Regimes and mechanisms of transient amplification in abstract and biological neural networks.

Neuronal networks encode information through patterns of activity that define the networks' function. The neurons' activity relies on specific connectivity structures, yet the link between structure and function is not fully understood. Here, we tackle this structure-function problem with a new conceptual approach. Instead of manipulating the connectivity directly, we focus on upper triangular matrices, which represent the network dynamics in a given orthonormal basis obtained by the Schur decomposition. This abstraction allows us to independently manipulate the eigenspectrum and feedforward structures of a connectivity matrix. Using this method, we describe a diverse repertoire of non-normal transient amplification, and to complement the analysis of the dynamical regimes, we quantify the geometry of output trajectories through the effective rank of both the eigenvector and the dynamics matrices. Counter-intuitively, we find that shrinking the eigenspectrum's imaginary distribution leads to highly amplifying regimes in linear and long-lasting dynamics in nonlinear networks. We also find a trade-off between amplification and dimensionality of neuronal dynamics, i.e., trajectories in neuronal state-space. Networks that can amplify a large number of orthogonal initial conditions produce neuronal trajectories that lie in the same subspace of the neuronal state-space. Finally, we examine networks of excitatory and inhibitory neurons. We find that the strength of global inhibition is directly linked with the amplitude of amplification, such that weakening inhibitory weights also decreases amplification, and that the eigenspectrum's imaginary distribution grows with an increase in the ratio between excitatory-to-inhibitory and excitatory-to-excitatory connectivity strengths. Consequently, the strength of global inhibition reveals itself as a strong signature for amplification and a potential control mechanism to switch dynamical regimes. Our results shed a light on how biological networks, i.e., networks constrained by Dale's law, may be optimised for specific dynamical regimes.

ALS Cognitive Behavioral Screen-Phone Version (ALS-CBS™-PhV): norms, psychometrics, and diagnostics in an Italian population sample.

BACKGROUND: Up to 50% of motor neuron disease (MND) patients show neuropsychological deficits which negatively affect prognosis and care. However, disability-related logistical issues and uneven geographical coverage of healthcare services may prevent MND patients from accessing neuropsychological evaluations. This study thus aimed to standardize for the Italian population the ALS Cognitive Behavioral Screen-Phone Version (ALS-CBS™-PhV), an MND-specific, telephone-based screening for frontotemporal dysfunction. METHODS: The cognitive section of the ALS-CBS™-PhV, the Italian telephone-based Mini-Mental State Examination (Itel-MMSE), and the Telephone Interview for Cognitive Status (TICS) was administered to 359 healthy individuals (143 males, 216 females; age, 52.7 ± 15.8; education, 13.1 ± 4.4). Norms were derived through equivalent scores. Validity, factorial structure, reliability, diagnostic accuracy, and item difficulty and discrimination were examined. Statistical equivalence between the telephone-based and in-person versions was tested. RESULTS: ALS-CBS™-PhV measures were predicted by age and education. The ALS-CBS™-PhV reflected a mono-component structure, converged with Itel-MMSE and TICS scores (rs = .23-.51) and was equivalent to its in-person format (t = .37; p = .72). Good internal (Cronbach's α = .61), test-retest (ICC = .69), and inter-rater (ICC = .96) reliability was detected. High accuracy was found when tested against both the Itel-MMSE and the TICS (AUC = .82-89). Backward digit span items were the most discriminative. DISCUSSION: The ALS-CBS™-PhV is a statistically solid screening test for frontotemporal disorders featuring MND. Its standardization allows for (1) improvements in tele-healthcare for MND patients, (2) epidemiological applications, and (3) effective assessments in decentralized clinical trials. The ALS-CBS™-PhV can be also suitable for assessing bedridden and visually impaired patients with motor disorders.

Psychosocial factors and multiple health risk behaviors among early adolescents: a latent profile analysis.

Early adolescence is a pivotal developmental period when multiple health risk behaviors, such as obesity and substance use, are often established. Several psychosocial factors, often considered traits, have been independently associated with these increases, including executive function (EF), mindfulness disposition (MD), perceived stress, distress tolerance (DT), and anhedonia. However, these factors have not been evaluated for their conjoint relationships to determine whether different patterns may signal greater or lesser risk for obesity and substance use, and whether the same patterns relate to obesity and substance use in the same ways (same magnitude of risk). To evaluate these patterns, a latent profile analysis was conducted, resulting in a three-profile model. Profile 1 (8% of sample) was characterized by the lowest levels of EF, MD, DT and highest levels of stress and anhedonia, profile 2 (44%) intermediate levels, and profile 3 (48%) the highest levels of EF, MD, DT and lowest levels of stress and anhedonia. Youth classified to profile 1 reported significantly greater levels of both obesogenic and substance use behaviors relative to other profiles. Findings suggest that adolescents engaging in obesogenic and substance use behaviors may share common profiles of psychosocial risk.

