Development of subtype selective GABAA modulators

Drugs modulating gamma-aminobutyric acid (GABA) transmission via the benzodiazepine (BZ) site on the gamma-aminobutyric acid type A (GABAA) receptor have been in widespread use for more than 40 years to treat anxiety, epilepsy, and sleep disorders. These drugs have been shown to be safe, well tolerated, and effective although the mechanism by they produce a myriad of pharmacologic effects remains elusive. In recent years it has been discovered that, although the GABAA receptor is widely distributed in the brain, the substructure and composition of the receptor differs from between brain regions. Termed "GABAA receptor subtypes" their discovery leads to speculation that different subtypes may mediate specific effects of BZs such as anxiety or sedation. The phenotypic analysis of transgenic knock-in and knock-out mice in which particular GABAA receptors were rendered insensitive to the effects of BZ while others were unaffected confirmed this speculation. Subsequently, subtype-specific GABAA ligands were developed that, for example, retained the anxiolytic effects of BZs but were devoid of their sedative effects. Therefore, it may be possible to develop effective anxiolytic compounds that have a much reduced side-effect profile compared with existing drugs.     

A confirmatory model for depression among Japanese American and part-Japanese American adolescents

A confirmatory model integrating Japanese ethnicity, cultural identity, and depression was developed (N = 140). The model incorporated the Center for Epidemiologic Studies-Depression Scale (CES-D), Major Life Events Scale, and Japanese Cultural Scale. Japanese American adolescents scored higher on the Japanese Cultural Scale and reported fewer depressive symptoms on the CES-D total and on 2 of the 3 CES-D factors than part-Japanese American adolescents. Predictors for depression were being Japanese American vs. part-Japanese American, female gender, and culturally intensified events. A significant interaction of behavior by self-identification was noted. The model had good overall fit and suggested that the formation of cultural identity may contribute to depressive symptoms experienced by adolescents, particularly adolescents of mixed heritage.     

Epidemiological Measurement of Children's and Adolescents' Exposure to Community Violence: Working with the Current State of the Science

A number of measures have been used in epidemiological studies of children's exposure to community violence, yet the quality of these instruments is not uniformly good. This paper undertakes a systematic review of the most commonly used (or most promising) self-report or interview-administered instruments, with regard to their conceptual bases and psychometric properties. Based on the review, recommendations are made for working with the current state of the science in order to move the field forward. A key recommendation is for sounder conceptualization of work in the field and greater transparency in the reporting of research, in order to facilitate the comparability of studies.     

Abstract analogies and positive transfer in artificial grammar learning.

Following Brooks and Vokey (1991), we show that positive transfer to new items generated from an artificial grammar in which the vocabulary has been changed from training to test can be based on "abstract analogy" to specific training items (specific similarity) rather than abstraction of a grammar and symbol remapping rules, even with remapping unique to each test item. The results confirm that transcendence over symbols provides no support for the implicit learning of abstract structure. Ironically, they also show that the effect of specific similarity does not depend on surface characteristics of the items, but the residual effect of grammaticality does.     

Intuition and autism: a possible role for Von Economo neurons

Von Economo neurons (VENs) are a recently evolved cell type which may be involved in the fast intuitive assessment of complex situations. As such, they could be part of the circuitry supporting human social networks. We propose that the VENs relay an output of fronto-insular and anterior cingulate cortex to the parts of frontal and temporal cortex associated with theory-of-mind, where fast intuitions are melded with slower, deliberative judgments. The VENs emerge mainly after birth and increase in number until age 4 yrs. We propose that in autism spectrum disorders the VENs fail to develop normally, and that this failure might be partially responsible for the associated social disabilities that result from faulty intuition.     

New approaches to demystifying insight

After a person has become stuck on a problem, they sometimes achieve a clear and sudden solution through insight--the so-called Aha! experience. Because of its distinctive experience, the origins and characteristics of insight have received considerable attention historically in psychological research. However, despite considerable progress in characterizing insight, the underlying mechanisms remain mysterious. We argue that research on insight could be greatly advanced by supplementing traditional insight research, which depends on a few complex problems, with paradigms common in other domains of cognitive science. We describe a large set of mini-insight problems to which multiple methods can be applied, together with subjective reports to identify insight problem-solving. Behavioral priming and neuroimaging methods are providing evidence about what, where, and how neural activity occurs during insight. Such evidence constrains theories of component processes, and will help to demystify insight.     

Extending neuropsychological assessments into the primary mental ability space

A battery of 17 neuropsychological tests (including the CERAD battery) and 17 psychometric ability tests were administered to a sample of 499 participants of the Seattle Longitudinal study who had been given the psychometric ability tests seven and 14 years earlier. The neuropsychological tests were projected into a 5-factor psychometric ability space by means of extension analysis. The concurrent regressions of the neuropsychology tests on the psychometric ability tests were then used to estimate neuropsychology test scores from the psychometric ability tests administered in 1984, 1991 and 1998. Neuropsychologists then rated the study participants as either normal, suspect or cognitively impaired in 1998. Changes in estimated test scores were computed over seven and fourteen years. Significant odds ratios between normal and cognitively impaired groups were found for all neuropsychological tests over the proximal period and for most tests over the 14-year period. Similar findings occurred for the odds ratios between the normal and suspect groups for the most proximal 7-year changes.     

Toward a taxonomy of attention shifting: Individual differences in fMRI during multiple shift types

Although task switching is often considered one of the fundamental abilities underlying executive functioning and general intelligence, there is little evidence that switching is a unitary construct and little evidence regarding the relationship between brain activity and switching performance. We examined individual differences in multiple types of attention shifting in order to determine whether behavioral performance and fMRI activity are correlated across different types of shifting. The participants (n=39) switched between objects and attributes both when stimuli were perceptually available (external) and when stimuli were stored in memory (internal). We found that there were more switchrelated activations in many regions associated with executive control—including the dorsolateral and medial prefrontal and parietal cortices—when behavioral switch costs were higher (poor performance). Conversely, activation in the ventromedial prefrontal cortex (VMPFC) and the rostral anterior cingulate was consistently correlated with good performance, suggesting a general role for these areas in efficient attention shifting. We discuss these findings in terms of a model of cognitive-emotional interaction in attention shifting, in which reward-related signals in the VMPFC guide efficient selection of tasks in the lateral prefrontal and parietal cortices.