Use of monetary reinforcers by cocaine-dependent outpatients.

Monetary reinforcers have not been widely used as contingent reinforcers in the treatment of drug abuse, despite their demonstrated effectiveness. This is primarily due to concern that drug abusers will use monetary reinforcers to procure drugs. The present study addressed this concern by examining 48 cocaine-dependent outpatients' biweekly self-reports of how they used their earned reinforcers. For each subject, their reinforcement usage was classified into 12 higher-order categories and 34 subcategories. Usage proportions were calculated for each. Results indicated that monetary reinforcers were used very infrequently to acquire drugs or alcohol (2%). Reinforcers were used primarily for daily life activities (25%) (e.g., food and gas), money-related uses (18%) (e.g., savings and repaying debts), personal use (15%) (e.g., cosmetics and clothes), and household items (11%) (e.g., rent and bills). These findings challenge the concern that drug abusers use monetary reinforcers to purchase drugs and have important implications for the use of contingent monetary reinforcers in treatment settings.     

The relationship between individual differences in gray matter volume and religiosity and mystical experiences: A preregistered voxel‐based morphometry study

The neural substrates of religious belief and experience are an intriguing though contentious topic. Here, we had the unique opportunity to establish the relation between validated measures of religiosity and gray matter volume in a large sample of participants (N = 211). In this registered report, we conducted a confirmatory voxel‐based morphometry analysis to test three central hypotheses regarding the relationship between religiosity and mystical experiences and gray matter volume. The preregisterered hypotheses, analysis plan, preprocessing and analysis code and statistical brain maps are all available from online repositories. By using a region‐of‐interest analysis, we found no evidence that religiosity is associated with a reduced volume of the orbito‐frontal cortex and changes in the structure of the bilateral inferior parietal lobes. Neither did we find support for the notion that mystical experiences are associated with a reduced volume of the hippocampus, the right middle temporal gyrus or with the inferior parietal lobes. A whole‐brain analysis furthermore indicated that no structural brain differences were found in association with religiosity and mystical experiences. We believe that the search for the neural correlates of religious beliefs and experiences should therefore shift focus from studying structural brain differences to a functional and multivariate approach.     

Effects of circuit resistance training on fitness attributes and upper-extremity pain in middle-aged men with paraplegia

OBJECTIVE: To examine the effects of circuit resistance exercise (CRT) training on muscle strength, endurance, anaerobic power, and shoulder pain in middle-aged men with paraplegia. DESIGN: Repeated testing. SETTING: Academic medical center. PARTICIPANTS: Seven men (age range, 39-58y) with motor-complete paraplegia from T5 to T12 and confirmed shoulder pain occurring during daily activities. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Subjects underwent a 4-month CRT program using alternating resistance maneuvers and high-speed, low-resistance arm exercise. One-repetition maximal force was measured before training and monthly thereafter. Pretraining and posttraining peak oxygen uptake (Vo(2)peak) was measured by graded arm testing. Anaerobic power was measured before and after training using a 30-second Wingate Anaerobic Test. Shoulder pain was self-evaluated by an index validated for people with spinal cord injury (Wheelchair Users Shoulder Pain Index [WUSPI]). RESULTS: Strength increases ranging from 38.6% to 59.7% were observed for all maneuvers (P range, .005-.008). Vo(2)peak increased after training by 10.4% (P=.01), and peak and average anaerobic power increased by 6% (P=.001) and 8.6% (P=.005), respectively. WUSPI scores +/- standard deviation were lowered from 31.9+/-24.8 to 5.7+/-5.9 (P=.008), with 3 of 7 subjects reporting complete resolution of shoulder pain. CONCLUSIONS: CRT improves muscle strength, endurance, and anaerobic power of middle-aged men with paraplegia while significantly reducing their shoulder pain.     

Development of Plate Reader and On-Line Microfluidic Screening to Identify Ligands of the 5-Hydroxytryptamine Binding Protein in Venoms

The 5-HT₃ receptor is a ligand-gated ion channel, which is expressed in the nervous system. Its antagonists are used clinically for treatment of postoperative- and radiotherapy-induced emesis and irritable bowel syndrome. In order to better understand the structure and function of the 5-HT₃ receptor, and to allow for compound screening at this receptor, recently a serotonin binding protein (5HTBP) was engineered with the Acetylcholine Binding Protein as template. In this study, a fluorescence enhancement assay for 5HTBP ligands was developed in plate-reader format and subsequently used in an on-line microfluidic format. Both assay types were validated using an existing radioligand binding assay. The on-line microfluidic assay was coupled to HPLC via a post-column split which allowed parallel coupling to a mass spectrometer to collect MS data. This high-resolution screening (HRS) system is well suitable for compound mixture analysis. As a proof of principle, the venoms of Dendroapsis polylepis, Pseudonaja affinis and Pseudonaja inframacula snakes were screened and the accurate masses of the found bioactives were established. To demonstrate the subsequent workflow towards structural identification of bioactive proteins and peptides, the partial amino acid sequence of one of the bioactives from the Pseudonaja affinis venom was determined using a bottom-up proteomics approach.     

