Glucocorticoid involvement in memory formation in a rat model for traumatic memory

Contextual fear conditioning under training conditions involving high stressor intensities has been proposed as an animal model for traumatic memories. The strength of memory for this task has been related to the intensity of the conditioning stressor and post-training corticosterone values. However, administration of a glucocorticoid receptor (GR) antagonist only attenuated memory for this task in rats conditioned at a moderate shock intensity (0.4 mA), but failed to influence conditioning in rats trained at a high shock intensity (1 mA). Here, we further questioned whether interfering with glucocorticoid action at the time of training might be effective in influencing contextual fear conditioning in rats trained under different shock intensities. Rats were subcutaneously injected with the glucocorticoid synthesis inhibitor metyrapone (50, 100 mg/kg) 90 min before being trained in the contextual fear conditioning task, at either 0.4 or 1 mA shock intensities. The results showed that metyrapone, in a dose-dependent manner: (i) attenuated long-term expression of contextual fear conditioning, both in 0.4- and 1 mA-trained rats; and (ii) efficiently prevented increased plasma corticosterone concentration. In addition to further supporting a facilitating role of glucocorticoids in memory consolidation, these findings suggest a critical involvement of these hormones in the formation of traumatic memories.     

Psychosocial Treatment Strategies in the MTA Study: Rationale, Methods, and Critical Issues in Design and Implementation

The Collaborative Multimodal Treatment Study of Children with Attention Deficit Hyperactivity Disorder (ADHD), the MTA, is the first multisite, cooperative agreement treatment study of children, and the largest psychiatric/psychological treatment trial ever conducted by the National Institute of Mental Health. It examines the effectiveness of Medication vs. Psychosocial treatment vs. their combination for treatment of ADHD and compares these experimental arms to each other and to routine community care. In a parallel group design, 579 (male and female) ADHD children, aged 7–9 years, 11 months, were randomly assigned to one of the four experimental arms, and then received 14 months of prescribed treatment (or community care) with periodic reassessments. After delineating the theoretical and empirical rationales for Psychosocial treatment of ADHD, we describe the MTA's Psychosocial Treatment strategy applied to all children in two of the four experimental arms (Psychosocial treatment alone; Combined treatment). Psychosocial treatment consisted of three major components: a Parent Training component, a two-part School Intervention component, and a child treatment component anchored in an intensive Summer Treatment Program. Components were selected based on evidence of treatment efficacy and because they address comprehensive symptom targets, settings, comorbidities, and functional domains. We delineate key conceptual and logistical issues faced by clinical researchers in design and implementation of Psychosocial research with examples of how these issues were addressed in the MTA study.Deceased     

Representation and working memory in early arithmetic

Working memory has been implicated in the early acquisition of arithmetic skill, but the relations among different components of working memory, performance on different types of arithmetic problems, and development have not been explored. Preschool and Grade 1 children completed measures of phonological, visual-spatial, and central executive working memory, as well as nonverbal and verbal arithmetic problems, some of which included irrelevant information. For preschool children, accuracy was higher on nonverbal problems than on verbal problems, and the best and only unique predictor of performance on the standard nonverbal problems was visual-spatial working memory. This finding is consistent with the view that most preschoolers use a mental model for arithmetic that requires visual-spatial working memory. For Grade 1 children, performance was equivalent on nonverbal and verbal problems, and phonological working memory was the best predictor of performance on standard verbal problems. For both age groups, problems with added irrelevant information were substantially more difficult than standard problems, and in some cases measures of the central executive predicted performance. Assessing performance on different components of working memory in conjunction with different types of arithmetic problems provided new insights into the developing relations between working memory and how children do arithmetic.     

Spatial learning in rats is impaired by microinfusions of protein kinase C-gamma antisense oligodeoxynucleotide within the nucleus accumbens

The nucleus accumbens (NAcc) has been shown to play a role in motor and spatial learning. Protein kinase C (PKC) has been implicated in the mechanisms of initiation and maintenance of long-term potentiation that is thought to be involved in the storage of long-term memory. In the present study, the importance of de novo synthesis of PKC-gamma within the NAcc in the acquisition and retention of spatial discrimination learning was assessed using an antisense knockdown approach. Separate groups of Long-Evans rats were exposed to acute microinfusions (6microg/microl) of PKC-gamma antisense oligodeoxynucleotide (AS-ODN), control oligodeoxynucleotide (C-ODN) or vehicle into the NAcc at 24 and 3h before each training session. Behavioral findings showed that the blockade of NAcc-PKC-gamma translation caused impairments in the early phase of learning and retention of spatial information. Biochemical experiments showed that PKC-gamma expression was reduced and Ca(2+)/phospholipid-dependent protein kinase C (PKC) activity was blocked significantly in the AS-ODN-treated rats in comparison with control rats. The present findings suggest that NAcc-PKC-gamma plays a role during the early acquisition of spatial learning. Also, retention test results suggest that NAcc-PKC-gamma may be working as an intermediate factor involved in the onset of molecular mechanisms necessary for spatial memory consolidation within the NAcc.     

