed, along with future research suggestions in relation to its genetic foundation and possible metabolomic signatures.

National Collegiate Athletic Association Athletic Trainers’, Head Coaches’, and Student-Athletes’ Perceptions of Professional Titles Used in Sport PsychologyA

The purpose of this convergent mixed-methods study was to explore National Collegiate Athletic Association (NCAA) Division I athletic trainer (AT), head coach, and student-athlete perceptions of three commonly used sport psychology professional titles in the United States: Certified Mental Performance Consultant (CMPC), mental conditioning coach, and sport psychologist. Participants included 73 ATs, 79 head coaches, and 76 student-athletes. Participants completed an online questionnaire that assessed their previous exposure to these professionals, the services they believed these professionals could provide, their confidence in sport psychology consultation from these professionals, and their stigma tolerance of these professionals. A series of Friedman tests found that ATs and student-athletes perceived significantly more confidence in the services of a sport psychologist compared to a CMPC and a mental conditioning coach. A series of Kruskal-Wallis tests revealed that student-athletes perceived significantly more stigma in using services from all three professionals than head coaches and ATs. Participants reported that sport psychologists could provide mental performance and mental health services, while CMPCs and mental conditioning coaches primarily provided mental performance services. However, short answer responses from many ATs and head coaches about CMPCs demonstrated some doubt and misunderstanding of this professional title.

Resting-state brain activation patterns and network topology distinguish human sign and goal trackers

The “Sign-tracker/Goal-tracker” (ST/GT) is an animal model of individual differences in learning and motivational processes attributable to distinctive conditioned responses to environmental cues. While GT rats value the reward-predictive cue as a mere predictor, ST rats attribute it with incentive salience, engaging in aberrant reward-seeking behaviors that mirror those of impulse control disorders. Given its potential clinical value, the present study aimed to map such model onto humans and investigated resting state functional magnetic resonance imaging correlates of individuals categorized as more disposed to sign-tracking or goal-tracking behavior. To do so, eye-tracking was used during a translationally informed Pavlovian paradigm to classify humans as STs (n = 36) GTs (n = 35) or as Intermediates (n = 33), depending on their eye-gaze towards the reward-predictive cue or the reward location. Using connectivity and network-based approach, measures of resting state functional connectivity and centrality (role of a node as a hub) replicated preclinical findings, suggesting a major involvement of subcortical areas in STs, and dominant cortical involvement in GTs. Overall, the study strengthens the translational value of the ST/GT model, with important implications for the early identification of vulnerable phenotypes for psychopathological conditions such as substance use disorder.

Visual imagination can influence visual perception - towards an experimental paradigm to measure imagination.

During visual imagination, a perceptual representation is activated in the absence of sensory input. This is sometimes described as seeing with the mind's eye. A number of physiological studies indicate that the brain uses more or less the same neural resources for visual perception of sensory information and visual imagination. The intensity of visual imagination is typically assessed with questionnaires, while more objective measures are missing. Aim of the present study was, to test a new experimental paradigm that may allow to objectively quantify imagination. For this, we used priming and adaptation effects during observation of ambiguous figures. Our perception of an ambiguous stimulus is unstable and alternates spontaneously between two possible interpretations. If we first observe an unambiguous stimulus variant (the conditioning stimulus), the subsequently presented ambiguous stimulus can either be perceived in the same way as the test stimulus (priming effect) or in the opposite way (adaptation effect) as a function of the conditioning time. We tested for these conditioning effects (priming and adaptation) using an ambiguous Necker Cube and an ambiguous Letter /Number stimulus as test stimuli and unambiguous variants thereof as conditioning stimuli. In a second experimental condition, we tested whether the previous imagination of an unambiguous conditioning stimulus variant - instead of its observation - can have similar conditioning effects on the subsequent test stimulus. We found no systematic conditioning effect on the group level, neither for the two stimulus types (Necker Cube stimuli and Letter /Number stimuli) nor for the two conditions (Real and Imaginary). However, significant correlations between effects of Real and Imaginary Condition were observed for both stimulus types. The absence of conditioning effects at the group level may be explained by using only one conditioning time, which may fit with individual priming and adaptation constants of some of our participants but not of others. Our strong correlation results indicate that observers with clear conditioning effects have about the same type (priming or adaptation) and intensity of imaginary conditioning effects. As a consequence, not only past perceptual experiences but also past imaginations can influence our current percepts. This is further confirmation that the mechanisms underlying perception and imagination are similar. Our post-hoc qualitative observations from three self-defined aphantasic observers indicate that our paradigm may be a promising objective measure to identify aphantasia.

