Marker-Assisted Recurrent Selection for Pyramiding Leaf Rust and Coffee Berry Disease Resistance Alleles in Coffea arabica L.

In this study, marker-assisted recurrent selection was evaluated for pyramiding resistance gene alleles against coffee leaf rust (CLR) and coffee berry diseases (CBD) in Coffea arabica. A total of 144 genotypes corresponding to 12 hybrid populations from crosses between eight parent plants with desired morphological and agronomic traits were evaluated. Molecular data were used for cross-certification, diversity study and resistance allele marker-assisted selection (MAS) against the causal agent of coffee leaf rust (Hemileia vastatrix) and coffee berry disease (Colletotrichum kahawae). In addition, nine morphological and agronomic traits were evaluated to determine the components of variance, select superior hybrids, and estimate genetic gain. From the genotypes evaluated, 134 were confirmed as hybrids. The genetic diversity between and within populations was 75.5% and 24.5%, respectively, and the cluster analysis revealed three primary groups. Pyramiding of CLR and CBD resistance genes was conducted in 11 genotypes using MAS. A selection intensity of 30% resulted in a gain of over 50% compared to the original population. Selected hybrids with increased gain also showed greater genetic divergence in addition to the pyramided resistance alleles. The strategies used were, therefore, efficient to select superior coffee hybrids for recurrent selection programs and could be used as a source of resistance in various crosses.

Autophagy modulates growth and development in the moss Physcomitrium patens.

Physcomitrium patens apical growing protonemal cells have the singularity that they continue to undergo cell divisions as the plant develops. This feature provides a valuable tool to study autophagy in the context of a multicellular apical growing tissue coupled to development. Herein, we showed that the core autophagy machinery is present in the moss P. patens, and characterized the 2D and 3D growth and development of atg5 and atg7 loss-of-function mutants under optimal and nutrient-deprived conditions. Our results showed that 2D growth of the different morphological and functional protonemata apical growing cells, chloronema and caulonema, is differentially modulated by this process. These differences depend on the protonema cell type and position along the protonemal filament, and growth condition. As a global plant response, the absence of autophagy favors the spread of the colony through protonemata growth at the expense of a reduction of the 3D growth, such as the buds and gametophore development, and thus the adult gametophytic and reproductive phases. Altogether this study provides valuable information suggesting that autophagy has roles during apical growth with differential responses within the cell types of the same tissue and contributes to life cycle progression and thus the growth and development of the 2D and 3D tissues of P. patens.

Predicting zebrafish (Danio rerio) embryo developmental toxicity through a non-conformational QSAR approach.

For many years, the frequent use of synthetic chemicals in the manufacture of veterinary drugs and plague control products has raised negative effects on human health and other non-target organisms, promoting the need to employ a practical and suitable methodology for early risk identification of several thousand commercial compounds. The zebrafish (Danio rerio) embryo has been emerged as one sustainable animal model for measuring developmental toxicity, an endpoint that is included in the regulatory procedures to approve chemicals, avoiding conventional and costly toxicity assays based on animal testing. In this context, the Quantitative Structure-Activity Relationships (QSAR) theory is applied to develop a predictive model based on a well-defined zebrafish embryo developmental toxicity database reported by the ToxCast™ Phase I chemical library of the Environmental Protection Agency (U.S. EPA). By means of four freely available softwares, a set with 28,038 non-conformational descriptors that encode the largest amount of permanent structural features are readily calculated. The Replacement Method (RM) variable subset selection technique provided the best regression models. Thereby, a linear QSAR model with proper statistical quality (Rtrain2 = 0.64, RMSEtrain = 0.49) is established in agreement with the Organization for Economic Co-operation and Development principles, accomplishing each internal (loo, l15 % o, VIF and Y-randomization) and external (Rtest2,Rm2, QF12, QF22, QF32 and CCC) validation criterion. The present QSAR approach provides a useful computational tool to estimate zebrafish developmental toxicity of new, untasted or hypothetical compounds, and it can contribute to the general lack of QSAR models in the literature to predict this endpoint.

Measuring multimorbidity beyond counting diseases: systematic review of community and population studies and guide to index choice.

