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.     

Attending and glancing

The activities of glancing and attending are rarely compared, yet they have significant affinities to the point where we may say that glancing is a mode of attending while the latter, in turn, often proceeds by glances. This paper explores these affinities, showing that each activity is a form of reactive spontaneity (James) and that each engages in a particular version of advertence. Mental as well as ordinary perceptual glances are examined, with examples being taken from laboratory studies, everyday life, meditation, and the psychotherapeutic technique of focusing. In the end, the two acts collaborate closely, enhance each other, and can be considered conterminous in many of their aims and procedures for reaching them.     

Look into my eyes: gaze direction and person memory

The current research considered the effects of gaze direction on a fundamental aspect of social cogition: person memory. It was anticipated that a person's direction of gaze (i.e., direct or averted) would impact his or her subsequent memorability, such that recognition would be enhanced for targets previously displaying direct gaze. In Experiment 1, participants were presented with faces displaying either direct or averted gaze in a person-classification (i.e., conceptual) task. Then, in a surprise memory test, they were required to report whether a presented face had been seen before. As expected, a recognition advantage was observed for targets displaying direct gaze during the initial classification task. This finding was replicated and extended in a second experiment in which participants initially reported the spatial location (i.e., perceptual task) of each face. We consider the implications of these findings for basic aspects of social-cognitive functioning and person perception.     

Adjustment to chronic low back pain--the relative influence of fear-avoidance beliefs, catastrophizing, and appraisals of control

The present study investigated the relative extent to which patients' adjustment to chronic low back pain (CLBP) was influenced by their fear-avoidance beliefs, their tendency to catastrophize, and their appraisals of control. Eighty-three CLBP patients completed a series of self-report measures before participating in a physical therapist-led intervention. Hierarchical multiple regression analyses revealed that patients' perceptions of their ability to decrease pain explained a small, but statistically significant, proportion of the variance in pain intensity. In addition, patients' levels of catastrophizing, as well as their fear-avoidance beliefs about both work and physical activity, were independently associated with levels of disability. Interestingly, however, when exploring the relative predictive utility of these three psychological factors, it became evident that fear-avoidance beliefs about physical activity (FABs-PA) were the only significant predictor of patients' disability. Specifically, those patients who exhibited higher levels of FABs-PA tended to report greater levels of disability, even after adjusting for age, sex and pain intensity.     

Cognitive defusion and self-relevant negative thoughts: examining the impact of a ninety year old technique

Cognitive defusion techniques are designed to reduce the functions of thoughts by altering the context in which they occur, rather than the attempting to alter the form, frequency, or situational sensitivity of the thoughts themselves. Applied technologies designed to produce cognitive defusion seem to lead to reductions in the believability of negative thoughts, but defusion techniques are generally only parts of complex packages and the role of defusion techniques per se is note yet known. The present study examined the impact of a cognitive defusion technique first described by Titchener nearly 90 years ago: rapidly repeating a single word. In series of eight single-case alternating treatment designs, this defusion technique was compared to a distraction task, and to a thought control task on reductions in the discomfort and believability of self-relevant negative thoughts. The cognitive defusion technique reduced both discomfort and believability more so than the comparison approaches. Control studies showed that the effect was probably not due to demand characteristics.     

Estimates of emotional and psychometric intelligence: evidence for gender-based stereotypes

The authors examined participants' estimates of own and parental psychometric intelligence (IQ) and emotional intelligence (EI). The authors asked 224 participants (82 men, 138 women, 4 people who did not report their gender) to estimate their own and their parents' IQ and EI scores on a normal distribution ranging from 55 to 145 points. The authors hypothesized that men would give higher IQ but lower EI self-estimates than women and that participants, regardless of gender, would rate their fathers as higher on IQ but lower on EI than their mothers. The results confirmed the hypotheses, supporting the view that people perceive psychometric intelligence as a primarily masculine attribute in contrast with emotional intelligence, which they perceive as a primarily feminine attribute. The results also showed that the intensity of the stereotypical perception of EI as a feminine attribute diminished when the authors asked participants to estimate their scores on a range of specific EI facets instead of providing a direct overall self-estimate.     