Characterizations of infinitesimal relative boundedness for higher order Schrödinger operators

Let m∈N and H=(−Δ)m/2+V be a higher order Schrödinger operators in the Euclidean space Rn with V∈Lloc1(Rn). In this paper, the authors characterize the infinitesimal relative boundedness and Trudinger's subordination for H on Lp(Rn) with p∈[1,∞), via the limit behavior of the family of operators {V(λ2−Δ)−m/2}λ∈(0,∞) and a generalized Kato-type class condition. The latter is weaker than the classical Kato class condition corresponding to the case p=1. All these characterizations are new even when H=−Δ+V is a second order Schrödinger operator.

Valenced tactile information is evoked by neutral visual cues following emotional learning

Abstract Learning which stimuli in our environment co-occur with painful or pleasurable events is critical for survival. Previous research has established the basic neural and behavioral mechanisms of aversive and appetitive conditioning; however, it is unclear precisely what information content is learned. Here we examined the degree to which aspects of the unconditioned stimulus (US)—sensory information versus affective salience—are transferred to the conditioned stimulus (CS). To decode what stimuli features (e.g., valence vs. discriminative somatosensation) are represented in patterns of brain activation elicited during appetitive (soft touch) and aversive (painful touch) conditioning to faces, a novel approach to using modeling with representational similarity analysis (RSA) based on theoretically driven representational patterns of interest (POIs) was applied to fMRI data. Once associations were learned through conditioning, globally, the CS reactivated US representational patterns showing conditioning-dependent reactivation in specific high-order brain regions: In the dorsal anterior cingulate cortex, the CS reactivated patterns associated with the affective salience of the US—suggesting that, with affective conditioning, these regions carry forward the affective associations of the experience.

An unescapable looming threat paradigm for assessing anxiety-like responses in rats.

Rapidly approaching visual stimuli (i.e. looming objects) are known to evoke unconditioned defense responses across species. In rodents, this threat reactivity repertoire includes freezing and fleeing behavior. Although components of the circuitry underlying unconditioned response to a looming threat have been elucidated, both a temporal characterization and drug effects on the freezing response have not yet been reported. Here, we describe a modified version of a looming threat task in which no escape route is available. In this task, we observed unconditioned freezing prior to, during, and after exposure to a looming threat stimulus. In Long Evans (LE) and Sprague-Dawley (SD) rats, we report looming stimulus-specific freezing response. We further explored the specificity and pharmacosensitivity of this response in male and female LE rats. Administration of a GABA-A receptor negative allosteric modulator (FG-7142) did not re-establish freezing in habituated animals; however, administration of a GABA-A receptor positive allosteric modulator (diazepam) in naïve LEs significantly reduced freezing during the post-looming period in a sex-dependent manner. Presentation of an unescapable looming stimulus results in freezing that extends beyond the acute threat exposure. Because freezing responses outlast the initial threat, and display only modest sensitivity to conventional anxiolytic therapy, this may represent a platform for screening agents in treatment-refractory anxiety.

DNAJC13 influences responses of the extended reward system to conditioned stimuli: a genome-wide association study.