OBJECTIVES: To identify and summarise existing indices for measuring multimorbidity beyond disease counts, to establish which indices include mental health comorbidities or outcomes, and to develop recommendations based on applicability, performance, and usage. DESIGN: Systematic review. DATA SOURCES: Seven medical research databases (Medline, Web of Science Core Collection, Cochrane Library, Embase, PsycINFO, Scopus, and CINAHL Plus) from inception to October 2018 and bibliographies and citations of relevant papers. Searches were limited to English language publications. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Original articles describing a new multimorbidity index including more information than disease counts and not focusing on comorbidity associated with one specific disease. Studies were of adults based in the community or at population level. RESULTS: Among 7128 search results, 5560 unique titles were identified. After screening against eligibility criteria the review finally included 35 papers. As index components, 25 indices used conditions (weighted or in combination with other parameters), five used diagnostic categories, four used drug use, and one used physiological measures. Predicted outcomes included mortality (18 indices), healthcare use or costs (13), hospital admission (13), and health related quality of life (7). 29 indices considered some aspect of mental health, with most including it as a comorbidity. 12 indices are recommended for use. CONCLUSIONS: 35 multimorbidity indices are available, with differing components and outcomes. Researchers and clinicians should examine existing indices for suitability before creating new ones. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017074211.

Evolutionary insights into FYVE and PHOX effector proteins from the moss Physcomitrella patens.

MAIN CONCLUSION: Genome-wide identification, together with gene expression patterns and promoter region analysis of FYVE and PHOX proteins in Physcomitrella patens, emphasized their importance in regulating mainly developmental processes in P. patens. Phosphatidylinositol 3-phosphate (PtdIns3P) is a signaling phospholipid, which regulates several aspects of plant growth and development, as well as responses to biotic and abiotic stresses. The mechanistic insights underlying PtdIns3P mode of action, specifically through effector proteins have been partially explored in plants, with main focus on Arabidopsis thaliana. In this study, we searched for genes coding for PtdIns3P-binding proteins such as FYVE and PHOX domain-containing sequences from different photosynthetic organisms to gather evolutionary insights on these phosphoinositide binding domains, followed by an in silico characterization of the FYVE and PHOX gene families in the moss Physcomitrella patens. Phylogenetic analysis showed that PpFYVE proteins can be grouped in 7 subclasses, with an additional subclass whose FYVE domain was lost during evolution to higher plants. On the other hand, PpPHOX proteins are classified into 5 subclasses. Expression analyses based on RNAseq data together with the analysis of cis-acting regulatory elements and transcription factor (TF) binding sites in promoter regions suggest the importance of these proteins in regulating stress responses but mainly developmental processes in P. patens. The results provide valuable information and robust candidate genes for future functional analysis aiming to further explore the role of this signaling pathway mainly during growth and development of tip growing cells and during the transition from 2 to 3D growth. These studies would identify ancestral regulatory players undertaken during plant evolution.

The Use of the Index of Ideality of Correlation to Build Up Models for Bioconcentration Factor.

We establish a QSPR analysis for the bioconcentration factor of 851 heterogeneous structural compounds. Linear models are proposed via two different approaches: i. the optimal descriptor method implemented in CORAL, and ii. multivariable linear regressions on the best molecular descriptors found with the Replacement Method on 44,216 structural descriptors. Such variables are derived with different freely available softwares, such as PaDEL, PyDescriptor, Mold2 , QuBiLs-MAS and ISIDA/Fragmentor. The same validation set is employed in order to compare the predictive performance between the so-obtained CORAL and RM based models. Finally, the comparison of several models for the bioconcentration factor confirms the ability of the so-called index of ideality of correlation to be a criterion of predictive potential in Quantitative Structure-Property Relationships.

A non-conformational QSAR study for plant-derived larvicides against Zika Aedes aegypti L. vector.

A set of 263 plant-derived compounds with larvicidal activity against Aedes aegypti L. (Diptera: Culicidae) vector is collected from the literature, and is studied by means of a non-conformational quantitative structure-activity relationships (QSAR) approach. The balanced subsets method (BSM) is employed to split the complete dataset into training, validation and test sets. From 26,775 freely available molecular descriptors, the most relevant structural features of compounds affecting the bioactivity are taken. The molecular descriptors are calculated through four different freewares, such as PaDEL, Mold2, EPI Suite and QuBiLs-MAS. The replacement method (RM) variable subset selection technique leads to the best linear regression models. A successful QSAR equation involves 7-conformation-independent molecular descriptors, fulfiling the evaluated internal (loo, l30%o, VIF and Y-randomization) and external (test set with Ntest = 65 compounds) validation criteria. The practical application of this QSAR model reveals promising predicted values for some natural compounds with unknown experimental larvicidal activity. Therefore, the present model constitutes the first one based on a large molecular set, being a useful computational tool for identifying and guiding the synthesis of new active molecules inspired by natural products.

