Behavioral Avoidance Test Research Articles

The Behavior Avoidance Test: Association With Symptom Severity and Treatment Outcome in Obsessive-Compulsive Disorder.

Behavior therapy of obsessive-compulsive disorder (OCD) aims to reduce avoidance, rituals, and discomfort in OCD-relevant situations. The Behavioral Avoidance Test (BAT) measures these behavior-related outcomes in individually challenging OCD-related situations. The association of the BAT with OCD severity measures and its relevance for treatment outcome is, however, still unclear. The current study investigates with a retrospective analysis of a subsample of a pilot study, (1) if reactions on the BAT are related to OCD severity measures in an OCD sample (n = 28), (2) if treatment with two variants of cognitive-behavior therapy (exposure and response prevention vs. metacognitive therapy) changes the BAT scores and (3) if these changes as well as pretreatment BAT avoidance are relevant for OCD treatment outcome as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Participants rated avoidance, ritual, and discomfort in three individually challenging OCD-related situations before and after therapy. For one of these situations, BAT dimensions were rated by the therapist and an independent rater in addition to the patients' ratings. Correlational analyses found significant correlations between BAT discomfort and OCD severity measures like the Y-BOCS. A repeated measures ANOVA with pre- and posttest scores showed that all three BAT dimensions significantly decreased during both treatments. Hierarchical regression analyses (controlling for Y-BOCS pretest scores) revealed that changes in BAT discomfort as well as pretreatment BAT avoidance scores predicted the Y-BOCS posttest score. These findings suggest that the BAT is a distinct measure of behavior-related outcomes partly being relevant for OCD treatment outcome.

Nothing to Fear but Fear Itself: A Mechanistic Test of Unconscious Exposure

BackgroundWhile effective, exposure therapy can be distressing, which creates problems with treatment acceptance. Can exposure be effectively delivered unconsciously—and thus without causing phobic people to experience distress? No study has tested this hypothesis in a sufficiently rigorous experiment that selected between mechanisms for reducing fear unconsciously. MethodsWe conducted a psychophysiological experiment of an unconscious exposure intervention to discern its mechanism of therapeutic action. We identified 98 highly spider-phobic participants with a validated fear questionnaire and a Behavioral Avoidance Test in which they gradually approached and exhibited impairment of a live tarantula, which was indicative of a DSM-5 diagnosis of specific phobia. These participants were randomized to viewing unconscious exposure to spiders, visible exposure to spiders, or unconscious exposure to flowers (control). In a novel psychophysiological design, concurrent changes in sympathetic arousal and subjective fear were monitored throughout exposure. Shortly thereafter, phobic participants approached the tarantula again in order to measure exposure-induced changes in real-life avoidance behavior and experienced fear. ResultsUnconscious exposure did not induce concurrent changes in sympathetic arousal or subjective fear, and subsequently reduced fear of the tarantula. Visible exposure to the same phobic stimuli, by contrast, induced significant arousal and fear, but did not affect fear of the tarantula. Levels of arousal during exposure moderated effects on fear of the tarantula: lower arousal during unconscious exposure, but not during conscious exposure, predicted greater fear reduction. ConclusionsUnconscious exposure reduces fear by generating new implicit learning of nonaversive, stimulus-response associations that facilitate fear extinction in phobic persons.

The behavior avoidance test: Association with symptom severity and treatment outcome in obsessive-compulsive disorder

The behavior avoidance test: Association with symptom severity and treatment outcome in obsessive-compulsive disorder

Transfer of exposure therapy effects to a threat context not considered during treatment in patients with panic disorder and agoraphobia: Implications for potential mechanisms of change

