Incomplete evidence that increasing current intensity of tDCS boosts outcomes

BACKGROUND: Transcranial direct current stimulation (tDCS) is investigated to modulate neuronal function by applying a fixed low-intensity direct current to scalp. OBJECTIVES: We critically discuss evidence for a monotonic response in effect size with increasing current intensity, with a specific focus on a question if increasing applied current enhance the efficacy of tDCS. METHODS: We analyzed tDCS intensity does-response from different perspectives including biophysical modeling, animal modeling, human neurophysiology, neuroimaging and behavioral/clinical measures. Further, we discuss approaches to design dose-response trials. RESULTS: Physical models predict electric field in the brain increases with applied tDCS intensity. Data from animal studies are lacking since a range of relevant low-intensities is rarely tested. Results from imaging studies are ambiguous while human neurophysiology, including using transcranial magnetic stimulation (TMS) as a probe, suggests a complex state-dependent non-monotonic dose response. The diffusivity of brain current flow produced by conventional tDCS montages complicates this analysis, with relatively few studies on focal High Definition (HD)-tDCS. In behavioral and clinical trials, only a limited range of intensities (1-2 mA), and typically just one intensity, are conventionally tested; moreover, outcomes are subject brain-state dependent. Measurements and models of current flow show that for the same applied current, substantial differences in brain current occur across individuals. Trials are thus subject to inter-individual differences that complicate consideration of population-level dose response. CONCLUSION: The presence or absence of simple dose response does not impact how efficacious a given tDCS dose is for a given indication. Understanding dose-response in human applications of tDCS is needed for protocol optimization including individualized dose to reduce outcome variability, which requires intelligent design of dose-response studies

Beyond the target area: an integrative view of tDCS-induced motor cortex modulation in patients and athletes

Transcranial Direct Current Stimulation (tDCS) is a non-invasive technique used to modulate neural tissue. Neuromodulation apparently improves cognitive functions in several neurologic diseases treatment and sports performance. In this study, we present a comprehensive, integrative review of tDCS for motor rehabilitation and motor learning in healthy individuals, athletes and multiple neurologic and neuropsychiatric conditions. We also report on neuromodulation mechanisms, main applications, current knowledge including areas such as language, embodied cognition, functional and social aspects, and future directions. We present the use and perspectives of new developments in tDCS technology, namely high-definition tDCS (HD-tDCS) which promises to overcome one of the main tDCS limitation (i.e., low focality) and its application for neurological disease, pain relief, and motor learning/rehabilitation. Finally, we provided information regarding the Transcutaneous Spinal Direct Current Stimulation (tsDCS) in clinical applications, Cerebellar tDCS (ctDCS) and its influence on motor learning, and TMS combined with electroencephalography (EEG) as a tool to evaluate tDCS effects on brain function

Intergenerational effects of maternal separation on cognitive abilities of adolescent rats

Early life adversity (ELA) is a predisposing factor for the development of behavioral and emotional disorders later in life. In humans, primates and rodents, interruption in the mother�infant relationships, and disorganized maternal care negatively influence appropriate behavioral responses and may cause cognitive deficits. Epidemiological studies suggest that ELA-induced behavioral alterations can be transmitted across generations. In this study, we investigated the cognitive abilities of male and female rats in the second filial (F2) generations whose mother, father, or both of their parents were undergoing a 180 min/day maternal separation (MS) paradigm during infancy (postnatal day (PND) 1-21). Cognitive abilities (in the open field, Morris water maze, and social interaction task) of F2 pups were tested during adolescence. Our results showed that although the mother-MS group of both sexes showed normal cognitive behavior, father-MS female pups showed more anxiety in the open field, and social interaction and spatial memory impaired in this group. These impairments were not pronounced in every detail in father-MS male pups. Moreover, rat pups that both parents experienced MS during infancy, showed normal cognitive behavior. Our data support the idea that MS-induced cognitive impairments could be transmitted across generations. Considerably, the experiences of one's parents could be inherited in the following generation in a sex-dependent manner. © 2020 International Society for Developmental Neuroscienc

Modelling of the Effect of Concentrated Nitration Conditions on the Efficiency of the Production of ,7-Dinitro-1,3,5,7-tetraazabicyclo[3,3,1]nonane (DPT)

3,7-Dinitro-1,3,5,7-tetraazabicyclo[3,3,1]nonane (DPT) is one of the most important intermediates in the synthesis of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX). A suitably modified Bachmann process, nitrolysis of solid hexamine in the presence of ammonium nitrate-nitric acid and acetic anhydride on a laboratory scale, is introduced to increase the efficiency, production capacity and purity of the DPT produced. Various quantitative and qualitative analytical methods were used for the identification and quality control of the product. A central composite design (CCD) of experiments was used to optimize the production process, increasing the production capacity, reducing the amount of acetic acid as the reaction medium to a suitable limit, and examining the effects of the main factors impacting on the efficiency of the nitration, e.g. the volume of ammonium nitrate-nitric acid solution, nitration temperature reactor addition time and volume of acetic anhydride. The overall results indicated that DPT was obtained with an efficiency of 64.58% and a production capacity of 20.77 (100 g·mL−1)

Increasing the Efficiency of the Production of 1,3,5,7-Tetranitro-1,3,5,7-tetrazocane (HMX)