Phosphatidylinositol 3-kinase function at very early symbiont perception: a local nodulation control under stress conditions?

Root hair curling is an early and essential morphological change required for the success of the symbiotic interaction between legumes and rhizobia. At this stage rhizobia grow as an infection thread within root hairs and are internalized into the plant cells by endocytosis, where the PI3K enzyme plays important roles. Previous observations show that stress conditions affect early stages of the symbiotic interaction, from 2 to 30 min post-inoculation, which we term as very early host responses, and affect symbiosis establishment. Herein, we demonstrated the relevance of the very early host responses for the symbiotic interaction. PI3K and the NADPH oxidase complex are found to have key roles in the microsymbiont recognition response, modulating the apoplastic and intracellular/endosomal ROS induction in root hairs. Interestingly, compared with soybean mutant plants that do not perceive the symbiont, we demonstrated that the very early symbiont perception under sublethal saline stress conditions induced root hair death. Together, these results highlight not only the importance of the very early host-responses on later stages of the symbiont interaction, but also suggest that they act as a mechanism for local control of nodulation capacity, prior to the abortion of the infection thread, preventing the allocation of resources/energy for nodule formation under unfavorable environmental conditions.

Quantitative structure-activity relationship (QSAR) analysis of plant-derived compounds with larvicidal activity against Zika Aedes aegypti (Diptera: Culicidae) vector using freely available descriptors.

BACKGROUND: We have developed a quantitative structure-activity relationship (QSAR) model for predicting the larvicidal activity of 60 plant-derived molecules against Aedes aegypti L. (Diptera: Culicidae), a vector of several diseases such as dengue, yellow fever, chikungunya and Zika. The balanced subsets method (BSM) based on k-means cluster analysis (k-MCA) was employed to split the data set. The replacement method (RM) variable subset selection technique coupled with multivariable linear regression (MLR) proved to be successful for exploring 18 326 molecular descriptors and fingerprints calculated with PaDEL, Mold2 and EPI Suite open-source softwares. RESULTS: A robust QSAR model (Rtrain2=0.84, Strain = 0.20 and Rtest2=0.92, Stest = 0.23) involving five non-conformational descriptors was established. The model was validated and tested through the use of an external test set of compounds, the leave-one-out (LOO) and leave-more-out (LMO) cross-validation methods, Y-randomization and applicability domain (AD) analysis. CONCLUSION: The QSAR model surpasses previously published models based on geometrical descriptors, thereby representing a suitable tool for predicting larvicidal activity against the vector A. aegypti using a conformation-independent approach. © 2018 Society of Chemical Industry.

The quantitative structure-insecticidal activity relationships from plant derived compounds against chikungunya and zika Aedes aegypti (Diptera:Culicidae) vector.

The insecticidal activity of a series of 62 plant derived molecules against the chikungunya, dengue and zika vector, the Aedes aegypti (Diptera:Culicidae) mosquito, is subjected to a Quantitative Structure-Activity Relationships (QSAR) analysis. The Replacement Method (RM) variable subset selection technique based on Multivariable Linear Regression (MLR) proves to be successful for exploring 4885 molecular descriptors calculated with Dragon 6. The predictive capability of the obtained models is confirmed through an external test set of compounds, Leave-One-Out (LOO) cross-validation and Y-Randomization. The present study constitutes a first necessary computational step for designing less toxic insecticides.

Concordancia entre la percepción materna y el estado nutricional de sus hijos antes y después de una intervención educativa / Concordance between maternal perception and child's nutritional status before and after an educational intervention

RESUMEN La malnutrición por exceso es un problema de salud y su rápida pesquisa mediante percepción materna (PM), permite intervenciones tempranas enfocadas a disminuir sus consecuencias y costos asociados. El objetivo fue determinar la concordancia entre PM y estado nutricional (EN) de sus hijos, antes y después de una intervención educativa. Participaron 116 diadas madre-hijo de 2 a 5 años, de 4 jardines de Viña del Mar, donde se determinó EN y PM mediante imágenes corporales de los niños. Posteriormente, 57 madres con PM erradas respecto a estado nutricional de su hijo participaron de una intervención educativa de 40 minutos cada 15 días por 3 meses. La concordancia entre el PM y estado nutricional fue evaluada con el test de Kappa. El EN de los niños fue: 3,4% bajo peso; 49,1% normal; 28,4% sobrepeso y 19,0% obesidad. Para la PM el 99,1% subestimó el EN de su hijo (Kappa= 0,022 y p= 0,610). Posterior a la intervención, mejoró la PM en 59,6% y un 40,3% continuó subestimando el EN (kappa= 0,362 y p= 0,000). En este estudio, la PM tiende a subestimar el EN de sus hijos y una intervención educativa mejoró la PM y la concordancia entre PM y el EN de ellos.

