Differential role of the hippocampal endocannabinoid system in the memory consolidation and retrieval mechanisms

CB1 cannabinoid receptors are abundantly expressed in the brain, with large concentrations present in the hippocampus, a brain structure essential for memory processing. In the present study, we have investigated the possible modulatory role of the endocannabinoid system in the dorsal hippocampus upon the different phases of memory processing of an aversive task. AM251, a selective antagonist of CB1 receptors, and anandamide, an endogenous agonist of cannabinoid receptors, were bilaterally infused into the dorsal hippocampus of male Wistar rats either before training, immediately after training, or before test in the step-down inhibitory avoidance (IA) task. Results showed that pre-training infusion of CB1 drugs did not influence the acquisition of the task. In contrast, post-training infusion of the CB1 antagonist disrupted while the antagonist facilitated memory consolidation of IA. The post-training results demonstrate that memory consolidation depends on the integrity of the endocannabinoid system in the CA1 region of the dorsal hippocampus. While we still have no direct proof of endocannabinoids released there after an aversive task such as IA, these results suggests that (a) AM251 acts blocking the binding of endogenously released cannabinoids and (b) exogenously supplemented anandamide may be adding its contribution to the action of the endogenously released pool. Considering our data and the higher density of CB1 receptors present in the GABAergic interneurons, we propose them as the putative target of the endocannabinoid modulation of memory, a hypothesis that needs to be proven. In addition, pre-test infusion of the CB1 receptor antagonist facilitated while infusion of the agonist did not affect memory retrieval of IA. The completely opposite action of the same drug upon memory at the post-training (consolidation) and pre-test (recall) contexts suggests that some durable change took place in the CA1 region during the consolidation process that modified the logical attributes of the pharmacological response, i.e., the drug response changed from memory disruption to memory facilitation. A similar phenomenon was previously described by us in the M4 cholinergic muscarinic subsystem in the hippocampus for the same task (Diehl, F., Fürstenau, L. O., Sanchez, G., Camboim, C., de Oliveira Alvares, L., Lanziotti, V. B., et al. (2007). Facilitatory effect of the intra-hippocampal pretest administration of MT3 in the inhibitory avoidance task. Behavioral Brain Research, 177(2), 227-231), but the biological nature of such change in the local neural circuitry remains to be investigated.     

Brief Behavioral Therapy for Pediatric Anxiety and Depression: Piloting an Integrated Treatment Approach

Mood and anxiety disorders in youth are disabling, distressing, and prevalent. Furthermore, depression and anxiety frequently co-exist, may share several etiological factors, and respond to similar interventions. In this paper, we report preliminary results from a treatment adaptation project designed to condense existing cognitive behavioral therapy protocols for anxiety and depression to their core components and combine them into a brief, integrated treatment suitable for the broad population of internalizing youth seen in primary care. Specifically, we discuss: (a) the rationale for targeting anxiety and depression in pediatric primary care and the deployment-focused treatment development model; (b) the content of our behaviorally based treatment program; and (c) clinical outcomes of 2 sample cases with comorbid depression and anxiety.     

Latent Trait Modeling with the Common beliefs Survey III: Using Item Response Theory to Evaluate an Irrational Beliefs Inventory

Assessment of irrational beliefs by such measures as the Common Beliefs Survey III (CBS) has traditionally relied upon classical test theory assumptions, in which the properties of specific test items are less important than the total test score as the aggregate of all item responses. An alternative approach using item response theory (IRT) methodology allows one to specify the parameters of difficulty and discrimination for each test item. Difficulty levels of CBS items range along a continuum of irrationality, the implied latent trait measured by responses to the questionnaire as a whole. We evaluated the CBS responses of 605 individuals from clinical and college settings, drawing from current and archival data. The original Likert scale ratings were recoded into dichotomous scores. Fourteen of the 54 items were highly or very highly discriminating in distinguishing respondents with high and low irrationality levels. However, discriminating items exhibited a very narrow range of difficulty; most functioned at a point a little above the halfway mark on the continuum of irrationality. Item characteristic curves and test information curves were very similar for female (n = 424) and male (n = 179) respondents. We derived a 4-item screening test for irrationality from our IRT analyses of the 54 CBS items. Further test development, focused on the selection and scaling of items with a much broader range of difficulty, would facilitate evaluation of the hierarchical structure of irrational beliefs. Portions of this paper were presented at the 39th Annual Convention of the Association for Behavioral and Cognitive Therapies, Washington, DC, November, 2005.     

How stable is happiness? Using the STARTS model to estimate the stability of life satisfaction

A common interpretation of existing subjective well-being research is that long-term levels of well-being are almost completely stable. However, few studies have estimated stability and change using appropriate statistical models that can precisely address this question. The STARTS model (Kenny & Zautra, 2001) was used to analyze life satisfaction data from two nationally representative panel studies. Results show that 34-38% of the variance in observed scores is trait variance that does not change. An additional 29-34% can be accounted for by an autoregressive trait that is only moderately stable over time. Thus, although life satisfaction is moderately stable over long periods of time, there is also an appreciable degree of instability that might depend on contextual circumstances.     