Further developments of exposure-based therapy (EBT) require more knowledge about transfer of treatment to non-trained everyday contexts. However, little is known about transfer effects of EBT.Using a standardized EBT protocol in 275 patients with panic disorder and agoraphobia we investigated the transfer of EBT to a highly standardized context during a Behavioral Avoidance Test (BAT; being entrapped in a small and dark test chamber) and not part of the exposure sessions. Patients of a treatment group underwent the BATs before treatment (t1), after a preparatory treatment phase (t2), and after an agoraphobic exposure phase (t3) and were compared with wait-list control patients, who repeated BAT assessments across the same time period.We found stronger reductions in avoidance behavior, reported fear, and autonomic arousal during the BAT from t1 to t3 in the treatment group patients who were anxious during t1 relative to the anxious but untreated patients. Fear reduction was related to treatment outcome indicating the contribution of transfer effects to successful EBT. Interestingly, reduction varied for different fear response systems suggesting different processes to may be involved in transfer effects. Importantly, final BAT assessment still evoked residual fear in the treatment group as compared to BAT non-anxious control patients, suggesting limited transfer effects – one possible reason for the return of symptoms in new situations.

Effectiveness of a stand-alone, smartphone-based virtual reality exposure app to reduce fear of heights in real-life: a randomized trial

Smartphone-based virtual reality (VR) applications (apps) might help to counter low utilization rates of available treatments for fear of heights. Demonstration of effectiveness in real-life situations of such apps is crucial, but lacking so far. Objective of this study was to develop a stand-alone, smartphone-based VR exposure app—Easy Heights—and to test its effectiveness in a real-life situation. We performed a single-blind, parallel group, randomized controlled trial. We recruited 70 participants with fear of heights, aged 18–60 years. Primary outcome was performance in a real-life Behavioral Avoidance Test (BAT) on a lookout tower after a single 1-h app use (phase 1) and after additional repeated (6 × 30 min) app use at home (phase 2). After phase 2, but not phase 1, participants in the Easy Heights condition showed significantly higher BAT scores compared to participants in the control condition (Cohen’s d = 1.3, p = 0.0001). Repeated use of our stand-alone, smartphone-based VR exposure app reduces avoidance behavior and fear, providing a low-threshold treatment for fear of heights.

Effects of adolescent experience of food restriction and exercise on spatial learning and open field exploration of female rats

The hippocampus carries out multiple functions: spatial cognition dorsally (DH) and regulation of emotionality-driven behavior ventrally (VH). Previously, we showed that dendrites of DH and VH pyramidal neurons of female rats are still developing robustly during adolescence and are altered by the experience of food restriction and voluntary exercise on a wheel. We tested whether such anatomical changes during adolescence impact anxiety-like behavior and spatial cognition. Four groups of female rats were evaluated for these behaviors: those with wheel access in its cage from postnatal day (P) 36-44 (EX); those with food access restricted to 1 hr per day, from P40 to 44 (FR); those with EX from P36 to 44, combined with FR from P40 to 44, which we will refer to as EX + FR; and controls, CON (no EX, no FR). Open field test for anxiety-like behavior and active place avoidance test for spatial cognition were conducted at P47-49, the age when food restricted animals have restored body weight, or at P54-56, to identify more enduring effects. Anxiety-like behavior was elevated for the EX and FR groups at P47-49 but not for the EX + FR group. By P54-56, the EX + FR and EX groups exhibited less anxiety-like behavior, indicating a beneficial delayed main effect of exercise. There was a beneficial main effect of food restriction upon cognition, as the FR group showed cognition superior to CONs' at P44-46 and P54-56, while the EX + FR animals also showed enhanced spatial learning at P54-56. EX + FR animals with best adaptation to the feeding schedule showed the best spatial learning performance but with a delay. The EX group exhibited only a transient improvement. These findings indicate that FR, EX, and EX + FR in mid-adolescence are all beneficial in reducing anxiety-like behavior and improving spatial cognition but with subtle differences in the timing of their manifestation, possibly reflecting the protracted maturation of the hippocampus.

Multimedia intervention for specific phobias: A clinical and experimental study.