Perception of place-of-articulation information in natural speech by monkeys versus humans

Four monkeys and 6 humans representing five different native languages were compared in the ability to categorize natural CV tokens of /b/ versus /d/ produced by 4 talkers of American English (2 male, 2 female) in four vowel contexts (/i, e, a, u/). A two-choice "left/right" procedure was used in which both percentage correct and response time data were compared between species. Both measures indicated striking context effects for monkeys, in that they performed better for the back vowels /a/ and /u/ than for the front vowels /i/ and /e/. Humans showed no context effects for the percentage correct measure, but their response times showed an enhancement for the /i/ vowel, in contrast with monkeys. Results suggest that monkey perception of place of articulation is more dependent than human perception on the direction of the F2 onset transitions of syllables, since back-vowel F2s differentiate /b/ and /d/ more distinctively. Although monkeys do not provide an accurate model of the adult human in place perception, they may be able to model the preverbal human infant before it learns a more speech-specific strategy of place information extraction.     

Orientational manoeuvres in the dark: dissociating allocentric and egocentric influences on spatial memory

Subjects in a darkroom saw an array of five phosphorescent objects on a circular table and, after a short delay, indicated which object had been moved. During the delay the subject, the table or a phosphorescent landmark external to the array was moved (a rotation about the centre of the table) either alone or together. The subject then had to indicate which one of the five objects had been moved. A fully factorial design was used to detect the use of three types of representations of object location: (i) visual snapshots; (ii) egocentric representations updated by self-motion; and (iii) representations relative to the external cue. Improved performance was seen whenever the test array was oriented consistently with any of these stored representations. The influence of representations (i) and (ii) replicates previous work. The influence of representation (iii) is a novel finding which implies that allocentric representations play a role in spatial memory, even over short distances and times. The effect of the external cue was greater when initially experienced as stable. Females out-performed males except when the array was consistent with self-motion but not visual snapshots. These results enable a simple egocentric model of spatial memory to be extended to address large-scale navigation, including the effects of allocentric knowledge, landmark stability and gender.     

Verbal mediation of number knowledge: evidence from semantic dementia and corticobasal degeneration

Patients with corticobasal degeneration (CBD) appear to have impaired number knowledge. We examined the nature of their number deficit while we tested the hypothesis that comprehension of larger numbers depends in part on verbal mediation. We evaluated magnitude judgments and performance on number conservation measures rooted in Piagetian theory in nonaphasic patients with CBD (n=13) and patients with a fluent form of progressive aphasia known as semantic dementia (SD; n=15). We manipulated the numbers of the arrays and the visual-spatial properties of the stimuli being compared during magnitude judgments and Piagetian conservation measures. CBD patients were consistently impaired judging the magnitudes of larger numbers (4-9), while they had minimal difficulty with smaller numbers (magnitudes < or = 3). By comparison, SD patients performed all measures of number knowledge at a ceiling level regardless of number magnitude. Neither patient group was significantly impacted by manipulations of the spatial properties of the stimuli. CBD patients' impairment with larger numbers despite minimal aphasia, and SD patients' intact performance despite an aphasia, challenge the proposal that understanding larger numbers depends on verbal mediation.     

Inhibition and attention deficit hyperactivity disorder in adults

The inhibitory account of attention deficit hyperactivity disorder (ADHD) was tested by examining the performance of college-aged adults on a variety of inhibitory tasks. The poorer performance of adults with ADHD compared with controls on negative priming, stopping, and continuous performance tasks, combined with similar group performances on a test of working memory capacity, indicates a specific inhibitory deficit as opposed to a general limitation in attentional capacity. Overall results provide evidence for extending the inhibitory deficit hypothesis to adult ADHD, not only for mechanisms of response (or motor) inhibition but also for mechanisms of cognitive inhibition.