ABSTRACT Overnutrition is a health problem and its rapid diagnosis through maternal perception (MP), allows for early intervention focused on reducing consequences and associated costs. The objective of this study was to determine the concordance between MP and child's nutritional status, before and after an educational intervention. Participants were 116 mother-child (2 to 5 years old) dyads from, from 4 daycare centers in Viña del Mar, Chile. Nutritional status was determined and MP was performed using children's body images. Subsequently 57 mothers with MP discordant with child's nutritional status participated in a 40-minute educational intervention every 15 days for 3 months. Concordance between MP and child's nutritional status was evaluated with Kappa. Nutritional status of the 116 children was: 3.4% underweight; 49.1% normal; 28.4% overweight, 19.0% obesity. MP indicated that 99.1% underestimated their child's nutritional status (Kappa = 0.022 and p= 0.610). After intervention, MP improved to 59.6% and 40.3% continued to underestimating child's nutritional status (kappa= 0.362 and p= 0.000). In this study, mothers tended to underestimate the nutritional status of their children. An educational intervention improved MP and the agreement between MP and child's nutritional status.

Behavioral effects of transcranial pulsed current stimulation (tPCS): Speed-accuracy tradeoff in attention switching task.

Transcranial pulsed current stimulation (tPCS) has been shown to increase inter-hemispheric coherence of brain oscillatory activity, mainly in fronto-temporal regions, leading to enhancement of functional connectivity across neural networks. The question is whether tPCS can modulate behavior significantly. Our aim was to identify the effects of tPCS on paired associative learning task (PALT) and attention switching task (AST), and to further categorize physiological autonomic responses by heart rate variability and electrodermal activity measurements before and after task performance. Thirty healthy volunteers were randomized to receive a single session of sham or active 2mA tPCS stimulation with a random frequency between 1 and 5Hz. We show that active tPCS significantly improved response time in the AST compared to sham stimulation, so that subjects who received active tPCS significantly exhibit decreased switching cost between repeat and switch trials. No differences were found in response accuracy on AST and PALT. No significant changes were observed in physiological parameters. Based on our results, we suggest that tPCS has a more pronounced effect on tasks that require the increase of functional connectivity across pre-existent neural circuitry, rather than on tasks that require the development of new learning circuits or the creation of new connections.

Clinically Effective Treatment of Fibromyalgia Pain With High-Definition Transcranial Direct Current Stimulation: Phase II Open-Label Dose Optimization.

Despite promising preliminary results in treating fibromyalgia (FM) pain, no neuromodulation technique has been adopted in clinical practice because of limited efficacy, low response rate, or poor tolerability. This phase II open-label trial aims to define a methodology for a clinically effective treatment of pain in FM by establishing treatment protocols and screening procedures to maximize efficacy and response rate. High-definition transcranial direct current stimulation (HD-tDCS) provides targeted subthreshold brain stimulation, combining tolerability with specificity. We aimed to establish the number of HD-tDCS sessions required to achieve a 50% FM pain reduction, and to characterize the biometrics of the response, including brain network activation pain scores of contact heat-evoked potentials. We report a clinically significant benefit of a 50% pain reduction in half (n = 7) of the patients (N = 14), with responders and nonresponders alike benefiting from a cumulative effect of treatment, reflected in significant pain reduction (P = .035) as well as improved quality of life (P = .001) over time. We also report an aggregate 6-week response rate of 50% of patients and estimate 15 as the median number of HD-tDCS sessions to reach clinically meaningful outcomes. The methodology for a pivotal FM neuromodulation clinical trial with individualized treatment is thus supported. ONLINE REGISTRATION: Registered in Clinicaltrials.gov under registry number NCT01842009. PERSPECTIVE: In this article, an optimized protocol for the treatment of fibromyalgia pain with targeted subthreshold brain stimulation using high-definition transcranial direct current stimulation is outlined.

Phosphatase and Tensin Homolog Is a Growth Repressor of Both Rhizoid and Gametophore Development in the Moss Physcomitrella patens.