Exposure is the treatment of choice for specific phobias. We present an experimental and clinical study on the efficacy of the progressive multimedia exposure procedure for specific phobias. The sample size consisted of 36 individuals, 7 men and 29 women (mean age: 29 years old), with different types of specific phobias. A combined between-groups (3x4) with repeated measures design was used, including several follow-ups up to 3 years. Participants were assigned to different groups: Experimental (10), Waiting List (12), and Control (14). As an evaluation method, a Behavioural Avoidance Test (BAT) with subjective anxiety and heart rate was used for images and videos, plus general and specific anxiety questionnaires for each phobia. The intervention was carried out in four phases of multimedia exposure: photographs, videos, simulated stimuli, and real stimulation. Anxiety and avoidance were significantly reduced in the experimental group, with a very large effect size (between d = 1.37 and 5.37). There were no significant changes in either the Control Group or the Waiting List Group. The treatment had a clinically significant impact on the daily life of the participants. This multimedia procedure was shown to be effective and to use few resources, thus allowing it to always be adapted to the individual characteristics of the participants.

Different diets with and without inclusion of antimicrobial additives alter the toxicity of swine manure to springtails and earthworms

The objective of this study was to measure the impact on part of soil fauna of application of non-stabilized (fresh) manure from post-weaning pigs fed diets formulated with or without dual-purpose wheat, and with or without the use of antimicrobial growth-promoting additives (100 mg kg-1 doxycycline + 50 mg kg-1 colistin + 250 mg kg-1 Zn oxide). Two species of edaphic organisms were evaluated, the springtails Folsomia candida and the earthworms Eisenia andrei, using ecotoxicological avoidance behavior tests. The treatments were swine manure from: RR: Reference Ration; WR: Wheat Reference; RA: Reference Ration + Antimicrobial Additives; WA: Wheat Reference + Antimicrobial Additives). The doses of waste used for treatments were as follows: 0, 5, 10, 20, 30, 40, 65 and 100 m³ ha-1 for the springtails and 0, 5, 10, 20, 30, 40 and 65 m³ ha-1 for the earthworms, applied in the Oxisol. The experimental design was completely randomized with five replicates. The use of non-stabilized swine manure did not affect the avoidance behavior of F. candida at any dose, regardless of the use of antimicrobial or wheat additives. For E. andrei, there was avoidance behavior at all treatments and doses used. These avoidance behaviors were related to the sensitivity of each species of soil organism. The avoidance behavior for earthworms was related to the doses of non-stabilized swine manure in soil and not to the various diets and/or the use of growth-promoting additives.

Caracterização e avaliação preliminar da ecotoxicidade de resíduo de indústrias de papelão

A indústria de papel e papelão é geradora de resíduos sólidos que demandam correto tratamento e disposição. O trabalho teve por objetivo caracterizar a composição de resíduos de duas empresas de papelão de Santa Catarina e avaliar sua ecotoxicidade. A caracterização foi feita com a determinação da umidade, cinzas e celulose. A ecotoxicidade foi avaliada com ensaios de fuga com minhocas (Eisenia andrei), ensaios de reprodução com colêmbolos (Folsomia candida) e com um teste de germinação e crescimento de raízes de alface (Lactuca sativa). Para as avaliações dos ensaios de toxicidade utilizou-se a ANOVA seguida dos testes de Tukey e/ou Dunnet e o teste exato de Fisher todos à p<0,05. Os Resíduos 1 e 2 apresentaram umidade de 87,23 e 60,80%, cinzas 11,18 e 55,12% e celulose 59,34 e 66,78%, respectivamente. Os ensaios de fuga e de reprodução não indicaram ecotoxicidade dos resíduos estudados para minhocas e colêmbolos quando comparados ao solo de plantio de pinus. Em relação ao crescimento de raízes, o Resíduo 1 apresentou toxicidade para as concentrações de 100, 75 e 50% do seu elutriato. Os resultados indicaram que os resíduos possuem características químicas, físicas e ecotoxicológicas que podem ser restritivas quanto a sua aplicação em solos agrícolas.