The effect of sensation seeking on alcohol use among middle school students: a latent state-trait analysis.

BACKGROUND: Sensation seeking has been implicated as a major risk factor for underage alcohol use, however little research into this personality trait has been conducted among children. OBJECTIVE: The current study examined if sensation seeking presents as a state or trait in children, and if the state or trait predicted future alcohol use. METHODS: A latent state-trait (LST) analysis was conducted among 552 individuals (54.3% female; age range 8-13; mean age 9.3) to determine the state or trait-based aspects of sensation seeking, and if this state or trait predicted future alcohol use. Sensation seeking behavior and lifetime alcohol use were assessed at four time points using two previously validated measures. RESULTS: Between 49.4% and 95.3% of individual differences in sensation seeking could be attributed to a stable underlying sensation seeking trait. Further, logistic regression of the stable trait of sensation seeking predicted future alcohol use. A one unit increase in the latent trait increased the odds a student would try alcohol by 7.83 times (95% CI = 1.49-41.11, p = .015). Standardized regression coefficients revealed that an increase of one standard deviation in the latent trait of sensation seeking increased the odds of experimentation with alcohol by 1.29 times (95% CI = 1.11-1.49, p = .001). CONCLUSION: Findings suggest sensation seeking presents as a stable trait during childhood, which can cause children to seek out a novel or exciting behaviors such as alcohol use. Future substance use interventions may need to account for the influence of the underlying trait.

Anhedonia, screen time, and substance use in early adolescents: A longitudinal mediation analysis.

INTRODUCTION: Screen time is associated with substance use risk among adolescents; however, less is known about the underlying factors that explain this association. METHODS: This research examined anhedonia, a facet of depression noted by the reduced capacity to experience pleasure, as a mediating factor in the relationship between screen time (hours spent watching television, using internet, and/or playing video games outside of school) and substance use (alcohol and/or cigarettes). We used a longitudinal survey design among a sample of students aged 9-11 years in the 4th to 6th grades in Southern California, United States of America [N = 709 (354 males)]. RESULTS: Structural equation modeling (SEM) findings revealed longitudinal mediation effects of anhedonia on the association between screen time and substance use, while controlling for baseline screen time, baseline individual and peer substance use, race/ethnicity, and gender. Moderation analysis based on a multiple-group approach revealed that gender was not a significant moderator of this mediation pathway. CONCLUSIONS: Adolescents may become desensitized and exhibit a blunted response to hedonic effects from increased screen time. This may result in increased anhedonia and greater risk for substance use through the need to compensate for the reduced experience of rewards. These findings have implications for future school-based substance use prevention and intervention programs.

Crystal Clear with Active Visualization: Understanding Medication Adherence Among Youth Living with HIV.

Adherence to antiretroviral therapy (ART) among youth remains low. We piloted an adapted active visualization device that demonstrates how ART works in the body. Youth living with HIV were randomized to: (1) standard care (n = 14) or the (2) adapted active visualization intervention (n = 14) and 71% of the sample (n = 19) were re-assessed on viral load, adherence behaviors, and illness perceptions 2.5 months later. Intervention youth had lower viral loads, reported less difficulty in adhering to ART, and more motivation and control over their HIV than standard care at follow-up. Active visualization may be an acceptable tool to address ART adherence among youth.

Corrigendum to "Longitudinal Screening Detects Cognitive Stability and Behavioral Deterioration in ALS Patients".

[This corrects the article DOI: 10.1155/2018/5969137.].

Mindfulness meditation and gene expression: a hypothesis-generating framework.

Recent research in functional genomics shows that social stressors affect the expression of immune response genes. These effects are mediated in part via our adaptive capacity for intracellular molecules to respond to extracellular signals, a process called signal transduction. Under this framework, one-way stressors can be transduced into cellular changes is through central nervous system (CNS) modulation of peripheral neural, endocrine, and molecular activity. Mindfulness meditation is a consciousness discipline used to cultivate attention and self-regulation, and may thus be relevant to the signal transduction process outlined in the social genomics literature. In this opinion article, we briefly review results from existing controlled trials that test the effects of mindfulness meditation on gene expression. We then speculate on a mind-body conceptual model, grounded in existing social genomics theory. In the spirit of hypothesis generation, we argue that mindfulness meditation changes brain activity patterns related to attention, self-regulation, and threat evaluation and so may alter the signal transduction process that regulates the expression of immune response genes.