This work introduces a suitable method for the optimization of selective synthesis of 1,3,5,7-tetranitro-1,3,5,7-tetrazocane (HMX), as one of the most well-known high explosives, from the aspects of production capacity and efficiency, by nitration of 3,7-dinitro-1,3,5,7-tetraazabicyclo[3,3,1]nonane (DPT). The effective factors in the productive capacity of HMX and the synthesis of a product from raw DPT with high capacity, purity, and efficiency have been identified. The required qualitative and quantitative analyses were performed for the identification and confirmation of the product quality. In order to optimize the process of increasing the capacity of HMX production and evaluation of the effects of different factors on the production capacity, a series of experiments were designed and performed by using central composite design (CCD). Practical studies and statistical analyses showed good conformity between the model presented and the actual results, allowing the selective production of HMX with an efficiency of greater than 70% and a high production capacity

Modelling of the Effect of Concentrated Nitration Conditions on the Efficiency of the Production of 3,7-Dinitro-1,3,5,7-tetraazabicyclo[3,3,1]nonane (DPT)

3,7-Dinitro-1,3,5,7-tetraazabicyclo[3,3,1]nonane (DPT) is one of the most important intermediates in the synthesis of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX). A suitably modified Bachmann process, nitrolysis of solid hexamine in the presence of ammonium nitrate-nitric acid and acetic anhydride on a laboratory scale, is introduced to increase the efficiency, production capacity and purity of the DPT produced. Various quantitative and qualitative analytical methods were used for the identification and quality control of the product. A central composite design (CCD) of experiments was used to optimize the production process, increasing the production capacity, reducing the amount of acetic acid as the reaction medium to a suitable limit, and examining the effects of the main factors impacting on the efficiency of the nitration, e.g. the volume of ammonium nitrate-nitric acid solution, nitration temperature reactor addition time and volume of acetic anhydride. The overall results indicated that DPT was obtained with an efficiency of 64.58% and a production capacity of 20.77 (100 g·mL−1)

Environmental enrichment and pain sensitivity; a study in maternally separated rats

Rodents are highly dependent on maternal care after birth. Maternal separation (MS) is an animal model for studying neglect and abuse. Depriving the pup of such care renders the animal with Hypothalamic�Pituitary�adrenal (HPA) dysfunction and these animals are more susceptible to anxiety and stress as well as poor cognition. These effects are due to abnormal brain development in these animals. We have tried to investigate how maternal separation can affect pain sensation and whether a non-pharmacological intervention such as enriched environment (EE) can restore an abnormal pain sensation. Animals were put into four groups MS, control (CTRL) and MS + EE and CTRL + EE groups that underwent EE after weaning until adulthood. These groups were tested for pain sensitivity with hot plate and tail flick for sensory pain and formalin for affect pain. The results showed that MS rats are more sensitive to pain in the hot plate test and formalin test, however, no significant difference was seen between groups for tail flick test. When MS rats experience EE their pain sensitivity is restored at the behavioral level. Further research is required to see how EE restores pain sensation in MS rats. © 2020 International Society for Developmental Neuroscienc

Incomplete Evidence that increasing current intensity of tDCS boosts outcomes

Background: Transcranial direct current stimulation (tDCS) is investigated to modulate neuronal function by applying a fixed low-intensity direct current to scalp. Objectives: We critically discuss evidence for a monotonic response in effect size with increasing current intensity, with a specific focus on a question if increasing applied current enhance the efficacy of tDCS. Methods: We analyzed tDCS intensity does-response from different perspectives including biophysical modeling, animal modeling, human neurophysiology, neuroimaging and behavioral/clinical measures. Further, we discuss approaches to design dose-response trials. Results: Physical models predict electric field in the brain increases with applied tDCS intensity. Data from animal studies are lacking since a range of relevant low-intensities is rarely tested. Results from imaging studies are ambiguous while human neurophysiology, including using transcranial magnetic stimulation (TMS) as a probe, suggests a complex state-dependent non-monotonic dose response. The diffusivity of brain current flow produced by conventional tDCS montages complicates this analysis, with relatively few studies on focal High Definition (HD)-tDCS. In behavioral and clinical trials, only a limited range of intensities (1-2mA), and typically just one intensity, are conventionally tested; moreover, outcomes are subject brain-state dependent. Measurements and models of current flow show that for the same applied current, substantial differences in brain current occur across individuals. Trials are thus subject to inter-individual differences that complicate consideration of population-level dose response. Conclusion: The presence or absence of simple dose response does not impact how efficacious a given tDCS dose is for a given indication. Understanding dose-response in human applications of tDCS is needed for protocol optimization including individualized dose to reduce outcome variability, which requires intelligent design of dose-response studies

Walnut Kernel administration to mothers during pregnancy and lactation improve learning of their pups. Changes in number of neurons and gene expression of NMDA receptor and BDNF in hippocampus in 80 days rat pups

Walnut (Juglans regia) from the Juglandaceae family contains high levels of omega 3 fatty acid, vitamin E and melatonin, hence its consumption is beneficial to would be mothers and their offspring. The current study was designed to determine the possible mechanism of walnut consumption by mothers during pregnancy and lactation and the positive effects on learning and memory processes in their offspring. Wistar adult female rats were placed into three groups: control (fed with pellet, 20 g daily during pregnancy and lactation), CASE 1 fed with Walnut Kernel (WK) 6% of food intake during pregnancy and lactation and CASE 2 (fed with WK, 9% of food intake during gestation and lactation). In order to evaluate offspring learning and memory, the Morris Water Maze (MWM) test was performed for their adult offspring at 80 days of age. Histological and molecular studies were utilized in order to discover the protective mechanism and efficacy of WK consumption. The results revealed that learning was significantly improved in the females of CASE 2, in comparison to controls, while there was no difference in memory among the different groups. In addition, the number of neurons significantly increased in the CASE 2 group compared to the control group. However, the molecular study demonstrated that there was no significant difference among the study groups. The results herein show that feeding mothers with WK may improve the learning competence of their pups and increase the number of neurons in both sexes. © 2020 Zahra Mahmoodian et al., published by Sciendo 2020