Enzyme assays and toxicity of pig abattoir waste in Eisenia andrei

Due to high global demand, large amounts of abbattoir waste are generated from pork production. Mismanagement of abattoir waste on agricultural lands can result in soil and water contamination with pathogens and contaminants like metals and nutrients. Therefore, possible effects on soil organisms prior to application should be evaluated. Thus, the aim of this study was to determine the effects of fresh pig abattoir waste (PAWf) and waste after stabilization processes on E. andrei through tests of avoidance behavior, acute toxicity and chronic toxicity. In order to do this, the waste was evaluated fresh (i.e., non-treated), and after aerated composting (PAWa), natural composting (PAWn) and vermicomposting (PAWv). In addition, we used a natural soil with no history of agricultural use as control soil. The evaluation was based on avoidance behavior, mortality, initial and final earthworm weight, and reproduction, in addition to a set of enzyme assays formed by acetylcholinesterase, lipid peroxidation, catalase and glutathione S-transferase measured over time. The ecotoxicological results showed that PAWf and PAWa increased AChE activity at different experimental periods, while PAWn decreased activity at 14 days compared to the control. PAWf and PAWa increased TBARS levels at 7 and 14 days, respectively. CAT activity decreased at 3, 7 and 14 days in PAWv, while GST activity increased at 3 days in PAWa and at 3 and 14 days in PAWf compared to the control. In the acute toxicity test, PAWa and PAWn had a toxic effect on E. andrei, resulting in 100% mortality at 14 days of exposure. Based on our findings, pig abattoir waste should undergo vermicomposting prior to agricultural application to soils.

Treating patients with driving phobia by virtual reality exposure therapy – a pilot study

ObjectivesVirtual reality exposure therapy (VRET) is a promising treatment for patients with fear of driving. The present pilot study is the first one focusing on behavioral effects of VRET on patients with fear of driving as measured by a post-treatment driving test in real traffic.MethodsThe therapy followed a standardized manual including psychotherapeutic and medical examination, two preparative psychotherapy sessions, five virtual reality exposure sessions, a final behavioral avoidance test (BAT) in real traffic, a closing session, and two follow-up phone assessments after six and twelve weeks. VRE was conducted in a driving simulator with a fully equipped mockup. The exposure scenarios were individually tailored to the patients’ anxiety hierarchy. A total of 14 patients were treated. Parameters on the verbal, behavioral and physiological level were assessed.ResultsThe treatment was helpful to overcome driving fear and avoidance. In the final BAT, all patients mastered driving tasks they had avoided before, 71% showed an adequate driving behavior as assessed by the driving instructor, and 93% could maintain their treatment success until the second follow-up phone call. Further analyses suggest that treatment reduces avoidance behavior as well as symptoms of posttraumatic stress disorder as measured by standardized questionnaires (Avoidance and Fusion Questionnaire: p < .10, PTSD Symptom Scale–Self Report: p < .05).ConclusionsVRET in driving simulation is very promising to treat driving fear. Further research with randomized controlled trials is needed to verify efficacy. Moreover, simulators with lower configuration stages should be tested for a broad availability in psychotherapy.

Eprinomectin antiparasitic affects survival, reproduction and behavior of Folsomia candida biomarker, and its toxicity depends on the type of soil

The objective of this study was to evaluate the toxicity of the antiparasitic agent eprinomectin in two subtropical soils, using ecotoxicological lethality, reproduction and avoidance behavior tests with springtails (Folsomia candida). Eprinomectin concentrations were 0 (control), 0.5, 1, 2, 4, 8, 12, 16 and 20 mg kg−1 of dry soil combined with either Entisol or Oxisol soils. Statistically significant toxic effects of eprinomectin on springtails were observed in both soils. Eprinomectin was lethal starting at 8 mg kg-1 of dry soil in Entisol, and 20 mg kg−1 of dry soil in Oxisol, with effects less than 50% at lethal concentrations. Reductions in the reproduction rate of the springtails were also observed starting at 8 mg kg−1 of dry soil in Entisol, and 0.5 mg kg−1 of dry soil in Oxisol. ECrepr50 value calculated for Entisol was 4.38 ± 0.62 mg kg-1 of dry soil; for Oxisol the ECrepr50 was above the highest tested concentration. For avoidance behavior, the effect occurred from 0.5 mg kg-1 of dry soil for both soils. In Entisol, all concentrations caused avoidance of more than 95%, and in Oxisol the ECavoi50 value was 1.33 ± 0.83 mg kg-1 of dry soil. We conclude that eprinomectin affected survival, reproduction and caused avoidance behavior of F. candida in both soils. The toxic effects were greater as the concentration in the soils increased. The effects in Oxisol were less intense than those in Entisol with respect to the affected springtails. This discrepancy may be attributed to the different physicochemical characteristics of the soils that determine the retention capacity for eprinomectin; in particular, there are greater contents of clay, organic matter and cation exchange capacity in Oxisol.

