Improved conceptual generation and selection with transcranial direct current stimulation in older adults

Normal aging is associated with deficits in various aspects of spoken language production, including idea generation and selection, and involves activity in frontal brain areas including left inferior frontal cortex (LIFG). These conceptual preparation processes, largely involving executive control, precede formulation and articulation stages and are critical for language production. Noninvasive brain stimulation (e.g., transcranial direct current stimulation, tDCS) has proven beneficial for age-related fluency and naming deficits, but this has not been extended to conceptual preparation mechanisms.We investigated whether tDCS could facilitate idea generation and selection in 24 older adults aged 60-80\ua0years. In the first phase, participants completed an idea generation test and a selection test with no stimulation. In the second phase they completed an alternate version of the tests in conjunction with either active or sham stimulation. Active stimulation applied 1-mA anodal tDCS over LIFG for the test duration (10\ua0min).\ua0 Responses were faster following active stimulation than following sham. Furthermore, improvements were specific to test conditions involving novel generation (p\ua0=\ua0.030) and selection (p\ua0=\ua0.001) and were not observed in control conditions for which these mechanisms were minimally involved.\ua0 We concluded that tDCS benefits conceptual preparation mechanisms. This preliminary evidence is an important step for addressing age-related decline in propositional language generation, which is integral to conversational speech. This approach could also be extended toward rehabilitation in neurological patients with deficits in these processes

Mentalizing in schizophrenia: A multivariate functional MRI study

Schizophrenia is associated with mentalizing deficits that impact on social functioning and quality of life. Recently, schizophrenia has been conceptualized as a disorder of neural dysconnectivity and network level analyses offers a means of understanding the underlying deficits leading to mentalizing difficulty. Using an established mentalizing task (The Triangles Task), functional magnetic resonance images (fMRI) were acquired from 19 patients with schizophrenia and 17 age- and sex-matched healthy controls (HCs). Participants were required to watch short animations of two triangles interacting with each other with the interactions either random (no interaction), physical (patterned movement), or mental (intentional movement). Task-based Partial Least Squares (PLS) was used to analyze activation differences and commonalities between the three conditions and the two groups. Seed-based PLS was used to assess functional connectivity with peaks identified in the task-based PLS. Behavioural PLS was then performed using the accuracy from the mental conditions. Patients with schizophrenia performed worse on the mentalizing condition compared to HCs. Task-based PLS revealed one significant latent variable (LV) that explained 42.9 of the variance in the task, with theLV separating the mental condition from the physical and random conditions in patients with schizophrenia, but only the mental from physical in healthy controls. The mental animations were associated with increased modulation of the inferior frontal gyri bilaterally, left superior temporal gyrus, right postcentral gyrus, and left caudate nucleus. The physical/random animations were associated with increased modulation of the right medial frontal gyrus and left superior frontal gyrus. Seed-based PLS identified increased functional connectivity with the left inferior frontal gyrus (liFG) and caudate nucleus in patients with schizophrenia, during the mental and physical interactions, with functional connectivity with the liFG associated with increased performance on the mental animations. The results suggest that mentalizing deficits in schizophrenia may arise due to inefficient social brain networks

Verbal Initiation, Suppression, and Strategy Use and the Relationship with Clinical Symptoms in Schizophrenia

Objectives: Individuals with schizophrenia have difficulties on measures of executive functioning such as initiation and suppression of responses and strategy development and implementation. The current study thoroughly examines performance on the Hayling Sentence Completion Test (HSCT) in individuals with schizophrenia, introducing novel analyses based on initiation errors and strategy use, and association with lifetime clinical symptoms. Methods: The HSCT was administered to individuals with schizophrenia (N=77) and age-and sex-matched healthy controls (N=45), along with background cognitive tests. The standard HSCT clinical measures (initiation response time, suppression response time, suppression errors), composite initiation and suppression error scores, and strategy-based responses were calculated. Lifetime clinical symptoms formal thought disorder (FTD), positive, negative were calculated using the Lifetime Dimensions of Psychosis Scale. Results: After controlling for baseline cognitive differences, individuals with schizophrenia were significantly impaired on the suppression response time and suppression error scales. For the novel analyses, individuals with schizophrenia produced a greater number of initiation errors and subtly wrong errors, and produced fewer responses indicative of developing an appropriate strategy. Strategy use was negatively correlated with FTD symptoms in individuals with schizophrenia. Conclusions: The current study provides further evidence for deficits in the initiation and suppression of verbal responses in individuals with schizophrenia. Moreover, an inability to attain a strategy at least partly contributes to increased semantically connected errors when attempting to suppress responses. The association between strategy use and FTD points to the involvement of executive deficits in disorganized speech in schizophrenia

In situ structure of an intact lipopolysaccharide-bound bacterial surface layer

Most bacterial and all archaeal cells are encapsulated by a paracrystalline, protective, and cell-shape-determining proteinaceous surface layer (S-layer). On Gram-negative bacteria, S-layers are anchored to cells via lipopolysaccharide. Here, we report an electron cryomicroscopy structure of the Caulobacter crescentus S-layer bound to the O-antigen of lipopolysaccharide. Using native mass spectrometry and molecular dynamics simulations, we deduce the length of the O-antigen on cells and show how lipopolysaccharide binding and S-layer assembly is regulated by calcium. Finally, we present a near-atomic resolution in situ structure of the complete S-layer using cellular electron cryotomography, showing S-layer arrangement at the tip of the O-antigen. A complete atomic structure of the S-layer shows the power of cellular tomography for in situ structural biology and sheds light on a very abundant class of self-assembling molecules with important roles in prokaryotic physiology with marked potential for synthetic biology and surface-display applications