Effects of task requirements on rapid natural scene processing: from common sensory encoding to distinct decisional mechanisms

Using manual responses, human participants are remarkably fast and accurate at deciding if a natural scene contains an animal, but recent data show that they are even faster to indicate with saccadic eye movements which of 2 scenes contains an animal. How could it be that 2 images can apparently be processed faster than a single image? To better understand the origin of this speed advantage in forced-choice categorization, the present study used a masking procedure to compare 4 tasks in which sensory, decisional, and motor aspects were systematically varied. With stimulus onset asynchronies (SOAs) above 40 ms, there were substantial differences in sensitivity between tasks, as determined by d' measurements, with an advantage for tasks using a single image. However, with SOAs below 30-40 ms, sensitivity was similar for all experiments, despite very large differences in reaction time. This suggests that the initial part of the sensory encoding relies on common and parallel processing across a large range of tasks, whether participants have to categorize the image or locate a target in 1 of 2 scenes.     

Unintentional Injury Risk in Children with Externalizing Behavior Disorders at Summer Camp

Children with externalizing behavior disorders such as attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) have greatly increased risk of unintentional injury, but it is unclear what mechanisms are responsible for that increased risk. This study followed 22 children participating in a summer camp for children with ADHD. Injury incidents were recorded daily and a set of primary symptoms of behavioral disorders were recorded at 15-min intervals over the course of the 6-week summer camp experience (roughly 300 h of observing each child). We predicted symptoms of ODD and CD would be more strongly related to injury incidence than symptoms of ADHD. Results from univariate Poisson regression models confirmed our prediction. Symptoms of ODD and CD—violations and intentional aggression in particular—were related to injury incidence but symptoms of ADHD were not. This finding is consistent with a growing body of evidence that oppositional, noncompliant, and aggressive behavior patterns might be primarily responsible for increased risk for injury among children with externalizing behavior disorders. Thanks to Sylvie Mrug, Peter Winslett, and the other staff members of the STP camp for their cooperation.     

Age and culture modulate object processing and object—scene binding in the ventral visual area

Behavioral differences in the visual processing of objects and backgrounds as a function of cultural group are well documented. Recent neuroimaging evidence also points to cultural differences in neural activation patterns. Compared with East Asians, Westerners’ visual processing is more object focused, and they activate neural structures that reflect this bias for objects. In a recent adaptation study, East Asian older adults showed an absence of an object-processing area but normal adaptation for background areas. In the present study, 75 young and old adults (half East Asian and half Western) were tested in an fMR-adaptation study to examine differences in object and background processing as well as object—background binding. We found equivalent background processing in the parahippocampal gyrus in all four groups, diminished binding processes in the hippocampus in elderly East Asians and Westerners, and diminished object processing in elderly versus young adults in the lateral occipital complex. Moreover, elderly East Asians showed significantly less adaptation response in the object areas than did elderly Westerners. These findings demonstrate the malleability of perceptual processes as a result of differences in cohort-specific experiences or in cultural exposure over time.     

The effects of explicit “Not Present” and “Don't Know” response options on identification decisions in computer-administered lineups

Eyewitness researchers recommend that “not present” and “don't know” response options should be presented with police lineups. Although it is important that witnesses—most of whom are unlikely to be familiar with the identification task—are fully cognizant of all response options available to them, an understanding of how explicit non-identification options affect performance is lacking. Across four experiments, including 3,633 participants and 8 different stimulus sets, we tested the effects of including non-identification options in computer-administered lineups. When explicit non-identification options were presented, target-present and -absent choosing decreased. This decrease in choosing was characterized by a shift from filler identifications to lineup rejections. ROC analyses revealed that there was no overall difference in discriminability between guilty and innocent suspects depending on response option condition. On balance, the findings suggest that, in addition to informing witnesses about acceptable responses, displaying non-identification response options does not undermine identification performance.     

Cooperative responding in rats: II. Performance on fixed-ratio schedules of mutual reinforcement

Coordinated responses of 5 dyads of rats were investigated under fixed-ratio (FR) schedules of mutual water reinforcement. Coordinated responding was defined as 2 consecutive lever-presses, 1 from each of 2 rats, occurring <.5 s apart. In the FR schedules, each coordinated episode was defined as 1 response in the FR sequence. The size of FR schedules was parametrically manipulated assuming the values of FR 1, 6, 12, 18, 24, 30, 50, and 9, in this order. Each FR remained in effect until responding reached stability. Under all conditions, pairs of rats received access to water simultaneously (mutual reinforcement). Rates and proportions of coordinated responding showed a bitonic inverted U-shaped function of ratio size. Postreinforcement pauses increased systematically as the interreinforcement interval increased. Local rates and proportions increased as a function of response location within ratios. Results of a control condition with relaxed temporal constraints for mutual reinforcement showed decreases in rates and proportion of coordinated responses, suggesting that the coordinated responses were controlled by the mutual reinforcement contingencies. The present experiment showed that coordinated responding is quantitatively affected by 3 properties of FR schedules: response requirement, reinforcement rates, and proximity to reinforcement.