Longitudinal Screening Detects Cognitive Stability and Behavioral Deterioration in ALS Patients.

Objective: To evaluate longitudinal cognitive/behavioral change over 12 months in participants enrolled in the ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS). Methods: We analyzed data from 294 ALS participants, 134 of whom were studied serially. Change over time was evaluated controlling for age, sex, symptom duration, education, race, and ethnicity. Using multiple regression, we evaluated associations among decline in ALS Functional Rating Scale-Revised (ALSFRS-R) scores, forced vital capacity (FVC), and cognitive/behavioral changes. Change in cognitive/behavioral subgroups was assessed using one-way analyses of covariance. Results: Participants with follow-up data had fewer baseline behavior problems compared to patients without follow-up data. We found significant worsening of behavior (ALS Cognitive Behavioral Screen (ALS CBS) behavioral scale, p < 0.001; Frontal Behavioral Inventory-ALS (FBI-ALS) disinhibition subscale, p = 0.044). Item analysis suggested change in frustration tolerance, insight, mental rigidity, and interests (p < 0.05). Changes in ALSFRS-R correlated with the ALS CBS. Worsening disinhibition (FBI-ALS) did not correlate with ALSFRS-R, FVC, or disease duration. Conclusion: We did not detect cognitive change. Behavioral change was detected, and increased disinhibition was found among patients with abnormal baseline behavioral scores. Disinhibition changes did not correlate with disease duration or progression. Baseline behavioral problems were associated with advanced, rapidly progressive disease and study attrition.

Genomic mechanisms of fatigue in survivors of colorectal cancer.

BACKGROUND: Many cancer survivors experience fatigue as a nagging symptom lasting years after treatment. To learn of the relevant biological pathways involved in fatigue among cancer survivors, the authors tested for an association between fatigue levels and leukocyte gene expression profiles and determined the specific mediating immune cell types. METHODS: A sample of 89 Hispanic/Latino adults aged 60.5 years, 62% of whom were male, who were diagnosed with colorectal cancer and were 2.9 years since diagnosis provided blood for transcriptome profiling and completed a validated measure of fatigue (Multidimensional Fatigue Symptom Inventory-Short Form). The authors applied genome-wide transcriptional profiling of leukocyte RNA to identify gene expression activity associated with fatigue, tested for the activity of specific transcription factors involved in previously established markers of inflammation and immunologic activation, and identified the specific cell types mediating these transcriptional alterations. RESULTS: In analyses adjusting for demographic and behavioral health risk factors, results linked fatigue with increased activation of B lymphocytes and CD8-positive T cells, as well as several transcription factors involved in immune activation (nuclear factor κB [NF-κB], signal transducer and activator of transcription [STAT], and cAMP responsive element-binding protein [CREB]). Results also replicated several specific genomic effects previously observed in fatigued cancer survivors, including upregulated expression of α-synuclein (SNCA) and hemoglobin subunits (HBA and HBB). CONCLUSIONS: Cancer survivors' heightened fatigue levels may be partially explained by activation of specific immune cell subsets, thereby providing a potential molecular biomarker for clinical interventions targeting the remediation of fatigue. Cancer 2018;124:2637-44. © 2018 American Cancer Society.

Mindfulness-Based Interventions and Sleep Among Cancer Survivors: a Critical Analysis of Randomized Controlled Trials.

PURPOSE OF REVIEW: The purpose of our critical examination is to present results and provide a synthesis of this body of work. RECENT FINDINGS: Sleep problems among cancer survivors are gaining research attention. To our knowledge, there have been six randomized control trials published from 2013 to 2015 that test the effects of mindfulness-based interventions (MBIs) on sleep as a primary or secondary outcome. Our examination of the literature highlights important methodological issues and variability among trials. We conclude our review by offering solutions to facilitate more scientific rigor in future studies.

Telephone based cognitive-behavioral screening for frontotemporal changes in patients with amyotrophic lateral sclerosis (ALS).