Reward system dysfunction is implicated in the pathogenesis of major psychiatric disorders. We conducted a genome-wide association study (GWAS) to identify genes that influence activation strength of brain regions within the extended reward system in humans. A homogeneous sample of 214 participants was genotyped and underwent functional magnetic resonance imaging (fMRI). All subjects performed the 'desire-reason dilemma' (DRD) paradigm allowing systematic investigation of systems-level mechanisms of reward processing in humans. As a main finding, we identified the single nucleotide variant rs113408797 in the DnaJ Heat Shock Protein Family Member C13 gene [DNAJC13], alias Receptor-Mediated Endocytosis 8 [RME-8], that was associated with the activation strength of the ventral tegmental area (VTA; p = 2.50E-07) and the nucleus accumbens (NAcc; p = 5.31E-05) in response to conditioned reward stimuli. Moreover, haplotype analysis assessing the information across the entire DNAJC13 locus demonstrated an impact of a five-marker haplotype on VTA activation (p = 3.21E-07), which further corroborates a link between this gene and reward processing. The present findings provide first direct empirical evidence that genetic variation of DNAJC13 influences neural responses within the extended reward system to conditioned stimuli. Further studies are required to investigate the role of this gene in the pathogenesis and pathophysiology of neuropsychiatric disorders.

Preserving precise choreography of bonds in Z-stereoretentive olefin metathesis by using quinoxaline-2,3-dithiolate ligand

The Z-alkene geometry is prevalent in various chemical compounds, including numerous building blocks, fine chemicals, and natural products. Unfortunately, established Mo, W, and Ru Z-selective catalysts lose their selectivity at high temperatures required for industrial processes like reactive distillation, which limits their synthetic applications. To address this issue, we develop a catalyst capable of providing Z-alkenes with high selectivity under harsh conditions. Our research reveals a dithiolate ligand that, stabilised by resonance, delivers high selectivity at temperatures up to 150 °C in concentrated mixtures. This distinguishes the dithioquinoxaline complex from existing Z-selective catalysts. Notably, this trait does not compromise the new catalyst’s usability under classical conditions, matching the activity of known stereoretentive catalysts. Density Functional Theory calculations were employed to understand the reaction mechanism and selectivity, and to investigate the poisoning that the catalyst may undergo and how it competes with catalytic activity. Furthermore, the quinoxaline-based catalyst enables the valorisation of bio-sourced alkene feedstocks and the production of agricultural sex pheromones for pest control.

Leveraging occasional reinforced extinction via mental imagery of the unconditioned stimulus to optimize extinction learning

Occasionally presenting the unconditioned stimulus (US) during extinction training (occasional reinforced extinction, ORE) either unpaired or paired with the conditioned stimulus (CS) provides initial evidence for a less pronounced return of fear. However, translating this approach into clinical practice is challenging due to ethical and practical concerns of exposing patients to the original USs. The present study investigated extinction of fear responses in a novel approach employing ORE using vivid fear imagery of the US instead of actually exposing to it. Three experimental groups underwent differential fear conditioning. Subsequently, participants either received a non-reinforced (standard extinction, N = 25), occasional paired (N = 26), or occasional unpaired (N = 25) reinforced extinction training, followed by assessments for spontaneous recovery, reinstatement, and reacquisition of fear responses. Response patterns during spontaneous recovery, reinstatement and reacquisition showed no benefit from either paired or unpaired imaginative ORE. The current findings suggest that incorporating fear imagery of the US in ORE so far does not result in reducing the return of fear. Further investigation is needed to determine whether imaginal ORE with adjustments could still be a readily applicable strategy for translating the ORE approach into clinical practice.

Investigation of the Versatile Utilization of Three-Dimensional Vertical Resistive Random-Access Memory in Neuromorphic Computing.

