L-type voltage-gated calcium channels in conditioned fear: a genetic and pharmacological analysis

Using pharmacological approaches, others have suggested that L-type voltage-gated calcium channels (L-VGCCs) mediate both consolidation and extinction of conditioned fear. In the absence of L-VGCC isoform-specific antagonists, we have begun to investigate the subtype-specific role of LVGCCs in consolidation and extinction of conditioned fear using a molecular genetics approach. Previously, we used this approach to demonstrate that the Ca(v)1.3 isoform mediates consolidation, but not extinction, of contextually conditioned fear. Here, we used mice in which the gene for the L-VGCC pore-forming subunit Ca(v)1.2 was conditionally deleted in forebrain excitatory neurons (Ca(v)1.2(cKO) mice) to address the role of Ca(v)1.2 in consolidation and extinction of conditioned fear. We demonstrate that Ca(v)1.2(cKO) mice consolidate and extinguish conditioned fear as well as control littermates. These data suggest that Ca(v)1.2 is not critical for these processes and together with our previous data argue against a role for either of the brain-expressed L-VGCCs (Ca(v)1.2 or Ca(v)1.3) in extinction of conditioned fear. Additionally, we present data demonstrating that the L-VGCC antagonist nifedipine, which has been used in previous conditioned fear extinction studies, impairs locomotion, and induces an aversive state. We further demonstrate that this aversive state can enter into associations with conditioned stimuli that are present at the time that it is experienced, suggesting that previous studies using nifedipine were likely confounded by drug toxicity. Taken together, our genetic and pharmacological data argue against a role for Ca(v)1.2 in consolidation of conditioned fear as well as a role for L-VGCCs in extinction of conditioned fear.     

Pain as a motivator of smoking: effects of pain induction on smoking urge and behavior

Tobacco smoking has been associated with the development and exacerbation of chronically painful conditions. Conversely, there is reason to believe that smokers may be motivated to use tobacco as a means of coping with their pain. To date, no controlled, experimental studies have tested for a causal relationship between pain and smoking motivation. The primary aim of the current study was to test the hypothesis that laboratory-induced cold pressor pain would enhance smoking motivation, as measured by self-reported urge to smoke and observation of immediate smoking behavior. Smokers (N=132) were randomly assigned to either pain or no pain conditions. Results indicated that situational pain increased urge ratings and produced shorter latencies to smoke. The relationship between pain and increased urge to smoke was partially mediated by pain-induced negative affect. The relationship between pain and shorter latency to smoke was fully mediated by pain-induced urge to smoke. This study provides the 1st experimental evidence that situational pain can be a potent motivator of smoking.     

Understanding the search for meaning in life: personality, cognitive style, and the dynamic between seeking and experiencing meaning.

Although several theories assert that understanding the search for meaning in life is important, empirical research on this construct is sparse. Three studies provide the first extensive effort to understand the correlates of the search for meaning in a multistudy research program. Assessed were relations between search for meaning and well-being, cognitive style, and the Big Five, Big Three, Approach/Avoidance, and Interest models of personality, with a particular emphasis on understanding the correlates of search for meaning that are independent of presence of meaning. Conceptual models of the relation between search and presence were tested. Findings suggest that people lacking meaning search for it; the search for meaning did not appear to lead to its presence. Study 3 found that basic motive dispositions moderated relations between search for meaning and its presence. Results highlight the importance of basic personality dispositions in understanding the search for meaning and its correlates.     

Lonely adolescents exhibit heightened sensitivity for facial cues of emotion

Contradicting evidence exists regarding the link between loneliness and sensitivity to facial cues of emotion, as loneliness has been related to better but also to worse performance on facial emotion recognition tasks. This study aims to contribute to this debate and extends previous work by (a) focusing on both accuracy and sensitivity to detecting positive and negative expressions, (b) controlling for depressive symptoms and social anxiety, and (c) using an advanced emotion recognition task with videos of neutral adolescent faces gradually morphing into full-intensity expressions. Participants were 170 adolescents (49% boys; M_age?=?13.65 years) from rural, low-income schools. Results showed that loneliness was associated with increased sensitivity to happy, sad, and fear faces. When controlling for depressive symptoms and social anxiety, loneliness remained significantly associated with sensitivity to sad and fear faces. Together, these results suggest that lonely adolescents are vigilant to negative facial cues of emotion.     