Effects of Vagus Nerve Stimulation on Sleep-related Breathing in Epilepsy Patients

Purpose: To describe the effects of vagus nerve stimulation (VNS) on sleep-related breathing in a sample of 16 epilepsy patients. Methods: Sixteen adults with medically refractory epilepsy (nine men, seven women, ages 21–58 years) underwent baseline polysomnograms (PSGs). Three months after VNS therapy was initiated, PSGs were repeated. In addition, patient 7 had a study with esophageal pressure monitoring, and patient 1 had a continuous positive airway pressure (CPAP) trial. Results: Baseline PSGs: One of 16 patients had an apnea–hypopnea index (AHI) >5 (6.8). Treatment PSGs: Five of 16 patients had treatment AHIs >5. Respiratory events were more frequent during periods with VNS activation (on-time) than without VNS activation (off-time; p = 0.016 ). Follow-up studies: Esophageal pressure monitoring in patient 7 showed crescendos in esophageal pressure during VNS activation, supporting an obstructive pattern. The CPAP trial of patient 1 showed that all respiratory events were associated with VNS stimulation at low CPAP levels. They were resolved at higher CPAP levels. Conclusions: Treatment with VNS affects respiration during sleep and should be used with care, particularly in patients with preexisting obstructive sleep apnea. The AHI after VNS treatment remained <5 in the majority of patients and was only mildly elevated (<12) in five patients. In one patient, CPAP resolved VNS-related respiratory events.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66447/1/j.1528-1157.2003.56202.x.pd

Ice Lines, Planetesimal Composition and Solid Surface Density in the Solar Nebula

To date, there is no core accretion simulation that can successfully account for the formation of Uranus or Neptune within the observed 2-3 Myr lifetimes of protoplanetary disks. Since solid accretion rate is directly proportional to the available planetesimal surface density, one way to speed up planet formation is to take a full accounting of all the planetesimal-forming solids present in the solar nebula. By combining a viscously evolving protostellar disk with a kinetic model of ice formation, we calculate the solid surface density in the solar nebula as a function of heliocentric distance and time. We find three effects that strongly favor giant planet formation: (1) a decretion flow that brings mass from the inner solar nebula to the giant planet-forming region, (2) recent lab results (Collings et al. 2004) showing that the ammonia and water ice lines should coincide, and (3) the presence of a substantial amount of methane ice in the trans-Saturnian region. Our results show higher solid surface densities than assumed in the core accretion models of Pollack et al. (1996) by a factor of 3 to 4 throughout the trans-Saturnian region. We also discuss the location of ice lines and their movement through the solar nebula, and provide new constraints on the possible initial disk configurations from gravitational stability arguments.Comment: Version 2: reflects lead author's name and affiliation change, contains minor changes to text from version 1. 12 figures, 7 tables, accepted for publication in Icaru

Acute inhalation of hypertonic saline does not improve mucociliary clearance in all children with cystic fibrosis

<p>Abstract</p> <p>Background</p> <p>Little is known of how mucociliary clearance (MCC) in children with cystic fibrosis (CF) and normal pulmonary function compares with healthy adults, or how an acute inhalation of 7% hypertonic saline (HS) aerosol affects MCC in these same children.</p> <p>Methods</p> <p>We compared MCC in 12 children with CF and normal pulmonary function after an acute inhalation of 0.12% saline (placebo), or HS, admixed with the radioisotope ^{99 m}technetium sulfur colloid in a double-blind, randomized, cross-over study. Mucociliary clearance on the placebo day in the children was also compared to MCC in 10 healthy, non-CF adults. Mucociliary clearance was quantified over a 90 min period, using gamma scintigraphy, and is reported as MCC at 60 min (MCC60) and 90 min (MCC90).</p> <p>Results</p> <p>Median [interquartile range] MCC60 and MCC90 in the children on the placebo visit were 15.4 [12.4-24.5]% and 19.3 [17.3-27.8%]%, respectively, which were similar to the adults with 17.8 [6.4-28.7]% and 29.6 [16.1-43.5]%, respectively. There was no significant improvement in MCC60 (2.2 [-6.2-11.8]%) or MCC90 (2.3 [-1.2-10.5]%) with HS, compared to placebo. In addition, 5/12 and 4/12 of the children showed a decrease in MCC60 and MCC90, respectively, after inhalation of HS. A <it>post hoc </it>subgroup analysis of the change in MCC90 after HS showed a significantly greater improvement in MCC in children with lower placebo MCC90 compared to those with higher placebo MCC90 (p = 0.045).</p> <p>Conclusions</p> <p>These data suggest that percent MCC varies significantly between children with CF lung disease and normal pulmonary functions, with some children demonstrating MCC values within the normal range and others showing MCC values that are below normal values. In addition, although MCC did not improve in all children after inhalation of HS, improvement did occur in children with relatively low MCC values after placebo. This finding suggests that acute inhalation of hypertonic saline may benefit a subset of children with low MCC values.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01293084">NCT01293084</a></p