Hippocampal-Prefrontal Theta Transmission Regulates Avoidance Behavior

Long-range synchronization of neural oscillations correlates with distinct behaviors, yet its causal role remains unproven. In mice, tests of avoidance behavior evoke increases in theta-frequency (∼8Hz) oscillatory synchrony between the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC). To test the causal role of this synchrony, we dynamically modulated vHPC-mPFC terminal activity using optogenetic stimulation. Oscillatory stimulation at 8Hz maximally increased avoidance behavior compared to 2, 4, and 20Hz. Moreover, avoidance behavior was selectively increased when 8-Hz stimulation was delivered in an oscillatory, but not pulsatile, manner. Furthermore, 8-Hz oscillatory stimulation enhanced vHPC-mPFC neurotransmission and entrained neural activity in the vHPC-mPFC network, resulting in increased synchrony between vHPC theta activity and mPFC spiking. These data suggest a privileged role for vHPC-mPFC theta-frequency communication in generating avoidance behavior and provide direct evidence that synchronized oscillations play a role in facilitating neural transmission and behavior.

Association of rs7688285 allelic variation coding for GLRB with fear reactivity and exposure-based therapy in patients with panic disorder and agoraphobia

The gene coding for glycine receptor β subunits (GLRB) has been found to be related to panic disorder and agoraphobia (PD/AG) and to be associated with altered insular BOLD activation during fear conditioning, as an intermediate phenotype of defensive system reactivity in healthy subjects. In a multicenter clinical trial on PD/AG patients we investigated in three sub-samples whether GLRB allelic variation (A/G; A-allele identified as «risk») in the single nucleotide polymorphism rs7688285 was associated with autonomic (behavioral avoidance test BAT; n = 267 patients) and neural (differential fear conditioning; n = 49 patients, n = 38 controls) measures, and furthermore with responding towards exposure-based cognitive behavioral therapy (CBT, n = 184 patients). An interaction of genotype with current PD/AG diagnosis (PD/AG vs. controls; fMRI data only) and their modification after CBT was tested as well. Exploratory fMRI results prior to CBT, revealed A-allele carriers irrespective of diagnostic status to show overall higher BOLD activation in the hippocampus, motor cortex (MC) and insula. Differential activation in the MC, anterior cingulate cortex (ACC) and insula was found in the interaction genotype X diagnosis. Differential activation in ACC and hippocampus was present in differential fear learning. ACC activation was modified after treatment, while no overall rs7688285 dependent effect on clinical outcomes was found. On the behavioral level, A-allele carriers showed pronounced fear reactivity prior to CBT which partially normalized afterwards. In sum, rs7688285 variation interacts in a complex manner with PD/AG on a functional systems level and might be involved in the development of PD/AG but not in their treatment.

Reducing avoidance in adults with high spider fear using perceptual discrimination training.

Fear overgeneralization is a central feature of anxiety disorders and can lead to excessive avoidance. As perceptual discrimination is a key component of fear overgeneralization, a perceptual discrimination training task was created aimed at improving perceptual discrimination and reducing fear overgeneralization. Participants with high spider fear were randomized into training or placebo conditions. After completing their assigned task, perceptual discrimination was tested. Thereafter, participants completed a behavioral avoidance test, consisting of five stimuli ranging from a paper spider to a live tarantula. Last, participants completed a threat/safety discrimination task using schematic morphs ranging from a flower to a spider, while self-report and skin conductance responses were collected. The training group showed better perceptual discrimination during the test than did the placebo group. Furthermore, as stimuli became increasingly similar to a live spider, participants in the training group exhibited decreased avoidance behavior. Finally, participants in the training group indicated that schematic morphs were less similar to a spider and showed less physiological arousal than did the placebo group. Together, these results attest to the possible clinical relevance of the perceptual discrimination training.