The continuous advancement of computing technologies such as the Internet of Things and artificial intelligence emphasizes the need for innovative approaches to data processing. Faced with limitations in processing speed due to the exponentially increasing volume of data, conventional von-Neumann computing systems are transforming into a new paradigm called neuromorphic computing, inspired by the efficiency of the human brain. We fabricate three-dimensional vertical resistive random-access memory (VRRAM), which is highly suited for neuromorphic computing, and demonstrate its value as an artificial synapse. Beyond simulating simple synaptic functionalities such as spike-rate-dependent plasticity, spike-timing-dependent plasticity, and paired-pulse facilitation, we propose specific applications and experimentally implement them. In pattern recognition simulations based on the weight update characteristics of the fabricated VRRAM, the accuracy achieved in pattern recognition using appropriate pulse schemes reaches 90.4%. Additionally, we demonstrate adaptive learning behavior on the device by mimicking Pavlov's dog experiment with combinations of applied voltage pulses. Finally, we employ suitable write/erase pulse trains to implement binary representations for decimal numbers ranging from 0 to 15, thereby illustrating the significant potential of local devices for edge computing applications.

Effect of chronic alcohol exposure and single-prolonged stress on conditioned fear behavior

The present study investigated the impact of chronic intermittent ethanol (CIE) exposure and single-prolonged stress (SPS) on the acquisition of fear memories in both male and female Wistar rats. Adult rats were first subjected to CIE by vapor inhalation followed by SPS. Following a subsequent 8-day incubation period, the rats underwent a Pavlovian fear conditioning procedure (tone-shock pairings) followed by cued-tone extinction training, and then testing of extinction recall memory and fear renewal memory. In control animals that had not been exposed to either CIE or SPS, female rats exhibited significantly lower levels of freezing compared to male rats during tone-shock pairings. This lower level of freezing in female rats during conditioning was associated with an increased speed of movement compared to males. Also compared to males, female rats exhibited lower levels of fear extinction, recall, and renewal. Exposure to CIE, SPS, or CIE+SPS had no effect on freezing during the cued-conditioning, extinction, or extinction recall phases of the testing procedure in either sex. In fear renewal, CIE exposure decreased freezing in male but not female rats, while SPS increased freezing in female but not male rats. CIE exposure significantly reduced freezing during the fear renewal phase. Taken together, these results provide further evidence that male and female rats adopt different avoidance strategies for threat responding. These results also revealed that prior exposure to CIE, SPS, or CIE+SPS had minimal effects on threat responding using conditioned freezing as an indicator of fear responsivity.

Dose-dependent effect of acute THC on extinction memory recall and fear renewal: a randomized, double-blind, placebo-controlled study.

Prior work from our lab and others demonstrates that the endocannabinoid system is a promising avenue for improving fear memory deficits in posttraumatic stress disorder (PTSD). Specifically, 7.5mg of delta-9-tetrahydrocannabinol (THC) decreases fear responding in healthy adults and increases prefrontal cortex activation during extinction learning and fear renewal in adults with PTSD. The present study will determine whether there is a dose-dependent effect of THC on short-term (24h) and long-term (one week) fear learning and memory in adults with PTSD. Using a randomized, double-blind, placebo-controlled design, N = 36 adults with PTSD completed the study and were randomized to receive placebo (PBO, n = 11), 5mg of THC (n = 11), or 10mg of THC (n = 14) prior to fear extinction learning. Participants completed a Pavlovian conditioning paradigm with extinction recall and fear renewal occurring 24h and one week later, where we measured concurrent functional imaging and behavioral responses. Twenty-four hours after drug administration, individuals with PTSD given 5mg of THC exhibited greater anterior cingulate cortex and prefrontal cortex activation during early fear renewal. One week later, individuals given 10mg of THC exhibited greater hippocampus activation during extinction recall and prefrontal cortex activation during fear renewal. These data suggest that dosing and timing are critical for facilitating fear memory processes in PTSD, and that low-dose oral THC prior to extinction learning can affect brain indices of fear learning and memory both acutely and one week after administration.