Biomarker profiles and their relation to clinical variables in mild cognitive impairment

The aim of the study was to compare clinical variables between MCI patients at different risk for Alzheimer’s disease (AD) according to their biomarker profile. Fifty-four percent out of 39 MCI patients had a low Aβ42 and high tau in cerebrospinal fluid (CSF) (high-risk), 26% either a low CSF Aβ42 or high CSF tau (intermediate-risk) and 20% a normal CSF Aβ42 and tau (low-risk). Both high- and intermediate-risk subjects differed from the low-risk group in episodic memory, executive functions and the preclinical AD scale (PAS), which combines a set of clinical parameters. Subjects at high risk did not differ from subjects with an intermediate risk. Aβ42 levels correlated with the MTA and PAS scores, tau levels with episodic memory. These correlations suggest that the biomarkers are not independent when compared to the other AD markers. Longitudinal studies are necessary to interpret the correlations between biomarkers, imaging, and neuropsychological markers.     

Molecular actions of smoking cessation drugs at α4β2 nicotinic receptors defined in crystal structures of a homologous binding protein

Partial agonists of the α4β2 nicotinic acetylcholine receptor (nAChR), such as varenicline, are therapeutically used in smoking cessation treatment. These drugs derive their therapeutic effect from fundamental molecular actions, which are to desensitize α4β2 nAChRs and induce channel opening with higher affinity, but lower efficacy than a full agonist at equal receptor occupancy. Here, we report X-ray crystal structures of a unique acetylcholine binding protein (AChBP) from the annelid Capitella teleta, Ct-AChBP, in complex with varenicline or lobeline, which are both partial agonists. These structures highlight the architecture for molecular recognition of these ligands, indicating the contact residues that potentially mediate their molecular actions in α4β2 nAChRs. We then used structure-guided mutagenesis and electrophysiological recordings to pinpoint crucial interactions of varenicline with residues on the complementary face of the binding site in α4β2 nAChRs. We observe that residues in loops D and E are molecular determinants of desensitization and channel opening with limited efficacy by the partial agonist varenicline. Together, this study analyzes molecular recognition of smoking cessation drugs by nAChRs in a structural context.     

Pregnancy prevention among American Indian men ages 18 to 24: the role of mental health and intention to use birth control

The Fort Peck Sexual Health Project: A Contextual Analysis of Native American Men is a community-based participatory research (CBPR) project that explores the extent to which knowledge, attitudes, and beliefs about sex, intimate relationships, and mental health influence sexual and reproductive health. For the purpose of this study, the influence of age, fatherhood, and mental health factors related to historical trauma and loss on young American Indian (AI) men's intention to use birth control was examined. In-depth interviews were conducted with 112 Native American men between the ages of 18 and 24 years. The mean age reported was 21 years. Thirty-eight percent of the young men reported having children. The young men reported experiences of historical trauma during their lifetime as well as emotional responses due to historical losses. Ninety-five percent reported that it was very important that they use some form of birth control to prevent their partner from getting pregnant within the next year. Logistic regression analysis indicated that, as age increased, young men were less likely to use birth control to prevent pregnancy. The young men who reported feelings of loss due to experiences related to historical trauma and loss were more likely to use birth control. Findings from this study suggest that public health efforts to educate AI men about planned pregnancies and the use of birth control may be most effective in adolescence. Public health programs that address mental health concerns such as the emotional responses due to historical losses may assist young AI men in their decision to use birth control.     

How learning to shake a rattle affects 8-month-old infants' perception of the rattle's sound: electrophysiological evidence for action-effect binding in infancy

Bidirectional action-effect associations play a fundamental role in intentional action control and the development of the mirror neuron system. However, it has been questioned if infants are able to acquire bidirectional action-effect associations (i.e., are able to intentionally control their actions). To investigate this, we trained 8-month-old infants for one week to use a novel rattle that produced a specific sound when shaken. Infants were also presented with another sound, which was not related to an action. Thereafter, infants' EEG responses to these two sounds and to an additional, unfamiliar sound were recorded. Infants displayed a stronger mu-desynchronization above cortical motor sites (i.e., motor resonance) when listening to the action-related sound than when hearing other sounds. Our results provide therefore electrophysiological evidence that infants as young as 8 months are able to acquire bidirectional action-effect associations and parallel findings of audiovisual mirror neurons in the monkey brain.     

Acquiring functional object knowledge through motor imagery?

A widely investigated question in the research on the acquisition of novel functional object representations is the role of the action system. Whereas most studies so far have investigated the role of active action training on the acquisition of object representation, we investigated whether people are able to acquire object representations by just imagining the use of novel objects, given that previous findings suggested that executed and imagined actions share a common representational format. To this end, participants trained the use of novel objects in a motor imagery condition. Training comprised the particular grip applied to the objects and the objects’ typical end location. Subsequently, participants’ object representations were assessed by means of an object detection task. The results show that participants responded slower when the novel objects were presented at functionally incorrect end locations, indicating that the participants had acquired functional knowledge about object use. Yet, there was no effect of correct versus incorrect grip. Altogether, the findings suggest that motor imagery can facilitate the acquisition of novel object representations, but point also to differences between first-hand action training and training by imagery.