Creating a Computerized Instrument for the Assessment of Blood-Injury-Injection Phobia.

A new computerized instrument (the Multimedia Behavioral Avoidance Test, or MBAT) for blood-injury-injection phobia (BII) assessment is presented. Analogous stimuli such as images and videos can also elicit anxiety responses; thus, they can be used for the assessment of phobia. The MBAT was applied to participants via computer, and subjective anxiety responses and time latency were recorded. The MBAT was composed of 30 original images and 30 videos related to blood, injury and injections. The MBAT was compared with other pencil-and-paper questionnaires for BII phobia, and heart rate was also measured with a pulsioximeter. The participants included 160 students and professionals (34.5% males, 65.6% females; mean 28.6 years old). The results showed a high reliability for internal consistency in images and videos (α = .98 both), with a single factor that groups all the items. In addition, the MBAT had high concurrent validity (r = .78 to .85) with the different anxiety scales compared. The MBAT diagnosed 12 participants with possible BII phobia. It is a useful instrument in the assessment of this kind of phobia because it is easier and quicker than pencil-and-paper questionnaires, it uses more objective measurements, and it is useful in planning subsequent exposure with images and videos.

Dichlorvos alters morphology and behavior in zebrafish (Danio rerio) larvae

Dichlorvos (2,2-dichlorovinyl-dimethylphosphate), an organophosphorus pesticide used for indoor insect and livestock parasite control, is among the most common commercially available pesticides. However, there are significant concerns over its toxicity, especially due to its relative stability in water, soil, and air. Zebrafish, an important developmental model, has been used for studying the effects of toxic compounds. The aim of this study was to evaluate the exposure to dichlorvos at early life stages (1 h postfertilization - 7 days postfertilization) in the zebrafish and its toxicological effects during the development, through morphological (7 days postfertilization), locomotor and social behavior analysis (7, 14, 30, 70, and 120 days postfertilization). Dichlorvos (1, 5, and 10 mg/L) exposure reduced the body length and heartbeat rate at 7 days postfertilization (dpf), as well as the surface area of the eyes (5 and 10 mg/L). The avoidance behavior test showed a significant decrease in escape responses at 7 (1, 5, and 10 mg/L) and 14 (5 and 10 mg/L) dpf zebrafish. The evaluation of larval exploratory behavior showed a reduction in distance traveled, mean speed (1, 5, and 10 mg/L) and time mobile (10 mg/L) between control and dichlorvos groups. In addition, the analysis performed on adult animals showed that the changes in distance traveled and mean speed remained reduced in 30 (1, 5, and 10 mg/L) and 70 dpf (5 and 10 mg/L), recovering values similar to the control at 120 dpf. The social behavior of zebrafish was not altered by exposure to dichlorvos in the early stages of development. Thus, the exposure to organophosphorus compounds at early stages of development induces an increased susceptibility to behavioral and neuronal changes that could be associated with several neurodegenerative diseases.

A functional genetic variation of SLC6A2 repressor hsa-miR-579-3p upregulates sympathetic noradrenergic processes of fear and anxiety

Increased sympathetic noradrenergic signaling is crucially involved in fear and anxiety as defensive states. MicroRNAs regulate dynamic gene expression during synaptic plasticity and genetic variation of microRNAs modulating noradrenaline transporter gene (SLC6A2) expression may thus lead to altered central and peripheral processing of fear and anxiety. In silico prediction of microRNA regulation of SLC6A2 was confirmed by luciferase reporter assays and identified hsa-miR-579-3p as a regulating microRNA. The minor (T)-allele of rs2910931 (MAFcases = 0.431, MAFcontrols = 0.368) upstream of MIR579 was associated with panic disorder in patients (pallelic = 0.004, ncases = 506, ncontrols = 506) and with higher trait anxiety in healthy individuals (pASI = 0.029, pACQ = 0.047, n = 3112). Compared to the major (A)-allele, increased promoter activity was observed in luciferase reporter assays in vitro suggesting more effective MIR579 expression and SLC6A2 repression in vivo (p = 0.041). Healthy individuals carrying at least one (T)-allele showed a brain activation pattern suggesting increased defensive responding and sympathetic noradrenergic activation in midbrain and limbic areas during the extinction of conditioned fear. Panic disorder patients carrying two (T)-alleles showed elevated heart rates in an anxiety-provoking behavioral avoidance test (F(2, 270) = 5.47, p = 0.005). Fine-tuning of noradrenaline homeostasis by a MIR579 genetic variation modulated central and peripheral sympathetic noradrenergic activation during fear processing and anxiety. This study opens new perspectives on the role of microRNAs in the etiopathogenesis of anxiety disorders, particularly their cardiovascular symptoms and comorbidities.