Iron in solution with aluminum matrix after non-equilibrium processing: an atom probe tomography study

In this paper, we report on the influence of rapid solidification and severe plastic deformation on the solid solubility of Fe in Al. Atom probe tomography, for the first time, was performed on fine (3–4 μm diameter) and coarse (~100 μm) as-atomised Al-5 at.% Fe powder and cryomilled Al-5 at.% Fe powder. The atomised powders exhibited negligible Fe in solution with Al, whereas the cryomilled powder contained ~2 at.% Fe in solution. Moreover, our results suggest that severe plastic deformation is preferable to atomisation/rapid solidification for increasing the non-equilibrium solid solubility of Fe in Al.     

The Differential Effects of Alzheimer's Disease and Lewy Body Pathology on Cognitive Performance: a Meta-analysis

Differential diagnosis of Alzheimer’s disease (AD) from normal aging and other dementia etiologies is imperative for disease specific treatment options and long-term care planning. Neuropathological confirmation is the gold standard for neurodegenerative disease diagnosis, yet most published studies examining the use of neuropsychological tests in the differential diagnosis of dementia rely upon clinical diagnostic outcomes. The present study undertook a meta-analytic review of the literature to identify cognitive tests and domains that allow for the differentiation of individuals with AD pathology from individuals with dementia with Lewy Bodies (DLB) pathology and pathology-free individuals. A comprehensive literature search yielded 14 studies that met the inclusion criteria for the present meta-analysis. Six studies comprised 222 decedents with AD compared to 433 normal controls, and eight studies comprised 431 cases of AD compared to 155 decedents with DLB. Results revealed that the effect of having neuropathologically confirmed AD versus DLB lowered performance in the memory domain, and having DLB decreased performance in the visuospatial domain. No single test differed significantly across the AD and DLB groups. For the AD and pathology free comparison, results indicated that that AD was associated with poorer performance on the memory and language domains. With respect to specific cognitive tests, AD produced lower scores on list learning tests, category fluency, and the Digit Symbol substitution test. The limited number of studies meeting inclusion criteria warrants formulation of guidelines for reporting in clinico-pathological studies; suggested guidelines are provided.     

A Cultural Adaptation of Dialectical Behavior Therapy in Nepal

Growing evidence exists on the potential for adapting evidence-based interventions for low- and-middle-income countries (LMIC). One opportunity that has received limited attention is the adaptation of psychotherapies developed in high-income countries (HIC) based on principles from LMIC cultural groups. Dialectical behavior therapy (DBT) is one such treatment with significant potential for acceptability in South Asian settings with high suicide rates. We describe a tri-phasic approach to adapt DBT in Nepal that consists of qualitative interviews with major Nepali mental health stakeholders (Study 1), an adaptation workshop with 15 Nepali counselors (Study 2), and a small-scale treatment pilot with eligible clients in one rural district (Study 3). Due to low literacy levels, distinct conceptualizations of mind and body, and program adherence barriers, numerous adaptations were required. DBT concepts attributable to Asian belief systems were least comprehensible to clients. However, the 82% program completion rate suggests utility of a structured, skills-based treatment. This adaptation process informs future research regarding the effectiveness of culturally adapted DBT in South Asia.     

On Being a Lone Dissenter

Asch's (1956) research on group pressure to conform implied that it is difficult to be a lone dissenter. Extending this to the analysis of voting patterns in the U.S. Supreme Court's 1953-2001 terms, it was found that of 4,178 decisions, the 8-1 split was the least common (10%). Unanimous decisions were most common (35%), followed by 5-4 splits (21%), 6-3 splits (20%), and 7-2 splits (14%). Large differences were found among the 29 Justices serving during this period as to how often they were lone dissenters, led by Justice William Douglas, who issued lone dissents on about 6% of the decisions on which he voted.