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a lipid phosphatase implicated in cellular proliferation and survival. In animal cells, loss of PTEN leads to increased levels of phosphatidylinositol (3,4,5)-trisphosphate, stimulation of glucose and lipid metabolism, cellular growth, and morphological changes (related to adaptation and survival). Intriguingly, in plants, phosphatidylinositol (3,4,5)-trisphosphate has not been detected, and the enzymes that synthesize it were never reported. In this study we performed a genetic, biochemical, and functional characterization of the moss Physcomitrella patens PTEN gene family. P. patens has four PTENs, which are ubiquitously expressed during the entire moss life cycle. Using a knock-in approach, we show that all four genes are expressed in growing tissues, namely caulonemal and rhizoid cells. At the subcellular level, PpPTEN-green fluorescent protein fusions localized to the cytosol and the nucleus. Analysis of single and double knockouts revealed no significant phenotypes at different developmental stages, indicative of functional redundancy. However, compared with wild-type triple and quadruple pten knockouts, caulonemal cells grew faster, switched from the juvenile protonemal stage to adult gametophores earlier, and produced more rhizoids. Furthermore, analysis of lipid content and quantitative real-time polymerase chain reaction data performed in quadruple mutants revealed altered phosphoinositide levels [increase in phosphatidylinositol (3,5)-bisphosphate and decrease in phosphatidylinositol 3-phosphate] and up-regulation of marker genes from the synthesis phase of the cell cycle (e.g. P. patens proliferating cell nuclear antigen, ribonucleotide reductase, and minichromosome maintenance) and of the retinoblastoma-related protein gene P. patens retinoblastoma-related protein1. Together, these results suggest that PpPTEN is a suppressor of cell growth and morphogenic development in plants.

Ion and lipid signaling in apical growth-a dynamic machinery responding to extracellular cues.

Apical cell growth seems to have independently evolved throughout the major lineages of life. To a certain extent, so does our body of knowledge on the mechanisms regulating this morphogenetic process. Studies on pollen tubes, root hairs, rhizoids, fungal hyphae, even nerve cells, have highlighted tissue and cell specificities but also common regulatory characteristics (e.g., ions, proteins, phospholipids) that our focused research sometimes failed to grasp. The working hypothesis to test how apical cell growth is established and maintained have thus been shaped by the model organism under study and the type of methods used to study them. The current picture is one of a dynamic and adaptative process, based on a spatial segregation of components that network to achieve growth and respond to environmental (extracellular) cues. Here, we explore some examples of our live imaging research, namely on cyclic nucleotide gated ion channels, lipid kinases and syntaxins involved in exocytosis. We discuss how their spatial distribution, activity and concentration suggest that the players regulating apical cell growth may display more mobility than previously thought. Furthermore, we speculate on the implications of such perspective in our understanding of the mechanisms regulating apical cell growth and their responses to extracellular cues.

Quantitative Structure-Antifungal Activity Relationships for cinnamate derivatives.

Quantitative Structure-Activity Relationships (QSAR) are established with the aim of analyzing the fungicidal activities of a set of 27 active cinnamate derivatives. The exploration of more than a thousand of constitutional, topological, geometrical and electronic molecular descriptors, which are calculated with Dragon software, leads to predictions of the growth inhibition on Pythium sp and Corticium rolfsii fungi species, in close agreement to the experimental values extracted from the literature. A set containing 21 new structurally related cinnamate compounds is prepared. The developed QSAR models are applied to predict the unknown fungicidal activity of this set, showing that cinnamates like 38, 28 and 42 are expected to be highly active for Pythium sp, while this is also predicted for 28 and 34 in C. rolfsii.

Optimal random frequency range in transcranial pulsed current stimulation indexed by quantitative electroencephalography.

Given the recent results provided by previous investigations on transcranial pulsed current stimulation (tPCS) demonstrating its modulatory effects on cortical connectivity; we aimed to explore the application of different random pulsed frequencies. The utility of tPCS as a neuromodulatory technique for cognition performance will come as additional frequency ranges are tested with the purpose to find optimal operational parameters for tPCS. This study was designed to analyze the effects of tPCS using the following random frequencies; 1-5, 6-10, and 11-15 Hz compared with sham on quantitative electroencephalographic changes in the spectral power and interhemispheric coherence of each electroencephalographic frequency band. This was a parallel, randomized, double-blinded, sham-controlled trial. Forty healthy individuals older than 18 years were eligible to participate. The main outcomes were differences in the spectral power analysis and interhemispheric coherence as measured by quantitative electroencephalography. Participants were randomly allocated to four groups of random frequency stimulation and received a single session of stimulation for 20 min with a current intensity of 2 mA delivered by bilateral periauricular electrode clips. We found that a random pulsed frequency between 6-10 Hz significantly increased the power and coherence in frontal and central areas for the alpha band compared with sham stimulation, while 11-15 Hz tPCS decreased the power for the alpha and theta bandwidth. Our findings corroborate the hypothesis that a random frequency ranging into the boundaries of 6-10 Hz induces changes in the naturally occurring alpha oscillatory activity, providing additional data for further studies with tPCS.