Brain metabolism and related connectivity in patients with acrophobia treated by virtual reality therapy: an 18F-FDG PET pilot study sensitized by virtual exposure

BackgroundThe aim of this pilot study is to investigate the impact of virtual reality exposure therapy (VRET) on brain metabolism and connectivity.Eighteen patients with acrophobia were assessed by an 18F-FDG PET scan sensitized by virtual exposure before treatment, and nine of them were assessed again after eight sessions of VRET. Statistical Parametric Mapping was used to study the correlations between metabolism and pretherapeutic clinical scores and to compare metabolism before and after VRET (p voxel < 0.005, corrected for cluster volume). Metabolic connectivity was evaluated through interregional correlation analysis.ResultsBefore therapy, a positive correlation was found between scores on the behavioural avoidance test and left occipital metabolism (BA17-18). After VRET, patients presented increased metabolism in the left frontal superior gyri and the left precentral gyrus, which showed increased metabolic connectivity with bilateral occipital areas (BA17-18-19), concomitant with clinical recovery.ConclusionsThis study highlights the exciting opportunity to use brain PET imaging to investigate metabolism during virtual exposure and reports the involvement of the visual-motor control system in the treatment of acrophobia by VRET.

Persistent synovial inflammation plays important roles in persistent pain development in the rat knee before cartilage degradation reaches the subchondral bone

BackgroundThe major complaint of knee osteoarthritis (OA) is persistent pain. Unlike acute inflammatory pain, persistent pain is usually difficult to manage since its pathology is not fully understood. To elucidate the underlying mechanisms of persistent pain, we established 2 different inflammation-induced arthritis models by injecting monoiodo-acetic acid (MIA) into the joint cavity and performed integrated analyses of the structural changes in the synovial tissue and articular cartilage, sensory neuron rearrangement, and pain avoidance behavior in a rat arthritis model.MethodsMale Wistar rats received intra-articular injections of MIA (0.2 mg/30 μL, low-dose group; 1 mg/30 μL, high-dose group) in the right knee and phosphate buffered saline (PBS; 30 μL, control group) in the left knee. Fluorogold (FG), a retrograde neural tracer, was used to label the nerve fibers for the identification of sensory neurons that dominate the joints in the dorsal root ganglion (DRG). Both knees were subjected to the intra-articular injection of 2% FG in PBS (5 μL) under anesthesia 5–7 days prior to sacrifice. We performed pain avoidance behavior tests (incapacitance and von Frey tests) at 0, 1, 3, 5, 7, 14, 21, and 28 days. At 5, 14, and 28 days, the rats were sacrificed and the knee joint and DRG were excised for histological assessment. The knee joints were stained with hematoxylin and eosin, safranin O, and calcitonin gene-related peptide (CGRP). The DRG were immunostained with CGRP.ResultsA transient inflammatory response followed by mild articular cartilage degeneration was observed in the low-dose MIA model versus persistent inflammation with structural changes in the synovial tissue (fibrosis) in the high-dose model. In the high-dose model, full-thickness cartilage degeneration was observed within 2 weeks post-MIA injection. The pain avoidance behavior tests indicated that persistent synovial inflammation and structural changes of the infrapatellar fat pad may play important roles in persistent knee joint pain before the articular cartilage degeneration reaches the subchondral bone.ConclusionsTransient inflammation without structural changes of the synovial tissues did not induce persistent pain in the rat knee joint before degradation of the articular cartilage reached the subchondral bone plate.