A facilitative role for corticosterone in the acquisition of a spatial task under moderate stress

Emotionally charged experiences alter memory storage via the activation of hormonal systems. Previously, we have shown that compared with rats trained for a massed spatial learning task in the water maze in warm water (25°C), animals that were trained in cold water (19°C) performed better and showed higher levels of the stress hormone corticosterone. Here, we examined whether manipulating the levels of corticosterone can determine the strength of spatial information acquisition and retention. Rats were injected with metyrapone (25, 50, and 75 mg/kg, i.p.) or with corticosterone (10 and 25 mg/kg, i.p.) and trained in a massed spatial task in either cold (19°C) or warm (25°C) water. We found that whereas animals injected with vehicle performed well in the spatial task in cold water (moderate stress), rats injected with the intermediate metyrapone dose showed impairment in performance. Moreover, whereas animals injected with vehicle on average did not perform well in warm water (mild stress), rats injected with the lower corticosterone dose showed improvement in performance in warm water. These two mirror experiments of corticosterone blockade and enhancement strongly suggest that corticosterone is instrumental in the acquisition and retention of the spatial learning task.     

The language-specific nature of grammatical development: evidence from bilingual language learners

The fact that early lexical and grammatical acquisition are strongly correlated has been cited as evidence against the view that the language faculty is composed of dissociable and autonomous modules (Bates & Goodman, 1997). However, previous studies have not yet eliminated the possibility that lexical-grammar associations may be attributable to language-general individual differences (e.g. children who are good at learning words are good at learning grammar). Parent report assessments of toddlers who are simultaneously learning English and Spanish (n = 113) allow an examination of the specificity of lexical-grammar relationships while holding child factors constant. Within-language vocabulary-grammar associations were stronger than cross-language relationships, even after controlling for age, proportion of language exposure, general language skill and reporter bias. Similar patterns were found based on naturalistic language samples (n = 22), ruling out a methodological artifact. These results are consistent with the view that grammar learning is specifically tied to lexical progress in a given language and provide further support for strong lexical-grammatical continuity early in acquisition.     

Effects of suppressing neutral and obsession-like thoughts in normal subjects: beyond frequency

Recent cognitive-behavioral theories on obsessive-compulsive disorder (OCD) show that deliberate attempts to suppress intrusive and undesirable thoughts lie at the genesis of clinical obsessions. In this paper the results of an experimental study on the suppression of neutral and obsession-like thoughts in normal subjects are presented. Eighty-seven university students performed in three experimental periods: (1) base-line monitoring, (2) experimental instruction, and (3) monitoring. For each of these periods, the frequency of the occurrence of a "white bear" thought or a personally relevant intrusive thought was registered. Half of the subjects received instructions to suppress the target-thought in period 2, and the other half were instructed to only monitor the target-thought in each of the experimental periods. Several measures were also obtained before and after the experiment: annoyance caused by the intrusion, suppression effort, subjective success, and evaluative appraisals of the target-thought. The results showed neither immediate nor delayed frequency increases of the target thought. However, evidence was found that deliberate thought suppression efforts, regardless of their content, had greater negative consequences than did non suppression. These results are discussed in relation to the recent cognitive proposals about OCD.     

Directed forgetting of related words: evidence for the inefficient inhibition hypothesis

Fifth-grade children and college students were asked to remember some words and to forget others in an item-cued-directed-forgetting task. Taxonomically related pairs of words and control pairs that were unrelated in meaning were used as stimuli. Children found it more difficult than did adults to ignore forget-cued words that followed associatively related words that were remember-cued. The results provide support for D. F. Bjorklund and K. K. Harnishfeger's (1990) inefficient inhibition hypothesis (i.e., that the efficiency of inhibitory mechanisms improves as children develop). The results also suggest that the inhibition is occurring primarily in the early stages of processing.     

The time course of attentional focusing in dyslexic and normally reading children

A cue size procedure was used to evaluate the time course of visuo-spatial attention in dyslexic and normally reading children. When a stimulus target is presented inside a large cue vs a small cue the identification time is slower. In the present study two cue-target delays (100 and 500 ms) were used. Results showed a slower time course of attentional focusing in dyslexics vs normal readers. Indeed, dyslexics exhibited no cue size effect at a shorter cue-target delay (100 ms), while it was present at a longer cue-target delay (500 ms). In contrast, a cue size effect was found at both cue-target delays in normally reading children. These results further support the hypothesis of sluggish automatic focusing of visual attention in dyslexics. This impairment could be a consequence of a general magnocellular deficit demonstrated previously in dyslexics.     

Sensitivity reductions in false recognition: a measure of false memories with stronger theoretical implications

Signal detection analyses of recognition memory indicate that a bias to respond "old" is large for critical words that are centrally related with previously encoded word lists, is small for words that are less related, and is not observed for unrelated words. Also, recognition sensitivity has not been previously shown to differ between those conditions, which has focused debate over how to explain false recognition on the bias differences. In 3 experiments, critical-word sensitivity was lower than sensitivity for other word types, but related-word sensitivity was not lower than sensitivity for unrelated words. Extant models that predict reduced critical-word sensitivity also predict lower sensitivity for related words than for unrelated words. These results provide crucial new constraints on theoretical explanations of false memories.