Cognitive effects and autonomic responses to transcranial pulsed current stimulation.

Transcranial pulsed current stimulation (tPCS) is emerging as an option in the field of neuromodulation; however, little is known about its effects on cognition and behavior and its neurophysiological correlates as indexed by autonomic responses. Our aim was to identify the effects of tPCS on arithmetic processing and risk-taking behavior, and to further categorize physiological autonomic responses by heart rate variability (HRV) and electrodermal activity measurements before, during, and after exposure to task performance and stimulation. Thirty healthy volunteers were randomized to receive a single session of sham or active stimulation with a current intensity of 2 mA and a random frequency between 1 and 5 Hz. Our results showed that tPCS has a modest and specific effect on cognitive performance as indexed by the cognitive tasks chosen in this study. There was a modest effect of active tPCS only on performance facilitation on a complex-level mathematical task as compared to sham stimulation. On autonomic responses, we observed that HRV total power increased while LF/HF ratio decreased in the tPCS active group compared to sham. There were no group differences for adverse effects. Based on our results, we conclude that tPCS, in healthy subjects, has a modest and specific cognitive effect as shown by the facilitation of arithmetical processing on complex mathematical task. These effects are accompanied by modulation of the central autonomic network providing sympathetic-vagal balance during stressful conditions. Although behavioral results were modest, they contribute to the understanding of tPCS effects and cognitive enhancement.

QSAR analysis on tacrine-related acetylcholinesterase inhibitors.

BACKGROUND: The evaluation of the clinical effects of Tacrine has shown efficacy in delaying the deterioration of the symptoms of Alzheimer's disease, while confirming the adverse events consisting mainly in the elevated liver transaminase levels. The study of tacrine analogs presents a continuous interest, and for this reason we establish Quantitative Structure-Activity Relationships on their Acetylcholinesterase inhibitory activity. RESULTS: Ten groups of new developed Tacrine-related inhibitors are explored, which have been experimentally measured in different biochemical conditions and AChE sources. The number of included descriptors in the structure-activity relationship is characterized by 'Rule of Thumb'. The 1502 applied molecular descriptors could provide the best linear models for the selected Alzheimer's data base and the best QSAR model is reported for the considered data sets. CONCLUSION: The QSAR models developed in this work have a satisfactory predictive ability, and are obtained by selecting the most representative molecular descriptors of the chemical structure, represented through more than a thousand of constitutional, topological, geometrical, quantum-mechanical and electronic descriptor types.

Intensity-dependent effects of transcranial pulsed current stimulation on interhemispheric connectivity: a high-resolution qEEG, sham-controlled study.

Defining optimal parameters for stimulation is a critical step in the development of noninvasive neuromodulation techniques. Transcranial pulsed current stimulation (tPCS) is emerging as another option in the field of neuromodulation; however, little is known about its mechanistic effects on electrical brain activity and how it can modulate its oscillatory patterns. The aim of this study was to identify the current intensity needed to exert an effect on quantitative electroencephalogram (qEEG) measurements. Forty healthy volunteers were randomized to receive a single session of sham or active stimulation at 0.2, 1, or 2 mA current intensity with a random frequency with an oscillatory pulsed range between 1 and 5 Hz. We conducted an exploratory frequency domain analysis to detect changes in absolute power for theta, alpha, and beta frequency bands and also interhemispheric coherence for alpha, theta, and four different sub-bands. Cognitive and nonspecific adverse effects were also recorded. Our results showed that both 1 and 2 mA can modulate interhemispheric coherence at the fronto-temporal areas for the theta band as compared with sham, while 2 mA also increased the low-beta and high-beta interhemispheric coherence at the same anatomical location. There were no group differences for adverse effects and participants could not guess correctly whether they received active versus sham stimulation. On the basis of our results, we conclude that tPCS is associated with an intensity-dependent facilitatory effect on interhemispheric connectivity. These results can guide future tPCS applications and will define its role as a neuromodulatory technique in the field.