Our objective was to establish a valid and reliable battery of measures to evaluate frontotemporal dementia (FTD) in patients with ALS over the telephone. Thirty-one subjects were administered either in-person or by telephone-based screening followed by the opposite mode of testing two weeks later, using a modified version of the UCSF Cognitive Screening Battery. Equivalence testing was performed for in-person and telephone based tests. The standard ALS Cognitive Behavioral Screen (ALS-CBS) showed statistical equivalence at the 5% significance level compared to a revised phone version of the ALS-CBS. In addition, the Controlled Oral Word Association Test (COWAT) and Center for Neurologic Study-Lability Scale (CNS-LS) were also found to be equivalent at the 5% and 10% significance level, respectively. Similarly, the Mini-Mental State Examination (MMSE) and the well-established Telephone Interview for Cognitive Status (TICS) were also statistically equivalent. Equivalence could not be claimed for the ALS-Frontal Behavioral Inventory (ALS-FBI) caregiver interview and the Written Verbal Fluency Index (WVFI). In conclusion, our study suggests that telephone-based versions of the ALS-CBS, COWAT, and CNS-LS may offer clinicians valid tools to detect frontotemporal changes in the ALS population. Development of telephone based cognitive testing for ALS could become an integral resource for population based research in the future.

Opinions of Japanese and American ALS caregivers regarding tracheostomy with invasive ventilation (TIV).

Our objective was to learn more about possible factors contributing to the higher rates of tracheostomy with invasive ventilation (TIV) for ALS patients in Japan compared with the United States by eliciting attitudes of caregivers of ALS patients in both countries. One hundred and fifty-four American caregivers from five, geographically-distributed ALS clinics and 66 Japanese caregivers from six sites in Japan completed questionnaires regarding TIV. Results showed that 33% of American caregivers were in favor of TIV for their family member compared to 53% of Japanese caregivers; 44% of American and 37% of Japanese caregivers were undecided; and 22% of American and 10% of Japanese caregivers were opposed (p <.01). Within patient-caregiver dyads, agreement in the American sample was fair, while the Japanese dyads showed poor agreement. Maintaining quality of life and patients reaching a milestone were the most common reasons for favoring TIV in the American and Japanese samples, respectively. Reasons for opposing TIV did not significantly differ. Findings suggest that caregiver preferences may influence actual choices for ALS patients. More frequent endorsement of TIV by Japanese vs. American caregivers is consistent with higher rates of TIV among Japanese patients. The results reflect the importance of caregivers' opinions in patient care.

R2oDNA designer: computational design of biologically neutral synthetic DNA sequences.

R2oDNA Designer is a web application that stochastically generates orthogonal sets of synthetic DNA sequences designed to be biologically neutral. Biologically neutral sequences may be used for directing efficient DNA assembly by overlap-directed methods, as a negative control for functional DNA, as barcodes, or potentially as spacer regions to insulate biological parts from local context. The software creates optimized sequences using a Monte Carlo simulated annealing approach followed by the elimination of sequences homologous to host genomes and commonly used biological parts. An orthogonal set is finally determined by using a network elimination algorithm. Design constraints can be defined using either a web-based graphical user interface (GUI) or uploading a file containing a set of text commands.

One-pot DNA construction for synthetic biology: the Modular Overlap-Directed Assembly with Linkers (MODAL) strategy.

Overlap-directed DNA assembly methods allow multiple DNA parts to be assembled together in one reaction. These methods, which rely on sequence homology between the ends of DNA parts, have become widely adopted in synthetic biology, despite being incompatible with a key principle of engineering: modularity. To answer this, we present MODAL: a Modular Overlap-Directed Assembly with Linkers strategy that brings modularity to overlap-directed methods, allowing assembly of an initial set of DNA parts into a variety of arrangements in one-pot reactions. MODAL is accompanied by a custom software tool that designs overlap linkers to guide assembly, allowing parts to be assembled in any specified order and orientation. The in silico design of synthetic orthogonal overlapping junctions allows for much greater efficiency in DNA assembly for a variety of different methods compared with using non-designed sequence. In tests with three different assembly technologies, the MODAL strategy gives assembly of both yeast and bacterial plasmids, composed of up to five DNA parts in the kilobase range with efficiencies of between 75 and 100%. It also seamlessly allows mutagenesis to be performed on any specified DNA parts during the process, allowing the one-step creation of construct libraries valuable for synthetic biology applications.

A comparative study on filtering protein secondary structure prediction.

Filtering of Protein Secondary Structure Prediction (PSSP) aims to provide physicochemically realistic results, while it usually improves the predictive performance. We performed a comparative study on this challenging problem, utilizing both machine learning techniques and empirical rules and we found that combinations of the two lead to the highest improvement.